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M Goldman

Publications and source records attributed to M Goldman.

At least 181 records · Page 10Linked to original sources
PubMed1997

Production and role of interleukin-10 in concanavalin A-induced hepatitis in mice.

Experimental T-cell-mediated hepatitis induced by concanavalin A (Con A) involves the production of proinflammatory cytokines. Because interleukin (IL)-10 is a potent anti-inflammatory cytokine derived from macrophages and T cells and is produced within the liver, we investigated the role of IL-10 in modulating the hepatotoxicity and the secretion of cytokines following in vivo injection of Con A. IL-10 is produced early in the serum after Con A challenge. Neutralization of endogenous IL-10 by monoclonal antibodies (mAbs) increases the secretion of tumor necrosis factor alpha (TNF-alpha) (+111%), interferon gamma (IFN-gamma) (+92%), and IL-12 (+730%) 8 hours after Con A injection, and increases the hepatotoxicity, assessed by serum alanine transaminase (ALT) (+174%) measurement and by histology, 24 hours after induction of hepatitis. Conversely, preadministration of recombinant IL-10 reduces the production of these proinflammatory cytokines (-47%, -80%, and -47% for TNF-alpha, IL-12, and IFN-gamma, respectively), and decreases neutrophil infiltration and ALT serum concentration (-74%) 8 hours after Con A challenge. We conclude that IL-10, either endogenously produced or exogenously added, has a hepatoprotective role in Con A-induced hepatitis, through its suppressive property on proinflammatory cytokine production, and that it might be of therapeutic relevance in human liver diseases involving activated T cells.

Animals↗
PubMed1997

Integrated retrospective radiation dose assessment.

Radiation dose reconstruction is used to estimate exposure to radiation that has occurred externally, e.g., from an atomic bomb, or internally, e.g., from radionuclide ingestion. This commentary reviews techniques for biological dosimetry that have been developed to estimate radiation doses from internal exposures, but which can also be used to estimate external exposures. The author argues for increased development and use of these biological tools.

Biomarkers↗
PubMed1997

Butenafine 1% cream in the treatment of tinea cruris: a multicenter, vehicle-controlled, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a potent antifungal agent related to the allylamines, has been used in Japan for treating various cutaneous mycoses including tinea cruris. OBJECTIVE: We compared the safety and efficacy of butenafine hydrochloride and its vehicle when used once daily for 2 weeks to treat tinea cruris. METHODS: Patients (n = 93) with tinea cruris and a positive potassium hydroxide examination and mycologic culture were enrolled. Of the 76 patients assessed for efficacy, 37 applied butenafine and 39 applied vehicle once daily for 2 weeks. Assessments were made at the end of the 2-week treatment period and 4 weeks after the end of treatment. RESULTS: Patients in the butenafine group had a higher mycologic cure rate by day 7 (66% vs 13%, p < 0.0001), with marked improvement 4 weeks after the end of treatment (81% vs 13%, p < 0.0001). They also had a higher rate of effective treatment at day 7 (29% vs 5%, p < 0.01) and at 4 weeks after treatment (73% vs 5%, p < 0.0001). Adverse events definitely related to butenafine treatment were limited to one case of burning sensation after application. CONCLUSION: Butenafine applied once daily for 2 weeks is effective in treating tinea cruris. The proportion of patients cured increased between the end of treatment and 4 weeks after treatment.

Administration, Topical↗
PubMed1997

Blood interleukin 10 levels parallel the severity of septic shock.

