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Biomedical subjects

M M Lederman

Publications and source records attributed to M M Lederman.

126 records · Page 7Linked to original sources

Measurement of glycosylated hemoglobins in black diabetic patients: a note of caution.

Inspection of chromatography columns used for measurement of glycosylated hemoglobins revealed that blood samples from certain black diabetic patients produced two residual hemoglobin bands after chromatography rather than one. The levels of glycosylated hemoglobin were significantly lower in these subjects than in other diabetics. Further investigation revealed that each of these subjects had the hemoglobin AS or AC phenotype. The presence of hemoglobin S or C appears to cause spuriously low levels of glycosylated hemoglobin as determined by ion exchange chromatography. Other means to assess diabetic control should be used for patients with these abnormal hemoglobins.

Black People↗

Toxic shock syndrome: clinicopathologic findings in a fatal case.

A 15 year old girl presented with a painful desquamative rash, fever, and profound hypotension. Despite antimicrobial therapy and intensive supportive measures, she died 80 hours after admission. The premortem skin biopsy and autopsy findings, which included subepidermal edema and blister formation, subacute vasculitis, and striking interstitial edema involving several organs, are consistent with a toxin mediated process. Current knowledge of the pathogenesis of the toxic shock syndrome and its differential diagnosis are discussed in light of the clinicopathologic findings in this case.

Adolescent↗

Pneumococcal immunization in adult diabetics.

The antibody responses of 102 adult insulin-treated diabetics who received 14-valent pneumococcal polysaccharide vaccine were measured. Grand mean preimmunization antibody levels were similar for diabetics, 255 ng protein N/ml, and controls, 234 ng protein N/ml. Postimmunization, the values in the diabetics, 1009 ng protein N/ml, and 834 ng protein N/ml in 48 healthy controls, were not significantly different. The height of antibody response in the diabetic group did not correlate with age, sex, duration of diabetes, insulin dose, concentration of glycosylated hemoglobin, fasting or 2-h postprandial glucose concentrations, or the presence of retinopathy. Side effects were minimal and occurred in 26%. Antibody response to pneumococcal polysaccharide vaccine is not impaired in adult diabetics. Pneumococcal immunization is safe and may reduce the frequency of pneumonia and its complications in the diabetic population.

Adult↗

Defective suppressor cell generation in juvenile onset diabetes.

Lymphocytes of juvenile onset, insulin-dependent diabetics failed to generate suppressor cell activity after preincubation with concanavalin A (Con A). The mean suppression of the autologous proliferative response to phytohemagglutinin (PHA) was 6.1 +/- 7.8% (mean +/- SEM) in the diabetics and 34.0 +/- 4.9% in 9 age-matched healthy controls (p less than 0.01). Cell mixing experiments identified the defect to be in the generation of suppressor cells rather than in the responses to their action. Plasma of insulin-dependent diabetics had no effect on the generation of suppressor activity. In contrast to our findings in insulin-dependent diabetics, Con A preincubation of lymphocytes from 4 maturity onset diabetics induced normal suppression of PHA responses. Defective immunoregulation is present in insulin-dependent diabetes and may underlie autoimmunity.

Adolescent↗

Generation of a soluble immune response suppressor factor (IRSF) by unstimulated leukocytes of healthy subjects.

Supernatants derived from unstimulated cultures of mononuclear leucocytes obtained from healthy subjects contained a factor(s) which consistently suppressed lymphocyte proliferative responses to antigens and mitogens. This factor(s) is produced by a non-adherent cell and was generated in vitro after 4 hr of culture. Cells from almost all healthy subjects produced this substance(s). Cell number and viability were not affected by it. Kinetic studies suggested that interference with antigen presentation was not the mechanism of its action. The release of this immune response suppressor factor(s) (IRSF) was not blocked by indomethacin and its biological activity was unrelated to levels of prostaglandin E2. Experiments with low-specific-activity thymidine showed that suppression was not due to release of unlabelled nucleotide. Preliminary characterization of IRSF revealed that it is heat-stable and partially dialysable through membranes with an exclusion size of 12,000 daltons. IRSF differs from previously reported soluble suppressor substances and may play a role in immunoregulation in health.

Adult↗

Human immunodeficiency virus 1 protease inhibitors in clinical practice: predictors of virological outcome.

