Methylprednisolone Treatment of Pregnant Women with Spinal Cord Injury

MP Treatment of Pregnant Women with Spinal Cord Injury


Wise Young PhD MD, Professor II & Director

W M Keck Center for Collaborative Neuroscience

Rutgers, State University of New Jersey

604 Allison Rd, Piscataway, NJ 08854-8082

tel: 732/445-2061, fax: 732/445-2063




Methylprednisolone (MP) is accepted therapy for acute spinal cord injury (SCI).  Unfortunately, due to fear that such high doses of MP would affect the fetus, the original clinical trials excluded pregnant women.  Thus, there is currently little data concerning the risks or benefits of MP treatment of pregnant women with spinal cord injury.  However, there is substantial information on the use of high dose corticosteroids in pregnant women with other conditions.  In this article, I will review the available data concerning the safety and use of MP in SCI, with particular emphasis on its use in pregnant women.

Potential Benefit of MP in SCI


Methylprednisolone (MP) was the first treatment that found to improves neurological recovery when given within 8 hours after SCI [1-12].  Although the effects of MP are modest, improving lost motor and sensory recovery by an average of 20% compared to placebo controls, even such small improvements can have significant effects on quality of life.  NASCIS 2 showed that high-dose MP did not significantly increase morbidity or mortality of spinal cord injury.  Dire predictions of increased gastric hemorrhage, aseptic femoral necrosis of hip joints, and even systemic infections turned out to be unfounded.


In the decade since the publication of NASCIS 2 in 1990, millions of people have received the NASCIS protocol of 30 mg/kg bolus followed by a 24-hour course of MP for spinal cord injury, pre-operatively treatment before spinal surgery, multiple sclerosis, and a variety of other conditions.  Despite such widespread use of the drug, relatively few complications have been reported.  However, many clinicians continue to feel nervous about the use of high dose MP therapy. Some have questioned the neurological significance of the improvement in neurological scores observed in the NASCIS trials [13-15], even though the trials utilized a neurological scoring approach that is similar to and well accepted amongst rehabilitation, neurosurgical, and orthopedic communities [16].


High-dose MP therapy is now used for many conditions besides spinal cord injury.  For example, pulsed high-dose MP (usually 1 gram) doses are used to treat polymyositis [17, 18], complications of interferon treatment of myelofibrosis [19], Wagner’s granulomatosis [20], systemic lupus erythrematosis [21-25], Marchifava-Bignami disease [26], hepatic regimen-related toxicity associated with stem cell transplants [27], acute psychosis related to multiple sclerosis [28], diffuse alveolar hemorrhage after bone marrow transplants [29, 30], cytopenia and hemolytic anemia due to Hodgkin’s disease [31], graft vs. host disease [32], dermatomyositis [33, 34], idiopathic thrombocytopenia [35], chemotherapy associated complications [36, 37], membranous [38] and other kinds of nephropathy [39], and lymphomas [40]. 


MP is also used to treat many types of neurological injuries besides the typical traumatic spinal cord injury.  For example, MP is used to treat lightning-induced blindness [41], spinal cord injuries associated with orthopedic instrumentation [42], traumatic optic neuropathy [43, 44].  Pre-operative administration of MP is commonly used in operations where the spinal cord will be manipulated, such as hemangioblastomas [45].  Finally, MP is the treatment of choice for secondary progressive and acute relapsing multiple sclerosis.

MP Use for Spinal Cord Injury


During the years that followed the first report of the beneficial effects of high-dose MP on spinal cord injury, less than half of people with spinal cord injury received the NASCIS protocol.  In the U.S., Gerhart, et al. [46] reported that between 1990-1991, only 46% of persons that were spinal cord injured in Colorado received the MP treatment according to the NASCIS protocol.  Interestingly, small and emergency triage facilities were significantly more likely to use the protocol that larger acute care hospitals and patients with initially incomplete injuries were less likely to receive the drug.


Adoption of MP treatment of spinal cord injury was similarly slow in other countries.  Botel, et al. [47] reported the German experience indicating that only 64.4% of patients treated between 1993-1995 came into hospital within the time period allowing MP treatments. This problem is significantly worse in third world countries where the average transport time from road accident to hospital may exceed 12 hours.  Gabler, et al. [48] examined the use of the NASCIS MP protocol at the University Clinic of Traumatology in Vienna.  A total of 31 patients received the drug, 27 were stabilized within 8 hours, 2 patients were not operated on because of poor prognosis, 2 patients were not operated on because their spinal fractures were deemed to be stable.  Followup of these patients showed that 18 incomplete showed significant recovery.  Three patients or 23% of those with complete tetraplegia showed nearly full recovery. 


MP use also depend on the country.  MP is consistently used in Scandinavia, Germany, Austria, Spain, and Italy.  Likewise, MP is now routinely given for spinal cord injury in Japan, Taiwan, Korea, and Brazil.  However, MP is not always given in England, France, and Australia where there is skepticism amongst doctors regarding the efficacy and safety of high-dose MP.  In many third world countries, the use of MP is limited by the expense of the drug and the transportation time of trauma victims to hospital.  Thus, for example, in India, China, and Mexico, MP is used consistently only in hospitals where funds are available for drug therapy and patients are transported to hospital within 8 hours after injury.


In most parts of the world, MP is being given to over 90% of people with acute spinal cord injury.  However, there are two exceptions.  First, MP is only being administered to about 50% of spinal cord injury due to gunshot and other penetrating wounds.  Second, MP may not be given to pregnant women.  This is because the original NASCIS trials excluded such patients and little data exists concerning the potential risks and benefits of the use of MP in such cases.   

Potential Complications of High-dose MP


The second National Acute Spinal Cord Injury Study or NASCIS 2 [3] gave a bolus dose of 30 mg/kg followed by 5.4 mg/kg/hour for 23 hours.  The study did find a trend for a slightly higher incidence of surgical wound infections, i.e. 7% in patients receiving the standard 24-hour course of MP compared to 3% in the placebo group.  This difference was not statistically significant and such infections can be readily treated with antibiotics.  NASCIS 3 [10, 11] found a significant increase in the severity of pneumonia in patients receiving a 48-hour course of MP compared to the standard 24-hour course.  The study found significantly greater improvement of neurological function of patients treated with the 48-hour course of MP when the treatment was started more than 3 hours after injury but no difference in neurological recovery in patients treated with the 24- or 48-hour courses started within 3 hours after injury.  Given the potential risk and the benefit, NASCIS recommended that the 48-hour MP treatment be given only in patients that did not receive start the drug within 3 hours after injury.


The NASCIS trials excluded three groups of patients:  spinal cord injury from gunshot and other penetrating wounds, people with diabetes or pre-existing metabolic diseases, and pregnant women.  In addition, NASCIS had too few patients over 60 years of age to allow a rigorous analysis of MP use in older patients.  Because little information is available concerning the risks and benefits of MP under these conditions, the decision to give MP depends on the comfort level of the doctors with the use of MP and the support facilities available to treat complications.


Matsumoto, et al. [49] recently did a prospective randomized and double-blind trial of high dose MP in 46 patients (average age 60.6 years, range 18-84).  Although the overall complication rate in the two treatment groups did not differ significantly (p=0.139), there was a trend for more complications (56.5%) in the MP group, compared to placebo (34.8%).  The trial, however, revealed a significant difference of pulmonary complications in older patients (>60 years old).  They concluded that older patients receiving methylprednisolone should be carefully watched for the possibility of increase pulmonary problems.


Hasse, et al. [50] reported on five cases of patients with spinal cord injury with severe hyperglycemia and nonketotic metabolic acidosis associated with multiple blunt injuries.  They suggested that these metabolic abnormalities were associated with epinephrine injection and aggravated by methylprednisolone, concluding that high-dose MP therapy should be avoided in patients with multiple injuries or patients that require catecholaminergic support. 


Gerndt, et al. [51] did a retrospective study of patients treated between 1990 and 1994, compared with those treated between 1986 to 1993 who did not receive methylprednisolone.  They report that steroid therapy was associated with a 2.6 fold increase in the incidence of pneumonia and an increase in ventilated and intensive care days. However, use of methylprednisolone was also associated with a decrease in duration of rehabilition and had no significant impact on other outcome parameters, including mortality.  This study is retrospective and many of the differences may be have been due to changes in care approaches.  For example, the decrease in rehabilitation days may be part of an overall trend to reduce the length of hospital stays. 


Sauerland, et al. [52] conducted a risk-benefit analysis of complication rates associated with high-dose methylprednisolone treatment given pre-operatively to surgical patients.  They located 51 studies where MP was given to elective cardiac and noncardiac surgery, as well as in patients with trauma.  Analysis of the pooled data showed no significant increase in complication rates due to MP usage.  In patients given high dose corticosteroids, there were trends for more gastrointestinal bleeding and wound complications but these were not statistically significant.  The only significant finding was a reduction of pulmonary complications (risk difference –3.5%) in trauma patients.  They conclude that methylprednisolone peri-operative use of high dose MP was not associated with increased complications and significantly lowered pulmonary complications.

Theorized complications of MP use


Many complications have been theorized to be associated with MP use in spinal cord injury.  In the 1980’s, when high-dose methylprednisolone was given to patients for the first time for spinal cord injury, there was great fear that high doses of a potent glucocorticoid would be dangerous.  Many doctors predicted that 2 grams of the drug would cause gastric hemorrhage, aseptic necrosis of the joints, and immunosuppression and severe infectious consequences.  The NASCIS clinical trials showed that none of these concerns were justified.


Prolonged corticosteroid use has long been associated with the development avascular necrosis (AVN) of the femoral head [53].  Wing, et al. [54] carried out a prospective cohort study, examining subjects treated between 1989-1996 with the 24-hour course of MP.  Patients that were younger than 18 and older than 75 were excluded, as were those with histories of hip or shoulder disease before the injury, excessive alcohol consumption, previous steroid use, or systemic lupus erythematosis.  On 59 patients that were examined at 6 months or longer after spinal cord injury, none showed evidence of AVN.  The investigators concluded that the incidence of AVN amongst patients treated with the standard NASCIS does was not higher than normal.


Qian, et al. [55] suggested that MP may damage the muscles of spinal cord injury patients and even proposed that the neurological iimprovement shown in NASCIS may have been related to the recovery from steroid myopathy instead of neuroprotective effects of MP.  This proposal is unfortunately not accompanied by any data that showed that the standard 24-hour course of MP caused steroid myopathy in patients and failed to consider the fact that MP treatment in the NASCIS studies were associated with both motor and sensory improvement.


Segal, et al. [56] assessed the clearance rate of MP in patients with acute spinal cord injury and showed that they had significantly lower clearance, i.e. 30.0±12.0 liter/hour, compared to normal values of 44.7±4.9 liter/hour without a significant change in distribution volume.  The clearance rate was less in people with higher levels of spinal cord injury.  This has led to fears that perhaps MP levels are higher than normal when given to patients with spinal cord injury. 


MP use in pregnant women


Animal studies suggest that glucocorticoids may affect the fetus.  For example, prlonged glucocorticoid therapy can cause an increased incidence of cleft palates in rabbits [57] and mice [58].  There were one report that methylprednisolone may have an oxytocic effect on myometrial contractions [59]. Isolated reports of abnormal fetal development have occurred in humans [60] associated with glucocorticoid use.  Prolonged glucocorticoid administration also affect lymphoid development in pregnant female rats [61-63], retarding fetalplacental maturation and reducing fetal survival.  Long-term corticosteroid administration can also cause premature delivery without accelerated lung development in sheep [64].  Intramammary corticosteroids, however, can slow lung development in the bovine fetuses [65] and other animals [66] due to steroid dose-dependent inhibition or stimulation of lecithin secretion by lung cells [67, 68]. Methylprednisolone may activated dormant viral and other infectious agents [69, 70]. 


A review of the literature, however, indicates widespread use of corticosteroids for many conditions in pregnant women without significant side effects. For example, corticosteroids are commonly used to ameliorate hyperemesis in pregnant women [71-75].  Corticosteroids are frequently used to treat autoimmune and inflammatory conditions during pregnancy, including Wegener’s granulomatosis [76-78], rheumatoid arthritis [79], inflammatory dermatological problems [80-83], immune thrombocytopenia [84], allergies [85] and asthma [86, 87], polymyositis [88], anaphylactoid and other nephropathies [89-92], thrombocytopenic purpura [93-100], aplastic anemia [101], ulcerative colitis [102], Takayasu arteritis [103], anti-phospholipid syndrome [104], and systemic lupus erythematosis [105-114]. 


MP is also commonly used to treat complications of infections during pregnancies, including measles encephalopathy [115] and other virus induced encephalomyelitis [116], Epstein-Barr virus infections [117], HIV-associated pneumocystis carii [118], herpes gestationis [119].  Likewise, MP is used to treat complications of chemotherapy [120] and to provide immunosuppression [121] for kidney [122, 123] and bone marrow transplants [124] in pregnant women.  Finally, MP is used to treat multiple sclerosis [125], idiopathic cervical dystonia [126], and facial diplegia [127] in pregnant women. 


There has been fear that MP may interfere with fertility and impregnation but several studies [134, 135] suggest that MP may actually improve fertility and the rate of pregnancy for certain conditions.  MP does not prevent pregnancy in women [136].  In animals, methylprednisolone treatment does not alter estrogen or progesterone levels [137] and may improve fertilization [138].  Lee, et al. [139] and others [140, 141] found that the corticosteroid immunosuppression does not prevent in-vitro fertilization procedures and may even increase fertilization rates [142], especially in older women [143]. In fact, one report suggests that intrauterine prednisone therapy allowed a successful pregnancy after 10 consecutive miscarriages [144].  MP is used to prevent placental dysfunction after fetal cardiac bypass procedures [133]. 


Effect of MP on Pregnancy and Fetus


Lockshin & Sammaritano [147] reviewed the subject of corticosteroid use in pregnancy recently.  They emphasized that the pharmacokinetics of corticosteroids change in pregnant women but pointed out corticosteroids are not teratogenic, that the corticosteroids do not enter the breast milk, and that clinical experience have shown no abnormalities of children of mothers treated with MP throughout pregnancy.  There may be an increased incidence of early and low birthweight babies but this may be due to the conditions that MP was being used to treat.  However, other reports suggest that MP can even help maintain pregnancies to term [145, 146]. 


Corticosteroids are sometimes deliberately used to treat the fetus or neonates.  Block, et al. [128] did a double-blind randomized study to assess the effects of betamethasone treatment to prevent respiratory distress syndrome (RDS) on 128 premature human infants.  The treatment significantly reduced RDS to 7% compared to 22.6% in placebo and 25% in methylprednisolone treated mothers. This suggests that MP does not penetrate the placental barrier as well as betamathasone and therefore can be used to treat the mother with minimal effects of fetal maturation.  Schmidt, et al. [129] likewise reported similar lack of good or bad effects on the fetus due to MP.  However, Anderson, et al. [130], showed that MP does penetrate into the fetal compartment.  In fact, MP is used at 48-72 hour pre-term to treat fetal lung surfactant proteoglycan composition [131].  Ovali, et al. [132] also reports that MP is more effective than intravenous immunoglobulins for fetal and neonatal autoimmune thrombocytopenia. 


Although MP has been used on many pregnant women, there have been relatively few reports of fetal complications .  Takahashi, et al. [148] reported that MP immunosuppression during pregnancy may cause severe B-lymphocyte deficiency in mothers.  Because of the lower B-lymphocyte levels, it may be advisable to delay vaccination in the babies [149].  MP also may suppress calcium uptake by fetal and neonatal intestines [150, 151].  On the other hand, high-dose MP is used to treat carditis and to induce lung maturation in fetuses. 


In summary, despite widespread use of MP and other corticosteroids in pregnant women, often in doses that are as high as those used for spinal cord injury, there have been few reports of any deleterious consequences of short-term MP use on the fetus or the mother.  In fact, many studies suggest that MP may be beneficial for autoimmune, infectious, and other diseases in pregnant women and may be beneficial for the mother and fetus.  Given the potential benefit of MP for spinal cord injury and the lack of evidence indicating a high rate of complications, the data suggests that the short-term high-dose MP used for spinal cord injury can be given to pregnant women.




1.             Young W (1990). NASCIS. National Acute Spinal Cord Injury Study. J Neurotrauma. 7 (3): 113-4. Summary: <>


2.             Hilton G and Frei J (1991). High-dose methylprednisolone in the treatment of spinal cord injuries. Heart Lung. 20 (6): 675-80. Summary: The Second National Acute Spinal Cord Injury Study (NASCIS II), published in 1990, illustrated the benefits of high-dose steroids in the treatment of acute spinal cord injury. Research into the use of high-dose steroids is reviewed, and proposed mechanisms of action are addressed. Implications for nursing include method and timing of administration and expected complications. A case study is also provided. <> San Francisco General Hospital, CA 94110.


3.             Bracken MB (1992). Pharmacological treatment of acute spinal cord injury: current status and future prospects. Paraplegia. 30 (2): 102-7. Summary: The history and results of the National Acute Spinal Cord Injury Studies (NASCIS) are briefly reviewed. The current status of pharmacological therapy for acute spinal cord injury and future prospects are also summarized. <> Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06510.


4.             Nockels R and Young W (1992). Pharmacologic strategies in the treatment of experimental spinal cord injury. J Neurotrauma. 9 Suppl 1: S211-7. Summary: Remarkable advances have been made in pharmacologic treatments of acute and chronic spinal cord injury. The recent National Acute Spinal Cord Injury Study (NASCIS) showed that very high dose methylprednisolone given within 8 hr after injury improves neurologic recovery. The mechanism is believed to be inhibition of lipid peroxidation. Many other drugs have been claimed to be beneficial in animal studies, including other lipid peroxidation inhibitors, free radical scavengers, opiate receptor blockers, NMDA receptor blockers, calcium channel blockers, inhibitors of arachidonic acid metabolism, and protease inhibitors. In chronic spinal cord injury, much progress also has been made. Myelin was found to possess factors that inhibit axonal regeneration. Blocking these factors enhances spinal cord regeneration. Monosialic gangliosides (GM1) were recently found to improve neurologic recovery in spinal-cord-injured patients. Given as late as 48-72 hr after injury, the mechanism of action is not well understood. However, the GM1 results give hope that recovery mechanisms can be manipulated pharmacologically. Nonregenerative therapy for chronic spinal cord injury is also being developed. Several drugs, including 4- aminopyridine and baclofen, respectively blockers of potassium channels and GABA-B receptors, improve conduction in demyelinated axons. These drugs may be useful for identifying patients who might benefit from remyelination therapy. Finally, NASCIS has complicated acute spinal cord injury studies. To bring a drug to clinical trial, an investigator must now determine the optimal treatment dose, timing, and duration over a range of injury severities, in comparison and combination with methylprednisolone. This requirement has so increased the scale of drug testing that multicenter laboratory trials may be necessary. <> Department of Neurosurgery, University of California, San Francisco General Hospital.


5.             Bracken MB and Holford TR (1993). Effects of timing of methylprednisolone or naloxone administration on recovery of segmental and long-tract neurological function in NASCIS 2. J Neurosurg. 79 (4): 500-7. Summary: Previous analyses of the National Acute Spinal Cord Injury Study (NASCIS) have not distinguished recovery of segmental function at the injury level from recovery of the long spinal tracts. Recovery at the injury level could be of considerable clinical significance, but long- tract recovery is the ultimate therapeutic goal. This analysis demonstrates that the greatest proportion of all neurological recovery and of recovery due to treatment with very high doses of methylprednisolone within 8 hours of injury occurs below the lesion. Methylprednisolone treatment administered early following injury has been found to improve recovery below the lesion in patients initially diagnosed as having complete or incomplete injuries; it also leads to greater (but still relatively small) improvement in the injury level. The analysis indicates that delayed treatment with methylprednisolone is associated with decreased neurological recovery. Naloxone administration also improved neurological function below the lesion in patients with incomplete injuries; these results support further experimental work with this drug. This observation of differential neurological response within a narrow treatment window has important implications for both experimental studies and clinical management. Early clinical management with high-dose methylprednisolone is supported by this analysis. <> Department of Epidemiology and Public Health, Yale University Medical School, New Haven, Connecticut.


6.             Bracken MB (1993). Pharmacological treatment of acute spinal cord injury: current status and future projects. J Emerg Med. 11 (Suppl 1): 43-8. Summary: The multicenter, double-blind, randomized second National Acute Spinal Cord Injury Study (NASCIS 2) was conducted to assess the effectiveness of methylprednisolone in improving neurological function after acute spinal cord injury. At 6 weeks, patients treated within 8 hours of injury with methylprednisolone, given as an initial bolus of 30 mg/kg followed by infusion of 5.4 mg/kg/h over 23 hours, demonstrated significantly greater improvement in motor function and touch sensation than did those receiving either naloxone or placebo. Improvement in pinprick sensation was also greater in the methylprednisolone group. These differences were maintained at 6 months and 1 year after injury. The recovery of motor and sensory function in methylprednisolone- treated patients was found to be due primarily to reductions in the severity of the lesion in the spinal cord itself rather than to improvements in the level of injury or root function. A new trial, NASCIS 3, is evaluating a 48-hour course of methylprednisolone infusion as well as treatment with tirilazad mesylate, an inhibitor of lipid peroxidation without glucocorticoid activity. <> Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06510.


7.             Hall ED and Braughler JM (1993). Free radicals in CNS injury. Res Publ Assoc Res Nerv Ment Dis. 71: 81-105. Summary: This chapter has reviewed the current state of knowledge regarding the occurrence and possible role of oxygen radical generation and lipid peroxidation in experimental models of acute CNS injury. Although much work remains, four criteria that are logically required to establish the pathophysiological importance of oxygen radical reactions have been met, at least in part. First of all, oxygen radical generation and lipid peroxidation appear to be early biochemical events subsequent to CNS trauma. Second, a growing body of direct or circumstantial evidence suggests that oxygen radical formation and lipid peroxidation are linked to pathophysiological processes such as hypoperfusion, edema, axonal conduction failure, failure of energy metabolism, and anterograde (wallerian) degeneration. Third, there is a striking similarity between the pathology of blunt mechanical injury to CNS tissue and that produced by chemical induction of peroxidative injury. Fourth, and most convincing, is the repeated observation that compounds that inhibit lipid peroxidation or scavenge oxygen radicals can block posttraumatic pathophysiology and promote functional recovery and survival in experimental studies. Nevertheless, the significance of oxygen radicals and lipid peroxidation ultimately depends on whether it can be demonstrated that early application of effective antifree radical or antiperoxidative agents can promote survival and neurological recovery after CNS injury and stroke in humans. The results of the NASCIS II clinical trial, which have shown that an antioxidant dosing regimen with methylprednisolone begun within 8 hr after spinal cord injury can significantly enhance chronic neurological recovery, strongly supports the significance of lipid peroxidation as a posttraumatic degenerative mechanism. However, ongoing Phase III trials with the more selective and effective antioxidant U74006F (tirilazad mesylate) will give a more clear-cut answer as to the therapeutic importance of inhibition of posttraumatic free radical reactions in the injured CNS. <> CNS Diseases Research Unit, Upjohn Company, Kalamazoo, Michigan 49001.


