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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 271 records · Page 15Linked to original sources
PubMed1997

Integrated community-based screening for cardiovascular diseases of childhood.

A screening programme in northern India, principally aimed at detecting and controlling rheumatic fever and rheumatic heart disease (RF/RHD) in children, also picks up individuals with congenital heart disease and other cardiovascular conditions, who are then referred for consultation and treatment. This strategy is clearly more ethical and cost-effective than screening programmes concerned exclusively with the control of RF/RHD.

Adolescent↗
PubMed1997

Solid cystic tumour of the pancreas-clinico-pathological study of three cases.

During a period of four years three cases of solid and cystic (papillary) tumour of the pancreas were encountered. The patients presented predominantly with chief complaints of lump abdomen associated with dull aching pain in right hypochondrium. Radiologically diagnosis was suspected in two cases. Excessive bleeding during surgery was observed in two cases. In two survivors no recurrence or distant metastasis was noted after surgical excision (follow up 6 months to 3.5 years), third patient died after eight hours of operation.

Adolescent↗
PubMed1997

The performance of hearing-impaired children on handedness and perceptual motor tasks.

The present study was designed to test for differences, if any, in children with impaired hearing compared with a control group of children with normal hearing (7-11-year-olds) in handedness, drawing, categorization, facial recognition, and play. Results indicated age differences in the performance of all the tasks. The children with hearing loss had more left-hand responses than the normal children did. For drawings, those whose hearing was impaired used more space and color. Both groups performed similarly on tasks of categorization and facial recognition. For play, children with hearing loss were more clumsy and accident prone than children in the control group. The results suggest that children with impaired hearing differ from those with normal hearing in tasks that are influenced by language processes and motor ability.

Child↗
PubMed1997

Immunization coverage among urban and rural children in the Shimla hills.

A cross sectional study was carried out to assess immunisation coverage among 257 urban and 339 rural children aged 13-36 months who were vaccinated at pulse polio booths in Shimla hills. 84.37% urban children and 57.59% rural children were fully vaccinated. BCG scar was negative in a large number of children, especially from rural areas. Increasing maternal education was associated with complete immunisation. OPV I-III dropouts were 3% among urban children and 15% among rural. The corresponding dropout rates for DPT I-III were 1% and 8% respectively. The immunisation coverage in this region was higher than others. Sustained efforts are required to achieve full immunisation coverage and eradicate polio and measles.

Child Welfare↗
PubMed1997

Comparative evaluation of fine needle aspiration cytology and biopsy of testis in diagnosis of male infertility.

Infertility has a fair degree of male factor contribution in its aetiology, hence needs complete evaluation of male partner especially the status of spermatogenesis. In the present study comparative evaluation of fine needle aspiration cytology (FNAC) and biopsy of testis showed 90% accuracy of FNAC in respect of histopathological diagnosis of spermatogenesis. FNAC is a safe, fairly accurate, outdoor investigation in infertile man and it is devoid of the complications of haematoma formation, suppression of spermatogenesis and antigenic stimulation as seen with testicular biopsy.

Adult↗
PubMed1997

Features of symptomatic gastroesophageal reflux disease in elderly patients.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is considered common in the elderly and may present with various symptoms, such as heartburn, regurgitation, dysphagia, or chest pain. In this study, we evaluated the patterns of symptomatic GERD and the spectrum of disease activity in the elderly. METHODS: We prospectively studied 476 predominantly male veterans who were referred for upper endoscopy because of symptoms or signs suggestive of upper gastrointestinal disease. All patients were interviewed immediately before the procedure by a physician who used a standardized symptom questionnaire. Endoscopic findings were categorized and graded according to their extent and severity. The prevalence, nature, and severity of esophageal symptoms and their relationship to endoscopic disease severity were then analyzed. Comparisons were made between two age groups, the young (age less than 65 yr old, mean age 55 yr, age range 30-65 yr), and the elderly (more than 66 yr old, mean age 72 yr, age range 66-90 yr). RESULTS: Heartburn without esophagitis was noted in 28% of young and 24% of elderly patients. Hiatal hernia without esophagitis was noted in 15 % of young and 18% of the elderly. The prevalence of various stages of GERD was similar in the two groups (p > 0.1, chi2 test; odds ratio: 0.983; 95% CI: 0.651-1.48). Quantitative esophageal symptom analysis revealed remarkably similar symptom severity scores for both groups for GERD stages I-IV, as well as for symptomatic controls. However, elderly patients with Barrett's esophagus were significantly less symptomatic than the young (symptom index 2.4 +/- 0.6 vs. 4.88 +/- 1.01, p < 0.02). CONCLUSIONS: Among symptomatic adults undergoing upper endoscopy, the elderly appear to have prevalence rates, patterns, and features of symptomatic GERD that are generally similar to those of their younger counterparts. Nevertheless, the severity of symptoms in the subgroup of elderly with Barrett's esophagus is significantly less than in the young and may contribute to poor or delayed recognition of disease.

