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Biomedical subjects

L Schlesinger

Publications and source records attributed to L Schlesinger.

At least 19 recordsLinked to original sources

Failure of trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia with concurrent leucovorin use.

Pneumocystis carinii is a common cause of pneumonia in patients with AIDS, however, the incidence has dropped with the availability of effective prophylactic regimens. First-line treatment for both acute Pneumocystis pneumonia and chronic prophylaxis is trimethoprim/sulfamethoxazole (TMP/SMX). This combination can cause hypersensitivity reactions as well as myelosuppression. The simultaneous administration of leucovorin during acute treatment has been shown to reduce the incidence of neutropenia, but may interfere with the efficacy of TMP/SMX. We report a case of P. carinii pneumonia in a patient with AIDS who failed TMP/SMX prophylaxis while taking leucovorin.

AIDS-Related Opportunistic Infections↗

Measures of prefrontal system dysfunction in posttraumatic stress disorder.

Clinical observations have suggested that individuals who have suffered traumatic stressful events exhibit disruption in abilities mediated by frontal brain systems. Therefore, this study employed tasks sensitive to frontal lobe dysfunction, including delayed response (DR), delayed alternation (DA), object alternation (OA), delayed matching-to-sample (DMTS), and delayed nonmatching-to-sample (DNMTS), with participants having posttraumatic stress disorder (PTSD). Compared to controls, the PTSD participants were unimpaired on DA and DMTS, but they showed deficits on DR, OA, and DNMTS tasks. This pattern of results suggests disruption of functioning in selective prefrontal brain systems. Results are discussed in the context of the neuropsychological features of PTSD, as well as possible neuropathological and etiological underpinnings of this disorder.

Adult↗

Development of a brief questionnaire for screening for multiple chemical sensitivity syndrome.

The objective of this study was to identify a parsimonious set of questions that has high sensitivity and specificity for screening for individuals with multiple chemical sensitivity (MCS) syndrome. We performed a cross-sectional survey using a case-control design. Subjects were derived from patients seen at an academically based Occupational and Environmental Medicine Clinic. Cases consisted of patients who fulfilled the Cullen definition for MCS. Controls were patients who had diagnoses excluding MCS and asthma and who were matched to cases by age and sex. Cases and controls filled out a screening questionnaire that, among things, elicited responses as to whether and how subjects reacted to 122 different types of environmental exposures. Data from 44 pairs of cases and controls were available for analysis. The average age of cases was 50.2 years, and 91% was female. Among cases, the most common exposure that was purported to incite MCS was 'indoor air quality contaminants (unspecified)' (59%), followed by solvents (27.3%). After randomly excluding five cases and controls, a stepwise selection procedure for two-group discriminant analysis revealed that the main contributors to the discrimination of the remaining cases and controls were self-reported reactions to copy machine emissions, marking pens, aftershave, window cleaner, nylon fabric, pine-scented products, and rayon material. When a positive response to these factors was used as the sole method for discriminating cases from controls, only one of 41 cases was misclassified as a control while none of the controls was misclassified as a case. When the same method was applied to the five excluded cases and five excluded controls, only one of the five cases was misclassified while none of the five controls was misclassified as a case. Among patients with MCS defined by the Cullen criteria in this clinical setting, having a reaction to these seven common potential exposures comprised a parsimonious set of factors that discriminated between MCS patients and age- and sex-matched normal controls. These questions may have utility in screening for individuals with MCS in general population survey studies.

Air Pollution, Indoor↗

Interleukin 1 and tumor necrosis factor in obese alcoholics compared with normal-weight patients.

We performed a liver biopsy and measured plasma concentrations of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), and spontaneous and lipopolysaccharide-stimulated in vitro monocyte production of IL-1 beta and TNF-alpha in 19 obese and 17 age-matched, normal-weight alcoholics admitted for treatment of their alcoholism. Nine healthy normal-weight alcoholics had cirrhosis in their liver biopsy (Fisher's exact test: P=0.031). A histologic score (derived from the sum of fat, necrosis, fibrosis, and inflammation in the biopsy) correlated with body mass index and the percentage body fat, calculated by using the sum of four skinfold-thickness measures. Plasma concentrations and spontaneous in vitro monocyte production of IL-1 beta and TNF-alpha were below detection limits. No significant differences were observed between normal-weight and obese alcoholics with or without cirrhosis and normal control subjects in lipopolysaccharide-stimulated monocyte production of IL-1 beta (6.5 +/- 0.8, 10.1 +/- 2.7, 7.9 +/- 1.6, and 5.28 +/- 4.24 micrograms/L, respectively) or TNF-alpha (2.8 +/- 0.4, 3.7 +/- 1.0, 3.0 +/- 0.44, and 1.97 +/- 1.01 micrograms/L, respectively). However, a positive correlation was found between IL-1 beta production and body mass index (r=0.333, P=0.047), percentage body fat (r=0.412, p=0.013), abdominal circumference (r=0.416, P=0.012), and total histologic score (r=0.331, P=0.049). A multiple-regression model accepted abdominal circumference as the only independent predictor of IL-1 beta production. TNF-alpha did not correlate with any of the above-mentioned indexes. We conclude that obese alcoholics have a higher frequency of histologic liver damage and that IL- 1 beta production by stimulated monocytes is related to abdominal fat accumulation.

