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Biomedical subjects

R Israeli

Publications and source records attributed to R Israeli.

At least 19 recordsLinked to original sources
PubMed2006

A phase I trial of pox PSA vaccines (PROSTVAC-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM) in patients with prostate cancer.

PURPOSE: Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA) targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM) to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM. METHODS: In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 x l0(8) pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 x 10(9) pfu of the booster recombinant fowlpox virus (PROSTVAC-F) both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79). The mean PSA at baseline was 434 (range 9-1424). RESULTS: There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE) occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA) through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients. CONCLUSION: This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.

Journal Article↗
PubMed2001

Retrospective stratification of a consecutive cohort of prostate cancer patients treated with a combined regimen of external-beam radiotherapy and brachytherapy.

PURPOSE: The evaluation of clinical variables that influence biochemical relapse-free survival in a cohort of patients treated by combined radiotherapy over a fixed interval. METHODS AND MATERIALS: Three hundred forty-eight patients diagnosed with clinical Stage T1--T3a prostate cancer were treated with a course of (103)Pd or (125)I brachytherapy followed by a limited course of external beam radiation formed the basis for study. All censored patients had a minimum 2-year follow-up. Biochemical relapse-free survival (BRFS) was estimated using a modified American Society for Therapeutic Radiology and Oncology consensus definition. Discrete "risk groups" were developed based on BRFS as influenced by pretreatment parameters. RESULTS: Significant risk factors contributing to biochemical failure were serum prostate-specific antigen (PSA) greater than 20 ng/mL, Gleason sum of 7 or greater, or clinical stage T2c or greater. Five-year biochemical control for those exhibiting no risk factor was 88%; one risk factor, 75%; two or more risk factors, 51%. The differences in BRFS among all three risk groups were statistically significant. Outcomes for patients presenting with PSA 10 to 20 ng/mL, but otherwise low-risk disease, fared no differently from those low risk patients presenting with PSA less than 10 ng/mL. CONCLUSIONS: Combined radiotherapy with (103)Pd or (125)I followed by external beam radiotherapy achieves a high rate of biochemical and clinical control in patients with low- to intermediate-risk clinically organ confined disease.

Analysis of Variance↗
PubMed1999

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↗
PubMed1999

Infected nonunion of the tibia.

The treatment of infected nonunited fractures of the tibia using the techniques of Ilizarov was compared with autogenous cancellous bone graft application under a well vascularized soft tissue envelope. There were 10 patients in the Ilizarov group and 17 in the bone graft group. Soft tissue coverage with a free vascularized or a rotational muscle flap was used more frequently among the patients having bone graft (71%) than the Ilizarov group (30%). All 27 patients had bony defects (average, 3.7 cm; range, 1-18 cm). At an average followup of 6 years, 26 patients had a functional limb, and one patient (Ilizarov group) ultimately required a below knee amputation. Three patients in each group required a second plate and bone graft procedure to gain union. Infection persisted in four patients (all in the Ilizarov group). If a well vascularized soft tissue envelope is present (particularly after flap coverage), bone grafting procedures are safe and efficacious. The Ilizarov technique may be best suited for the treatment of very proximal or distal metaphyseal nonunions and nonunions associated with large leg length discrepancies.

Adult↗
PubMed1989

Upstream regulatory elements of murine alpha 4-interferon gene confer inducibility and cell type-restricted expression.

