The New England journal of medicine
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Case Reports
Central nervous system toxicity after liver transplantation. The role of cyclosporine and cholesterol.
We describe severe central nervous system (CNS) toxicity, manifested by confusion, cortical blindness, quadriplegia, seizures, and coma, associated with cyclosporine treatment in three patients undergoing liver transplantation. CT and magnetic resonance studies disclosed a severe, diffuse disorder of the white matter. All side effects and radiographic findings were reversed with discontinuation or a reduction in the dose of cyclosporine. ⋯ A retrospective analysis of 54 liver transplantations performed in 48 patients revealed that 13 patients had symptoms of CNS toxicity associated with the use of cyclosporine. These patients' total serum cholesterol levels in the first week after transplantation were reduced as compared with those in patients without symptoms (mean +/- SE, 94 +/- 4 mg per deciliter vs. 132 +/- 6, or 2.44 +/- 0.10 mmol per liter vs. 3.43 +/- 0.16). We conclude that cyclosporine therapy for immunosuppression in liver transplantation may cause a syndrome of encephalopathy, seizures, and white-matter changes and that this is most likely to occur in patients with low total serum cholesterol levels after transplantation.
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Case reports of sudden death during exertion have not established an association between the sickle-cell trait (hemoglobin AS) and exercise-related death. To test this association, all deaths occurring among 2 million enlisted recruits during basic training in the U. S. ⋯ Among black recruits the relative risk of sudden unexplained death (hemoglobin AS vs. non-hemoglobin S) was 27.6 (95 percent confidence interval, 9 to 100; P less than 0.001), whereas among all recruits this risk was 39.8 (95 percent confidence interval, 17 to 90; P less than 0.001). The relative risk of sudden unexplained death among all recruits increased with age (P less than 0.04), from 13 (ages 17 to 18) to 95 (ages 26 to 30). We conclude that recruits in basic training with the sickle-cell trait have a substantially increased, age-dependent risk of exercise-related sudden death unexplained by any known preexisting cause.
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We found a large deletion (more than 10 kilobases) in the gene for the low-density-lipoprotein receptor in 63 percent of French Canadians with heterozygous familial hypercholesterolemia. The deletion also occurred in homozygous form in four of seven French Canadian homozygotes. ⋯ This deletion has not been observed in any other ethnic group. It can be detected by analysis of genomic DNA from blood leukocytes, thus allowing direct diagnosis of familial hypercholesterolemia in a majority of affected French Canadians.
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Randomized Controlled Trial Clinical Trial
A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock.
The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. ⋯ In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.