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Biomedical subjects

M Kumar

Publications and source records attributed to M Kumar.

At least 37 records · Page 2Linked to original sources

Gene therapy for murine glycerol kinase deficiency: importance of murine ortholog.

A glycerol kinase (Gyk) knock-out (KO) mouse model permits improved understanding of glycerol kinase (GK) deficiency (GKD) pathogenesis, however, early death of affected mice limits its utility. The purpose of this work was to delay death of affected males to investigate thoroughly their phenotypes. An adenoviral vector carrying the human (Adeno-XGK) or mouse (Adeno-XGyk) GK gene was injected into KO mice within 24 h of birth. Adeno-XGK did not change KO mouse survival time despite liver GK activity greater than 100% of wild type. However, Adeno-XGyk improved KO mouse survival time greater than two-fold. These investigations demonstrate that gene replacement therapy for Gyk KO mice is more efficacious using murine Gyk than human GK. These studies expand our understanding of GKD pathogenesis in the murine model, and show that while murine GKD is more severe than in humans, GKD mice have similar metabolic disturbances to affected humans with hypoglycemia and acidemia.

Adenoviridae↗

Multiple versus single lumen umbilical venous catheters for newborn infants.

BACKGROUND: Multiple lumen umbilical venous catheters (ML-UVCs) instead of single lumen UVCs (SL-UVCs) may decrease the need for additional venous lines. Although it seems self-evident that ML-UVCs would reduce the need of additional venous lines, the rates of associated complications might be different. OBJECTIVES: To compare the effectiveness and the safety of ML-UVCs versus SL-UVCs in terms of need of additional vascular access, rates of complications, morbidity and mortality in newborn infants. SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the MEDLINE (1966 - February 2005), EMBASE (1980- February 2005), CINAHL (1982 - February 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2004) and Science Direct (subject area: medicine, journal and abstract database; 1967 to February 2005). Literature search also included a manual search of the abstracts of scientific meetings published in Pediatric Research (1990-2004). Additional citations were sought using references in articles retrieved from searches. Subject experts were contacted to identify the unpublished and ongoing studies. SELECTION CRITERIA: Randomized and quasi-randomized controlled clinical trials comparing safety and efficacy of multiple versus single lumen umbilical venous catheter in neonates (both term and preterm) who were in need of umbilical venous catheter insertion for vascular access in first four weeks of life. DATA COLLECTION AND ANALYSIS: Each review author performed data extraction independently and differences were resolved by discussion. The following outcomes were determined: total number of additional peripheral intravenous lines per baby in first week and first four weeks of life, total number of additional percutaneously and surgically placed central venous lines per baby in first four weeks of life, and other safety and efficacy measures. The treatment effect estimators used were RR, RD, and WMD when appropriate along with their 95% CI. If RD was statistically significant, then number needed to treat (NNT) or number needed to harm (NNH) was calculated. MAIN RESULTS: Three studies qualified for inclusion in this review (Khilnani 1991; Loisel 1996; Soupre 1998). There was a decrease in the ML-UVCs group in the number of additional PIVs used in the first week of life [WMD -1.42, (95% CI -1.74, -1.10), p<0.00001, number of infants (n) = 99]. There was no significant effect on the number of additional PIVs used in the first four weeks of life [MD -2.30, (95% CI -6.65, 2.05), n=36]. There was an increase in catheter malfunction in the ML-UVCs group [typical RR 3.69 (95% CI 0.99, 13.81), p=0.05; RD 0.15 (95% CI 0.03, 0.27), p=0.01; NNH was 7, 95% CI 4, 33; n=99]. The following outcomes were not significantly different in the two groups: clinical sepsis, catheter related blood stream infection, catheter-associated thrombosis, complications related to catheter malposition in heart and great vessels, NEC and early neonatal mortality. AUTHORS' CONCLUSIONS: The use of ML-UVCs in comparison to SL-UVCs in neonates is associated with decrease in the usage of PIVs in first week of life, but an increase in catheter malfunctions. As the quality of included randomized studies is poor and the estimates of clinically important complications are imprecise, no firm recommendations can be made regarding the choice of UVC. Adequately powered, properly randomized and properly blinded controlled trials are needed that address the effectiveness and safety of ML-UVCs (double and triple lumen) in comparison to SL-UVCs. These studies should also address the impact of type of catheter material.