Adult↗
PubMed1996

Cyclosporine protects glomeruli from FSGS factor via an increase in glomerular cAMP.

Cyclosporine (CsA) administration to patients with recurrent focal segmental glomerulosclerosis (FSGS) after transplantation results in remission of proteinuria. We have shown that sera from patients with recurrent FSGS can increase the glomerular albumin permeability (Palbumin) and that increase in glomerular cAMP levels can alter the permeability characteristics of glomeruli in vitro. The purpose of this study was to determine if the increased glomerular levels of cAMP were related to the protective effects of CsA on an increase in Palbumin by FSGS sera. Glomeruli from Sprague-Dawley rats following intraperitoneal administration of CsA (25 mg/kg/day), cremophore (25 mg/kg/day), or saline for 5 days were incubated with 1:50 dilution of serum from three FSGS patients or with pooled normal human serum prior to calculation of Palbumin. Glomerular cAMP was measured by radioimmunoassay. Glomerular ultrastructural changes were assessed by transmission electron microscopy (TEM). Serum from three FSGS patients markedly increased Palbumin of glomeruli from saline or cremophore treated rats (saline, 0.68+/-0.08; 0.72+/-0.07; 0.70+/-0.07; and cremophore, 0.79+/-0.05; 0.81+/-0.02; 0.79+/-0.01; n=25 glomeruli in each group). In contrast Palbumin of glomeruli from CsA treated rats was not increased by any of the three FSGS sera tested (0.03+/-0.02; 0.04+/-0.05; 0.02+/-0.07, n=25 glomeruli in each group). Glomerular cAMP (pmol/mg of protein) increased 5 fold in CsA treated rats (328+/-26; 5 rats) compared with cremophore or saline treated rats (87+/-24 and 65+/-23, P<0.01; 5 rats in each group). The glomerular basement membrane appeared to be thickened and the lamina densa had an irregular appearance after treatment with CsA. No ultrastructural changes of glomerular epithelial or endothelial cells were evident. We conclude that CsA may have a direct protective effect on the glomerular filtration barrier in FSGS. We postulate that increased levels of glomerular cAMP by CsA may play an important role in protecting the glomerular Palbumin effect of the FSGS factor and may contribute to remission of proteinuria in FSGS patients.

Albumins↗
PubMed1996

The diet and gut microflora influence the distribution of enteroendocrine cells in the rat intestine.

Several functions of the gut are locally influenced by peptides and biogenic amines released from enteroendocrine cells. The aim of the present study was to assess whether the luminal stimulus of diet or microbial flora or diet-microbial interactions have an influence on the distribution of enteroendocrine cells along the crypt-surface axes of the small and large intestine. The effects of diet and indigenous flora were investigated by comparing the numbers of argyrophil and serotonin immunoreactive cells in the jejunum and colon of germ free and conventional rats fed either a purified diet containing fine ingredients or a commercial diet containing crude fibre of cereal origin. The effect of human flora were analysed in germ-free rats inoculated with human faecal organisms. 1. Feeding the commercial diet reduced the number of argyrophil endocrine cells in the jejunum and serotonin immunoreactive cells in the colon of germ-free animals but increased the serotonin immunoreactive cells in the colon of conventional animals. 2. The rat flora increased the serotonin immunoreactive cells in the colon of animals fed a commercial diet and decreased in those fed a purified diet. 3. Inoculation of human flora increased the numbers of serotonin immunoreactive cells both in the jejunum and colon. The results provide evidence that the dietary changes and diet-microbial interactions can affect the regional number of enteroendocrine cells.

Animals↗
PubMed1996

Hip stiffness following mixed conformal neutron and photon radiotherapy: a dose-volume relationship.

