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Biomedical subjects

M Kumar

Publications and source records attributed to M Kumar.

At least 19 recordsLinked to original sources
PubMed2007

A randomized controlled trial of lamivudine to treat acute hepatitis B.

UNLABELLED: The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40). Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin > or = 10.0 mg/dL; and (3) international normalized ratio (INR) > or = 1.6. At week 4, HBV DNA levels were significantly lower (P = 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti-HBs titers (P = 0.096). All HBeAg-positive patients in both groups lost e antigen and anti-HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively (P = 0.132). CONCLUSION: Though lamivudine causes a greater decrease in levels of HBV DNA, it does not cause significantly greater biochemical and clinical improvement as compared to placebo in patients with acute hepatitis B.

Acute Disease↗
PubMed2006

A novel dodecapeptide from a combinatorial synthetic library exhibits potent antifungal activity and synergy with standard antimycotic agents.

There has been a marked expansion in the discovery of new antifungal peptides. This paper describes a novel dodecapeptide, H-Arg-Trp-Trp-Arg-D-Trp-D-Phe-Ile-D-Phe-His-Trp-Arg-Trp-NH(2), derived from a previously described nonapeptide and synthesized by the combinatorial approach. Further, interaction of this peptide with antifungals such as amphotericin B, flucytosine and fluconazole was studied by checkerboard analysis and time-kill assay to obtain the dynamic picture with respect to time. The best synergistic activity was observed with a combination of peptide and fluconazole, followed by peptide and flucytosine.

Amino Acid Sequence↗
PubMed2006

Gene therapy of diabetes using a novel GLP-1/IgG1-Fc fusion construct normalizes glucose levels in db/db mice.

Glucagon-like peptide (GLP-1), a major physiological incretin, plays numerous important roles in modulating blood glucose homeostasis and has been proposed for the treatment of type 2 diabetes. The major obstacles for using native GLP-1 as a therapeutic agent are that it must be delivered by a parenteral route and has a short half-life. In an attempt to develop a strategy to prolong the physiological t(1/2) and enhance the potency of GLP-1, a fusion protein consisting of active human GLP-1 and mouse IgG(1) heavy chain constant regions (GLP-1/Fc) was generated. A plasmid encoding an IgK leader peptide-driven secretable fusion protein of the active GLP-1 and IgG(1)-Fc was constructed for mammalian expression. This plasmid allows for expression of bivalent GLP-1 peptide ligands as a result of IgG-Fc homodimerization. In vitro studies employing purified GLP-1/Fc indicate that the fusion protein is functional and elevates cAMP levels in insulin-secreting INS-1 cells. In addition, it stimulates insulin secretion in a glucose concentration-dependent manner. Intramuscular gene transfer of the plasmid in db/db mice demonstrated that expression of the GLP-1/Fc peptide normalizes glucose tolerance by enhancing insulin secretion and suppressing glucagon release. This strategy of using a bivalent GLP-1/Fc fusion protein as a therapeutic agent is a novel approach for the treatment of diabetes.

Animals↗
PubMed2006

Permanent sensory nerve impairment following third molar surgery: a prospective study.

OBJECTIVE: This prospective study reports the proportion of permanent sensory impairment of the inferior alveolar and lingual nerves and the factors influencing such prevalence after the removal of mandibular third molars under local anesthesia. STUDY DESIGN: There were 1,087 patients with 1,087 mandibular third molars removed under local anesthesia from 1998 to 2003. Standardized data collection included the patient's name, age, gender, radiographic position of extracted tooth, grade of surgeon, proximity of the inferior alveolar nerve, and the prevalence of lingual and/or inferior alveolar nerve paresthesia. RESULTS: Inferior alveolar nerve injury was 4.1% 1 week after surgery and decreased to 0.7% after 2 years of follow-up, and alteration in tongue sensation occurred in 6.5% of patients 1 week after surgery and decreased to 1.0% after 2 years of follow-up. CONCLUSION: The experience of the operator was found to be a significant factor in determining both permanent lingual nerve (P=.022) and permanent inferior alveolar nerve paresthesia (P=.026).

Adolescent↗
PubMed2006

Heavy metal load of soil, water and vegetables in peri-urban Delhi.

