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Biomedical subjects

M Shapiro

Publications and source records attributed to M Shapiro.

At least 73 records · Page 4Linked to original sources

Pemphigus vulgaris induced by D-penicillamine therapy in a patient with systemic sclerosis.

D: -Penicillamine-induced pemphigus occurs infrequently, typically in patients with rheumatoid arthritis. We describe a patient with systemic sclerosis who experienced this complication 3 months after starting D -penicillamine therapy. Nikolsky's sign, histopathologic findings, and direct immunofluorescence all confirmed the diagnosis. Termination of disease progression required intravenous pulse glucocorticoids, azathioprine, and 3 courses of plasmapheresis. The presentation, treatment, and etiology of D -penicillamine-induced pemphigus are reviewed, and the incidence of this complication in scleroderma patients is examined.

Aged↗

The relationship between dorsolateral prefrontal neuronal N-acetylaspartate and evoked release of striatal dopamine in schizophrenia.

Schizophrenia has been linked to abnormal dopamine function, recently to excessive amphetamine-induced release of striatal dopamine, and also to pathology of prefrontal cortical neurons. It has been hypothesized that prefrontal pathology is a primary condition that leads to dopamine dysregulation. We evaluated in vivo the relationship between neuronal integrity in dorsolateral prefrontal cortex, assessed as N-acetylaspartate (NAA) relative concentrations measured with proton magnetic resonance spectroscopic imaging, and amphetamine-induced release of striatal dopamine, assessed with 11C-raclopride Positron Emission Tomography (PET) in patients with schizophrenia and in healthy subjects. In the patients, NAA measures in dorsolateral prefrontal cortex selectively predicted striatal displacement of 11C-raclopride after amphetamine infusions (rho = -0.76, p < .02). In contrast, NAA measures in other cortical regions and in healthy subjects did not show any correlation. These results support the hypothesis that in schizophrenia neuronal pathology of dorsolateral prefrontal cortex is directly related to abnormal subcortical dopamine function.

Adult↗

Parental assessment of behavior in Chinese adoptees during early childhood.

The Parent Rating Scale of the Behavior Assessment Scale for Children (PRS-BASC) was used to examine the behavior of 45 Chinese adoptees. In all but one case, results from the 9 BASC-PRS scales ranged in the average, or normal, range. Thus, as a group, no deviations from normal behavior were revealed. However, the variability of ratings for several scales--Hyperactivity, Aggression, Conduct Problems, and Attention Problems--indicated a greater potential for at-risk behavior. Age of adoption from China was not a significant influence on parents' perceptions of adoptees' behavior. However, older adoptees were more likely to be rated hyperactive or aggressive than younger children, while younger adoptees were more likely to exhibit withdrawal.

Acculturation↗

Evaluation of chlorhexidine and povidone iodine activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis using a surface test.

Most published studies of the activity of biocides against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) have been based on suspension tests. This study was undertaken to provide information on the effect of chlorhexidine and povidone iodine on bacteria dried on to surfaces, a situation in which biocide activity is known to be reduced. The inactivation of MRSA (10 strains), methicillin-sensitive Staphylococcus aureus (MSSA, 10 strains), VRE (nine strains) and vancomycin-sensitive Enterococcus faecalis (VSE, 10 strains) by 0.5% aqueous chlorhexidine gluconate or 10% povidone iodine was evaluated by applying the European surface test method. Povidone iodine was equally active against resistant and sensitive strains of both species with microbicidal effects (ME), i.e. the log(10)concentration of micro-organisms compared with controls treated with distilled water, after 1.5 min of 3.14 and 3.49 for VRE and VSE respectively, and 3.47 and 3.78 for MRSA and MSSA. Chlorhexidine was equally active against VRE and VSE (ME 3.37 vs. 3. 56 after 7 min, respectively), but was significantly less active against MRSA as opposed to MSSA (ME 3.07 vs. 3.83 after 10 min, P= 0. 017).

Anti-Infective Agents, Local↗

Critical care medicine education of surgeons: recommendations from the Surgical Section of the Society of Critical Care Medicine.

