Outcomes of intensive care for patients with human immunodeficiency virus infection.

BACKGROUND: Intensive care for patients with human immunodeficiency virus is common, costly, and associated with high morbidity. Accurate and up-to-date outcome and prognostic data are needed to effectively counsel patients and to make difficult decisions regarding admission to the intensive care unit. METHODS: We reviewed the medical charts of 394 adults infected with human immunodeficiency virus who received intensive care at San Francisco General Hospital, San Francisco, Calif, from 1992 to 1995, and we performed a multivariate analysis to learn which factors were predictive of poor outcomes. RESULTS: Respiratory failure (47%), sepsis (12%), and neurologic disease (11%) were the most common indications for admission to the intensive care unit. Overall, 63% of the patients survived hospitalization; survival rates were 27%, 18%, 13%, and 11% at 1, 2, 3, and 4 years, respectively. Independent predictors of hospital mortality were low serum albumin level, Acute Physiology Score, mechanical ventilation, and a diagnosis of Pneumocystis carinii pneumonia during admission to the intensive care unit. Low CD4+ cell count, low serum albumin level, and mechanical ventilation predicted poor long-term survival. Of the 121 patients who had a CD4+ cell count less than 50 cells/microL (0.05x10(9)/L) and a serum albumin level less than 25 g/L and required mechanical ventilation, 7% survived for 2.5 years or more after hospital discharge. CONCLUSIONS: In this series, which is the largest to date of patients admitted to the intensive care unit with human immunodeficiency virus infection, we found that long-term survival rates were low. However, even among patients who had multiple risk factors for mortality, a substantial minority survived, with a few patients achieving long-term survival.

Susceptibility to cell death is a dominant phenotype: triggering of activation-driven T-cell death independent of the T-cell antigen receptor complex.

The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant.

Activation-driven T cell death. I. Requirements for de novo transcription and translation and association with genome fragmentation.

We have observed that stimuli that are mitogenic for normal T cells can induce cell death in transformed T cell hybridomas. "Activation-driven cell death" can be triggered by the presentation of appropriate Ag as well as by treatment with lectins and antibodies specific for the T cell Ag receptor complex and other activation structures on the T cell surface, such as Thy-1 and Ly-6. The activation-driven lethal process is cell autonomous, is associated with a fragmentation of the cell's genome characteristic of the "suicide process" induced in immature T cells by glucocorticoids and in target cells by cytotoxic T lymphocytes, and is dependent upon transcription and translation, presumably associated with the expression of new gene products. We hypothesize that activation-driven cell death may be involved in vivo in the clonal deletion of auto-reactive T cells during T cell ontogeny.

The modified bovine heterograft in vascular access for chronic hemodialysis.

The results of 100 modified bovine heterografts constructed in 93 patients for subcutaneous arteriovenous fistulas for chronic hemodialysis have been reviewed. Fifty-seven patients had the bovine heterograft inserted as the primary method of vascular access. Twenty-eight patients had complications consisting of graft thrombosis and stenosis, graft infection, and hemorrhage that required additional surgical procedures. Three patients with diabetes mellitus developed ischemia of the hand. Fourteen patients have died but none of the deaths could be attributable to the use of the bovine heterograft. In our experience the modified bovine heterograft has enjoyed a higher patient acceptance as compared to other methods of vascular access for hemodialysis. The chief advantage of the bovine graft has been the ability to use the graft in any patient as a means of immediate dialysis.