Peri-urban lands are often used for production of vegetables for better market accessibility and higher prices. But most of these lands are contaminated with heavy metals through industrial effluents, sewage and sludge, and vehicular emission. Vegetables grown in such lands, therefore, are likely to be contaminated with heavy metals and unsafe for consumption. Samples of vegetables i.e., spinach (Spinacia oleracea L.) and okra (Abelmoschus esculentus L.); soil and irrigation water were collected from 5 peri-urban sites of New Delhi to monitor their heavy metal loads. While heavy metal load of the soils were below the maximum allowable limit prescribed by the World Health Organization (WHO), it was higher in irrigation water and vegetable samples. The spinach and okra samples showed Zn, Pb and Cd levels higher than the WHO limits. The levels of Cu, however, were at their safe limits. Metal contamination was higher in spinach than in okra. Spatial variability of metal contamination was also observed in the study. Bio-availability of metals present in soil showed a positive relationship with their total content and organic matter content of soil but no relationship was observed with soil pH. Washing of vegetables with clean water was a very effective and easy way of decontaminating the metal pollution as it reduced the contamination by 75 to 100%.

Abelmoschus↗
PubMed2006

Ketamine for treatment of catheter related bladder discomfort: a prospective, randomized, placebo controlled and double blind study.

BACKGROUND: Intraoperative urinary catheterization might cause postoperative catheter related bladder discomfort (CRBD). We evaluated the efficacy of ketamine as a treatment modality for CRBD. METHODS: Fifty-four, ASA physical status I and II, male and female adult patients, having CRBD after elective percutaneous nephrolithotomy were randomized into two equal groups of 27 each. In the postoperative period, patients who complained of CRBD received medication depending upon group allocation. Group 1 (Control) received placebo, Group II (Ketamine) received i.v. ketamine 250 microg kg(-1). After induction of anaesthesia patients were catheterized with a 16 Fr Foley's catheter and the balloon was inflated with 10 ml distilled water. Grading of CRBD was done as none, mild, moderate and severe by a blinded observer at 0, 1, 2 and 6 h after operation. RESULTS: Ketamine reduced the incidence of CRBD (P<0.001) at 2 and 6 h along with reduction in severity (P<0.05) at 1 h compared with control. Higher incidence of mild sedation was observed in the ketamine group (P<0.05) which was not associated with any untoward effects. Operative time and intraoperative fentanyl requirement were similar in both the groups. CONCLUSION: I.V. ketamine (250 microg kg(-1)) is an effective treatment for reducing the incidence and severity of postoperative CRBD.

Adult↗
PubMed2006

Gamma-aminobutyric acid up- and downregulates insulin secretion from beta cells in concert with changes in glucose concentration.

AIMS/HYPOTHESIS: The role of gamma-aminobutyric acid (GABA) and A-type GABA receptors (GABA(A)Rs) in modulating islet endocrine function has been actively investigated since the identification of GABA and GABA(A)Rs in the pancreatic islets. However, the reported effects of GABA(A)R activation on insulin secretion from islet beta cells have been controversial. METHODS: This study examined the hypothesis that the effect of GABA on beta cell insulin secretion is dependent on glucose concentration. RESULTS: Perforated patch-clamp recordings in INS-1 cells demonstrated that GABA, at concentrations ranging from 1 to 1,000 micromol/l, induced a transmembrane current (I(GABA)) which was sensitive to the GABA(A)R antagonist bicuculline. The current-voltage relationship revealed that I(GABA) reversed at -42+/-2.2 mV, independently of glucose concentration. Nevertheless, the glucose concentration critically controlled the membrane potential (V (M)), i.e., at low glucose (0 or 2.8 mmol/l) the endogenous V (M) of INS-1 cells was below the I(GABA) reversal potential and at high glucose (16.7 or 28 mmol/l), the endogenous V (M) of INS-1 cells was above the I(GABA) reversal potential. Therefore, GABA dose-dependently induced membrane depolarisation at a low glucose concentration, but hyperpolarisation at a high glucose concentration. Consistent with electrophysiological findings, insulin secretion assays demonstrated that at 2.8 mmol/l glucose, GABA increased insulin secretion in a dose-dependent fashion (p<0.05, n=7). This enhancement was blocked by bicuculline (p<0.05, n=4). In contrast, in the presence of 28 mmol/l glucose, GABA suppressed the secretion of insulin (p<0.05, n=5). CONCLUSIONS/INTERPRETATION: These findings indicate that activation of GABA(A)Rs in beta cells regulates insulin secretion in concert with changes in glucose levels.

Animals↗
PubMed2006

Activin receptor-like kinase 7 induces apoptosis of pancreatic beta cells and beta cell lines.

