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Biomedical subjects

R Garg

Publications and source records attributed to R Garg.

At least 19 recordsLinked to original sources
PubMed2007

U-500 insulin: why, when and how to use in clinical practice.

Some patients with type 2 diabetes mellitus (T2DM) have severe insulin resistance. Their insulin requirements are significantly greater. These patients need to take 2-3 injections at the same time to take the correct insulin dose or to redial the insulin pen. When daily insulin requirements are in excess of 300 units/day, the volume of the injected insulin becomes an issue. Large-volume injection can cause discomfort and lead to poor concordance with treatment. Using high-strength insulin e.g. U-500 insulin can reduce the volume of the injected insulin. Despite publications of small case reports or case series, no universal guidelines exist on the use of U-500 insulin. We discuss common sense approaches when considering the use of U-500 insulin in clinical practice.

Diabetes Mellitus, Type 2↗
PubMed2005

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.

BACKGROUND: Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis. OBJECTIVES: The aim of this review is to establish the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), to identify the most effective antibiotic treatment for CDAD in adults and to determine the need for stopping the causative antibiotic during therapy. SEARCH STRATEGY: MEDLINE (1966 to 2003), EMBASE (1980 to 2003), Cochrane Central Database of Controlled Trials and the Cochrane IBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial". SELECTION CRITERIA: Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. Probiotic trials are excluded. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to C. difficile cytotoxin and/or stool culture negative; recurrence of diarrhea; recurrence of fecal C. difficile cytotoxin and/or positive stool culture; patient response to cessation of prior antibiotic therapy; sepsis; emergent surgery: fecal diversion or colectomy; and death. DATA COLLECTION AND ANALYSIS: Data were analyzed using the MetaView statistical package in Review Manager. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study. When appropriate, the results of included studies were combined for each outcome. For dichotomous outcomes, pooled RR and 95% CI were calculated using a fixed effect model, except where significant heterogeneity was detected, at which time the random effects model was used. Data heterogeneity was calculated using MetaView. MAIN RESULTS: Of eleven studies identified, two were subsequently excluded because patients were stool positive for C. difficile, but did not have diarrhea or because the study was not a randomized controlled trial. All of the remaining nine studies involved patients with diarrhea who recently received antibiotics for an infection other than C. difficile. The definition of diarrhea ranged from at least two loose stools per day with an associated symptom such as rectal temperature > 38(o)C, to at least six loose stools in 36 hours. In terms of symptomatic cure, metronidazole, bacitracin and fusidic acid were not shown to be less effective than vancomycin. Teicoplanin may be slightly more effective than vancomycin with a relative risk of 1.21 [95% CI 1.00 to 1.46] and a p-value of 0.06. In terms of initial symptomatic resolution, vancomycin is more effective than placebo with a relative risk of 6.75 [95% CI 1.16 to 48.43] and a p-value of 0.03. This result should be interpreted with caution given the small number of patients in this comparison (12 in the vancomycin group and nine in the placebo group) and the poor methodological quality of the trial. Metronidazole, bacitracin, teicoplanin, fusidic acid and rifaximine are as effective as vancomycin for initial symptomatic resolution. The other secondary outcomes measured in this review: surgery, sepsis and death occurred infrequently in all of the studies. AUTHORS' CONCLUSIONS: Current evidence leads to uncertainty whether mild CDAD needs to be treated. Patients with mild CDAD may resolve their symptoms as quickly without treatment. The only placebo-controlled study shows vancomycin's superior efficacy. However, this result should be treated with caution due to the small number of patients enrolled and the poor methodological quality of the trial. The Johnson study of asymptomatic carriers also shows that placebo is better than vancomycin or metronidazole for eliminating C. difficile in stool during follow-up. If one does decide to treat, then two goals of therapy need to be kept in mind: improvement of the patient's clinical condition and prevention of spread of C. difficile infection to other patients. Given these two considerations, one should choose the antibiotic that brings both symptomatic cure and bacteriologic cure. In this regard, teicoplanin appears to be the best choice because the available evidence suggests that it is better than vancomycin for bacteriologic cure and has borderline superior effectiveness in terms of symptomatic cure. Teicoplanin is not readily available in the United States, which must be taken into account when making treatment decisions in that country.

Adult↗
PubMed2005

Function and regulation of RhoE.

