Training in infectious diseases.
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Biomedical subjects
Publications and source records attributed to M Levin.
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A comparative analysis of Emergency Department (ED) utilization by 2936 older-adults, old, and old-old patients was conducted in the only hospital available for residents of a vast geographical region. All patients (45+) who arrived at the ED during the first week of every even month from September 1986 to August 1987 were selected for the study. No significant differences were found among the three groups with regard to sociodemographic characteristics other than age. Data showed that the old-old use the ED approximately twice as much as the old and the older-adults; they also use the ED more often than the two other groups during the winter season. These two findings indicate the utility of viewing the old-old not only as a part of the elderly population, but also as a unique risk group. Hospitalization rates present a different pattern: they double in each age group moving from the youngest to the oldest. Complaints of an internal medicine nature are more often presented by the two groups of the elderly in comparison to the older-adults, and are followed by more frequent hospitalizations in internal medicine wards. Such findings have practical implications, and should be taken into consideration by policymakers.
An exploratory study of emergency department (ED) utilization, comparing Israeli adult Jews and Bedouin Arabs was conducted. The data interpretation derived from the premise that health services utilization reflects not only morbidity patterns but characteristics of both subcultures and the structure of health services. The Bedouins in the study are a Moslem traditional society going through a rapid process of urbanization and modernization, with a relative deficiency in primary health services. Data were collected from the general ED admissions registry. Patients (17+) who arrived at the ED during the first week of every even month of one calendar year were selected for this study (6815 Jews and 583 Bedouins). The findings indicate that, in general Bedouins use the ED significantly less than Jews. They adjust to the structure of the ED services and use them, more than Jews, as a primary service. Yet, the hospitalization rates of the two populations are similar. In both subcultures the pattern of gender differences changes after the age of 45. The change, however, is in the opposite direction. Differences in ED usage among Bedouin age-sex groups are discussed in terms of changes in social status during a period of socio-cultural transition.
We evaluated the effect of dipyridamole (5 mg/kg/day) for 12 months on renal and platelet function in 53 children with insulin dependent diabetes mellitus (IDDM) in a prospective double blind placebo controlled trial. Urine albumin excretion (expressed as the geometric mean albumin to creatinine concentration ratio (UA/UC) was measured every three months throughout the study. At 12 months, the geometric mean UA/UC was no different in diabetic children receiving dipyridamole, 0.60 mg/mmol, when compared with those receiving placebo, 0.87 mg/mmol. Glomerular filtration rate, urinary excretion of retinol binding protein, and N-acetyl-beta-D-glucosaminidase (NAG), blood pressure, and spontaneous platelet aggregation in response to stirring whole blood did not differ between the two groups at 12 months. Subgroup analysis to include only those children with high UA/UC before entry into the study also failed to show an effect of the drug on UA/UC. Eleven children had either persistently high UA/UC (n = 8: four on dipyridamole, four on placebo) or progression to high UA/UC (n = 3: two on dipyridamole, one on placebo). These children had significantly higher urinary excretion of retinol binding protein and NAG, bigger kidneys, and higher diastolic blood pressure both before and after treatment than the remaining 42 children, whereas there was no difference in spontaneous platelet aggregation between the two groups. These observations on the associations between UA/UC and other parameters of renal function suggest that measurement of 'tubular' proteins and diastolic blood pressure as well as UA/UC may contribute to the identification of those at risk of developing nephropathy.
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Two different methods for evaluating platelet antibody were used to study 12 normal subjects and 24 patients consisting primarily of intravenous drug users (IVDUs) who were positive for human immunodeficiency virus (HIV). Total platelet-associated immunoglobulin G (IgG) and immunoglobulin M (IgM) were measured by enzyme-lined immunosorbent assay on platelet lysate, and platelet surface-associated IgG and IgM were measured by semiquantitative flow cytometry. IgG and IgM values showed significant correlations between the two measurement methods. Mean platelet surface IgG and total IgG were 3.6 and 4.3 times greater, respectively, in IVDUs than in controls, and platelet IgM was also significantly higher in IVDUs than in controls as measured by both techniques. Although mean platelet immunoglobulin levels were higher in the IVDUs with thrombocytopenia than in IVDUs with normal platelet counts, these differences did not achieve significance. These data show that platelet IgG and IgM levels are increased in IVDU-associated HIV infection and suggest that these increases are not confined to patients manifesting thrombocytopenia. The herein described platelet surface antibody and total platelet antibody measurements appear to be equally useful in studying this patient population. Specific details for generating platelet-associated immunofluorescence units are discussed.
