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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 91 records · Page 5Linked to original sources

Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis.

This paper reviews the histomorphological aspects of angiogenesis and neoangiogenesis, quantitative and qualitative, and their applications in prognostic evaluation of neoplastic diseases. The merits and weak points of intratumoral microvessel density (MVD), a widely regarded bona fide predictor of tumour growth, metastases and patient survival, are discussed. Total microvascular area (TVA) has been found useful in recent prognostic studies utilizing newer immunohistochemical vascular markers. Of particular significance is the fact that MVD and TVA are most predictive of patient outcome in those tumours that induce significant neoangiogenesis, namely carcinomas of breast and prostate, and haematological malignancies. In contrast, carcinomas of lung and urinary bladder do not show significant associations of MVD and TVA with poor prognosis, reflecting differences in angiogenic mechanisms. In gliomas, MVD appears to correlate with outcome in high-grade, but not low-grade tumours, and does not correlate with tumour cellularity in the infiltrating portions of the tumour, reflecting a paucity of neoangiogenesis and directional vascular growth. Recent studies have found CD105, Tie-2/Tek and vascular endothelial growth factor receptors to be the best markers of neoangiogenesis. The vascular parameters so measured correlate better with overall and disease-free survival in breast, colon and lung carcinoma than panendothelial markers such as CD31. A correlation of vascular patterns with prognosis has been established in ocular melanomas, glioblastomas and squamous carcinomas of head and neck region. Vascular networks with closed loops are closely associated with mortality due to metastases in uveal melanomas. Fewer bizarre glomeruloid vessels and prominent classical capillary pattern was an independent predictor of longer survival in glioblastoma. Therefore a judicious combination of quantitative and qualitative microscopic angiogenic parameters, with emphasis on neoangiogenesis and vascular patterns wherever applicable, should be an integral component of a more consistent tumour staging system for accurate prognostic evaluation of tumours, selection of optimal anti-angiogenic therapy and pertinent research.

Humans↗

Physiological upper limits of ventricular cavity size in highly trained adolescent athletes.

OBJECTIVES: To define physiological upper limits of left ventricular (LV) cavity size in trained adolescent athletes. DESIGN: Cross sectional echocardiographic study. SETTING: British national sports training grounds and Olympic Medical Institute. SUBJECTS: 900 elite adolescent athletes (77% boys) aged 15.7 (1.2) years participating in ball, racket, and endurance sports and 250 healthy controls matched for age, sex, and size. MAIN OUTCOME MEASURES: LV end diastolic cavity size. RESULTS: Compared with controls, athletes had a larger LV cavity (50.8 (3.7) v 47.9 (3.5) mm), a difference of 6%. The LV cavity was > 54 mm in 18% athletes, whereas none of the controls had an LV cavity > 54 mm. The LV cavity exceeded predicted sizes in 117 (13%) athletes. Among the athletes with LV dilatation, 78% were boys, LV size ranged from 52-60 mm, and left atrial diameter and LV wall thickness were enlarged. Systolic and diastolic function were normal. None of the athletes in the study had an LV cavity size > 60 mm. LV cavity size correlated with age, sex, heart rate, and body surface area. CONCLUSION: Highly trained junior athletes usually have only modest increases in LV cavity size. A proportion of trained adolescent athletes have LV cavity size exceeding predicted values but, in absolute terms, LV cavity rarely exceeds 60 mm as in patients with dilated cardiomyopathy. In highly trained adolescent athletes with an LV cavity size > 60 mm and any impairment of systolic or diastolic function, the diagnosis of dilated cardiomyopathy should be considered.

Adolescent↗

Organization and evolution of highly repeated satellite DNA sequences in plant chromosomes.

A major component of the plant nuclear genome is constituted by different classes of repetitive DNA sequences. The structural, functional and evolutionary aspects of the satellite repetitive DNA families, and their organization in the chromosomes is reviewed. The tandem satellite DNA sequences exhibit characteristic chromosomal locations, usually at subtelomeric and centromeric regions. The repetitive DNA family(ies) may be widely distributed in a taxonomic family or a genus, or may be specific for a species, genome or even a chromosome. They may acquire large-scale variations in their sequence and copy number over an evolutionary time-scale. These features have formed the basis of extensive utilization of repetitive sequences for taxonomic and phylogenetic studies. Hybrid polyploids have especially proven to be excellent models for studying the evolution of repetitive DNA sequences. Recent studies explicitly show that some repetitive DNA families localized at the telomeres and centromeres have acquired important structural and functional significance. The repetitive elements are under different evolutionary constraints as compared to the genes. Satellite DNA families are thought to arise de novo as a consequence of molecular mechanisms such as unequal crossing over, rolling circle amplification, replication slippage and mutation that constitute "molecular drive".

