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Biomedical subjects

V Sundaram

Publications and source records attributed to V Sundaram.

At least 19 recordsLinked to original sources

Variation in anaesthesia for the laser treatment of retinopathy of prematurity--a survey of ophthalmologists in the UK.

PURPOSE: Laser treatment for retinopathy of prematurity (ROP) may be associated with systemic stress for the infant. No national consensus on the optimum method of anaesthesia for the treatment of ROP currently exists. This study ascertains the anaesthetic practices employed for the treatment of ROP by ophthalmologists in the United Kingdom (UK), and also their attitudes towards these practices. MATERIALS AND METHODS: A postal questionnaire was sent to 46 consultant ophthalmologists identified as performing treatment for ROP in the UK. The consultants were asked to estimate the annual number of babies with ROP that they treated with laser, what methods of anaesthesia they employed, for comments regarding the arrangements for, and types of anaesthesia employed and whether they believed that the neonatal stress response to laser treatment was associated with a significant risk of systemic complications. RESULTS: In all, 35 (76%) questionnaires were returned. A total of 30 (86%) respondents reported performing laser treatment for ROP. Of these, 15 (50%) used general anaesthesia for all cases and 11 (37%) intravenous sedation combined with topical anaesthesia for all cases. Oral sedation combined with topical anaesthesia, rectal chloral hydrate and paracetamol combined with topical anaesthesia, intravenous ketamine combined with topical anaesthesia, and subtenon's local anesthesia were used by one (3%) respondent each. There were no ophthalmologists using subconjunctival or topical anaesthetic alone or treating without anaesthesia. CONCLUSION: This survey reveals considerable variation in practice among UK ophthalmologists regarding the anaesthetic methods employed in the treatment of ROP, and their beliefs regarding the systemic stress associated with treatment.

Anesthesia↗

Adjustable versus non-adjustable sutures for strabismus.

BACKGROUND: Strabismus, or squint, can be defined as a deviation from perfect ocular alignment and can be classified in many ways according to its aetiology and presentation. Treatment can be broadly divided into medical and surgical options, with a variety of surgical techniques being available, including the use of adjustable or non-adjustable sutures for the extra ocular muscles. There exists an uncertainty as to which of these techniques produces a better surgical outcome, and also an opinion that the adjustable suture technique may be of greater benefit in certain situations. OBJECTIVES: The objectives of this review were to examine whether adjustable or non-adjustable sutures are associated with a more accurate long-term ocular alignment following strabismus surgery and to identify any specific situations in which it would be of benefit to use a particular method. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL on The Cochrane Library (which includes the Cochrane Eyes and Vision Group Trials Register) (Issue 3 2004), MEDLINE (1966 to July 2004), EMBASE (1980 to August 2004), LILACS (Latin American and Caribbean Literature on Health Sciences) (July 2004). We contacted experts in the field for further information. There were no language restrictions in the electronic searches. SELECTION CRITERIA: We planned to include only randomised controlled trials comparing adjustable to non-adjustable sutures for strabismus surgery. DATA COLLECTION AND ANALYSIS: No studies were found that met the inclusion criteria for this review. MAIN RESULTS: No studies were found that met the inclusion criteria for this review, therefore none were included for analysis. Results of non-randomised studies that compared these techniques are reported. AUTHORS' CONCLUSIONS: No reliable conclusions could be reached regarding which technique (adjustable or non-adjustable sutures) produces a more accurate long-term ocular alignment following strabismus surgery or in which specific situations one technique is of greater benefit than the other. High quality randomised controlled trials are needed to obtain clinically valid results and to clarify these issues.

Humans↗

Identification and synthesis of potential impurities of rabeprazole sodium.