A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.
Studies using cationic probes have suggested that a reduction in glomerular anionic sites, composed principally of the glycosaminoglycan heparan sulphate, is responsible for the abnormal glomerular permeability in the congenital nephrotic syndrome (CNS). We therefore analysed the glycosaminoglycan content of the glomerular basement membrane (GBM) from an infant who died of CNS and from an infant who died of unrelated causes. We also measured the urinary excretion of glycosaminoglycans in children with nephrotic syndrome, both congenital and acquired, and in healthy children. Heparan sulphate constituted 59% of the glycosaminoglycan content of the GBM in the normal infant, the other principal glycosaminoglycan being chondroitin sulphate. In the GBM from the infant with CNS the heparan sulphate was greatly reduced, constituting only 3% of total glycosaminoglycans. The urinary excretion of heparan sulphate was significantly increased in CNS (expressed both in relation to creatinine and to chondroitin sulphate) compared with normal children and to those with acquired nephrotic syndrome. Diminished GBM content of heparan sulphate may be responsible for the abnormal glomerular permeability in CNS and may be a consequence of defective incorporation of heparan sulphate into the GBM with subsequent loss into the urine.
A 14-year-old female had a large, nontender abdominal mass on a routine sports physical examination. Following evaluation by ultrasound and computed tomography scan there was an initial attempt at drainage. The mass was subsequently removed. The diagnosis was epidermoid cyst of the spleen. In this report, we discuss the epidemiology and management of a splenic cyst, a rarely encountered diagnosis in adolescents, and emphasize the life-saving potential of the abdominal examination in sports medicine.
To further define the clinical, pathologic, and biochemical features of hemorrhagic shock and encephalopathy syndrome, we studied 25 affected children (aged 3 months to 14 years) admitted to a single center between 1982 and 1985. A prodromal illness comprising vomiting, diarrhea, listlessness, and fever was present in 84% of the cases. Acute onset of shock, convulsions and coma, bleeding (or laboratory evidence of disseminated intravascular coagulation), elevated plasma activity of hepatic enzymes, acidosis, and impaired renal function was present in every case. Twenty patients died, and all the survivors are neurologically damaged. At postmortem examination, intravascular microthrombi coexisting with hemorrhages and petechiae were found in most organs. Centrilobular liver necrosis and cerebral edema were prominent features. No microbiologic cause for the disorder was identified, but decreased plasma levels of the protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin, together with increased levels of circulating proteolytic enzymes, were frequently present. An overrepresentation of the uncommon variant phenotypes of alpha 1-antitrypsin was found in first-degree relatives of affected patients (four had the MZ phenotype, and one each the MS or MC phenotype, of 19 relatives studied). Abnormal accumulation of alpha 1-antitrypsin was detected immunohistochemically in the livers of six of the patients. Defective protease inhibitor production or release may be involved in the pathogenesis of the disorder.
We postulated that the reduction of surface negative charge on the glomerular capillary wall, which is believed to underlie the proteinuria of steroid-responsive nephrotic syndrome (SRNS), might be due to the presence of a cationic substance which binds to and neutralizes the negative charge on cells and membranes. Using a method to detect charge neutralizing substances based on inhibition of binding of the cationic dye Alcian blue 8GX to heparin, plasma and urine from children with SRNS were found to contain a protease-sensitive charge-neutralizing factor, which was not present in plasma or urine of healthy individuals. This factor has been partially purified from SRNS plasma and urine by ion exchange chromatography on QAE Sephadex, gel filtration on Sephadex G150, and FPLC on Mono-S. This cationic protein, which binds to and neutralizes the charge on heparin, may also neutralize the negative charge on the glomerular capillary wall and may thus be involved in the pathogenesis of SRNS.
