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Biomedical subjects

S Madhavan

Publications and source records attributed to S Madhavan.

At least 19 recordsLinked to original sources
PubMed2006

IL-6 protects enterocytes from hypoxia-induced apoptosis by induction of bcl-2 mRNA and reduction of fas mRNA.

Interleukin-6 (IL-6) has been shown to rescue enterocytes from hypoxia-induced apoptosis when given orally following hemorrhagic shock. In vitro models using an intestinal epithelial cell line (IEC-6) cultured with lipopolysaccharide (LPS) under low O2 conditions, to mimic intestinal conditions, show that these cells also undergo apoptosis, which can be reduced by subsequent culture with IL-6. To examine further the mechanisms of rescue, we cultured normal rat intestinal epithelial cells (IEC-6) under both normoxic and hypoxic conditions and analyzed their responses to LPS and IL-6. We showed that IEC-6 expressed IL-6 receptor on its surface. Further, IEC-6 cells could be rescued from hypoxia-induced apoptosis by co-culture with IL-6. RNase protection assay (RPA) examination revealed that under hypoxic conditions, IEC-6 cells that were resistant to apoptosis showed reduced fas expression and increased bcl-2 expression after co-culture with LPS+IL-6.

Animals↗
PubMed2006

Biomechanical signals exert sustained attenuation of proinflammatory gene induction in articular chondrocytes.

OBJECTIVES: Physical therapies are commonly used for limiting joint inflammation. To gain insight into their mechanisms of actions for optimal usage, we examined persistence of mechanical signals generated by cyclic tensile strain (CTS) in chondrocytes, in vitro. We hypothesized that mechanical signals induce anti-inflammatory and anabolic responses that are sustained over extended periods. METHODS: Articular chondrocytes obtained from rats were subjected to CTS for various time intervals followed by a period of rest, in the presence of interleukin-1beta (IL-1beta). The induction for cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP)-9, MMP-13 and aggrecan was analyzed by real-time polymerase chain reaction (PCR), Western blot analysis and immunofluorescence. RESULTS: Exposure of chondrocytes to constant CTS (3% CTS at 0.25 Hz) for 4-24 h blocked more than 90% (P<0.05) of the IL-1beta-induced transcriptional activation of proinflammatory genes, like iNOS, COX-2, MMP-9 and MMP-13, and abrogated inhibition of aggrecan synthesis. CTS exposure for 4, 8, 12, 16, or 20 h followed by a rest for 20, 16, 12, 8 or 4h, respectively, revealed that 8h of CTS optimally blocked (P<0.05) IL-1beta-induced proinflammatory gene induction for ensuing 16 h. However, CTS for 8h was not sufficient to inhibit iNOS expression for ensuing 28 or 40 h. CONCLUSIONS: Data suggest that constant application of CTS blocks IL-1beta-induced proinflammatory genes at transcriptional level. The signals generated by CTS are sustained after its removal, and their persistence depends upon the length of CTS exposure. Furthermore, the sustained effects of mechanical signals are also reflected in their ability to induce aggrecan synthesis. These findings, once extrapolated to human chondrocytes, may provide insight in obtaining optimal sustained effects of physical therapies in the management of arthritic joints.

Aggrecans↗
PubMed2004

Recurrent Miller Fisher syndrome.

Miller Fisher syndrome (MFS) is a variant of Guillan Barre syndrome characterized by the triad of ophthalmoplegia, ataxia and areflexia. Recurrences are exceptional with Miller Fisher syndrome. We are reporting a case with two episodes of MFS within two years. Initially he presented with partial ophthalmoplegia, ataxia. Second episode was characterized by full-blown presentation characterized by ataxia, areflexia and ophthalmoplegia. CSF analysis was typical during both episodes. Nerve conduction velocity study was fairly within normal limits. MRI of brain was within normal limits. He responded to symptomatic measures initially, then to steroids in the second episode. We are reporting the case due to its rarity.

Adult↗
PubMed2004

Restrictive cardiomyopathy due to primary plasma cell leukemia.

The causes of restrictive cardiomyopathy are numerous, of which neoplastic infiltration is also known. Plasma cell leukemia is considered as the, most severe form of multiple myeloma, is an extremely rare condition. Among them, primary plasma cell leukemia has got an incidence of one in one million only. We report a case summary of a patient who was admitted with clinical features suggestive of restrictive cardiomyopathy, the underlying disorder was primary plasma cell leukemia. With chemotherapy the restrictive physiology was relieved supporting the diagnosis of plasma cell infiltration in the myocardium. We report this case due to rarity of the disease itself and its rare presentation.