OBJECTIVES: To ascertain whether prolonged suppression of viral replication can be achieved in clinical practice and to identify factors associated with virological outcome. DESIGN: Retrospective observational study. SETTING: University-affiliated human immunodeficiency virus (HIV) clinic in Cleveland, Ohio. PARTICIPANTS: Patients treated with regimens that included protease inhibitors between June 1995 and December 1997. We identified 366 patients; 310 had sufficient virological follow-up data to be included. MAIN OUTCOME MEASURE: Virological success was defined as plasma HIV-RNA levels lower than 400 copies/mL at the last clinic visit. Virological failure was subdivided according to the maximum degree of suppression of viral replication achieved. Multivariate analysis was performed to identify baseline factors associated with virological outcome. RESULTS: Virological success was achieved by 47% of patients at a median follow-up of 335 days. The median CD4+ cell count increase and HIV-RNA level decrease were 0.10x10(9)/L (100 cells/microL) and greater than 1.3 log10 in patients who achieved virological success, and 0.010x10(9)/L and 0.32 log10 for those who did not. In multivariate analysis the likelihood of virological success was diminished in women (P<.02) and in patients who missed 2 or more clinic visits in the prior year (P<.001), and decreased when the regimen was started earlier (P<.04). Patients with a lower nadir CD4+ cell count (P<.04) and higher peak plasma HIV-RNA levels (P<.001) also had a decreased likelihood of virological success. CONCLUSIONS: More than half the patients who started a regimen that included protease inhibitors in an academic clinical practice failed to achieve durable suppression of viral replication and also experienced a poorer immunologic outcome as determined by CD4+ cell count increase. Missed clinic visits, more advanced disease, and higher plasma HIV-RNA levels may predict failure.

Adolescent↗

Prognostic factors in acquired immunodeficiency syndrome.

To identify prognostic factors in acquired immunodeficiency syndrome (AIDS), the authors studied an inception cohort of 45 patients in a non-endemic area (Group I). The probability of survival was 67% six months after the diagnosis of AIDS and 32% at 12 months. As shown by multivariate Cox regression analysis, survivals were shorter (p less than 0.01) in patients 35 years old or older and in those who had anemia when AIDS was diagnosed. In patients with neither of these poor prognostic factors, the 12-month survival was 64%; in patients with one factor, it was 22%; and in patients with both factors, 0%. The prognostic significance of these two factors was validated in a second inception cohort of 50 patients (Group II): in patients with zero, one, and two poor prognostic factors, the 12-month survivals were 80%, 58%, and 26%, respectively. Other poor prognostic factors in Group I included disseminated Mycobacterium avium-intracellulare and the development of new opportunistic infections or neoplasms. The authors conclude that clinically important prognostic factors can be identified in AIDS patients. These findings should be considered in planning therapeutic trials and in counseling patients.

Acquired Immunodeficiency Syndrome↗

Septic arthritis caused by Bacteroides fragilis.

As improvements in bacteriologic techniques have enhanced the recovery of anaerobic bacteria from clinical specimens, there has been an increasing awareness of the role of anaerobes in disease. Bacteroides fragilis is the most common anaerobic organism found in clinical specimens. Although it is the anaerobe most frequently associated with bacteremia and a common isolate in intraabdominal infections, infections of the female genital tract, wounds, and abscesses, B. fragilis is a rare cause of septic arthritis. The isolation of this organism from four patients with septic arthritis in three Cleveland hospitals between 1978 and 1982 suggests that septic arthritis due to B. fragilis may be a more common clinical entity than previously appreciated. In this report we describe these cases and review the pertinent literature.

Adult↗

Invasive infection with Saccharomyces cerevisiae: report of three cases and review.

Saccharomyces cerevisiae (brewer's or baker's yeast) is a common colonizer of human mucosal surfaces, but its role as a clinically important pathogen has been unclear. We report three cases of life-threatening invasive infection with S. cerevisiae resulting in pneumonia, liver abscess and sepsis, and disseminated infection with cardiac tamponade, respectively. A review of the English-language literature reveals 14 other cases of saccharomyces infection in humans. Severe immunosuppression, prolonged hospitalization, prior antibiotic therapy, and/or prosthetic cardiac valves are the settings where saccharomyces infection has been observed. Because Saccharomyces can be a common saprophytic contaminant, biopsy and pathologic confirmation of infection are often necessary for a definitive diagnosis. Amphotericin B is the treatment of choice for serious infections with this organism.

Aged↗

Alternaria infection in a patient with acquired immunodeficiency syndrome: case report and review of invasive alternaria infections.

A 31-year-old man with AIDS developed a necrotic lesion on his nasal septum due to Alternaria alternata. Excision and treatment with amphotericin B resulted in cure. This case expands the spectrum of opportunistic pathogens that infect patients with AIDS. Visceral and mucosal infections due to Alternaria have been reported in at least seven other patients.

Acquired Immunodeficiency Syndrome↗

Nonsurgical cure of pulmonary mucormycosis.

Pulmonary mucormycosis is an unusual infection which appears to occur with increased frequency in diabetics. We report the development of pulmonary mucormycosis in an adult onset diabetic which resolved with medical therapy alone. Computerized tomography proved useful in assessing his response to therapy.