PERSPECTIVE: The role of surgeons in critical care medicine has a long and esteemed past. The presence of surgeons in intensive care units provides specific insights and perspectives to the care of surgical patients sometimes not fully appreciated by the non-surgical practitioners caring for the same patients. The training and education of surgeons is becoming more complex, fragmented, and lengthy. The knowledge base and skill set required to manage critically ill or injured surgical patients is also becoming more extensive but has the potential of becoming lost in the process of providing the overall educational program for surgical trainees. Simultaneously, nonsurgical specialties are continuing to train individuals with special skills in critical care medicine and the concept of "hospitalists" is becoming more accepted by institutions across the United States. The certification exams in critical care medicine remain under the aegis of the individual medical specialty boards, and there is still not a unified examination process in critical care. Surgeons, in particular, have tremendous pressures these days to spend more clinical time in the operating room, and the task of consistently conducting high quality research is also becoming arduous. This list of reasons could continue but are simply examples for why surgeons need to spend focused attention on how best to train and educate upcoming surgical trainees in regards to the principles of critical care medicine. The critically ill or injured patients need this focused attention and the specialty of surgical critical care medicine needs this attention. The Surgical Section of the Society of Critical Care Medicine has developed this position statement in the hopes that ongoing discussion and refinement of this particular aspect of surgery will continue on several levels.

Critical Care↗

Cutaneous microenvironment of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative individuals, with special reference to Staphylococcus aureus colonization.

A cross-sectional quantitative study of cutaneous bacterial and yeast flora at seven body sites in 99 human immunodeficiency virus-seropositive and 50 seronegative military personnel was performed. Statistically significant differences in carriage rates were only observed for Staphylococcus aureus on the foreheads of seropositive individuals. Seronegative individuals demonstrated staphylococcal carriage rates 1.3 to 2 times as great as those of historical controls (defined as healthy individuals not receiving any medications) at five of six body sites. We conclude that seropositive military personnel do not exhibit statistically significant elevations in densities and carriage rates of the microorganisms examined (except Staphylococcus aureus), relative to seronegative individuals. Seropositive individuals may be predisposed to staphylococcal carriage. The elevated staphylococcal carriage rates of military personnel undergoing basic training warrants a formal evaluation of the impact of training exercises on cutaneous flora. The information gained may serve to limit the spread of infection during training exercises and battlefield conditions.

Adolescent↗

Enhancement in activity of homologous and heterologous baculoviruses infectious to beet armyworm (Lepidoptera: Noctuidae) by an optical brightener.

The nuclear polyhedrosis virus (NPV) from the beet armyworm, Spodoptera exigua (Hübner) (SeMNPV), was the most active virus tested against the beet armyworm (LC50 = 4.1 PIBs/mm2), followed by nuclear polyhedrosis viruses from the alfalfa looper, Autographa californica (Speyer) (AcMNPV; LC50 = 92.6 PIBs/mm2), and the celery looper, Anagrapha falcifera (Kirby) (AfMNPV; LC50 = 195.7 PIBs/mm2). In the case of the nuclear polyhedrosis virus from the bollworm, Helicoverpa armigera (Hübner), LC50s could only be obtained for five/six replicates, whereas LC50s could only be obtained for two/six replicates for the nuclear polyhedrosis virus from the wax moth, Galleria mellonella (L.) (GmMNPV). When an optical brightener Tinopal LPW was added to virus suspensions, LC50 values were reduced by 130-fold for both SeMNPV and AcMNPV and by 300-fold for AfMNPV. The addition of Tinopal LPW greatly increased the activities of HaMNPV and GmMNPV. In terms of speed of kill, Tinopal LPW reduced the LT50s for all nuclear polyhedrosis viruses by 30-40%.

Animals↗

Effect of two granulosis viruses on the activity of the gypsy moth (Lepidoptera: Lymantriidae) nuclear polyhedrosis virus.