PURPOSE: The aim of this study was to investigate the relation between interleukin (IL) 10, tumor necrosis factor alpha (TNF alpha), IL-1, and IL-6 levels in patients with septic shock and relate these cytokine levels to the development of organ failure. PATIENTS AND METHODS: In 11 patients with septic shock of recent onset, blood was sampled for determinations of TNF, IL-1, IL-6, and IL-10. The degree of organ failure was scored for four organ systems (respiratory, hepatic, renal, hematologic) in the first 48 hours of the study. RESULTS: The APACHE II score was 21 +/- 4. Three patients died. IL-10 levels were directly correlated with TNF levels (r = 0.73, P < .05) and IL-6 levels (r = 0.67, P < .05); and inversely correlated with total C3 (r = -0.73, P < .05) and CH50 (r = -0.68, P < .05). Both IL-10 and TNF levels were correlated to the organ failure score (r = 0.75 and r = 0.68, both P < .01). Six patients with high IL-10 levels (> 60 pg/mL) had lower C3 (37 +/- 11 v 62 +/- 10 mg/dL) and CH50 (32 +/- 7 v 68 +/- 19%), and higher organ failure scores (5.7 +/- 0.8 v 3.8 +/- 1.3) than those with low IL-10 levels (all P < .05). CONCLUSION: Although IL-10 has an inhibitory effect on the production of cytokines, it is released together with TNF and IL-6 in patients with septic shock. IL-10 blood levels are directly related to the severity of inflammation and the development of organ failure in septic shock.

APACHE↗
PubMed1997

Assessment of endocrine functions in children following severe head trauma.

The goal of the present study was to assess endocrine functions in children following severe head trauma. Subjects included 21 children between the ages of 3 years and 18 years 6 months, referred to the Pediatric Rehabilitation Unit at Sheba Medical Center, Israel, between 1984 and 1995. Each was examined 4 months to 11 years following the first admission, undergoing a complete physical examination, including neurologic assessment, biochemical and baseline endocrine profiles, and bone age determination. A GnRH stimulation test was performed in prepubescent children who had advanced bone age. Sixteen children had experienced the head trauma before, or at onset of puberty, according to their chronologic ages. Two children had completed puberty before the head trauma. A 12-year-old male who sustained head trauma at 10 years 6 months of age was found to have Tanner grade 3 pubertal stage and advanced bone age. In addition, 3 prepubescent children also had advanced bone age with no other signs of precocious puberty and a normal GnRH test. For all children studied, the biochemical and hormonal laboratory measurements were in the normal range. Endocrine abnormalities were not found in children examined 4 months or more following severe head trauma. We conclude that clinical monitoring of endocrine status after severe head trauma is sufficient; specific hormonal measurements are not required unless warranted by abnormal physical signs.

Adolescent↗
PubMed1997

IL-12 inhibits in vitro immunoglobulin production by human lupus peripheral blood mononuclear cells (PBMC).

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by polyclonal B cell activation and by the production of anti-double-stranded (ds) DNA antibodies. Given the inhibitory effects of IL-12 on humoral immune responses, we investigated whether IL-12 displayed such an activity on in vitro immunoglobulin production by SLE PBMC. Spontaneous IgG, IgG1, IgG2, IgG3 and IgM antibody production was dramatically reduced by addition of IL-12. These results were confirmed by Elispot assays detecting IgG- and anti-dsDNA-secreting cells. While IL-6 and TNF titres measured in PBMC supernatants were not modified by addition of IL-12, interferon-gamma (IFN-gamma) titres were up-regulated and IL-10 production down-regulated. Since addition of IFN-gamma did not down-regulate immunoglobulin production and since the inhibitory activity of IL-12 on immunoglobulin synthesis was not suppressed by anti-IFN-gamma antibody, we concluded that the effect of IL-12 on immunoglobulin production was not mediated through IFN-gamma. Our data also argue against the possibility that down-regulation of endogenous IL-10 production was responsible for the effect of IL-12. Thus, inhibition of IL-10 production by IFN-gamma was not accompanied by inhibition of immunoglobulin production, and conversely, restoration of IL-10 production by anti-IFN-gamma antibody did not suppress the inhibitory activity exerted by IL-12 on immunoglobulin production. Taken together, our data indicate that reduction of excessive immunoglobulin and anti-dsDNA antibody production by lupus PBMC can be achieved in vitro by IL-12, independently of IFN-gamma and IL-10 modulation.

Adult↗
PubMed1997

Interleukin-10 modulates susceptibility in experimental cerebral malaria.

