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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 37 records · Page 2Linked to original sources
PubMed2005

Osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disorder of multifactorial etiology characterized by loss of articular cartilage and periarticular bone remodelling. OA causes joint pain, typically worse with weight-bearing and activity as well as can manifest with stiffness after inactivity. It can present as localized, generalized or as erosive osteoarthritis. Primary osteoarthritis is mostly related to aging, whereas, secondary osteoarthritis is caused by another disease or condition. X-rays, arthrocentesis and arthroscopy remain the main diagnostic tools. Blood tests are performed to exclude diseases that can cause secondary osteoarthritis. The treatment of osteoarthritis includes non-pharmacological management, pharmacological treatment in the form of drugs which can modify symptoms, symptomatic slow acting drugs for OA or structure modifying OA drugs depending upon the clinical requirement of the patient. Patients with persistent pain and progressive limitation of daily activities despite medical management may be the candidates for surgery.

Acetaminophen↗
PubMed2004

Using aromatase inhibitors in the neoadjuvant setting: evolution or revolution?

Despite improvements in the management of patients with early breast cancer, the prognosis for women with locally advanced breast cancer (LABC) remains poor. The potential goals of neoadjuvant treatment for this disease include down-sizing tumours to allow breast conservation as well as the possibility of improving survival rates. Neoadjuvant treatment was initially dominated by chemotherapy, which increased rates of breast conserving surgery, but to date has demonstrated no survival benefit over standard adjuvant chemotherapy. With recent advances in endocrine therapy, and rapid and routine assessment of predictive factors of response such as estrogen (ER), progesterone (PR) and Her2 nu receptor status, endocrine therapy has come to the forefront of research investigating a neoadjuvant alternative to chemotherapy. Early studies of neoadjuvant endocrine therapy mainly evaluated the role of tamoxifen in the treatment of elderly postmenopausal women with LABC who were unselected for ER/PR status and were unsuitable for either surgery or chemotherapy. Response rates in these patients were found to be inferior to those traditionally obtained from trials with neoadjuvant chemotherapy. Paralleling the superiority that third-generation aromatase inhibitors have shown over tamoxifen in the metastatic and adjuvant settings however, AIs have also demonstrated superiority in the neoadjuvant setting. Recent studies have shown response rates for neoadjuvant treatment with aromatase inhibitors in carefully selected hormone receptor positive patients to be comparable to those seen with neoadjuvant chemotherapy. This is particularly important as hormone receptor positive tumours have repeatedly been shown to have lower response rates to neoadjuvant chemotherapy than hormone receptor negative tumours. Neoadjuvant endocrine treatment with aromatase inhibitors has therefore evolved from being an experimental effort to palliate women with LABC unsuitable for surgery or chemotherapy, to representing a viable and possibly preferred alternative for postmenopausal women with hormone receptor positive large tumours or LABC. Further benefits of neoadjuvant trials include allowing the study of predictive biomarkers of disease in order to provide insight into therapy resistance and sensitivity, and identifying promising systemic therapies for additional testing in larger adjuvant trials.

Anastrozole↗
PubMed2004

Isolation and characterization of a haploid germ cell specific sperm associated antigen 9 (SPAG9) from the baboon.

Previously, we cloned and sequenced a sperm specific antigen, designated as HSS (EMBL nomenclature human sperm associated antigen 9: hSPAG9) from human testis (Shankar et al.: Biochem Biophys Res Commun 243:561-565, 1998). The present study was conducted to isolate baboon proteomic homologue in order to find out whether the baboon can provide a suitable model for examining its immunocontraception effects. Baboon SPAG9 (bSPAG9) was cloned and sequenced from the baboon testis cDNA library. The baboon cDNA contained open reading frame encoding 760 amino acids. A 90.6 and 96.8% homology between baboon and human SPAG9 was found at protein and DNA levels. Analysis for tissue specificity by Northern blot procedure using various baboon tissues indicated that bSPAG9 was specifically expressed only in the baboon testis. Further, cell type expression analysis by in situ hybridization in baboon testis demonstrated the expression of bSPAG9 mRNA transcript only in the round spermatid suggesting haploid germ cell expression. Anti-human SPAG9 antibodies recognized the acrosomal compartment region of baboon sperm in indirect immunofluorescence (IIF). Flow cytometry analysis showed surface localization of bSPAG9 in live baboon sperm. The amino acid sequence data for nonhuman primate SPAG9 suggest that antibodies generated by vaccinating baboon with hSPAG9 will recognize nonhuman primate SPAG9, supporting the testing of SPAG9 contraceptive vaccine based on hSPAG9 in the nonhuman primate model.

