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Biomedical subjects

A S Levin

Publications and source records attributed to A S Levin.

At least 37 records · Page 2Linked to original sources

A phase II study of effect of addition of trichosanthin to zidovudine in patients with HIV disease and failing antiretroviral agents.

Patients infected with HIV, including those with AIDS-related complex and AIDS, and failing treatment with antiretroviral agents such as zidovudine, have been evaluated following addition of trichosanthin to the antiretroviral agent regimen. This ribosomal inhibitory protein is specifically cytotoxic for HIV-infected macrophages and lymphocytes. Ninety-three patients were treated with trichosanthin, using a schedule of weekly, then monthly, intravenous injections of 1.2 mg of drug in combination with antiretroviral agents, usually zidovudine. Side effects included myalgias, fevers, mild elevation in liver function tests, and mild-moderate anaphylactic reactions, which respond well to therapy with steroids and/or benedryl. Reversible mental status changes were noted in two patients, both receiving concomitant therapy with ddI. Clinical responses to trichosanthin treatment were monitored primarily by changes in laboratory parameters, particularly levels of CD4+ T lymphocytes. In the total population evaluated for efficacy (85 patients) there was a significant increase in CD4+ cell levels after initiation of trichosanthin therapy. A second analysis performed on 72 patients measured the rate of change of CD4+ cells during therapy, using an "area under the curve" analysis. During therapy there was a median increase of 1.2 cells/mm3/month. In patients in the top 25th percentile, this increase was greater than 8.4 cells/mm3/month. In 59 of the 72 patients, responses could also be monitored by comparing the rate of loss of CD4+ cell levels on antiretroviral agents (zidovudine or ddI) alone, during the year prior to initiation of trichosanthin, to the rate of change when trichosanthin was added to the treatment regimen. During the period before trichosanthin treatment (311 +/- 11.7 days) the median loss of CD4+ cells was 6.91 cells/mm3/month. Addition of trichosanthin to the treatment regimen resulted in a median gain of 1.1 CD4+ cells/mm3/month.

Adolescent↗

Distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae strains isolated in Brazil from 1988 to 1992.

Forty-two serotypes were identified among 288 Streptococcus pneumoniae strains isolated from patients living in Brazil. Serotyping was determined by the capsular typing test (Quellung reaction). Types 14 (10.4%), 6B (9.8%), 23F (8.0%), 5 (7.3%), 19F (6.9%), 6A (6.0%), and 1 and 4 (4.6%) were the most commonly identified strains. Two hundred twenty (76.4%) of the strains were of serotypes that are included in the 23-valent pneumococcal polysaccharide vaccine. If vaccine-related serotypes are also considered, the proportions of coverage in the vaccine are 82.3% (if type 6B alone is added) and 85.7% (if all the vaccine-related types are considered to be cross-protecting). Decreased susceptibility to penicillin, which was identified by using the 1-microgram oxacillin disk method as a screening test, was detected in 70 (26.7%) strains. The MICs of nine antimicrobial agents were determined by using the procedures recommended by the National Committee for Clinical Laboratory Standards. Seventy (35.9%) of the strains were resistant to tetracycline, 57 (29.2%) were resistant to sulfamethoxazole-trimethoprim, 3 (1.5%) were resistant to rifampin, 2 (0.80%) were resistant to penicillin, and 1 (0.5%) was resistant to chloramphenicol. The two penicillin-resistant strains were also resistant to or had decreased susceptibilities to cephalosporins. Forty-seven (17.9%) of the strains were intermediately resistant to penicillin, 17 (8.7%) were intermediately resistant to tetracycline, 13 (6.7%) were intermediately resistant to chloramphenicol, 12 (6.1%) were intermediately resistant to erythromycin, and 6 (3.1%) were intermediately resistant to rifampin.

Brazil↗

Neurological reactions in HIV-infected patients treated with trichosanthin.

Trichosanthin is a ribosome-inactivating protein that is being studied as a possible treatment for patients infected with human immunodeficiency virus (HIV). We report the clinical and pathological features in two patients who experienced neurological reactions to trichosanthin. Both patients were neurologically asymptomatic prior to treatment but developed coma and multifocal neurological deficits after treatment. Neuropathological examination revealed regions of severe, multifocal necrosis with histiocytic infiltrates. These reactions to trichosanthin may be mediated by soluble factors released by HIV-infected macrophages.

Acquired Immunodeficiency Syndrome↗

An outbreak of nosocomial Legionnaires' disease in a renal transplant unit in São Paulo, Brazil. Legionellosis Study Team.

From June 1989 to March 1990 there were eight cases of Legionnaires' disease caused by Legionella pneumophila serogroup 1 in a renal transplant unit. There were seven cases of pneumonia and one case of pleural effusion. A study was conducted to identify the source of the outbreak. Legionella anisa was cultured from tap water. Twenty-seven staff members of the unit were serologically tested and antibody titres were positive in two. The probable source of infection was the potable water system. Control measures were hyperchlorination and heating of the water, after which there were no further cases during 5 months' follow up. We believe this is the first reported Legionnaires' disease outbreak in Latin America.