Cardiomyopathy, Restrictive↗
PubMed2003

Experimental and theoretical multiple kinetic isotope effects for an SN2 reaction. An attempt to determine transition-state structure and the ability of theoretical methods to predict experimental kinetic isotope effects.

The secondary alpha-deuterium, the secondary beta-deuterium, the chlorine leaving-group, the nucleophile secondary nitrogen, the nucleophile (12)C/(13)C carbon, and the (11)C/(14)C alpha-carbon kinetic isotope effects (KIEs) and activation parameters have been measured for the S(N)2 reaction between tetrabutylammonium cyanide and ethyl chloride in DMSO at 30 degrees C. Then, thirty-nine readily available different theoretical methods, both including and excluding solvent, were used to calculate the structure of the transition state, the activation energy, and the kinetic isotope effects for the reaction. A comparison of the experimental and theoretical results by using semiempirical, ab initio, and density functional theory methods has shown that the density functional methods are most successful in calculating the experimental isotope effects. With two exceptions, including solvent in the calculation does not improve the fit with the experimental KIEs. Finally, none of the transition states and force constants obtained from the theoretical methods was able to predict all six of the KIEs found by experiment. Moreover, none of the calculated transition structures, which are all early and loose, agree with the late (product-like) transition-state structure suggested by interpreting the experimental KIEs.

Journal Article↗
PubMed2003

The use of pharmacy immunization services in rural communities.

Pharmacies have been recommended as alternative sites for the delivery of immunization services, especially to medically underserved adults and children in inner cities and rural areas. Currently, 35 of 50 states in the USA have legalized the administration of vaccines by pharmacists on the basis of certain training requirements and specific protocols. Since the role of pharmacists is expected to expand, it is important to assess the factors that would enable them to improve the delivery of immunization services and the acceptance of these services by communities. It is particularly important for pharmacists to have knowledge of community circumstances and be able to respond to community needs. This case study of a pharmacy immunization programme (PIP) in rural West Virginia assessed how well pharmacists were aware of community circumstances and which community factors affected the utilization of pharmacy-delivered immunizations. Our findings suggest that although pharmacists played important roles as facilitators, hosts and motivators in PIP, they overestimated the trust placed in them by community members. The convenient locations of pharmacies and the convenient times when they offered immunization services were found to be the determining factors of mothers' decisions to take their children to these places for their vaccinations. The study concludes that as the use of pharmacies as sources of immunization is expected to continue to expand, pharmacists should take these factors into consideration when they decide to offer immunizations.

Chi-Square Distribution↗
PubMed2003

Photosynthetic responses of soybean to soybean aphid (Homoptera: Aphididae) injury.

The soybean aphid, Aphis glycines Matsumara, was discovered in the United States in the summer of 2000. Since that initial discovery, the aphid has spread across northern soybean production regions. In 2001, we examined the physiological responses of soybeans to low aphids densities (fewer than 50 aphids/leaf). In this study, we determined photosynthetic rates, leaf fluorescence responses, and photosynthetic responses to variable carbon dioxide and light levels. In addition, analyses for chlorophyll content and stable carbon isotope ratios were used to differentiate potential differences in stomatal versus mesophyll limitations to photosynthesis. We observed rate reductions of up to 50% on infested leaflets, including lealets with no apparent symptoms of aphid injury (such as chlorosis). Differences in fluorescence data indicated that photoelectron transport was not impaired. These results indicate that substantial physiological impact on soybean is possible even at low aphid densities. Also, the conventional view of aphid injury acting through reductions in chlorophyll content and light-harvesting reactions of photosynthesis is not supported by our findings in this system.

Animals↗
PubMed2003

Primary antiphospholipid antibody syndrome presenting as venous infarct and deep vein thrombosis.

We report the case of a young lady with primary antiphospholipid antibody syndrome, who had two spontaneous abortions and cerebral venous thrombosis and subsequently deep vein thrombosis of the leg veins. Three classes of antiphospholipid antibodies (IgG, IgM, IgA) were elevated. There was no clinical or laboratory evidence for other autoimmune or systemic illnesses. We are presenting the case due to the rarity of the same.

Abortion, Spontaneous↗
PubMed2001

Carbon isotopic ratios of atmospheric CO(2) affect the delta(13)C values of heterotrophic growth in Nicotiana tabacum.