In this study, we examined the effects of interleukin-10 (IL-10) on the outcome of experimental cerebral malaria (CM), a lethal neurological syndrome that occurs in susceptible strains of mice after infection with Plasmodium berghei ANKA (PbA). Constitutive IL-10 mRNA levels were significantly higher in the spleen and brain of resistant animals. In vivo neutralization of endogenous IL-10 in CM-resistant mice induced the neurological syndrome in 35.7% of these mice, as opposed to 7.7% in controls. IL-10 inhibited PbA antigen-specific interferon-gamma (IFN-gamma) production in vitro but not tumour necrosis factor (TNF) serum levels in vivo. Susceptible mice, on the other hand, were significantly protected against CM when injected with recombinant IL-10. Overall, our findings suggest that IL-10 plays a protective role against experimental cerebral malaria.

Animals↗
PubMed1997

Human monoclonal Fab fragments recovered from a combinatorial library bind specifically to the platelet HPA-1a alloantigen on glycoprotein IIb-IIIa.

BACKGROUND AND OBJECTIVES: Certain clinical conditions are related to the presence of platelet-specific alloantibodies in the patient's serum. We studied the molecular diversity of HPA-1a antibodies to analyze some peculiarities of this antibody response. MATERIALS AND METHODS: Human antibody Fab fragments that bind to the platelet alloantigen HPA-1a on glycoprotein IIb-IIIa (GPIIbIIIa) were generated by using a recombinant phage display system. We established an immunoglobulin G1, kappa combinatorial library from the peripheral blood lymphocytes of a person undergoing a severe posttransfusion purpura. RESULTS: Characterization of Fab clones selected from the fifth round of antigen-specific panning of this library demonstrates a highly specific reactivity to the HPA-1a alloantigen. The nucleotide sequence analysis of representative HPA-la-specific clones reveals at least 3 distinct V1 and 3VH gene segments that present an extensive degree of mutation as demonstrated by comparison of gene usage and homologies to the nearest germline genes. CONCLUSIONS: These human HPA-la-specific Fab reagents should allow us to better understand the molecular mechanism involved in HPA-la alloimmunization.

Amino Acid Sequence↗
PubMed1997

Evaluation of donor skin disinfection methods.

BACKGROUND: Because most bacteria isolated from contaminated platelet concentrates are thought to originate from the donor's skin, the efficacy of four methods of skin disinfection was compared. STUDY DESIGN AND METHODS: Contact plates were used for antecubital skin cultures after they were demonstrated to be easier to use and at least as sensitive as a swab system. One antecubital fossa of each subject was disinfected by a standard method, the use of a povidone-iodine swabstick containing 0.75-percent available iodine followed by the use of a povidone-iodine swabstick containing 1-percent available iodine. The other arm was disinfected with either a 70-percent isopropyl alcohol scrub followed by an ampoule of 2-percent iodine tincture (Group 1; n = 126); a green-soap sponge followed by a 70-percent isopropyl alcohol swab, used for donors who are allergic to iodine (Group 2; n = 30); or a 0.5-percent chlorhexidine gluconate and 70-percent isopropyl alcohol sponge followed by an ampoule of 0.5-percent chlorhexidine gluconate and 70-percent isopropyl alcohol (Group 3; n = 40). Contact plate cultures were done before and after disinfection, and colonies counted after a 48-hour 37 degrees C incubation period. RESULTS: Similar numbers of bacteria grew from both antecubital fossae of the same subject before disinfection (p = 0.71). Compared to the standard povidoneiodine method, isopropyl alcohol and tincture of iodine resulted in significantly less bacterial growth (p < 0.001), the green soap and isopropyl alcohol method resulted in significantly more bacterial growth (p < 0.001), and the chlorhexidine gluconate and isopropyl alcohol method resulted in similar amounts of bacterial growth (p > 0.3). CONCLUSION: Isopropyl alcohol scrub followed by iodine tincture is more efficacious than povidone-iodine as measured by contact plate cultures. For donors who are allergic to iodine, chlorhexidine gluconate and isopropyl alcohol is more efficacious than green soap and isopropyl alcohol.

1-Propanol↗
PubMed1997

Autologous donation error rates in Canada.

