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Biomedical subjects

M A Fischl

Publications and source records attributed to M A Fischl.

At least 91 records · Page 5Linked to original sources

The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.

AIDS-Related Complex↗

The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

AIDS-Related Complex↗

Evaluation of heterosexual partners, children, and household contacts of adults with AIDS.

Forty-five adults with the acquired immunodeficiency syndrome (AIDS) and their 45 spouses, 109 children, and 29 household contacts were studied for evidence of heterosexual, perinatal, and household spread of human T-cell lymphotropic virus type III (HTLV-III) infection. Of the 45 spouses enrolled, 26 (58%) had antibody to HTLV-III, including 12 (71%) of 17 male spouses and 14 (50%) of 28 female spouses. Of the 12 seropositive male spouses, nine were seropositive at enrollment and three had seroconversion. Of the 14 seropositive female spouses, four were seropositive at enrollment and ten seroconverted. Lack of barrier contraceptive use and oral sex were associated with seroconversion. Of the 109 children enrolled, 15 had AIDS or an AIDS-related illness, two had evidence of passive transfer of maternal antibodies, and two had HTLV-III infection acquired outside the household. None of the 90 seronegative children seroconverted. Of 29 household contacts studied, none developed antibody to HTLV-III.

Acquired Immunodeficiency Syndrome↗

Response of human-immunodeficiency-virus-associated neurological disease to 3'-azido-3'-deoxythymidine.

Four patients with human-immuno-deficiency-virus-associated neurological disease were treated with 3'-azido-3'-deoxythymidine (AZT). Three (two with chronic dementia, and one with chronic dementia and peripheral neuropathy) improved as assessed by clinical examination, psychometric tests, nerve conduction studies, and/or positron emission tomography; there was no improvement in the fourth patient who presented with paraplegia. These results support the hypothesis that certain AIDS-virus-associated neurological abnormalities are reversible by antiretroviral chemotherapy.

Acquired Immunodeficiency Syndrome↗

Use of whole blood methods in assessment of immune parameters in immunodeficiency states.

Whole blood (WB) methods requiring less than 4 ml heparinized peripheral blood were used to define mononuclear cell phenotype, lymphocyte proliferation, and natural cell-mediated cytotoxicity (CYT) in samples from normal controls and patients with immunodeficiency states of acquired immunodeficiency syndrome (AIDS) and AIDS-related complexes (ARC). Results from two-color direct immunofluorescence staining of blood samples with monoclonal antibodies (Mabs) conjugated to phycoerythrin (PE) or to fluorescein isothiocyanate (FITC) and flow cytometry for the determination of mononuclear cells reactive with T11, T4, T8, B1, and NKH.1 surface markers were compared to one-color indirect immunofluorescence analysis with unlabeled Mabs and FITC-labeled goat anti-mouse IgG and flow cytometry. We found that two-color analysis was as sensitive as one-color analysis in detecting abnormal subset distribution in the patient groups. Functional properties of mononuclear cells (MNC) in WB samples and after density gradient separation were studied by mitogen-induced lymphocyte proliferation and CYT. Although the means of the groups studied varied depending on method used, results using WB methods clearly delineated the expected differences between the immunodepressed patients and normal subjects. The effects of sample storage on results obtained with WB methods for surface marker analysis, lymphocyte proliferation, and natural killer activity were also examined.

AIDS-Related Complex↗

Patient tolerance to interferon: clinical and laboratory assessments.

Toxicity has been associated with interferon therapy, predominantly in immunocompromised patients. Side effects appear to be dose-related and were difficult to manage. However, interferon was well-tolerated and some of the toxicity may be related to the immunocompromised state.

Adult↗

ICU survival of patients with the acquired immunodeficiency syndrome.

The ICU records of 31 patients with the acquired immunodeficiency syndrome were reviewed. Of 23 (74%) patients admitted for respiratory failure requiring intubation and mechanical ventilation, 20 (87%) patients had Pneumocystis carinii and/or cytomegalovirus pneumonia. Of the eight patients admitted without respiratory failure, five (63%) were monitored after brain biopsy. Respiratory failure patients remained in the ICU for 10 +/- 1 days, compared to 5 +/- 1 days for those without respiratory failure (p less than .05). Overall mortality was 24 patients (77%); 21 (91%) of 23 respiratory failure patients died, compared to three (38%) of the eight without respiratory failure (p less than .01). All seven ICU survivors lived to hospital discharge.

Acquired Immunodeficiency Syndrome↗

Salmonella bacteremia as manifestation of acquired immunodeficiency syndrome.

Multiple opportunistic infections are characteristic of the acquired immunodeficiency syndrome (AIDS). Although bacterial pathogens have presented few problems, we have noted an emerging problem with salmonellal infection among patients with AIDS. A review of all stool and blood cultures from adults between January 1982 and July 1984 showed that 80 stool cultures were positive for Salmonella species; serogroup B was the most common isolated. Eight (10%) were isolated from patients with AIDS. Nineteen blood cultures were positive for Salmonella species. Six (32%) were isolated from patients with AIDS: three were positive for Salmonella serogroup B; two yielded Salmonella choleraesuis; and one yielded Salmonella serogroup D. In three (50%), Salmonella bacteremia was a presenting manifestation of AIDS. Bacteremias were recurrent in five patients. Thus, it appears that AIDS not only predisposes patients to serious salmonellal infections but also compromises their ability to eradicate these bacteria.

Acquired Immunodeficiency Syndrome↗

Mothers of infants with the acquired immunodeficiency syndrome. Evidence for both symptomatic and asymptomatic carriers.