Acrosome↗
PubMed2004

Aromatase inhibitors in the adjuvant setting: bringing the gold to a standard?

The death rate from breast cancer is falling rapidly in most developed countries due, at least in part, to the use of adjuvant endocrine therapy in women with endocrine responsive disease. In post-menopausal women tamoxifen has been the gold standard for nearly 20 years. More recently the aromatase inhibitors (AI) have become established in the management of advanced breast cancer and are being evaluated in the adjuvant setting in trials that include tens of thousands of women. Recently, data have emerged that provide increasingly strong evidence supporting the use of AI in the adjuvant setting. Anastrozole as initial adjuvant endocrine treatment has shown superiority over tamoxifen in terms of disease free survival, and impressive reductions in the risk of recurrence have been demonstrated in trials evaluating the switch from tamoxifen to an AI, either letrozole after 5 or exemestane after 2-3 years of tamoxifen respectively. The data from these recent publications, and the potential impact on routine care of women with post-menopausal breast cancer is discussed.

Aged↗
PubMed2004

Cytokine expression pattern in the genital tract of Chlamydia trachomatis positive infertile women - implication for T-cell responses.

Human genital infection caused by Chlamydia trachomatis is thought to be immunologically mediated, resulting in local recruitment of lymphocyte subsets and inducing the production of cytokines. Little information is available about the role of lymphocyte recruitment and the regulation of cytokine production in the genital tract of C. trachomatis positive infertile women. We have evaluated the recruitment of lymphocyte subsets in the genital tract and production of Th1/Th2 cytokines in cervical secretions and laparoscopic specimens from the fallopian tubes of C. trachomatis positive infertile women (n = 17) and compared them with controls, viz. C. trachomatis negative infertile women (n = 20) using ELISA and flow cytometry. None of these patients were found to be infected either with Candida sps., bacterial vaginosis, Trichomonas vaginalis, Neisseria gonorrhoeae, Mycoplasma hominis or Ureaplasma urealyticum in the cervix. Flow cytometric analysis of cervical secretions in Chlamydia positive women revealed recruitment of both CD4 and CD8 lymphocytes to the genital tract was up-regulated and a variation in the production rates of different cytokines in cervical secretions and fallopian tube was observed. We found that the immune responses in cervical secretions were of Th0 type, since all the analysed cytokines, viz. IFN-gamma, TNF-alpha, IL-10 and IL-12 were up-regulated. As, both CD4 and CD8 cells contribute to the production of IFN-gamma and IL-10, these results suggest that along with CD4 cells, CD8 lymphocytes also may be important for local regulation of Th1/Th2 responses in the genital tract during C. trachomatis infection.

Adult↗
PubMed2004

Effect of insulin hypoglycemic stress on nociceptive responses to mu- and kappa-opioid receptor agonists at LH-surge in female rats.

In a randomized, prospective, controlled and crossover study, the effects of insulin hypoglycemic stress on nociceptive responses to mu- and kappa-opioid receptor directed drugs during steroid-induced preovulatory LH-surge were seen in ovariectomized female rats. Ovariectomized rats were equally distributed in two groups of 10. In group 1 rats, LH-surge was induced by sequential treatment with estradiol benzoate 7.5 micro g/rat s.c. and progesterone 5 mg/rat s.c., whereas in group 2 rats, vehicles of estradiol benzoate and progesterone were given in a sequential manner. A third group consisted of sham-operated rats, which received no treatment. Rats were exposed to insulin-induced hypoglycemic stress 1 h before the peak of LH-surge. Antinociceptive responses of morphine, buprenorphine and pentazocine were observed at peak LH-surge during hypoglycemic stress. Increased nociceptive responses to noxious stimulus and decreased percent maximal possible effect for morphine, buprenorphine and pentazocine at LH-surge were significantly (p < 0.01) reversed during insulin hypoglycemic stress. There was a significant (p < 0.01) decrease in the ED(50) values of morphine, buprenorphine and pentazocine during hypoglycemic stress. The present study indicates that insulin hypoglycemic stress is responsible for increased antinociceptive activities of morphine, buprenorphine and pentazocine and decreased sensitivity to noxious stimulus in ovariectomized rats with or without steroid-induced LH-surge.