Catheterization, Peripheral↗

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents.

BACKGROUND: The continued endeavour to design novel, non-detergent molecules that can be useful as topical, prophylactic contraceptives has led to the discovery of substituted isoxazolecarbaldehydes as a new class of compounds exhibiting both spermicidal and acrosin inhibitory activities simultaneously. METHODS: Normal human semen samples were used to detect the spermicidal and acrosin inhibitory activities of the new compounds. Lactobacillus, HeLa and Candida cultures were used to determine the safety of compounds towards normal vaginal flora, their cytotoxicity and anti-fungal activity. Supravital staining and the hypo-osmotic swelling test (HOST) were used to detect the effect on sperm membrane integrity. Nonoxynol-9 (N-9) was used as a reference standard. RESULTS: The 5- and 3-substituted isoxazolecarbaldehydes showed significant spermicidal [minimum effective concentration (MEC)=0.005-2.5%] and acrosin inhibitory (IC50=3.9-58 x 10(-4) mol/l) activities in several molecules along with weak fungicidal activity against Candida albicans. Lineweaver-Burk and Dixon plot analysis of a representative structure showed non-competitive inhibition of human acrosin enzyme, and the most potent acrosin inhibitors also considerably diminished the induction of the acrosome reaction by Ca2+ ionophore. Some compounds were found to be significantly safer than N-9 towards Lactobacillus acidophilus in vitro at their respective spermicidal MECs. In the cytotoxicity assay, the IC50 of these compounds towards the HeLa cell line was of the same order as N-9 (0.9-0.1 mmol/l); however, in contrast, the compounds exhibited only a moderate effect on sperm membrane integrity. CONCLUSIONS: This study indicates that 5- and 3-substituted isoxazolecarbaldehydes are 'first generation' multifunctional, spermicidal molecules that hold promise for development as topical contraceptives with useful associated activities that can add considerably to their effectiveness, safety and prophylaxis.

Acrosin↗

Analysis of local orientation gradients in deformed single crystals.

Grain fragmentation and local orientation gradients in deformed single crystals are characterized using electron backscatter diffraction (EBSD) to obtain statistically reliable information. Interrogation of the dislocation substructure is accomplished by extracting information gleaned from small point-to-point misorientations as measured by EBSD. Along with an estimate of the geometrically necessary dislocation (GND) content, the point-to-point deviation from an average grain orientation is described by an orientation difference vector defined in Rodrigues space. Mapping of parameters such as GND, and divergence and gradient fields created from analysis of the difference vectors provide an alternative approach to obtain quantitative information and images from EBSD data.

Journal Article↗

Benign recurrent intrahepatic cholestasis.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare cause of cholestasis in children. The disease may start in infancy or early childhood. Jaundice persists or recurs throughout life but does not lead to chronic liver disease or cirrhosis. Treatment is mostly symptomatic. The condition has not been reported in Indian children. We report an interesting case of BRIC in a 9-year-old boy who had recurrent episodes of jaundice since when he was 1 yr old.

Child↗

Modulatory influence of Adhatoda vasica Nees leaf extract against gamma irradiation in Swiss albino mice.

The radiomodulatory influence of ethanolic extract of Adhatoda vasica Nees leaf extract against radiation-induced hematological alterations in peripheral blood of Swiss albino mice was studied at various post-irradiation intervals between 6 h to 30 days. Oral administration of A. vasica leaf extract (800 mg/kg body weight) prior to whole body irradiation showed a significant protection in terms of survival percentage and hematological parameters. Mice exposed to radiation (8.0 Gy) without A. vasica leaf extract pre-treatment exhibited signs of radiation sickness like anorexia, lethargicity, ruffled hairs and diarrhoea and such animals died within 25 days post-irradiation. The dose reduction factor (DRF = 1.6) for A. vasica leaf extract was calculated from LD50/30 values. A significant decline in hematological constituents (RBCs, WBCs, Hb and Hct) was evident till day 15 and no animal could survive beyond day 25. Conversely, animals pre-treated with A. vasica leaf extract showed 81.25% survival till 30 days after exposure and a gradual recovery was noted in the hematological values. However, these hematological values remained significantly below the normal even till day 30. A significant decrease in blood reduced glutathione (GSH) content and increase in lipid peroxidation (LPO) level was observed in control animals (Radiation alone). However, A. vasica leaf extract pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level. A significant increase in the serum alkaline phosphatase activity and decrease in acid phosphatase activity was observed in A. vasica leaf extract pretreated irradiated animals during the entire period of study.

