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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 451 records · Page 25Linked to original sources
PubMed1999

Variation in the isocentre of a Philips linear accelerator (SL-20) used for stereotactic radiosurgery/stereotactic radiotherapy.

Stereotactic irradiation, either in the form of stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) of brain lesions requires high precision and submillimetre accuracy in the isocentre, the main determinants being gantry and couch rotations. It is thus necessary to evaluate the isocentre variation due to gantry and couch rotations in the particular setup for SRS/SRT. This paper describes variation in the isocentre of a Philips (now Elekta) SL-20 linear accelerator modified for adapting a couch-mounted radiosurgery system. By considering the isocentre as defined by a mechanical index as the standard, the variations in the isocentre of the linear accelerator were independently measured for the gantry and for couch rotations. The variation in the isocentre for gantry rotation was found to be between 0.1 mm and 0.9 mm, conforming to the submillimetre accuracy required for SRS/SRT. However, the isocentre variation due to couch rotation varied considerably, possibly because the couch is of the RAM type. The isocentre variation due to couch rotation is rectified by microadjusting the couch mount at the time of treatment using a laser target localizing frame. It is our conclusion that a modified linear accelerator can be used for performing SRS/SRT after careful and separate evaluation of the isocentre stability due to gantry and couch rotations.

Brain Neoplasms↗
PubMed1999

Gene repair using chimeric RNA/DNA oligonucleotides.

An experimental strategy has been developed for the site-specific alteration of genomic DNA. The approach is based on the observation that oligonucleotides containing complementary RNA/DNA hybrid regions are more active than duplex DNA in homologous pairing reactions in vitro. The chimeric molecules are designed with a homologous targeting sequence comprised of a DNA region flanked by blocks of 2'-O-methyl RNA residues (the chimeric strand), its complementary all-DNA strand, thymidine hairpin caps, a single-strand break, and a double-stranded clamp region. The oligonucleotide can align in perfect register with a genomic target except for the designed single base pair mismatch, which is recognized and corrected by harnessing the cell's endogenous DNA repair system. The mechanism of repair has been studied using mammalian cell-free extracts and bacterial systems and has revealed a mismatch correction pathway distinct from homologous recombination. The chimeric molecules have been demonstrated to be effective in the alteration of single nucleotides in episomal and genomic DNA in cell culture, as well as genomic DNA of cells in situ. This is a potentially powerful strategy for gene repair for the myriad hepatic genetic diseases caused by point mutations.

Animals↗
PubMed1999

Aneurysmal bone cysts of the skull: report of three cases.

We report three cases of aneurysmal bone cysts of the skull, a rare site for this type of lesion. The patients were 11, 15 and 44 years old, the duration of symptoms being 72, 24 and 6 months, respectively. The lesions were painful in two cases. Computed tomography in all three cases was suggestive of aneurysmal bone cysts. En bloc excision of the bone cysts demonstrated no dural involvement. There were neither mitotic figures nor any other associated pathology on histopathological examination. Two cases were recurrence free at follow-up of 8 months and 3 years, and the third patient was thought to be recurrence free at 2 years.

Adolescent↗
PubMed1999

5-Fluorouracil induces defects in platelet function.

Platelet factor-3 (PF(3)) availability and platelet aggregation to ADP (4 micromol/l) and adrenaline (1.2 micromol/l) were evaluated in patients being treated with 5-fluorouracil (5-FU) for gastrointestinal malignancy. It produced a significant reduction in platelet aggregation and platelet factor-3 (PF(3)) availability ( P < 0.001) without being associated with thrombocytopenia. The changes in platelet aggregation occurred during the first week of chemotherapy and continued with subsequent courses. This acquired abnormality may be responsible for a haemorrhagic diathesis even without obvious thrombocytopenia. Study of platelet function is important and may be considered to assess the haematological toxicity in patients being treated with systemic 5-FU therapy.

Journal Article↗
PubMed1999

Enhanced thermogenesis in rats by a composite Indian herbal preparation-I and its mechanism of action.