PURPOSE: To determine the relationship between dose, volume, and the incidence of hip stiffness in patients who received conformal neutron irradiation for prostate cancer. METHODS AND MATERIALS: A series of dose-searching studies using neutron irradiation for prostate cancer were performed to determine the optimal dose, fraction size, field size, technique, and proportions of photon and neutron dose. Neutron doses ranged from 9 to 20 Gy and photon doses ranged from 0 to 38 Gy. Data were analyzed by using a hip stiffness grading scale. RESULTS: Hip stiffness was recorded on follow-up examination in 30% of patients (40 out of 132) treated with fast neutrons or mixtures of fast neutron and photon radiation for prostate cancer. Hip stiffness was categorized as none (Grade 0, 92 patients), mild (Grade 1, 24 patients), moderate (Grade 2, 10 patients), or severe (Grade 3, 6 patients). The incidence of hip stiffness differed significantly by dose and volume in the five dose levels studied (p < 0.001). CONCLUSIONS: By using a mixture of conformal neutron and photon irradiation and limiting the total neutron dose to less than 13 Gy, hip stiffness toxicity could be reduced to acceptable levels.

Aged↗
PubMed1996

Conformal mixed neutron and photon irradiation in localized and locally advanced prostate cancer: preliminary estimates of the therapeutic ratio.

PURPOSE: To determine the incidence of chronic toxicity and the probability of biochemical and histologic complete response among patients with nonmetastatic prostate cancer, treated with three dimensional (3D) conformal mixed neutron and photon irradiation. METHODS AND MATERIALS: Between November 1991 and December 1994, 151 patients with prostate cancer were entered in three prospective dose-finding studies of conformal mixed neutron and photon irradiation. Patients with low stage, low to intermediate grade prostate cancer (T1-2NXM0, Gleason Score < or = 7) received 38 Photon Gy (PhGy) plus 9 (51 patients) or 10 (53 patients) Neutron Gy (NGy) to the prostate and seminal vesicles. Forty-seven patients with locally advanced prostate cancer (T3-4 N0-1 M0 and/or Gleason Score > or = 8) received 15 NGy + 18 PhGy to the prostate and seminal vesicles and 9 NGy + 18 PhGy to the pelvic lymph nodes. RESULTS: The median follow-up was 16 months (range: 3-30 months). There was no Grade 3-5 GI or GU toxicity recorded. At 20 months, the actuarial rates of Grade 2 GI morbidity were 6 and 29% for the 9-10 and 15 NGy protocols, respectively (p = 0.07). At 20 months, the incidences of Grade 2 GU morbidity were 4 and 16%, respectively (p = 0.08). Stiffness in flexing or abducting the hips was seen in 20 and 42% of patients receiving 9-10 and 15 NGy, respectively (p = 0.01). Potency was maintained in 65% of all patients. Among patients with an initial PSA < or = 10, 100% had a 12-month PSA < 2 and 78% < 1 ng/ml. Negative postradiation biopsies were seen in 30% of patients 6 months, 79% at 12 months, and 84% of patients at 18 months. CONCLUSION: The use of conformal mixed neutron and photon irradiation has been well tolerated with no severe bladder or rectal complications observed. However, because of the enhanced toxicity seen with 15 NGy, the current maximum dose levels of neutron irradiation have been limited to 11 NGy.

Adenocarcinoma↗
PubMed1996

Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis.

BACKGROUND: Heavy proteinuria and progressive renal injury recur after transplantation in up to 40 percent of patients with renal failure caused by idiopathic focal segmental glomerulosclerosis. A circulating factor may be responsible for this recurrence. METHODS: To determine whether patients with focal segmental glomerulosclerosis have a circulating factor capable of causing glomerular injury, we tested serum samples from 100 patients with the disorder in an in vitro assay of glomerular permeability to albumin. Of the 56 patients who had undergone renal transplantation, 33 had recurrences. Sixty-four patients, many of whom had undergone transplantation, were being treated with dialysis. Thirty-one patients with other renal diseases and nine normal subjects were also studied. RESULTS: The 33 patients with recurrent focal segmental glomerulosclerosis after transplantation had a higher mean (+/-SE) value for permeability to albumin (0.47+/-0.06) than the normal subjects (0.06+/-0.07) or the patients who did not have recurrences (0.14+/-0.06). After plasmapheresis in six patients with recurrences, the permeability was reduced (from 0.79+/-0.06 to 0.10+/-0.05, P = 0.008), and proteinuria was significantly decreased. Patients with corticosteroid-sensitive nephrotic syndrome or with membranous nephropathy after transplantation had low levels of serum activity. The circulating factor bound to protein A and hydrophobic-interaction columns and had an apparent molecular mass of about 50 kd. CONCLUSIONS: A circulating factor found in some patients with focal segmental glomerulosclerosis is associated with recurrent disease after renal transplantation and may be responsible for initiating the renal injury.