Sixteen mothers of 22 infants with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were followed up for evidence of clinical and immunologic abnormalities. With one exception, all mothers were clinically well at delivery but had evidence of immune dysfunction, with T-cell abnormalities and inverted T4/T8 ratios and/or elevation of serum immunoglobulin levels, particularly of IgG. During a follow-up period that averaged 30 months, AIDS developed in five of the mothers and AIDS-related complex in seven. Twelve subsequent pregnancies in 11 mothers produced four affected infants, suggesting that mothers can be persistently infected. Six mothers were delivered of subsequent infants who remain unaffected. These results suggest that the mothers are the likely source of infection in non-transfusion-associated cases of AIDS or AIDS-related complex in infants, that mothers have persistent immunologic abnormalities, and that they are at increased risk of developing AIDS or AIDS-related complex.

Acquired Immunodeficiency Syndrome↗

Kaposi's sarcoma of the tracheobronchial tree. Clinical, bronchoscopic, and pathologic features.

Two homosexual men with disseminated Kaposi's sarcoma presented with paroxysms of a nonproductive cough probably related to the presence of tumor in the airways. At bronchoscopy, multiple, flat, brightly red to violaceous lesions were seen throughout the tracheobronchial tree. In both patients the bronchial biopsies were nondiagnostic, and one patient had excessive bleeding after the procedure. Autopsies confirmed the presence of Kaposi's sarcoma in the trachea and bronchi. The bronchoscopic appearance of Kaposi's sarcoma of the tracheobronchial tree is characteristic, and bronchial biopsy is probably unnecessary when the diagnosis of Kaposi's sarcoma has already been made by biopsy of more accessible lesions. Furthermore, bronchial biopsy may be hazardous because of excessive bleeding.

Adult↗

Upper airway obstruction secondary to acquired immunodeficiency syndrome-related Kaposi's sarcoma.

A 45-year-old man with a history of intravenous drug use presented with acute respiratory distress. A pulsus paradoxus of 42 mm Hg, accessory respiratory muscle use and stridor were present. Examination of the oropharynx revealed multiple 1 to 2 cm purple lesions of the gingiva and hard palate. A purple tumor mass in the posterior pharynx obstructed the view of the larynx. An emergency tracheostomy was performed resulting in hemorrhage into the respiratory tract. Autopsy revealed disseminated Kaposi's sarcoma and large blood clots in the trachea and main stem bronchus. This case illustrates the occurrence of life threatening involvement of the upper aerodigestive tract with Kaposi's sarcoma and hemorrhagic complications resulting from surgical manipulation.

Acquired Immunodeficiency Syndrome↗

Decreased natural cell-mediated cytotoxicity per effector cell in acquired immunodeficiency syndrome.

Natural cell-mediated cytotoxicity (CYT) was determined using whole blood samples from 32 patients with the acquired immunodeficiency syndrome (AIDS) and 12 with AIDS-related complexes (ARC) and correlated with the number of putative natural killer cells (NK) bearing surface marker Leu 11a. Mean percent cytotoxicity (%CYT) was significantly lower in AIDS and ARC patients compared to that of normal controls. Mean %NK cells in AIDS patients was significantly higher than in normals, while %NK cells in ARC patients did not differ significantly from that of normals. In contrast, the absolute number of NK (NNK) cells in AIDS patients did not differ significantly from that of normals, while the NNK cells in ARC patients was significantly lower than those in normals. When the data were expressed in kinetic lytic units per NK cell (KLU/NK = maximum number of K562 cells killed per NK cell in 4 hours), significantly lower KLU/NK were observed in both AIDS and ARC patients compared to that in normals. Our data show that NK cells in AIDS and ARC patients are in a less active state compared to those in normals.

Acquired Immunodeficiency Syndrome↗

Enteric coccidiosis among patients with the acquired immunodeficiency syndrome.

Ten patients were identified at Jackson Memorial hospital/University of Miami Hospitals and Clinics with enteric coccidial infection due to Cryptosporidium spp. or Isospora belli. All had the acquired immunodeficiency syndrome as manifested by Kaposi's sarcoma or multiple opportunistic infections, or both. They presented with profuse diarrhea associated with weakness, anorexia, and weight loss. Routine examinations of stools for eggs and parasites as performed by the hospital laboratory were negative in all patients. Sugar flotation and modified acid fast techniques were used in the Tropical Disease Laboratory to identify oocysts of Cryptosporidium spp. in stools of seven patients. Malabsorption, characterized by a low 5-hour D-xylose and positive fecal fat, was observed in 6/6 of these patients. In three other patients Isospora belli oocysts were identified in stool specimens or via a duodenal string test. Spiramycin was the only drug found to be effective in treating patients with cryptosporidiosis. Patients with Isospora belli responded to a prolonged course of trimethoprim-sulfamethoxazole.

Acquired Immunodeficiency Syndrome↗

Glomerular lesions in the acquired immunodeficiency syndrome.

Between January 1982 and December 1983, 75 patients with the acquired immunodeficiency syndrome were identified in our hospitals: 35% used intravenous drugs, 50% had proteinuria in excess of 0.5 g/dL, and 10% were nephrotic. Glomerular changes seen at autopsy in 36 patients included frequent mesangial lesions and deposits associated with mild asymptomatic proteinuria. Focal and segmental glomerular sclerosis was found in 5 patients and 4 of these had the nephrotic syndrome. Whereas reversible episodes of acute renal failure were not uncommon, terminal episodes of acute renal insufficiency occurred in 14 patients. The short survival of these patients may prevent the development of chronic renal failure.

Acquired Immunodeficiency Syndrome↗