Aged↗

Antibody response to pneumococcal polysaccharides in insulin-dependent diabetes mellitus.

Twenty-one insulin-dependent diabetics and 11 healthy control children were immunized with polyvalent pneumococcal polysaccharide vaccine. Serum antibody to pneumococcal polysaccharides was measured by radioimmunoassay before and after immunization. Although there were some differences in type-specific antibody concentrations between diabetic and control subjects, the overall antibody concentrations preimmunization, 3-4 wk postimmunization, and 6-7 wk postimmunization were similar in both populations. In both groups antibody response to immunization correlated strongly with preimmunization antibody concentration. Among the diabetic subjects there was no correlation between antibody responses and duration of disease, insulin dose, or concentration of glycosylated hemoglobin. Insulin-dependent diabetic subjects have a serum antibody response to pneumococcal polysaccharides equivalent to that of controls, and in both populations the magnitude of the antibody response correlates with preimmunization antibody levels.

Adolescent↗

Acquired immunodeficiency syndrome: case reporting at a university hospital.

BACKGROUND: Planning and allocating resources for care of patients with acquired immunodeficiency syndrome (AIDS) requires accurate assessment of disease incidence. OBJECTIVE: To assess the accuracy and completeness of AIDS case reporting at our institution, we reviewed all inpatient and outpatient records of patients with AIDS seen at University Hospitals of Cleveland, Ohio, between January 1983 and July 1990. METHODS: The patients were identified through review of hospital discharge summaries, ambulatory clinic listings, and laboratory identification of opportunistic infections. RESULTS: We found that 24 of 291 AIDS cases (8%) seen at this institution had not been reported to state health departments. Of the 24 patients with unreported AIDS, 16 had received an AIDS diagnosis at other institutions, 11 had never been hospitalized at this institution, and 2 had used pseudonyms. CONCLUSIONS: Review of AIDS case reporting can ascertain the magnitude of underreporting; the profile of patients who were unreported may be used to evaluate the accuracy of reporting elsewhere and to identify systematic problems in case reporting methods.

Acquired Immunodeficiency Syndrome↗

HIV nephropathy and the Duffy antigen/receptor for Chemokines in African Americans.

BACKGROUND AND OBJECTIVES: HIV nephropathy (HIVAN) is markedly racially biased in its distribution, occurring in about 10% of HIV infected African Americans according to some studies. Based upon previous laboratory and epidemiological studies, the Duffy promoter polymorphism, which occurs almost exclusively in individuals of African descent, has been postulated to be the predisposing factor. We aimed to explore that relationship by directly genotyping individuals with HIV nephropathy to determine the proportion homozygous for this mutation to test the hypothesis it was responsible for the genetic component of this disease. We anticipated that if the polymorphism was associated with HIV nephropathy all individuals would be homozygous for this mutation. METHOD: Individuals with HIVAN proven on biopsy were identified from previous studies and a pre-existing clinical database. This diagnosis was confirmed by an experienced pathologist examining the biopsies in a blinded fashion. PCR and RFLP strategies were used on the biopsy samples to genotype for the Duffy promoter polymorphism. The cases were compared to a control population of HIV seronegative African Americans. RESULTS: Twenty African American individuals with HIV nephropathy were successfully genotyped. Only nine were homozygous for the promoter mutation. Nine were heterozygous and two homozygous wild type. Furthermore, the frequency of the polymorphism did not differ from the background rate in the African American population (OR = 0.788 95% confidence intervals 0.378-1.64). CONCLUSION: The Duffy promoter polymorphism was not disproportionately represented in persons with HIVAN calling into question any significant role in the pathogenesis of HIVAN.

AIDS-Associated Nephropathy↗

Cytokines and cytokine therapies in HIV infection.

HIV infection is characterized by a variety of disturbances in the regulation of cytokine expression. These disturbances include a general decrease in the expression of type 1 T-helper cytokines, an increase in expression of proinflammatory cytokines, a possible increase in type 2 helper cytokines, and increased expression of antiviral interferons and TGF-beta. These perturbations may contribute to HIV disease pathogenesis by contributing to the impaired cellular immune responses and cell loss that characterize HIV infection and AIDS and by accelerating replication of HIV-1. Treatment trials utilizing cytokines and their inhibitors may provide useful adjuncts in the management of HIV-1 disease, and at the same time they can be designed to help clarify the role of cytokine dysregulation in the pathogenesis of HIV-1 disease. Although powerful combinations of antiretroviral drugs can reduce plasma HIV levels below the limits of detection, it is not clear that full immunological reconstitution is a consequence of these interventions. Trials of immune-based therapies, including trials of cytokines and their inhibitors, are therefore an increasingly important component of our treatment research agenda.

Chemokines↗