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Biomedical subjects

I Salit

Publications and source records attributed to I Salit.

10 recordsLinked to original sources

A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group.

BACKGROUND: Bacteremia with the Mycobacterium avium complex is common in patients with the acquired immunodeficiency syndrome (AIDS), but the most effective treatment for this infection remains unclear. METHODS: We randomly assigned 229 patients with AIDS and M. avium complex bacteremia to receive either rifampin (600 mg daily), ethambutol (approximately 15 mg per kilogram of body weight daily), clofazimine (100 mg daily), and ciprofloxacin (750 mg twice daily) (the four-drug group) or rifabutin (600 mg daily), ethambutol (as above), and clarithromycin (1000 mg twice daily) (the three-drug group). In the three-drug group the dose of rifabutin was reduced by half after 125 patients were randomized, because 24 of 63 patients had uveitis. RESULTS: Among 187 patients who could be evaluated, blood cultures became negative more often in the three-drug group than in the four-drug group (69 percent vs. 29 percent, P<0.001). Among patients treated for at least four weeks, the bacteremia resolved more frequently in the three-drug group (78 percent vs. 40 percent, P<0.001). In the three-drug group, bacteremia resolved more often with the 600-mg dose of rifabutin than with the 300-mg dose (P=0.025), but the latter regimen was more effective than the four-drug regimen (P<0.05). The median survival was 8.6 months in the three-drug group and 5.2 months in the four-drug group (P = 0.001). The median Karnofsky performance score was higher in the three-drug group than in the four-drug group from week 2 to week 16 (P<0.05). Mild uveitis developed in 3 of the 53 patients receiving the 300-mg dose of rifabutin, an incidence about one quarter that observed with the 600-mg dose (P<0.001). CONCLUSIONS: In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

AIDS-Related Opportunistic Infections

Treatment with letrazuril of refractory cryptosporidial diarrhea complicating AIDS.

Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment was continued for > or = 10 days and for as long as there was a response. The majority of subjects (91%), had previously failed paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril. The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril. Microbiologic response is variable and relapse high. Rash is a major limiting side effect of the drug.

Acetonitriles

A multicenter randomized double-blind placebo-controlled trial of adjunctive corticosteroids in the treatment of Pneumocystis carinii pneumonia complicating the acquired immune deficiency syndrome.

A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severe Pneumocystis carinii pneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (PO2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for > 6 days, or a partial PO2 < 70 mm Hg while breathing room air 10 days after initiation of treatment. There was no statistically significant difference in the primary end point between patients randomized to corticosteroid (CS) or placebo (PL) (p = 0.522; 95% CI = -0.30, 0.16). The incidence of superinfections during therapy or of other HIV-associated infections or malignancies in the 6 months following treatment for PCP was not significantly different between the two groups. More patients randomized to placebo had to discontinue treatment with trimethoprim-sulfamethoxazole because of hypersensitivity than those randomized to corticosteroids (p = 0.039). We conclude that addition of corticosteroids does not significantly affect the outcome of PCP in patients with HIV and a PO2 < 70 mm Hg on room air at presentation but lowers the incidence of hypersensitivity reactions to trimethoprim-sulfamethoxazole.

AIDS-Related Opportunistic Infections

Programmed cell death induced by HIV type 1 antigen stimulation is associated with a decrease in cytotoxic T lymphocyte activity in advanced HIV type 1 infection.

The immune competence of peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus-seropositive (HIV+) patients was studied by assessing cytotoxic T lymphocyte (CTL) activity following recall HIV antigen stimulation. Target cells were HLA-A-matched EBV-transformed B cells expressing HIV-1 antigen. In the presence of recombinant IL-2 (rIL-2, 2 or 10 U/ml), about 50% of PBMCs from HIV+ asymptomatic patients responded to HIV-1 antigen stimulation in vitro with increased cytotoxic activity. In contrast, PBMCs from patients with overt AIDS, cultured in medium containing rIL-2 (2 U/ml) and HIV-1 antigen, showed no increase in cytotoxic activity; in the presence of rIL-2 (10 U/ml) and HIV-1 antigen, an inhibitory effect on CTL activity was observed. This inhibitory effect was associated with programmed cell death (apoptosis) of CD8+ lymphocytes and cells of both gamma/delta TcR-positive and -negative phenotypes. However, prior to the apoptosis, different TcR phenotypes of T lymphocyte reacted differently to HIV-1 antigen stimulation. The HIV-1 antigen initially appeared to cause gamma/delta TcR-positive T lymphocytes to proliferate and/or differentiate and later induced cell death. Whereas, prior to the apoptosis, no proliferation of gamma/delta TcR-negative T lymphocytes induced by HIV-1 antigen was observed.

