Mental health. Over the rainbow.
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Biomedical subjects
Publications and source records attributed to S Payne.
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A highly sensitive method for light microscopic immunohistochemistry is described. The increased sensitivity compared with current methodologies is based on the horseradish peroxidase-catalysed deposition of biotinylated tyramine at the sites of immunoreactivity, followed by the detection of the biotin with streptavidin biotin horseradish peroxidase complex. This method is of general applicability in immunohistochemistry and has several important advantages over currently used immunohistochemical detection procedures. The most significant advantage is that several antibodies which to data have been non-reactive, even in antigen-retrieval formalin-fixed, was-embedded sections, now show strong and reproducible immunoreactivity using biotinylated tyramine amplification. In addition, many other antibodies can be used at significantly higher dilutions.
Proton electron double resonance imaging (PEDRI) was used for monitoring in vivo the distribution, metabolism and, in particular, the excretion mechanism of the exogenous nitroxide free radical proxyl carboxylic acid (PCA) in the rat. PCA clearance half-lives through liver, abdominal vessels, and renal tissues were determined from a series of PEDRI images for normal rats (n = 5) and rats treated with probenecid (n = 5), a competitive inhibitor of the tubular secretion process. The approximately doubled renal half-lives of the treated animals suggest that tubular secretion accounts for about 50% of PCA renal loss in the normal rat and reabsorption is insignificant. PCA binding to bovine serum albumin was investigated by X-band ESR and the bound fraction was found to be less than 10% of the total PCA. Most probably, PCA binds to hydrophilic sites. Blood PCA concentration investigated by X-band ESR exhibited biphasic behavior and PEDRI results confirmed the in vivo metabolic reduction of PCA by rat liver cells.
The vasoactive effects of the arachidonic acid-derived cyclooxygenase product, prostaglandin F2 alpha and PGH2 analogue U46619, on ex vivo perfused (25 microliters/min) bovine retinal microcirculation were assessed. First, we determined the ability of the cultured bovine retinal microvascular endothelial cells to synthesize eicosanoids from 14C-arachidonic acid. Bovine retinal microvascular endothelial cell cultures synthesized detectable amounts of PGE2, PGF2 alpha, PGI2, and PGH2 analogue; PGI2 product being slightly greater. The central retinal arteriole was cannulated and microcirculation continuously perfused with PSS with constant flow. Vasoactive compounds were applied in ten-fold concentration increments to PSS in the muscle chamber containing retinal preparation. The diameters of retinal microarterioles were measured using a closed-circuit video camera system. In ex vivo bovine retinal microvascular model studies, PGF2 alpha and PGH2 analogue U46619, caused dose-dependent vasoconstriction of all vessels, and these responses were attenuated by specific TP (TXA2) receptor antagonist, SQ 29,548, at 10(-6) M.
This study provides evidence of a significantly (P = 0.018) increased level of expression of the stable conformation of p53 in normal urothelial cells, cultured in vitro from bladder biopsies obtained from normal smokers without malignant disease of any site. With two significant exceptions, non-smokers showed low or no expression of this protein. Past smokers appeared to segregate into high or low p53 expressers, but the expression was not correlated with years since quitting smoking or with pack years smoked. The mean data in this group were not quite significantly different (P = 0.08) from the non-smoker group, due to the wide inter-patient variation. For most of the smoker group, pack years correlated with p53 expression with a mean unit of 1.7 +/- 0.37% p53 per pack year but there was a small group of very heavy smokers who showed lower than expected expression (approximately 0.3-0.8% p53 per pack year). These were statistical outliers (Grubbs test). No explanation could be found for this. Over-expression of p53 protein, often correlates with mutations in the gene, but may also indicate that breakdown of wild-type p53 has slowed. SSCP analysis of the biopsy material was not possible on all patients due to ethical constraints on the amounts of tissue which could be taken but in the cases where it was possible the association between loss of p53 protein function and mobility shifts in p53 exons 5-8 was confirmed with smokers having 3.5 times the number of mobility shifts detected in non-smoker DNA. Thus the results may point to a role for the early abrogation of p53 protein function in bladder carcinogenesis induced by cigarette smoking.
