Vascular access for hemodialysis.
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Biomedical subjects
Publications and source records attributed to A Singh.
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The standard local management for Paget's disease of the nipple is currently mastectomy although this may well represent overtreatment. The place of breast conserving surgery is somewhat uncertain. We have reviewed the casenotes of 146 patients with Paget's disease of the nipple, and compared the mortality and recurrence rates between 74 women who had undergone mastectomy and 31 women who had breast conserving surgery. There was no significant difference in either local or overall treatment failure rates between these two treatment groups. We conclude that breast conserving treatment maybe an appropriate alternative to mastectomy for the management of Paget's disease, where clear margins of excision can be achieved. However, a randomized prospective study is needed to confirm this.
The results of surgical management in 54 patients with intramedullary spinal cord tumours are presented. Cervical tumours were most frequent (25/54) followed by thoracic (16/54) and then lumbar (14/54). Ependymomas and astrocytomas were the most common tumour types. Total tumour removal was possible in just over half of the cases. Surgical complications included: two deaths, six patients with CSF leaks and one with wound infection. Postoperatively three patients had worsening of their motor deficit (unable to walk) and three patients had worsening of urinary sphincter function. Conversely, three patients who were unable to walk preoperatively were able to walk postoperatively, whilst four patients with sphincter disturbance showed improvement. Total tumour removal was not associated with increased risk of postoperative neurological deficit. Long-term follow up (2-18 years) was possible in 40 patients; 90% were still independently mobile. Our results compare favourably with other European studies and data from the North American units which have pioneered this surgery.
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Although a wide range of microorganisms have been discovered that are able to degrade highly stable, toxic xenobiotics, still many pollutants persist in the environment. Recent advances in the field of r-DNA technology has provided solutions to these problems. One important factor limiting the bioremediation of sites contaminated with certain hazardous wastes is the slow rate of degradation. This slow rate limits the practicality of using bacteria in remediating contaminated sites. It is possible to extend the range of substrates that an organism can utilize. It is even possible to endow an organism with the ability to degrade a predetermined range of xenobiotics. Because biotechnological processes are based on natural activities of microorganisms and constitute variations in classic domestic waste treatment processes, they are publicly more accepted. This is an area where genetic engineering can make a marked improvement by manipulating catabolic genes of microorganisms. Advances in r-DNA technology have opened up new avenues to move toward the goal of genetically engineered microorganisms to function as "designer biocatalysts" in which certain desirable biodegradation pathways or enzymes from different organisms are brought together in a single host with the aim of performing specific detoxification. In the last 2 decades much progress has been made in this direction, and as a result catabolic genes have been cloned and characterized for organochlorines, polychlorinated biphenyls, chlorobenzoates, naphthalene etc. The aim of this review is to provide an insight in the recent advances made on characterization and expression of catabolic genes that encode the degradation/detoxification of these persistent and toxic xenobiotic compounds.
PURPOSE: The study was undertaken to determine whether acute supplementation with zinc or vitamin E would modify neuroendocrine responses to physiologic stress. METHODS: Specifically, the effects of exhaustive running on blood glucose, lactate, ACTH, cortisol, growth hormone, prolactin, catecholamine, and interleukin 6 (IL-6) concentrations were determined in 10 eumenorrheic runners after supplementation with zinc (25 mg), vitamin E (400 IU), or placebo. Subjects ran at 65-70% of their VO2max, to exhaustion, on a treadmill during the follicular phase of their menstrual cycles over three cycles. RESULTS: There were no significant differences associated with supplementation for any of the hormonal and metabolic measures. Exercise, however, significantly (P<0.05) increased plasma lactate, ACTH, prolactin, and catecholamine concentrations, all of which peaked immediately after exercise (POST). Plasma cortisol concentrations were significantly (P<0.05) elevated at POST, and a further increase was noted 1 h after exercise. IL-6 concentrations rose linearly throughout exercise and reached peak values at POST. Exercise-induced changes were transient in that all measures returned to baseline within 24 h. CONCLUSIONS: Acute supplementation with zinc or vitamin E did not influence the effects of exhaustive running on metabolic and endocrine responses in women. The effects of chronic supplementation on neuroendocrine responses to exercise remain to be determined.
PURPOSE: Recent work indicates that among the normal population, persons can be classified as low (LR) or high (HR) stress responders based on hypothalamic-pituitary-adrenal (HPA) axis responses to high-intensity exercise. We studied whether differential activation of the HPA axis affected cytokine production and expression of selected lymphocyte subsets in HR and LR in response to high-intensity exercise after placebo and dexamethasone (DEX; 4 mg). METHODS: Healthy HR (N = 12) and LR (N = 10) underwent two exercise tests at 90% of VO2max, 8 h after placebo or DEX. Expression of lymphocyte surface markers (CD3+, CD4+, CD8+, CD56+), adhesion molecule markers (intercellular adhesion molecule-1/ICAM-1: CD54+ and L-selectin: CD62L+), and concentrations of plasma interleukin 6 (IL-6) were examined before and after exercise. RESULTS: Baseline percentages of CD8+ and CD56+ cells were significantly higher, and concentrations of IL-6 and percentages of CD4+ cells were significantly lower in HR as compared with LR. The percentage of CD54+ and CD62L+ cells was not significantly different in HR and LR. DEX significantly reduced the percentage of CD3+ and CD4+ and increased the percentage of CD8+ and CD56+ subsets; the percent of cells expressing CD54+ increased, whereas CD62L+ decreased. Exercise-induced changes in the percentage of lymphocyte subsets were similar to those induced by DEX. CONCLUSION: In summary, HR and LR have different baseline patterns of IL-6 and lymphocyte subsets, which may reflect differential sensitivity to endogenous glucocorticoids. However, exogenous glucocorticoids induced similar patterns of lymphocyte expression in HR and LR.
