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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 253 records · Page 14Linked to original sources
PubMed1993

An eye irritation test protocol and an evaluation and classification system.

An in vivo test protocol and an evaluation and classification system for the determination of eye irritation potential of chemicals and mixtures (substances) is proposed. The protocol uses two or three rabbits and reduces distress in test animals. The test substances are classified as non-irritant, irritant or severe irritant to meet regulatory needs. They may be classified on the basis of past experience with similar compounds or mixtures. Screens such as structure-activity relationships, pH extremes, validated and accepted in vitro tests, severe dermal irritation (primary dermal irritation index > or = 5) or severe dermal toxicity (lethality at < 200 mg/kg body weight) should be used to classify irritant or severe irritant materials when one or more of the screens can provide convincing evidence. For suspected severe irritant materials, the proposed in vivo test permits the use of one rabbit and instillation of 0.01 ml (0.01 g) of the test material into the cornea. Materials that are not classified irritant or severe irritant by screens or severe irritant by one rabbit test are tested in two or three rabbits; 0.1 ml (0.1 g) is instilled into the conjunctival sac. The responses (corneal opacity, iritis and conjunctival redness) are scored according to the modified Draize scoring system at 24, 48 and 72 hr and 7 days post-instillation. A rabbit is considered positive when corneal opacity of 1 or above, iritis of 1 or above or conjunctival redness of 2 or above is present at 24, 48 or 72 hr post-instillation. The material is classified as a severe irritant when the rabbit in the one-animal test or two or more rabbits in the standard test have responses of corneal opacity of 3 or above and iritis of 2 at 24, 48 or 72 hr, or positive responses on day 7 after instillation. The material is classified as an eye irritant when two or more rabbits are positive but the responses are not severe and they clear 7 days after instillation. The material is classified as a non-irritant when no more than one rabbit is positive. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of US Federal agencies.

Animals↗
PubMed1993

The retinoid X receptor enhances the function of the peroxisome proliferator activated receptor.

The peroxisome proliferator activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of non-genotoxic rodent hepatocarcinogens termed peroxisome proliferators. A key marker of peroxisome proliferator action is the peroxisomal enzyme acyl-CoA oxidase that is elevated about 10-fold in the liver of treated rodents. We have shown previously that a peroxisome proliferator response element (PPRE) is located 570 bp upstream of the rat acyl-CoA oxidase gene and that PPAR binds to it. We show here that the retinoid X receptor (RXR) is required for PPAR to bind to the PPRE and that the RXR ligand, 9-cis retinoic acid, enhances PPAR action. These results therefore suggest that retinoids may modulate the action of peroxisome proliferators.

Acyl-CoA Oxidase↗
PubMed1993

Prison experience of injecting drug users in Glasgow.

Five hundred three injecting drug users in Glasgow recruited by a multisite and citywide sampling strategy were questioned regarding their drug-taking behaviour during episodes of custody over the six months prior to interview. Fifty-two percent had been in custody during the past 6 months, 16% of these had injected while in custody. Of these 73% borrowed injecting equipment and 78% handed on used equipment to others. All those who shared, cleaned their injecting sets before use. Over half of those who injected had a source of new sets. While the potential exists for spread of HIV among drug users while in custody there is clear understanding among them of the route by which the virus is spread and also the will to prevent it.

Cross-Sectional Studies↗
PubMed1993

Regulatory agency considerations and requirements for validation of toxicity test alternatives.

When developing an alternative toxicity test, one must first determine whether the alternative assay is to be used as a screen or as a replacement for the traditional toxicity test. An assay used as a screen will require less stringent acceptance criteria, for it is designed to answer fewer and less complex questions (e.g., the assessment of only potential teratogenicity). An assay used as a replacement will be used to establish hazard or lack thereof (safety). In other words, a replacement assay must clearly establish whether or not a chemical is a teratogen. One should also have knowledge of and experience with the in vivo assay to be replaced. This knowledge should be of not only the procedural aspects of the test but also the regulatory information it provides (i.e., how the results are used for hazard determination). Thorough consideration of the regulatory information is critical for a test intended to be used as a replacement. Validation should include intralaboratory and interlaboratory reproducibility of results from a standard protocol, an assessment of the qualitative and quantitative aspects of the test responses, and the use of a sufficient number of chemicals representative of the defined category of interest.

Animals↗
PubMed1993

Improved collisional excitation rates for interstellar water.

Theoretical rate constants among the lowest 45 para and 45 ortho rotational levels of water in collisions with He atoms have been calculated for temperatures between 20 and 2000 K using a recently improved theoretical interaction potential. These values are about 30%-40% larger than those reported previously (Palma et al. 1988b) but relative sizes of different state-to-state rates have not changed significantly. Successive improvements to the theoretical description of this system now appear to have converged.

Astronomical Phenomena↗
PubMed1993

An enhanced sensitivity K-shell x-ray fluorescence technique for tibial lead determination.