8.             Young W (1993). Secondary injury mechanisms in acute spinal cord injury. J Emerg Med. 11 (Suppl 1): 13-22. Summary: Experimental studies in animal spinal cord injury models suggest that preservation of a relatively small number of spinal axons can support neurological recovery. The second National Acute Spinal Cord Injury Study (NASCIS 2) was the first clinical trial to demonstrate that a treatment given after injury can enhance neurological recovery. In this trial, patients treated with high-dose methylprednisolone within 8 hours of spinal cord injury recovered more sensory and motor function than did those treated with placebo. In addition to demonstrating the first effective pharmacological intervention in central nervous system injury, NASCIS 2 identified several critical issues that must be investigated in future preclinical and clinical research. These include drug dose, initiation time, and duration of treatment, as well as combination therapy and injury severity. Addressing these issues systematically will require more reproducible animal models and more accurate outcome measures. <> Department of Neurosurgery, New York University Medical Center, NY 10016.


9.             Shepard MJ and Bracken MB (1994). The effect of methylprednisolone, naloxone, and spinal cord trauma on four liver enzymes: observations from NASCIS 2. National Acute Spinal Cord Injury Study. Paraplegia. 32 (4): 236-45. Summary: In order to determine the impact of extremely large doses of methylprednisolone, naloxone, or of spinal cord injury itself, on liver enzymes, we examined the results of SGOT, SGPT, alkaline phosphatase and total bilirubin tests obtained 24 hours, 3 and 10 days after the end of the study drug infusions in spinal cord injured patients entered in the National Acute Spinal Cord Injury Study. The mean values of four liver enzymes, the amount of change between 24 hours and 3 and 10 days post infusion, and the proportion of liver enzyme levels considered to be abnormal did not appear to be affected by either drug protocol. Even when controlling for drug protocol and severity of injury (complete vs incomplete), variation in enzyme levels appeared to be the result of the spinal cord injury, not study drugs. Spinal cord injury is routinely treated with the NASCIS dose of methylprednisolone in many countries. It is reassuring to find no evidence of compromised liver function from this steroid protocol. <> Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, Connecticut 06520-8034.


10.          Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL, Jr., Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR and Young W (1997). Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. Jama. 277 (20): 1597-604. Summary: OBJECTIVE: To compare the efficacy of methylprednisolone administered for 24 hours with methyprednisolone administered for 48 hours or tirilazad mesylate administered for 48 hours in patients with acute spinal cord injury. DESIGN: Double-blind, randomized clinical trial. SETTING: Sixteen acute spinal cord injury centers in North America. PATIENTS: A total of 499 patients with acute spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS) centers within 8 hours of injury. INTERVENTION: All patients received an intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients in the 24-hour regimen group (n=166) received a methylprednisolone infusion of 5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167) received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of tirilazad mesylate every 6 hours for 48 hours. MAIN OUTCOME MEASURES: Motor function change between initial presentation and at 6 weeks and 6 months after injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks and 6 months. RESULTS: Compared with patients treated with methylprednisolone for 24 hours, those treated with methylprednisolone for 48 hours showed improved motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and 6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after injury. Patients who received the 48-hour regimen and who started treatment at 3 to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6 months, to show more improvement in 6-month FIM (P=.08), and to have more severe sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group and the tirilazad group, but other complications and mortality (P=.97) were similar. Patients treated with tirilazad for 48 hours showed motor recovery rates equivalent to patients who received methylprednisolone for 24 hours. CONCLUSIONS: Patients with acute spinal cord injury who receive methylprednisolone within 3 hours of injury should be maintained on the treatment regimen for 24 hours. When methylprednisolone is initiated 3 to 8 hours after injury, patients should be maintained on steroid therapy for 48 hours. <>


11.          Bracken MB (2000). Pharmacological interventions for acute spinal cord injury. Cochrane Database Syst Rev. 2: Summary: BACKGROUND: Acute spinal cord injury is a devastating condition typically affecting young people with a preponderance of males. Pharmacological treatment in the early hours of the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life. OBJECTIVES: To review randomized trials of pharmacological therapies for acute spinal cord injury. SEARCH STRATEGY: The review draws on the search strategy developed by the Cochrane Injuries Group. In addition, files of the National Acute Spinal Cord Injury Study have been reviewed. SELECTION CRITERIA: All published or unpublished randomized controlled trials of pharmacological treatment for acute spinal cord injury in any language. DATA COLLECTION AND ANALYSIS: Data have been abstracted from original trial reports. For the NASCIS, Japanese and French trials, additional data (e.g. SDs) have been obtained from the original authors. MAIN RESULTS: There are few trials in this area of medical care. Only one therapy has been extensively studied, methylprednisolone sodium succinate, which has been shown to improve neurologic outcome up to one year post injury if administered within 8 hours of injury and in a dose regimen of: bolus 30mg/kg administered over 15 minutes with a maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial was replicated in a Japanese trial but not in the one from France. Data has been obtained from the latter study to permit appropriate meta-analysis of all three trials. This analysis indicates significant recovery in motor function after methylprednisolone therapy. A more recent trial indicates that if methylprednisolone therapy is given for an additional 24 hours (for a total of 48 hours), additional improvement in motor neurologic function and functional status is observed. This is particularly observed if treatment cannot be started until between 3 to 8 hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries and a modified regimen found to improve recovery after surgery for lumbar disc disease. REVIEWER'S CONCLUSIONS: High dose methylprednisolone steroid therapy is the only pharmacological therapy shown to have efficacy in a Phase Three randomized trial when it can be administered within 8 hours of injury. High dose methylprednisolone has been accepted as standard therapy in many countries. A recent trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours if start of treatment must be delayed to between 3 and 8 hours after injury. There is an urgent need for more randomized trials of pharmacological therapy for acute spinal cord injury. <> Department of Epidemiology and Public Health, Yale School of Medicine, 60 College street, Box 20834, New Haven, Connecticut 06520-8034, USA.


12.          Shepard MJ and Bracken MB (1999). Magnetic resonance imaging and neurological recovery in acute spinal cord injury: observations from the National Acute Spinal Cord Injury Study 3. Spinal Cord. 37 (12): 833-7. Summary: STUDY DESIGN: Data are from a multicenter, randomized, double blind clinical trial of acute spinal cord injury. OBJECTIVES: To evaluate the prognostic value of magnetic resonance imaging (MRI) for randomized patients in the National Acute Spinal Cord Injury Study 3 (NASCIS). SETTING: Sixteen spinal cord injury centers throughout the United States and Canada. METHODS: Of 499 patients randomized in NASCIS 3 between December 1991 and September 1995, MRI was electively done on 191 patients within 72 h of injury. Indications of hemorrhage, edema, and contusion were recorded by standard protocol. Neurological impairment as determined by motor function, response to pin prick and light touch was assessed at admission to the participating center and 6 weeks after injury. Change in neurological function was obtained by subtracting the score of each neurological parameter at admission from that measured at 6 weeks. Spinal cord surgery performed within the 3 days after injury was noted. Data were analyzed by: chi square, analysis of variance, multiple logistic regression and linear regression models. RESULTS: Patients with hemorrhage were much more likely to have a complete injury (OR=2.88, 95 Cl 1.32, 6.23); however this association was much reduced when the initial neurological examination was taken into account (AOR=1.43, 95% Cl 0.55, 3.73) and was no longer a significant predictor of injury. MRI evidence of cord edema was the strongest predictor of reduced improvement in motor function (-3.34 points, P=0.06) and light touch sensation (-3.41 points, P=0.05) at 6 weeks. CONCLUSIONS: Cord hemorrhage, contusion, and edema on MRI were not associated with diagnosis of a complete cord injury after neurological assessment from the initial clinical examination was taken into account. Prediction of a worse 6 week neurological status was weakly associated with the presence of edema diagnosed by MRI. As MRI technology improves, these diagnostic and predictive capabilities need to be re-assessed. SPONSORSHIP: NASCIS 3 was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, Washington, DC, USA. Pharmacia and Upjohn provided study drugs and placebos; they also monitored data quality, and funded additional tests, in accordance with Food and Drug Administration regulatory requirements. Dr Bracken has served as an occasional paid consultant to Pharmacia and Upjohn. <> Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA.


13.          Nesathurai S (1998). Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials. J Trauma. 45 (6): 1088-93. Summary: The National Acute Spinal Cord Injury Study (NASCIS) 2 and 3 trials are often cited as evidence that high-dose methylprednisolone is an efficacious intervention in the management of acute spinal cord injury. Neither of these studies convincingly demonstrate the benefit of steroids. There are concerns about the statistical analysis, randomization, and clinical end points. Even if the putative gains are statistically valid, the clinical benefits are questionable. Furthermore, the benefits of this intervention may not warrant the possible risks. This paper comments on these two clinical trials. <> Boston University School of Medicine and New England Regional Spinal Cord Center, Boston Medical Center, Massachusetts 02118-2393, USA.


14.          Hurlbert RJ (2000). Methylprednisolone for acute spinal cord injury: an inappropriate standard of care. J Neurosurg. 93 (1 Suppl): 1-7. Summary: OBJECT: Since publication in 1990, results from the National Acute Spinal Cord Injury Study II (NASCIS II) trial have changed the way patients suffering an acute spinal cord injury (SCI) are treated. More recently, recommendations from NASCIS III are being adopted by institutions around the world. The purpose of this paper is to reevaluate carefully the results and conclusions of these studies to determine the role they should play in influencing decisions about care of the acutely spinal cord-injured patient. METHODS: Published results from NASCIS II and III were reviewed in the context of the original study design, including primary outcomes compared with post-hoc comparisons. Data were retroconverted from tabular form back to raw form to allow direct inspection of changes in treatment groups. These findings were further analyzed with respect to justification of practice standards. Although well-designed and well-executed, both NASCIS II and III failed to demonstrate improvement in primary outcome measures as a result of the administration of methylprednisolone. Post- hoc comparisons, although interesting, did not provide compelling data to establish a new standard of care in the treatment of patients with acute SCI. CONCLUSIONS: The use of methylprednisolone administration in the treatment of acute SCI is not proven as a standard of care, nor can it be considered a recommended treatment. Evidence of the drug's efficacy and impact is weak and may only represent random events. In the strictest sense, 24-hour administration of methylprednisolone must still be considered experimental for use in clinical SCI. Forty-eight- hour therapy is not recommended. These conclusions are important to consider in the design of future trials and in the medicolegal arena. <> University of Calgary Spine Program, Foothills Hospital and Medical Centre, Alberta, Canada.


15.          Coleman WP, Benzel D, Cahill DW, Ducker T, Geisler F, Green B, Gropper MR, Goffin J, Madsen PW, 3rd, Maiman DJ, Ondra SL, Rosner M, Sasso RC, Trost GR and Zeidman S (2000). A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury. J Spinal Disord. 13 (3): 185-99. Summary: From the beginning, the reporting of the results of National Acute Spinal Cord Injury Studies (NASCIS) II and III has been incomplete, leaving clinicians in the spinal cord injury (SCI) community to use or avoid using methylprednisolone in acute SCI on the basis of faith rather than a publicly developed scientific consensus. NASCIS II was initially reported by National Institutes of Health announcements, National Institutes of Health facsimiles to emergency room physicians, and the news media. The subsequent report in the New England Journal of Medicine implied that there was a positive result in the primary efficacy analysis for the entire 487 patient sample. However, this analysis was in fact negative, and the positive result was found only in a secondary analysis of the subgroup of patients who received treatment within 8 hours. In addition, that subgroup apparently had only 62 patients taking methylprednisolone and 67 receiving placebo. The NASCIS II and III reports embody specific choices of statistical methods that have strongly shaped the reporting of results but have not been adequately challenged or or even explained. These studies show statistical artifacts that call their results into question. In NASCIS II, the placebo group treated before 8 hours did poorly, not only when compared with the methylprednisolone group treated before 8 hours but even when compared with the placebo group treated after 8 hours. Thus, the positive result may have been caused by a weakness in the control group rather than any strength of methylprednisolone. In NASCIS III, a randomization imbalance occurred that allocated a disproportionate number of patients with no motor deficit (and therefore no chance for recovery) to the lower dose control group. When this imbalance is controlled for, much of the superiority of the higher dose group seems to disappear. The NASCIS group's decision to admit persons with minor SCIs with minimal or no motor deficit not only enables statistical artifacts it complicates the interpretation of results from the population actually sampled. Perhaps one half of the NASCIS III sample may have had at most a minor deficit. Thus, we do not know whether the results of these studies reflect the severely injured population to which they have been applied. The numbers, tables, and figures in the published reports are scant and are inconsistently defined, making it impossible even for professional statisticians to duplicate the analyses, to guess the effect of changes in assumptions, or to supply the missing parts of the picture. Nonetheless, even 9 years after NASCIS II, the primary data have not been made public. The reporting of the NASCIS studies has fallen far short of the guidelines of the ICH/FDA and of the Evidence-based Medicine Group. Despite the lucrative "off label" markets for methylprednisolone in SCI, no Food and Drug Association indication has been obtained. There has been no public process of validation. These shortcomings have denied physicians the chance to use confidently a drug that many were enthusiastic about and has left them in an intolerably ambiguous position in their therapeutic choices, in their legal exposure, and in their ability to perform further research to help their patients. <> WPCMath, Annapolis, Maryland 21401, USA.


16.          El Masry WS, Tsubo M, Katoh S, El Miligui YH and Khan A (1996). Validation of the American Spinal Injury Association (ASIA) motor score and the National Acute Spinal Cord Injury Study (NASCIS) motor score. Spine. 21 (5): 614-9. Summary: STUDY DESIGN: In this study the motor scores of 62 consecutive acute spinal cord-injured patients were retrospectively reviewed. OBJECTIVE: The reliability of the American Spinal Injury Association and National Acute Spinal Cord Injury Study motor scores, compared with the conventional motor scores, was retrospectively assessed. SUMMARY OF BACKGROUND DATA: The reliability of the American Spinal Injury Association and National Acute Spinal Cord Injury Study scores has not as yet been confirmed. METHODS: Sixty-two consecutive adult patients admitted within 7 days of acute spinal cord injury between April, 1983, and September, 1992, were evaluated. The motor deficit percentage and the motor recovery percentage of each of the American Spinal Injury Association and the National Acute Spinal Cord Injury Study motor scores were compared with those of the conventional motor score. From the initial and final motor score, the motor deficit percentage and motor recovery percentage were calculated. There were 38 patients with cervical and thoracic lesions, 12 patients with dorso-lumbar lesions, and 12 patients with lower lumbar lesions. The average follow-up period was 41 months. RESULTS: Both the American Spinal Injury Association motor score and the National Acute Spinal Cord Injury Study motor score were representative of the conventional motor score for the evaluation of the motor deficit percentage and the motor recovery percentage in all levels (P < 0.0001). The differences in all correlation coefficients between the American Spinal Injury Association motor score and the National Acute Spinal Cord Injury Study motor score were not statistically significant in all levels and in every group. CONCLUSIONS: The American Spinal Injury Association and National Acute Spinal Cord Injury Study motor scores can both be used for the neurological quantification of motor deficit and motor recovery. <> Midlands Centre for Spinal Injuries, Robert Jones & Agnes Hunt Orthopaedic and District Hospital.


17.          Tomsic M and Sifrer F (2000). Acute respiratory distress syndrome in a polymyositis patient with the anti-Jo-1 antibody. Wien Klin Wochenschr. 112 (15-16): 728-31. Summary: We report a case of a 66-year-old caucasian woman suffering from polymyositis with the anti-Jo-1 antibody. Shortly after admission to our hospital, despite the fact that the patient was given intravenous pulse methylprednisolone (1000 mg/day for 3 consecutive days), she developed severe, ventilatory-dependent, acute respiratory distress syndrome. Evaluation for infectious or noninfectious aetiologies of acute respiratory distress syndrome was unrevealing. Bronchoalveolar lavage disclosed neutrophilic alveolitis. Histological examination of a transbronchial biopsy revealed an interstitial fibrosing process and cuboidalisation of the alveolar epithelium. In addition to high-dose methylprednisolone the patient was given intravenous pulse cyclophosphamide fortnightly for six weeks and afterwards every 4 weeks. All symptoms resolved and arterial blood gases returned to normal. Remission has been maintained with azathioprine. One year after onset, polymyositis is in complete remission. This is the first report of a patient suffering from polymyositis with the anti-Jo-1 antibody who survived such a complication. Intravenous pulse cyclophosphamide was probably a life saving therapy. <> Department of Rheumatology, University Medical Centre Ljubljana, Slovenia.


18.          Takeda T, Tsutsumi A, Ogura N, Jodo S, Amasaki Y, Nakabayashi T, Fujisaku A, Kobayashi S and Koike T (1995). [A case of mixed connective tissue disease with acute interstitial pneumonitis]. Nihon Rinsho Meneki Gakkai Kaishi. 18 (3): 303-7. Summary: A 43-years-old woman was admitted to the Hokkaido University Hospital because of high fever, muscle weakness and dyspnea in May 1993. She had has muscle weakness of upper extremities since December 1992. She had developed swollen hand, polyarthralgia and Raynaud's phenomenon. High fever and severe dyspnea developed in May 1993. Chest roentogenogram was normal in April 1993. Physical examination showed Velcro rales in both lower lung fields. Her laboratory data showed increased muscle enzymes, high titers of anti-nuclear-antibody (1: 1280) and anti-RNP- antibody (index 199.4 (normal < 7)). Anti-DNA, anti-Sm and anti-Jo-1- antibodies were all negative. Blood gas analysis showed severe hypoxemia. Chest roentogenogram revealed diffuse bilateral interstitial infiltrates prominent in the bases. Diagnosis of mixed connective tissue disease with acute interstitial pneumonitis was made. She was treated with steroid pulse therapy (methylprednisolone 1 g x 3 days) followed by high dose oral prednisolone (60 mg/day), and diffuse interstitial infiltrates disappeared within one week. Prednisolone could be tapered to 17.5 mg/day without relapse. Acute interstitial pneumonitis is a rare complication of mixed connective tissue disease, but may be life threatening. In such cases, high dose steroid therapy should be started without delay. <> Department of Internal Medicine II, Hokkaido University School of Medicine.


19.          Nakamura F, Andoh A, Minamiguchi H, Hodohara K, Fujiyama Y and Bamba T (1997). A case of interstitial pneumonitis associated with natural alpha- interferon therapy for myelofibrosis. Acta Haematol. 97 (4): 222-4. Summary: A 55-year-old man with myelofibrosis was treated with natural alpha- interferon with a good hematologic response. Initially, he had anemia, leukocytosis, thrombocytosis and hepatospleomegaly. A bone marrow biopsy showed replacement with fibrosis with an increase in megakaryocytes. Natural alpha-interferon (alpha-IFN) was started at a dose of 3 x 10(6) units/day. The leukocyte and platelet counts gradually normalized, and the liver and spleen decreased in size. However, the patient complained of a dry cough and dyspnea on the 61st treatment day, when the accumulated dose of alpha-IFN treatment had reached 1.8 x 10(8) units. He subsequently developed acute respiratory failure (PaO2 < 60 mm Hg) with bilateral lung infiltrations, suggesting the occurrence of interstitial pneumonitis associated with alpha- interferon therapy. Immediately, the alpha-interferon was discontinued and high-dose methylprednisolone (1.5 g/day) was administered for 3 days. This treatment was followed by oral prednisone therapy. Steroid therapy brought about gradual improvement as suggested by a repeat radiograph. Since high levels of fibrogenic cytokines, such as PDGF and TGF-beta, have been reported in patients with myelofibrosis, it is necessary to pay attention to interstitial pneumonia as a complication in alpha-IFN therapy for myelofibrosis. <> Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.


20.          Foltz V, Koeger AC, de Sauverzac C, de Person JF, Bourgeois P and Fautrel B (2001). Relapse of Wegener's granulomatosis. Concerning a case after 20 years of remission. Joint Bone Spine. 68 (3): 262-6. Summary: Immunosuppressive drugs have transformed the prognosis of systemic Wegener's granulomatosis. Nowadays, the main residual problem is illness relapses, for which management is largely undefined. We describe the case of a patient, aged 47 in 1977. The diagnosis of Wegener's granulomatosis was made when faced with polyarthralgias, cutaneous vasculitis, rhinitis, dyspnea, hemoptysis and global decline of her physical condition. The treatment associated high-dose corticotherapy and intramuscular cyclophosphamide for 1 year. This treatment led to a complete remission. Twenty years later, the patient was hospitalized for reoccurrence of rhinitis, dyspnea and right knee effusion associated with biological inflammatory syndrome, renal insufficiency and antibodies against polymorphonuclear neutrophil cytoplasm, type c-ANCA. Chest CT-scan disclosed parenchymal infiltrates. Wegener relapse was diagnosed and the combination of three methylprednisolone perfusions followed by oral prednisone (1 mg/kg/d) and a monthly bolus of cyclophosphamide led to a new remission. Nevertheless, 4 months after beginning the treatment the patient died from an infectious complication (Pneumocystis carinii and aspergillosis). Relapses of Wegener's granulomatosis are frequent and difficult to predict. Moreover, some cases occur very early. The remarkable efficiency of cyclophosphamide to induce remission is however shaded by the high rate of relapse. Other drugs are studied to identify more efficient therapy, able to both induce remission and prevent relapses, but reliable data are still missing to determine the best therapeutic regimen. <> Rheumatology Unit, Pitie-Salpetriere Hospital, Paris, France.


21.          Kwong KL, Chu R and Wong SN (2000). Parkinsonism as unusual neurological complication in childhood systemic lupus erythematosus. Lupus. 9 (6): 474-7. Summary: Parkinsonism complicating systemic lupus erythematosus (SLE) is extremely rare. We report two girls with SLE who developed extrapyramidal parkinsonian features after an initial stormy course. One patient presented with generalized tonic clonic seizure and was then noted to have akinetic mutism and masked face. MRI brain revealed abnormal signals in bilateral basal ganglia and single photon emission computed tomography (SPECT) showed hypoperfusion in the same area. EEG background was slow and disorganized. Symptoms persisted despite high dose intravenous methylprednisolone and cyclophosphamide. Intravenous immunoglobulin (IVIG) was prescribed empirically and was followed by complete recovery. Both EEG and MRI brain were normal on follow-up. The second patient was found unconscious and then developed bradykinesia, mutism and shuffling gait. MRI and SPECT both detected abnormalities in basal ganglia. EEG was slow. Intravenous immunoglobulin was given after methylprednisolone and cyclophosphamide. This was followed by clinical improvement. The pathogenesis of basal ganglia injury in SLE, along with the management of cerebral lupus and the mechanisms of action of IVIG, are discussed. <> Department of Paediatrics, Tuen Mun Hospital, Hong Kong, NT, SAR China.