Heterotrophic Nicotiana tabacum (L. CV. Wisconsin 38) plants are enriched in 13C relative to the carbon sources in their growth medium. We examined whether carboxylation via phosphoenolpyruvate carboxylase contributes to the enrichment. Achlorophyllous plants were produced using an inhibitor of carotenoid synthesis and were grown on sucrose with known delta(13)C values. Groups of plants were exposed to air with different delta(13)C values as well as to CO(2)-free air. The delta(13)C values of heterotrophic plants were greater than the sucrose source in all treatments and this enrichment increased as 13CO(2)/12CO(2) ratios increased in the source air. Rubisco activity was ruled out as a cause for the enrichment observed as 13CO(2)/12CO(2) ratios increased because the delta(13)C values of heterotrophic plants were similar when exposed to high 13CO(2) while grown in the light or dark. Neither was enrichment due to the adsorption of 13CO(2) in the high 13CO(2) treatment because dead plants did not exhibit this effect when subjected to the same atmospheric treatments. Carboxylation by PEP carboxylase is a likely mechanism causing the 13C-enriched values of living white tissues relative to their organic carbon sources. These results experimentally support suggestions that the anaplerotic activity of PEP is responsible for the 13C-enrichment commonly observed where heterotrophic inputs to growth are large such as in very young leaves.

Journal Article↗
PubMed2001

High and low serum potassium associated with cardiovascular events in diuretic-treated patients.

OBJECTIVE: To determine the relationship of moderately high and low concentrations of serum potassium with cardiovascular disease events among treated hypertensive patients. DESIGN: An observational cohort study with prospectively collected data. SETTING: A worksite treatment program for mild hypertension. PATIENTS: All program participants with baseline and at least one annual follow-up measure of serum potassium; 7,653 individuals with 6.7 years mean follow-up met these criteria. MAIN OUTCOME MEASURES: Outcome events were admissions to hospital because of cardiovascular disease, and deaths. The research question regarding serum potassium categories was formulated after data collection. The serum potassium concentration (mean +/- 2SD) of the study population was used to define low (3.0-3.5 mmol/l), high (5.1-5.9 mmol/l) and middle (3.6-5.0 mmol/l) categories. RESULTS: Individuals with low (n = 146) and high (n = 226) serum potassium had significantly greater risk for cardiovascular disease events than those in the middle category (n = 7,281). Multivariate adjusted hazard ratios from Cox models were 2.6 [95% confidence intervals (CI) 1.5-4.4] for the low potassium group and 1.7 (95% CI 1.0-2.7) for the high potassium group, with the middle group as reference. Among 1,679 individuals who regularly took diuretics, hazard ratios were 4.3 (95% CI 2.4-7.9) for the low potassium group and 6.7 (95% CI 2.8-15.9) for the high group. Neither low nor high potassium was significantly associated with outcome events for those not regularly using diuretics. CONCLUSIONS: These data confirm an association of mild hypokalemia with increased cardiovascular events among diuretic-treated hypertensive patients. In addition, we have found a similar increased cardiovascular risk associated with modest hyperkalemia among these patients. Whether modification of these serum potassium concentrations would alter that risk remains to be determined.

Cardiovascular Diseases↗
PubMed2000

Prevention of renal ischemia-reperfusion-induced injury in rats by picroliv.

Picroliv is a potent antioxidant extracted from the roots and rhizome of Picrorhiza kurrooa. It has been shown to impart significant hepatoprotective activities, partly by modulation of free radical-induced lipid peroxidation. Lipid peroxidation and reactive oxygen species are associated with tissue injury in post-ischemic acute renal failure. The efficacy of picroliv was assessed in an in vivo model of renal ischemia-reperfusion injury (IRI) in rats at a dose of 12 mg/kg orally for 7 days. The animals were killed at various times after reperfusion. Increased lipid peroxidation and apoptotic cell number reflected the oxidative damage following renal IRI. Picroliv-pretreated rats exhibited lower lipid peroxidation, improved antioxidant status, and reduced apoptosis, indicating better viability of renal cells. Immunohistochemical studies revealed that picroliv pretreatment attenuated the expression of intercellular adhesion molecule-1 in the glomerular region. These results suggested that picroliv pretreatment protects rat kidneys from IRI, perhaps by modulation of free radical damage and adhesion molecules.

Animals↗
PubMed2000

Myocardial infarction in treated hypertensive patients: the paradox of lower incidence but higher mortality in young blacks compared with whites.