Rabeprazole sodium (1, Achiphex) is a gastric proton pump inhibitor. It causes dose-dependent inhibition of acid secretion and is useful as an anti-ulcer agent. In the process for the preparation of 1, two potential unknown impurities were identified in HPLC at levels ranging from 0.05-0.8%. Based on mass spectral data vide LC-MS, the two impurities were characterized as 2-{[(4-chloro-3-methyl-2-pyridinyl) methyl] sulfinyl}-1H-bezimidazole (2, chloro analogue of rabeprazole) and 2-[{(4-methoxy-3-methyl-2-pyridinyl)methyl}sulfinyl]-1H-benzimidazole (3, methoxy analogue of rabeprazole). The structures were unambiguously established by independently synthesizing them and co-injecting in HPLC. To our knowledge, the compounds 2 and 3 have not been reported as process impurities elsewhere.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Physical violence, self rated health, and morbidity: is gender significant for victimisation?

STUDY OBJECTIVE: To analyse gender differences in associations between physical violence and self rated health and self reported morbidity among a random sample of adults in Denmark. DESIGN AND SETTING: Two questions on self rated health and self reported morbidity respectively, were obtained from a cross sectional national health interview survey conducted among 12 028 adults (16 years +) in Denmark in 2000. A question on six different forms of physical violence was obtained from a supplementary self administered questionnaire given to the same sample. The reporting period for experienced physical violence was the past 12 months and for morbidity symptoms, the past 14 days. MAIN RESULTS: Men aged 16-24 years were significantly more likely to have experienced violence than women (OR = 3.2, 95% CI = 2.3 to 4.2). Female victims of physical violence were significantly more likely to rate their health as poor (OR = 2.02, 95% CI = 1.41 to 2.89) and to report anxiety (OR = 2.14, 95% CI = 1.35 to 3.37), depression (OR = 2.36, 95% CI = 1.55 to 3.60), and stomach ache (OR = 1.58, 95% CI = 1.01 to 2.47) than female non-victims. Male victims of physical violence were only significantly more likely to report stomach ache (OR = 1.73, 95% CI = 1.03 to 2.89) than male non-victims. CONCLUSIONS: Associations between physical violence and poor self rated health and self reported morbidity were found to be significant for women, but not for men. It is probable that gender differences in experiences of violence, as well as gender differences in health related self perception, contribute to a gender specific process of victimisation. Improved knowledge about the relation between gender specific violence and victimisation as a gender specific consequence is essential for targeting violence prevention.

Adolescent↗

Factors influencing the care-seeking behaviour of chest symptomatics: a community-based study involving rural and urban population in Tamil Nadu, South India.

Our aim was to identify the factors that influence the care-seeking behaviour of chest symptomatics in urban and rural areas in South India. We conducted in-depth interviews with 649 participants: 80% of 310 urban residents and 63% of 339 rural people had sought care (P < 0.01), 93% within 1 month of onset of symptoms. Private health care facilities were the first and preferred point of contact for 57% of urban and 48% of rural participants; the major reasons were proximity to residence and their perception that good-quality care would be available there. Symptomatics who did not seek care attributed their inaction to insufficient severity of symptoms (51%), unaffordability (46%) and lack of time due to work pressures (25%). Socio-economic factors such as literacy and family income significantly influenced care-seeking behaviour. Our results indicate that most chest symptomatics seek care promptly; their initial response is to go to the nearest private health care facility, shifting to another if they are dissatisfied. Fifty per cent of the participants who did not seek care felt that their symptoms were not severe.

Adolescent↗

Evaluation of the phenol ammonium sulfate sedimentation smear microscopy method for diagnosis of pulmonary tuberculosis.

We compared the sensitivity and specificity of the phenol ammonium sulfate (PhAS) sediment smear microscopy method for detection of acid-fast bacilli with those of direct smear microscopy, using culture results for Mycobacterium tuberculosis as the "gold standard." The sensitivities of the PhAS and direct smear methods were 85% (465 of 547) and 83% (454 of 547), respectively, and the specificity of each method was 97%. The PhAS method was better accepted by the laboratory technicians and safer but necessitates an overnight sedimentation, which delays reporting of results until 1 day after sputum collection.