Brazil↗

A phase I/II study of trichosanthin treatment of HIV disease.

Trichosanthin, a ribosomal inhibitor protein, blocks HIV replication in lymphocytes and macrophages. This agent was used to treat 51 patients with advanced HIV disease in a dose-escalation study in which three injections were administered over a 9-21-day period in a dose range of 10-30 micrograms/kg per injection. The maximum tolerated dose was estimated to be 30 micrograms/kg. Reversible but severe fatigue and myalgias were the major dose-limiting side-effects; mild leucocytosis and elevations in serum transaminases were noted and were reversible. Non-dose-related reversible mental status changes were seen in six patients and were considered to be associated with the drug. This was usually manifest as dementia, but progressed to coma in two patients. This reversed, but the sequelae resulted in death in one patient. Decreases in serum p24 antigen levels were noted 1 month after the first infusion in 10 of 18 patients who entered the study with elevated levels; one converted to negative. Values usually remained low to the end of the study period (2 months). In those patients with CD4+ cell levels greater than 50 x 10(6) cells/l significant decreases in sedimentation rate and increases in CD4+ cell numbers were also noted. These changes were found at all dose levels but only in patients receiving three infusions.

Adult↗

Association between clinical symptoms and lymphocyte abnormalities in a population with chronic domestic exposure to industrial solvent-contaminated domestic water supply and a high incidence of leukaemia.

An unusually high incidence of leukaemia and recurrent infections was noted in children exposed in utero to domestic water supply contaminated with industrial solvents including trichloroethylene, perchloroethylene and 1,2-transdichloroethylene. Medical and laboratory investigations were carried out on 28 family members of the patients with leukaemia with particular emphasis on the immunological system to determine if they displayed symptoms associated with acute or chronic exposure to these chlorinated hydrocarbons. The principal organ systems affected were neurological, immunological and cardiological. Damage to these systems was found in all subjects by history, physical and laboratory parameters. Damage to the immunological system was manifest by altered ratios of T lymphocyte subpopulations, increased incidence of auto-antibodies, increased infections and recurrent rashes.

Adult↗

[Information value of right precordial ECG leads in the diagnosis of right ventricular myocardial infarct].

An analysis of the right ECG precordial leads in 61 patients with left ventricular posteroinferior myocardial infarction and in 55 patients with combined affection of the right and left ventricular posteroinferior walls revealed a high informative value of ST segment elevation for recognition of right ventricular myocardial infarction on the 1st day. Further on the formation of the QS complex in V3R-5R leads was of certain value. Combined assessment of ST segment elevation and the QS formation in the right precordial leads significantly increased diagnostic potentialities in the detection of right ventricular myocardial infarction.

Diagnosis, Differential↗

"Toxic torts".

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Humans↗

Copper metabolism in American retinitis pigmentosa patients.

Serum copper, serum caeruloplasmin, and urinary copper excretion were measured in 38 American patients (and 15 family members) with recessive, dominant, and X-linked forms of retinitis pigmentosa. No abnormalities were found, in contrast to the findings of a recent study on Indian patients. Our data argue against a role for copper metabolism in ordinary retinitis pigmentosa.

Adolescent↗

Copper and zinc levels in serum from human patients with sarcomas.

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in 19 patients with sarcomas, 12 of which were osteosarcomas at various stages. Patients with primary or metastatic osteosarcoma had elevated SCL, whereas amputated osteosarcoma patients who were clinically tumor-free had nearly normal SCL. Patients with primary osteosarcoma had elevated SZL, those with metastases had depressed zinc levels, and amputated patients who were clinically tumor-free and nearly normal SZL. Thus, the ratio of SCL:SZL in metastatic osteosarcoma patients is higher than in patients with primary osteosarcoma. SCL and SZL are compared to clinical histories for selected patients. Patients with the more advanced disease and poorest prognoses had the most elevated SCL and highest SCL:SZL ratios. It appears that the determination of SCL and SZL in osteosarcoma patients may be of value in prognosis and therapy evaluation; furthermore, the ratio of SCL:SZL may be useful in discriminating between patients with primary and metastatic osteosarcoma.

Adolescent↗

Circadian rhythm of stimulated lymphocyte blastogenesis. A 24 hour cycle in the mixed leukocyte culture reaction and with SKSD stimulation.

The in vitro measurement of stimulated T lymphocyte blastogenesis by the incorporation of 14C-thymidine can be shown to be an acceptable and precise measurement with highly significant variations in blastogenesis over a 24 hr period. This circadian rhythm for human T lymphocyte blastogenesis has been demonstrated with specific antigen (SKSD) and in mixed leukocyte culture (MLC). The hours of peak reactivity were different for the SKSD stimulation and the MLC reaction. This biologic cycle in T cell reactivity has significant implications for the immunologic response.

Adult↗