22.          Kashihara K, Shiro Y, Shohmori T, Nomura A and Hara H (1997). [A man with systemic lupus erythematosus presenting with spastic paraplegia]. No To Shinkei. 49 (10): 915-8. Summary: We report a 38-year-old man systemic lupus erythematosus who presented with an acute onset of paraplegia and urinary retention. The man had a 12-year history of nodular cutaneous mucinosis and arthralgia. In 1994, he was admitted to our hospital with a sudden onset of weakness and numbness of the right leg followed by an emergence of similar symptoms in the left leg. His elder sister had died at 16 years of age after suffering from systemic lupus erythematosus for 6 years. On examination, the patient had skin rash on his chest, back, head, forehead, and extremities. The neurological examination revealed that his tongue deviated to the right on protrusion. The muscle power was reduced to 2-3/5 in the right leg and to 4/5 in the left leg. The sensory disturbance was noted in the lower extremities with predominant involvement of the right leg. Reflexes were increased in the right biceps, triceps, both patellas, and Achilles tendons. Babinski sign was noted bilaterally. Urinary retention and constipation were also noted. The results of the blood cell count and hepatic and renal function tests were normal. Serum levels of C-reactive protein and complements (C3, C4, CH50) were also normal. Serological examinations showed increased anti-DNA antibody (14 U/ml, [normal, < 6]). Antinuclear antibody was positive at a titer of 1:1380. CSF study showed an increased protein concentration of 83 mg/dl and an IgG level of 14 mg/dl with a normal number of cells. MR images revealed a T1-low, T2- high signal lesion at the upper part of the left ventral medulla. MR images of the brain and spinal cord were normal. The patient was diagnosed as having SLE. High-dose intravenous methylprednisolone (1 g/day) pulse treatment that was started 25 days after the onset of neurological symptoms, produced partial relief. Our case presented with paraplegia with a focal lesion in the left upper ventral part of the medulla on MR images. The incidence of male SLE is low, and paraplegia is a rare complication of SLE. Thus, the medullary lesion in SLE observed in our case appears to be rare. SLE should be considered as a cause of acute onset paraplegia or myelopathy. <> Department of Neurology, Okayama University Medical School, Japan.


23.          Ballou SP (1987). Systemic lupus erythematosus. Controversies in management. Postgrad Med. 81 (8): 157-9, 163-4. Summary: At the core of the controversy surrounding the management of systemic lupus erythematosus are the two issues of when to treat and what treatment to use. On the basis of a review of the recent medical literature, the following conclusions can be drawn: Patients with isolated serologic or histologic renal abnormalities in the absence of clinical disease activity probably should not be treated. Such abnormalities primarily serve to indicate the need for close follow-up and to heighten the physician's concern about the possible development of clinical symptoms. For those patients with systemic manifestations who require corticosteroids, a regimen of single daily doses is appropriate. The dose should be tapered as rapidly as the degree of symptomatic control allows; a switch to alternate-day therapy can be considered as symptoms become quiescent. Intravenous methylprednisolone therapy may be used for patients with very severe systemic disease, particularly acute nephritis. In addition, use of immunosuppressive agents should be considered for all patients with clinically serious renal disease. <>


24.          Leikin JB, Arof HM and Pearlman LM (1986). Acute lupus pneumonitis in the postpartum period: a case history and review of the literature. Obstet Gynecol. 68 (3 Suppl): 29S-31S. Summary: A patient is described who developed acute lupus pneumonitis in the puerperium. The difficulty in arriving at this diagnosis and the confusion with infectious etiologies of postpartum illness is described. Other manifestations of pulmonary disease in systemic lupus erythematosis are discussed, and the literature regarding acute lupus pneumonitis in the postpartum period is reviewed. <>


25.          Giordano M, Gallo M, Chianese U, Maniera A and Tirri G (1986). Acute pancreatitis as the initial manifestation of systemic lupus erythematosus. Z Rheumatol. 45 (2): 60-3. Summary: A 20-year-old female with three laboratory ARA criteria pro SLE (LE cells, FANA, and positive Coombs test with hemolytic anemia), not under steroid therapy, developed polyarthritis, erythematous rash and acute pancreatitis simultaneously. The latter regressed with high doses of 6- methylprednisolone. Twenty-five months after remission of pancreatitis, no new clinical manifestations (of SLE) have appeared. In another 74 cases of SLE with an average follow-up of 3 years and 8 months there were no other cases of pancreatitis. <>


26.          Kikkawa Y, Takaya Y and Niwa N (2000). [A case of Marchiafava-Bignami disease that responded to high-dose intravenous corticosteroid administration]. Rinsho Shinkeigaku. 40 (11): 1122-5. Summary: We report a 63-year-old male who presented acute confusional state with prominent rigidity of all extremities. The patient had a long history of alcoholism and was in poor physical condition and malnourished. The diagnosis of Marchiafava-Bignami disease was indicated by T2-weighted MRI demonstrating high signal intensity in the corpus callosum. Because Wernicke's encephalopathy was suspected as a complication, thiamine therapy was applied, but there was no clinical improvement. Immediately after high-dose intravenous corticosteroid administration was started, his symptoms rapidly resolved except for mild cognitive impairment. It is supposed that edematous change in the early stages of Marchiafava- Bignami disease causes impairment of the blood-brain barrier. Steroid therapy may prevent such a process by means of its the anti-edema effect and by normalizing blood-brain barrier. The present case suggests that corticosteroid therapy has beneficial effects for Marchiafava-Bignami disease. <> Department of Neurology, Shimotsuga General Hospital.


27.          Khoury H, Adkins D, Brown R, Trinkaus K, Vij R, Miller G, Goodnough LT and DiPersio J (2000). Does early treatment with high-dose methylprednisolone alter the course of hepatic regimen-related toxicity? Bone Marrow Transplant. 25 (7): 737-43. Summary: Hepatic regimen-related toxicity (RRT) is a serious complication of stem cell transplantation. Cytokine activation may be involved in the pathogenesis. Corticosteroids are potent inhibitors of cytokine production, and, therefore could play a role in the treatment of hepatic RRT. Between January 1994 and June 1998, 28 of 782 consecutive transplant patients (3.6%) developed hepatic RRT (20 veno-occlusive disease (VOD) and eight liver dysfunction of uncertain etiology (LDUE) as defined by Seattle criteria), and were treated with high-dose methylprednisolone (MP, 500 mg/m2 i.v. every 12 h for six doses), initiated upon increase in serum total bilirubin to > or =4 mg/dl. Other causes of liver dysfunction were excluded. Response to therapy with high-dose MP was defined as reduction in total bilirubin by 50% within 10 days of initiation of MP. Overall, 17 patients (61%) responded to treatment (12 patients with VOD, five patients with LDUE). The bilirubin in responding patients decreased from a mean of 8.6 mg/dl (range, 4-17.9) at the start of MP to 4.1 mg/dl (range, 0.5-17.9) 10 days later. There were no statistically significant differences between responders and non-responders in the day treatment with high-dose MP was initiated (P = 0.38), total serum bilirubin (P = 0.17) and percent weight gain at the time high-dose MP was started (P = 0.10) or the calculated probability of fatal outcome from VOD (18% for responders, 23% for non-responders; P = 0.30). A lower pre-transplant DLCOc was observed among non-responders (P = 0.04). At 100 days post-transplant, hepatic RRT resolved in all 13 survivors who responded to high-dose MP, and in one non-responding patient. No serious toxicities due to high- dose MP were observed. We conclude that resolution of hepatic RRT occurred in the majority of patients treated with high-dose MP in this study; however, randomized controlled trials are required to determine the efficacy of high-dose MP for treatment of hepatic RRT. <> Washington University School of Medicine, Division of Bone Marrow Transplantation and Stem Cell Biology, St Louis, MO 63110-1093, USA.


28.          Iniguez C, Campos R, Larrode P, Mauri JA and Morales F (2000). [Steroid treatment of acute psychosis associated with multiple sclerosis]]. Rev Neurol. 31 (9): 841-4. Summary: INTRODUCTION: Psychiatric disorders are common in patients suffering from multiple sclerosis (MS). Psychosis is a rare complication in this condition. We present two patients with MS and psychosis. CLINICAL CASES: Case 1. A 45-year-old man was admitted to the hospital because an acute psychosis. The diagnosis of clinical definitive MS was made two years before. Cranial magnetic resonance imaging (MRI) and single positron emission computerized tomography (SPECT) showed lesions in the left temporal lobe. He was treated with a 3-day course of high-dose corticosteroid and neuroleptic. The patient's status gradually improved within the following weeks. Case 2. A 41-year-old man with MS was hospitalized in a Psychiatric Department for acute psychosis. He was treated with high-dose of neuroleptic. Thereafter two remissions and relapses of MS have occurred. In 1998, the patient was evaluated in the Service of Psychiatric for new paranoid acute psychosis. CONCLUSIONS: Psychosis is not a prominent feature of the disease, occurring in 5% of cases. The relationship between lesions of the central nervous system and psychiatric illness has not been established although some reports have implicated the temporal lobe. The propensity of steroids to exacerbate psychosis usually argues against this option, but steroids could theoretically improve psychosis related to acute demyelination. <> Servicio de Neurologia, Hospital Clinico Universitario, Juan Bosco, 15, E-50009 Zaragoza.


29.          Haselton DJ, Klekamp JG, Christman BW and Barr FE (2000). Use of high-dose corticosteroids and high-frequency oscillatory ventilation for treatment of a child with diffuse alveolar hemorrhage after bone marrow transplantation: case report and review of the literature. Crit Care Med. 28 (1): 245-8. Summary: BACKGROUND: Other than relapse, pulmonary complications are the most common cause of mortality in patients who undergo bone marrow transplantation (BMT). Diffuse alveolar hemorrhage (DAH) is one noninfectious pulmonary complication of BMT. Presenting clinical findings include nonproductive cough usually without hemoptysis, dyspnea, hypoxemia, a decrease in hematocrit, and diffuse infiltrates on chest radiograph. PATIENT: We report a case of DAH after allogeneic BMT in a 6-yr-old female patient. Although a chest radiograph revealed patchy bilateral alveolar densities and large volumes of bright red blood were suctioned from the endotracheal tube, there was no evidence of coagulopathy and no infectious agent was identified on examination of bronchoalveolar lavage fluid, blood, and urine. INTERVENTION: The child was treated with high-dose corticosteroids and high-frequency oscillatory ventilation and experienced a complete clinical recovery from her pulmonary disease. RESULTS: The definition, presenting symptoms, findings and timing, and associated risk factors of DAH after BMT are reviewed. Prospective hypotheses for the pathogenesis of DAH after BMT are presented. Evidence for the role of high-dose corticosteroids for treatment of DAH after BMT and the role of high- frequency oscillatory ventilation for treatment of acute hypoxemic respiratory failure in children with diffuse alveolar disease is also reviewed. CONCLUSION: This case supports the contention that early treatment with high-dose corticosteroids is warranted in children with DAH after BMT. <> Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.


30.          Metcalf JP, Rennard SI, Reed EC, Haire WD, Sisson JH, Walter T and Robbins RA (1994). Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group. Am J Med. 96 (4): 327-34. Summary: BACKGROUND: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation and is associated with very high mortality. This disorder's association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pulmonary hemorrhage syndromes provided the rationale for this study. METHODS: We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that has occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. RESULTS: Overall survival at the end of the follow-up period was significantly higher for the high- dose corticosteroid group compared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive therapy alone (P = 0.198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups (P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections (P > 0.4, all comparisons). CONCLUSIONS: In this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, and further prospective studies are warranted to verify the effectiveness of the treatment. <> Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-2465.


31.          Ertem M, Uysal Z, Yavuz G and Gozdasoglu S (2000). Immune thrombocytopenia and hemolytic anemia as a presenting manifestation of Hodgkin disease. Pediatr Hematol Oncol. 17 (2): 181-5. Summary: A very unusual clinical presentation of Hodgkin disease with immune thrombocytopenia and autoimmune hemolytic anemia is reported. A 6.5- year-old boy presented with thrombocytopenia, Coombs' positive hemolytic anemia, and multiple small posterior cervical lymph nodes. After a course of high-dose methylprednisolone therapy with a diagnosis of Evans syndrome, complete response for thrombocytopenia and partial response for anemia was achieved. Six weeks later there was a sudden increase in the size of left posterior cervical lymph nodes and a biopsy was compatible with Hodgkin disease, mixed cellularity type. The child was successfully treated with chemotherapy and radiation therapy. He has been off therapy for 28 months and has no clinical or laboratory evidence of autoimmune cytopenia. A combination of immune thrombocytopenia and autoimmune hemolytic anemia may be associated with Hodgkin disease. The recognition of this clinical picture as a complication of Hodgkin disease has important implications. This complication appeares to be managed best by the definitive treatment of Hodgkin disease. <> Ankara University School of Medicine, Department of Pediatrics, Turkey.


32.          Schmuth M, Vogel W, Weinlich G, Margreiter R, Fritsch P and Sepp N (1999). Cutaneous lesions as the presenting sign of acute graft-versus-host disease following liver transplantation. Br J Dermatol. 141 (5): 901-4. Summary: Acute graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation but is only rarely observed after solid organ transplantation. We describe a 68-year-old man who developed a maculopapular eruption 7 days following orthotopic liver transplantation for cirrhosis with malignant transformation due to haemochromatosis. At day 20, the patient complained of nausea, vomiting, diarrhoea and fever. Skin biopsy revealed a lymphocytic infiltrate at the dermoepidermal interface, vacuolization of basal cells and epidermal dyskeratosis. Immunohistochemistry showed HLA-DR and intercellular adhesion molecule-1 expression of lesional keratinocytes. HLA-typing of peripheral blood lymphocytes demonstrated circulating lymphocytes of donor origin. Endoscopy revealed extensive erosions of the oesophagus, stomach and duodenum that on histology disclosed multifocal loss of crypts, lymphocytic infiltrates and epithelial cell death. A diagnosis of acute GVHD was made, and high- dose immunosuppressive therapy with azathioprine and methylprednisolone was instituted. The skin and gastrointestinal symptoms subsided within 4 weeks, but the patient died from severe infectious complications 105 days after transplantation. We conclude that acute GVHD is a rare but potentially fatal complication of liver transplantation. Skin lesions are an early sign of acute GVHD and thus represent an important tool for early diagnosis. <> Department of Dermatology, University of Innsbruck, Innsbruck, Austria.


33.          See Y, Martin K, Rooney M and Woo P (1997). Severe juvenile dermatomyositis complicated by pancreatitis. Br J Rheumatol. 36 (8): 912-6. Summary: We report two boys with juvenile dermatomyositis (JDM) complicated by pancreatitis. One also had hepatitis and probably mild bowel vasculitis, while the other had catastrophic bowel vasculitis with multiple perforations. Both were on corticosteroids, but had features of active vasculitis. The former improved with high-dose i.v. pulsed methylprednisolone, while the latter improved only after immunosuppression with i.v. methylprednisolone, cyclophosphamide and plasmapheresis. Although bowel vasculitis is a known complication of severe JDM, pancreatitis and hepatitis are extremely rare. We have found in a literature search only three other reports of pancreatitis complicating JDM. We wish to alert physicians that pancreatitis may develop in JDM. It should be considered as a differential diagnosis in the child with active disease who develops abdominal pain. Control of vasculitis with adequate immunosuppression, as well as general supportive measures, may be valuable in the treatment of pancreatitis in JDM. <> Department of Rheumatology, Great Ormond Street Hospital for Sick Children, London.


34.          Miyaoka Y, Urano Y, Nameda Y, Shigekiyo T, Horie T, Sano N and Arase S (1997). A case of dermatomyositis complicated by thrombotic thrombocytopenic purpura. Dermatology. 194 (1): 68-71. Summary: A 60-year-old man with dermatomyositis was admitted to our hospital because of dyspnea and hypertension. He had high fever and convulsive seizures after admission. Laboratory examinations showed hemolytic anemia, thrombocytopenia, and renal failure. A clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) was made. He failed to respond to plasma exchange therapy, pulse therapy with methylprednisolone, high-dose gamma-globulin therapy, and antiplatelet therapies with ticlopidine, dipyridamole and a prostacyclin analog of beraprost sodium. He died on his 17th day in hospital. Autopsy examination revealed widespread microthrombi in his kidneys, lungs, spleen, and intestine. Only seven cases of dermatomyositis or polymyositis complicated by TTP have been cited in the literature. TTP was fatal in 6 of these 7 cases. Early diagnosis and prompt treatment may improve the outcome of TTP patients with dermatomyositis. Dermatologists should keep in mind that TTP occasionally arises as a serious complication of dermatomyositis. <> Department of Dermatology, School of Medicine, University of Tokushima, Japan.


35.          Ozsoylu S (1998). Oral megadose methylprednisolone for idiopathic thrombocytopenic purpura. Am J Obstet Gynecol. 178 (6): 1368. Summary: <>


36.          Hermans C, Straetmans N, Michaux JL and Ferrant A (1997). Pericarditis induced by high-dose cytosine arabinoside chemotherapy. Ann Hematol. 75 (1-2): 55-7. Summary: Pericarditis is a rare side effect of chemotherapy. We report here the case of a patient treated with high-dose cytosine arabinoside (HD ara- c) who developed severe pericarditis. Interruption of HD ara-c and initiation of corticosteroid treatment were effective in resolving the pericardial effusion. This case illustrates this rare but potentially life-threatening cardiac complication of HD ara-c therapy as well as the beneficial effect of corticosteroid treatment. <> Hematology Department, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels, Belgium.


37.          Harigaya H, Matsubara K, Nigami H and Baba K (1997). Interstitial pneumonitis probably induced by cyclophosphamide in nephrosis. Acta Paediatr Jpn. 39 (3): 364-7. Summary: A case of interstitial shadows associated with oral cyclophosphamide therapy in a 32-month-old girl with steroid-resistant nephrotic syndrome, who was admitted to the Nishi-Kobe Medical Center with systemic edema, is reported. Due to the lack of response to prednisolone, cyclophosphamide was also administered orally at a dose of 3 mg/kg per day, 4 weeks after the start of steroid therapy. Approximately 3 weeks after the combination treatment she developed a fever, dry cough and cyanosis. Radiographic examination showed diffuse ground-glass shadow in both lungs, presumably indicating that she had interstitial pneumonitis. Her pulmonary signs and symptoms deteriorated despite various antimicrobial treatments. A discontinuation of cyclophosphamide and the administration of high-dose methylprednisolone yielded a dramatic improvement. These findings suggest that the diffuse pulmonary disease in this case was induced by cyclophosphamide. Since interstitial pneumonitis may be fatal and irreversible, attention should be paid to this rare complication even in patients undergoing low-dose oral cyclophosphamide treatment. <> Department of Pediatrics, Nishi-Kobe Medical Center, Japan.


38.          Koethe JD, Gerig JS, Glickman JL, Sturgill BC and Bolton WK (1986). Progression of membranous nephropathy to acute crescentic rapidly progressive glomerulonephritis and response to pulse methylprednisolone. Am J Nephrol. 6 (3): 224-8. Summary: There have been only sporadic reports of membranous nephropathy (MN) evolving into acute crescentic rapidly progressive glomerulonephritis (AC-RPGN). A patient with MN developed acute oliguric renal failure with a serum creatinine (SCr) of 8.4 mg/dl after 5 years of normal renal function. Biopsy now revealed epithelial crescent formation superimposed on MN. Pulse methylprednisolone resulted in significant improvement in renal function, with a SCr of 2.2 mg/dl at 6 months. No other favorable outcomes occurred in the 4 previous case reports of MN evolving into RPGN. AC-RPGN should be considered a treatable etiology of acute renal failure in the setting of MN. <>


39.          Leichter HE, Jordan SC, Cohen AH, Ettenger RB, Salusky IB and Fine RN (1986). Postpartum renal failure in a patient with membranoproliferative glomerulonephritis type II. Am J Nephrol. 6 (5): 382-5. Summary: The previously reported detrimental effects of pregnancy on the course of membranoproliferative glomerulonephritis type II (MPGN type II) are limited and are usually considered to be mild. Based on these reports, a 19-year-old female with the diagnosis of MPGN type II who had stable renal function (creatinine 0.9 mg/dl) and a mild nephrotic syndrome with hypertension for 5 years of close follow-up was advised to complete her pregnancy. After a full-term pregnancy, complicated only by moderate nephrotic syndrome, a healthy female infant was born. Two weeks after delivery, the patient presented with acute renal failure and malignant hypertension, without evidence of hemolysis of hepatic failure. Immunologic parameters, including, C3, C4, antinuclear antibodies, circulating immune complexes as well as antibodies to glomerular basement membrane antigen and tubular basement membrane antigen were negative. Peritoneal dialysis was initiated and a renal biopsy was performed which showed MPGN type II with 50% crescents. Despite pulse therapy with methylprednisolone, renal function did not improve, resulting in the need for chronic dialysis. Although no specific nephritogenic mechanism was shown, the course of this patient should be considered when counseling female patients with MPGN type II, regarding the possibility of pregnancy exacerbating their disease, or resulting in rapidly progressive renal failure. <>


40.          Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F and Romaguera JE (1995). Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 13 (7): 1734-41. Summary: PURPOSE: We report the results of a prospective trial in which patients with relapsing non-Hodgkin's lymphomas were sequentially treated with two regimens (mesna, ifosfamide, mitoxantrone, and etoposide [MINE], and etoposide, methylprednisolone, cytarabine, and cisplatin [ESHAP]) if they had no history of disease resistance to these drugs. PATIENTS AND METHODS: Ninety-two patients received MINE (mesna 4 g/m2, ifosfamide 4 g/m2, mitoxantrone 8 mg/m2, and etoposide 195 mg/m2) for a maximum of six courses followed by ESHAP (etoposide 240 mg/m2, methylprednisone 500 mg/d, high-dose cytarabine 2 g/m2, and cisplatin 100 mg/m2) for three courses to consolidate complete response (CR) or for a maximum of six cycles after a partial response (PR) or no response to MINE. Pretreatment serum levels of lactate dehydrogenase (LDH) and beta 2-microglobulin (beta 2M) were documented in 80 of 92 patients. RESULTS: The response rate to MINE-ESHAP was 69% (48% CRs and 21% PRs), with a median survival time of 24 months and median time to treatment failure of 12 months. The median time to treatment failure according to histology was as follows: low-grade histologies, 16 months; low-grade transformed to intermediate-grade, 8 months; and intermediate-grade, 5 months. The most serious complication was myelosuppression, which resulted in two deaths due to neutropenic sepsis. A risk factor model based on beta 2M and LDH levels before salvage treatment showed three categories of risk, with 36-month survival rates as follows: low (beta 2M < 3 mg/dL and LDH normal), 61%; intermediate (beta 2M > or = 3 mg/dL or LDH above normal), 23%; and high (beta 2M > or = 3 mg/dL and LDH above normal), 0%. CONCLUSION: MINE-ESHAP is an effective salvage strategy for patients with recurrent lymphoma. Toxicity was acceptable. Factors that determine prognostic categories at relapse merit further study. <> Department of Hematology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.


