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Biomedical subjects

S Sherwin

Publications and source records attributed to S Sherwin.

16 recordsLinked to original sources
PubMed2002

Genetic susceptibility to fibrocalculous pancreatic diabetes in Bangladeshi subjects: a family study.

Fibrocalculous pancreatic diabetes (FCPD) is an uncommon cause of diabetes, seen mainly in developing countries. A family-based study was carried out in 67 Bangladeshi families, consisting of a proband with FCPD and both parents, to determine whether an association exists between FCPD susceptibility and either the major histocompatiblity complex (MHC) or insulin gene (INS) loci. HLA-DQB1 typing was done using allele-specific primers, and INS was typed using the restriction enzyme HphI. Three microsatellites (TNFa, TNFc and TNFd), from within and flanking the TNF-LT locus, were used for MHC Class IV typing and a PCR-RFLP assay was used to define the -308G/A TNF promoter polymorphism. The extended transmission disequilibrium test (ETDT) was used for statistical analysis. An overall association was observed between FCPD and HLA-DQB1 (P = 0.003), that was largely due to a positive association with HLA-DQB1*0302 and a negative association with HLA-DQB1*0202. Although no association was found between FCPD and TNF-LT microsatellite markers a trend was observed for TNFc (P = 0.037, Pc = 0.15). No association was found between FCPD and INS (P = 0.26). This study confirms an association between FCPD and the MHC using a family-based study design and the stringent ETDT analysis; a novel protective association was found with HLA-DQB1*0202 in Bangladeshi FCPD subjects. The genetic susceptibility to FCPD has features both similar and dissimilar to T1DM.

Bangladesh↗
PubMed2001

Feminist ethics and the metaphor of AIDS.

This paper looks at a range of metaphors used within HIV/AIDS discussions and research in support of the claim that bioethicists should pay serious attention to metaphors. Metaphors shape the ways we think about problems and the types of solutions we investigate. HIV/AIDS is an especially rich field for the investigation of metaphor, since the struggles for dominance among different metaphorical options has been very evident. In the field of medical research as well as in the area of public policy, different metaphors support different strategies and, therefore, the choice of metaphor has ethical significance. I argue that feminists should engage in these debates since they have an interest in the metaphors selected. They can also learn to be more self-conscious in choosing politically liberating metaphors in other bioethics contexts.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Moral perception and global visions.

Because moral perception plays an essential role in guiding morally responsible behaviour, agents have a responsibility to develop their capacities in this area. There are several strategies agents can (and should) pursue in order to improve their skills at moral perception. I appeal to insights derived from the work of feminist epistomologists [sic] and philosophers of science to argue that feminist approaches to multiculturalism are particularly valuable tools for improving moral perception.

Bioethics↗
PubMed1991

Organ specific cytokine therapy. Local activation of mononuclear phagocytes by delivery of an aerosol of recombinant interferon-gamma to the human lung.

In the context of the central role of the alveolar macrophage in host defense of the respiratory epithelial surface, and the ability of IFN-gamma to activate mononuclear phagocytes, we have evaluated strategies to use rIFN-gamma to activate human alveolar macrophages in vivo. To accomplish this, rIFN-gamma was administered to nonsmoking normals, the amounts of IFN-gamma quantified in serum and respiratory epithelial lining fluid (ELF) and the status of IFN-gamma related activation of blood monocytes and alveolar macrophages was evaluated by quantifying the expression of mRNA transcripts of IP-10, a gene induced specifically by IFN-gamma. Systemic administration (subcutaneous) of maximally tolerated amounts of rIFN-gamma (250 micrograms) was followed by detectable levels of IFN-gamma in serum but not ELF, the expression of IP-10 transcripts in blood monocytes but not alveolar macrophages, and multiple systemic adverse effects. To circumvent the inability of systemic administration to reach respiratory ELF and activate alveolar macrophages, rIFN-gamma (250-1,000 micrograms) was inhaled as an aerosol once daily for 3 d. Strikingly, while IFN-gamma was not detected in serum it was detectable in respiratory ELF in a dose-dependent fashion. Further, alveolar macrophages, but not blood monocytes, expressed IP-10 mRNA transcripts and, importantly, inhalation of aerosolized rIFN-gamma was not associated with local or systemic adverse effects. Thus, it is feasible to use rIFN-gamma to activate alveolar macrophages by targeting the cytokine directly to the lung. These data suggest a potential strategy for targeted cytokine therapy, without systemic side effects, to augment respiratory tract defenses in individuals at risk for or with lung infection.