Adult↗

Immune depression induced by protein calorie malnutrition can be suppressed by lesioning central noradrenaline systems.

Depressed immune function is well documented in protein calorie malnutrition (PCM). Also, central noradrenergic hyperactivity has recently been reported in malnourished animals. Increase in central noradrenaline activity could be responsible for cell-mediated immune depression. The present study is designed to address this hypothesis by testing whether neurotoxic lesion of central noradrenergic systems by 6-hydroxydopamine (6-OHDA) could improve lymphoproliferative response to mitogens and interleukin (IL)-1 production in PCM rats. A significant enhancement of lymphoproliferative response to concanavalin A (ConA) and in IL-1 production was observed in spleen mononuclear cells of PCM rats injected intracerebroventricularly with 120 micrograms of 6-OHDA, as compared with solvent injected and untreated PCM animals. A significant decrease in brain noradrenaline levels was produced in the drug-injected animals. These results suggest that central noradrenergic hyperactivity is one of the mechanisms involved in the immunodepression produced by malnutrition.

Animals↗

Depressed immune response in malnourished rats correlates with increased thymic noradrenaline level.

Depressed immune response is well documented in protein-calorie malnutrition (PCM). Also, central and peripheral noradrenaline (NA) activities have been reported to be increased in malnourished animals. Since increases in central and peripheral NA may inhibit immune function, it is possible that malnutrition-induced immunodepression could be mediated by noradrenergic hyperactivity. To address this hypothesis the effect of malnutrition on cell-mediated immune response, as well as on NA levels of the median eminence, spleen and thymus was studied in PCM rats. Decreased lymphoproliferative response and IL-1 production by mononuclear macrophages was observed in PCM. Besides, increased NA concentration was detected in thymuses of PCM rats, while unchanged levels of this neurotransmitter were observed in median eminence and spleen. These data suggest a positive correlation between malnutrition-induced immunodepression and sympathetic noradrenergic activity in thymus, an organ implicated in immune cell differentiation during early development.

Animals↗

Zinc supplementation impairs monocyte function.

Zinc has been shown to be involved in many functions of the immune system. This study was conducted to examine the effect of zinc supplementation on phagocytic, fungicidal and metabolic activity of blood monocytes of marasmic infants during nutritional rehabilitation. A controlled, double-blind design was used in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same, unfortified formula. Evaluation of phagocytic-fungicidal capacity, growth, zinc, copper and iron status was performed in both groups on admission and after 60 and 105 days of nutritional rehabilitation. Although energy, copper and iron intakes were similar in the two groups, a decrease in the number of infants able to phagocytose one or more Candida buds was observed after 60 days of zinc supplementation compared to admission (p < 0.03). No change in phagocytic ability was detected between admission and 60 days in the control group. The number of infants with depressed fungicidal activity increased significantly after 105 days of nutritional rehabilitation in the zinc-fortified group as compared to controls (p < 0.04). The number and duration of impetigo episodes was significantly greater in the group fed the zinc-fortified formula. These results suggest that zinc supplements at the RDA level may impair monocyte function.

Candida albicans↗

Comorbidity of fibromyalgia with medical and psychiatric disorders.

PURPOSE: Patients with fibromyalgia have been reported to display high rates of several concomitant medical and psychiatric disorders, including migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. To test further these and other possible associations, we assessed the personal and family histories of a broad range of medical and psychiatric disorders in patients with fibromyalgia. PATIENTS AND METHODS: Subjects were 33 women (mean age 42.1 years) who each met American College of Rheumatology criteria for fibromyalgia and presented to a rheumatologist at a tertiary referral center. They received the Structured Clinical Interview for DSM-III-R (SCID); a supplemental interview, in SCID format, for other medical and psychiatric disorders, including migraine, irritable bowel syndrome, and chronic fatigue syndrome; and an interview for family history of medical and psychiatric disorders. RESULTS: Patients with fibromyalgia displayed high lifetime rates of migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. They also exhibited high rates of familial major mood disorder. CONCLUSIONS: The finding that migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder are frequently comorbid with fibromyalgia is consistent with the hypothesis that these various disorders may share a common physiologic abnormality.

