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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 37 records · Page 2Linked to original sources

Mechanised one-day fat clearance method to increase the lymph node yield in rectal cancer specimens.

The Royal College of Pathologists' guidelines for reporting colorectal cancer state that all lymph nodes in a colorectal cancer specimen should be sampled, regardless of site or size. The only means by which one can be certain that all nodes have been sampled is to clear the fat and visualise the lymph nodes. Methods of fat clearance have been available for many years, but few are acceptable in routine practice. Here, a simple, effective and economical solution to the problem is described, which should be amenable to any laboratory with a spare or back-up tissue-processing machine.

Adipose Tissue↗

Early carbon monoxide intoxication: happy to be poisoned?

Carbon monoxide poisoning is the commonest cause of death by poisoning in the UK and chronic exposure is thought to be a frequently missed diagnosis. Early recognition of carbon monoxide poisoning is vital to institute prompt treatment and to prevent exposure to others. An incident of mass exposure to carbon monoxide is presented where euphoria, lasting several hours, was the only symptom reported in approximately one quarter of the casualties. This has not been reported previously and we believe that mild carbon monoxide intoxication should be included in the list of differential diagnoses of inappropriate euphoria.

Adolescent↗

Vapor-phase photo-oxidation of methanol over nano-size titanium dioxide clusters dispersed in MCM-41 host material part 2: catalytic properties and surface transient species.

We report in this paper on the ultraviolet-assisted vapor-phase oxidation of methanol at room temperature, with the help of nano-size clusters of titanium dioxide dispersed in an MCM-41 silicate matrix. The surface species formed during the adsorption/oxidation of methanol and the transformation that they undergo as a result of ultraviolet irradiation were monitored using in-situ Fourier transform infrared and thermal desorption spectroscopy techniques. Parallel experiments conducted on TiO2/MCM, bulk titania, and pristine MCM-41 samples helped in identifying the individual role of titanium dioxide and host matrix in these processes. The photo-catalytic oxidation of methanol, at concentrations of 0.1 to 1.1 mol% in air, gave rise to formation of CO2 and H2O as products, for both the TiO2/MCM and bulk TiO2 samples. No such reaction occurred on titania-free MCM. Furthermore, the rate of reaction depended upon the TiO2 content of a sample and also on the concentration of methanol in reaction mixture. Thus, the rate of conversion increased progressively with the increase in TiO2 loading from 5 to 21 wt% in TiO2/MCM samples, particularly for the experiments with high concentration of methanol. For low methanol concentration (0.1 mol%) in air, the effect of titania content in MCM was very small. The specific activity (per g of titania) of a sample, on the other hand, showed an inverse relationship with the loading of titanium dioxide in a sample. Infrared and temperature-programmed desorption results revealed that the mode of CH3OH adsorption and the reactivity of the transient species formed during the oxidation process were independent of the size of dispersed titania particles. Thus, the particles of approximately 2-6 nm size, present in TiO2/MCM, exhibited a chemisorption behavior similar to that of the bulk titania. The results of the present study provide strong evidence that the hydroxyl groups, both on the host matrix and at the titania sites, participate independently in the formation of methoxyl groups and at the same time promote the heterogeneous photo-catalytic oxidation of methanol molecules via formation of transient formate groups. Our results also show that the effect of titania crystallite size in the photo-catalytic properties relate mainly to the larger surface area and hence to the enhanced number of chemisorption sites, rather than to the changes in electronic properties.

Catalysis↗

Karyotypic analysis of adult pluripotent stem cells.

Three categories of precursor cells have been identified in postnatal mammals: tissue-committed progenitor cells, germ layer lineage-committed stem cells and lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate precursors of differentiated tissues. Germ layer lineage stem cells can be induced to form multiple cell types belonging to their respective ectodermal, mesodermal, and endodermal embryological lineages. Pluripotent stem cells will form somatic cell types from all three primary germ layer lineages. Progenitor cells demonstrate a finite life span before replicative senescence and cell death occur. Both germ layer lineage stem cells and pluripotent stem cells are telomerase positive and display extensive capabilities for self-renewal. Stem cells which undergo such extensive replication have the potential for undergoing mutations that may subsequently alter cellular functions. Gross mutations in the genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear aberrant. This study was designed to determine whether any gross genomic mutations occurred within the adult pluripotent stem cells. Karyotypic analysis was performed using pluripotent stem cells purified from adult male rats using established procedures. Giemsa Banding was used in conjunction with light microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase spreads have been analyzed. We found that the metaphase spreads averaged 42 chromosomes and concluded that these pluripotent stem cells isolated from adult rats have a normal karyotype.