The three Rnd proteins, Rnd1, Rnd2 and RhoE/Rnd3, are a subset of Rho family proteins that are unusual in that they bind but do not hydrolyse GTP, and are therefore not regulated by the classical GTP/GDP conformational switch of small GTPases. Increased expression of each Rnd protein induces loss of stress fibres in cultured fibroblasts and epithelial cells, acting antagonistically to RhoA, which stimulates stress fibre formation. RhoE is farnesylated and localizes partly on membranes, including the Golgi and plasma membrane, and in the cytosol. RhoE inhibits RhoA signalling in part by binding to the RhoA-activated serine/threonine kinase ROCK I (Rho-associated kinase I), thereby preventing it from phosphorylating its targets. RhoE activity is itself regulated by phosphorylation by ROCK I on multiple sites. RhoE phosphorylation enhances its stability, leading to an increase in RhoE levels. In addition, phosphorylation reduces its association with membranes and correlates with its ability to induce loss of stress fibres. RhoE also acts independently of ROCK to inhibit cell cycle progression, in part by preventing translation of cyclin D1, and to inhibit transformation of fibroblasts by oncogenic H-Ras. RhoE is therefore a multifunctional protein whose localization and actions are regulated by phosphorylation.

Animals↗
PubMed2005

Immunostimulatory cellular responses of cured Leishmania-infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of Leishmania donovani.

Development of an effective immunoprophylactic agent for visceral leishmaniasis (VL) has become imperative due to the increasing number of cases of drug resistance and relapse. Live and killed whole parasites as well as fractionated and recombinant preparations have been evaluated for vaccine potential. However, a successful vaccine against the disease has been elusive. Because protective immunity in human and experimental leishmaniasis is predominantly of the Th1 type, immunogens with Th1 stimulatory potential would make good vaccine candidates. In the present study, the integral membrane proteins (IMPs) and non-membranous soluble proteins (NSPs), purified from promastigotes of a recent field isolate, Leishmania donovani stain 2001, were evaluated for their ability to induce cellular responses in cured patients (n = 9), endemic controls (n = 5) of visceral leishmaniasis (VL) and treated hamsters (n = 10). IMPs and NSPs induced significant proliferative responses (SI 6.3 +/- 4.1 and 5.6 +/- 2.3, respectively; P < 0.01) and IFN-gamma production (356.3 +/- 213.4 and 294.29 +/- 107.6 pg/ml, respectively) in lymphocytes isolated from cured VL patients. Significant lymphoproliferative responses against IMPs and NSPs were also noticed in cured Leishmania animals (SI 7.2 +/- 4.7 & 6.4 +/- 4.1, respectively; P < 0.01). In addition, significant NO production in response both IMPs and NSPs was also noticed in macrophages of hamsters and different cell lines (J774A-1 and THP1). These results suggest that protective, immunostimulatory molecules are present in the IMP and NSP fractions, which may be exploited for development of a subunit vaccine for VL.

Adolescent↗
PubMed2005

Comparison of cough of 2 and 3 weeks to improve detection of smear-positive tuberculosis cases among out-patients in India.

SETTING: Governmental health facilities in six districts of India. OBJECTIVE: To estimate the prevalence of cough and to compare the detection of smear-positive tuberculosis (TB) among out-patients with cough of > or =2 or > or =3 weeks. DESIGN: Trained health workers questioned each out-patient for presence of cough. Those with cough > or =2 weeks underwent sputum microscopy. RESULTS: Of 55561 out-patients interviewed, 2210 (4%) had cough > or =2 weeks, of whom 267 had sputum-positive TB, compared to 182/1370 with cough > or =3 weeks. The 31% who did not spontaneously complain of cough were less likely to be sputum-positive than those who did (45/680 [7%] vs. 222/1530 [15%], P < 0.001), but they accounted for 45/267 smear-positive cases. Using cough > or =2 weeks as the screening criterion, the estimated number of smears performed per day at each primary and secondary health care facility was respectively 8 and 19, compared to 5 and 12 using cough > or =3 weeks. CONCLUSION: The detection of smear-positive TB cases can be substantially improved by actively eliciting history of cough from all out-patients, and by changing the screening criterion for performing sputum microscopy among out-patients from cough > or =3 weeks to > or =2 weeks. Before implementing this change nationally, its programmatic feasibility should be assessed.

Adolescent↗
PubMed2004

Gender disparities in tuberculosis: report from a rural DOTS programme in south India.

SETTING: Tiruvallur District, south India. OBJECTIVES: To examine gender differences in tuberculosis among adults aged >14 years with respect to infection and disease prevalence, health care service access, care seeking behaviour, diagnostic delay, convenience of directly observed treatment (DOT), stigma and treatment adherence. METHODS: Data were collected from 1) community survey, 2) self-referred out-patients seeking care at governmental primary health institutions (PHIs), 3) tuberculosis suspects referred for sputum microscopy at PHIs, and 4) tuberculosis patients notified under DOTS. Community survey results were compared with those for patients notified at PHIs. RESULTS: In the community, 66% of males and 57% of females had tuberculosis infection. The prevalence of smear-positive tuberculosis was 568 and 87/100,000, respectively, among males and females. Fewer males than females attended PHIs (68 men for every 100 women). Females constituted 13% of all smear-positive patients detected in the community survey, and 20% of those detected at PHIs (P < 0.05). The probability of notification decreased significantly with age among both males and females. Significantly more females than males felt inhibited discussing their illness with family (21% vs. 14%) and needed to be accompanied for DOT (11% vs. 6%). Males had twice the risk of treatment default than females (19% vs. 8%; P < 0.01). CONCLUSIONS: Despite facing greater stigma and inconvenience, women were more likely than men to access health services, be notified under DOTS and adhere to treatment. Men and elderly patients need additional support to access diagnostic and DOT services.