This paper reports on an ethnographic investigation of a palliative day care unit. The aim of the study was to explore communication processes amongst patients with terminal disease, in an 'open awareness' context. The research involved participant observation over a period of 7 weeks. Detailed field notes were written and documentary information gathered on site. Analysis of the data showed that in the day care environment, patients readily talked about cancer, illness and death. Five themes were identified in the content of such 'death talk': talk about illness, symptoms and treatment, stories about illness and death, talk about patient deaths, talk regarding bereavement, and talk concerning personal mortality. In addition to content, it is maintained that the form of the patients' talk is pertinent to an understanding of the discursive context of palliative day care. It is proposed that the light-hearted and humorous nature of patient 'death talk' serves an important psychological function in allowing patients to distance themselves from their own deaths whilst simultaneously permitting an acknowledgement of their terminal condition. This suggests that the provision of an appropriate 'social' environment for patients with terminal disease may be as important to patients as one-to-one counselling by clinical nurse specialists.
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BACKGROUND: Dietary supplementation with L-arginine enhances natural cytotoxicity in peripheral blood lymphocytes but its effect on infiltrating lymphoreticular cells within a tumour microenvironment is unknown. The effects of dietary supplementation with L-arginine on tumour-infiltrating lymphocytes (TILs) in patients with colorectal cancer were evaluated. METHODS: Eighteen patients received either a standard hospital diet (controls) or a standard diet supplemented with 30 g per day of L-arginine for 3 days before surgery. Tumour biopsies were taken at surgery and lymphocyte subsets (CD antigens) and macrophages examined immunohistochemically. RESULTS: Tumours from patients receiving L-arginine contained increased numbers of specific cell subsets within the tumour which expressed CD16 (P = 0.004) and CD56 (P = 0.001) surface markers, when compared with tumours from control patients. There were no differences in the total number of T and B cells, T helper and T suppressor cells. CONCLUSION: Dietary supplementation with L-arginine significantly alter the spectrum of TILs in human colorectal cancers in vivo. These findings have important implications for new strategies in anticancer treatment.
All prior studies on human age-related chromosomal analysis were done using only metaphase figures derived from lymphocyte cultures in vitro. However, we believe that this procedure may provide only partial information, since the chromosomal abnormalities probably hidden in non-dividing and/or terminally differentiated leukocytes will not be detected by this method. We, therefore, have attempted to analyze the nature and extent of chromosome-specific aneuploidy at interphase by fluorescence in situ hybridization (FISH) in differentiated myeloid cells in vivo derived from various age-group people. Our data from an analysis of 30,032 cells derived from 12 healthy donors indicate that there is an increase in the mean percentages of myeloid cells with chromosome-specific aneuploidy in the older groups as opposed to that of the younger groups. This increase is applicable to all the three cell types examined (promyelocytes, metamyelocytes and polymorphs). In both the younger and older females, the relatively higher mean frequencies of cells with aneuploidy were noted for chromosome nos. 4, 6 and the X, whereas the lowest mean frequencies of cells with aneuploidy were consistently observed for chromosome no. 3. In the younger and older male donors, similar to the female donors except the X chromosome the higher percentages of aneuploid cells were observed for chromosome nos. 4 and 6 whereas the lowest mean frequencies of aneuploid cells were noted for chromosome no. 3. Among the five autosomes studied, chromosome no. 3 consistently yielded the lowest frequency of aneuploidy in all the three cell types derived from both the younger and older groups of males and females. This could presumably mean that the maintenance of a very high frequency of cells with disomy for chromosome no. 3 might be more beneficial for the process of survival and/or differentiation of myeloid cells as compared to that of other autosomes such as chromosome nos. 4 and 6. Among the five autosomes studied, chromosome no. I exhibited the highest rate of increment in the aneuploidy values of both males and females with advancing age.