Animals↗

Dissociation of clinical and laboratory diagnosis in hypothyroidism.

AIMS OF THE STUDY: To assess the significance of clinical versus biochemical diagnosis of hypothyroidism using a clinical scoring index and optimize the therapeutic dose of levothyroxine in Indian patients. METHODOLOGY: Three hundred and eighty eight cases of primary hypothyroidism (male:female ratio 1:5.8) were clinically classified as hypothyroid, euthyroid or inconclusive by Billewicz score. TSH estimation was repeated at 6-8 week intervals and appropriate adjustments in levothyroxine dosage made till the TSH was within the normal range. RESULTS: Of 388 biochemically confirmed hypothyroid subjects less than one fourth (21.6%) could be classified as hypothyroid, almost one half were euthyroid (48.4%) and the remaining (29.9%) fell in the inconclusive category according to Billewiz score. Of 227 patients who returned for complete follow up there was a positive correlation of replacement dose with age and initial weight in females, but not in males. Baseline TSH values were not found to have a significant correlation with the initial dose. The mean replacement dose of levothyroxine (T4) in our subjects was 109.4 +/- 24.05 microg/d (range 1.25-3.84 microg/kg). CONCLUSION: Clinical parameters alone fare poorly in establishing an unequivocal diagnosis of hypothyroidism. A biochemical confirmation is mandatory. The replacement done of T4 was found to be independent of the basal TSH level.

Adolescent↗

Primary amyloidosis presenting with predominant lymphnodal masses.

A 50 year young farmer presented with clinical features of bilateral carpal tunnel syndrome and generalized lymphadenopathy including paratracheal and retroperitoneal lymphodes. The histological diagnosis confirmed primary amyloidosis of lymphnodes. Presentation of primary amyloidosis as lymphnodal mass with deposition of amyloid in carpal tunnel is extremely rare and can only be diagnosed by histochemistry. The clinical response to drugs is variable and needs surgical intervention for decompressive therapy which can improve the symptoms of carpal tunnel syndrome.

Amyloidosis↗

Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor.

The etiology of fetal membrane (FM) rupture is unknown. A hypothesis that the FM weakens by a process of collagen remodeling and apoptosis to facilitate rupture has been proposed. Human FMs reportedly exhibit a zone of altered histology, postulated to be the FM rupture site, but concomitant FM weakness has not been demonstrated. We hypothesized that a discrete zone of FM with marked weakness, histological change, and evidence of remodeling and apoptosis, develops in late gestation in the FM overlying the cervix. FM tissue from women undergoing prelabor cesarean delivery were perioperatively marked to identify the FM overlying the cervix, cut with a procedure that facilitates remapping the rupture strength of FM pieces to their former location and orientation on a three-dimensional model, and tested for strength. A 10-cm FM zone centered at the cervical mark was compared with the remaining FM. Mean rupture strength within the cervical zone was 55% of the remaining FM. The cervical zone also exhibited increased MMP-9 protein, decreased tissue inhibitor of metalloproteinases-3 (TIMP-3) protein, and increased PARP cleavage coincident with the previously reported zone of altered histology. A discrete zone of weakness is present in term prelabor FMs overlying the cervix and has biochemical characteristics consistent with tissue remodeling and apoptosis.

Apoptosis↗

Adjuvant biofeedback following anal sphincter repair: a randomized study.