41.          Norman ME and Younge BR (1999). Association of high-dose intravenous methylprednisolone with reversal of blindness from lightning in two patients. Ophthalmology. 106 (4): 743-5. Summary: OBJECTIVE: To report possibly beneficial effects of treatment with high- dose corticosteroids given intravenously to two patients with loss of vision after lightning strikes. DESIGN: Case reports. PARTICIPANTS: Two patients who suffered the effects of a lightning strike. INTERVENTION: High-dose intravenous methylprednisolone (NASCIS-2 Protocol). MAIN OUTCOME MEASURES: Vision recovery, pupil responses, and optic nerve appearance. RESULTS: One patient had unilateral ophthalmoscopically visible abnormality with light perception vision and a relative afferent defect in that eye; vision recovered to 20/25. The other patient had no light perception, nonreactive pupils, and normal fundus examinations in both eyes; vision recovered bilaterally to normal (20/20). CONCLUSIONS: High-dose intravenous corticosteroid treatment in these patients may have had a role in their visual recovery. <> Seacoast Ophthalmology, Portsmouth, New Hampshire 03801, USA.


42.          Loncan LI, Sempere DF and Ajuria JE (1998). Brown-Sequard syndrome caused by a Kirschner wire as a complication of clavicular osteosynthesis. Spinal Cord. 36 (11): 797-9. Summary: A case of spinal cord injury caused by delayed migration of a Kirschner wire is reported. Some cases of distant injuries caused by bone wires, and acupuncture needles have been published, but this is the first reported case of delayed thoracic spinal cord damage caused by the migration of a clavicular wire. A 22-year-old male patient was admitted with a clinical picture of spinal shock after performing physiotherapeutic exercises. Two months prior to this, the patient had undergone surgical treatment for a clavicular fracture in a different clinical center. Imaging showed a clavicular wire had migrated into the spinal canal. An early prescription of a spinal cord methyl- prednisolone protective treatment (NASCIS II), the surgical extraction of the foreign body and the rehabilitation exercises were the keys to a quick recovery. <> Servicio Regional de Neurocirugia, Hospital Miguel Servet, Zaragoza, Espana.


43.          Sherman AL, Cardenas DD and Swedberg S (1997). Management of traumatic optic neuropathy with coexistent spinal cord injury: a case report. Arch Phys Med Rehabil. 78 (9): 1012-4. Summary: Traumatic optic neuropathy (TON) causes blindness of varied severity and occurs infrequently as a complication of closed head injury. A case is presented of TON that occurred in a patient who suffered complete T4 paraplegia from a motorcycle accident but in whom no severe head injury took place. In this case, high-dose intravenous methylprednisolone was begun for the spinal cord injury and repeated 24 hours later for the TON. Vision improved from near total blindness to 20/400 in the left eye (OS) and 20/130 in the right eye (OD). Two weeks later, however, the patient's vision suddenly worsened. Magnetic resonance imaging (MRI) using fat suppression confirmed a lesion along the optic nerve consistent with TON. A third course of methylprednisolone again led to improved vision. The steroids were then tapered orally over 2 weeks and the patient had no further relapses. Moderate to severely impaired vision of 20/ 400 OS and 20/130 OD continues to interfere with the patient's function and spinal cord rehabilitation program. It was concluded that a steroid taper was important in maintaining initial visual gains in this case. Awareness of TON and careful attention to the patient's clinical course can minimize deficit and maximize functional outcomes. <> Department of Rehabilitation Medicine, University of Washington, Seattle 98195, USA.


44.          Steinsapir KD and Goldberg RA (1994). Traumatic optic neuropathy. Surv Ophthalmol. 38 (6): 487-518. Summary: Knowledge concerning the pathophysiologic mechanisms of traumatic optic neuropathy is limited. The optic nerve is a tract of the brain. Therefore, the cellular and biochemical pathophysiology of brain and spinal cord trauma and ischemia provide insight into mechanisms that may operate in traumatic optic neuropathy. The dosage of methylprednisolone (30 mg/kg/6 hours) which was successful in the National Acute Spinal Cord Injury Study 2 (NASCIS 2) evolved from the unique pharmacology of corticosteroids as antioxidants. The management of traumatic optic neuropathy rests on an accurate diagnosis which begins with a comprehensive clinical assessment and appropriate neuroimaging. The results of medical and surgical strategies for treating this injury have not been demonstrated to be better than those achieved without treatment. The spinal cord is a mixed grey and white matter tract of the brain in contrast to the optic nerve which is a pure white matter tract. The treatment success seen with methylprednisolone in the NASCIS 2 study may not generalize to the treatment of traumatic optic neuropathy. Conversely, if the treatment does generalize to the optic nerve, NASCIS 2 data suggests that treatment must be started within eight hours of injury, making traumatic optic neuropathy one of the true ophthalmic emergencies. Given the uncertainties in the treatment, ophthalmologists involved in the management of traumatic optic neuropathy are encouraged to participate in the collaborative study of traumatic optic neuropathy. <> Orbital and Ophthalmic Plastic Surgery Division, Jules Stein Eye Institute, UCLA School of Medicine.


45.          Pietila TA, Stendel R, Schilling A, Krznaric I and Brock M (2000). Surgical treatment of spinal hemangioblastomas. Acta Neurochir. 142 (8): 879-86. Summary: BACKGROUND: The routine use of magnetic resonance imaging (MRI) in recent years for the diagnostic assessment of the spinal column and especially for screening patients with von Hippel-Lindau (vHL) disease has shown that spinal hemangioblastomas (sHBs) are more common than assumed so far. Since most sHBs are thus discovered while they are still asymptomatic, especially in vHL disease, the question arises whether and when these tumors should be treated. The present article reports the results of the surgical treatment of sHBs using the protocol described below and compares them to the course in a control group of patients with conservatively treated sHBs. PATIENTS AND METHODS: A total of 30 sHBs were treated microsurgically in 15 patients. Hemangioblastoma-associated cysts were merely opened in 14 cases, drained with the help of Teflon cotton in 2 of these cases, and not opened in 4 instances. Laminoplasties were performed with insertion of absorbable, MRI-compatible microosteosynthesis plates. Perioperatively, all patients were administered methylprednisolone according to the NASCIS (National Acute Spinal Cord Injury Study) scheme, and sensory evoked potentials were monitored intra-operatively in all cases. Nine patients in whom the course of primarily conservative treatment of a total of 17 asymptomatic sHBs was documented served as controls. The follow-up time was 7 to 51 months (mean 20) after surgery and 10 to 51 months (mean 21) in the control group. FINDINGS. Preoperative HB-associated pareses showed transient postoperative deterioration (n = 5). The other accompanying neurological deficits improved in 6 HBs and remained unchanged in all other HBs (n = 19), of which 16 had been asymptomatic before surgery. In the control group, 6 HBs (in 6 different patients) became permanently symptomatic despite subsequent surgical treatment according to the study protocol. INTERPRETATIONS: With the new diagnostic tools now available, microsurgical removal of spinal hemangioblastomas has a low morbidity rate, suggesting that surgical treatment should be considered even for asymptomatic sHBs in certain circumstances. <> Department of Neurosurgery, Free University of Berlin, Germany.


46.          Gerhart KA, Johnson RL, Menconi J, Hoffman RE and Lammertse DP (1995). Utilization and effectiveness of methylprednisolone in a population- based sample of spinal cord injured persons. Paraplegia. 33 (6): 316-21. Summary: The announcement and publication of the second National Acute Spinal Cord Injury Study (NASCIS II) project's findings regarding the role of high dose methylprednisolone in improving neurological outcomes following acute traumatic spinal cord injury generated widespread excitement and interest. To determine the association between this interest and actual use and implementation of the protocol, Colorado's comprehensive population-based spinal cord injury surveillance data were examined. The medical records of 218 SCI survivors injured between May 1, 1990 and December 31, 1991, and of 145 persons spinal cord injured 2 years later, during 1993, were reviewed to determine the rapidity and extent of NASCIS II implementation by Colorado's hospitals, factors associated with use and non-use of the protocol, changing usage trends over time, and the short term neurological outcomes of patients who received the protocol. Clear documentation of the protocol's usage was present for only 46% of the reported patients' medical records in 1990-91, and 61% in 1993. Small, emergency triage facilities were significantly more likely to use the protocol than larger acute care hospitals, and patients with initially incomplete injuries were less likely to receive the drug. There were no significant differences in neurological outcomes, using the Frankel classification system, between those who received the protocol and those who did not. The limitations and implications of these findings are discussed. <> Craig Hospital, Rocky Mountain Regional Spinal Injury System, Englewood, Colorado, USA.


47.          Botel U, Glaser E and Niedeggen A (1997). The surgical treatment of acute spinal paralysed patients. Spinal Cord. 35 (7): 420-8. Summary: Following the basic principles of Sir Ludwig Guttmann in respect of the comprehensive care and management of spinal cord injured patients, the German SCI centers try to admit those freshly injured preferably on the first day of onset, providing spinal surgery and intensive care. In our series of recent comprehensive spinal paralysed patients admitted from Jan 1st 1993 to Dec 31st 1995 178 patients requested operative decompression and stabilization out of a total of 255 patients. 51.4% of the patients had been operated within the first 24 h, but 10.5% later than 2 weeks. A high incidence of reoperations (45.2%) must be noted in cases operated prior to the admittance to the SCI center due to failures of instrumentation or lack of anterior reconstruction. Nineteen patients with various spinal tumors underwent surgical treatment, and seven patients with spondylitis and severe neurological deficit. Only 64.4% of the 1st day admissions came in time for administration of high dose methylprednisolone according to the NASCIS II study. The additional pelvic and long bone fractures were operated on following the principles of the Swiss AO, thus achieving immediate mobilization as was also possible after surgical spine stabilization. Neurological recovery could only be found in those with incomplete lesions in more than 50% but also two with neurological deterioration had to be accepted in the paraplegic cohort. Eight who were tetraplegic and 14 with paraplegia died within the first 3 months, but nine with paraplegia had a tumor or spondylitis. <> Department of Neurotraumatology and Spinal Cord Injuries, BG Kliniken Bergmannsheil, University Hospital, Bochum, Germany.


48.          Gabler C and Maier R (1995). [Clinical experiences and results of high-dosage methylprednisolone therapy in spinal cord trauma 1991 to 1993]. Unfallchirurgie. 21 (1): 20-9. Summary: Studies in animals and especially the NASCIS II study illustrated the neuroprotective effects of methylprednisolone, but they are disputed. At the University Clinic of Traumatology, Vienna, 31 patients with spinal cord injuries were given methylprednisolone as a bolus of 30 mg/kg body weight followed by a maintenance dose of 5.4 mg/kg body weight/h for another 23 hours. Twenty-seven patients were stabilised within 8 hours, 2 patients were not operated on, because of their low prognosis. Two patients could be treated conservatively, because the spinal fractures were supposed to be stabile. Then follow-up studies of these patients were between 1 and 3.2 years. All patients (100%) with incomplete neurologic deficits (n = 18) showed a significant recovery and even 3 patients (23.1%) with primarily a complete tetraplegia (n = 13) showed a nearly entire recovery. Compared to these results we look back at 113 patients with complete and incomplete neurologic deficits who were treated at the I. University Clinic of Traumatology, Vienna, and would have got methylprednisolone following our current management procedures. <> Universitatsklinik fur Unfallchirurgie, Wien.


49.          Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M and Yamada H (2001). Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury. Spine. 26 (4): 426-30. Summary: STUDY DESIGN: A prospective, randomized, and double-blind study comparing high-dose methylprednisolone sodium succinate (MPSS) with placebo, in the treatment of patients with acute cervical spinal cord injury. OBJECTIVES: To evaluate the complications of high-dose MPSS in patients with acute cervical spinal cord injury when administered within 8 hours of injury. SUMMARY OF BACKGROUND DATA: High-dose therapy with MPSS has been demonstrated to improve the recovery of motor function in patients with acute cervical spinal cord injury. However, little is known about the follow-up complications. METHODS: Forty-six patients, 42 men and 4 women (mean age, 60.6 years; range, 18-84), were included in the study: 23 in the MPSS group and 23 in the placebo group. They were treated without surgery for spinal cord injury in the cervical spine, and were enrolled in the trial if a diagnosis had been made and treatment had begun within 8 hours. Complications of high-dose therapy with MPSS were compared with placebo treatment throughout the study period and up to 2 months after injury. RESULTS: The MPSS group had 13 patients (56.5%) with complications, whereas the placebo group had 8 (34.8%). The difference between the two groups was not statistically significant (P = 0.139). There were eight instances of pulmonary complication with MPSS (34.8%) and one instance (4.34%) with placebo (P = 0.009). There were four instances of gastrointestinal complication (17.4%) with MPSS and none with placebo (P = 0.036). Pulmonary (complications were more prevalent in patients aged more than 60 years (P = 0.029). CONCLUSION: Aged patients with cervical spinal injury may be more likely to have pulmonary side effects (P = 0.029) after high-dose therapy with MPSS and thus deserve special care. <> Department of Orthopaedic Surgery, Wakayama Medical College, Wakayama City, Wakayama, Japan.


50.          Hasse W, Weidtmann A and Voeltz P (2000). [Lactic acidosis: a complication of spinal cord injury in multiple trauma]. Unfallchirurg. 103 (6): 495-8. Summary: Large-dose methylprednisolone has been advocated to lessen neurologic deficits in spinal cord injury for nearly a decade despite confounding statistical results in the Second National Acute Spinal Cord Injury Study (NASCIS-2). Recent retrospective studies found lack of significant functional improvement, increases in the incidence of infectious complications and an increase in ventilated and intensive care days in steroid-treated groups. We report on five cases with severe hyperglycemia and nonketotic metabolic acidosis in otherwise non- diabetic patients with multiple blunt injuries and an associated spinal cord injury. Those adverse effects were induced by epinephrine and aggravated by methylprednisolone. We conclude that high-dose methylprednisolone should be avoided in multiple injured or otherwise compromised patients potentially needing catecholamine support. <> Abteilung fur Anasthesie, Intensiv- und Rettungsmedizin, Berufsgenossenschaftliches Unfallkrankenhaus Hamburg.


51.          Gerndt SJ, Rodriguez JL, Pawlik JW, Taheri PA, Wahl WL, Micheals AJ and Papadopoulos SM (1997). Consequences of high-dose steroid therapy for acute spinal cord injury. J Trauma. 42 (2): 279-84. Summary: OBJECTIVE: High-dose Solu-Medrol (Upjohn, Kalamazoo, Mich) therapy has become standard care in the management of acute spinal cord injury (ASCI). This study attempts to define the adverse effects that Solu- Medrol therapy has on these patients. DESIGN: Retrospective review with historical control. MATERIALS AND METHODS: From May 1990 to April 1994, all patients with ASCI admitted within 8 hours of injury received high- dose Solu-Medrol per the National Acute Spinal Injury Study (NASCIS-2) protocol. Their demographic and outcome parameters were compared with those of a group admitted from March 1986 to December 1993 with an associated ASCI who received no steroid therapy. MEASUREMENTS AND MAIN RESULTS: Steroid therapy was associated with a 2.6-fold increase in the incidence of pneumonia and an increase in ventilated and intensive care days. However, it was associated with a decrease in duration of rehabilitation and had no significant impact on other outcome parameters, including mortality. CONCLUSIONS: Although the NASCIS-2 protocol may promote early infectious complications, it has no adverse impact on long-term outcome in patients with ASCIs. <> Division of Trauma, Burn, and Emergency Surgery, University of Michigan, Ann Arbor, USA.


52.          Sauerland S, Nagelschmidt M, Mallmann P and Neugebauer EA (2000). Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review. Drug Saf. 23 (5): 449-61. Summary: BACKGROUND: A single preoperative high dose of methylprednisolone (15 to 30 mg/kg) has been advocated in surgery, because it may inhibit the surgical stress response and thereby improve postoperative outcome and convalescence. However, these potential clinical benefits must be weighed against possible adverse effects. OBJECTIVE: To conduct a risk- benefit analysis using a meta-analysis, to compare complication rates and clinical advantages associated with the use of high dose methylprednisolone in surgical patients. METHODS: Randomised controlled trials of high dose methylprednisolone in elective and trauma surgery were systematically searched for in various literature databases. Outcome data on adverse effects, postoperative pain and hospital stay were extracted and statistically pooled in fixed-effects meta-analyses. RESULTS: We located 51 studies in elective cardiac and noncardiac surgery, as well as traumatology. Pooled data failed to show any significant increase in complication rates. In patients treated with corticosteroids, nonsignificantly more gastrointestinal bleeding and wound complications were observed; the 95% confidence interval boundaries of the numbers-needed-to-harm were 59 and 38, respectively. The only significant finding was a reduction of pulmonary complications (risk difference -3.5%; 95% confidence interval -1.0 to -6.1), mainly in trauma patients. CONCLUSION: For patients undergoing surgical procedures, a perioperative single-shot administration of high dose methylprednisolone is not associated with a significant increase in the incidence of adverse effects. In patients with multiple fractures, limited evidence suggests promising benefits of glucocorticoids on pulmonary complications. <> 2nd Department of Surgery, University of Cologne, Germany.


53.          Slavc I, Urban C, Schwingshandl J, Ritter G and Trauner R (1987). [Aseptic bone necroses as a late complication following successful treatment of leukemias and severe aplastic anemia]. Klin Padiatr. 199 (6): 449-52. Summary: Aseptic bone necrosis is a well known complication after corticosteroid treatment in adults and several hundred cases have been reported. Alterations in fat metabolism with vascular occlusion due to fat embolization, as well as microtraumata and osteoporosis are discussed as etiologic factors. In contrast, aseptic bone necrosis in relation to corticosteroid treatment is rare in children and adolescents. We therefore report 3 patients, aged from 10 to 18 years, suffering from severe aplastic anemia, meningeal relapse after acute lymphocytic leukemia and acute myelocytic leukemia respectively, who developed aseptic bone necrosis 6, 11, and 20 months following the onset of corticoid therapy. The patients survive from 28+ to 50+ months after diagnosis of their initial hematologic disease, as it can be expected today for increasing numbers of patients. We therefore believe, that aseptic bone necrosis may represent a serious therapy related complication and suggest that, diagnostic examination in patients with suspicious complaints of the hip, shoulder or knee should also exclude the possibility of a bone necrosis after leucemic relapse has been ruled out. Since radiological changes only develop several weeks to months after the onset of the clinical symptoms and because of the disabling consequences for patients, misdiagnosed at the beginning, a 99 technetium bone scan should be done as early as possible. Corticosteroids, despite their serious side effects are still being considered as a important part of hematologic therapy and are not being omitted in the near future, so that the earliest possible diagnosis of bone necrosis will remain of great importance.(ABSTRACT TRUNCATED AT 250 WORDS). <> Universitats-Kinderklinik Graz.


54.          Wing PC, Nance P, Connell DG and Gagnon F (1998). Risk of avascular necrosis following short term megadose methylprednisolone treatment. Spinal Cord. 36 (9): 633-6. Summary: We conducted a prospective cohort study to determine whether administration of large doses of the corticosteroid methylprednisolone following spinal cord injury as recommended in the National Acute Spinal Cord Injury Study-2 (NASCIS-2) protocol results in an increased incidence of avascular necrosis (AVN) of the femoral or humeral head. All subjects were patients treated by a spinal cord injury physician in an Acute Spinal Cord Injury Unit between 1989 and 1996 where some received the megadose steroids while others did not. Patients younger than 15 years and older than 75 years were excluded, as were those with any hip or shoulder disease, with pelvic fracture, or with a history of predisposition to AVN by hip dislocation, excessive alcohol consumption, previous high dose steroid use, or systemic lupus erythematosus. Screening for AVN of the femoral and humeral heads was performed at a minimum of 6 months following injury, using magnetic resonance imaging (MRI). The films were read by a radiologist blinded to the treatment protocol received by the individual subject. Among the 59 spinal cord injured patients who received steroids (age 15-64 years (mean 32 years)), five were female. Among the 32 spinal cord injured subjects who did not receive steroids (age 16 to 65 years (mean 34 years)), seven were female. There was no case of AVN found in either group. Using binomial distribution, we conclude that the true incidence of AVN among the methylprednisolone treated group is less than 5% (alpha < 0.05) and therefore continue to recommend short term (24 h) methylprednisolone therapy. <> Vancouver Hospital and Health Sciences Centre, BC, Canada.


55.          Qian T, Campagnolo D and Kirshblum S (2000). High-dose methylprednisolone may do more harm for spinal cord injury. Med Hypotheses. 55 (5): 452-3. Summary: Because of the National Acute Spinal Cord Injury Studies (NASCIS), high- dose methylprednisolone became the standard of care for the acute spinal cord injury. In the NASCIS, there was no mention regarding the possibility of acute corticosteroid myopathy that high-dose methylprednisolone may cause. The dosage of methylprednisolone recommended by the NASCIS 3 is the highest dose of steroids ever being used during a 2-day period for any clinical condition. We hypothesize that it may cause some damage to the muscle of spinal cord injury patients. Further, steroid myopathy recovers naturally and the neurological improvement shown in the NASCIS may be just a recording of this natural motor recovery from the steroid myopathy, instead of any protection that methylprednisolone offers to the spinal cord injury. To our knowledge, this is the first discussion considering the possibility that the methylprednisolone recommended by NASCIS may cause acute corticosteroid myopathy. <> Department of Physical Medicine & Rehabilitation, UMDNJ - New Jersey Medical School, Newark, New Jersey, USA.