BACKGROUND: Despite the impressive decline in coronary heart disease death rates, a mortality differential between blacks and whites persists. Our study objective was to determine whether excess mortality among well-controlled hypertensive black men compared with whites is due to differences in disease incidence or in case fatality. METHODS AND RESULTS: Of 3382 male subjects (1266 blacks and 2116 whites) enrolled between 1973 and 1996 and followed up through 1997 in a work-site hypertension control program, 2343 were followed up until 60 years of age, and 1884 were followed up until >60 years of age (either continuing after 60 years [n=845] or beginning treatment at >/=60 years [n=1039]), with a mean follow-up of 5.2 and 5.5 years, respectively. During follow-up, 186 myocardial infarction (MI) events (including 31 revascularizations) occurred, with 63 in patients <60 years and 123 in patients >/=60 years of age. Age-adjusted MI incidence was nearly twice as high for whites as blacks in younger (6.3 versus 3.4/1000 person-years) and older (14.1 versus 7.5 person-years) subjects. In contrast, the age-adjusted case fatality rate was 3-fold higher for younger blacks than for whites (37.8% versus 12.2%). In older patients, case fatality did not differ significantly between blacks and whites (37.6% versus 50. 3%). In separate Cox regression analyses, among younger blacks but not younger whites, history of diabetes and smoking were significantly associated with both incidence and fatality. CONCLUSIONS: In these treated male hypertensive patients with good blood pressure control (139.6/85.7 mm Hg), young blacks, despite a lower MI incidence, had higher MI mortality than did their white counterparts. Their higher case fatality rate was associated with fewer coronary artery revascularizations and a higher prevalence of diabetes and smoking.

Adult↗
PubMed2000

Maternal mortality in New York City: excess mortality of black women.

To assess maternal mortality in New York City, birth certificates and mortality records for New York City from 1988 through 1994 were linked and examined. During these 7 years, maternal mortality in New York City (defined by the International Classification of Diseases, 9th edition [ICD-9], as 630-676) per 100,000 live births significantly exceeded that of the country as a whole (20.2 vs. 8.2, respectively). Within New York City, an even greater variation of maternal mortality by race/ethnicity was noted, with the mortality ratio of whites, blacks, and Hispanics being 7.1, 39.5, and 14.4 per 100,000 live births, respectively. Socioeconomic characteristics such as educational attainment, marital status, and income influenced maternal mortality more in non-blacks than blacks. Analyses of cause-specific mortality revealed that, overall, ectopic pregnancy, embolism, and hypertension were the leading causes of death. However, the major factors explaining the excess maternal mortality among blacks were hypertension (mortality ratio of blacks to whites 5.57, 95% confidence interval 2.30-13.39), ectopic pregnancy (4.78, 95% confidence interval 2.40-9.51), and abortion (4.58, 95% confidence interval 1.72-12.22). These findings confirm a persisting gap in maternal death between black and white women. Indeed, if all New Yorkers who became pregnant enjoyed the survival of the city's non-Hispanic white residents, the difference in maternal mortality between the city and the nation would be eliminated.

Adolescent↗
PubMed2000

Assessing managed care's role in promoting preventive care.

The current trend of managed health care systems opens the door to more effective control of chronic diseases through preventive care. The goal of this study was to assess managed care's role in promoting preventive care. A mail survey was conducted of a national sample of 1,200 directors, associated with preventive care, in managed care organizations (MCOs) in the U.S. Data was obtained on perceived effectiveness, degree of importance, and likelihood of support for implementation of strategies recommended (case management, utilization review programs, selective contracting, and cost sharing) for ensuring appropriate utilization of preventive services. Also, information was collected on interventions perceived effective in encouraging plan members to utilize and providers to offer preventive services. Response rate was 17.3%. Case management and prospective and concurrent utilization review programs were perceived most effective, important, and likely to receive support for implementation while cost sharing (using deductibles and coinsurance) and retrospective utilization review programs ranked low on all dimensions. Plan member-directed interventions perceived effective in encouraging utilization of preventive services included telephone and mail reminders while computer-generated reminders and medical record audits with feedback were perceived effective in encouraging providers to offer such services. Results identified preferred MCO strategies and interventions for ensuring appropriate utilization of preventive services. Further research is needed to develop methods to encourage people at high risk for chronic diseases not currently utilizing preventive services to receive such services.

Case Management↗
PubMed2000

Serum potassium and cardiovascular mortality.