We have identified and functionally characterized DNA sequences that are required for the inducible and cell-restricted expression of the murine alpha 4-interferon gene. Hybrid plasmids in which the alpha 4 promoter region or its 5' deletions were inserted upstream of the CAT gene were constructed, and the expression of these hybrid genes was studied in mouse L-cells both in permanent and transient assays with comparable results. Inducible expression was not affected by deletions up to -109; however, when the deletion was extended to -96, inducibility by Newcastle disease virus was abolished; however, this hybrid plasmid was expressed constitutively. Further deletion to -88 did not permit either constitutive or inducible expression. Insertion of the 35-base pair-long sequence (-109 to -75 base pairs) from the alpha 4 promoter region 5' of the minimal alpha 4 or human immunodeficiency virus promoter region, conferred inducibility to these two inactive promoters. The 5' deleted hybrids or plasmids containing the inducible element were induced only at low levels in transfected NIH/3T3 cells that do not express endogenous alpha 4 gene efficiently, indicating that the inducible region also determines the cell-specific expression. A tandem repeat of AGTGAA, which is present in the -109 to -88 region of alpha 4 in two copies, showed both basal levels of expression and inducibility in L-cells, while its analogue AATGAA was highly inducible but was not expressed constitutively. The inducibility of the synthetic hexamer repeats did not show cell type-restricted expression, suggesting that their response does not fully reflect the range of expression observed for the inducible region and the endogenous alpha genes.

Animals↗
PubMed1988

Synthesis, antiviral activity, and conformational characterization of mouse-human alpha-interferon hybrids.

Reciprocal hybrids were constructed between human and mouse interferons (IFNs), and their antiviral activity was examined on different target cells and compared to the activity of the parental molecules. In addition, we used a number of predictive algorithms on a data base of the available alpha-interferon sequences to propose a working model for the overall conformation of the alpha-interferon molecule that is consistent with the structural predictions. Remarkable conservation within the predicted alpha-helical segments of the interferon molecule was observed. We propose that the observed changes in the activity and specificity of the hybrids obtained are largely due to the sequences present in the loops at the ends of the major helical structures; these are less conserved, contain beta-bends, and are generally hydrophilic and flexible. The data on the constructed mouse-human hybrids have shown that the activity on human cells is contributed by determinants present in the N-terminal 122 amino acids of human IFN, thus implicating one or more loops within this region (e.g. loops 1-12, 25-38, 70-74, and 103-113). The activity on bovine cells appears to be localized mainly in sequence 60-121, implicating the role of loops 70-74 and/or 103-113 of the human IFN molecule. The specificity of mouse IFN for mouse cells is in some or all of the loops (70-74, 103-113, 134-139, and 163-166) in the C-terminal sequence. The proposed working model should provide guidelines for the study of the specificity of action in molecular terms.

Amino Acid Sequence↗
PubMed1986

Pulmonary function screening and monitoring in occupational health.

Lung function testing among occupationally exposed workers has demonstrated its usefulness in risk evaluation and, once risks are identified, in medical surveillance. Its usefulness for screening and biological monitoring for effects of exposure is not yet established; in part, this is due to some failure to understand the requirements for screening and for monitoring, and in part, it is due to some unresolved questions as to procedures and their interpretation. The use of screening in occupational groups in general and those exposed to inhalational risks is evaluated. The current recommendation is that priority for screening be given to risk factor reduction, including smoking cessation. Problems associated with screening relate to procedures, equipment, and interpretation of data. An agenda is proposed for an international effort to determine principles for epidemiological use of lung function tests for prevention of occupational pulmonary disease risks.

Adult↗
PubMed1984

Monitoring of unfavorable reproductive outcome (URO) among occupationally exposed groups.

In the Negev Region of Israel, population 300,000, with a centralized health care and health data system, we propose to monitor associations of occupational exposure with the following URO (approximate rates in parenthesis): infertility (10%), spontaneous abortion (10%), stillbirth (1%), pregnancy complications (5%), specific birth defects (1%), all birth defects (5%), low birth weight (5%), neonatal morbidity (5%); all URO (25%). Critical covariates include smoking, age, contraceptive use, coexisting disease, parity, spouse exposures, and past reproductivity history. Currently exposed women are estimated to include 150 in hospital operating rooms, 200 laboratory workers, 75 chemical production workers and 20 in mercury thermometer factory; men include 5000 in chemical production, 1000 in agricultural chemical use, 100 in chemical laboratories and 200 in university and hospital laboratories. Adjusting for expected turnover rates, we estimate that overall exposures which have risks of increased URO will include about 5000 men and 1000 women. Since priority in research resources goes to most feasible detection and prevention combinations, we define and examine "minimal detectable risk ratios" based on expected populations sizes and incidences for a two year cohort study with estimated one "exposed pregnancy" per five person years in this young population. We tabulate these risk ratios using a cutoff for false positive at p=0.05 and false negative at p=0.1. Sex ratio changes represent outcomes relatively easily detected. Proposed application of these criteria to Negev populations and an example of such applications to published work place exposures to dioxins are shown.