BACKGROUND: Although certain transfusion risks are eliminated by the use of autologous blood, clerical errors may still occur. In addition, because of differences in donor selection criteria and donor-patient expectations, the consequences of certain errors may be different in autologous and allogeneic donations. STUDY DESIGN AND METHODS: In January 1996, autologous donation error rates in Canada from 1989 to November 1995 were estimated by 1) a detailed questionnaire sent to hospitals supplied by the Canadian Red Cross, Blood Services, Transfusion Center of Quebec at Montreal autologous donation program (n = 31), 2) a review of that institution's quality assurance non-compliance reports, and 3) a detailed questionnaire sent to other Canadian Red Cross centers with autologous donation programs (n = 16) and hospital-based autologous programs in Canada (n = 3). The total number of autologous donations collected was determined from Canadian Red Cross annual reports and information supplied by hospital-based programs. RESULTS: There were 113 errors reported for 16,873 units collected by the Montreal center (1/149 units) based on collection center and hospital data. The most frequent errors were the late receipt of units for surgery (25% of errors) or the receipt of units in the wrong hospital (23%). Other Canadian programs reported 166 errors for approximately 53,500 units collected (1/322 units). However, this figure was based mainly on collection center, and not hospital, data. The most frequent errors were in labeling (48%) and component preparation (25%). One unit of autologous fresh-frozen plasma was transfused to the wrong recipient. Errors were more frequent if components were produced, if units were drawn in hospitals for interhospital transfer, or it units were shipped between Red Cross centers. CONCLUSION: Errors are not infrequent in autologous donation programs. Autologous transfusion should not be considered as being without risk.

Blood Donors↗
PubMed1997

Hepatoprotective role of interleukin 10 in galactosamine/lipopolysaccharide mouse liver injury.

BACKGROUND & AIMS: Interleukin (IL)-10 is a potent anti-inflammatory cytokine. Its role in modulating liver injury induced by galactosamine and lipopolysaccharide (Gal/LPS) was investigated. METHODS: The effects of recombinant IL-10 (rIL-10), anti-IL-10 monoclonal antibodies, or gadolinium chloride (GdCl3) pretreatment were studied in mice challenged with Gal/LPS. Tumor necrosis factor (TNF) alpha and IL-10 serum concentrations were measured and liver injury was assessed by alanine aminotransferase (ALT) serum concentrations and by histology. RESULTS: (1) IL-10 is produced early and together with TNF-alpha after Gal/LPS challenge. (2) Anti-IL-10 pretreatment increases TNF-alpha (+443%, P = 0.04), ALT (+160%, P = 0.04) serum levels, and the percentage of severe necrosis compared with control monoclonal antibodies. (3) Administration of rIL-10 30 minutes before Gal/LPS decreases TNF-alpha (-67%, P = 0.02), ALT (-94%, P = 0.01) serum concentrations, and the proportion of severe necrosis. The hepatoprotective effect is still observed when rIL-10 is injected 30 or 120 minutes after Gal/LPS. (4) GdCl3 pretreatment protects against hepatotoxicity, decreases TNF-alpha, but increases IL-10 serum concentrations. CONCLUSIONS: These results indicate that IL-10 protects the liver in the Gal/LPS mouse model. Increased IL-10 and decreased TNF-alpha secretion are potentially involved in the hepatoprotection observed after GdCl3 pretreatment.

Animals↗
PubMed1997

Role of reactive oxygen intermediates in interleukin 10 release after cold liver ischemia and reperfusion in mice.

BACKGROUND & AIMS: Reactive oxygen intermediates and cytokines are key effectors in reperfusion injury after liver ischemia. We hypothesized that reactive oxygen intermediates act as a signal for the release of tumor necrosis factor (TNF) and interleukin 10 (IL-10) after reperfusion of cold-preserved livers. METHODS: An endotoxin-free isolated perfused mouse liver system was designed. Harvested mouse livers were stored at 4 degrees C for 0-28 hours and reperfused for 90 minutes with a warm oxygenated Hank's balanced salt solution (alone or with additives). Cytokine messenger RNA (mRNA) from whole liver was measured by reverse-transcription polymerase chain reaction. Cytokine protein levels and liver injury assessed by alanine aminotransferase levels were evaluated in liver effluent during reperfusion. RESULTS: TNF and IL-10 mRNA and protein concentrations were increased after reperfusion of ischemic livers. N-Acetylcysteine and allopurinol dramatically decreased TNF (-64% and -62%) and IL-10 (-49% and -57%) levels in the effluents, as did an inhibitor of the transcription factor NF-kappaB mobilization (-73% and -76% for TNF and IL-10, respectively). Liver injury was decreased by -40%, -43%, and -54% for the three inhibitors, respectively. CONCLUSIONS: Reactive oxygen intermediates are involved in TNF and IL-10 release after reperfusion of cold-preserved livers.