56.          Segal JL, Maltby BF, Langdorf MI, Jacobson R, Brunnemann SR and Jusko WJ (1998). Methylprednisolone disposition kinetics in patients with acute spinal cord injury. Pharmacotherapy. 18 (1): 16-22. Summary: STUDY OBJECTIVE: To evaluate the pharmacokinetics of high-dose methylprednisolone in patients with acute spinal cord injury (ASCI). DESIGN: Open-label study of consecutive patients with ASCI, and retrospective review of able-bodied controls. SETTING: Emergency Medicine Department of a large, urban, university-affiliated, tertiary care trauma center. PATIENTS: Eleven men with ASCI. INTERVENTIONS: Methylprednisolone sodium succinate 30 mg/kg intravenous bolus, followed by 5.4 mg/kg/hour for 23 hours, administered according to the second National Acute Spinal Cord Injury Study (NASCIS 2) protocol. MEASUREMENTS AND MAIN RESULTS: The total systemic clearance of methylprednisolone was significantly less in acutely injured patients (mean +/- SD 30.04 +/- 12.03 L/hr) than in historically reported able- bodied controls (44.70 +/- 4.90 L/hr). An inverse correlation between the neurologic level of injury and systemic clearance was seen. No differences in volume of distribution were discernible between patients (126.90 L) and controls (135.45 L). CONCLUSION: Patients with acute spinal cord injury administered methylprednisolone according to the NASCIS 2 protocol had an apparent decrease in total systemic clearance of the drug without a commensurate change in volume of distribution. Additional studies are warranted to confirm these findings and assess the potential impact of diminished clearance on the efficacy of the agent in ASCI. <> Medical and Spinal Cord Injury Service, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.


57.          Walker BE (1967). Induction of cleft palate in rabbits by several glucocorticoids. Proc Soc Exp Biol Med. 125 (4): 1281-4. Summary: <>


58.          Zawoiski EJ (1980). Effect of L-glutamic acid on glucocorticoid-induced cleft palate in gestating albino mice. Toxicol Appl Pharmacol. 56 (1): 23-7. Summary: <>


59.          Mossman RG and Conrad JT (1969). Oxytocic and modulating effects of water-soluble hydrocortisone and methylprednisolone upon in vitro contractions of myometrium. Am J Obstet Gynecol. 105 (6): 897-908. Summary: <>


60.          Somodi Z (1983). [Steroid therapy of the mother, dextrocardia and developmental anomalies in the offspring]. Orv Hetil. 124 (48): 2935-6. Summary: <>


61.          Besedovsky HO (1971). [Influence of administration of glucocorticoids on the development of lymphoid organs in pregnant rats]. Sangre. 16 (4): 371-6. Summary: <>


62.          Scott JR, Feldbush TL and Covault JM (1977). A study of maternal lymphoid organs and the progeny following treatment with immunomodulating agents during pregnancy. Clin Exp Immunol. 30 (3): 393-402. Summary: Whether differences in foetoplacental weight and post-implantation mortality in rodents are secondary to heterosis and inbreeding depression or antigenic differences between mother and foetus has been a continuing controversy. To determine whether non-specific depression or stimulation of the maternal immune system affects the success of the foetoplacental allograft, groups of virgin Fischer (Ag-B1) females of similar age and weight mated with DA (Ag-B4) males were treated with daily intraperitoneal injections of: (a) saline, (b) methylprednisolone (MP), 1-0 mg/kg, (c) cyclophosphamide (CY), 3.0 mg/kg, or (d) azathioprine (AZ), 3.0 mg/kg; or they were injected intraperitoneally on the fifth day of gestation with: (a) B. pertussis, 1.0 ml, (b) C. parvum, 0.2 ml, or (c) BCG, 0.1 ml. None of the immunostimulating agents were detrimental to the progeny, but the immunosupprissive drugs caused an increased percentage of foetal deaths and foetoplacental growth retardation. The reduced foetal and placental size induced by CY or AZ could be partially blocked by simultaneous maternal treatment with BCG. Analysis of mean maternal weight gain, spleen weight assays, changes in the lymph nodes draining the uterus and comparison of data from non-pregnant animals and syngeneic pregnancies treated with these agents suggest that immunosuppressive drugs reduce foetal survival rates and produce foetoplacental growth retardation via a combination of immunological and cytotoxic mechanisms. <>


63.          Scott JR (1977). The effect of immunosuppressive drugs and immunostimulating agents on reproductive performance. Transplant Proc. 9 (2): 1403-7. Summary: <>


64.          Tauesch HW, Jr., Avery ME and Sugg J (1972). Premature delivery without accelerated lung development in fetal lambs treated with long-acting methylprednisolone. Biol Neonate. 20 (1): 85-92. Summary: <>


65.          Hagg DD and Schiltz RA (1973). Effect of intramammary corticosteroid administration during late gestation in cattle. Mod Vet Pract. 54 (5): 29 passim. Summary: <>


66.          Eckert H, Gerner R, Schulz J, Wernicke K, von L and Halberstadt E (1975). [Influence of corticoids on fetal lung maturity]. Arch Gynakol. 219 (1-4): 331-3. Summary: <>


67.          Gerner R and Halberstadt E (1976). [Experimental investigations in regard to the optimal stimulation of lecithin synthesis in the fetal lung via glucocorticoids (author's transl)]. Z Geburtshilfe Perinatol. 180 (3): 189-93. Summary: On the basis of curves illustrating the effects of dosage on experimental animals, it was shown that glucocorticoids inhibit as well as stimulate lecithin synthesis in the fetal lung. Equivalent doses of corticoids produce comparable results. It was established that the concentration necessary to produce an optimal stimulation of lecithin synthesis was 0.5 to 2.0 mg/kg body weight. <>


68.          Gerner R, Halberstadt E and Fortmeyer HP (1976). [In vivo and in vitro investigations of the effect of decortilen (16- methylenprednisolone) on lecithin synthesis in the fetal lung (author's transl)]. Z Geburtshilfe Perinatol. 180 (3): 183-8. Summary: Lecithin synthesis in fetal lungs of the rat over three-fold methylation and over choline and CDP-choline was quantitatively determined via the incorporation rate of marked metabolites. The ability of decortilen to influence both modes of synthesis was investigated. In vivo and in vitro, the glucocorticoid stimulates lecithin formation, which can be as high as 200%, only over choline and CDP-choline. <>


69.          Johnson JW, Eddy GA and Pedersen CE, Jr. (1976). Biological properties of the M-44 strain of Coxiella burneti. J Infect Dis. 133 (3): 334-8. Summary: The attenuated M-44 strain of Coxiella burneti was investigated for biological characteristics affecting its use as a live vaccine. After 25 serial passages in guinea pigs, the strain did not develop phase I properties detectable by the microagglutination test. Infectious organisms were not detected in untreated guinea pigs later than 12 weeks after inoculation; however, infection could be reactivated at later times by the production of stress (by pregnancy or drug treatment) in guinea pigs that had recovered. Evidence of reactivated infection was observed in recovered pregnant animals just before parturition at 46 weeks after infection, in methyl prednisolone-treated animals at 56 weeks, and in cyclophosphamide-treated guinea pigs at 96 weeks. A low rate of intercage and intracage infection was recorded. <>


70.          Dubey JP and Lindsay DS (1990). Neosporosis in dogs. Vet Parasitol. 36 (1-2): 147-51. Summary: A bitch was inoculated subcutaneously and intramuscularly with Neospora caninum tachyzoites on Day 35 of pregnancy. Eight pups were born 28 days later. Five pups became ill and necropsies were performed before 20 days of age. Three pups and the bitch remained clinically normal for 7 weeks after parturition when they were intramuscularly injected with 40 mg kg-1 methylprednisolone acetate weekly to activate chronic N. caninum infection. Necropsies were performed 48, 17, 18, and 18 days respectively after administration of corticosteroids. Hepatic necrosis, pneumonia, encephalomyelitis, and myonecrosis were the main changes seen in these dogs. <> U.S. Department of Agriculture, Livestock and Poultry Sciences Institute, Beltsville, MD 20705.


71.          Zucconi G and Pannuti P (1967). [Hyperemesis in the first trimester of pregnancy: causes and therapeutic advances]. Osp Ital Chir. 17 (6): 719-26. Summary: <>


72.          Iwamoto Y, Okuda B, Miyata Y, Tachibana H and Sugita M (1994). [Beneficial effect of steroid pulse therapy on Wernicke-Korsakoff syndrome due to hyperemesis gravidarum]. Rinsho Shinkeigaku. 34 (6): 599-601. Summary: A 25-year-old woman suffered from hyperemesis gravidarum when she was seven weeks pregnant. Since her vomiting continued, she received intravenous dextrose and electrolytes without thiamine in a hospital. One month later, she developed gait disturbance, followed by confusion and dysarthria. On admission to our department, she was confusional and had ataxic dysarthria. Spontaneous and gaze evoked nystagmus was present. Limb coordination was bilaterally ataxic. Based on her clinical course and symptoms, she was diagnosed as having Wernicke's encephalopathy. From the admission day, intravenous infusion of vitamin B1 (600 mg/day) was started. A few days later, her consciousness and limb ataxia began to improve. However, truncal ataxia and polyneuropathy became evident. Eight weeks after onset, she developed Korsakoff's psychosis such as anterograde and retrograde amnesia, disorientation and confabulation. We administered large amounts of corticosteroid (methylprednisolone 500 mg/day) in order to reduce brain edema or stabilize the impaired blood-brain barrier. Soon after, her psychosis began to improve gradually. She recovered remarkably from the psychosis, but she was left with persistent nystagmus, mild ataxic gait and polyneuropathy. The present case suggests that corticosteroid may have the beneficial effect on Wernicke-Korsakoff syndrome. <> Fifth Department of Internal Medicine, Hyogo College of Medicine.


73.          Safari HR, Fassett MJ, Souter IC, Alsulyman OM and Goodwin TM (1998). The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am J Obstet Gynecol. 179 (4): 921-4. Summary: OBJECTIVE: The study compared the efficacy of methylprednisolone with that of promethazine for the treatment of hyperemesis gravidarum. STUDY DESIGN: Patients with a normal-appearing intrauterine pregnancy of < or = 16 weeks' gestation with hyperemesis gravidarum (persistent vomiting and large ketonuria despite outpatient therapy) were admitted to the hospital for continuous intravenous hydration and offered participation in the study. Patients meeting study criteria were randomly assigned to receive (from identical-appearing dispensers packaged in advance with a 2-week supply) oral methylprednisolone, 16 mg 3 times daily, or oral promethazine, 25 mg 3 times daily. After 3 days the methylprednisolone was tapered completely during the course of 2 weeks whereas the promethazine was continued without change for 2 weeks. For patients who continued to vomit after 2 days the study medication was discontinued. Patients receiving study medication at discharge continued to take the remainder of the assigned medication from the packaged pill dispensers. Patients were followed up weekly. The study outcomes, as established in advance, were (1) improvement of symptoms within 2 days of starting therapy and (2) readmission for hyperemesis within 2 weeks of starting the study. RESULTS: Forty patients were enrolled in the course of 11 months (20 per group). There were no significant differences between the groups with respect to maternal age, gravidity, parity, gestational age at entry, number of previous admissions, or > 5% body weight loss. Three patients in the methylprednisolone group and 2 in the promethazine group failed to stop vomiting within 2 days. One patient from the promethazine group was unavailable for follow-up. No patient from the methylprednisolone group but 5 of the 17 patients receiving promethazine were readmitted for hyperemesis within 2 weeks of discharge (P = .0001). There were no adverse effects noted for either drug. CONCLUSION: A short course of methylprednisolone is more effective than promethazine for the treatment of hyperemesis. <> Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, USA.


74.          Safari HR, Alsulyman OM, Gherman RB and Goodwin TM (1998). Experience with oral methylprednisolone in the treatment of refractory hyperemesis gravidarum. Am J Obstet Gynecol. 178 (5): 1054-8. Summary: OBJECTIVE: Our purpose was to describe the effect of oral methylprednisolone on the course of refractory hyperemesis gravidarum. STUDY DESIGN: Patients with intractable hyperemesis gravidarum were candidates for oral methylprednisolone. Forty-eight milligrams per day was given for 3 days followed by a tapering dose over 2 weeks. If vomiting recurred after 2 weeks of therapy or during tapering, the medication was restarted or extended but not longer than 1 month total. RESULTS: Seventeen of 18 patients (94%) were free of vomiting and were able to tolerate a regular diet within 3 days. Seven did not have further symptoms during their pregnancies. Nine vomited during or after tapering, but 7 of these responded to extension or reinstitution of therapy. Four of 6 patients on total parenteral nutrition at the start of therapy had a complete response within 3 days. CONCLUSIONS: A short course of oral methylprednisolone appears to be a reasonable therapeutic alternative for intractable hyperemesis. <> Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, USA.


75.          Subramaniam R, Soh EB, Dhillon HK and Abidin HZ (1998). Total parenteral nutrition (TPN) and steroid usage in the management of hyperemesis gravidarum. Aust N Z J Obstet Gynaecol. 38 (3): 339-41. Summary: <> Department of Obstetrics and Gynaecology, University of Malaya Medical Centre, Kuala Lumpur, West Malaysia.


76.          Froud PJ and Henderson AH (1971). The treatment of Wegener's granulomatosis with immunosuppressive- cytotoxic drugs. J Laryngol Otol. 85 (7): 703-10. Summary: <>


77.          Fields CL, Ossorio MA, Roy TM and Bunke CM (1991). Wegener's granulomatosis complicated by pregnancy. A case report. J Reprod Med. 36 (6): 463-6. Summary: A 23-year-old woman who presented in the 17th week of her third intrauterine pregnancy was diagnosed as having active Wegener's granulomatosis. Therapy, consisting of corticosteroids, cyclophosphamide and hemodialysis, was instituted and maintained until delivery. Although Wegener's granulomatosis complicated by pregnancy has been reported previously, this is the first reported patient to be treated successfully with the above agents during the second and third trimesters without apparent harm to her or her infant. <> Division of Respiratory and Environmental Medicine, University of Louisville School of Medicine, Kentucky 40292.


78.          Luisiri P, Lance NJ and Curran JJ (1997). Wegener's granulomatosis in pregnancy. Arthritis Rheum. 40 (7): 1354-60. Summary: This report describes a case of severe limited Wegener's granulomatosis (WG) presenting in the third trimester of pregnancy with pansinusitis and necrotizing pneumonitis. The patient was treated successfully with a combination of corticosteroids and cyclophosphamide (CYC). The outcomes in the mother and the newborn were excellent. In a review of the English-language literature, we found 10 similar cases of WG with 13 pregnancies. WG occurring during pregnancy may have a more aggressive course and may require more aggressive treatment compared with WG occurring at other times. The treatment options for WG in pregnancy are discussed. <> University of Chicago, Illinois 60637, USA.


79.          Crocker IP, Baker PN and Fletcher J (2000). Neutrophil function in pregnancy and rheumatoid arthritis. Ann Rheum Dis. 59 (7): 555-64. Summary: BACKGROUND: Pregnancy exerts suppressive effects on rheumatoid arthritis (RA). An attenuation in neutrophil function in late pregnancy which may explain this amelioration has previously been reported. OBJECTIVE: A longitudinal investigation of neutrophil activity in healthy pregnant women (n=9) and pregnant patients with RA (n=9), compared with age matched non-pregnant patients with RA (n=12) and healthy controls (n=22). METHODS: Neutrophil activation was measured in response to the physiological receptor agonists, n-formyl-methionyl- leucyl-phenylalanine (fMLP) and zymosan activated serum (ZAS). Superoxide anion production (respiratory burst) was determined by lucigenin enhanced chemiluminescence (LUCL); secondary granule lactoferrin release by enzyme linked immunosorbent assay (ELISA); and CD11b, CD18, and CD62L expression by flow cytometric analysis. RESULTS: Stimulated neutrophil LUCL was significantly reduced in both pregnant women with RA and healthy pregnant women in the second (fMLP 43% and 69%, ZAS 43% and 59%, respectively) and third trimesters (fMLP 24% and 44%, ZAS 32% and 38%, respectively). Responses returned to normal within eight weeks of delivery and unstimulated levels remained unchanged throughout pregnancy. Basal and stimulated CD11b, CD18, and CD62L expression showed no variations throughout gestation for both pregnancy groups. Likewise, stimulated lactoferrin release and plasma lactoferrin remained unchanged. Certain morphological differences in RA neutrophils were highlighted by the flow cytometric analysis. Moreover, resting neutrophils and stimulated cells from patients with RA, including pregnant subjects, showed a marked increase in LUCL, but a reduction in CD11b, CD18, and CD62L. Low dose prednisolone and methylprednisolone had no effect on neutrophil parameters over the period of treatment with non-steroidal anti-inflammatory drugs. CONCLUSION: The attenuation to neutrophil respiratory burst in both healthy and RA pregnancies may offer an explanation for the pregnancy induced remission of this inflammatory disorder. <> The Medical Research Centre, Nottingham University, Nottingham City Hospital NHS Trust, Hucknall Road, Nottingham NG5 1PB, UK.


80.          Weitgasser H (1972). [Long-term corticoid therapy in dermatology]. Arch Dermatol Forsch. 244: 403-5. Summary: <>


81.          Harris A, Webley M, Usherwood M and Burge S (1995). Dermatomyositis presenting in pregnancy. Br J Dermatol. 133 (5): 783-5. Summary: We report the onset of dermatomyositis in a woman pregnant 38-weeks who subsequently delivered a healthy infant. The disease improved rapidly following delivery. The association of dermatomyositis with pregnancy is unusual, and fetal outcome may be adversely affected. <> Department of Dermatology, Stoke Mandeville Hospital NHS Trust, Aylesbury, Bucks, U.K.


82.          Virgili A, Corazza M, Vesce F, Garutti P, Mollica G and Califano A (1995). Pemphigus in pregnancy. Acta Derm Venereol. 75 (2): 172-3. Summary: <>


83.          Henson TH, Tuli M, Bushore D and Talanin NY (2000). Recurrent pustular rash in a pregnant woman. Arch Dermatol. 136 (8): 1055-60. Summary: <> University of Tennessee, Memphis, USA.


84.          Wood L and Jacobs P (1989). Emergency caesarean section and symptomatic immune thrombocytopenic purpura. Am J Hematol. 31 (1): 67-8. Summary: A 24-year-old woman presented in labour with profound purpuric bleeding due to idiopathic immune thrombocytopenia. She was assessed as requiring immediate caesarean section for cephalopelvic disproportion and foetal distress. In view of her platelet count of 21 x 10(9)/L she was prepared with intravenous methylprednisolone, isovolaemic plasma exchange, and infusion of 400 mg/kg of gammaglobulin and 5 x 10(11) allogeneic platelets. Six hours after commencing the procedure, at a time when her platelet count was 97 x 11(9)/L, she went uneventful operation and with no further therapy this level subsequently reached 175 x 10(9)/L, at which time an uneventful operation was performed. The mother and her normal, full-term infant have been discharged; both are well and at follow-up have normal platelet counts. This experience illustrates that major surgery can safely be undertaken in severely thrombocytopenic patients, even as an emergency procedure, using this regimen. <> University of Cape Town Leukaemia Centre, South Africa.


85.          Brown HM and Storey G (1975). Treatment of allergy of the respiratory tract with beclomethasone dipropionate steroid aerosol. Postgrad Med J. 51 (Suppl 4): 59-64. Summary: <>


86.          Wendel PJ, Ramin SM, Barnett-Hamm C, Rowe TF and Cunningham FG (1996). Asthma treatment in pregnancy: a randomized controlled study. Am J Obstet Gynecol. 175 (1): 150-4. Summary: OBJECTIVE: Our purpose was to study the effect of inhaled corticosteroids on asthma exacerbations in pregnancy. STUDY DESIGN: We prospectively studied 84 pregnant women with 105 asthma exacerbations. Women were hospitalized if the forced expiratory volume in 1 second was < 70% after sequential bronchodilator therapy. They were randomly assigned to receive either intravenous aminophylline and inhaled beta 2- adrenergic receptor agonist or intravenous methylprednisolone and a beta 2-adrenergic receptor agonist. At discharge women were randomly assigned to receive either inhaled beclomethasone, beta 2-adrenergic receptor agonist, and an oral corticosteroid taper or a beta 2- adrenergic receptor agonist and a corticosteroid taper. RESULTS: Sixty- five (62%) of 105 women with exacerbation required hospitalization. Aminophylline did not shorten response time or decrease hospital stay. Readmission rate was decreased by 55% in women given inhaled beclomethasone (33% vs 12%, p < 0.05, odds ratio 3.63, 95% confidence interval 1.01 to 13.08). Pregnancy-induced hypertension and cesarean delivery were increased over those of the general population. CONCLUSIONS: Intravenous aminophylline offers no therapeutic advantages. Continuous inhaled corticosteroids reduced the need for subsequent admissions. <> Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, USA.


87.          Schatz M (1997). Asthma treatment during pregnancy. What can be safely taken? Drug Saf. 16 (5): 342-50. Summary: 'Safe' pharmacological therapy for gestational asthma is defined as therapy during which the apparent risks of the drug appear to be lower than the maternal and potential fetal risks of uncontrolled asthma that could result if the drug were not used. Major malformations occur in 2 to 4% of all newborns, 1% of which can be attributed to medication in general. Information regarding the effects of drugs administered during pregnancy may come from animal studies, human case reports, and prospective cohort studies. Based on a review of the available information, it is recommended that mild asthma during pregnancy be managed with inhaled beta 2-agonists, as required; step therapy for moderate asthma would include inhaled sodium cromoglycate (cromolyn sodium), inhaled beclomethasone dipropionate and oral theophylline. Severe gestational asthma should be treated with oral corticosteroids at the lowest effective dosage. The pharmacological management of acute asthma during pregnancy should include nebulised beta 2-agonists and ipratropium bromide, and intravenous methylprednisolone. Intravenous aminophylline would not generally be recommended, unless the patient requires hospitalisation. Optimal medical practice medico-legal considerations demand that the patient's informed consent be obtained for that recommended gestational management programme. <> Department of Allergy-Immunology, Kaiser-Permanente Medical Center, San Diego, California, USA.


88.          Ishikawa S, Takei Y, Maruyama T, Koyama S and Hanyu N (2000). [A case of polymyositis presenting pregnancy with acute respiratory failure]. Rinsho Shinkeigaku. 40 (2): 140-4. Summary: A 33-year-old pregnant woman developed respiratory difficulty with bilateral pleural effusion 31 weeks into gestation. On admission she had an elevated serum level of creatine kinase, but muscle weakness in the extremities was mild. After an immediate and successful Cesarean section, she developed respiratory failure and mechanical ventilation was required. The patient was diagnosed as having polymyositis from the limb muscle biopsy. She was treated with dexamethasone at a dose of 8 mg, methylprednisolone++, 1 g daily for three days, and then prednisolone 60 mg daily. One week later the serum level of creatine kinase was normalized and the patient was weaned from ventilator support. The dose of prednisolone was tapered 10 mg every week and she was discharged two months after delivery without prednisolone. A chest CT scan revealed no interstitial pneumonitis or aspiration pneumonia, so her respiratory failure seemed to be ascribable to polymyositis- related respiratory muscle weakness and pleural effusion. However, severe involvement of respiratory muscles without generalized marked muscle weakness is extremely rare, and pleural complications have usually been described in association with pulmonary parenchymal diseases. During the following two years polymyositis has not recurred in this patient and there have been no data indicative of other overlapping collagen diseases. Reports of polymyositis which occurred during pregnancy are rare, and the pathogenesis and clinical outcome of these patients need to be carefully investigated. <> Department of Neurology, Nagano Red Cross Hospital.