Administration, Oral↗

Acupressure for prevention of pre-operative anxiety: a prospective, randomised, placebo controlled study.

Pre-operative anxiety is associated with many unwanted effects such as increased analgesic and anaesthetic requirement, postoperative pain and prolonged hospital stay. In the present study, we investigated the effects of acupressure on pre-operative anxiety and bispectral index (BIS) values. Seventy-six adults, ASA grade I and II, undergoing elective surgery, were randomly assigned to two equal groups. Group 1 (control) received acupressure at an inappropriate site and group 2 (acupressure) received acupressure at extra 1 point. The study was conducted during the pre-operative period and the duration of the study was 40 min (acupressure was applied for 10 min and thereafter patients were observed for another 30 min). Anxiety was recorded on a visual stress scale (VSS) at the start of the study and thereafter at 10 and 40 min. BIS was recorded at 0, 2, 5, 10, 12, 15, 30 and 40 min. The VSS decreased in both groups following pressure application for 10 min: median VSS (interquartile range) were 5 (1) vs. 8 (1) in the acupressure and 7 (0) vs. 8 (1) in the control groups (p < 0.001). Both pre-operative anxiety and BIS decreased significantly during acupressure application at extra 1 point (p < 0.001). Acupressure is effective in decreasing both pre-operative anxiety and BIS; however, these effects are not sustained 30 min following release of acupressure. Further studies are needed to elucidate the duration for which acupressure is effective.

Acupressure↗

Immunolocalization of secretory proteins of Aspergillus fumigatus using monospecific polyclonal antibodies in a murine model.

The incidence of life-threatening mycoses caused by opportunistic fungi has increased dramatically in recent years with members of the genera Candida and Aspergillus being the most commonly encountered species. Prompt initiation of antifungal therapy for good prognosis of such cases is highly dependent on accurate diagnosis. The potential of metabolic antigens in the diagnosis of aspergillosis was investigated in the present study. Two proteins of 18 and 70 kDa were identified with success rate of 35% and 60% respectively based on their reactivity with patient sera of clinically diagnosed cases of aspergillosis. The antibodies raised against 70 and 18 kDa proteins in rabbits were found to be useful in detection of A. fumigatus in the kidneys of a mouse model of aspergillosis.

Animals↗

Foreign bodies in the ear: a simple technique for removal analysed in vitro.

OBJECTIVE: Foreign bodies in the ear are mainly encountered in children. This can often pose a problem especially in an accident and emergency department where a microscope or expert help is not routinely available. This paper presents a simple, safe, and effective way of ear syringing. The ease and simplicity of the procedure along with the equipment are described. METHOD AND RESULT: The equipment consists of a "disposable" sterile kit, consisting of a 20 ml syringe, saline at body temperature and 14 or 16 gauge cannula (without the needle). An in vitro experiment was conducted to calculate the pressure generated by the water jet on the eardrum. The pressure was well below the pressure required to burst a tympanic membrane, and hence this technique is safe to use. CONCLUSIONS: Ear syringing is an effective and easy way of removing most foreign bodies. A detailed history and an otoscopic examination must precede the procedure. The novel method of syringing described in this paper with the usual safeguards could be a useful adjunct in the management of this common condition.

Disposable Equipment↗

A study of chorda tympani nerve injury and related symptoms following middle-ear surgery.

This is a prospective study that looks into the prevalence of chorda tympani nerve (CTN) injury and related symptoms following varying degrees of trauma to the nerve during three common types of middle-ear operation: myringoplasty, tympanotomy and mastoidectomy. The number of patients with CTN-related symptoms varied widely between the three groups. Increased occurrence of the nerve related symptoms and a prolonged recovery time were observed in the tympanotomy group. Stretching of the nerve produced more symptomatic cases than cutting it in the myringoplasty and mastoidectomy groups. Recovery was complete in 92 percent of the symptomatic patients by 12 months. It is important to inform patients about the possibility of CTN injury during middle-ear operations, and it should also be emphasized that symptoms related to CTN injury can occur irrespective of the type of damage to the nerve.