A novel irradiation-detection geometry capable of enhancing sensitivity for the measurement of tibial lead content by K-shell x-ray fluorescence (XRF) is described. The high-count-rate system comprised a small-area high-specific-activity (0.147 GBq mm-2) 109Cd source and a large-area (nominally 20 cm2) uncollimated detector, forming an axially symmetric back-scattering arrangement. Precisions in the range +/- 4.9 to +/- 14.2 micrograms Pb (g bone mineral)-1 have been obtained in a study of a cohort of 63 controls and 73 workers industrially exposed to lead. These precisions are comparable with those obtained in results using earlier systems, but at reduced source activities (less than 50% of the activity of other systems) and with significant reduction in measurement time (some 30% less than the measurement times of other systems). Subsequent investigation of detector collimation resulted in a marginal improvement in energy resolution, but the restriction in detected photon fluence meant that there was an insignificant change in detection sensitivity. For the resistive feedback preamplifier used in this study a maximum energy rate of the order of 7000 MeV s-1 was found to limit measurement precisions significantly. Higher-count-rate detector systems offer a basis for obtaining mean precisions down to +/- 3 micrograms Pb (g bone mineral)-1 at one standard deviation.

Humans↗
PubMed1993

Direct detection of infectious human immunodeficiency virus type 1 (HIV-1) immune complexes in the sera of HIV-1-infected persons.

The sera of human immunodeficiency virus type 1 (HIV-1)-infected subjects were examined for the presence of infectious HIV-1-antibody complexes by their ability to infect Fc gamma receptor (Fc gamma R)-bearing cells. Infection of Fc gamma R-bearing cells by a serum in which half of the p24 antigen was present in a form of immune complexes was inhibited by aggregated human immunoglobulin. Then in studies on 22 sera, 9 sera produced p24 antigen during 14 days of culture in U937 cells. HIV-1 p24 production was inhibited or delayed by the pretreatment of cells with aggregated human immunoglobulin in 6 of the 9 sera that were infectious. These results may reflect interactions between virus-antibody complexes and Fc gamma R-bearing cells in vivo because serum itself was used as the source of virus and virus-antibody complexes. The results indicate that infectious HIV-1 immune complexes are present in the circulation of HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1993

HIV risk behaviours among female prostitute drug injectors in Glasgow.

This paper focuses upon HIV-related risk behaviours of 51 female drug injecting prostitutes, interviewed as part of a serial cross-sectional study of injecting drug users in Glasgow. Forty-five per cent injected with used needles and syringes in the 6 months prior to interview. Condom use in private sexual relations was low with only 9% of those with primary partners and 22% of those with casual partners reporting consistent use of condoms with these partners. In contrast, use of condoms for all commercial sexual encounters was almost universal. Prevalence of HIV was 2.2%. Despite this low prevalence, we conclude that the level of injecting-related and private sexual risk behaviours reported here requires the continuing monitoring of drug injecting prostitutes in Glasgow.

Adolescent↗
PubMed1993

Dengue virus-specific human CD4+ T-lymphocyte responses in a recipient of an experimental live-attenuated dengue virus type 1 vaccine: bulk culture proliferation, clonal analysis, and precursor frequency determination.

We analyzed the CD4+ T-lymphocyte responses to dengue, West Nile, and yellow fever viruses 4 months after immunization of a volunteer with an experimental live-attenuated dengue virus type 1 vaccine (DEN-1 45AZ5). We examined bulk culture proliferation to noninfectious antigens, determined the precursor frequency of specific CD4+ T cells by limiting dilution, and established and analyzed CD4+ T-cell clones. Bulk culture proliferation was predominantly dengue virus type 1 specific with a lesser degree of cross-reactive responses to other dengue virus serotypes, West Nile virus, and yellow fever virus. Precursor frequency determination by limiting dilution in the presence of noninfectious dengue virus antigens revealed a frequency of antigen-reactive cells of 1 in 1,686 peripheral blood mononuclear cells (PBMC) for dengue virus type 1, 1 in 9,870 PBMC for dengue virus type 3, 1 in 14,053 PBMC for dengue virus type 2, and 1 in 17,690 PBMC for dengue virus type 4. Seventeen CD4+ T-cell clones were then established by using infectious dengue virus type 1 as antigen. Two patterns of dengue virus specificity were found in these clones. Thirteen clones were dengue virus type 1 specific, and four clones recognized both dengue virus types 1 and 3. Analysis of human leukocyte antigen (HLA) restriction revealed that five clones are HLA-DRw52 restricted, one clone is HLA-DP3 restricted, and one clone is HLA-DP4 restricted. These results indicate that in this individual, the CD4+ T-lymphocyte responses to immunization with live-attenuated dengue virus type 1 vaccine are predominantly serotype specific and suggest that a multivalent vaccine may be necessary to elicit strong serotype-cross-reactive CD4+ T-lymphocyte responses in such individuals.

Adult↗
PubMed1993

Mortality among injecting drug users: a critical reappraisal.