89.          Plauche WC (1980). Henoch-Schonlein (anaphylactoid) nephropathy in pregnancy. Obstet Gynecol. 56 (4): 515-7. Summary: A rare case of Henoch-Schonlein nephropathy in pregnancy is described. The course of the patient's stable nephrotic syndrome was unchanged in early and middle pregnancy. The early third trimester was complicated by superimposed pregnancy-induced hypertension and deterioration of renal and placental function. Methylprednisolone was employed to induce fetal pulmonary surfactant maturation in this high-risk obstetric case; premature delivery was required at 31 weeks' gestation. The 1320-g infant survived without respiratory distress syndrome. The mother tolerated surgery well and within a week after surgery was approaching her prepregnancy renal status. <>


90.          Komatsuda A, Wakui H, Yasuda T, Imai H, Miura AB, Tsuda A and Nakamoto Y (1994). Successful delivery in a pregnant women with crescentic IgA nephropathy. Intern Med. 33 (11): 723-6. Summary: A 27-year-old Japanese female developed nephrotic syndrome and impaired renal function during pregnancy. A renal biopsy performed at 21 weeks of gestation revealed crescentic IgA nephropathy. She was treated with steroid pulse therapy followed by conventional steroid therapy. Although the nephrotic syndrome was persistent, the impaired renal function did not deteriorate after the treatment. A live infant was delivered by cesarean section at 37 weeks of gestation. After the delivery, both the nephrotic syndrome and renal insufficiency improved gradually. The indications for renal biopsy and treatments for active IgA nephropathy during pregnancy are discussed. <> Third Department of Internal Medicine, Akita University School of Medicine.


91.          Chen HH, Lin HC, Yeh JC and Chen CP (2001). Renal biopsy in pregnancies complicated by undetermined renal disease. Acta Obstet Gynecol Scand. 80 (10): 888-93. Summary: BACKGROUND.: The aim of this retrospective study was to verify the role of renal biopsy in pregnancies complicated by renal dysfunction. METHODS.: A series of 15 percutaneous renal biopsies performed in 15 pregnant women with renal disease presenting during pregnancy over the past 10 years (1990-1999) were reviewed. RESULTS.: All the patients underwent renal biopsy before 30 weeks of gestation. The indications for renal biopsy were renal dysfunction of unknown cause or symptomatic nephrotic syndrome (NS). Patients with toxemia were excluded. Eight women had lupus nephritis, including five with diffuse crescenteric changes and three with a mesangial proliferative pattern. Three had chronic glomerulonephritis (CGN), two had mesangial proliferative glomerulonephritis and one each had diabetic nephrosclerosis and endocapillary proliferative glomerulonephritis. There were no significant complications except in one patient who experienced gross hematuria. Early induction of labor was recommended for the four patients with diabetic nephrosclerosis or CGM. The other 11 patients received intravenous pulse methylprednisolone or high dose oral prednisolone therapy. The responses to steroid therapy in these 11 patients were as follows: five achieved complete remission of NS, three achieved incomplete remission, and three achieved partial remission. After 2 years' follow-up, seven mothers achieved complete remission, three had died, three developed chronic renal failure (CRF), and two progressed to end stage renal failure (ESRF) requiring chronic hemodialysis. Fourteen of the 15 pregnancies resulted in live births and the other child was stillborn. CONCLUSIONS.: Renal biopsy performed during pregnancy is not contraindicated. The results of histopathological studies are extremely useful in counseling regarding continuation or termination of pregnancy, potential maternal and fetal outcome, and recommending specific therapeutic modalities. <> Departments of Nephrology,Mackay Memorial Hospital, and the National Taipei Nursing College Hospital, and the Department of Obstetrics and Gynecology, Mackay Memorial Hospital, all of Taipei, Taiwan, R.O.C.


92.          Horita Y, Tsunoda S, Inenaga T, Kawano Y, Ishibashi-Ueda H, Chiba Y and Takishita S (2001). Pregnancy outcome in nephrotic syndrome with mixed connective tissue disease. Nephron. 89 (3): 354-6. Summary: We describe two pregnancies of a young woman with mixed connective tissue disease. In June 1983, she was diagnosed as having Raynaud's phenomenon, arthralgia, and proteinuria. She then developed nephrotic syndrome. Methylprednisolone was initially prescribed at a large dose of 1 g/day which was slowly tapered to 5 mg/day. The proteinuria disappeared. During both pregnancies (the first beginning in December 1988 and the second in May 1992), the patient was placed on a prednisolone maintenance dose (5 mg/day). Both neonates were born healthy at term with no complications. Continuing prednisolone may be useful in pregnant women, and aggressive treatment to prevent mixed connective tissue disease exacerbation may be appropriate during pregnancy. <> Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, Osaka, Japan.


93.          Cesari M, Aieta M, Frejaville C, Fortuna A and Pulanco M (1982). [2 cases of idiopathic thrombopenic purpura in pregnancy]. Minerva Ginecol. 34 (1-2): 57-61. Summary: <>


94.          Berchtold P and McMillan R (1989). Therapy of chronic idiopathic thrombocytopenic purpura in adults. Blood. 74 (7): 2309-17. Summary: Chronic ITP is a common hematologic illness. Approximately three fourths of the patients respond to corticosteroids or splenectomy and need no further treatment. Patients refractory to these two therapeutic approaches are relatively resistant to present forms of treatment and are at much greater risk for morbidity and mortality. Future clinical studies evaluating therapy in this refractory group would be best performed in a cooperative group setting in which large numbers of patients could be treated in a prospective randomized manner. <> Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, La Jolla, CA 92037.


95.          Vianelli N, Gugliotta L, Catani L, Baravelli S and Tura S (1993). Thrombotic thrombocytopenic purpura: relapse and pregnancy. Haematologica. 78 (4): 259. Summary: <>


96.          Bachman WR and Brennan JK (1996). Refractory thrombotic thrombocytopenic purpura treated with cyclosporine. Am J Hematol. 51 (1): 93-4. Summary: <>


97.          Timuragaoglu A, Surucu F, Nalcaci M, Dincol G and Pekcelen Y (1997). Anemia and thrombocytopenia due to parvovirus B-19 infection in a pregnant woman. J Med. 28 (3-4): 245-9. Summary: Anemia and thrombocytopenia in a patient with parvovirus B-19 and hepatitis C infection is reported. A seven month-pregnant 20 year-old patient had been first found to be anemic and thrombocytopenic 40 days before admission to our hospital and she had been given methylprednisolone and red cell transfusions. She gave birth to a healthy baby after only eight months of pregnancy. Ten days after delivery she was admitted to our hospital because of anemia and thrombocytopenia which did not respond to treatment. On admission, the blood count showed hemoglobin 8.1 g/dL, hematocrit 23.7%, white blood cells 11,200/microL, platelets 1000/microL, and reticulocytes 0.6%. Bone marrow smear and biopsy revealed erythroblastopenia and the absence of megakaryocytes. Liver enzymes were also high (alanine aminotransferase 1469 Units/L and aspartate aminotransferase 981 Units/L). In serologic studies PVB-19 IgM was found to be positive and hepatitis C virus RNA was detected. Red cell and platelet values returned to normal levels after cessation of methylprednisolone and concomitantly PVB-19 IgG was found positive in association with IgM in repeated determinations. PVB-19 was thought to be responsible for both anemia and thrombocytopenia. <> Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Turkey.


98.          Mori Y, Wada H, Tamaki S, Minami N, Shiku H, Ihara T, Omine M and Kakisita E (1999). Outcome of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in Japan. Clin Appl Thromb Hemost. 5 (2): 110-2. Summary: We examined 159 patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in Japan. The subjects were divided in three groups; 90 patients with thrombotic thrombocytopenic purpura, 51 patients with verotoxin-induced hemolytic uremic syndrome, and 18 patients with drug-induced hemolytic uremic syndrome. Eighty-two percent of the patients with thrombotic thrombocytopenic purpura had associated neurological disorders and 78% of drug-induced hemolytic uremic syndrome associated with pulmonary edema. Renal insufficiency was noted in the 69% cases with both hemolytic uremic syndrome groups. Seventeen patients with thrombotic thrombocytopenic purpura had systemic lupus erythematosus and 6 were pregnant. Autoantibody were positive in 53% of thrombotic thrombocytopenic purpura. Seventy-seven percent of patients with thrombotic thrombocytopenic purpura received plasma exchange at 4,000 mL/day three times a week, 71% antithrombotic agents, and 78% steroid administration, respectively. However, 27% of the patients with hemolytic uremic syndrome were treated by hemodialysis in addition to antithrombotic agents. When drug-induced hemolytic uremic syndrome was diagnosed, the drug was immediately discontinued and the patients were treated with antiplatelet agents. Seventy-four percent of the patients with thrombotic thrombocytopenic purpura were alive at 26 weeks compared with 95% of those with hemolytic uremic syndrome. As thrombotic thrombocytopenic purpura had a high mortality rate in Japan, we should carry out early diagnosis and early treatment. <> Second Department of Internal Medicine, Mie University School of Medicine, Tsu-city, Japan.


99.          Widmer A, Bruhwiler H, Krause M and Luscher KP (1999). [Severe autoimmune thrombocytopenia in pregnancy]. Z Geburtshilfe Neonatol. 203 (6): 258-60. Summary: Maternal thrombocytopenia is a frequent finding in pregnancy. The clinically important causes of maternal thrombocytopenia in pregnancy are gestational thrombocytopenia and autoimmune thrombocytopenia. We report a case of refractory idiopathic thrombocytopenic purpura by a 30- year-old pregnant woman, gravida 3, para 2, successfully treated with high dose corticosteroids and immune globulins. <> Frauenklinik, Thurgauisches Kantonsspital, Munsterlingen.


100.      Radoncic E, Delmis J, Pfeifer D and Mayer D (2000). Successful treatment of alloimmune thrombocytopenia using corticosteroid therapy in a woman with two consecutive neonatal deaths-- case report. Acta Med Croatica. 54 (3): 125-7. Summary: Alloimmune thrombocytopenia is a serious fetal disorder resulting from platelet-antigen incompatibility between the mother and the fetus. In mild cases, the diagnosis is usually made upon detection of neonatal thrombocytopenia, but serious consequences such as fetal intracranial hemorrhage and/or unexplained fetal death may complicate the disorder. Various treatment modalities are suggested in the management of alloimmune thrombocytopenia, however, none has yet been confirmed as obviously superior. We report on the successful use of corticosteroids during pregnancy in a woman with a history of two consecutive neonatal deaths due to severe thrombocytopenia and HPA 5b platelet-specific antigen incompatibility. <> Modern Medical Centre, Schoool of Medicine, University of Zagreb, Zagreb, Croatia.


101.      Robak T, Olszanska-Skorek T, Krykowski E, Kasznicki M and Wilczynski J (1993). [Therapeutic problems during pregnancy and delivery in two women with aplastic anemia]. Acta Haematol Pol. 24 (2): 183-9. Summary: We have observed two cases of aplastic anaemia diagnosed during the second trimester of pregnancy. In both patients a cesarean section was performed (in 32 and 37 week of gestation). During the course of pregnancy the patients received transfusions of erythrocytes and platelets. In one case high doses of methylprednisolone were administered. The same patient was given immunoglobulins IV prior to the delivery and the number of platelets increased to 100 x 10(9)/L. One baby had respiratory distress syndrome and died 3 months after birth. The second baby is 9 months old now and is in good health. Haematological improvement did not occur post partum and immunosuppressive treatment with antithymocyte globulin and cyclosporine was performed in both patients. Despite of that remissions did not occur and one patient died 7 months after delivery. The second patient still has haematological problems and is red cell and platelet transfusion dependent. We discuss the pathogenetic aspects of aplastic anaemia occurring during pregnancy, as well as the therapeutic problems before and after delivery. <> II Kliniki Chorob Wewnetrznych AM, Lodzi.


102.      Futami H, Kodaira M, Furuta T, Hanai H and Kaneko E (1998). Pyoderma gangrenosum complicating ulcerative colitis: Successful treatment with methylprednisolone pulse therapy and cyclosporine. J Gastroenterol. 33 (3): 408-11. Summary: A 32-year-old woman with ulcerative colitis had a relapsed of pyoderma gangrenosum during puerperium. Both the pyoderma gangrenosum and ulcerative colitis had been well controlled with oral prednisolone, but ulcerative colitis relapsed in pregnancy, and pyoderma gangrenosum relapsed in the puerperium. The pyoderma gangrenosum responded to methylprednisolone pulse therapy initially, but relapsed when prednisolone was tapered. A second trial of pulse therapy combined with cyclosporine resulted in complete remission of the pyoderma gangrenosum, and no recurrence was recognized after prednisolone was tapered. This is a very rare case of successful treatment with methylprednisolone pulse therapy combined with cyclosporine for pyoderma gangrenosum complicating ulcerative colitis. <> First Department of Medicine, Hamamatsu University of Medicine, Japan.


103.      Bloechle M, Bollmann R, Chaoui R, Birnbaum M and Bartho S (1995). [Pregnancy in Takayasu arteritis]. Z Geburtshilfe Neonatol. 199 (3): 116-9. Summary: We report the course of pregnancy in a patient with Takayasu's arteritis type I and describe the diagnostical and therapeutical management with repeated Doppler-sonography. Immunosuppressive therapy was reduced in pregnancy and could be maintained on a low level even after delivery. In the third trimester arterial blood pressure raised up to 190/60 mm Hg and was sufficiently lowered by prescription of verapamil. Repeated Doppler-sonographic investigation beginning with 20 weeks of gestation revealed indices in the normal range during the whole pregnancy. After 37 weeks of gestation a healthy infant was delivered vaginally. The post partum course was uneventful. <> Universitatsfrauenklinik Charite, Humboldt-Universitat zu Berlin.


104.      Wislowska M (1999). Successful treatment of catastrophic antiphospholipid syndrome in a pregnant woman. Clin Exp Rheumatol. 17 (2): 261. Summary: <>


105.      Blanda A, Catinella M, Cigolotti AC and Gambaro P (1991). [Systemic lupus erythematosus and pregnancy. Report of a clinical case]. Minerva Ginecol. 43 (9): 415-8. Summary: After a review of the literature, we present a case of a twice-pregnant patient who, affected by SLE, had successful outcomes for the conceptuses with a therapy based on cloroquine first and corticosteroids subsequently. The two pregnancies, however, seemed to be correlated with the temporary exacerbation of disease activity. <> II Divisione di Ostetricia e Ginecologia, Ospedale Maggiore, Novara.


106.      Cameron JS (1991). Pathogenesis and treatment of lupus nephritis. Nippon Jinzo Gakkai Shi. 33 (5): 443-6. Summary: <> Renal Unit, Guy's Campus UMDS, London, UK.


107.      Oviasu E, Hicks J and Cameron JS (1991). The outcome of pregnancy in women with lupus nephritis. Lupus. 1 (1): 19-25. Summary: We analysed the outcome of pregnancy in patients with pre-existing lupus nephritis, seen in a tertiary referral centre for nephrology. Fifty-three pregnancies in 25 patients who already had clinical and histological evidence of lupus nephritis were recorded between January 1970 and June 1989, and data were analysed retrospectively. All 53 pregnancies occurred in patients with more or less stable disease, while three pregnancies during which lupus first presented were excluded. Six pregnancies were ended by therapeutic abortions (four for social reasons), and in eight spontaneous abortion occurred. Thus, 39 deliveries occurred, 28 at 36 weeks or more, while 11 were delivered prematurely, of which one was a stillbirth. After allowance was made for therapeutic abortions, the fetal loss rate (9/47) was 19%. Seventeen Caesarian sections were performed in the 39 completed pregnancies (44%), 11 as emergencies. Although the overall fetal loss, incidence of premature births and Caesarian section rate were all higher than expected for a population of normal women, neither initial histology, treated hypertension, the presence of proteinuria or a nephrotic syndrome showed statistically significant relationships with the outcome of completed pregnancies. In no case was maternal renal function affected irreversibly, although proteinuria increased substantially during pregnancy in six patients, and creatinine clearance fell during pregnancy, also in six patients. No 'flares' in systemic disease were seen, but all patients save five were treated with a brief period of high-dose oral corticosteroids or intravenous methylprednisolone in the postpartum period. No case of neonatal lupus or congenital heart block was observed.(ABSTRACT TRUNCATED AT 250 WORDS). <> Renal Unit, UMDS, London, UK.


108.      Cameron JS (1994). Lupus nephritis in childhood and adolescence. Pediatr Nephrol. 8 (2): 230-49. Summary: Lupus nephritis in childhood usually presents after the age of 10 years, and presentation under 5 years is very rare. More males (F:M ratio 4.5:1) are affected than in adult-onset cases, but the ratio is the same in prepubertal and pubertal children. The incidence of clinically evident renal disease is greater at onset than in adults (82%), the usual presentation being with proteinuria, 50% having a nephrotic syndrome. Half the children show World Health Organisation class IV nephritis in renal biopsies. Neuropsychiatric lupus is present at onset in 30%, may complicate 50% at some point and remains a major problem. Prognosis has improved greatly over the past 30 years, at least in part the result of immunosuppressive treatment. Treatment of the initial phase may be guided by the severity of the renal biopsy appearances, more aggressive treatment including cytotoxic agents, i.v. methylprednisolone and perhaps plasma exchange, although the value of exchange is not established. Controversy persists as to the most effective cytotoxic treatment in the acute phase, both oral and i.v. cyclophosphamide and azathioprine being used in different units. In the chronic maintenance phase it seems established both clinically and histologically that addition of a cytotoxic agent improves outcome, but again the drug and route of administration are contentious. Azathioprine has the advantage of being safe for pregnancy and not gonadotoxic, whilst i.v. cyclophosphamide has been demonstrated to improve results over prednisolone alone in controlled trials and has advantages in non-compliant patients. No trial comparing the two regimes has been carried out, and one is needed. Today children much less commonly go into renal failure, and the main causes of actual death (15% of patients over 10 years) are now infections and extra- renal manifestations of lupus, principally neurological. Morbidity of the disease and the treatment remain a major problem, especially when treatment exacerbates complications of the disease itself, such as infections, osteonecrosis, thrombosis, vascular disease and possibly neoplasia. <> Renal Unit, Guy's Hospital, London, UK.


109.      Tulokas S (1994). [The activation of lupus in pregnancy and its successful immunological treatment]. Duodecim. 110 (23-24): 2223-6. Summary: <> Tampereen yliopiston kliinisen laaketieteen laitos.


110.      Faedda R, Palomba D, Satta A, Pirisi M, Tanda F and Bartoli E (1995). Immunosuppressive treatment of the glomerulonephritis of systemic lupus. Clin Nephrol. 44 (6): 367-75. Summary: To evaluate the results, the long-term prognosis and the rates of complication of an immunosuppressive regimen with corticosteroids and cyclophosphamide in the treatment of the nephritis of systemic lupus erythematosus, 21 patients with lupus glomerulonephritis were studied. Renal biopsies were performed in 17/21 of them and indicated diffuse proliferative (6 patients), diffuse mesangial (4) and membranous (7) glomerulonephritis. Treatment was structured in 4 phases: 1) induction with methylprednisolone 250 mg i.v. for 7-14 days, and cyclophosphamide 100-200 mg p.o., q.d., or 20 mg/kg i.v. every 28 days; 2) maintenance with prednisone p.o., 2 mg/kg q.o.d. for 45 days, and cyclophosphamide as before; 3) tapering, with reduction of prednisone by 15% each month for 4 months; 4) indefinite maintenance with prednisone slowly tapered to the least effective q.o.d. dose and cyclophosphamide discontinued after six months of treatment. This cycle was repeated in the event of a relapse. After a first immunosuppressive cycle, 20/21 patients achieved remission of glomerulonephritis. Plasma creatinine fell from 97 +/- 6 to 80 +/- 3 microMol/l (p < 0.01). Proteinuria fell from 2.1 +/- 0.4 to 0.2 +/- 0.4 g/d (p < 0.0001) and the nephrotic syndrome, present in 8 patients, disappeared. After an average of 20 +/- 7 months, 8 patients relapsed: all remitted again after a repeat cycle, but 1 later progressed to end-stage renal failure during pregnancy. After an average of 56 months 4 out of these 8 patients relapsed again: 1 progressed to end-stage renal disease following an abortion and 3 remitted completely after a third cycle. Thus, 18 out of 21 patients are presently in remission with an average dose of prednisone of 13.7 mg/day after an average follow-up of 52 +/- 38 months (range 2 to 156). Three patients are presently off treatment. In 16 patients with extended follow-up of 2 to 13 years, anti-nuclear antibodies, anti-DNA antibodies, albuminuria and cylindruria fell below post-cycle levels (p < 0.001 for all). We conclude that intensive immunosuppression with steroids and cyclophosphamide can achieve excellent long-term results in the treatment of systemic lupus with glomerulonephritis. <> Istituto di Patologia Medica, Universita degli Studi, Sassari, Italy.


111.      Krane NK, Thakur V, Wood H and Meleg-Smith S (1995). Evaluation of lupus nephritis during pregnancy by renal biopsy. Am J Nephrol. 15 (3): 186-91. Summary: Patients with lupus nephritis frequently exhibit increasing proteinuria, hypertension and deterioration of renal function due to either active lupus nephritis, chronic lupus nephritis and/or superimposed preeclampsia during pregnancy. Percutaneous renal biopsies were therefore performed in 3 women with systemic lupus erythematosus during pregnancy and immediately postpartum in a fourth woman to evaluate their renal disease during pregnancy. Mean serum creatinine at renal biopsy was 2.9 mg/dl, with a mean creatinine clearance of 66 ml/min and protein excretion of 5.3 g/day. All patients had grade IV lupus nephritis and received pulse methylprednisolone immediately; 3 received cyclophosphamide. All 3 patients with crescent formation developed endstage renal disease within 3 years. The fourth patient has normal renal function 3 years after biopsy. Percutaneous renal biopsies during pregnancy in women with lupus nephritis provide an accurate histopathologic diagnosis and are important in providing appropriate therapy, counseling and prognosis. <> Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.


