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March 8, 2001
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Recombinant Human Activated Protein C for Severe Sepsis
In severe sepsis, a systemic inflammatory response and activation of the clotting system may contribute to the disease process. Activated protein C has antiinflammatory and antithrombotic properties, and its levels may be reduced in sepsis. In this large clinical trial, the effects of an infusion of human recombinant activated protein C were compared with those of an infusion of placebo. Treatment resulted in a reduction in the rate of death from 30.8 percent to 24.7 percent, a 19.4 percent relative reduction.
Despite antibiotic therapy and intensive medical care, mortality in the severe sepsis syndrome remains high. The use of recombinant activated protein C is a novel approach. Although the reduction in mortality was not large, it represents an important advance in therapy for this serious problem.
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Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease
Transplantation of human embryonic dopamine neurons into the putamen may have beneficial effects in patients with Parkinson's disease. In this study, 40 patients were randomly assigned to undergo transplantation or sham surgery and were followed for one year in a double-blind protocol. At one year, the scores for the primary outcome -- a global rating of improvement or worsening of symptoms -- were similar in the two groups overall, although the scores did improve with transplantation in the patients who were 60 years old or younger. Dyskinesia developed in 5 of 33 patients who eventually received transplants.
Although some symptoms did improve with the transplantation procedure in the younger patients, the development of dyskinesia is worrisome. The results do not support the use of this procedure as it was performed in this study.
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Initial Plasma HIV-1 RNA Levels in Women and Men
There have been conflicting data on the question of whether plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA differ in men and women. In this prospective study of 156 male and 46 female injection-drug users with HIV-1 infection, the initial HIV-1 RNA levels after seroconversion were about three times as high in men as in women. The median initial CD4+ lymphocyte count and the rate of progression to AIDS did not differ according to sex, however.
The initial levels of HIV-1 RNA are lower in women than in men. The current recommendation that antiretroviral treatment be initiated when the viral load is higher than 20,000 copies per milliliter means that, at the time of seroconversion, substantially fewer women than men are eligible for such treatment.
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Effect of Long-Term Dialysis on the Subsequent Survival of Renal Allografts
It is not known whether the transplantation of a kidney from a living donor without the previous initiation of long-term dialysis affects long-term allograft survival. In this study, transplantation without previous dialysis ("preemptive" transplantation) was associated with a substantial reduction in the rate of acute rejection (5.5 percent, as compared with 14.6 percent for transplantation after dialysis) and graft failure (3.8 percent vs. 5.8 percent) during a mean follow-up period of 406 days.
Transplantation of a kidney from a living donor without the previous initiation of dialysis seems to reduce the occurrence of acute rejection and increase the long-term survival of the allograft. However, the results in the group that underwent transplantation without previous dialysis may have been better because the patients in this group were healthier and more compliant. These results suggest that kidney transplantation should be performed as soon as possible in patients with end-stage renal disease for whom a living donor is available.
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High Serum IgG4 Concentrations in Patients with Sclerosing Pancreatitis
Sclerosing pancreatitis is characterized by irregular narrowing of the main pancreatic duct, hypergammaglobulinemia, and a favorable response to glucocorticoid therapy. In this study, serum IgG4 and total IgG concentrations and serum concentrations of immune complexes, including the IgG4 subclass of immune complexes, were higher in patients with sclerosing pancreatitis than in various controls. Glucocorticoid therapy resulted in clinical improvement and decreases in serum concentrations of IgG4 and immune complexes.
The results of this study indicate that sclerosing pancreatitis is a distinct disease entity, with characteristic clinical, pathological, and immunologic findings. It may be caused by the deposition of immune complexes in the pancreatic ducts. Furthermore, measurements of serum IgG4 can help to distinguish this disorder from pancreatic cancer, with which it can sometimes be confused.
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