AIMS: To evaluate the impact of adjuvant biofeedback following sphincter surgery. METHODS: Thirty-eight patients were randomized into sphincter repair or sphincter repair plus biofeedback groups. Outcome measures included a symptom questionnaire, patient's rating of satisfaction with continence function and improvement, change in continence score, quality of life and anorectal physiology. Endoanal ultrasonography was also performed pre- and post-operatively. RESULTS: Immediately following surgery, there was no statistically significant difference in any of the functional or physiological variables between the groups. Continence and patient satisfaction scores improved with a mean difference of -0.48 (95% CI: -3.30-2.33, P = 0.73) and 1.03 (95% CI: -1.40-3.46, P = 0.39), respectively. Only the difference in embarrassment scores reached statistical significance (mean) 0.56 (95% CI: 0.12-0.99, P = 0.014). Resting and squeeze pressures also improved. Thirteen of 14 in the biofeedback and 11 of 17 (control) reported symptomatic improvement. In the biofeedback group, although not statistically significant continence and satisfaction scores improved and were sustained over time. In the control group, continence and satisfaction scores changed little between 3 and 12 months (P = NS). Quality of life measures improved within the biofeedback group but there was no statistical difference between the groups. CONCLUSION: Following surgery continence function improves in all patients but adjuvant biofeedback therapy improves quality of life and maintains symptomatic improvement over time.

Adult↗

Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the acetylcholinesterase inhibitor donepezil in a placebo-controlled trial in patients with mild cognitive impairment (MCI). METHODS: A total of 270 patients with MCI were enrolled in a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive donepezil (n = 133; 5 mg/day for 42 days, followed by forced dose escalation to 10 mg/day) or placebo (n = 137). Primary efficacy measures were the New York University (NYU) Paragraph Delayed Recall test and the Alzheimer disease (AD) Cooperative Study Clinician's Global Impression of Change for MCI (ADCS CGIC-MCI). Secondary efficacy measures included the modified AD Assessment Scale-cognitive subscale (ADAS-cog), the Patient Global Assessment (PGA), and additional neuropsychologic measures. Efficacy analyses were performed on intent-to-treat (ITT) and fully evaluable (FE) populations. RESULTS: Primary efficacy measures of the NYU Paragraph Recall test and the ADCS CGIC-MCI did not show significant treatment effects in the ITT population. Some secondary measures showed effects favoring donepezil. More donepezil-treated patients showed improvements in ADAS-cog total scores, in tests of attention and psychomotor speed, and in PGA scores. More donepezil-treated than placebo-treated patients experienced adverse events, most of which were mild to moderate and transient. CONCLUSION: Although significant treatment effects were not seen in the primary efficacy measures, outcomes on secondary measures suggest promising directions for further evaluation of donepezil treatment in patients with MCI.

Aged↗

Diverticular disease of the colon: ethnic differences in frequency.

BACKGROUND: Colonic diverticular disease is more common in Western populations than in developing countries. AIM: To determine whether the frequency of colonic diverticular disease is different in British patients of Indian-subcontinent Asian origin compared with other ethnic groups. METHODS: All colonoscopies performed over a 3-year period in a London hospital were studied. Patients of Indian-subcontinent Asian origin were identified by name. RESULTS: Five of 134 Indian-subcontinent Asian males (4%) had colonic diverticular disease, compared with 278 of 1268 patients of other ethnic groups (22%; P < 0.001). Five of 91 Indian-subcontinent Asian females (6%) had colonic diverticular disease, compared with 333 of 1486 patients of other ethnic groups (23%; P < 0.001). Although patients of Indian-subcontinent Asian origin (54.8 +/- 15.8 years) were younger than those of other ethnic groups (60.3 +/- 17.8 years; P < 0.0001), the ethnic difference in the frequency of diverticular disease persisted even when age was taken into account. CONCLUSION: There is a lower frequency of colonic diverticular disease in Indian-subcontinent Asians presenting for colonoscopy, compared with other ethnic groups. This cannot be explained by sex or age differences. Our findings require confirmation, but may provide opportunities for research into the aetiology of colonic diverticular disease.

Adult↗

Functional and physiological outcome following transanal repair of rectocele.