Adolescent↗

Effect of glycaemic control on apoptosis in diabetic wounds.

OBJECTIVE: To study the effect of glycaemic control on apoptosis in chronic ulcers in diabetic patients and the differential roles of insulin and oral hypoglycaemic agents (OHAs). METHOD: Ten non-diabetic (group I) and 20 diabetic patients (groups II and III), with a wound of more than four weeks' duration, who were attending the wound clinic at University Hospital, Varanasi, India were recruited. The 10 patients in group 11 received insulin and the 10 in group III an oral hypoglycaemic agent; all had diabetic foot ulcers. Wound biopsy and other routine investigations were performed. Both DNA fragmentation and morphological changes under light microscopy (apoptotic index) were used as determinants of apoptosis. Different variables, including fasting and post-prandial blood sugar, serum low-density lipoprotein (LDL) and markers of microangiopathy, such as proteinuria and diabetic retinopathy, were compared with apoptosis. RESULTS: DNA fragmentation in groups I, II and III was 40.00 +/- 2.97, 45.26 +/- 3.21 and 60.8 +/- 3.13 respectively (p < 0.01). Near linear correlation was observed with blood sugar level, particularly post-prandial blood sugar (p < 0.05) and DNA fragmentation. DNA fragmentation was significantly correlated with serum LDL and proteinuria, and it was much greater in the OHA group than in the insulin group (p < 0.05). Similarly, in the diabetic patients with background retinopathy the DNA fragmentation was 46.50 +/- 3.42 (n=3) in the insulin group and 66.70 +/- 6.48 (n=4) in the OHA group (p < 0.05). CONCLUSION: There is a significant increase in apoptosis in diabetic wounds with poorly controlled blood sugar and microangiopathy. This increase was greater in patients on OHAs than those on insulin, and it contributes to delayed wound healing. Morphological markers do not appear to be a reliable index of apoptosis in the diabetic wound.

Administration, Oral↗

Spatial distribution of Salmonella, Escherichia coli O157:H7, and other bacterial populations in commercial and laboratory-scale sprouting mung bean beds.

The reliability of testing spent irrigation water to assess the microbiological status of sprouting mung bean beds has been investigated. In commercial trials, the distribution of opportunistic contaminants within 32 bean sprout beds (25 kg of mung beans per bin) was assessed 48 h after germination. The prevalence of generic Escherichia coli, thermotolerant coliforms, and Aeromonas in sprouts (n = 288) was 5, 11, and 39%, respectively, and 57, 70, and 79% in the corresponding spent irrigation water samples (n = 96). Contamination was heterogeneously distributed within the seedbed. In laboratory trials, beans inoculated with a five-strain cocktail of either Salmonella or E. coli O157:H7 (10(3) to 10(4) CFU/g) were introduced (1 g/500 g of noninoculated seeds) at defined locations (top, middle, or base), and the beans were then sprouted for 48 h. When seeds inoculated with pathogens were introduced at the base or top of the seedbed, the pathogens were typically restricted to these sites and resulted in 44% of the spent irrigation water samples returning false-negative results. Introducing inoculated beans into the middle or at the presoak stage enhanced the distribution of both pathogens within the subsequent sprout bed and resulted in comparable levels recovered in spent irrigation water. The study demonstrated that even though screening a single sample of spent irrigation water is more reliable than testing sprouts directly, it does not provide an accurate assessment of the microbiological status of sprouting mung bean beds. Such limitations may be addressed by ensuring that bean batches are mixed prior to use and by taking spent irrigation water samples from multiple sites at the latter stages of the sprouting process.

Agriculture↗

Microplate nitrate reductase assay versus Alamar Blue assay for MIC determination of Mycobacterium tuberculosis.

A rapid colorimetric, microplate based nitrate reductase assay (NRA) method for minimum inhibitory concentration (MIC) determination of clinical isolates of Mycobacterium tuberculosis was compared with the microplate Alamar Blue assay (MABA), presently in vogue. Reproducible results were obtained in 7 days by NRA. The NRA method was found to be inexpensive, suitable for MIC determination against M. tuberculosis and can be suggested as an ideal substitute to MABA.

Biological Assay↗

Sterilisation of extracted human teeth for educational use.