Adult↗
PubMed1996

Conformationally constrained analogues of diacylglycerol. 10. Ultrapotent protein kinase C ligands based on a racemic 5-disubstituted tetrahydro-2-furanone template.

5,5-Bis(hydroxymethyl)tetrahydro-2-furanone and its isomer 4,4-bis(hydroxymethyl)tetrahydro-2-furanone were investigated as possible templates for the construction of conformationally constrained analogues of the biologically important second messenger, diacylglycerol (DAG). The former lactone contains embedded within its structure an exact glycerol moiety, while in the latter the ring oxygen has been transposed to the other side of the carbonyl group. All target compounds were synthesized as racemates from 1,3-dihydroxy-2-propanone. The 5,5-bis(hydroxymethyl)tetrahydro-2-furanone proved to be the better template for the construction of DAG surrogates that were demonstrated to have high binding affinities for the biological target, protein kinase C (PK-C). The simplest target compounds derived from this template (3e and 3f) have one of the hydroxyl moieties functionalized either as a myristate or as an oleate ester. The simplest target compound (9c) derived from the ineffective 4,4-bis-(hydroxymethyl)tetrahydro-2-furanone template was investigated only with a myristoyl acyl chain. Reducing the long acyl chain to an acetyl moiety and attaching a compensating lipophilic chain to the lactone ring as an alpha-alkylidene moiety produced compounds 10e and 10f (Z-isomers) and 11e and 11f (E-isomers), which were constructed on the more effective 5,5-bis(hydroxymethyl)tetrahydro-2-furanone template. Targets 14c (Z-isomer) and 15c (E-isomer) were derived, in turn, from 4,4-bis(hydroxymethyl)tetrahydro-2-furanone. The affinities of these ligands for PK-C were assessed in terms of their ability to displace bound [3H-20]phorbol 12,13-dibutyrate (PDBU) from the single isozyme PK-C alpha. The biological data support the hypothesis that the increase in binding affinity for PK-C shown by some of these constrained DAG mimetics appears to be entropic in nature. Two of the designed ligands (10e and 10f) showed the highest affinities (34 and 24 nM, respectively) reported so far for a DAG analogue. Assuming that the interaction between these racemic compounds and PK-C is stereospecific, the potency of the active enantiomer is anticipated to double.

4-Butyrolactone↗
PubMed1996

Conformationally constrained analogues of diacylglycerol. 11. Ultrapotent protein kinase C ligands based on a chiral 5-disubstituted tetrahydro-2-furanone template.

Conformationally constrained analogues of diacylglycerol (DAG) built on a racemic 5(-)[(acyloxy)-methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template were shown previously to have excellent binding affinities for protein kinase C (PK-C). Since the interaction of PK-C with DAG is stereospecific, it was anticipated that PK-C would bind tightly to only one enantiomeric form of the compounds constructed with this new lactone template. Separation of enantiomers by chiral HPLC was discarded due to the ease with which acyl migration occurs in these class of compounds, and a total chiral synthesis was undertaken. Prior to chemical synthesis, the selection of the "correct" enantiomeric template was predicted by a molecular conformational analysis that compared the two enantiomers of DAG in their presumed "active" conformation with the two enantiomeric lactone templates. This presumed "active" conformation for DAG was derived from a previously developed pharmacophore model that uses the molecule of a potent phorbol diester as the ideal rigid template. The results from this analysis indicated that the "correct" lactone template corresponded to the inactive (R)-isomer of DAG. This analysis also predicted that the lactone template corresponding to the active (S)-DAG enantiomer would not fit adequately into the pharmacophore. The chiral syntheses of target compounds 2, 4, and 6, constructed on the selected, and presumably "correct" lactone template, were achieved from a common bicyclic intermediate (5R,8R,9R)-8,9-O-isopropylidene-2-keto-1,7-dioxaspiro[4.4]nonane (10) that was synthesized from commercially available 1,2:3,5-di-O-isopropylidene-alpha-D-threo-apiofuranose (7) by a very effective spirolactonization approach. On the basis of their ability to inhibit the binding of [3H-20]phorbol 12,13-dibutyrate (PDBU) to PK-C alpha, the enantiomeric ligands 2, 4, and 6 were twice as potent as the corresponding racemates. These results confirm that binding of these lactones is stereospecific and consistent with a binding mechanism similar to that of DAG.