Blood mononuclear cells (MNC) were stimulated with VZV in the form of live cell-associated virus, glutaraldehyde-fixed VZV-infected fibroblasts or an extracted VZV antigen. After 7 days of culture with live virus, IL2 receptors (IL2R) were found on CD4 and CD8 cells while cultures stimulated with fixed or extracted antigen had IL2R only on CD4 cells. Clones derived by limiting dilution from these cultures were tested for specificity by cytotoxicity to autologous VZV-superinfected B lymphoblasts, and by proliferation in the presence of antigen and antigen presenting cells. The CD8+ clones were not VZV specific in tests of cytotoxicity or proliferation. 50% of the CD4+ clones with specificity for VZV also proliferated in cultures stimulated with individual VZV glycoproteins gp I, II or III. Included amongst these were clones cytotoxic for lymphoblast targets prepared with live VZV. Most of the VZV-specific T cell clones which failed to lyse targets prepared with live VZV lysed targets prepared with heat killed VZV. Target cells were susceptible to lysis after VZV antigens were no longer demonstrable on the cell surface by immunofluorescence and monoclonal antibodies to VZV glycoproteins failed to block cytotoxicity. 5 of 8 VZV-specific CD4+ clones provided antigen-specific help to B cells for IgG antibody production. The data are consistent with the view that CD4+ T cells respond to processed VZV antigen fragments, and that these fragments include epitopes present on gp I, gp II and gp III. Additionally, some the cloned progeny of VZV specific T cells were bifunctional (expressing cytotoxicity and help for B cells) in tissue culture.
The effect of selective glucocorticoid or mineralocorticoid deficiency upon arterial pressure was evaluated in unanesthetized adult spontaneously hypertensive rats (SHR). Adrenalectomized SHR were replaced with 6 micrograms/24 h aldosterone (ALDO), 10 microgram/24 h dexamethasone (DEX), or both aldosterone and dexamethasone (ALDO + DEX) by IP osmotic mini-pumps. These were compared to sham-operated SHR (SHAM) and adrenalectomized SHR given no steroid replacement (ADX). Drinking fluid for all groups was 1% NaCl + 2.5% glucose. Six days after adrenalectomy, intra-arterial mean arterial pressure (MAP) fell from 174 +/- 2 to 149 +/- 6 mm Hg in ALDO (n = 8, P less than .01) and from 179 +/- 4 to 125 +/- 4 in ADX (n = 6, P less than .01). In contrast, MAP rose in SHAM from 171 +/- 4 to 179 +/- 5 mm Hg (n = 7, P less than .01), in ALDO + DEX from 161 +/- 3 to 184 +/- 4 mm Hg (n = 7, P less than .01), and in DEX from 162 +/- 2 to 181 +/- 4 mm Hg (n = 7, P less than .01). The results indicate that when diet salt intake is high, glucocorticoid action is necessary for the full expression of hypertension in adult SHR.
We investigated the associations between albuminuria, metabolic control, glomerular filtration, blood pressure, and platelet function in children with insulin dependent diabetes mellitus. The geometric mean (95% tolerance levels) albumin excretion (expressed as the geometric mean albumin to creatinine ratio on two overnight urine collections (UA/UC], in 60 diabetic children was 0.72 (0.80-6.9) mg/mmol, significantly greater than in 45 normal children (geometric mean 0.41 (0.14-1.17]. Mean (SD) glomerular filtration rate, measured by 51Cr edetic acid clearance during constant infusion, was significantly greater in diabetic children (129 (20) ml/min/1.73 m2) compared with normal controls (109 (13]. Mean (SD) renal length for height standard deviation score was +0.25 (1.1); systolic blood pressure standard deviation score was 0.15 (0.65), and diastolic blood pressure was 0.51 (0.82). Spontaneous platelet aggregation, expressed as percentage fall in platelet count in stirred whole blood after 2 minutes was 17.8 (9.2)% in the diabetic compared with 12.3 (7.9)% in normal children. UA/UC correlated with renal length and of the children with UA/UC above the normal range, 70% also had a glomerular filtration rate above the normal range. There was a weak correlation between UA/UC and glycated haemoglobin (HbA1c). All children with spontaneous platelet aggregation above normal had had diabetes for more than seven years. These cross sectional data define some of the early markers and inter-relationships that may be important in the development of nephropathy.