Animals↗
PubMed1997

Psychological characteristics of child cochlear implant candidates and children with hearing impairments.

OBJECTIVE: To describe the psychological status of deaf children with hearing parents who were seeking a cochlear implant and to compare them with deaf children with hearing parents who were not seeking a cochlear implant. DESIGN: A sample of children consecutively referred for a cochlear implant at the University of Iowa Hospitals and Clinics was contrasted on a number of standardized psychological measures with a cohort of children from Boys Town National Research Hospital, who had hearing impairments and whose families had not sought a cochlear implant. RESULTS: Although the comparison group evidenced more externalizing and social problems than the implant group, the means of both groups fell well within the normal range. Similarly, although mothers of the implant group rated their child's home as characterized by more positive and supportive interactions than did mothers of the children in the comparison group, both group means were well within the average range. On measures of intelligence, the two groups also did not differ. CONCLUSION: Overall, the study indicated that children with hearing impairments and their families who were seeking cochlear implants are not significantly different from children with hearing impairments whose parents were not seeking a cochlear implant. The results provided no support for the notion that children with hearing impairments from families seeking a cochlear implants for their child evidence more behavioral deviance than children with hearing impairments whose parents have not sought an implant.

Adolescent↗
PubMed1997

Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson's disease. Methodology and 6-month to 1-year follow-up in 3 patients.

In order to launch a new transplantation program for Parkinson's disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Créteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 microliters of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the 'on' periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson's Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of 18F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.

Brain Tissue Transplantation↗
PubMed1997

The Russian radiation legacy: its integrated impact and lessons.

Information about the consequences of human exposure to radiation in the former Soviet Union has recently become available. These data add new insights and provide possible answers to several important questions regarding radiation and its impact on occupational and public health. The 1986 Chernobyl accident initiated a major and early increase in childhood thyroid cancer that resulted from ingestion of iodine-131 (131I) by young children living in the most heavily contaminated areas of Belarus, Ukraine, and Russia. No significant additional cancer or other adverse medical effects have yet been reported in the affected populations and among clean-up workers. Major psychological stress independent of radiation dose has been observed in those people thought to be exposed. During the early days of the atomic energy program in the former Soviet Union, some unfortunate events occurred. The country's first atomic test in Semipalatinsk in 1949 exposed over 25,000 people downwind from the blast to significant doses of fission products, especially 131I. During the late 1940s and the early 1950s nuclear material production facilities were developed near Chelyabinsk in the South Ural Mountains, which resulted in major releases into the environment and significant overexposures for thousands of workers and nearby populations. Chronic radiation sickness was observed early in exposed workers, and increases in leukemia and other cancers were also reported. The series of plutonium inhalation-related lung cancers and fatalities among workers exposed in that first decade appears to be unique. Long-term consequences of chronic radiation sickness and four decades of follow-up are being described for the first time. Villagers downstream from the plant consumed high levels of 137Cs and 90Sr and, it is reported, manifested increases in leukemia from internal and external exposures. Although the 40-year databases for retrospective dosimetry epidemiology studies are just beginning to be integrated and evaluated, preliminary evaluations suggest that there may be graded, significant dose-rate amelioration factors for cancer and leukemia risks in workers and the general population relative to the risk data on the Japanese atomic bomb survivors. Even for plutonium-induced lung cancers in workers, such a dose-rate effect may be evident. These experiences give us insight into the consequences of protracted radiation at high and low doses and rates. If these findings are validated and confirmed, they can provide information that reduces some of the uncertainties in retrospective radiation dosimetry and radiation risk estimates (especially for low-level, chronic exposures) for activities related to medicine as well as the handling of nuclear materials and nuclear facility decommissioning, decontamination, and demilitarization.

Adult↗