STUDY OBJECTIVE: The aim was to quantify all cause mortality among injecting drug users. DESIGN: This was a retrospective analysis of 1989 data on injecting drug users and mortality obtained from three independent agencies: the Procurator Fiscal's Office, the General Register Office, and the Scottish HIV-test register. SETTING: Greater Glasgow, Scotland. SUBJECTS: Drug injectors, estimated population 9424. MAIN RESULTS: 81 names were found using the three sources to identify deaths. After removing duplicates, 51 deaths were found. This represented a mortality rate of 0.54% in the estimated population. Among female injectors the mortality rate was 0.85%, significantly higher than the rate of 0.42% among male injectors (95% CI for the true difference in mortality rates between female and male injectors was 0.31%-0.55%). Over 90% of deaths were attributed to overdose or suicide. Although AIDS caused only one death, 19% of cases (5/27) whose HIV antibody status could be ascertained were positive. The mortality rate among HIV positive injectors (3.8%) was significantly higher than among HIV negative injectors (0.49%). CONCLUSIONS: Comprehensive coverage using three data sources revealed a far greater annual number of all cause deaths among injectors than would have been expected from previous research. The observed mortality rate was lower than in previous studies where the denominators used to calculate rates had an element of underenumeration. For the foreseeable future it is unlikely that AIDS will have much impact on mortality among injectors in Glasgow, because of the low prevalence of HIV infection among injectors in the city, and because HIV positive injectors are dying for reasons other than AIDS; rather, overdose and suicide will continue to be the main causes of death.

Adolescent↗
PubMed1993

Results of a Southwest Oncology Group phase III trial of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide in advanced ovarian cancer.

Cisplatin combined with cyclophosphamide has been considered a very active treatment for advanced ovarian cancer. Unfortunately, cisplatin is associated with dose-limiting neurotoxicity, as well as possible neuropathy, ototoxicity, and occasional renal dysfunction. Carboplatin, a cisplatin analogue, is active against advanced ovarian cancer, with a presumed lower incidence of emesis, ototoxicity, neuropathy, and renal dysfunction. The Southwest Oncology Group initiated a phase III randomized trial, in which 342 patients with stage III (suboptimal disease) and stage IV ovarian cancer were randomly assigned to treatment with six courses of intravenous cisplatin 100 mg/m2 plus cyclophosphamide 600 mg/m2 or carboplatin 300 mg/m2 plus cyclophosphamide 600 mg/m2. The median survival for the cisplatin arm was 17.4 months; for the carboplatin arm, median survival was 20.0 months. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the p = 0.02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. There was less thrombocytopenia in the cisplatin arm (p < 0.001); however, there was less nausea and emesis (p < 0.001 for courses one to five), renal toxicity (p < 0.001), anemia (p < 0.001), hearing loss (p < 0.001), and neuromuscular toxicity (p < 0.001) in the carboplatin arm. Carboplatin/cyclophosphamide proved to have a significantly better therapeutic index than cisplatin/cyclophosphamide in these patients with advanced ovarian cancer.

Adult↗
PubMed1993

Longer term functional outcome and societal implications of upper limb fractures in the elderly.

To ascertain how they cope with upper limb fractures and the implications for health and social services (H&SS) a cohort of elderly patients was followed up. 42 of the original 51 (82%) patients were interviewed almost one and a half years after sustaining their fracture. Information was collected on ability to perform activities of daily living (ADL), general health, and use of H&SS help from informal carers. Although there was an overall improvement in the ability to perform ADL, many (26%) patients reported a residual difficulty. Informal carers provided most of the support with some contribution from the statutory agencies. Demographic changes with increasing numbers of elderly and increasing employment of married women--the traditional carers, and epidemiological changes with increasing age-specific incidence of upper limb fractures mean that H&SS provision in the future will need to be increased.

Activities of Daily Living↗
PubMed1993

Autologous bone marrow transplantation for pediatric Hodgkin's disease: a case-matched comparison with adult patients by the European Bone Marrow Transplant Group Lymphoma Registry.

PURPOSE: We analyzed the outcome of autologous bone marrow transplantation (ABMT) in pediatric and adult patients with Hodgkin's disease (HD) by means of a case-controlled study. PATIENTS AND METHODS: Eighty-one pediatric HD patients who had undergone ABMT and who had been reported to the European Bone Marrow Transplant Group (EBMTG) Lymphoma Registry were compared with a case-matched group of 81 adult patients who had undergone the same procedure. The case-matching was performed following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. RESULTS: The PFS rate was not significantly different between the groups (39% for the pediatric group v 48% for the adult group). The overall relapse/progression rates for the groups were 52% and 40%, respectively. This was not a statistically significant difference and the sites of relapse were similar. There was no significant difference in the incidence or causes of procedure-related morbidity or mortality of the two groups. CONCLUSION: This study suggests that patients with pediatric HD have the same outcome at ABMT as their adult counterparts; however, long-term complications will need to be carefully monitored.

Adolescent↗