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Metabolic alkalosis has previously been shown to have an antimagnesiuric influence. To further clarify this phenomenon, short-term clearance studies were performed on intact anesthetized rats subjected to 0.9% saline infusion, 0.15 M NaHCO3 infusion or acute respiratory alkalosis. The experimental protocols resulted in a similar degree of natriuresis in each of the three groups. The increase in plasma pH value was similar both in animals treated with NaHCO3 and animals with respiratory alkalosis. Filtered loads of Mg did not differ in the three experimental groups. However, only acute metabolic alkalosis was associated with a reduction in the absolute rate of Mg excretion (saline: 0.49 +/- 0.05 mu Eq/min; 0.15 M NaHCO3: 0.29 +/- 0.04 mu Eq/min; acute respiratory alkalosis: 0.48 +/- 0.03 mu Eq/min) and fractional Mg excretion (saline: 40.3 +/- 5.3%; 0.15 NaHCO3: 18.7 +/- 1.4%; acute respiratory alkalosis: 37.2 +/- 6.9%). A similar decrease in urinary Mg excretion in animals treated with bicarbonate infusion was observed following removal of the parathyroid gland. Moreover, for any given rate of urinary Na excretion, Mg excretion was lower in bicarbonate-treated animals than in rats infused with saline solution. Intact animals treated with increasing doses of NaHCO3 revealed a statistically significant inverse correlation between the Mg to Na clearance ratio and urinary and plasma bicarbonate concentration. In contrast, such a correlation was not observed during respiratory alkalosis. The findings suggest that bicarbonate ion directly stimulates tubular magnesium reabsorption independent of the presence or absence of parathyroid hormone.
The influence of incremental or bulk filling techniques, and reapplication of unfilled resin (impregnation) to the margins with an enamel bonding agent, on marginal adaptation was evaluated in Class II composite restorations by clinical, radiographic, scanning electron microscope (SEM) and dye penetration techniques. Cavities were prepared in 80 extracted permanent posterior teeth. All cavity walls were treated with polyacrylic acid for 10 seconds. The enamel was etched for 1 minute, rinsed, dried, and lined with Scotchbond. Forty cavities were filled by increments of P30 and 40 cavities in bulk. The margins of the restorations of 20 teeth in each group were re-etched for 30 seconds and Concise Enamel Bond reapplied. The clinical scores were excellent for all restorations. Radiographic examination showed twice as many bubbles in the incrementally filled restoration than in the group filled in bulk. In 53 teeth, a radiolucent area between the dentin and the restorative material was found. After sectioning, this area was found to correspond to a hard material. The SEM revealed excellent margins in the groups of teeth that were impregnated with an unfilled resin, whereas 13 teeth without impregnation showed defective margins. The dye penetration, as a test for marginal leakage, was minimal at the occlusal surface of all teeth. At the cervical surface, 10.5% of the impregnated teeth showed severe dye penetration compared to 18% of the nonimpregnated teeth. No correlation was found between dye penetration at the cervical surface and the thickness of the residual enamel in this area.(ABSTRACT TRUNCATED AT 250 WORDS)
HUS has now emerged as a common clinical and pathologic syndrome that may result from a variety of disease processes. On the basis of clinical and epidemiologic criteria, several distinct subgroups of the disorder have been distinguished, the most common of which are the result of infectious processes, whereas the rarer forms may be genetically determined or acquired defects in vascular homeostasis. A related group of bacterial toxins, verotoxins, and Shiga toxin, produced by a variety of species of enteric pathogens, have been implicated in the pathogenesis of typical childhood HUS. In the few years since verotoxin-producing organisms were first incriminated as the possible etiologic agents of HUS, there has been a remarkable growth in knowledge of the biology of verotoxin and its role, not only in HUS but in hemorrhagic colitis and childhood diarrhea. The availability of purified toxin and new tools for detection of verotoxin and verotoxin-producing organisms, such as monoclonal antibodies and probes for DNA hybridization, should enable definitive studies of the epidemiology and pathogenesis of verotoxin-associated HUS to be undertaken. The growing understanding of HUS should eventually lead to improved treatment and ultimately to prevention of this serious childhood disorder.