BACKGROUND: Rectoceles are traditionally repaired transvaginally and sexual dysfunction can be a significant complication. The aim of this study was to evaluate the functional and physiological outcome following transanal repair of rectoceles. METHODS: Forty-five patients of mean age 57.1 (range 34-78) years with a symptomatic anterior rectocele, selected by contrast retention greater than 15 per cent on isotope defaecography, underwent transanal repair of rectocele. Preoperative and postoperative symptoms were assessed by means of a questionnaire. A proportion of patients underwent anorectal physiology and isotope defaecography before and after surgery. RESULTS: Median(range) follow-up was 24 (2-50) months. One patient developed a wound infection after surgery. Thirty-five patients reported an excellent, good or fair result, with seven reporting a moderate and three a poor result. There was a reduction in incomplete evacuation (P < 0.001) confirmed by isotope defaecography (mean(s.d.) rectal emptying before surgery 57(14) per cent versus 76(9) per cent after surgery; P = 0.020), and a reduction in vaginal (P < 0.001) and perineal (P = 0.004) digitation. Symptomatic feeling of prolapse (vaginal bulging) was significantly improved (P < 0.001). There was no increase in incontinence (P = 0.688). Resting and squeeze anal canal pressures were unchanged after operation. Surgery did not result in sexual dysfunction. CONCLUSION: Transanal repair of rectocele is a safe alternative to posterior colporrhaphy. It provides improvement in symptoms, reflected by anatomical improvement with minimal complications and no increase in dyspareunia.

Adult↗

Strictureplasty.

BACKGROUND: Advances in the use of bowel-sparing surgery for Crohn's disease have led to the development of strictureplasty as an important technique to conserve small bowel length and reduce morbidity associated with malabsorption. METHODS: A literature review of long-term studies on strictureplasty was undertaken, and evidence of its safety and efficacy was evaluated. RESULTS: The safety and efficacy of strictureplasty is confirmed in retrospective studies carried out over a period of 5-10 years, particularly when employed in patients at risk of short bowel syndrome, but certain questions regarding bowel function and disease activity after surgery remain unanswered. There is also concern that diseased tissue is left in situ after strictureplasty; this tissue has the potential for malignant transformation in the long term. CONCLUSION: Strictureplasty has been used in surgery for Crohn's disease for the past 25 years. Studies have proven its efficacy in the treatment of carefully selected patients at risk of malabsorption owing to short bowel syndrome.

Crohn Disease↗

Average versus maximum grip strength: which is more consistent?

The average of three consecutive measurements is the most frequently used method for grip strength assessment. The purpose of this study was to compare the consistency of the maximum value with that of the average value of three consecutive measurements of grip strength. One hundred healthy volunteers participated in this study. Three measurements of grip strength were taken on two occasions separated by 2 weeks. For each hand, two average values and two maximum values were obtained. Ninety-five per cent limits of agreement for the average method were - 8.3 (-23%) to +7.2 (+20%)kg and for the maximum method were - 8.8 (-23%) to + 8 (+21%)kg. Both methods of grip strength assessment were found to be highly consistent with no statistically significant difference.

Adult↗

Optical characterization of mammalian tissues by laser reflectometry and Monte Carlo simulation.

The optical characterization of various goat organs/tissues, by measurement of the spatial variation of the diffuse reflectance from the surface by laser multi-probe reflectometer, is carried out. For determination of the optical parameters, these profiles are matched by iterative procedures with that obtained by Monte Carlo simulation by best-fit procedure with chi value 0.99. The first set of measurements is carried out with milk phantom. Thereafter, the absorption and scattering coefficients and anisotropy parameter of goat's heart, lungs, kidney, liver, spleen, skeletal muscle, brain and adipose tissues are measured. These parameters vary over a wide range, which is in agreement with results reported by others. Based on these data, their laser scattering profiles along the depth in terms of depth of penetration (DP) and maximum scattered beam width (MSBW) are determined. These are maximum (0.030 and 0.038 m) for kidney and minimum (0.007 and 0.006 m) for spleen, respectively. The backscattered intensity measured 0.002, 0.004 and 0.006 m away from the beam entry point shows the maximum contribution from the respective depths, irrespective of the nature of the organs/tissues.

Animals↗

Hydrogen peroxide induced apoptosis in amnion-derived WISH cells is not inhibited by vitamin C.