OBJECTIVE: A composite Indian herbal preparation-I (CIHP-I) containing ingredients derived from 7 different plants and asphalt was tested for its adaptogenic activity and its mechanism of action was investigated. DESIGN: CIHP-I was tested using the cold-hypoxia-restraint (C-H-R) animal model in which the restrained rats were exposed to 5 degrees C at 428 mm Hg atmospheric pressure. Rectal temperature (Trec) of the rats was continuously monitored during the exposure and the recovery periods. The time for fall of Trec to 23 degrees C and its recovery to 37 degrees C were used as indices of endurance and the adaptogenic activity. Carbohydrate and lipid parameters were investigated to find out the nature of fuel being used during thermogenesis. RESULTS: After 12 weeks of administration of an oral dose of 7.5 mg/kg(-1)/day(-1), CIHP-I was found to possess significant adaptogenic activity. CIHP-I helped improve resistance to C-H-R induced hypothermia (Trec 23 degrees C) in animals by increased mobilization of free fatty acids (FFA) from adipose tissue. Blood glucose and muscle glycogen levels were maintained. CIHP-I treatment restricted the release of creatine phosphokinase (CPK) into the circulation during C-H-R exposure. CONCLUSIONS: The results suggested that CIHP-I is a strong adaptogen. It improved cold resistance during C-H-R exposure and enhanced recovery from hypothermia. The energy-dependent cell membrane permeability was maintained. Stored lipids were mobilised and possibly used for thermogenesis in preference to carbohydrates.

Adipose Tissue↗
PubMed1999

Optimum duration of splinting after endopyelotomy.

OBJECTIVE: Endopyelotomy is a well-accepted modality of treatment for pelviureteral junction (PUJ) obstruction, but the time period of stenting is debatable. The present study was aimed at evaluating the optimum duration and effectiveness of splinting after endopyelotomy. PATIENTS AND METHODS: Twenty-nine consecutive patients with primary PUJ obstruction were randomized to have an external splint (for economic reasons) for 2 weeks or 4 weeks. Thirteen patients in each group were available for evaluation. The groups were comparable in age, sex, symptoms, and preoperative glomerular filtration rate (GFR). All patients underwent antegrade endopyelotomy with placement of an 8F-12F polyethylene splint across the PUJ. A nephrostogram was performed after removal of splint at 2 or 4 weeks. Nondraining units were managed by putting in a 6F double-J stent for 6 weeks and considered failures. Patients were evaluated at 3, 6, and 12 months for symptomatic improvement, change in GFR, and drainage pattern on a diuretic renogram. RESULTS: At 1 year, a nonobstructed curve pattern was seen in 70% and improvement in GFR in 54% of the patients in the 2-weeks group, whereas in the 4-weeks group, these values were 54% and 39%, respectively. All patients in the 4-weeks group and 90% of those in the 2-weeks group were symptom free at 1 year of follow-up. Morbidity in terms of tube-related complications was comparable. CONCLUSION: Two weeks of splinting is as effective as 4 weeks in the successful outcome of endopyelotomy.

Adolescent↗
PubMed1999

Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells.

Recent evidence suggests that apical and basolateral endocytic pathways in epithelia converge in an apically located, pericentriolar endosomal compartment termed the apical recycling endosome. In this compartment, apically and basolaterally internalized membrane constituents are thought to be sorted for recycling back to their site of origin or for transcytosis to the opposite plasma membrane domain. We report here that in the epithelial cell line Madin-Darby Canine Kidney (MDCK), antibodies to Rab11a label an apical pericentriolar endosomal compartment that is dependent on intact microtubules for its integrity. Furthermore, this compartment is accessible to a membrane-bound marker (dimeric immunoglobulin A [IgA]) internalized from either the apical or basolateral pole, functionally defining it as the apical recycling endosome. We have also examined the role of a closely related epithelial-specific Rab, Rab25, in the regulation of membrane recycling and transcytosis in MDCK cells. When cDNA encoding Rab25 was transfected into MDCK cells, the protein colocalized with Rab11a in subapical vesicles. Rab25 transfection also altered the distribution of Rab11a, causing the coalescence of immunoreactivity into multiple denser vesicular structures not associated with the centrosome. Nevertheless, nocodazole still dispersed these vesicles, and dimeric IgA internalized from either the apical or basolateral membrane was detected in endosomes labeled with antibodies to both Rab11a and Rab25. Overexpression of Rab25 decreased the rate of IgA transcytosis and of apical, but not basolateral, recycling of internalized ligand. Conversely, expression of the dominant-negative Rab25T26N did not alter either apical recycling or transcytosis. These results indicate that both Rab11a and Rab25 associate with the apical recycling system of epithelial cells and suggest that Rab25 may selectively regulate the apical recycling and/or transcytotic pathways.