Ammonium Sulfate↗

Yield of continued monthly sputum evaluation among tuberculosis patients after culture conversion.

SETTING: New York City. OBJECTIVE: To evaluate the yield of continued monthly sputum monitoring after culture conversion. DESIGN: A retrospective review of tuberculosis patients verified between 1 January 1995 and 31 December 1996 who had: 1) pulmonary tuberculosis with organisms susceptible to isoniazid and rifampin; 2) culture conversion; and 3) completed therapy. We assessed time to smear and culture conversion and number of persons who developed a positive culture after culture conversion (culture reversion). RESULTS: Of 1440 patients, 379 were cared for by tuberculosis control program providers and 1061 were cared for by other providers; 813 (56%) were initially smear-positive. After the fifth month, 44 (5.3%) were smear-positive; four of these were culture-positive. Eighteen (1.3%) had culture reversions; eight were smear-positive. Excluding one specimen per patient collected at treatment completion, 7967 sputum samples were collected after culture conversion. The minimum estimated cost per culture reversion detected was $26,557. CONCLUSION: Continued monthly monitoring of sputum after culture conversion identified a very small number of patients who had culture reversion. However, patients who cannot tolerate or adhere to a standard regimen may need continued monitoring to assess response to treatment. For all patients a specimen should be collected at the end of treatment to document cure.

Adolescent↗

Inhibition of neurofibromin and p120 GTPase activating protein (GAP) by dietary fatty acids.

Neurofibromin and p120 GTPase activating protein (p120 GAP) down-regulate the activity of cellular Ras proteins. How the activity of these two proteins is controlled is not yet clear. In this study, we analyzed the effects of eight nutritionally relevant fatty acids on GTPase stimulatory activity of full-length neurofibromin and p120 GAP. The fatty acids tested were: saturated stearic acid, monounsaturated oleic acid, three omega-6 and three omega-3 polyunsaturated fatty acids. The analysis was performed by Ras immunoprecipitation GTPase assay. The full-length p120 GAP expressed in insect Sf9 cells and the immunoaffinity purified full-length neurofibromin were used. Neurofibromin was readily inhibited by stearic and oleic acid, but p120 GAP was not inhibited even at high concentrations (> 80 microM). Neurofibromin was also inhibited by low concentrations of all the polyunsaturated fatty acids tested (IC50 of 6 to 16 microM). p120 GAP was 2-3 fold less sensitive to inhibition by these fatty acids. The GTPase stimulatory activity of neurofibromin was also inhibited by arachidonic and oleic acid in the presence of a lipid mixture representing the major lipid components of the cell membrane. Chimeric proteins of neurofibromin and p120 GAP were used to determine that differential sensitivity to fatty acid inhibition maps to the catalytic domain of the proteins. These results indicated that fatty acids can modulate the GTPase function of the c-Ha-Ras protein by inhibiting the GTPase stimulatory activity of two Ras regulators, full-length neurofibromin and p120 GAP, at physiologically relevant concentrations in vitro.

Animals↗

Differential regulation of neurofibromin and p120 GTPase-activating protein by nutritionally relevant fatty acids.

Arachidonic acid, phosphatidic acid, and other lipids inhibit the catalytic fragment of neurofibromin more potently than that of p120 guanosine triphosphatase-activating protein (GAP). The effects of fatty acids other than arachidonic acid on full-length neurofibromin and p120 GAP, to our knowledge, have not been studied. In this study, we analyzed the effects of eight nutritionally relevant fatty acids on guanosine triphosphatase (GTPase) stimulatory activity of full-length neurofibromin and p120 GAP. The fatty acids tested were saturated stearic acid, monounsaturated oleic acid, and three n-6 and three n-3 polyunsaturated fatty acids. Analysis was performed by Ras immunoprecipitation GTPase assay. The full-length p120 GAP expressed in insect Sf9 cells and immunoaffinity-purified full-length neurofibromin were used. In contrast to neurofibromin, which was readily inhibited by stearic and oleic acid, p120 GAP was only weakly inhibited even at high concentrations (> 80 microM). Neurofibromin was also two- to threefold more sensitive to inhibition by other fatty acids tested. A chimeric protein in which the neurofibromin catalytic domain was fused to the NH2-terminal sequences of p120 GAP was used to determine that differential sensitivity to fatty acid inhibition maps to the catalytic domain of the proteins. These results indicate that nutritionally relevant fatty acids can modulate the GTPase function of c-Ha-Ras protein by inhibiting GTPase stimulatory activity of two Ras regulators, full-length neurofibromin and p120 GAP, at physiologically relevant concentrations in vitro.

