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Biomedical subjects

P Krishnamurthy

Publications and source records attributed to P Krishnamurthy.

At least 19 recordsLinked to original sources
PubMed2006

Deficiency of beta1 integrins results in increased myocardial dysfunction after myocardial infarction.

OBJECTIVE: To study the role of beta1 integrins in left ventricular (LV) remodelling after myocardial infarction (MI). METHODS AND RESULTS: LV structural and functional alterations were determined in wild-type (WT) and beta1 integrin heterozygous knockout (hKO) mice one month after MI. MI increased beta1 integrin expression in both groups; however, the increase was lower in hKO. Infarct size was similar in WT and hKO mice, whereas lung wet weight to dry weight ratio was increased in the hKO-MI mice (5.17 (SE 0.13) v 4.60 (0.15) in WT-MI, p < 0.01). LV end systolic and end diastolic diameters were significantly higher and percentage fractional shortening was significantly lower in hKO-MI. The ratio of peak velocity of early LV filling (E wave) to that of the late LV filling (A wave) and the isovolumic relaxation time (IVRT) were increased in both MI groups but the increase in IVRT was significantly higher in hKO-MI group than in WT-MI mice. Langendorff perfusion analysis indicated reduced peak LV developed pressure and increased LV end diastolic pressure in both MI groups. The reduction in peak LV developed pressure (36.7 (2.2) v 53.4 (1.9) mm Hg, p < 0.05) and increase in LV end diastolic pressure was higher in hKO-MI than in WT-MI. Increase in fibrosis was not different between the two MI groups. The increase in myocyte circumference was higher in the hKO-MI group (p < 0.001 v WT-MI). The number of apoptotic myocytes was significantly higher in hKO-MI than in WT-MI mice (p < 0.005) three days after MI. The number of necrotic myocytes was not different between the two MI groups. CONCLUSION: beta1 integrins are crucial in post-MI remodelling with effects on LV function, hypertrophy and apoptosis.

Animals↗
PubMed2006

Role of ABCG2/BCRP in biology and medicine.

The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must homodimerize to acquire transport activity. ABCG2 is found in a variety of stem cells and may protect them from exogenous and endogenous toxins. ABCG2 expression is upregulated under low-oxygen conditions, consistent with its high expression in tissues exposed to low-oxygen environments. ABCG2 interacts with heme and other porphyrins and protects cells and/or tissues from protoporphyrin accumulation under hypoxic conditions. Individuals who carry ABCG2 alleles that have impaired function may be more susceptible to porphyrin-induced toxicity. Abcg2 knock-out models have allowed in vivo studies of Abcg2 function in host and cellular defense. In combination with immunohistochemical analyses, these studies have revealed how ABCG2 influences the absorption, distribution, and excretion of drugs and cytotoxins.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2006

Repeated sputum microscopy is not essential for monitoring tuberculosis treatment response.

SETTING: This study was conducted in two districts in India where DOTS has been implemented. There are 39 microscopy centres in Anantpur district and 34 in Nellore district (one per 100,000 population), each with a trained microscopist. Periodic follow-up sputum microscopy is performed for all tuberculosis (TB) patients on treatment, with two sputum specimens examined on each follow-up. Results are recorded in a laboratory register. OBJECTIVE: To determine whether examining two sputum specimens for follow-up is useful for assessing treatment outcome. DESIGN: A retrospective study using data from laboratory registers of all microscopy centres for 2002 in Anantpur and 2003 (January-June) in Nellore. RESULTS: Of 5086 follow-up examinations done in Anantpur and 1028 in Nellore, 8% were acid-fast bacilli positive. One additional positive result was obtained on examination of a second sputum specimen. This result did not significantly add to the assessment of treatment outcome. CONCLUSION: The yield of a second on-the-spot sputum specimen is negligible, provided that the first smear is from an overnight specimen. From the data available, it is evident that repeated follow-up smears are not essential for documenting treatment outcome.

Antitubercular Agents↗
PubMed2005

Community prevalence of hepatitis B infection and modes of transmission in Tamil Nadu, India.