Sixty intact, non-carious and unrestored teeth extracted due to periodontal disease were used to determine the most effective method of sterilisation. The teeth were divided into six groups, each containing 10 teeth. Group 1 teeth were immersed in 10% formalin for seven days, group 2 teeth were immersed in 3% hydrogen peroxide for seven days, group 3 teeth were immersed in 2.6% sodium hypochlorite for seven days, group 4 teeth were boiled in water at 100 degrees C for 20 minutes, group 5 teeth were autoclaved at 121 degrees C at 15 lbs psi for 30 minutes, and group 6 teeth were immersed in normal saline for seven days. After the treatment, the teeth were individually inoculated into trypticase soy broth and incubated for 48 hours. A questionnaire survey was also conducted to determine the awareness of dental students regarding infection due to extracted human teeth and the common disinfection/sterilisation methods used. Autoclaving at 121 degrees C, 15 lbs psi for 30 minutes and immersion in 10% formalin for seven days were effective in disinfecting/sterilising extracted human teeth. Chemicals such as 2.6% sodium hypochlorite, 3% hydrogen peroxide and boiling in water were not effective. The results indicate that autoclaving for 30 minutes or immersion in 10% formalin for seven days could be effectively used for disinfection/sterilisation of extracted human teeth.

Dental Disinfectants↗

Carnitine supplementation for preterm infants with recurrent apnea.

BACKGROUND: Apnea of prematurity is a common problem in preterm infants in the neonatal intensive care setting (NICU), often delaying their discharge home or transfer to a step down unit. Premature infants are at increased risk of carnitine deficiency. Carnitine supplementation has been used for both prevention and treatment of apnea. OBJECTIVES: To determine whether treatment with carnitine will reduce the frequency of apnea, the duration of ventilation and the duration of hospital stay in preterm infants with recurrent apnea. SEARCH STRATEGY: Computerised searches were carried out by two reviewers independently. Searches were made of MEDLINE (1966 to May 2004), EMBASE (1980 to May 2004), CINAHL (1982-2004 June 2004,1st week), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), abstracts of annual meetings of the Society for Pediatric Research (1995-2004), and contacts were made with the subject experts. SELECTION CRITERIA: Only randomized or quasi-randomized treatment trials of preterm infants with a diagnosis of recurrent apnea of prematurity were considered. Trials were included if they involved treatment with carnitine compared to placebo or no treatment, and measured at least one of the following outcomes: failure of resolution of apneas, the duration of ventilation and the duration of hospital stay. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the papers for inclusion criteria and quality. Corresponding authors were contacted for further information where needed. MAIN RESULTS: No eligible trials were identified. REVIEWERS' CONCLUSIONS: Despite the plausible rationale for the treatment of apnea of prematurity with carnitine, there are insufficient data to support its use for this indication. Further studies are needed to determine the role of this treatment in clinical practice.

Apnea↗

Prediction of progression in pTa and pT1 bladder carcinomas with p53, p16 and pRb.

Currently available prognostic tools appear unable to adequately predict recurrence and progression in non muscle-invasive bladder carcinomas. We aimed to assess the prognostic value of immunohistochemical evaluation of the cell cycle markers p53, p16 and pRb. Paraffin blocks were obtained from 78 cases of pTa and pT1 transitional cell carcinomas, for which long-term follow-up was available. Representative sections were stained using antibodies against p53, p16 and pRb. Altered marker expression was found in 45, 17 and 30% of cases, respectively. Concurrent alteration of two or three markers occurred in 19% of cases, and was significantly associated with grade and stage. In univariate survival analysis, the concurrent alteration of any two markers was significantly associated with progression. The greatest risk was produced by alteration of both p53 and p16, which increased the risk of progression by 14.45 times (95% confidence interval (CI) 3.10-67.35). After adjusting for grade and stage, this risk was 7.73 (CI 1.13-52.70). The markers did not generally predict tumour recurrence, except in the 25 pT1 tumours. In these, p16 alteration was associated with a univariate risk of 2.83 (CI 1.01-7.91), and concurrent p53 and p16 alteration with a risk of 9.29 (CI 1.24-69.50). Overall, we conclude that the immunohistochemical evaluation of p53 and p16 may have independent prognostic value for disease progression, and may help guide management decisions in these tumours.

Adult↗