Animals↗

Neurofibromin colocalizes with mitochondria in cultured cells.

Mutations in neurofibromatosis type 1 target the gene coding for neurofibromin. While neurofibromin is able to accelerate the rate of GTP hydrolysis by cellular Ras proteins, its biological function is not well understood. To gain information regarding its function, the intracellular localization of neurofibromin was analyzed in cultured cell lines using polyclonal antisera raised against four neurofibromin-specific peptides, three from the carboxyl terminus and one from the amino terminus. In methanol-fixed cells distinct rod-like structures distributed throughout the cytoplasm were recognized by the antisera. Similar structures were seen with each antiserum, including affinity-purified antibodies, and in each of the cultured cell lines tested. Similar structures were seen in paraformaldehyde-fixed cells. Double staining experiments showed that these structures colocalize with mitochondria, but not with actin, beta-tubulin, or endoplasmic reticulum. When actin or tubulin structures within the cell were disrupted by separate antimitotic drugs, these stained structures retained their shape. Neurofibromin association with mitochondria was confirmed biochemically when highly purified mitochondrial fractions from bovine heart tissue were shown in Western analysis to contain neurofibromin. This association might be helpful in predicting identification of some of the cellular proteins with which neurofibromin interacts.

3T3 Cells↗

Reduced expression of neurofibromin in human meningiomas.

Meningiomas are common, mostly benign, tumours arising from leptomeningeal cells of the meninges, which frequently contain mutations in the neurofibromatosis type 2 (NF2) gene. In this study, we analysed a protein product of the neurofibromatosis type 1 (NF1) gene, neurofibromin, in human established leptomeningeal cells LTAg2B, in 17 sporadic meningiomas and in a meningioma from a patient affected by NF2. The expression level of neurofibromin was determined by immunoblotting and immunoprecipitation with anti-neurofibromin antibodies. The functional status of neurofibromin was analysed through its ability to stimulate the intrinsic GTPase activity of p21 ras. In the cytosolic extracts of four sporadic meningiomas and in the NF2-related meningioma, the expression level and the GTPase stimulatory activity of neurofibromin were drastically reduced compared with the level present in the human brain, human established leptomeningeal cells LTAg2B and the remaining 13 meningiomas. Our results suggest that neurofibromin is expressed in leptomeningeal cells LTAg2B and in most meningiomas, i.e. tumours derived from these cells. The reduced expression and GTPase stimulatory activity of neurofibromin was found in about 23% of meningiomas and in the single NF2-related meningioma analysed. These results suggest that decreased levels of neurofibromin in these tumours may contribute to their tumorigenesis.

Adult↗

Inhibition of low-density lipoprotein oxidation by oral herbal mixtures Maharishi Amrit Kalash-4 and Maharishi Amrit Kalash-5 in hyperlipidemic patients.