BACKGROUND AND OBJECTIVE: There have been very few community based studies on prevalence of hepatitis B virus (HBV) infection in India. We undertook this study to determine the prevalence of HBV infection in a southern State of India, Tamil Nadu and to describe the important factors related to transmission of the virus in the community. METHODS: Analysis of stored blood samples from a representative population of Tamil Nadu from an earlier community cluster survey on sexually transmitted diseases (STD) prevalence using proportionate to population size (PPS) technique was done. Serum markers of HBV viz., hapatitis B surface antigen (HBsAg), hepatitis B e antigen (HBe Ag) and antibody to surface antigen (anti-HBs) were performed. RESULTS: 1981 subjects were screened in the study. HBsAg prevalence was 5.7 per cent (CI 4.6- 6.8) with 23.5 per cent (25/106) of these having positive HBe-antigen. Community seroprevalence (HbsAg + anti-HBs) of hepatitis B infection was 27.4 per cent (CI: 25.3-29.5) with the highest prevalence of 32.7 per cent (CI: 30.2-35.2) noted in the 15-20 yr age group. Significant independent association (OR 1.4; P=0.006) was detected with family history of exposure to HBV infection by logistic modeling. Other risk factors noted to have significant association were use of disposable needles during injection (OR 0.5; P=0.02) in men, smoking (OR 3; P=0.04) and use of condom (OR 0.6; P=0.08) in women. INTERPRETATION AND CONCLUSION: This community based study shows a high prevalence of hepatitis B infection in the state of Tamil Nadu with the highest prevalence being in the younger (15-20 yr) age group. High prevalence rate in childhood with e-antigenemia seen in 23.5 per cent of HBsAg positive subjects suggest childhood transmission. Poor injection practices and high-risk sexual behavior were found to be additional risk factors for transmission of the disease in the community.

Adolescent↗
PubMed2002

Dengue fever outbreaks in two villages of Dharmapuri district in Tamil Nadu.

BACKGROUND & OBJECTIVES: Dengue fever is an important public health problem in India. In recent years this disease has extended to rural areas also due to rapid urbanization. In Tamil Nadu, fever outbreaks were reported in two villages of Dharmapuri district during May and September 2001 with clinical symptoms suggestive of dengue fever. Epidemiological, virological and entomological investigations were carried out in these two villages to ascertain the etiology of the outbreaks. METHODS: Paired serum samples were collected from febrile patients clinically suspected to have dengue and were tested for the presence of IgM antibodies to dengue virus by MAC ELISA. Samples were also tested by Dengue Duo IgM/IgG rapid strip. Surveys of larval and adult Aedes mosquitoes were carried out before and after anti-larval and anti-adult measures were implemented. Female Ae. aegypti mosquitoes collected in Mampatti village were tested individually for the presence of dengue-2 viral antigen by indirect immunofluorescence assay (IIFA). In addition, two pools of female Ae. aegypti mosquitoes were tested for the presence of dengue viral antigen by ELISA and then subjected to Toxo-IFA system for demonstration of dengue virus. RESULTS: A total of 124 and 267 fever cases with clinical symptoms and signs suggestive of dengue were reported in Kadumuchandiram and Mampatti villages of Dharmapuri district, respectively. Serodiagnosis revealed that 13 of 31 and 14 of 52 patients tested were positive for dengue-2 virus by MAC ELISA in Kadumuchandiram and Mampatti villages respectively. Dengue Duo rapid strip test also detected 14 (of 31 tested) patients positive for dengue virus specific IgM antibodies in Kadumuchandiram village and 8 (of 12 tested) in Mampatti village. Application of temephos and fogging with pyrethrum 2 per cent extract were found to be effective against immatures and adults respectively. Both the pools of Ae. aegypti tested for the presence of dengue viral antigen were positive by ELISA and one mosquito (tested individually) was positive by IIFA. Supernatants of two pools were found to be positive for dengue-2 virus by Toxo-IFA. INTERPRETATION & CONCLUSION: Virological and serological investigations confirmed that the outbreaks of fever were due to dengue virus infection. High breeding of Ae. aegypti in the study villages, detection of dengue-2 viral antigen and isolation of dengue-2 virus in Ae. aegypti mosquitoes confirmed the etiology.

Dengue↗
PubMed2000

Chemoprophylaxis against leprosy: expectations and methodology of a trial.