AIMS/HYPOTHESIS: Activin receptor-like kinase 7 (ALK7), a member of the type I receptor serine/threonine kinases of the TGF-beta superfamily, was recently reported to regulate cell proliferation and apoptosis. We hypothesised that ALK7 may play a role in modulating pancreatic beta cell proliferation and/or apoptosis. METHODS: We detected ALK7 expression in beta cells using RT-PCR, immunostaining and western blotting. Constitutively active, dominant negative or wild-type ALK7 was introduced into beta cells using adenoviral delivery. Proliferation was assessed using (3)H-thymidine incorporation and apoptosis was quantified using terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling detection, DNA degradation analysis and caspase-3 assays. RESULTS: Induction of constitutively active ALK7 in beta cells resulted in growth inhibition and enhanced apoptosis; no effect was seen with INS-1 cells expressing wild-type or dominant negative ALK7. Elevated glucose concentrations and fatty acid (palmitate) markedly increased expression levels of ALK7 transcripts and proteins in INS-1 and rat islets and increased beta cell apoptosis. Activation of ALK7 increased Smad2 phosphorylation, reduced protein kinase B (Akt) kinase activity and was associated with increased levels of the bioactive forms of caspase-3, whereas co-expression of constitutively active ALK7 with dominant negative Smad2 or constitutively active Akt significantly diminished ALK7-induced growth inhibition and apoptosis in INS-1 cells. Although overexpression of constitutively active Akt significantly reduced ALK7-induced growth inhibition and ALK7-enhanced beta cell apoptosis, ALK7-stimulated Smad2 phosphorylation was not affected. CONCLUSIONS/INTERPRETATION: These results suggest that the pancreatic beta cell apoptosis induced by ALK7 activation occurs via the activation of two distinct downstream pathways: the suppression of Akt activation and the activation of the Smad2-caspase-3 cascade.

Activin Receptors, Type I↗
PubMed2006

Effect of prevailing local treatment options of breast cancer on survival outside controlled clinical trials: experience of a specialist breast unit in North India.

BACKGROUND: This study aimed at analyzing different treatments of breast cancer (BC) prevalent in the region, their effect on patients' survival, and discusses the most suitable method within available resources. METHODS: The study was set up at a tertiary care hospital in north India. We retrospectively reviewed data of 473 female BC patients who attended the departments of Surgical Oncology and Radiotherapy from January 1997 to December 1999. Patients with cTNM stage IV and inoperable stage III were included; those who defaulted or were lost to follow-up were excluded. Out of 473 patients, 372 were selected. The selected patients were divided into groups on the basis of place and type of local treatment they received: (1) local excision only, (2) standard breast conservation therapy (BCT), (3) total mastectomy (TM) + axillary lymph node dissection + radiotherapy (RT), and (4) modified radical mastectomy (MRM) + RT. Data regarding recurrence and survival were analyzed in December 2005. Minimum follow-up was 6 years. RESULTS: Overall recurrence rates were significantly higher in patients operated elsewhere (P <0.0001). Of 194 operated at our Breast Unit, 25 (14.6%) of 171 MRM patients and none of 23 BCT had recurrence. Of 178 patients operated elsewhere, 44 (100%), 6 (42.9%), 41 (41%), and 8 (40%) developed recurrence in groups 1, 2, 3, and 4 respectively. Overall survival was significantly better in patients with MRM at our unit versus TM outside (93.6% vs. 80%). CONCLUSIONS: Several types of treatment from improper local excision alone, BCT, TM, to a carefully done MRM are prevalent here. Properly done, MRM yields significant local control with survival benefit and appears to remain the gold standard in management of our BC patients.

Adult↗
PubMed2006

Spatial orientation of the facial nerve in relation to parotid tumours.

OBJECTIVE: The aim of this study was to identify the distribution of parotid tumours within the gland in relation to the facial nerve branches. Documentation revealing such a relationship has not been reported previously. METHOD: A prospective study involving 111 patients was carried out over a period of 18 years in a specialist otolaryngology unit within a district general hospital. The relationship of the facial nerve to the tumour was graded into six types. The grading system was then employed to categorize each case. RESULTS: More than two-thirds of the tumours were pleomorphic adenomas. The majority of these were located in the body and not in the tail of the parotid gland. In 50 per cent of these cases, the tumour was in close association with the two major divisions of the facial nerve. In the case of Warthin's tumours, 47 per cent were located in the tail, below the lower division of the facial nerve.

Adenocarcinoma↗
PubMed2006

Predictive indicators for thyroid cartilage involvement in carcinoma of the larynx seen on spiral computed tomography scans.