Analgesics, Opioid↗
PubMed2004

A risk reduction approach for schizophrenia: the Early Psychosis Intervention Programme.

Schizophrenia is a serious mental disorder with a profound impact on patients, their caregivers and society. Most patients who develop schizophrenia experience a prodromal phase where there is a change in premorbid functioning prior to the onset of frank psychotic symptoms. Once psychosis sets in, the subsequent course can be variable but schizophrenia tends to run a chronic course, resulting in considerable disabilities. The prognosis of schizophrenia could potentially be improved by reducing the duration of untreated psychosis (DUP). The Early Psychosis Intervention Programme (EPIP) in Singapore adopts a risk-reduction approach. It seeks to reduce the DUP through public education, networking with the primary healthcare providers (general practitioners, counsellors, traditional healers), and the screening of conscripts into the Singapore Armed Forces. Integral to this programme is a service for those in the prodromal phase of psychosis, that addresses the concerns of stigmatisation and pharmacotherapeutic interventions. Our tertiary prevention strategies aim to reduce mortality and morbidity, and to improve the quality of the lives of the individuals diagnosed with this disorder through a comprehensive and holistic management programme that comprises case-management, the judicious use of antipsychotics, and various psychosocial interventions. Since EPIP's initiation in April 2001, there has been a steady increase in the number of individuals screened and accepted into the programme. Our networking strategy is gaining momentum and there has been a significant increase in the number of primary healthcare providers whom we have trained to identify early signs of psychosis. However, there remain various challenges which we are yet to overcome.

Combined Modality Therapy↗
PubMed2004

Post-SARS psychological morbidity and stigma among general practitioners and traditional Chinese medicine practitioners in Singapore.

INTRODUCTION: The severe acute respiratory syndrome (SARS) outbreak has been unique in recent history in its rapidity of transmission, its concentration in healthcare settings, and the large number of healthcare workers who have been infected. This study aims to examine the psychological impact of SARS on general practitioners (GPs) and traditional Chinese medicine (TCM) practitioners in Singapore. MATERIALS AND METHODS: Two months after the SARS outbreak, all the GPs and TCM practitioners in Singapore were mailed a set of self-reported questionnaires, which included the General Health Questionnaire (GHQ), the Impact of Event Scale-R (IES-R), and a questionnaire to measure the perception of stigma. RESULTS: A total of 721 (29%) GPs and 329 (22%) TCM practitioners responded to the survey. Significantly more GPs had worked in SARS affected facilities and had been directly involved in the care of patients with SARS than the TCM practitioners (P <0.001). Those GPs who were directly involved in the care of patients with SARS were significantly more likely to be GHQ case as compared to those not involved in the care of patients with SARS (P = 0.02; OR = 2.9; 95% CI, 1.3-6.3). The mean score of the GHQ somatic, anxiety and social dysfunction subscales were significantly higher in GPs as compared to TCM Practitioners (P <0.001). The GHQ total score as well as the subscales was significantly correlated with the IES-R and stigma subscales (P <0.05). CONCLUSION: The fear, uncertainty and stigma caused by SARS are associated with psychological distress among some of the primary healthcare providers in Singapore.

Adult↗
PubMed2003

Surface trapping and AFM detection of DNA topological intermediates generated from an oxidative chemical nuclease.

Direct observation of DNA topological intermediates generated from a 'chemical nuclease' treatment has been made by atomic force microscopy (AFM). The intermediates were trapped at the mica-water interface and imaging was carried out in the dynamic force mode. Complete conversion from supercoiled circular state to relaxed circular/linear state has been observed over a time scale of 8 min. Implication of such studies in complementing gel electrophoresis data has been predicted.

Aluminum Silicates↗
PubMed2003

Particle size of liposomes influences dermal delivery of substances into skin.