Adult↗

Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants.

This study attempted to define the possible contribution of zinc nutrition to immunocompetence and growth in severely malnourished infants. The effect of zinc supplementation was evaluated in marasmic infants during nutritional rehabilitation by using a controlled double-blind design in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same non-supplemented formula. Evaluation of immunocompetence, growth, and zinc, copper, and iron status was performed on admission and at 30, 60, and 105 d of nutritional rehabilitation. Although energy intake was similar in both groups, the zinc-supplemented infants had significantly higher linear growth gain, and their immune function improved as demonstrated by conversion of their delayed hypersensitivity skin reactions, enhanced lymphoproliferative response to PHA, and increased salivary IgA concentrations. Thus, the use of a zinc-fortified formula during nutritional rehabilitation can prevent the development of zinc deficiency and improve growth and immune function.

Copper↗

Resurgence of tuberculosis.

Since 1985 there has been an 18% increase in the number of cases of tuberculosis nationally. Even more alarming is the increasing incidence of multidrug-resistant tuberculosis which presents a serious public health problem, particularly for HIV-infected patients.

Anti-Bacterial Agents↗

Immunogenicity of Salmonella typhi Ty21a vaccine for young children.

An attenuated Salmonella typhi Ty21a vaccine was administered to 18 infants and toddlers (less than or equal to 24 months old) to determine its safety and immunogenicity. The vaccination (10(9) CFU per dose, three doses) was well tolerated. However, after the vaccination there was no evidence of a humoral or cellular immune response to S. typhi. The vaccine used was known to be immunogenic for older children and adults. The results support the view that the immunogenicity of Ty21a is age dependent.

Administration, Oral↗

Functional capacity of colostral leukocytes from women delivering prematurely.

The phagocytic, bactericidal, and metabolic activity of colostral leukocytes from mothers delivering preterm infants was compared with that of colostral leukocytes from mothers of term infants. In addition, the proliferative capacity of colostral lymphocytes was compared. Preterm adherent colostral leukocytes had a significantly higher phagocytic index than term colostral adherent leukocytes. Mean +/- SEM values were 5.4 +/- 0.5 versus 2.7 +/- 0.2, respectively (p less than 0.001). Bactericidal capacity against Escherichia coli and nitroblue tetrazolium reduction of preterm and term colostral leukocytes were comparable. Lymphocyte proliferative response was equivalent in preterm and term milk. We conclude that colostral leukocytes from preterm mothers are at least as functional in their antimicrobial activity and possibly phagocytose even better than the colostral cells of mothers of term infants.

Adult↗

Immunity to Salmonella typhi: considerations relevant to measurement of cellular immunity in typhoid-endemic regions.

Experiments were performed in Baltimore, Maryland and in Santiago, Chile, to determine the level of Salmonella typhi antigen-driven in vitro lymphocyte replication response which signifies specific acquired immunity to this bacterium and to determine the best method of data analysis and form of data presentation. Lymphocyte replication was measured as incorporation of 3H-thymidine into desoxyribonucleic acid. Data (ct/min/culture) were analyzed in raw form and following log transformation, by non-parametric and parametric statistical procedures. A preference was developed for log-transformed data and discriminant analysis. Discriminant analysis of log-transformed data revealed 3H-thymidine incorporation rates greater than 3,433 for particulate S. typhi, Ty2 antigen stimulated cultures signified acquired immunity at a sensitivity and specificity of 82.7; for soluble S. typhi O polysaccharide antigen-stimulated cultures, ct/min/culture values of greater than 1,237 signified immunity (sensitivity and specificity 70.5%).

Adolescent↗

Anemia of a mild viral infection: the measles vaccine as a model.

To define the hematologic changes during a mild viral infection, 93 infants were immunized with live attenuated measles virus and studied prospectively at 0, 4, 9, 14, 21, and 30 days. Hemoglobin concentration decreased significantly by days 9 and 14. The decrease was greater than 1.0 g/dL in 8.6% and greater than 0.6 in 24.3% of the infants. Of the nonanemic infants, 22% became anemic. Serum iron and percentage saturation of transferrin decreased, whereas serum ferritin increased significantly. Mean cell volume, iron-binding capacity, protoporphyrin, and haptoglobin did not show changes. Reticulocyte index and erythropoietin increased significantly at 30 days. Leukocyte counts, Zetacrit, and C-reactive protein did not help to predict the hemoglobin decrease. These results suggest that a mild viral infection in infants induces a significant decrease in hemoglobin that may persist for 14 to 30 days and may be difficult to distinguish from iron deficiency.

Anemia↗