Targeted disruption of the transforming growth factor-beta 1 (TGF-beta 1) gene in mice results in the development of a massive multifocal inflammatory disease in many tissues. Because no detectable pathogen was identified, we examined whether autoimmune mechanisms played a role in initiating or maintaining the inflammatory disease. The serum of TGF-beta 1 knockout mice contained elevated titers of antibodies to nuclear antigens (ssDNA, dsDNA, Sm, and RNP) as well as reactivity against the 16/6 idiotype (16/6 Id). In addition, Ig deposits were detected in renal glomeruli of TGF- beta 1 knockout mice. Transplantation of TGF-beta 1 knockout hematopoietic cells into normal irradiated recipients resulted in a similar profile of autoantibody production as well as in the induction of inflammatory lesions. Our results describe autoimmune activity that ensues when the TGF-beta 1 cytokine is absent.
Neospora caninum is a cyst-forming coccidian parasite which is now recognised as a major cause of abortion and neonatal mortality in cattle and other livestock. This study describes the primary DNA structure of the transcribed spacer region of the rDNA of N. caninum. Of importance is that the sequence data generated have been used to develop a species-specific PCR test for N. caninum DNA, which will prove valuable in epidemiology studies on neosporosis.
In the three decades since the concept of "awareness" was introduced to describe the nature of communication between dying people and their carers, there has been a radical change in hospital policies and medical practice. It is now common for the majority of cancer patients to be given full information about their disease and prognosis. Hospices provide a model of care in which death and dying are dealt with in an open manner. While this approach has been welcomed by the majority of people, a minority might still prefer a more limited awareness. An inevitable part of hospice care is the exposure to, and awareness of, people who are dying. There is little empirical data that considers the impact of death on fellow patients. This pilot investigation compared psychological morbidity, perceptions of comfort and/or distress, and descriptions of a "good death" in hospice cancer patients who reported witnessing a fellow patient's death (n = 34) with patients who did not have this experience (n = 33). Patients were assessed using the Hospital Anxiety and Depression scale, an Events Checklist and a semi-structured interview. The results indicate that patients witnessing a death were significantly less depressed than those who did not. Awareness of dying was found to be both comforting and distressing, although overall patients reported more comforting than distressing events. A "good death" was defined by patients in terms of symptom control, including dying in their sleep, being pain free, quietness and dignity. Narratives were used to describe the meaning of a "good death". Quantitative and qualitative analyses have been undertaken to provide a complex interpretation of these issues.
A series of 30 cases of male breast cancer in the North-East of Scotland is reviewed. The aims of the study were to document clinico-pathological and immunocytochemical features (available for 25) of these patients and to establish which factors could predict prognosis. Tumours were studied for the expression of oestrogen receptors (ERs), the oestrogen-dependent proteins pS2 and cathepsin D, the oncoprotein products of c-erb-B2 and the p53 tumour-suppressor-gene derived protein. Clinico-pathological features documented were in agreement with those reported by other authors. The overall 5-year survival was 53%. Tumour grade and lymph-node status influenced prognosis. In this series, 64% of the tumours expressed ERs, 50% pS2, 46% cathepsin D, 42% the c-erb-B2 transmembrane oncoprotein and 54% p53. In contrast to female breast cancer, the presence of either substantial amounts of ERs or the oestrogen-dependent protein pS2 correlated with poorer prognosis in males. This correlation has not previously been documented.