Adolescent↗
PubMed2004

Vitamin A levels in sputum-positive pulmonary tuberculosis patients in comparison with household contacts and healthy 'normals'.

OBJECTIVE: To estimate serum vitamin A in pulmonary tuberculosis (PTB) patients at the start and end of anti-tuberculosis treatment. DESIGN: Serum vitamin A was estimated in 47 PTB patients (pre and post treatment), 46 healthy household contacts and 30 healthy 'normals'. RESULTS: Mean serum vitamin A in patients at the start of treatment was 21.2 microg/dl, which was significantly lower than in household contacts (42.2 microg/dl) and healthy 'normals' (48.1 microg/dl). The vitamin A levels in patients increased following treatment. CONCLUSION: The low vitamin A levels observed in patients returned to normal at the end of anti-tuberculosis treatment without vitamin A supplementation.

Adult↗
PubMed2004

A survey of tuberculosis hospitals in India.

SETTING: Hospitals with beds for tuberculosis (TB) in India. OBJECTIVES: To assess diagnostic and treatment practices at institutions offering secondary or tertiary level care for TB patients, and to determine the resources being used at these institutions. DESIGN: Countrywide cross-sectional survey of TB hospitals using a mailed semi-structured questionnaire sent to all 105 hospitals with 100 or more beds and to all State Directorate Health Services. RESULTS: The 94 hospitals that returned the questionnaire had 15773 TB beds, one third of the total TB beds in the country. Nearly 1 million patients sought treatment in the TB hospitals and one third were diagnosed with TB; the ratio of smear-positive to smear-negative patients was 1:2.7. Sixty-four per cent of hospitals prescribed unobserved rifampicin in the continuation phase, and 56% of sputum smear-positive patients were hospitalised. The annual expenditure for the TB hospitals was more than the total annual budget for the TB control programme of the country. CONCLUSIONS: In view of the high number of patients seen and the suboptimal practices observed, urgent steps should be taken to ensure implementation of correct diagnostic and treatment policies in hospitals with TB beds.

Cross-Sectional Studies↗
PubMed2003

IARC carcinogens reported in cigarette mainstream smoke and their calculated log P values.

Cigarette smoke is a complex aerosol of minute liquid droplets (termed the particulate phase) suspended within a mixture of gases (CO(2), CO, NO(x), etc.) and semi-volatile compounds. The International Agency for Research on Cancer (IARC) has classified a number of the chemical constituents reported in cigarette mainstream smoke (MS) as carcinogens. Previously, we published a series of historical reviews reporting that 11 IARC Group 1 (known human), nine Group 2A (probable human) and 48 Group 2B (possible human) carcinogens have been observed in MS. Here, we expand the list of IARC classified carcinogens from 68 to 81 compounds (11 Group 1, 14 Group 2A and 56 Group 2B) reported in MS. A number of the IARC compounds reported in MS are found in the vapor phase including three Group 1, eight Group 2A and 18 Group 2B constituents. Several IARC MS compounds are found in both the vapor and particulate phases including two in Group 1, one in Group 2A and one in Group 2B. Forty-eight IARC MS carcinogens are found in the particulate phase only. Lipophilicity, as determined by the base 10 logarithm of the calculated octanol-water partition coefficient and denoted as Clog P, is reported for each of the 71 non-metallic MS IARC carcinogens. Clog P correlates with a number of biological activities including in vitro mutagenicity and carcinogenicity in rodents, and in the absence of any additional toxicological or epidemiological data, a high log P compound is more likely to be carcinogenic than a low log P compound.

Animals↗
PubMed2003

Nutritional evaluation and shelf life studies of papads prepared from wheat-legume composite flours.