Two granulosis viruses (GV) were tested as enhancers for the gypsy moth nuclear polyhedrosis virus (LdMNPV). Helicoverpa armigera (Hübner) CV (HaGV) had no detrimental effect upon larval growth and development, but in combination with LdMNPV it reduced both the LC50 and the LT50 for the NPV. In addition, the combination also adversely affected the growth and development of gypsy moth larvae. The LC50 of LdMNPV was reduced by as much as 300-fold (HaGV at 10(-2) dilution) and the LT50 was reduced by as much as 18% (HaGV at 10(-2) dilution). Spodoptera frugiperda (J. E. Smith) GV reduced the LC50 of LdMNPV by as much as 13-fold but had no effect upon the LT50.

Animals↗

Access of vulnerable groups to antiretroviral therapy among persons in care for HIV disease in the United States. HCSUS Consortium. HIV Cost and Services Utilization Study.

OBJECTIVE: To employ the behavioral model of health services use in examining the extent to which predisposing, enabling, and need factors explain the treatment of the HIV-positive population in the United States with highly active antiretroviral therapy (HAART). DATA SOURCE: A national probability sample of 2,776 adults under treatment for human immunodeficiency virus (HIV) infection. STUDY DESIGN: The article uses data from the baseline and six-month follow-up surveys. The key independent variables describe vulnerable population groups including women, drug users, ethnic minorities, and the less educated. The dependent variable is whether or not a respondent received HAART by December 1996. DATA COLLECTION: All interviews were conducted using computer-assisted personal interview instruments designed for this study. Ninety-two percent of the baseline interviews were conducted in person and the remainder over the telephone. PRINCIPAL FINDINGS: A multistage logit regression shows that the predisposing factors that have previously described vulnerable groups in the general population with limited access to medical care also define HIV-positive groups who are less likely to gain early access to HAART including women, injection drug users, African Americans, and the least educated (odds ratios, controlling for need, ranged from 0.35 to 0.59). CONCLUSIONS: Those HIV-positive persons with the greatest need (defined by a low CD4 count) are most likely to have early access to HAART, which suggests equitable access. However, some predisposing and enabling variables continue to be important as well, suggesting inequitable access, especially for African Americans and lower-income groups. Policymakers and clinicians need to be sensitized to the continued problems of African Americans and other vulnerable populations in gaining access to such potentially beneficial therapies. Higher income, anonymous test sites, and same-day appointments are important enabling resources.

Adult↗

Viral clearance without destruction of infected cells during acute HBV infection.

Viral clearance during hepatitis B virus (HBV) infection has been thought to reflect the destruction of infected hepatocytes by CD8(+) T lymphocytes. However, in this study, HBV DNA was shown to largely disappear from the liver and the blood of acutely infected chimpanzees long before the peak of T cell infiltration and most of the liver disease. These results demonstrate that noncytopathic antiviral mechanisms contribute to viral clearance during acute viral hepatitis by purging HBV replicative intermediates from the cytoplasm and covalently closed circular viral DNA from the nucleus of infected cells.

Acute Disease↗

Change in lactate production in Myc-transformed cells precedes apoptosis and can be inhibited by Bcl-2 overexpression.