Because of the great efficacy of multidrug therapy (MDT), it had been hoped that the widespread use of MDT would bring about a rapid decrease of the incidence of leprosy. To the present, a decrease of incidence has not been observed, possibly because of the long incubation period of the disease, and because general implementation of MDT is still recent. Other reasons, such as environmental sources of infection or the role of healthy carriers in transmitting Mycobacterium leprae, cannot be excluded. Therefore, one must seek alternative or supplementary strategies, such as chemoprophylaxis. Household contacts of leprosy patients are at greater risk of developing leprosy than is the general population. Therefore, a randomized, controlled trial of chemoprophylaxis, using a single 10 mg/kg dose of rifampicin, or a placebo, is planned in nine projects in India, among the household contacts of newly detected leprosy patients. Based upon assumptions of a protective efficacy of the chemoprophylaxis of 50%, an annual incidence of 2 per 1000 contacts, a desired power of the study of 90%, and a level of significance of 95%, 15,000 household contacts will be allocated randomly by household to each arm of the study, and followed for 5 years. Considered as household contacts will be all persons living in the same household as an index case and sharing the same kitchen. Pregnant women and infants will be excluded. To be certain that transmission of the organisms from the index case cannot occur once the prophylaxis is administered, rifampicin will be administered 2 months after diagnosis of the index case. Diagnosis of leprosy will be clinical, and confirmed independently. Although household contacts usually constitute only a small proportion of the new patients detected in a control programme, their high-risk status makes them particularly appropriate for a study of the potential effect of chemoprophylaxis. Following the trial, one could evaluate the usefulness and feasibility of using the same strategy in other population-groups, based on the number of persons necessary to treat to prevent one case.

Drug Therapy, Combination↗
PubMed1999

Effects of angiogenic growth factors on endothelium-derived prostacyclin production by ovine uterine and placental arteries.

Uteroplacental and fetoplacental arteries produce substantial amounts of prostacyclin (PGI2). Because angiogenic growth factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) are increased in pregnancy, we hypothesized that treatment of uterine and fetoplacental arteries with bFGF, VEGF, and EGF would further enhance the pregnancy-induced increase in PGI2 production. Duplicate uterine (UA) and fetoplacental (PA) artery (primary branch off of the umbilical cord = pPA; cotyledonary or tertiary = tPA) explants from seven late gestation sheep were placed in tissue culture (RPMI; 37 degrees C) for 24 h alone or with (1-100 ng/mL) bFGF, VEGF, or EGF. To evaluate the endothelial contribution to basal and stimulated PGI2 production and to determine whether it is de novo, arteries with and without endothelium from three additional late gestation ewes, tissues were incubated in the absence or presence of growth factors with or without meclofenamate (1 microM). The stable metabolite of PGI2, 6-keto-PGF1 alpha, was measured in culture media and expressed as ng/mg wet wt 24 h. PGI2 production by UA increased (p < 0.05) from 5.43 +/- 0.26 at control to 8.93 +/- 0.99 with 100 ng/mL bFGF. Although VEGF produced a similar response, EGF did not increase PGI2 production in UA. In pPA, 100 ng/mL bFGF induced a 2.2-fold increase (p < 0.01) in PGI2 production from 1.94 +/- 0.14 to 4.20 +/- 0.31; VEGF and EGF were without effect. In tPA, 50 and 100 ng/mL bFGF increased PGI2 production from 1.98 +/- 0.14 to 3.5 +/- 1.05 and 3.96 +/- 0.46 (p < 0.02). In tPA, VEGF did not increase PGI2 production; however, 10, 50, and 100 ng/mL EGF, enhanced (p < 0.03) PGI2 production from 1.98 +/- 0.14 to 3.39 +/- 0.62, 3.62 +/- 0.26, and 2.93 +/- 0.20. Endothelium removal and meclofenamate treatment caused a 90% and 100% decrease, respectively, in basal PGI2 production, with no recovery after treatment with growth factors. We conclude that PGI2 production is augmented by bFGF in UA, pPA and tPA, by VEGF in UA, and by EGF in tPA during ovine pregnancy. Basal and stimulated PGI2 secretion is endothelium-derived via de novo synthesis. bFGF, VEGF, and EGF, in addition to angiogenesis, may modulate PGI2 production, further enhancing blood flow to the growing uteroplacental bed.

Animals↗
PubMed1999

Identification of a novel penicillin-binding protein from Helicobacter pylori.