Low-density lipoprotein (LDL) oxidation is central to the pathogenesis of atherosclerosis. We have shown previously that the herbal mixtures Maharishi Amrit Kalash-4 (MAK-4) and Maharishi Amrit Kalash-5 (MAK-5) inhibit LDL oxidation induced by cupric ions (Cu+2) and endothelial cells in vitro and that MAK-4 reduces atherosclerosis in Watanabe heritable hyperlipidemic rabbits that were fed this herbal mixture. This study evaluates the antioxidant activity of MAK-4 and MAK-5 in vivo. Ten hyperlipidemic patients prescribed stable hypolipidemic therapy were treated with MAK-4 and MAK-5 for 18 weeks. Plasma lipoprotein, plasma lipid peroxide, and LDL oxidation studies were performed every 6 weeks. Apolipoprotein A, apolipoprotein B, and lipoprotein (a) levels were measured at baseline and 18 weeks. After 12 weeks of treatment with MAK-4 and MAK-5, a time-dependent increase in the lag phase and delay in the propagation phase of oxidation of LDL by Cu+2 and endothelial cells was seen. Lag phases at baseline and after 6, 12, and 18 weeks of MAK-4 and MAK-5 ingestion were 6.66 hours +/- 0.19 (mean +/- standard error of mean), 6.77 hours +/- 0.31, 7.22 hours +/- 0.24, and 18.00 hours +/- 0.73, respectively, for Cu(+2)-catalyzed LDL oxidation. Lag phases were 14.89 hours +/- 0.77, 13.33 hours +/- 0.50, 20.22 hours +/- 0.76, and 20.00 hours +/- 0.79, respectively, for endothelial cell-induced LDL oxidation. The levels of plasma lipid peroxide did not change significantly. No significant changes were seen in the plasma lipoproteins and the levels of apolipoprotein A, apolipoprotein B, and lipoprotein (a). The results show that MAK-4 and MAK-5 inhibit LDL oxidation in patients with hyperlipidemia. Therefore, MAK-4 and MAK-5 may be useful in the prevention and treatment of atherosclerosis.

Adult↗

Reduced expression of schwannomin/merlin in human sporadic meningiomas.

OBJECTIVE: The neurofibromatosis type 2 gene is frequently mutated in sporadic meningiomas. The protein product of the neurofibromatosis type 2 gene is called schwannomin or merlin. Its expression in leptomeningeal cells from which meningiomas are derived and the characteristics of mutated forms in meningiomas, to our knowledge, have not been previously studied. METHODS: Immunoblotting and immunoprecipitation experiments with two specific antibodies were used to determine the size and subcellular distribution of schwannomin/merlin in rabbit and human brain tissue and established human leptomeningeal LTAg2B cells. Immunoblotting was used to determine the expression level of schwannomin/merlin in 14 human sporadic meningiomas. RESULTS: Both antibodies detect a protein of approximately 66 kDa, which is predominantly expressed in the Triton X-100-insoluble fraction of the brain and LTAg2B cells. The levels of schwannomin/merlin were severely reduced in eight tumors (57%) when compared with the expression levels in the human brain, LTAg2B cells, and the remaining six meningiomas. All six tumors with the normal schwannomin/merlin expression were of meningotheliomatous type. In contrast, all other histological types and one meningotheliomatous tumor with psammoma bodies were deficient in the 66-kDa schwannomin/merlin. Although nonsense mutations leading to premature stop codons are common in the neurofibromatosis type 2 gene in meningiomas, we found no evidence of truncated schwannomin/merlin forms in the tumors analyzed. CONCLUSION: The absence of complete schwannomin/merlin in almost 60% of primary sporadic meningiomas seems to be an important factor in meningioma tumorigenesis. The development of meningotheliomatous meningiomas is probably linked to alterations in other oncogenes or tumor suppressor genes.

Adult↗

Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation.