Animals↗
PubMed1999

Unusual consequences of heroin overdose: rhabdomyolysis, acute renal failure, paraplegia and hypercalcaemia.

A 29-yr-old man, known to be a heroin addict, was found at home totally unrousable, bent on his hips in the lotus position. On admission, he required frequent ventricular defibrillation, external pacing and infusion of calcium. A diagnosis of rhabdomyolysis caused by heroin and cocaine overdose was made. He developed paraplegia below T12, acute renal failure, acute compartment syndrome in one leg and a coagulation defect. Despite a fasciotomy, a through-knee amputation of the leg was required. Haemodialysis was required for 26 days, and this period was complicated by increased serum calcium concentrations, which was treated with disodium pamindrate. Calcium deposits were palpable in the muscles and could be seen in vessels on limb x-rays. After 34 days, he was eventually discharged to a general surgical ward and subsequently into the community.

Acute Kidney Injury↗
PubMed1999

Neurophysiological effects of stimulation through electrodes in the human subthalamic nucleus.

The effects of stimulation through macroelectrodes implanted in the subthalamic nucleus (STN) were studied in 14 patients with parkinsonism. Single stimuli delivered directly to the STN electrodes with an external stimulator modulated voluntary electromyography (EMG) of contralateral muscles in most patients. A short-latency facilitation ('peak') was attributed to the activation of the corticospinal system. A longer latency inhibition ('dip'), often preceded or followed by facilitations, appeared to arise from the activation of large-diameter fibres running parallel to the electrode and to be transmitted through the motor cortex. It is possible that the dip could result from the inhibition of thalamocortical neurons. With high-frequency stimulation ( approximately 100 Hz) the peaks occurred at the stimulus frequency; the dips became confluent and outlasted the duration of the stimulus train. There was no evidence that high-frequency stimulation produced 'blocking'. The studies were repeated in 12 patients a mean of 5.8 months after implantation of the stimulator. The same short-latency effects were obtained. They were present on 7 out of 23 sides at the settings in use and on the majority of sides if the stimulus intensity was slightly increased. There was no clear relationship between these short-latency effects and the patients' overall clinical improvement; the effects may result from the spread of current to large-fibre systems near the STN. In five patients, high-frequency stimulation on one side immediately reduced tremor in the contralateral limbs. This effect arose from the activation of large-diameter fibres and, like the dip, had about the same threshold at each of the contacts. Frequencies as low as 70 Hz were sufficient. We conclude that the control of tremor by STN stimulation is due to the activation of a large-fibre system.

Adult↗
PubMed1999

Vitamin A administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity.

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs.

Antibody Formation↗
PubMed1999

Ocular extramedullary myeloid cell tumour in children: an Indian study.

Thirty-two children with extramedullary myeloid cell tumour (EMT) who constituted 41 per cent of children with acute myeloid leukaemia (AML) were studied to ascertain their laboratory characteristics and potential problems in diagnosis. The diagnosis, established by peripheral blood smear and/or bone marrow examination, was AML (n = 29) and refractory anaemia with excess blasts in transformation (RAEB-t; n = 3). The six referred patients in whom the diagnosis had been missed, and two cases wrongly reported as histiocytosis on aspiration cytology, were those in whom a peripheral blood smear had not been examined. It is concluded that diagnostic work-up of proptosis must include a full haemogram, meticulous peripheral blood smear examination, repeated if necessary, and bone marrow examination where relevant. RAEB-t cases with extramedullary myeloid cell tumour should be classified as acute myeloid leukaemia.