The Helicobacter pylori genome encodes four penicillin-binding proteins (PBPs). PBPs 1, 2, and 3 exhibit similarities to known PBPs. The sequence of PBP 4 is unique in that it displays a novel combination of two highly conserved PBP motifs and an absence of a third motif. Expression of PBP 4, but not PBP 1, 2, or 3, is significantly increased during mid- to late-log-phase growth.

Amino Acid Sequence↗
PubMed1999

Pace of leprosy elimination and support teams in Bihar state, India.

Despite the extensive implementation of multiple drug therapy (MDT) in most leprosy-endemic countries world-wide since 1982, bringing about a remarkable reduction in prevalence, there are still regions at the sub-national level where the implementation of MDT remains difficult. The state of Bihar (population 86.3 million) in India is a good example of such a region. Previously rated as one of the most highly endemic states, it still contributes about 21% of the total caseload in India and about 12% of the global caseload. For various reasons, case-finding and drug treatment have lagged behind the progress made in most other states in the country and in 1996, the Damien Foundation India Trust (DFIT) volunteered technical support to increase the pace of elimination. Sixteen out of the 39 districts in the state were allocated, with a population of 41.8 million. Support teams, including a Medical Advisor and a Non-Medical Supervisor, both with over 10 years experience of leprosy work and control programmes, were provided to assist and work alongside government staff in case detection, treatment delivery, case-holding and discharge in their respective areas of operation. New case detection by intensive survey increased by 394% and total new case detection by 226% during the year 1996-1997, with similar trends in the following year. Striking improvements were also observed in MDT coverage, treatment regularity, monitoring and discharge of patients and in the training of local staff. This collaboration between a non-government agency (DFIT) and the staff of the National Leprosy Eradication Programme in 16 out of 39 districts in the State of Bihar has clearly been extremely successful. Similar approaches in the remaining districts of Bihar, and in other parts of India, where the infrastructure is available but inadequate, may contribute significantly to achieving the elimination goal at national and sub-national levels.

Drug Therapy, Combination↗
PubMed1998

Helicobacter pylori containing only cytoplasmic urease is susceptible to acid.

Helicobacter pylori, an important etiologic agent in a variety of gastroduodenal diseases, produces large amounts of urease as an essential colonization factor. We have demonstrated previously that urease is located within the cytoplasm and on the surface of H. pylori both in vivo and in stationary-phase culture. The purpose of the present study was to assess the relative contributions of cytoplasmic and surface-localized urease to the ability of H. pylori to survive exposure to acid in the presence of urea. Toward this end, we compared the acid resistance in vitro of H. pylori cells which possessed only cytoplasmic urease to that of bacteria which possessed both cytoplasmic and surface-localized or extracellular urease. Bacteria with only cytoplasmic urease activity were generated by using freshly subcultured bacteria or by treating repeatedly subcultured H. pylori with flurofamide (1 microM), a potent, but poorly diffusible urease inhibitor. H. pylori with cytoplasmic and surface-located urease activity survived in an acid environment when 5 mM urea was present. In contrast, H. pylori with only cytoplasmic urease shows significantly reduced survival when exposed to acid in the presence of 5 mM urea. Similarly, Escherichia coli SE5000 expressing H. pylori urease and the Ni2+ transport protein NixA, which expresses cytoplasmic urease activity at levels similar to those in wild-type H. pylori, survived minimally when exposed to acid in the presence of 5 to 50 mM urea. We conclude that cytoplasmic urease activity alone is not sufficient (although cytoplasmic urease activity is likely to be necessary) to allow survival of H. pylori in acid; the activity of surface-localized urease is essential for resistance of H. pylori to acid under the assay conditions used. Therefore, the mechanism whereby urease becomes associated with the surface of H. pylori, which involves release of the enzyme from bacteria due to autolysis followed by adsorption of the enzyme to the surface of intact bacteria ("altruistic autolysis"), is essential for survival of H. pylori in an acid environment. The ability of H. pylori to survive exposure to low pH is likely to depend on a combination of both cytoplasmic and surface-associated urease activities.

Benzamides↗
PubMed1998

A comparative study of the cost and effectiveness of a modified system of MDT drug delivery system in a high endemic district (Nalagonda) of South India.