OBJECTIVES: Recent studies have shown that the spiral computed tomography (CT) scan is a sensitive imaging modality for predicting neoplastic invasion of thyroid cartilage. The objectives of our study were: to assess the accuracy of pre-operative spiral CT in predicting thyroid cartilage involvement in patients with carcinoma of the larynx; and to elucidate the factors that would accurately indicate cartilage involvement. MATERIAL AND METHODS: Medical records, including spiral CT scans and pathological reports, were reviewed for 27 patients who had undergone laryngectomy in two major hospitals in south Wales. A consultant radiologist with special interest in cross-sectional imaging re-evaluated the scans to assess neoplastic involvement of the thyroid cartilage, based on definite, objective criteria. These criteria included: soft tissue asymmetry; loss of medullary space; spiky or irregular surface; distortion of cartilage framework; and abnormal soft tissue on both sides of the cartilage. The radiological findings were then correlated with the histopathological evidence of cartilage invasion by the tumour. RESULTS: Out of the 27 cases, 15 had evidence of histological invasion of thyroid cartilage. The most specific criterion to predict thyroid cartilage involvement was the presence of tumour on both sides of the cartilage (specificity of 91 per cent, sensitivity of 66 per cent). Combining two criteria increased both the sensitivity and the specificity to 86 and 91 per cent, respectively.

Carcinoma↗
PubMed2006

A score for predicting salvage and outcome in Gustilo type-IIIA and type-IIIB open tibial fractures.

Limb-injury severity scores are designed to assess orthopaedic and vascular injuries. In Gustilo type-IIIA and type-IIIB injuries they have poor sensitivity and specificity to predict salvage or outcome. We have designed a trauma score to grade the severity of injury to the covering tissues, the bones and the functional tissues, grading the three components from one to five. Seven comorbid conditions known to influence the management and prognosis have been given a score of two each. The score was validated in 109 consecutive open injuries of the tibia, 42 type-IIIA and 67 type-IIIB. The total score was used to assess the possibilities of salvage and the outcome was measured by dividing the injuries into four groups according to their scores as follows: group I scored less than 5, group II 6 to 10, group III 11 to 15 and group IV 16 or more. A score of 14 to indicate amputation had the highest sensitivity and specificity. Our trauma score compared favourably with the Mangled Extremity Severity score in sensitivity (98% and 99%), specificity (100% and 17%), positive predictive value (100% and 97.5%) and negative predictive value (70% and 50%), respectively. A receiver-operating characteristic curve constructed for 67 type-IIIB injuries to assess the efficiency of the scores to predict salvage, showed that the area under the curve for this score was better (0.988 (+/- 0.013 SEM)) than the Mangled Extremity Severity score (0.938 (+/- 0.039 SEM)). All limbs in group IV and one in group III underwent amputation. Of the salvaged limbs, there was a significant difference in the three groups for the requirement of a flap for wound cover, the time to union, the number of surgical procedures required, the total days as an in-patient and the incidence of deep infection (p < 0.001 for all). The individual scores for covering and functional tissues were also found to offer specific guidelines in the management of these complex injuries. The scoring system was found to be simple in application and reliable in prognosis for both limb-salvage and outcome measures in type-IIIA and type-IIIB open injuries of the tibia.

Adolescent↗
PubMed2006

Inactivation of escherichia coli 0157:H7 and Salmonella on mung beans, alfalfa, and other seed types destined for sprout production by using an oxychloro-based sanitizer.

The efficacy of a stabilized oxychloro-based food grade sanitizer to decontaminate seeds destined for sprout production has been evaluated. By using mung bean seeds as a model system, it was demonstrated that the sanitizer could be used to inactivate a five-strain cocktail of Escherichia coli O157:H7 or Salmonella introduced onto beans at 10(3) to 10(4) CFU/g. Salmonella was more tolerant to stabilized oxychloro than was E. coli O157:H7, with sanitizer levels of >150 and >50 ppm, respectively, being required to ensure pathogen-free sprouts. The decontamination efficacy was also found to be dependent on treatment time (>8 h optimal) and the seed-to-sanitizer ratio (>1:4 optimal). Stabilized oxychloro treatment did not exhibit phytotoxic effects, as germination and sprout yields were not significantly (P > 0.05) different as compared with untreated controls. Although human pathogens could be effectively eliminated from mung beans, the aerobic plate count of native microflora on sprouts grown from treated seed was not significantly (P > 0.05) different from the controls. The diversity of microbial populations (determined through 16S rRNA denaturing gradient gel electrophoresis analysis) associated with bean sprouts was not significantly affected by the sanitizer treatment. However, it was noted that Klebsiella and Herbasprillum (both common plant endophytes) were absent in sprouts derived from decontaminated seed but were present in control sprouts. When a further range of seed types was evaluated, it was found that alfalfa, cress, flax, and soybean could be decontaminated with the stabilized oxychloro sanitizer. However, the decontamination efficacy with other seed types was less consistent. It appears that the rate of seed germination and putative activity of sanitizer sequestering system(s), in addition to other factors, may limit the efficacy of the decontamination method.

Chlorine Compounds↗