Centromere↗

A profile of Perthes' disease in Greater Glasgow: is there an association with deprivation?

It has been reported that there is an association between Perthes' disease and poverty. We examined the demographic data of a group of 240 children (263 hips) who presented with Perthes' disease in Greater Glasgow, where the mean deprivation scores are substantially greater than in the rest of Scotland, to see if this association applied and whether other clues to the aetiology of Perthes' disease could be found. There were 197 boys and 43 girls; 39 (16.25%) had a family history of Perthes' disease. Bone age in this series was heavily skewed towards the lower percentiles. The mean number of siblings was 1.9, with 31 (12.9%) being an only child. Maternal age at the birth of the first child showed no preponderance of older mothers. Maternal smoking during and after pregnancy was noted in 132 (55%), which compared with the 52% reported in the population of Greater Glasgow in general. Of the children in our series, 60 (25%) were in social class IV and V. However, this applies to more than half of the population of Greater Glasgow. There was no significant evidence of a preponderance of Perthes' disease in the most deprived groups. The aetiology of Perthes' disease is likely to be multifactorial and may include a genetic or deprivation influence resulting in delayed bone age.

Age Determination by Skeleton↗

Long-term results of the uncemented low contact stress total knee replacement in patients with rheumatoid arthritis.

We analysed the long-term clinical and radiological results of 63 uncemented Low Contact Stress total knee replacements in 47 patients with rheumatoid arthritis. At a mean follow-up of 12.9 years (10 to 16), 36 patients (49 knees) were still alive; three patients (five knees) were lost to follow-up. Revision was necessary in three knees (4.8%) and the rate of infection was 3.2%. The mean clinical and functional Knee Society scores were 90 (30 to 98) and 59 (25 to 90), respectively, at final follow-up and the mean active range of movement was 104 degrees (55 degrees to 120 degrees ). The survival rate was 94% at 16 years but 85.5% of patients lost to follow-up were considered as failures. Radiological evidence of impending failure was noted in one knee.

Aged↗

A team approach to musculo-skeletal disorders.

INTRODUCTION: The majority of patients with musculo-skeletal problems referred to hospitals in the UK have to wait for months, if not over a year, before finally seeing an orthopaedic surgeon. In Stobhill Hospital, Glasgow, the waiting time for an out-patient appointment was 182 days in 1995, with only 20% of the referrals requiring surgery. The aim of this paper was to reduce the out-patient waiting times based on a co-ordinated team approach. METHODS: An outpatient musculo-skeletal service was developed over a 7-year period at Stobhill Hospital. The traditional consultant-based model, in which the consultant and a trainee saw all new patients referred to the hospital, was gradually replaced with a team approach, based on continuous reconfiguration of the roles of the orthopaedic surgeon and rheumatologist and extending the roles of nurses, physiotherapists and podiatrists. This was achieved by: (i) protocol-based daily triage for all referrals to the most appropriate health professional in the team, by the senior out-patient nursing staff; (ii) allocation of appointments based on clinical priority, with a fast-track for urgent cases; and (iii) improvement of inter-disciplinary communication, facilitating the retraction as well as the extension of traditional roles. RESULTS: Despite the number of GP referrals to the orthopaedic out-patient department at Stobhill nearly doubling in a period of 5 years, the out-patient waiting time decreased by about 50% (90 days from 182 days). This reduction in waiting times improved patient and GP satisfaction levels. We also noticed an improved morale and personal development of the health professionals as they saw patients appropriate to their skills and expertise. CONCLUSION: The team's experience demonstrates the effectiveness of a team approach in tackling what is often seen as the insoluble problem of orthopaedic waiting times. This is based on excellent communication and collaboration, with a clear aim of improving patient care that is evidence based.

Clinical Protocols↗

Microsporidia: emerging ocular pathogens.