4-Butyrolactone↗
PubMed1996

Conformationally constrained analogues of diacylglycerol. 12. Ultrapotent protein kinase C ligands based on a chiral 4,4-disubstituted heptono-1,4-lactone template.

Conformationally constrained analogues of diacylglycerol (DAG) built on a 5(-)[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template (1, Chart 1) were shown previously to bind tightly to protein kinase C alpha (PK-C alpha) in a stereospecific manner. These compounds, however, racemized readily through rapid acyl migration and lost biological potency. In order to circumvent this problem, the "reversed ester" analogues were designed as a new set of PK-C ligands. This reversal of the ester function produced some new DAG mimetics that are embedded in a C-4 doubly-branched heptono-1,4-lactone template. The reversed ester analogues were impervious to racemization, and their chemically distinct branches facilitated the enantiospecific syntheses of all targets. Compound 2, the simplest reversed ester analogue of 1 (Chart 1), exhibited a 3.5-fold reduction in binding affinity toward PK-C alpha which we attributed to the loss of a stabilizing gauche interaction that caused the ester branch in 2 to be more disordered than in the normal ester 1. However, conversion of the propanoyl branch of 2 into a propenoyl branch restored binding affinity (3 versus 5). As expected, the compounds bound to the enzyme with strict enantioselectivity (3 and 5 versus 4 and 6). Functionalization of the propenoyl-branched compounds as alpha-alkylidene lactones, in a manner which proved successful with the 5(-)[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template (9 and 10), produced stable compounds with equivalent ultrapotent binding affinities for PK-C alpha (7 and 8). The additional incorporation of the propenoyl-branched carbonyl into a gamma-lactone ring was performed (11-14) not only to derive a possible additional entropic advantage but also to confirm the spatial disposition of this carbonyl function in the ligand-enzyme complex. Although no additional entropic advantage was derived, the high binding affinities displayed by compounds 11 and 12 helped to establish the correct orientation of the equivalent carbonyl group in PK-C-bound DAG. As expected, these DAG analogues activated PK-C alpha. The most potent agonist, compound 8, stimulated phosphorylation of the alpha-pseudosubstrate peptide, and in primary mouse keratinocytes it caused inhibition of binding of epidermal growth factor with an ED50 of approximately 1 microM. In contrast to the phorbol esters, compound 8 did not induce acute edema or hyperplasia in skin of CD-1 mice, and its pattern of downregulation with several PK-C isozymes was different from that of phorbol 12-myristate 13-acetate (PMA).

4-Butyrolactone↗
PubMed1996

Lectin binding reveals divergent carbohydrate expression in human and mouse Peyer's patches.

The nature of cell-associated carbohydrates in the human intestine that may mediate transepithelial transport of bacterial and dietary lectins and their processing by the lymphoid cells of Peyer's patches is not known. Because the cell surface carbohydrate receptors for lectins may vary in different species, the glycoconjugates of human and mouse follicle-associated epithelium and gut-associated lymphoid tissue were compared. A panel of 27, mainly recently isolated, lectins were used to identify glycoconjugate expression in M-cells, enterocytes, goblet cells, lymphocytes and macrophages in mouse and human intestine. Mouse M-cells were exclusively labelled by fucose-specific lectins but in human follicle-associated epithelium no distinct M-cell staining pattern was observed. In the human Peyer's patches, Bryonia dioica lectin bound selectively to paracortical T-lymphocytes and Chelidonium majus lectin to germinal centre B-cells. Certain mannose-specific lectins (Galanthus nivalis, Hippeastrum hybrid) stained the tingible body macrophages in the germinal centre of human Peyer's patches but labelled the macrophages in the paracortical T-cell region of the mouse. The results indicate distinct differences in glycosylation between mouse and human Peyer's patches and their associated lymphoid cells. When considering cell surface glycoconjugates as target molecules for the gut immune system, care has to be taken to choose the appropriate lectin for each species.

Animals↗