BACKGROUND: The impact of serum potassium on mortality is inadequately defined. OBJECTIVE: To determine the association of serum potassium with mortality. METHODS: We analyzed NHANES I Epidemiological Follow-up Study data from 1974-1992. Of 2,992 subjects with baseline serum potassium, 156 were excluded because their vital status was not known. A total of 2,836 subjects with serum potassium within 2.7-5.4 mmol/L were studied. All-cause and cardiovascular mortality were assessed controlling for sociodemographic status, smoking, medical history, and clinical characteristics. RESULTS: At baseline, mean age was 46.6 years, and mean serum potassium was 4.07 mmol/L. Subjects were stratified into three groups by mean +/-1 standard deviation of serum potassium: low, 2.7-3.7 mmol/L (N = 477); middle, 3.8-4.4 mmol/L (N = 1,982); and high, 4.5-5.4 mmol/L (N = 377). The cardiovascular mortality rate per 1,000 person-years adjusted for age, gender, and race for the high serum potassium group (8.1) was significantly higher than the middle (5.3) and low (6.5) serum potassium groups. Further analysis, controlling for age, gender, race, smoking status, cholesterol, and history of diabetes, renal disease, and cardiovascular disease, revealed that the increased cardiovascular mortality among subjects with moderately increased serum potassium was most prominent in those reporting use of diuretics (hazard ratio, 2.65; 95% confidence interval [95% CI], 1.20 to 5.85) and those with abnormal renal function (hazard ratio, 1.89; 95% CI, 1.05 to 3.41). CONCLUSION: In this general population sample with mostly normal serum potassium, higher serum potassium was independently associated with increased cardiovascular mortality.

Cardiovascular Diseases↗
PubMed2000

Pulse pressure: a predictor of cardiovascular mortality among young normotensive subjects.

Wide pulse pressure has been associated with increased cardiovascular disease events among hypertensive subjects. To test the hypothesis that this association also exists among normotensive subjects, data from the first National Health and Nutritional Examination Survey and the 1992 Epidemiological Follow-up Study were analyzed. The study group included 7346 participants, aged 25-74 years, with baseline blood pressure levels <140/90 mmHg and without a history of hypertension. Deaths from cardiovascular disease and all other causes were determined. At entry, mean age and blood pressure level were 43.4 years and 118/76 mmHg. During an average follow-up period of 17.4 years, there were 1443 (19.6%) deaths, 557 of them ascribed to cardiovascular disease. Age-race-adjusted cardiovascular mortality was significantly higher for those in the highest quartile of pulse pressure (> or = 50 mmHg). However, after stratification into age <55 years and > or = 55 years, and controlling for other cardiovascular risk factors, increased pulse pressure was associated with cardiovascular mortality only in younger men and women. In these subjects, men and women with pulse pressures > or = 48, and > or = 46 mmHg, respectively, had a relative risk (95% confidence in terval) of 2.35 (1.21-4.38) and 2.90 (1.34-4.98) for cardiovascular mortality with those with pulse pressures of less than 36 and 34 mmHg, respectively (p < 0.05) as reference. While systolic blood pressure by itself was a weaker predictor of cardiovascular mortality than pulse pressure, diastolic and mean arterial pressure were not predictive at all. No measure of blood pressure was related to mortality in those aged > or = 55 years. In conclusion, among young subjects, but not older normotensive persons, at very low risk of cardiovascular disease, a wide pulse pressure is associated with increased cardiovascular mortality.

Adult↗
PubMed2000

Tunicamycin enhances the anticellular activity of interferon by inhibiting G1/S phase progression in 3T3 cells.

We have shown earlier that the cell growth inhibitory activity of interferon (IFN) is significantly enhanced by tunicamycin (TM) (Maheshwari et al., Science 219, 1339-1341, 1983). In this report, we investigated various regulatory points of synergistic action between TM and IFN-alpha/beta that inhibit cell growth in NIH 3T3 cells. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) viability assays showed a dose-dependent increase in percentage inhibition of the cells when treated with either TM or IFN. When doses of TM and IFN that had no significant inhibition on cell viability were used in combination, there was a pronounced suppression of DNA synthesis (tritiated thymidine incorporation). Flow cytometry studies revealed that individual treatments with either IFN or TM that did not alter the cell cycle profile, when combined, resulted in an impaired cell cycle by inhibiting G1/S progression. The blockage of G1/S transition was associated with reduction of cyclin-dependent kinase (CDK4) activity. The mRNA (analyzed by ribonuclease protection assay) and protein levels (assayed by Western blotting) of cyclins D1, D3, and CDK4 were downregulated by combined treatment with IFN and TM. An increase in the expression of p27/kipl, an inhibitor of CDK4, was observed in cells that were treated with both IFN and TM. These studies suggest that insufficient formation of the active cyclin/CDK complex could possibly be deferring the cells from normal cycling and may be responsible for the ability of TM to enhance cell growth inhibition induced by IFN.

3T3 Cells↗