112.      Nishiyama S and Miyawaki S (1995). [Systemic lupus erythematosus and antiphospholipid antibody syndrome in a patient with congenital ichthyosiform erythroderma]. Ryumachi. 35 (4): 688-92. Summary: A 23-year-old woman, who had nonbullous congenital ichthyosiform erythroderma since her childhood, was diagnosed as nephrotic syndrome caused by systemic lupus erythematosus (SLE). She was pregnant but experienced fetal loss at the age of 25. Although 10 mg/day of oral prednisolone was administered, low levels of serum complement, proteinuria, thrombocytopenia (6.0 x 10(4)/mm3) and biological false positive for STS continued. When she was 27 years old, right hemichorea developed. She was admitted to our hospital at the age of 28 because of low levels of serum complement, high titers of anti ds-DNA antibody, profuse proteinuria, gingival bleeding and thrombocytopenia (1.5 x 10(4)/mm3). The nephrotic syndrome gradually improved after 1 g/day of methylprednisolone for 2 days and the oral prednisolone dosage was then increased up to 40 mg/day, and was tapered to 10 mg/day. Epileptic attack (minor seizure) occurred at the age of 29. Continuous low levels of serum complement and high titers of anti ds-DNA antibody were improved by adding 50 mg/day of cyclophosphamide. However, high levels of beta 2 GPI dependent anticardiolipin antibody and lupus anticoagulant activity were observed throughout the study. Our patient was a very rare case of congenital ichthyosis with typical antiphospholipid antibody syndrome and SLE. A few cases of acquired ichthyosis associated with SLE has been reported, and ichthyosis developed only in active stage of SLE. However, our patient's ichthyosiform lesions were not changed throughout the course. <> Center for Adult Diseases Kurashiki, Minami Kurashiki Hospital, Rheumatic Diseases Center.


113.      Meleg-Smith S and Krane NK (1997). A pregnant woman with lupus Tulane Renal Biopsy Conference. J La State Med Soc. 149 (11): 451-4. Summary: <> Department of Medicine, Section of Nephrology, Tulane University School of Medicine, USA.


114.      Dooley MA and Falk RJ (1998). Immunosuppressive therapy of lupus nephritis. Lupus. 7 (9): 630-4. Summary: Aggressive immunosuppressive therapy should be considered for patients with proliferative lupus nephritis as the risk for progression to end stage renal disease is high. Intermittent intravenous cyclophosphamide therapy improves renal survival; longer duration of therapy is associated with fewer relapse of nephritis and decreased risk of diminished renal function. While azathioprine therapy does not differ statistically from steroids alone in prolonging renal survival, this therapy may be considered in patients with few risk factors for progression to renal insufficiency. Methylprednisolone as a single therapy does not prolong renal survival compared with regimens including cyclophosphamide. Plasmapheresis remains under study but has not shown additional benefit in treatment of severe lupus nephritis. The potential roles for cyclosporin A and mycophenylate mofetil in the therapy of proliferative lupus nephritis remain to be defined. Supportive care including rigorous control of hypertension, consideration of angiotensin receptor inhibition or blockade to reduce proteinuria and prolong renal function, control of hyperlipidemia, prevention of osteoporosis, and prevention of pregnancy remain important clinical goals. Current research efforts focus on genetic and socioeconomic factors involved in racial differences in expression of lupus nephritis, hormonal manipulation to preserve gonadal function during cyclophosphamide therapy, and the potential impact on lupus activity of estrogen-containing oral contraceptives or postmenopausal hormone replacement therapy. <> Department of Medicine, The University of North Carolina at Chapel Hill School of Medicine, 27599-7280, USA.


115.      Haraguchi T and Yabuki S (1998). [A case of measles encephaloneuropathy in a pregnant women]. No To Shinkei. 50 (8): 761-5. Summary: We reported a patient with measles encephaloneuropathy. A 26-year-old woman in her 15th week of gestation became febrile and developed cutaneous eruption typical of measles on July 1 1997. Five days after appearance of the rash, fetal death was identified and the fetus was removed. Following the operation, she became comatous. Neurological examination revealed neck stiffness, flaccid paralysis of the four limbs, and decreased sweating in the lower limbs. CSF protein was 143 mg/dl with cell count of 1365/mm3. Myelin basic protein in CSF was positive. High titers of antimeasles antibodies were found in the serum and the cerebrospinal fluid. EEG revealed a predominance of slow waves. In MRI obtained earlier in her illness, high signal intensity areas were noted to spread in the brain stem and external capsule on T2- weighted images. However, T1-weighted image was unremarkable. Serial electrophysiological studies suggested demyelination of the motor nerves. With combination of methylprednisolone and immunoglobulin therapy, she made a remarkable recovery without any neurologic sequelae. We believe that the measles encephalitis in our patient is predominantly demyelinating due to an immunologic reaction in a pathophysiological aspect. We should pay attention to coincident poly- radiculoneuropathy in the early stage of measles encephalopathy. <> Department of Neurology, Kochi Prefectural Central Hospital, Japan.


116.      Shah AK, Tselis A and Mason B (2000). Acute disseminated encephalomyelitis in a pregnant woman successfully treated with plasmapheresis. J Neurol Sci. 174 (2): 147-51. Summary: <> Department of Neurology, Wayne State University, Detroit Medical Center, Detroit, MI 48201, USA.


117.      Mihara H, Kato Y, Tokura Y, Hattori Y, Sato A, Kobayashi H, Imamura A, Daimaru O, Miwa H and Nitta M (1999). [Epstein-Barr virus-associated hemophagocytic syndrome during mid-term pregnancy successfully treated with combined methylprednisolone and intravenous immunoglobulin]. Rinsho Ketsueki. 40 (12): 1258-64. Summary: A 32-year-old woman in the 16th week of pregnancy was admitted to our hospital because of high fever. Laboratory findings disclosed pancytopenia and extremely elevated serum LDH and ferritin levels. Coagulation tests showed disseminated intravascular coagulation. Serum soluble interleukin-2 receptor, tumor necrosis factor-alpha, and interleukin-6 levels were high, but serum interferon-gamma was below the detectable limit. Reactive Epstein-Barr virus (EBV) infection was diagnosed on the basis of a high titer of IgG antibodies to the EBV capsid antigen and early antigen. EBV was demonstrated in the peripheral blood and bone marrow cells by polymerase chain reaction. Mature histiocytosis and hemophagocytosis were detected in the bone marrow. A diagnosis of EBV-associated hemophagocytic syndrome (EBV-AHS) was made. Neither prednisolone (PSL 30 mg/day, P.O.) nor methylprednisolone (m-PSL) pulse therapy (1,000 mg/day for 3 days) induced a response. Thereafter, treatment with m-PSL pulse therapy (1,000 mg/day for 3 days) and i.v. administrations of high-dose immunoglobulin (20 g/day for 3 days) in combination with acyclovir (750 mg/day) and gabexate mesilate (2 g/day) induced remission of the disease. Maintenance therapy consisted of PSL (5 mg/day, P.O.) and camostat mesilate (600 mg/day, P.O.). The patient delivered a healthy male infant in the 35th week of pregnancy via natural birth. Reports of pregnant women with EBV-AHS are rare, and the choice of therapy has not yet been established. The present case study suggested the above combination treatment is useful and safe, and capable of changing the fulminant course of EBV-AHS during pregnancy without the use of anticancer drugs. <> 2nd Department of Internal Medicine, Aichi Medical University.


118.      Albino JA and Shapiro JM (1994). Respiratory failure in pregnancy due to Pneumocystis carinii: report of a successful outcome. Obstet Gynecol. 83 (5 Pt 2): 823-4. Summary: BACKGROUND: The incidence of infection with the human immunodeficiency virus (HIV) is rising rapidly among women of reproductive age. Pneumocystis carinii pneumonia during pregnancy may be the first manifestation of HIV infection. If respiratory failure ensures, the outcome has been reported as almost invariably fatal. CASE: A 31-year- old African-American woman at 28 weeks' gestation was admitted with bilateral perihilar interstitial infiltrates. Laboratory evaluation revealed hypoxemia and an elevated serum lactic dehydrogenase level. Although she denied risk factors for HIV infection, she was treated immediately for P carinii infection with trimethoprim-sulfamethoxazole and methylprednisolone. Her respiratory status deteriorated and she required intubation. Bronchoscopy confirmed the diagnosis, and CD4 lymphocyte depletion confirmed immunosuppression. The patient responded to treatment and recovered completely. CONCLUSION: A high index of suspicion must be maintained for the diagnosis of P carinii and previously unsuspected HIV infection during pregnancy. The early manifestations may be subtle and progress over weeks until respiratory failure rapidly ensues. With timely diagnosis and management, the outcome of P carinii pneumonia in pregnancy can be successful. <> Pulmonary/Critical Care Division, St. Luke's Hospital, New York, New York.


119.      Ponnighaus JM, Ziegler H and Kowalzick L (1998). [Herpes gestationis--oral corticosteroids cannot be avoided]. Zentralbl Gynakol. 120 (11): 548-50. Summary: An immunpathologically proven gestational herpes case is presented. Herpes gestationis may begin at any stage of pregnancy but it is usually seen during the second trimester. As a rule oral prednisolone therapy is required. We report on a patient who initially insisted on local therapy only. However this local treatment with steroids proved to be insufficient. <> Hautklinik, Vogtlandklinikum Plauen GmbH.


120.      Grekas DM, Vasiliou SS and Lazarides AN (1984). Immunosuppressive therapy and breast-feeding after renal transplantation. Nephron. 37 (1): 68. Summary: <>


121.      Ramsey-Goldman R and Schilling E (1997). Immunosuppressive drug use during pregnancy. Rheum Dis Clin North Am. 23 (1): 149-67. Summary: Women with rheumatic diseases frequently need treatment throughout pregnancy and lactation. Physicians must confront the dual challenge of monitoring the possible effects of the underlying maternal disease and the medications on both mother and child. It is essential that the maternal disease be well controlled before, during, and after pregnancy to ensure the best possible outcome for the mother and child. Corticosteroids have been used extensively and safely in pregnant patients with systemic lupus erythematosus and rheumatoid arthritis; there have been no reports of congenital malformations in the exposed infants. There is considerable experience using azathioprine during pregnancy if the maternal condition requires use of a cytotoxic drug; there has been no increased risk of congenital malformations in the exposed infants. There is limited information on the safety of other medications, including 6-mercaptopurine, cyclophosphamide, and cyclosporine. Methotrexate is contraindicated during pregnancy, and chlorambucil should be avoided because there are other effective immunosuppressive agents available for use. Corticosteroids (prednisone and methylprednisolone) can be used safely during lactation. All other immunosuppressive medications, azathioprine and 6-mercaptopurine, chlorambucil, cyclophosphamide, cyclosporine, and methotrexate, are contraindicated during lactation. <> Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA.


122.      Pabelick C, Kemmer F and Koletzko B (1991). [Clinical findings in newborn infants of mothers with kidney transplants]. Monatsschr Kinderheilkd. 139 (3): 136-40. Summary: Renal transplant patients who become pregnant require continued immunosuppression. Little is known on the risk of infants born under these conditions. We observed 6 neonates of renal transplant patients, of whom 4 were premature and 3 small for gestational age (SGA). There were no congenital malformations. Transient thrombopenia in 1 preterm baby probably resulted from maternal immunosuppression. Further 232 cases were published since 1980. Among the total of 238 patients, including our observations, rates for prematurity (49%) and SGA-infants (29%) were high, 6% had congenital malformations. Maternal immunosuppression with Cyclosporin A, as compared to Azathioprine, seems to carry a higher risk of prematurity (66 vs. 43%) and SGA-babies (56 vs. 19%). On the contrary, Azathioprine might be more muta- and teratogenic. At present, no data are available on the long-term outcome of these children. <> Abteilung fur Allgemeine Padiatrie, Universitats-Kinderklinik, Dusseldorf.


123.      Rowemeier H, Kemmer FW, Somville T and Grabensee B (1993). [Pregnancy after kidney transplantation]. Dtsch Med Wochenschr. 118 (18): 649-55. Summary: The course of 13 pregnancies in 12 women (mean age 28 [19-34] years) after renal transplantation was analysed retrospectively. The average period from renal transplantation to the beginning of pregnancy was 45 [7-144] months. All patients received methylprednisolone for immunosuppression, while seven each additionally received azathioprine and/or cyclosporin. At the onset of pregnancy the transplant function was good or only slightly impaired in 11 women (serum creatinine 1.3 [0.8-1.8] mg/dl). But in one patient, a diabetic with nephrotic syndrome, serum creatinine concentration was raised to 2.4 mg/dl. In six patients the cyclosporin dosage had to be increased during the pregnancy. Severe complications were: acute rejection in the 16th week of pregnancy; acute renal failure during a recurrence of haemolytic- uraemic syndrome in the 36th week; and severe renal anaemia (haemoglobin 6.7 g/dl). An irreversible rise in creatinine concentration occurred in five women and hypertension got worse in eight. The mean duration of pregnancy was 35.5 (32-38) weeks. The average birth weight was low (1892 g [970-2560 g]): five children were dystrophic. The dystrophy rate was the same under cyclosporin as under the conventional immunosuppressants. The findings indicate that pregnancy after renal transplantation presents a high risk for mother and child. It demands intensive joint care by obstetrician, paediatrician and nephrologist. <> Abteilung fur Nephrologie, Universitat Dusseldorf.


124.      Lipton JH, Derzko C, Fyles G, Meharchand J and Messner HA (1993). Pregnancy after BMT: three case reports. Bone Marrow Transplant. 11 (5): 415-8. Summary: A case of successful pregnancy after BMT in a 24-year-old woman with ALL, conditioned with CY, L-asparaginase, methylprednisolone and total body irradiation (TBI) is reported. A second case of two spontaneously aborted pregnancies in a woman transplanted for ALL at the age of 29 years using CY and TBI conditioning and a third case, this time a successful pregnancy in a woman transplanted for AML at age 27 years using CY and TBI conditioning are also described. There are now 6 successful live births after TBI reports of, versus 16 following regimens in which no TBI is used. This is the first report of a successful pregnancy reported in a female transplanted when older than 25 years using any TBI-containing regimen. <> Department of Medicine, Princess Margaret Hospital/Ontario Cancer Institute, University of Toronto, Canada.


125.      Nagasawa H, Takashima S, Hirade S and Inoue H (1997). [A case of multiple sclerosis with relapses during the third trimester of pregnancy]. Rinsho Shinkeigaku. 37 (10): 933-6. Summary: We report a 31-year-old woman with a relapse of multiple sclerosis during the third trimester of pregnancy. She had been treated palliatively after the relapse until occurrence of a new symptom and new lesions on MRI, and then she had Cesarean section. After surgery, steroid pulse therapy was started and the symptoms and lesions on MRI resulted in improvement. As a strategy to treat patients with multiple sclerosis in their third trimester of pregnancy, it is appropriate to evaluate disease activity using MRI and to start steroid pulse therapy after delivery. <> Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University.


126.      Kumar R, Maraganore DM, Ahlskog JE and Rodriguez M (1997). Treatment of putative immune-mediated and idiopathic cervical dystonia with intravenous methylprednisolone. Neurology. 48 (3): 732-5. Summary: A young pregnant woman developed a persistent dystonic head tremor a few days after Rho (D) immune globulin administration; further deterioration occurred after a second administration of Rh(o) (D) immune globulin with the development of marked retrocollis. This persisted and she was treated 2 months later with a 5-day course of intravenous (1 g daily) methylprednisolone (IVMP) with resolution of her condition. We proceeded to treat similarly the next four patients with idiopathic cervical dystonia who were seen in our practice and who had current symptoms of less than 6 months duration. One also experienced persistent resolution and another had a marked, but transient, improvement after each of two separate courses of IVMP. The other two patients did not have improvement. This suggests a possible autoimmune pathogenesis for a limited subset of cervical dystonia. However, identifying which cases of recent-onset cervical dystonia will respond to IVMP therapy has yet to be determined. <> Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.


127.      Mari I, Pouchot J, Grasland A and Vinceneux P (2000). [Facial diplegias during pregnancy]. Presse Med. 29 (40): 2213-5. Summary: BACKGROUND: Facial diplegia is a rare event, most commonly of unknown origin. We report the case of a woman who presented bilateral Bell's palsy a few days after a normal delivery. CASE REPORT: Five days after the delivery of gemellary pregnancy, a 34-year old woman developed complete bilateral facial palsy. No treatment was initially prescribed. She was first seen in our department two weeks after the onset of her illness. The diagnostic work-up was negative and we considered that our patient had bilateral Bell's palsy. Treatment with methylprednisolone and intravenous acyclovir, initiated since admission, have had very limited effect. DISCUSSION: As has already been shown for facial palsy, idiopathic facial diplegia, although exceptional, seems to be more frequent during the last trimester of pregnancy and in the early puerperium. Seven cases have been reported in the literature over the last 30 years. We discuss here the pathophysiology. <> Service de Medecine Interne V, Hopital Louis Mourier, Colombes.


128.      Block MF, Kling OR and Crosby WM (1977). Antenatal glucocorticoid therapy for the prevention of respiratory distress syndrome in the premature infant. Obstet Gynecol. 50 (2): 186-90. Summary: A double-blind study was designed to investigate the effects of antenatal glucocorticoids on the incidence of respiratory distress syndrome (RDS) in 128 premature human infants. There was a significant reduction (P less than 0.05) in the incidence of RDS in the betamethasone-treated infants to 8.7% compared to an incidence of 22.6% in the saline-treated controls and 25.0% in infants whose mothers received methylprednisolone. The effectiveness of betamethasone in reducing RDS was limited to premature infants delivered to mothers with intact fetal membranes and with an initial L/S ratio less than 2.0. The time between administration of the glucocorticoid and delivery did not significantly affect the incidence of RDS in this study. The failure of methylprednisolone to reduce the development of RDS in premature infants suggests its potential use in maternal therapy during pregnancy with minimal effects on fetal maturation. <>


129.      Schmidt PL, Sims ME, Strassner HT, Paul RH, Mueller E and McCart D (1984). Effect of antepartum glucocorticoid administration upon neonatal respiratory distress syndrome and perinatal infection. Am J Obstet Gynecol. 148 (2): 178-86. Summary: A double-blind, randomized study comparing the antepartum use of betamethasone (12 mg), methylprednisolone (125 mg), and hydrocortisone (250 mg) was performed to evaluate effect on neonatal respiratory distress syndrome and perinatal infection. Of 144 mothers and 149 infants entered, 92 mothers and 97 infants were available for analysis. The betamethasone-treated group had a significantly reduced incidence of severe respiratory distress syndrome (4%) compared with the control group (26%; p = 0.038); this effect was confined to patients who received at least two doses. No similar effect was found in the methylprednisolone or hydrocortisone groups. Neonatal infection and neonatal mortality rate were not affected by glucocorticoid use. Maternal infection was significantly increased in hydrocortisone- treated patients who were delivered vaginally compared with control patients (all patients: 50% versus 9.5%, p less than 0.05; with ruptured membranes: 63% versus 15%, p = 0.04). No similar increase in maternal infection was found with betamethasone or methylprednisolone use. <>


130.      Anderson GG, Rotchell Y and Kaiser DG (1981). Placental transfer of methylprednisolone following maternal intravenous administration. Am J Obstet Gynecol. 140 (6): 699-701. Summary: Seven normal patients in labor at term were given 125 mg of methylprednisolone hemisuccinate intravenously shortly before delivery. Analysis of maternal and cord plasma samples indicated that both the hemisuccinate and free alcohol forms of the corticosteroid were transported in pharmacologic levels to the fetal compartment. Since methylprednisolone may have less of an infection-potentiating effect than other commonly used corticosteroids, use of it as a stimulator of fetal lung surfactant deserves further investigation. <>


131.      Obladen M (1978). Factors influencing surfactant composition in the newborn infant. Eur J Pediatr. 128 (3): 129-43. Summary: In order to evaluate the surfactant maturation of the neonate, tracheal aspirates were analyzed in 84 newborn infants with 12h of birth. Using 2-dimensional thin-layer chromatography, 9 different phospholipids were identified. Dynamic surface tension measurements were performed with a modified Wilhelmy balance. Five different groups of infants with typical phospholipid patterns were characterized: i.e., 1. Normal term newborn. 2. RDS in the preterm infant. 3. Acceleration of lung maturity in preterm infants without RDS. 4. Retardation in term infants with RDS. 5. Therapeutic induction of pulmonary maturity in preterm infants following maternal glucocorticoid administration. Mature lung effluent contains high concentrations of phosphatidylcholine (PC) and phsophatidylglycerol (PG). In infants with RDS, PC is low and PG absent. Accelerated lung maturity was observed after chronic prenatal stress, such as prolonged rupture of the membranes, chronic vaginal bleeding, and maternal hepatitis or drug addiction. Retardation of pulmonary maturity was seen in infants with alpha-1-AT-deficiency, maternal diabetes and maternal hypothyroidism. Administration of methylprednisolone to the mother 24 h to 72h before birth induced both the synthesis of PC and PG in the preterm infants, resulting in an almost full-term phospholipid pattern as early as 31 weeks of gestation. The significance of these factors on the pathogenesis of RDS is discussed. <>


132.      Ovali F, Samanci N, Ermis B, Akdogan Z and Dagoglu T (1998). Alternative therapies for neonatal autoimmune thrombocytopenia. Vox Sang. 74 (3): 198-200. Summary: OBJECTIVE: This study was performed to test whether corticosteroids were superior to intravenous immunoglobulins (IVIG) in the treatment of neonatal autoimmune thrombocytopenia (NAT). METHODS: All cases received IVIG, and unresponsive cases received corticosteroids. RESULTS: Of 7 babies who received IVIG, only 1 responded. The 6 remaining cases received corticosteroids thereafter, and all of them responded well to this therapy. CONCLUSIONS: Corticosteroids may be more effective than IVIG in NAT. <> Department of Obstetrics and Gynecology, Istanbul Faculty of Medicine, Istanbul University, Turkey.


133.      Sabik JF, Heinemann MK, Assad RS and Hanley FL (1994). High-dose steroids prevent placental dysfunction after fetal cardiac bypass. J Thorac Cardiovasc Surg. 107 (1): 116-24; discussion 124-5. Summary: Surgical treatment of certain congenital heart lesions in utero may have a therapeutic advantage over postnatal repair or palliation. For fetal heart surgery to be possible, a method to support the fetal circulation is necessary. Early experimental attempts at fetal cardiac bypass were unsuccessful because of increased placental vascular resistance during and after fetal cardiac bypass, which led to decreased placental flow, fetal asphyxia, and death. Our laboratory has demonstrated that the administration of indomethacin (a cyclooxygenase inhibitor) during fetal cardiac bypass prevents this increase in placental vascular resistance during and after fetal cardiac bypass. The specific mechanism by which indomethacin achieves this effect is likely to be either by inhibiting the production of a placental vasoconstrictive prostaglandin or by diverting substrate from the cyclooxygenase pathway to the lipoxygenase pathway, thereby potentially increasing the production of a placental vasodilating leukotriene. To examine these potential mechanisms in more detail, we inhibited both prostaglandin and leukotriene synthesis at the phospholipase stage with high-dose steroids. Fourteen fetal lambs were used in the study. Six animals received indomethacin (3 mg/kg), four received high-dose steroids (Solu-Medrol 50 mg/kg), and four animals were used as controls. Observations were made during a 1-hour prebypass period, a 30- minute bypass period, and a 2-hour postbypass period. Placental blood flow and placental vascular resistance were calculated at four times during the experiments: before sternotomy; after sternotomy; during bypass at 30 minutes; and 30 minutes after cessation of bypass. Similar to indomethacin, high-dose steroid administration during fetal cardiac bypass prevents the rise in placental vascular resistance and preserves placental blood flow during and after fetal cardiac bypass. This study suggests that the production of a placental vasoconstrictive prostaglandin is responsible for the increase in placental vascular resistance and decrease in placental blood flow observed after fetal cardiac bypass. <> Department of Cardiovascular Surgery, Children's Hospital of Boston, Harvard Medical School, Mass.