Acute Disease↗
PubMed1999

Prognostic value of serum C-reactive protein in kala-azar.

The currently recommended protocol for treatment of kala-azar (KA) necessitates repeated bone marrow/splenic aspiration to monitor the response and duration of therapy as well as to detect resistance and change to alternative drugs. These procedures being invasive, there is a pressing need for less invasive diagnostic tools for this purpose. We have evaluated the role of C-reactive protein (CRP) in 201 children with visceral leishmaniasis at different stages of the disease to work out the relationship, if any, between CRP levels and disease activity, including response to therapy. The subjects belonged to the 2-12 year age group in whom CRP estimation was done on admission, every 5th day during treatment, and repeated on follow-up at 2 and 6 months. The levels were compared with those of 50 randomly chosen age-matched healthy children who served as controls. The mean serum CRP value in the study group before the commencement of treatment was 62.96 +/- 1.03 mg/l, which was significantly higher (p < 0.001) in comparison to the control group. Commencement of treatment resulted in a simultaneous decline in serum CRP. Parasitic clearance from the spleen was faster in patients with an initial low serum CRP level (< 60 mg/l) in comparison to patients with high levels (> 60 mg/l). During treatment, mean serum CRP levels were significantly higher in late responders than in early responders (p < 0.001). Correlation of CRP levels to indicate the presence or absence of parasites suggested a cut-off level of 12 mg/l by day 10, with a sensitivity of 82.5 per cent, specificity of 78.5 per cent, positive predictive value of 92 per cent, and negative predictive value of 60.2 per cent. Our observations suggest a promising role for CRP estimation every 5-10 days during therapy in visceral leishmaniasis for monitoring the response to therapy and to detect possible resistance.

Antimony Sodium Gluconate↗
PubMed1999

Loss of heterozygosity at chromosome 9p21 (INK4-p14ARF locus): homozygous deletions and mutations in the p16 and p14ARF genes in sporadic primary melanomas.

Loss of heterozygosity (LOH) was determined in 45 sporadic primary melanomas at six polymorphic microsatellite markers that flank the INK4a (p16-p14ARF) locus on chromosome 9p21. We also determined allelic loss at two markers on chromosome 9q and two markers at the Rb locus on chromosome 13. Homozygous deletion of the p16 and p14ARF genes was determined by a fluorescent-based quantitative multiplex polymerase chain reaction method. LOH at one or more polymorphic microsatellite markers on locus 9p21 was found in 32 of the melanomas (71%). The highest proportion of LOH was found at markers D9S736 and D9S104, which are telomeric and centromeric to the INK4 locus, respectively. Five melanomas showed LOH at all the analysed markers located on chromosome 9p21. LOH at markers D9S942 and D9S974, which are located close to the p16 and p14ARF genes, was found in 39% and 46% of melanomas, respectively. Analysis of the marker D9S257 on 9q22.1 showed LOH in 13 melanomas (44% of the informative cases). A subset of melanomas with LOH at the INK4 locus also carried inactivating mutations within the p16 coding sequence. Four melanomas carried homozygous deletions at the p16-p14ARF locus. Our results suggest, besides the involvement of the INK4 locus in sporadic melanomas, the possibility of the existence of additional tumour suppressor loci on chromosome 9.

Alleles↗
PubMed1999

Pneumoencephalus and convulsions after ventriculoscopy: a potentially catastrophic complication.

A nine-year-old boy with hydrocephalus underwent ventriculoscopy under general anesthesia. After introduction of ventriculoscope the patient had sudden bradycardia, hypotension, and shrinkage of ipsilateral cerebral hemisphere. The ventriculostomy was abandoned. At the end of anesthesia and endotracheal extubation, the patient developed generalized convulsions. Reexploration of wound did not reveal anything significant; however, postoperative CT scan of head showed massive pneumoencephalus. The patients received elective ventilation of lungs for 24 hours and made complete recovery. The authors describe the reasons for these complications and further management.

Bradycardia↗
PubMed1999

Validation of an optical flow method for tag displacement estimation.