As a result of Myc-dependent transcription of the LDH-A gene, Myc-transformed cells (Rat1-Myc) exhibit increased lactate production rates (LPR) even under aerobic conditions (the Warburg effect). Recently, the increased susceptibility to stress-induced apoptosis associated with Myc transfection has been linked to the overexpression of the LDH-A gene. In this report we demonstrate that the overexpression of the anti-apoptotic protein Bcl-2 in Rat1-Myc cells (Rat1-Myc-Bcl-2) reduces the molar ratio of lactate production to glucose consumption (Y(L/G)). The Bcl-2 induced reduction in Y(L/G) may be associated with reduced expression of the LDH-A gene, or a decrease in LDH-A activity. Stimulation of apoptosis by staurosporine, a protein kinase C inhibitor, reduces the LPR in Rat1-Myc cells in a dose-dependent manner. The staurosporine effect on the LPR is rapid and precedes the execution phase of apoptosis as defined by caspase activation and PARP cleavage. This effect on LPR is completely blocked by Bcl-2 overexpression. Serum starvation alone does not affect the LPR of Rat1-Myc or Rat1-Myc-Bcl-2 cells; however, the effect of staurosporine on the LPR of Rat1-Myc cells is potentiated by serum starvation. These data demonstrate that Bcl-2 overexpression reduces the Y(L/G) in Rat1-Myc cells, perhaps via a reduction in the activity or expression of the LDH-A gene, and this reduction may desensitize cells to some pro-apoptotic stimuli. The reduction in LPR in response to staurosporine may be an early step in the induction of apoptosis in Rat1-Myc cells. By abolishing the reduction in LPR, Bcl-2 may protect Rat1-Myc cells from staurosporine-induced apoptosis. Moreover, the lack of effect by serum starvation on the LPR supports a model in which serum starvation induces apoptosis through a pathway distinct from that of the staurosporine and glucose-dependent apoptotic pathway(s) in Myc-transformed cells.

Animals↗

Hypoxia-selective nitrobenzyloxycarbonyl derivatives of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines.

Some 4- and 2-(nitrobenzyloxycarbonyl)-1, 2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines (4, 6, and 7) were synthesized and evaluated for their ability to exert preferential toxicity to hypoxic EMT6 mammary carcinoma cells using a colony-forming assay. Of these, the 4,5-dimethoxy-2-nitro analogue 6 (50 microM, 1-h exposure) caused greater than 3 logs of kill of hypoxic cells, with relatively minor toxicity to corresponding aerobic cells. The ability of 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues to reach and kill hypoxic cells of solid tumors was also demonstrated using intradermally implanted EMT6 solid tumors in mice. In addition, a possible source of toxicity to normal tissue, i. e., the activation of the 4-nitrobenzyl derivative 4 by glutathione S-transferase-catalyzed thiolysis, was essentially eliminated by replacing one of the benzylic methylene protons by a methyl group. The 4-nitro (4) and 4,5-dimethoxy-2-nitro (6) analogues also appear to be reduced more easily under acidic conditions (pH 6.0) than under neutral conditions, as measured by differential pulse polarography. Since the pH in hypoxic regions is often lower than that in adjacent aerobic regions, this property should aid in the cytotoxic action of these agents against hypoxic cells of solid tumors.

Animals↗

Puerperal and intrapartum group A streptococcal infection.

OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection.

Abdominal Pain↗

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus.

The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus. Four chimpanzees were immunized with 1 of 2 licensed recombinant hepatitis B vaccines. Shortly after the chimpanzees developed antibodies to hepatitis B surface antigen (anti-HBs), they were challenged intravenously with mutant HBV strain AS. Two unvaccinated chimpanzees served as positive controls. The 4 vaccinated chimpanzees did not develop evidence of HBV infection or hepatitis during 2 years following virus challenge. In contrast, the 2 unvaccinated chimpanzees developed HBV infection and hepatitis. Serum anti-HBs in the vaccinated chimpanzees reacted not only with wild-type surface antigen, but also with mutant surface antigen by competition enzyme-linked immunosorbent assay (ELISA). Thus, immunization of chimpanzees with licensed recombinant hepatitis B vaccines stimulates anti-HBs that is broadly reactive and affords protection against infection with a surface gene mutant of HBV, suggesting that properly immunized individuals are not at significant risk of infection with this prototype variant strain of HBV.

Animals↗

Outbreak of bloodstream infections associated with dialysis machine waste ports in a hemodialysis facility.

Eight cases of gram-negative bloodstream infection without a clinically evident source occurred at a hemodialysis unit in Jerusalem between February and September 1997. All infections could be traced to three of the 13 dialysis machines in use. Epidemiological investigation, including pulsed-field gel electrophoretic characterization of organisms isolated from the patients and dialysis machines, implicated the Waste Handling Option system of the machines as the source of the infections. Discontinuation of the Waste Handling Option system use was associated with prompt cessation of the outbreak.

Adult↗