Microsporidia are eukaryotic, spore forming obligate intracellular parasites, first recognized over 100 years ago. Microsporidia are becoming increasingly recognized as infectious pathogens causing intestinal, ocular, sinus, pulmonary, muscular and renal diseases, in both immunocompetent and immunosuppressed patients. Ocular microsporidiosis, though uncommon, could be isolated or part of systemic infections. It occurs mainly in two forms: keratoconjunctivitis form, mostly seen in immunocompromised individuals; stromal keratitis form seen in immunocompetent individuals. Recent reports indicate increasing number of cases of ocular microsporidiosis in immunocompetent individuals. The ocular cases present as superficial keratitis in AIDS patients, and these differ in presentation and clinical course from the cases seen in immunocompetent individuals which mainly appear to be as deep stromal keratitis. For most patients with infectious diseases, microbiological isolation and identification techniques offer the most rapid and specific determination of the etiologic agent, however this does not hold true for microsporidia, which are obligate intracellular parasites requiring cell culture systems for growth. Therefore, the diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves, either in scrapings or tissues. Although the diagnosis of microsporidiosis and identification of microsporidia by light microscopy have greatly improved during the last few years, species differentiation by these techniques is usually impossible and electron microscopy may be necessary. Immuno fluorescent-staining techniques have been developed for species differentiation of microsporidia, but the antibodies used in these procedures are available only at research laboratories at present. During the last 10 years, molecular techniques have been developed for the detection and species differentiation of microsporidia.

Americas↗

Synthesis and anti-inflammatory activity of some heterocyclic derivatives of phenothiazine.

Some new 10-{[5'-amino-(1"-ace tyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-thiadiazol-2'-yl] methyl}-phenothiazines (11-16) and 10-{[5'-amino-(1"-acetyl-5"-substituted aryl-2"-pyrazolin-3"-yl)-1',3',4'-oxadiazol-2'-yl]methyl}phenothiazines (26-31) have been synthesized from 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-thiadiazol-2'-yl)]methyl}phenothiazines (5-10) and 10-{[5'-substituted benzylideneacetylamino-(1',3',4'-oxadiazol-2'-yl)]methyl}phenothiazines (20-25), respectively. All these compounds of the present series have been screened in vivo for their anti-inflammatory and acute toxicity. Compounds 16 and 31 were found to be potent members of the present series, which showed 46.2% and 48.0% anti-inflammatory activity, respectively, at a dose of 50 mg/kg p.o., while standard drug, phenylbutazone, exhibited 44.52% anti-inflammatory activity at same dose. However, 10-{[5'-amino-(1"-acetyl-5"-(o-methoxyphenyl)-2"-pyrazolin-3"-yl)-1',3',4'-oxadiazol-2'-yl]methyl}phenothiazine (31) was found to be most active and less ulcerogenic compound of this series. The structure of these compounds have been elucidated by IR, 1H NMR, mass spectroscopy and elemental analysis.

Algorithms↗

A descriptive hospital based study of children with autism.

The clinical and neurodevelopmental profile of 51 children with Autistic disorder, from a referral population was studied. A detailed history and examination was undertaken. The development/intelligence quotient and social quotient were assessed. Standard diagnostic tests were applied in children above 2 years of age. Younger children were evaluated with a screening test and re-evaluated at 2 years. It was observed that a correct diagnosis had been made in only 5.8% of children prior to referral. The mean age of presentation was 3.28 years. Ninety-six percent of the autistic children had developmental delay. Qualitative impairment in social interaction and communication was more commonly observed than restricted interests and activities. Forty-seven (92.15%) children were severely autistic and 4 (7.84%) mildly to moderately autistic. All children less than 2 years were confirmed to have Autistic disorder later.

Autistic Disorder↗

Granulomatous inflammation in Acanthamoeba keratitis: an immunohistochemical study of five cases and review of literature.