The development of palliative care originated from shortcomings in mainstream health services. Palliative care aims to cater for both the psycho-social needs of dying patients and the allieviation of their physical symptoms. This is reflected by the good and bad death perceptions of palliative care workers, though increasing signs of institutionalization in palliative care have challenged the idealization of a good death. This study aimed to investigate the health professionals' perception of both a good and a bad death and their perception of patients' awareness context. Seventy questionnaires were distributed to nurses and social workers. The 50 returned questionnaires revealed that health professionals perceived a good death as controlling the patients' physical symptoms and psychologically preparing them, whilst a bad death was perceived as the inability to control pain and deal with any psychological distress. Factor analysis identified three main factors (lack of patient distress, patient control and staff's supporting role perceptions) in the perception of a good death whereas four main factors (the negative effect of death on the family, a patient's non-acceptance of death, not dealing with patients' fears and the age of a dying person) were identified with the perception of a bad death. Overall, health professionals perceived themselves to be open and sensitive in communicating with patients although over half felt poorly supported by other staff.
Recent changes to nurse education within the United Kingdom (UK) have proved to be a source of great confusion in many respects, much of which is based on a manifest lack of appreciation of the nature and basis of the changes which are in fact driven by the requirements of European integration. This paper argues that the lack of clarity and publicity, 'transparency', in the process of transposing the requirements of European policy relating to nurse education into UK domestic policy can be blamed for aspects of the lingering confusion within the profession.
AIMS: To characterise further the proliferative compartment of the normal cervix and to document its alteration, if any, in the various grades of cervical intraepithelial neoplasia (CIN), particularly changes to the basal epithelial layer; to hypothesise as to the diagnostic and biological significance of any observed differences. METHOD: Proliferative compartments from 86 cervical biopsy specimens (10 normal, 11 with koilocytic change only, 12 CIN I, nine CIN II, and 44 CIN III) were determined using microwave antigen retrieval and a standard three-step Streptavidin biotin peroxidase immunocytochemical technique incorporating the MIB-1 monoclonal antibody (directed against the Ki-67 antigen). Immunoreactivity was assessed as occupying either the lower one third, lower two thirds or all three thirds of the squamous epithelium. Basal cell positivity was also quantitated. RESULTS: Specimens without CIN showed a thin suprabasal proliferative compartment two to four cells thick. True basal positivity was infrequent. With increasing grade of CIN, the growth compartment stretched evermore superficially so that in lesions of CIN III almost the full thickness of epithelium was cycling. In all grades of CIN, basal cell proliferation was significantly increased. CONCLUSIONS: In normal cervix, the parabasal layers represent the main proliferative pool with the basal layer providing a reserve. When CIN supervenes, this proliferative compartment expands commensurate with the grade of dysplasia and as basal turnover is increased specifically the intimate relation between epithelium and basement membrane might be disturbed, facilitating invasion. The diagnostic utility of these changes in growth compartments is limited.
This study tests whether the rate of inappropriate hospital admissions is high in areas with high medical admission rates. Seventy small geographic areas were formed by grouping Massachusetts ZIP codes by similarity of hospital use. Appropriateness of hospital admission was measured both by applying the Appropriateness Evaluation Protocol and by applying physicians' judgment to the medical records of patients age sixty-five and older who were admitted for treatment of a medical condition in 1990-1992. No relationship between hospital admission rate and inappropriate admission rate was found, which calls into question the common assumption that areas with higher hospital use have more inappropriate use of hospital care.
To investigate whether Epstein-Barr virus (EBV) infection of the uterine cervix plays a significant role in cervical carcinogenesis, 30 preinvasive squamous lesions were subjected to in situ hybridization for (EBER-1,-2, and BHLF1) EBV transcripts which are expressed in latent and lytic infection, respectively. Twenty cases were known to contain EBV sequences by previous polymerase chain reaction (PCR) analysis. Irrespective of EBV PCR status or histological grade, none of the 30 cases demonstrated EBV transcripts in squamous epithelial cells. Two cases showed very occasional EBER-positive stromal cells, most probably representing resident cervical lymphocytes. These findings suggest that EBV plays no part in early cervical carcinogenesis.