The present study was carried out to develop papads from wheat and legume blends and to analyze them for organoleptic acceptability, nutritional quality, and keeping quality. Papad is a dehydrated product prepared from dhals or rice. A firm but pliable dough is made from the flours of dhals or rice with addition of suitable seasoning. It is shaped into balls, rolled out thin, dried and toasted over open fire so as to give a light, crisp product. Mung flour papads were kept as control and wheat flour, chickpea flour, and pea flour were used to supplement mung flour papads. Three different proportions (10, 20, 30%) of each flour were used to supplement Mung flour. Papads with wheat flour (10%), chickpea flour (20%), and pea flour (10%) level of supplementation were found to be most acceptable and these papads were subjected to nutritional evaluation. Protein content significantly increased on supplementation with legume flours at all levels. Fat content was significantly higher in chickpea flour supplemented papads. Ash content varied significantly from 10.17 to 10.78% in papads. Total carbohydrates decreased significantly on supplementation with chickpea flour. Copper content increased significantly on supplementation. A significant decrease in phytic acid and trypsin inhibitor of supplemented papads was found. In vitro protein digestibility significantly increased on supplementation but a significant decrease in in vitro starch digestibility was found in supplemented papads. Storage studies showed that chickpea flour and pea flour supplemented papads can be stored safely for 60 days and wheat flour supplemented papads for 30 days both at room and refrigeration temperatures.

Digestion↗
PubMed2002

Risk factors associated with default, failure and death among tuberculosis patients treated in a DOTS programme in Tiruvallur District, South India, 2000.

OBJECTIVE: To identify risk factors associated with default, failure and death among tuberculosis patients treated in a newly implemented DOTS programme in South India. DESIGN: Analysis of all patients registered from May 1999 through April 2000. A community survey for active tuberculosis was underway in the area; patients identified in the community survey were also treated in this programme. RESULTS: In all, 676 patients were registered during the period of the study. Among new smear-positive patients (n = 295), 74% were cured, 17% defaulted, 5% died and 4% failed treatment. In multivariate analysis (n = 676), higher default rates were associated with irregular treatment (adjusted odds ratio [AOR] 4.3; 95%CI 2.5-7.4), being male (AOR 3.4; 95%CI 1.5-8.2), history of previous treatment (AOR 2.8; 95%CI 1.6-4.9), alcoholism (AOR 2.2; 95%CI 1.3-3.6), and diagnosis by community survey (AOR 2.1; 95%CI 1.2-3.6). Patients with multidrug-resistant tuberculosis (MDR-TB) were more likely to fail treatment (33% vs. 3%; P < 0.001). More than half of the patients receiving Category II treatment who remained sputum-positive after 3 or 4 months of treatment had MDR-TB, and a large proportion of these patients failed treatment. Higher death rates were independently associated with weight <35 kg (AOR 3.8; 95%CI 1.9-7.8) and history of previous treatment (AOR 3.3; 95%CI 1.5-7.0). CONCLUSIONS: During this first year of DOTS implementation with sub-optimal performance, high rates of default and death were responsible for low cure rates. Male patients and those with alcoholism were at increased risk of default, as were patients identified by community survey. To prevent default, directly observed treatment should be made more convenient for patients. To reduce mortality, the possible role of nutritional interventions should be explored among underweight patients.

Adult↗
PubMed2001

Stereocontrolled synthesis of the diene and triene macrolactones of oximidines I and II: organometallic coupling versus standard macrolactonization.

[structure: see text]. Stereocontrolled construction of the 12-membered diene and triene lactones 1, 2, and 3, characteristic of the antitumor agent oximidines I and II, are reported and were based on an intramolecular Castro-Stephens coupling for the construction of a cyclic enyne or dienyne followed by stereoselective reduction of the cyclic alkyne for introduction of the cis-olefin of the targets. A comparison of the effectiveness of this protocol is made with standard macrolactonization.

Antineoplastic Agents↗
PubMed2001

Radical toxicity of phenols: a reference point for obtaining perspective in the formulation of QSAR.

In this report we discuss some of the surprising ways phenols interact in vivo and how some of their toxic activity can be understood in terms of QSAR and in fact can be related via electronic terms to be similar to processes of simple chemical reactions. A simple two-term QSAR is found to be a good predictor of estrogenic toxicity. However, it is also shown that even the simplest of phenols can yield quite unexpected results than can be elucidated via QSAR. We still have a long way to go before we can predict under what conditions a phenol will produce toxic effects such as cancer and how much phytophenols one can consume before reaping a toxic reaction.

Free Radicals↗
PubMed2001

Searching for allosteric effects via QSARs.

A study of our database of 7,000 QSARs involving chemical-biological interaction uncovered 11 examples where the QSARs all contain inverted parabolas based on molecular refractivity. That is, biological activity first decreases with increase in MR and then increases. Two of the examples are for enzymes: cyclooxygenase and trypsin. The others are for various receptors. The results seem to be best rationalized by the larger compounds inducing a change in a receptor unit that allows for a new mode of interaction.

Allosteric Regulation↗
PubMed2001

Possible allosteric effects in anticancer compounds.

We have found in this report, and an earlier one, that in a variety of instances an inverted parabolic relationship between biological activity and CMR or logP is observed. That is, activity first decreases as CMR or logP increases and then turns about and increases. This could be attributed to the ligands causing a change in the receptor structure. The present report considers QSAR for a variety of resistant and sensitive cancer cells.

Antineoplastic Agents↗