PURPOSE: Acanthamoeba keratitis usually presents as a necrotizing stromal inflammation. We report a rare presentation of granulomatous inflammation in Acanthamoeba keratitis METHODS: Retrospective clinico-pathologic case series. RESULTS: Five corneal tissues (3 corneal buttons, 2-eviscerated contents) from patients suffering from severe Acanthamoeba keratitis not responding to anti-Acanthamoeba treatment, revealed a florid granulomotous inflammation with multinucleated giant cells in the posterior stroma and around Descemet's membrane. Phagocytosed parasites were noted within the giant cells. Vascularization of the corneal stroma was noted in two cases. Immunophenotyping revealed a predominance of T lymphocytes and macrophages. Clinically, four of five cases had shown features of limbal and scleral involvement. CONCLUSION: Granulomatous inflammation in the posterior corneal stroma, is not an uncommon finding in Acanthamoeba keratitis and could possibly be immune-mediated, contributing to persistence and progression of disease. CLINICAL RELEVANCE: Presence of granulomatous inflammation in Acanthamoeba keratitis, in most cases is associated with limbal and scleral involvement and therefore could be considered as one of the poor prognostic markers. Further studies are required to ascertain the specific clinical features and appropriate management strategies in these cases.

Acanthamoeba↗

Phenotypic & genotypic conservation of ompL1 & lipL41 among leptospiral isolates of Andaman Islands.

BACKGROUND & OBJECTIVES: The leptospiral antigens that are conserved among the diverse pathogenic leptospires have potential importance in the development of new serodiagnostic and immunoprotective strategies. The present study was therefore carried out to find out the phenotypic conservation of the leptospiral proteins OmpL1 and LipL41, and the genetic conservation of ompL1 and lipL41 genes among the leptospiral isolates of Andaman Islands and among the reference strains. METHODS: In one dimensional SDS-PAGE the leptospiral samples prepared from strains of various leptospiral serovars were run and transferred on to nitrocellulose paper and probed with pooled convalescent phase human sera to find out the phenotypic conservation of the protein fragments at 31 and 41 kDa. Further, the proteins were indirectly confirmed as OmpL1 and LipL41 by using specific rabbit hyperimmune sera. Specific primers were utilized to amplify the fragments to study the genetic conservation of ompL1 and lipL41. Further, these two fragments were sequenced and BLAST analysis was done with the whole genome of Leptospira interrogans serovar Lai for comparison. RESULTS: Analysis of individual immunoblots using patient sera showed that the OmpL1 and LipL41 were conserved among all the isolates used in the study. Further, these two proteins were probed with specific rabbit hyperimmune sera of OmpL1 and LipL41 for confirming the fragments and it was found to be conserved among all the isolates. The PCR based amplification further showed that the genes ompL1 and lipL41 were conserved among the leptospiral isolates studied. Sequencing followed by BLAST analysis of these showed 97 per cent similarity with the whole genome sequence and low score values in comparison with other bacterial species. INTERPRETATION & CONCLUSION: The antigenic and genetic conservation of the two proteins, OmpL1 and LipL41, indicated that these could be potential candidates for development of diagnostic test systems for leptospirosis.

Animals↗

RNA fingerprinting of microbial community in the rhizosphere soil of grain legumes.

Microbial structural and expression profiles of the rhizospheres of three legumes, faba beans, peas and white lupin, were compared by RNA-arbitrarily primed PCR technique. Two different primers, M13 reverse and 10-mer primers, were used in the amplification and products resolved on non-denaturing polyacrylamide gel. With both DNA and RNA profiles Lupinus and Pisum rhizospheres were more similar to each other than to Vicia rhizosphere. The RAP-PCR products were also dot blotted and probed for bacterial peptidase transcripts. Plant-dependent rhizosphere effect was evident by the marked absence of transcripts for bacterial neutral metallopeptidase in Lupinus rhizosphere. The results of dot blot were further confirmed by RT-PCR for the expression of bacterial neutral metallopeptidase in the three rhizospheres.

Bacteria↗

The role of pre-operative templating in primary total knee replacement.

Templating of preoperative X-rays is routinely performed before a total knee replacement. We performed this retrospective study on preoperative templating in primary total knee replacement to assess its accuracy and reproducibility. Preoperative radiographs of 47 patients were templated twice by two observers separately after a gap of 3 months. The size of actual implant used was compared to the size predicted by templating. Data were analysed to assess inter and intra-observer variation. Templating was accurate for both tibial and femoral components in only 53.2% of observations. This study also revealed that templating is a highly-subjective and observer-dependent technique. Inter-observer and intra-observer mismatch was present in 46.8% and 43.6% of readings respectively. We conclude from this study that preoperative templating is neither accurate nor reproducible.

Arthroplasty, Replacement, Knee↗