Chemical Industry↗
PubMed1984

Monitoring for neurotoxic effects from low level exposures to organophosphate pesticides.

Data from small scale studies on low level and delayed neurotoxic effects from exposure to organophosphate pesticides suggest the need for monitoring those at risk in agriculture and industry, as well as residents repeatedly exposed to aerosol drift from aerial spraying. A pilot program is put forth with the aim of determining whether such effects occur in exposed populations, and if they do, assessing their incidence, distribution and severity, as well as the efficacy of control programs.

Aryldialkylphosphatase↗
PubMed1983

Acute central nervous system changes due to intoxication by Manzidan (a combined dithiocarbamate of Maneb and Zineb).

A 42-year old man sprayed Manzidan (a combined dithiocarbamate of Maneb and Zineb) on a cucumber plantation, twice during a week. Behavioural changes appeared after the first application, and loss of consciousness, convulsions and right hemiparesis after the second application with diffuse slow rhythm in the EEG. Both the behavioural and CNS symptomatology disappeared spontaneously after a few days. The previous history of the patient, the sudden appearance and spontaneous disappearance of the symptoms and a dose-response relationship strongly suggest that Maneb and Zineb were the cause of the illness.

Adult↗
PubMed1983

Acute intoxication due to exposure to maneb and zineb. A case with behavioral and central nervous system changes.

The dithiocarbamates are considered chemicals of low toxicity. They are known to cause dermatitis, conjunctivitis, rhinitis, pharyngitis, and bronchitis in humans. Central nervous system effects in humans have not been found, but some cases have been reported in experimental animals. This case report concerns a 42-year-old man previously in good health, who sprayed a combined dithiocarbamate of maneb and zineb on a cucumber plantation twice during a week, the second time with a more concentrated solution than the first. Behavioral changes appeared after he walked through the sprayed area following the first application, and loss of consciousness, convulsions, and right hemiparesis with diffuse slow rhythm in the electroencephalogram occurred after the second exposure. Both the behavioral and central nervous system symptomatology disappeared spontaneously after a few days. An electroencephalogram was normal two weeks later. The absence of a positive previous history of the patient, the sudden appearance and spontaneous disappearance of the symptoms, and the apparent dose-response relationship strongly suggested that maneb and zineb were the cause of the illness.

Acute Disease↗
PubMed1981

Occupational exposure to dust containing free silica in a ceramics factory.

In a ceramics plant employing 225 workers, respirable dust was collected into personal samplers worn by exposed workers. Analysis by X-ray diffraction documented exposures to free silica greater than 50 micrograms/m3-the permissible exposure level or threshold limit value-time weighted average proposed by the U.S. National Institute of Occupational Safety and Health-in 15 of 25 determinations. Excessive exposures were produced by dust with quartz content less than or equal to 8% by weight. If there had been such exposures to free silica-containing dust in the past, X-ray findings compatible with silicosis, described in a group of workers employed for 5 to 23 years prior to this study could be accounted for. The exposures appeared to be due to failure to incorporate established principles for prevention of dust exposure when the plant was designed. Routine determination of free silica content, even at trace and low levels, is necessary to assess the potential hazard for silicosis in dusty workplaces.

Air Pollutants↗