Acquired Immunodeficiency Syndrome

Lack of correlation between phenotype activation markers of CD8 lymphocytes and cytotoxic T lymphocyte (CTL) function in HIV-1 infection: evidence for rescue with rIL-2.

CTL activity against HIV-1 antigens expressed on HLA-A-matched EBV-transformed B target cells was detected in 33% (6/18) of freshly isolated PBMC (FPBMC) from patients in the early stages of HIV-1 infection (CDCII). No CTL activity was detected in FPMBC in patients with AIDS (CDCIV). However, the presence of CTL activity did not correlate with the expression of CTL activation markers. A dual-color flow cytometric examination revealed that the CD8+ lymphocytes bearing the memory (CD29) and activation (S6F1) surface molecules increased in number as the HIV-1 infection progressed. This functional and phenotypic discrepancy in memory CD8+ lymphocytes suggests that the memory CD8+ lymphocytes have lost cytotoxic function and become "paralyzed" as the HIV disease progresses. Incubation of PBMC of HIV(+) patients with rIL-2 reactivated predominantly HIV-specific CTL. However, rIL-2 stimulation also activated a "polyclonal or polyreactive" cytotoxic function. The reactivation of CTL function is rIL-2 dosage dependent and the amount of rIL-2 required for reactivation is associated with the severity of the disease. HIV antigen specific CTL in HIV(+) patients can be selectively expanded by HIV antigen stimulation in the presence of rIL-2. These results suggest that the in vivo IL-2 deficiency occurring in HIV-1 infection may be responsible in part for the "paralysis" of HIV specific CTL activity. Such activity can be rescued nonspecifically by exogenous rIL-2 stimulation and expanded specifically by HIV-1 antigen stimulation.

Antigens, Surface

Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome.

Sleep physiology, viral serology and symptoms of 14 patients with chronic fatigue syndrome (CFS) were compared with 12 healthy controls. All patients described unrefreshing sleep and showed a prominent alpha electroencephalographic nonrapid eye movement (7.5-11.0 Hz) sleep anomaly (p less than or equal to 0.001), but had no physiologic daytime sleepiness. There were no group differences in Epstein-Barr virus (EBV) antibody titers. The patient group had more fibrositis tender points (p less than 0.0001), described more somatic complaints (p less than 0.0001), and more depressive symptoms (p less than 0.0001). Patients with CFS do not show evidence for a specific chronic EBV infection, but show altered sleep physiology, numerous tender points, diffuse pain, and depressive symptoms. These features are similar to those found in fibromyalgia syndrome.

Adult

Invasive fungal infection in the immunosuppressed host.

Immunosuppression, whether arising as a consequence of disease (haematopoietic and lymphoreticular malignancies) or therapy (against hemograft rejection or malignancy results in a higher than normal incidence of invasive fungal infections such as candidiasis, aspergillosis, mucormycosis and cryptococcosis. Normal host defense mechanisms, both immunologic and non-immunologic, are not fully functional and may contribute to the pathogenesis of these diseases.Candida, normally a superficial colonizer, may invade the gastrointestinal, respiratory or urinary tracts. Aspergillus and mucor species may cause hemorrhagic or necrotising pneumonias and secondarily spread to the brain. Cryptococcus may infect the meninges in the appropriate host. Therapeutics for these diseases is limited. Amphotericin B may alter the course of any of the four diseases. Fluorocystosine has found some use in the treatment of candidiasis and cryptococcosis.

Amphotericin B