Increased reactive oxygen species (ROS) have been identified as a potential cause of remodelling and apoptotic change in fetal membrane. Vitamin C has been suggested as a therapeutic agent to prevent ROS induced chorio-amnion apoptosis. The purpose of this study was to determine whether hydrogen peroxide (HP), a ROS, initiates apoptosis in the WISH cell model and whether vitamin C would inhibit HP induced apoptosis. HP induced apoptosis in WISH cells; as assessed by cytochrome-c release from mitochondria, Poly-(ADP-ribose)-Polymerase (PARP) cleavage, nuclear matrix protein (NMP) release and DNA fragmentation analysis. HP induced dose dependent release of cytochrome-c, PARP cleavage, NMP release, and DNA fragmentation. HP also increased PGE(2)release in parallel with apoptosis in WISH cells, in a manner similar to that reported with other apoptotic agents. Vitamin C pre-incubation caused cytochrome-c release earlier, and at lower HP doses, than HP alone. It had no effect on HP induced PARP cleavage, but enhanced DNA fragmentation, and induced NMP release on its own. Vitamin C partially suppressed dose dependent HP induced PGE(2)release. We conclude that HP causes apoptosis in WISH cells and vitamin C pre-incubation does not inhibit, and may accelerate and exacerbate, HP induced apoptosis.

Amnion↗

Vitamin C exacerbates hydrogen peroxide induced apoptosis and concomitant PGE2 release in amnion epithelial and mesenchymal cells, and in intact amnion.

This study was undertaken to investigate the effect of hydrogen peroxide (HP), a reactive oxygen species, and vitamin C, an antioxidant, on apoptosis and prostaglandin (PGE(2)) release in human amnion epithelial and mesenchymal cells, and intact amnion. Amnion cells and explants were incubated with and without HP and vitamin C. Cytoproliferation assay for viability, DNA fragmentation and PARP cleavage for apoptosis, EIA for PGE(2), and western blots for cyclooxygenases (COX) were performed. In amnion cells and explants, HP (0-5 mm) induced dose dependent apoptosis as per DNA fragmentation and PARP cleavage. HP (0-0.5 mm) also induced PGE(2)release concomitant with apoptosis in both cell types. In amnion explants, HP (0-10 mm) induced COX-2 protein and PGE(2)release concomitant with apoptosis. Vitamin C (0.01-10 mm), alone, enhanced epithelial but inhibited mesenchymal cell viability. It induced PGE(2)release in amnion explants. Vitamin C (1 mm) failed to inhibit HP induced apoptosis, but instead exacerbated it in epithelial and mesenchymal cells, and amnion explants. Vitamin C (0-10 mm) enhanced HP induced PGE(2)in mesenchymal cells. HP induces concomitant apoptosis and PGE(2)release in amnion epithelial and mesenchymal cells, and in intact amnion explants. HP induced apoptosis is not inhibited but enhanced by vitamin C.

Amnion↗

Electrophysiological and pharmacological characterization of K+-currents in muscle fibres isolated from the ventral sucker of Fasciola hepatica.

Fibres isolated from the ventral sucker of Fasciola hepatica were identified as muscle on the basis of their contractility, and their actin and myosin staining. They were voltage-clamped at a holding potential of -40 mV and depolarization-activated outward currents were characterized both electrophysiologically and pharmacologically. Activation was well fitted by a Boltzmann equation with a half-maximal potential of + 9 mV and a slope factor of -14.3 mV, and the kinetics of activation and deactivation were voltage-sensitive. Tail current analysis showed that the reversal potential was shifted by +46+/-3 mV when E(K) was increased by 52 mV, confirming that this was a K+-current with electrophysiological characteristics similar to delayed rectifier and Ca2+-activated K+-currents in other tissues. The peak current at + 60 mV was inhibited by 76+/-6% by tetrapentylammonium chloride (1 mM) and by 84+/-7% by Ba2+ (3 mM), but was completely resistant to block by tetraethylammonium (30 mM), 3,4-diaminopyridine (100 microM) and 4-aminopyridine (10 mM). Penitrem A, a blocker of high-conductance Ca2+-activated K+-channels reduced the current at +60 mV by 23+/-5%. When the effects of Ca2+-channel blocking agents were tested, the peak outward current at + 60 mV was reduced by 71+/-7% by verapamil (30 microM) and by 59+/-4% by nimodipine (30 microM). Superfusion with BAPTA-AM (50 microM), which is hydrolysed intracellularly to release the Ca2+-buffer BAPTA, also decreased the current by 44+/-16%. We conclude that voltage-and Ca2+-sensitive K+-channels are expressed in this tissue, but that their pharmacology differs considerably from equivalent channels in other phyla.

Actins↗