Third world countries, including India, lack sophisticated investigations to assess the progression of HIV disease. Hence, this study was undertaken to determine the clinical mucocutaneous markers of HIV disease and to establish its relationship with the stage of the disease. This was an observational institutional study of 75 patients with mucocutaneous disorders and HIV infection recruited over a period extending from September of 1996 to June of 1998. The patients with mucocutaneous lesions were staged according to the Centers for Disease Control classification system for HIV infection (1986). The most frequent mode of acquisition of HIV infection was heterosexual contact (96%). The patients were broadly categorized into two groups. The AIDS group was comprised of patients who were in group IV and the early HIV infection group included patients in group II and III; none were detected in group I. Forty-eight cases belonged to the AIDS group, and 27 belonged to the early HIV infection group. A total of 207 dermatoses were diagnosed and grouped as fungal, viral, bacterial, or miscellaneous. The common mucocutaneous disorders in order of frequency observed in this study were: candidiasis, dermatophytosis, herpes simplex, oral aphthae, xerosis/ichthyosis, scabies, HPV infection, molluscum contagiosum, and psoriasis. Xerosis/acquired ichthyosis and giant molluscum contagiosum were characteristically seen in group IV of HIV disease, whereas oral candidiasis, oral aphthae, papular dermatitis of HIV, and psoriasis were early warning signs. The mean number of dermatoses per patient in group IV was 3.15; in group III, it was 2.41; and in group II, it was 1.5. There was a statistically significant difference between the early HIV infection group and AIDS group with regard to number of dermatoses. Apart from syphilis and human papilloma virus infection, the treatment outcomes were satisfactory.
Human immunodeficiency virus type 1 (HIV-1) infection is highly compartmentalized, with distinct viral genotypes being found in the lungs, brain, and other organs compared with blood. CCR5 and CXCR4 are the principal HIV-1 coreceptors, and a number of other molecules support entry in vitro but their roles in vivo are uncertain. To address the relationship between tissue compartmentalization and the selective use of entry coreceptors, we generated functional env clones from primary isolates derived from the lungs and blood of three infected individuals and analyzed their use of the principal, secondary, orphan, and virus-encoded coreceptors for fusion. All Env proteins from lung viruses used CCR5 but not CXCR4, while those from blood viruses used CCR5 or CXCR4 or both. The orphan receptor APJ was widely used for fusion by Env proteins from both blood and lung viruses, but none used the cytomegalovirus-encoded receptor US28. Fusion mediated by the secondary coreceptors CCR2b, CCR3, CCR8, and CX3CR1 and orphan receptors GPR1, GPR15, and STRL33 was variable and heterogeneous, with relatively broad utilization by env clones from isolates of one subject but limited use by env clones from the other two subjects. However, there was no clear distinction between blood and lung viruses in secondary or orphan coreceptor fusion patterns. In contrast to fusion, none of the secondary or orphan receptors enabled efficient productive infection. These results confirm, at the level of cofactor utilization, previous observations that HIV-1 populations in the lungs and blood are biologically distinct and demonstrate diversity within lung-derived as well as blood-derived quasispecies. However, the heterogeneity in coreceptor utilization among clones from each isolate and the lack of clear distinction between lung- and blood-derived Env proteins argue against selective coreceptor utilization as a major determinant of compartmentalization.
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Many HIV-1 isolates at the late stage of disease are capable of using both CXCR4 and CCR5 in transfected cell lines, and are thus termed dual-tropic. Here we asked whether these dual-tropic variants also use both coreceptors for productive infection in a natural human lymphoid tissue microenvironment, and whether use of a particular coreceptor is associated with viral cytopathicity. We used 3 cloned dual-tropic HIV-1 variants, 89.6 and its chimeras 89-v345.SF and 89-v345.FL, which use both CCR5 and CXCR4 in transfected cell lines. In human lymphoid tissue ex vivo, one variant preferentially used CCR5, another preferentially used CXCR4, and a third appeared to be a true dual-tropic variant. The 2 latter variants severely depleted CD4(+) T cells, whereas cytopathicity of the virus that used CCR5 only in lymphoid tissue was mild and confined to CCR5(+)/CD4(+) T cells. Thus, (a) HIV-1 coreceptor usage in vitro cannot be unconditionally extrapolated to natural microenvironment of human lymphoid tissue; (b) dual-tropic viruses are not homogeneous in their coreceptor usage in lymphoid tissue, but probably comprise a continuum between the 2 polar variants that use CXCR4 or CCR5 exclusively; and (c) cytopathicity toward the general CD4(+) T cell population in lymphoid tissue is associated with the use of CXCR4.