Hypothyroidism is frequently associated with hypercholesterolemia and an increased risk for atherosclerosis, whereas hyperthyroidism is known to precipitate angina or myocardial infarction in patients with underlying coronary heart disease. We have shown previously that L-T4 functions as an antioxidant in vitro and inhibits low density lipoprotein (LDL) oxidation in a dose-dependent fashion. The present study was designed to evaluate the changes in LDL oxidation in subjects with hypothyroidism and hyperthyroidism. Fasting blood samples for LDL oxidation analyses, lipoprotein determinations, and thyroid function tests were collected at baseline and after the patients were rendered euthyroid. The lag phase (mean +/- SEM hours) of the Cu+2-catalyzed LDL oxidation in the hypothyroid state and the subsequent euthyroid states were 4 +/- 0.0.65 and 14 +/- 0.68 h, respectively (P < 0.05). The lag phase during the hyperthyroid phase was 6 +/- 0.55 h, and that during the euthyroid phase was 12 +/- 0.66 h (P < 0.05). The total and LDL cholesterol levels were higher in hypothyroidism than in euthyroidism and were lower in hyperthyroidism than in the euthyroid state. We conclude that LDL has more susceptibility to oxidation in both the hypothyroid and hyperthyroid states. Thus, the enhanced LDL oxidation may play a role in the cardiac disease process in both hypothyroidism and hyperthyroidism.

Adult↗

Neopterin as a marker for cell-mediated immunity in patients with pulmonary tuberculosis.

SETTING: Cell-mediated immunity (CMI) involves macrophage activation and T cell proliferation. These two parameters are compared in this study. OBJECTIVE: To ascertain the role of neopterin as a biochemical marker for CMI in patients with pulmonary tuberculosis. DESIGN: We measured neopterin levels in serum and the culture supernatants of peripheral blood mononuclear cells (MNC) after stimulation with purified protein derivative (PPD) in 11 patients with pulmonary tuberculosis and 10 healthy individuals. Lymphocyte proliferative response to PPD was carried out in these two groups. RESULTS: The mean concentration of serum neopterin was significantly higher in patients than in controls (P < 0.01). The spontaneous release of neopterin was significantly higher in culture supernatants of MNC from patients when compared with those of healthy controls (P < 0.05). Release of neopterin from MNC stimulated with PPD, however, was similar in both groups. The neopterin release and the stimulation index (SI) in lymphocyte proliferation assay were not comparable, suggesting that these two parameters do not run in parallel for measuring the status of CMI. However, serum concentration of neopterin was inversely related to the SI in a large proportion of subjects (66%). CONCLUSION: Measurement of neopterin, a soluble product of immune cells (macrophage), may provide information on the state of CMI.

Adult↗

Activated neutrophils inhibit Na(+)-K(+)-ATPase in canine renal basolateral membrane.

To examine the effects of activated neutrophils (PMNs) on Na(+)-K(+)-ATPase, phorbol 12-myristate 13-acetate (PMA)-stimulated PMNs were incubated with canine renal cortical basolateral membrane (BLM), and BLM ouabain-sensitive Na(+)-K(+)-ATPase activity was subsequently quantified. Na(+)-K(+)-ATPase activity decreased to 40.0 +/- 8.7% (SE) of control in the presence of activated PMNs, from 0.89 +/- 0.12 to 0.34 +/- 0.05 mumol Pi.mg protein-1.min-1. This inhibition coincided with a decrease in the apparent Michaelis constant (Km) for ATP from 0.18 +/- 0.02 to 0.05 +/- 0.01 mM. Inclusion of catalase (CAT) and superoxide dismutase (SOD) in the BLM/PMN/PMA incubation mixture resulted in partial preservation of enzyme activity, with an increase to 57.0 +/- 4.6% of control with CAT alone and to 70.0 +/- 5.3% with both CAT and SOD. SOD alone had no protective effect. Neither the myeloperoxidase inhibitor azide nor the hypochlorous acid scavenger L-methionine preserved enzyme activity. Hydroxyl radical scavengers and iron chelators were also ineffective in attenuating Na(+)-K(+)-ATPase inhibition by activated PMNs. These results indicate that activated PMNs mediate a decrease in BLM Na(+)-K(+)-ATPase activity characterized by a reduction in maximum velocity and Km for ATP that appears to be mediated in part by reactive oxygen metabolites.

Animals↗