In the present study, the influence of vesicle size on the penetration of two fluorescently labeled substances into the human skin was investigated. For the measurements either a hydrophilic fluorescent compound [carboxyfluorescein (CF)] or a lipophilic one [1,1'-dioctadecyl-3,3,3',3'-tertramethylindocarbo-cyanine perchlorate (DiI)] were encapsulated into vesicles. Liposomal formulations were prepared by extruding the vesicles through polycarbonate membrane filters with pores of different sizes. In vitro penetration studies into human abdominal skin were performed by using the Franz diffusion cell and a standardized skin stripping technique in attempt to find an optimum size for topical drug delivery by liposomes. Confocal laser scanning microscopy (CLSM) was used to visualize the effect of penetration ability of liposomal DiI. The maximum DiI fluorescence in the skin was observed with smaller liposomes of 71 nm diameter. The liposomes with a size of 120 nm diameter showed statistically enhanced penetration of CF into the skin as compared to larger ones. The results indicated that the CF penetration was inversely related to the size of the liposomes, which was confirmed by the data of the confocal laser scanning microscopy studies.

Administration, Topical↗
PubMed2003

Efflux of human and mouse amyloid beta proteins 1-40 and 1-42 from brain: impairment in a mouse model of Alzheimer's disease.

Brain to blood transport is believed to be a major determinant of the amount of amyloid beta protein (AbetaP) found in brain. Impaired efflux has been suggested as a mechanism by which AbetaP can accumulate in the CNS and so lead to Alzheimer's disease (AD). To date, however, no study of the efflux of the form of AbetaP most relevant to AD, AbetaP1-42, has been conducted, even though a single amino acid substitution in AbetaP can greatly alter efflux. Here, we examined the efflux of AbetaP mouse1-42, mouse1-40, human1-42, and human1-40 in young CD-1, young senesence accelerated mouse (SAM) P8, and aged SAMP8 mice. The SAMP8 mouse with aging spontaneously overproduces AbetaP and develops cognitive impairments reversed by AbetaP-directed antibody or phosphorothioate antisense oligonucleotide. CD-1 mice transported all forms of AbetaP, although mouse1-42 and human1-40 were transported faster than the other forms. There was a decrease in the saturable transport of mouse1-42 in SAMP8 mice regardless of age. Efflux of mouse1-40 and human1-42 was only by a non-saturable mechanism in young SAMP8 mice and their efflux was totally absent in aged SAMP8 mice. These differences in the efflux of the various forms of AbetaP among the three groups of mice supports the hypothesis that impaired efflux is an important factor in the accumulation of AbetaP in the CNS.

Aging↗
PubMed2003

Liposomes increase skin penetration of entrapped and non-entrapped hydrophilic substances into human skin: a skin penetration and confocal laser scanning microscopy study.

Liposomes have been extensively studied and suggested as a vehicle for topical drug delivery systems. However, the mechanism by which liposomes deliver drugs into intact skin is not fully understood. In the present study, we have tried to understand the mechanism of transport of hydrophilic drugs into the skin using liposomes. The effect of separation of the non-entrapped, hydrophilic fluorescent compound, carboxyfluorescein (CF), from liposomally entrapped CF was investigated by measuring the penetration of CF across human skin under non-occlusive conditions in vitro using Franz diffusion cells. The fluorescent dye, CF, was incorporated into the liposomes and applied onto the skin. After a 6 and 12h incubation period, the amount of CF in the epidermal membrane and the full thickness skin was determined by fluorescence spectroscopy or by confocal laser scanning microscopy (CLSM). The liposomal formulation containing CF both inside and outside the vesicles showed statistically enhanced penetration of CF into the human stratum corneum (SC) as compared to the formulations containing CF only outside of the liposomes and CF in Tris buffer. The CLSM results revealed that the formulation in which CF was present outside the liposomes showed bright fluorescence intensity in the SC and very weak fluorescence in the viable epidermis. However, the CF in Tris buffer failed to show any fluorescence in the viable epidermis. The results indicated that phospholipid vesicles not only carry the entrapped hydrophilic substance, but also the non-entrapped hydrophilic substance into the SC and possibly into the deeper layers of the skin.

Diffusion Chambers, Culture↗