Fall in the case load (from 17,000 to 4,500), has changed the disease profile and introduction of fixed duration Therapy (FDT) has made management of leprosy cases rather easy in Nalgonda, a backward district in Andhra Pradesh. The system of drug delivery which was conceived for managing large case load, however, remains unchanged, thereby resulting not only in considerable wastage of resources but also in hampering other activities like case detection and patient care. This study was undertaken to develop and assess a modified system of drug delivery in terms of the cost and effectiveness, its overall effect on other activities in the programme and its acceptability by the field staff. Four Leprosy Control Units (LCUs) were selected and were randomly assigned either to study (Gudibanda, Suryapet) or control (Nalgonda, Bhuvanagiri) group. In the study group the modified drug delivery system replaced the existing system. The modified system consisted of the para medical worker being made responsible for patients at all the DDPs in his subcentre. The clinics were managed alternately by medical officers and non medical supervisors every month. In the control group each clinic was managed by medical officers every month and it covered two sub centers with each drug delivery point being assisted by a para medical worker. The study revealed that the modified system resulted in a saving of 130 man-days a month, a 30% saving in use of vehicle, a 30% saving in POL and improvement in case detection. There was no change in the clinic attendance and drug consumption compliance in the units where modified system was introduced.

Cost-Benefit Analysis↗
PubMed1994

Acute thoracic aortic occlusion resulting from complex aortic dissection and presenting as paraplegia.

Acute paraplegia from an aortic occlusion or dissection is a surgical emergency. Prompt recognition and treatment may mitigate irreversible spinal cord injury. Aortography is commonly used when an aortic lesion is suspected as the cause of acute paraplegia. Transesophageal echocardiography is becoming increasingly used for the evaluation of aorta, diagnosing aortic dissection promptly at the bedside, and was able to define the cause of the spinal cord ischemia.

Acute Disease↗
PubMed1994

The influence of operational factors in the profile of monolesional leprosy cases in south India.

A comparison of the profile of monolesional cases among new PB cases detected in a Government Leprosy Control Unit (GLCU) and the field area of a Central Leprosy Teaching and Research Institute (CLTRI), both located in South India, demonstrates that the proportion of monolesional cases among new cases detected between 1987 and 1991 was higher in children than adults, higher in females than males (only in the CLTRI)--over 95% were the tuberculoid type. A significantly increasing trend in this proportion could be seen in the GLCU but not in the CLTRI; an explanation of this is based on the difference in operational aspects in case detection methodology adopted by the 2 areas--e.g. intersurvey interval and mode of case detection. Such studies, focusing on single skin lesions, help us in understanding the role of various possible operational factors in influencing the behaviour of the disease.

Adult↗
PubMed1992

Initial intensive therapy for multibacillary leprosy patients--in retrospect.

We analysed the results of 4845 multibacillary (MB) patients being treated with multidrug treatment (MDT) in the Srikakulam District of Andhra Pradesh, India. Of these, 2309 (47.7%) patients were given an initial 14-day intensive therapy with rifampicin, clofazimine and dapsone, followed by the WHO recommended pulse therapy. The rest of the cases were given only pulse therapy. The improvement in terms of bacteriological clearance and the proportion of cases declared released from treatment (RFT) was found to be significantly higher among patients treated with only pulse therapy. Clinic attendance was found to be better and more regular in patients treated with intensive therapy, and no relapses were seen with either therapy. The implications of these findings on the operational aspects of programme implementation are discussed.

Humans↗
PubMed1991

Seroepidemiological study of leprosy in a highly endemic population of south India based on an ELISA using synthetic PGL-I.

As part of a continuing longitudinal immuno-epidemiological study, blood samples were collected by finger prick from 4243 individuals living in a highly endemic area for leprosy in South India. The samples were tested for IgM antibodies against phenolic glycolipid-I using an ELISA. Seropositivity defined as optical density greater than or equal to 0.2000 was marginally higher in the age group 10-30 years and in females. There was no evidence for a higher level in contacts than in non-contacts. The future prospect for the large scale use of this ELISA in high-endemic populations in special epidemiological investigations or routine control programs as a serological tool to detect leprosy infection appears questionable.

Adolescent↗
PubMed1987

School health--preparation of teacher for health education.

In India where the school children form a significant and important segment of the population, the health needs are so great, that a well planned "School Health Programme" is absolutely necessary. Teacher preparation for health education has its rightful place in it.

Adult↗