We present a validation study of an optical-flow method for the rapid estimation of myocardial displacement in magnetic resonance tagged cardiac images. This registration and change visualization (RCV) software uses a hierarchical estimation technique to compute the flow field that describes the warping of an image of one cardiac phase into alignment with the next. This method overcomes the requirement of constant pixel intensity in standard optical-flow methods by preprocessing the input images to reduce any intensity bias which results from the reduction in stripe contrast throughout the cardiac cycle. To validate the method, SPAMM-tagged images were acquired of a silicon gel phantom with simulated rotational motion. The pixel displacement was estimated with the RCV method and the error in pixel tracking was <4% 1000 ms after application of the tags, and after 30 degrees of rotation. An additional study was performed using a SPAMM-tagged multiphase slice of a canine left ventricle. The true displacement was determined using a previously validated active contour model (snakes). The error between methods was 6.7% at end systole. The RCV method has the advantage of tracking all pixels in the image in a substantially shorter period than the snakes method.

Animals↗
PubMed1999

Alteration of skin protein kinase C alpha protein and mRNA levels during induced mouse hair growth.

Protein kinase C (PKC) has been implicated in regulation of hair growth. In this study, the role of PKC alpha in induced mouse hair growth was studied. Hair growth in C57BL6 mice, a well known model for hair growth research, was induced by plucking the telogen hair. PKC alpha protein levels during the induced hair growth cycle were analyzed by Western immunoblot and mRNA levels were measured by RT-PCR. At 1 day and 4 days postdepilation, when the induced hair cycle was in early and midanagen, the PKC alpha protein level was decreased. At 10 days after depilation, when the induced hair cycle was in mature anagen, the PKC alpha protein level was increased. At 17 days after plucking the hair, when the induced hair cycle was in early catagen, PKC alpha protein returned to the control level. PKC alpha mRNA was relatively unchanged at 1 day and 4 days after plucking the hair but significantly elevated at 10 days postdepilation. At 17 days after hair growth induction, PKC alpha mRNA reverted to the control level. These results suggest that: 1) in early and mid anagen of the induced hair growth cycle, PKC alpha was downregulated posttranscriptionally. This downregulation may play a role in the induction of hair growth; 2) in mature anagen of induced hair growth cycle, PKC alpha was overexpressed, and this overexpression may play a part in maintaining the hair growth. Since the expression of PKC alpha was roughly correlated with mouse skin pigmentation, we hypothesize that PKC alpha may regulate hair growth partially through modulation of skin melanogenesis.

Animals↗
PubMed1999

The potential role of skin protein kinase C isoforms alpha and delta in mouse hair growth induced by diphencyprone-allergic contact dermatitis.

The levels of protein kinase C (PKC) isoforms alpha and delta in mouse hair growth induced by diphencyprone (DPCP)-allergic contact dermatitis (ACD) were studied. BALB/c mice were sensitized by 2% DPCP in acetone on one side of their shaved backs and rechallenged with 0.1% DPCP on the same side weekly for 2 weeks. The opposite side treated with acetone served as a control. Before each elicitation, mice were shaved again in order to observe the hair growth that followed. Enhancement of hair growth on DPCP treated skin was observed in 94% of mice after first elicitation and significant hair growth was shown in all mice after second elicitation. No remarkable hair growth was seen on the control side. Western immunoblot analysis revealed that the level of skin PKC alpha on the DPCP treated side was decreased at 2 and 4 days after sensitization and returned to the control level after first elicitation. At 5 days after the second elicitation, a higher level of PKC alpha was detected. The level of PKC delta remained at the control level and increased at 5 days after second elicitation. These results suggest that: 1) In the first week after sensitization, PKC alpha was down-regulated. This down-regulation may play a role in DPCP-ACD induced hair growth; 2) after the elicitation, PKC alpha was over-expressed and this over-expression was roughly correlated with the enhancement of mouse hair growth, suggesting that over-expression of PKC alpha may also play a part in the proliferation of hair follicle cells; and 3) overexpression of PKC delta after second elicitation may have an inhibitory effect on hair growth that keeps hair growth in balance.

Allergens↗