134.      Cohen J, Malter H, Elsner C, Kort H, Massey J and Mayer MP (1990). Immunosuppression supports implantation of zona pellucida dissected human embryos. Fertil Steril. 53 (4): 662-5. Summary: The effect of low dose immunosuppression with methylprednisolone during the first 4 days after oocyte retrieval on potential immune cell invasion of partially zona dissected embryos in utero was investigated in alternate in vitro fertilization patients (n = 32). The incidence of pregnancy was significantly higher in patients receiving methylprednisolone (7 of 18, 39%) than in control patients (1 of 14, 7%). Twenty-eight percent (11 of 39) of the embryos replaced in the corticosteroid treated patients implanted, whereas only 7% (2 of 31) of embryos in control patients had a fetal heart beat. There were no side effects reported in any of the patients receiving corticosteroids. It can be concluded that methylprednisolone supports implantation of embryos with small holes in their zonae. However, the actual mechanisms of corticosteroid support on the interaction between immune cells and micromanipulated embryos are not well understood. <> Reproductive Biology Associates, Emory University School of Medicine, Atlanta, Georgia.


135.      Polak de Fried E, Blanco L, Lancuba S and Asch RH (1993). Improvement of clinical pregnancy rate and implantation rate of in- vitro fertilization-embryo transfer patients by using methylprednisone. Hum Reprod. 8 (3): 393-5. Summary: A prospective non-randomized study was undertaken to test whether immunosuppression improves implantation and pregnancy rates in an in- vitro fertilization-embryo transfer (IVF-ET) programme in patients with tubal factor infertility. Treatment involved ovarian stimulation, transvaginal oocyte retrieval, IVF-ET, and assessment of short-term administration of large doses of corticosteroids (60 mg of methyl- prednisone x 4 days). When compared to the group that did not receive immunosuppressive doses of methylprednisone (group A; mean age 31.85 +/- 4.09 years), those subjects who were treated (group A2) showed a statistically significant increase in pregnancy (P < 0.01) and take home baby rate (P < 0.01). Similar results were observed in subjects who received corticosteroids in their first IVF-ET attempt (group B; mean age 34.32 +/- 4.98 years). Our results suggest that immunosuppressive doses of corticosteroids administered for a short period of time to patients undergoing IVF-ET could significantly improve the implantation and pregnancy rates. Possible mechanisms of action of corticosteroids are proposed. <> Centro de Salud Reproductiva (CER), Buenos Aires, Argentina.


136.      Phocas I, Sarandakou A, Rizos D and Chryssikopoulos A (1991). Hormonal patterns in a successful pregnancy of a patient with late- onset 21-OH deficiency taking methylprednisolone; a case report. Eur J Obstet Gynecol Reprod Biol. 41 (2): 151-8. Summary: A successful pregnancy of a young woman with late-onset congenital adrenal hyperplasia (LOCAH) is reported. Exogenous glucocorticoids are the most commonly used regimen in such cases both for suppression of adrenal overstimulation and avoiding masculinization of a female fetus. In our LOCAH patient methylprednisolone has been used for treatment. We present the management and the outcome of this pregnancy, as well as the hormonal follow-up. <> 2nd Department of Obstetrics and Gynecology, University of Athens, Areteion University Hospital, Greece.


137.      Seiner SJ, Schramm W and Keyes PL (1992). Effect of treatment with methylprednisolone on duration of pseudopregnancy and on macrophages and T lymphocytes in rabbit corpora lutea. J Reprod Fertil. 96 (1): 347-53. Summary: The potential role of macrophages and T lymphocytes in the destruction of the corpus luteum at the end of the luteal phase was investigated by treating pseudopregnant rabbits with the immunosuppressant glucocorticoid methylprednisolone. Eleven specific pathogen-free New Zealand White rabbits were injected with pregnant mares' serum gonadotrophin (40 iu, i.m.), followed 2 days later by human chorionic gonadotrophin (40 iu, i.v.) to stimulate ovulation. The following day (day 1 of pseudo-pregnancy) all animals had an oestradiol-filled Silastic capsule implanted s.c., to ensure that oestradiol, the luteotrophic hormone in this species, would not be limiting. From day 10 of pseudopregnancy, three animals were injected with a low dose of methylprednisolone (2 mg kg-1 per day) until day 20. Three other animals were injected with a higher dose of methylprednisolone (20 mg kg-1 per day) from day 13 of pseudopregnancy until day 19. Five animals served as control, vehicle-injected animals. Blood samples were taken at intervals and assayed for progesterone. Immunofluorescence was used to stain luteal tissue for macrophages, T lymphocytes and class II antigens, and positive cells were counted under high-power magnification. Methylprednisolone treatment reduced (by about 70%), but did not eliminate, the macrophages in the regressing corpora lutea. In contrast, the high dose of methylprednisolone essentially eliminated T lymphocytes, and reduced (by about 90%) the number of cells expressing class II antigen in the luteal tissue. Despite the effects of methylprednisolone on these cells, serum progesterone profiles were not altered by treatment with methylprednisolone, and pseudopregnancy was of normal duration.(ABSTRACT TRUNCATED AT 250 WORDS). <> Department of Physiology, University of Michigan, Ann Arbor 48109.


138.      Velilla E, Grossmann M, Egozcue J and Santalo J (1999). Effect of 6 beta-methylprednisolone on mouse pregnancy rate. Hum Reprod. 14 (1): 207-10. Summary: The aim of this study was to evaluate the effect of methyl-prednisolone on the pregnancy rate in mice. For this reason, zona pellucida-intact and zona pellucida-free embryos at the blastocyst stage were transferred to recipient mice at day 2.5 of pseudopregnancy. Embryo transfer was performed into non-immunodepressed and immunodepressed groups of recipient mice using 0.3 or 0.6 microgram/g of 6 beta- methylprednisolone. A higher implantation and developmental rate of zona-free embryos transferred to the immunodepressed group of recipients was observed after using the higher dose of methylprednisolone. <> Departament de Biologia Cellular i Fisiologia, Universitat Autonoma de Barcelona, Spain.


139.      Lee KA, Koo JJ, Yoon TK, Do BR, Ko JJ and Cha KY (1994). Immunosuppression by corticosteroid has no effect on the pregnancy rate in routine in-vitro fertilization/embryo transfer patients. Hum Reprod. 9 (10): 1832-5. Summary: Immunosuppression by exogenous corticosteroids has been used to improve the rates of embryo implantation and pregnancy in in-vitro fertilization (IVF) patients who have micromanipulated embryos replaced. The present study was conducted, in a prospective design, to evaluate effects of corticosteroid on the pregnancy rate in IVF/embryo transfer patients who have non-micromanipulated embryos replaced. Infertile women < 40 years old with tubal factor were included in this study. Patients were grouped according to the different follicle stimulation protocols, and received various doses of 16 beta- methylprednisolone (0, 16 or 60 mg/day) for 4 days from the day of oocyte retrieval. The mean age, duration of infertility, length of folliculogenesis and serum oestradiol concentrations at the time of human chorionic gonadotrophin (HCG) injection were not significantly different between control and corticosteroid-treated groups of patients. Short-term immunosuppression by 16 beta-methylprednisolone administration did not show any effects on the pregnancy and miscarriage rates in IVF/embryo transfer patients. Also, immunosuppression showed no dose effects in any groups. There was no relationship between the types of follicle stimulation protocols and the effect of 16 beta-methylprednisolone. Therefore, we concluded that short-term immunosuppression by exogenous corticosteroids in IVF/embryo transfer patients who have embryos with intact zona pellucida replaced has neither positive nor negative effects on pregnancy rates. <> Infertility Medical Centre, CHA General Hospital, Seoul, Korea.


140.      Moffitt D, Queenan JT, Jr., Veeck LL, Schoolcraft W, Miller CE and Muasher SJ (1995). Low-dose glucocorticoids after in vitro fertilization and embryo transfer have no significant effect on pregnancy rate. Fertil Steril. 63 (3): 571-7. Summary: OBJECTIVE: To determine the effect on pregnancy rate (PR) of low-dose glucocorticoid treatment in cycles without micromanipulation. DESIGN: Randomized, prospective, double-blinded, placebo-controlled trial. SETTING: One university-based tertiary infertility center and two private infertility centers. PATIENTS: All patients receiving standard stimulation IVF-ET or transfer of cryopreserved embryos at the participating facilities from January to September 1993 were asked to participate in this study. Patients having micromanipulation were excluded from this study. INTERVENTIONS: Participating patients were randomized to either 16 mg oral 6-alpha-methylprednisolone for four evenings starting the evening of retrieval or the evening before thawing cryopreserved embryos or to placebo administered in an identical fashion. Both groups were treated with 250 mg oral tetracycline four times per day starting with initiation of the study medication and continuing for 4 days. Cryopreservation and stimulation cycles were managed according to pre-established protocols for all patients. A clinical pregnancy was confirmed by an appropriately rising hCG titer and a gestational sac on ultrasound. RESULTS: A total of 206 stimulation patients and 61 cryopreservation patients were randomized and had an ET. Patient characteristics were similar between groups. The clinical pregnancy and implantation rates between placebo and glucocorticoid groups were 35.9% versus 40.8% and 12.8% versus 11.7% for stimulation cycles and 30.3% versus 25% and 9.9% versus 7.4% for cryopreservation cycles, respectively. None of these differences were statistically significant. CONCLUSIONS: Glucocorticoid plus antibiotic treatment at these doses for transfers of nonmicromanipulated embryos does not appear to have a significant effect on pregnancy or implantation rates. <> Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk.


141.      Mantzavinos T, Phocas I, Sarandakou A, Kanakas N, Arvaniti K and Zourlas PA (1996). Serum markers of immune activation in women undergoing in-vitro fertilization and embryo transfer. Hum Reprod. 11 (11): 2412-7. Summary: We evaluated serum concentrations of two early and sensitive markers of immune activation, interleukin-2 receptor (sIL-2R) and intercellular adhesion molecule-1 (ICAM-1) in two age-matched groups of in-vitro fertilization (IVF)-embryo transfer women, group I (n = 26) without and group II (n = 40) with methylprednisolone (MPD) supplementation of the luteal phase, on the days of oocyte retrieval (sample A) and embryo transfer (B), and second (C) and 13th (D) days post-transfer and in 20 normally cycling women (controls) on the day of luteinizing hormone (LH) peak. No difference in the outcome of the IVF-embryo transfer was observed between groups I and II. In sample A, both immunomarker concentrations showed no significant difference between the two groups of IVF women, while they were significantly higher (P < 0.01) than values in controls. In cycles in which conception occurred, significantly higher immunomarker concentrations were observed in sample A of both groups I and II compared with those in unsuccessful cycles of the same group. A significant decrease of both sIL-2R and ICAM-1 was noticed in sample B only in group II (P < 0.0001 and P < 0.001 respectively; paired t-test) that continued further in the late luteal phase only in the case of conception, independently of MPD supplementation. These data suggest that (i) due to multiple ovulations, IVF-embryo transfer women show elevated concentrations of sIL-2R and ICAM-1 at oocyte retrieval; (ii) since, even at oocyte retrieval stage, high concentrations of immunomarkers are associated with IVF-embryo transfer success, sIL-2R and ICAM-1 could be used as early indicators for conception cycles; (iii) transient suppression of T cell activity by MPD supplementation following IVF-embryo transfer does not improve pregnancy rate. <> 2nd Department of Obstetrics and Gynecology, University of Athens, Areteion Hospital, Greece.


142.      Mottla GL, Smotrich DB, Gindoff PR and Stillman RJ (1996). Increasing clinical pregnancy rates after IVF/ET. Can immunosuppression help? J Reprod Med. 41 (12): 889-91. Summary: OBJECTIVE: To evaluate the safety and efficacy of immunosuppression as an adjunct to improving the success of in vitro fertilization/embryo transfer (IVF-ET). STUDY DESIGN: A randomized, double-blind, placebo- controlled clinical trial. RESULTS: Seventy-five patients were randomized to receive either prednisone (39 patients, 51%) or placebo (36 patients, 49%). Patients in both groups had similar ages and numbers of preembryos transferred. CONCLUSION: Both the implantation and clinical pregnancy rates were higher in the prednisone group (16% vs. 11% and 43.5% vs. 32.3%, respectively). However, these differences did not achieve statistical significance. Evaluation of the ongoing pregnancy rate revealed little difference between the prednisone- treated patients (30.7%) and those receiving placebo (28.0%). There were no side effects reported by patients in either group. <> Montgomery Fertility Institute, Bethesda, Maryland 20817, USA.


143.      Lanzendorf SE, Nehchiri F, Mayer JF, Oehninger S and Muasher SJ (1998). A prospective, randomized, double-blind study for the evaluation of assisted hatching in patients with advanced maternal age. Hum Reprod. 13 (2): 409-13. Summary: The objective of this study was to determine if assisted hatching improved the rates of implantation, clinical pregnancy and ongoing pregnancy for in-vitro fertilization (IVF) patients aged > or =36 years. On the day of oocyte aspiration, consenting patients were randomized according to whether all embryos underwent the hatching procedure (hatched; n = 41) or all embryos remained unhatched (controls; n = 48). Patients in both groups were treated with methylprednisolone and doxycycline starting on the day of oocyte retrieval and continuing for 4 days. The hatching procedure was performed approximately 55 h after insemination on all potential embryos for transfer and employed the release of acidified acid Tyrode's medium against the zona pellucida to create an opening approximately 20 microm in diameter. No significant differences were noted in the mean age, number of oocytes aspirated and number of embryos transferred between the hatched and control groups. In addition, no significant differences were observed in the rates of implantation (11.1 versus 11.3%), clinical pregnancy (39.0 versus 41.7%) and ongoing pregnancy (29.3 versus 35.4%) between the hatched and control groups respectively. These results suggest that assisted hatching may have no significant impact on IVF success rates in the patient population studied. <> The Howard and Georgeanna Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk 23507, USA.


144.      Ogasawara M and Aoki K (2000). Successful uterine steroid therapy in a case with a history of ten miscarriages. Am J Reprod Immunol. 44 (4): 253-5. Summary: A woman experienced ten unexplained first trimester miscarriages. Uterine steroid therapy was performed just before her 11th pregnancy. Prednisolone was inserted into the uteral cavity before ovulation and her 11th pregnancy resulted in success. Our experience in this case confirms the potential usefulness of this treatment for patients with unexplained recurrent miscarriages. <> Department of Obstetrics and Gynecology, Nagoya City University Medical School, Japan.


145.      Schlembach D, Munz W and Fischer T (2000). Effect of corticosteroids on HELLP syndrome: a case report. J Perinat Med. 28 (6): 502-5. Summary: The HELLP syndrome is associated with a high rate of prematurity, which is the major cause of neonatal morbidity and mortality. Several studies have demonstrated the feasibility of prolongation of pregnancies complicated by HELLP syndrome. Until now the role of an additive pharmacological regimen, and particularly the role of corticosteroids, is still not clear. We report a case of a successful prolongation of a pregnancy complicated by HELLP syndrome and note a direct relationship with application and withdrawal of corticosteroids. A 26-year old primigravida was admitted with HELLP syndrome in the 25th week of gestation. We commenced a therapy with 40 mg methylprednisolone i.v. once daily, with clinical symptoms and biochemical parameters improving within two days. On day 6 we discontinued steroid medication with a consecutive deterioration of all biochemical data and clinical symptoms. Corticosteroids were recommenced and within two hours an improvement of all symptoms and laboratory data was observed. Overall we were able to prolong the pregnancy for 33 days. This case report underlines the beneficial effect of corticosteroids in patients with HELLP syndrome. Thus steroids might be helpful for postponing deliveries in very preterm gestation and for stabilizing the maternal status. <> Department of Obstetrics and Gynecology, University of Erlangen- Nuremberg, Germany.


146.      Fischer T, Wallukat G, Schneider MP, Schlembach D, Munz W and Homuth V (2001). HELLP syndrome in the 18th week of gestation in association with elevated angiotensin AT(1)-receptor autoantibodies. Eur J Obstet Gynecol Reprod Biol. 97 (2): 255-7. Summary: We present a 24-year-old woman with a twin pregnancy who was with a typical HELLP syndrome at the 18th week of pregnancy. One fetus was dead, while the other was severely growth retarded. Our patient had agonistic autoantibodies directed at the angiotensin AT(1)-receptor. Termination of the pregnancy proved necessary. This report is the first to our knowledge associating HELLP syndrome with angiotensin AT(1)- receptor antibodies. Since the antibodies may have a pathogenic significance, their removal could permit the prolongation of pregnancy in preeclamptic and HELLP syndrome patients. <> Department of Gynecology and Obstetrics, University of Erlangen/Nuremberg, Universitaetsstrasse 21, D-91054, Erlangen, Germany.


147.      Lockshin MD and Sammaritano LR (1998). Corticosteroids during pregnancy. Scand J Rheumatol Suppl. 107: 136-8. Summary: In pregnancy, pharmacokinetics of corticosteroids changes. Systemic corticosteroids are not teratogenic. Pregnant women receiving corticosteroid therapy suffer the same side effects and benefits as do treated women who are not pregnant. Clinical experience suggests no abnormalities of children of mothers treated with usual doses of prednisone and methylprednisolone throughout pregnancy, but premature rupture of amniotic membranes and low birthweight babies may occur. Betamethasone and dexamethasone are used to treat the fetus. The effect on the fetus of bolus doses of methylprednisolone is unknown. Very little corticosteroid ingested by the mother enters her breast milk. Corticosteroid therapy in pregnancy is appropriate to control clinically active maternal illness; to treat an in utero infant suffering from neonatal lupus-associated carditis; in stress doses (in corticosteroid-treated patients) for labor and delivery: and, pre- delivery, to induce fetal lung maturation. <> Cornell University Medical College, Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, New York, NY 10021, USA.


148.      Takahashi N, Nishida H and Hoshi J (1994). Severe B cell depletion in newborns from renal transplant mothers taking immunosuppressive agents. Transplantation. 57 (11): 1617-21. Summary: There have been several reports of successful pregnancies of kidney transplant mothers receiving immunosuppressive agents such as CsA and/or AZA. However, few papers have investigated immune function of neonates from those mothers. We investigated the lymphocyte subpopulations and T cell subsets in cord blood of newborn infants from those mothers. The subjects were 6 infants born to mothers following renal transplantation, who all were receiving CsA, AZA, and methylprednisolone. Cord blood and peripheral blood at 1 month and 3 months of age were obtained from the subjects. Control samples were obtained from 5 normal newborns. The polyclonal antibody used to investigate B cells was anti-F(ab')2 fragment of human immunoglobulin. Direct immunofluorescence staining and flow cytometry were used for the investigation. The number of B cells and the percentage of B cell in total mononuclear cells were significantly lower in the subjects than in normal controls. There was no significant difference between numbers of CD2+, CD4+, or CD8+ cells in the subjects and the controls. This severe B cell depletion remained low at 1 month and 3 months of life in many cases. From our result, it is very possible that the B cell line is more sensitive to immunosuppressants in utero than the T cell line. Infants of mothers taking immunosuppressive agents during their pregnancy should be followed carefully for possible insufficiency of immune function. <> Maternal and Perinatal Center, Tokyo Women's Medical College, Japan.


149.      Di Paolo S, Schena A, Morrone LF, Manfredi G, Stallone G, Derosa C, Procino A and Schena FP (2000). Immunologic evaluation during the first year of life of infants born to cyclosporine-treated female kidney transplant recipients: analysis of lymphocyte subpopulations and immunoglobulin serum levels. Transplantation. 69 (10): 2049-54. Summary: BACKGROUND: In rodents, CsA has been shown to affect T-cell development, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the effect of the immunosuppressive drug on the immune system of the human fetus. METHODS: We examined six infants born to female kidney transplant recipients who had received cyclosporine and methylprednisolone throughout their pregnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months after birth, and two-color flow cytometric immunophenotyping of lymphocytes was performed. RESULTS: Total T cells, as well as CD4+ and CD8+ T cells, were low at birth, but normalized thereafter. Among T-cell activation markers, the expression of CD25, the alpha chain of the interleukin-2 receptor, was below the normal range or low range throughout the study period, and HLA-DR expression was extremely low at birth and failed to increase up to 12 months. The number of total B cells was lower than normal at birth, but steeply increased over time. In contrast, B-cell subset bearing CD5 antigen was severely depleted throughout the first year of life. Total IgG concentration was significantly lower than in controls at 2 months, mainly because of subnormal levels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 months. Finally, infants showed normal numbers of true natural killer (NK) cells (CD3-CD16+CD56+), whereas the expression of CD57 antigen, defining non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8+ and CD8- subsets. Of note, none of the infants had clinical evidence of an immunodeficient state. CONCLUSIONS: continuous exposure to CsA in utero seemingly impairs T-, B-, and NK- cell development and/or maturation, and most of its effects are still apparent at 1 year, which might suggest that conventional vaccinations should be delayed in these infants. <> Department of Emergency and Organ Transplant, University of Bari Policlinico, Italy.


150.      Younoszai MK and Ghishan FK (1978). In vivo intestinal calcium absorption in infant rats: influence of methylprednisolone and vitamin D. Proc Soc Exp Biol Med. 158 (2): 174-8. Summary: <>


151.      Ghishan FK and Meneely RL (1982). Intestinal maturation: the effect of glucocorticoids on in vivo net magnesium and calcium transport in the rat. Life Sci. 31 (2): 133-8. Summary: We investigated with an in vivo single pass perfusion technique, the effect of glucocorticoids on net magnesium and calcium absorption from the small and large intestine of suckling and adolescent rats. In control rats, rates of net magnesium and calcium absorption were several fold greater in both small and large intestinal segments of suckling rats compared to corresponding rates in segments of adolescent rats. Methylprednisolone 30 mg/kg body weight daily for three days, suppressed significantly net magnesium and calcium absorption from the small and large intestinal segments of suckling rats only. Methylprednisolone had no effect on either net magnesium or calcium absorption in adolescent rats. The mechanism(s) responsible for the observed decrease in net magnesium and calcium absorption in the suckling period by glucocorticoids are discussed. <>

©Wise Young PhD, MD

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