Actins↗
PubMed1990

Widespread intradermal accumulation of mononuclear leukocytes in lepromatous leprosy patients treated systemically with recombinant interferon gamma.

Intradermal administration of recombinant interferon gamma (rIFN-gamma) to lepromatous leprosy patients has converted the local histology toward a tuberculoid pattern. However, such changes have been confined to the site of injection. In contrast, in the present study, marked, intradermal accumulation of CD3+, CD4+, CD8+, and CD1a+ T cells and Leu-M5+ mononuclear phagocytes was induced at a distance from the sites of administration, in a dose-dependent manner, by 10 daily intramuscular injections of 10-30 micrograms rIFN-gamma/m2. Mononuclear cell infiltration began within 3 d of onset of rIFN-gamma therapy and persisted at least 8 wk. Intramuscular administration of rIFN-gamma to lepromatous patients receiving concurrent chemotherapy can safely induce widespread histologic features of an upgrading reaction.

Adult↗
PubMed1988

Tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts.

PURPOSE: The intralesional administration of recombinant interferon alpha has led to resolution of genital warts in 50 to 70 percent of cases. However, continuous warts do not respond to such treatment, and human papillomavirus (HPV) infection of other anatomic sites remains untreated, so infection may continue to be transmitted. Since interferons have shown promise as effective therapies for genital warts, we decided to investigate the tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts. PATIENTS AND METHODS: Nineteen women and nine men with refractory genital warts were treated in an open-label, dose-response trial of intramuscular recombinant human interferon gamma. RESULTS: Complete responses were seen in two (7 percent) and partial responses were seen in 13 (46 percent). Of 12 women with concomitant cervical HPV infection, eight demonstrated resolution with therapy. Response rates were higher in those patients who had warts less than nine months (73 percent) prior to therapy and in women (63 percent). Responses were not associated with HPV type. Flu-like symptoms during treatment were frequent but well tolerated. Transient abnormal laboratory results were more frequent with daily administration than with three times weekly therapy. Eleven of 16 subjects treated with cryotherapy after treatment with interferon experienced long-term remissions. CONCLUSIONS: In ambulatory patients with refractory genital warts, recombinant human interferon gamma appears to be biologically active and to have few adverse effects. The high efficacy rate achieved in subjects treated with cryotherapy after treatment with interferon suggests that further studies of combination therapy with these modalities are warranted.

Adolescent↗
PubMed1984

Recombinant leukocyte A interferon: an active agent in advanced cutaneous T-cell lymphomas.

High-dose recombinant leukocyte A interferon (50 X 10(6) U/m2 body surface area, intramuscularly, three times weekly) was tested in a clinical trial involving patients with advanced cutaneous T-cell lymphomas to determine its effectiveness and toxicity. All 20 patients had advanced stages of disease refractory to two or more standard therapies. Objective partial remissions lasting 3 months to more than 25 months (median, 5 months) were documented in 9 patients. The major dose-limiting toxicity was a severe influenza-like syndrome with malaise, anorexia, depression, weight loss, and decreased performance status; this effect was reversible after dose reductions in all patients and did not recur with re-escalation of doses in 10 patients. This interferon preparation is highly effective in the treatment of advanced refractory cutaneous T-cell lymphomas, and new schedules to reduce toxicity and achieve complete responses, combined treatment with chemotherapy or serotherapy, and its use in earlier stages of disease should be investigated.

Adult↗
PubMed1984

The pharmacokinetics of 99mTc HIDA in man and its relationship to intra-gastric bile acids.

We have examined the pharmacokinetics of 99mTc diethyl HIDA in five patients with a T-tube inserted into their common bile duct after choledocotomy. Blood clearance was rapid with 27.5% of the injected dose in the circulation at 2.5 min and 5% at 30 min. The peak bile excretion of 15.4% occurred between 45 and 60 min after injection of the HIDA. By 2 h 69% of the dose was excreted in the bile and 14% in the urine. In a second group of 33 patients a naso-gastric tube was passed after injection of HIDA. The patients drank 400 ml of 10% dextrose and aliquots of the stomach contents were aspirated every 10 min for an hour. In specimens with a pH greater than 4, the amount of HIDA correlated well (p less than 0.01) with the amount of bile acid determined by an enzymatic method.

Adult↗