Healthy men exhibit a differential hypothalamic-pituitary-adrenal axis (HPA) response to exercise stress and fall into two groups: high responders (HR) and low responders (LR). The present study examined whether HR to physical stress also exhibit higher HPA reactivity to psychological stress than LR. We examined 14 HR and 13 LR classified based on their ACTH responses to high intensity exercise after pretreatment with dexamethasone. Both groups were of similar age, height, weight, and fitness level. Trait anxiety scores on the Spielberger Trait Anxiety Scale were not different. Subjects underwent a psychological stress test consisting of an interview and mental arithmetic. This test raised heart rate, blood pressure, and plasma ACTH and cortisol levels in both HR and LR. HR tended to have higher heart rates and blood pressures in anticipation of the psychological stress test than LR. ACTH responses of HR were higher, although not significantly, throughout the psychological stress test than LR. HR had a significantly (P < 0.05) greater net integrated cortisol response to the psychological stress than LR. This suggests that the adrenal cortexes of the HR are hypertropic and/or hypersensitive to ACTH. We conclude that men who are highly responsive to exercise stress are also highly responsive to psychological stress.
Prostaglandin E2 (PGE2) and cytokines, such as interleukin-6 (IL-6) or tumour necrosis factor a (TNFalpha) can regulate aromatase activity. In the present study we have compared their abilities to stimulate aromatase activity in fibroblasts derived from 'normal' breast adipose tissue proximal to a tumour or breast tumours. PGE2, TNFalpha and IL-6 plus its soluble receptor (IL-6sR) all increased aromatase activity in these cells. Basal aromatase activity and the degree of aromatase stimulation by these factors were greater in fibroblasts derived from 'normal' breast tissue than from breast tumours. The ability of IL-6+IL-6sR to increase aromatase activity was only marginally reduced by the PG synthesis inhibitor, indomethacin, indicating that IL-6+IL-6sR does not appear to act via induction of PG synthesis. The ability of PGE2 to stimulate aromatase activity in fibroblasts derived from 'normal' breast tissue was potentiated by IL-6sR suggesting that PGE2 may act via induction of IL-6. This was confirmed by measurement of IL-6 in conditioned medium collected from these cells. A significant increase in IL-6 concentrations was detected in conditioned medium collected from cells treated with PGE2. It is concluded that in some fibroblasts PGE2 may exert part of its regulatory effect on breast tissue aromatase activity via induction of IL-6.
Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opportunity to study the mechanism of carcinogenesis. During the recent past a number of compounds have been tested for their anticarcinogenic potential specially constituents of our diet. The enzyme gamma-glutamyl transpeptidase (GGT) which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acid and has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, GGT activity induced by carcinogenic polycyclic aromatic hydrocarbons, viz. 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a) pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbinol (I3C) in mouse skin. DAS and I3C are constituents of garlic and cruciferous vegetables respectively. A significant inhibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity in mouse skin by pretreatment with DAS/I3C. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis.
Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opportunity to study the mechanism of carcinogenesis. During the recent past a number of compounds have been tested for their anticarcinogenic potential specially constituents of human diet. The enzyme gamma-glutamyl transpeptidase (GGT), which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acids, has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, GGT activity induced by carcinogenic polycyclic aromatic hydrocarbons, viz. 7,12-dimethyl-benz(a)anthracene (DMBA) and benzo(a)pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbinol (I3C) in mouse skin. DAS and I3C are constituents of garlic. A significant inhibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity by pretreatment of DAS/I3C in mouse skin. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis.
Epidemiological survey for respiratory diseases among agricultural industry workers, such as bakeries, poultry farms, granaries and a sugar refinery was carried out using a medical questionnaire on various respiratory symptoms such as cough, breathlessness, rhinitis. The questionnaire was filled up by two doctoral students during personal visits to these work environments. The survey revealed that 40-59% of workers in different occupational work environments suffered from one or more respiratory ailments. As much as 36-40% of the workers reported work-related symptoms which is close to similar data from Western countries. A higher incidence of respiratory disorders was recorded in workers with longer duration of employment. Older workers suffered more than the young ones. Family history of atopy was found to have least effect on the incidence of cough, breathlessness and rhinitis in the workers. Smoking was found to have definite impact on the incidence of cough and breathlessness
Five cases of hydatid disease of abdomen and thorax were diagnosed by fine needle aspiration cytology (FNAC) under ultrasound guidance. The age of patients ranged from 25-50 years, with a median age of 37 years. Male to female ratio was 2:3. None of the cases were clinically diagnosed as hydatid disease, but ultrasonography raised suspicion in two cases. The location of cyst in four cases was liver and one aspiration was done from lung. Smears from all cases showed features consistent with hydatid disease. None of the patients showed any untoward allergic reaction following FNAC.