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Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 91 records · Page 5Linked to original sources

Primary intratesticular leiomyosarcoma in a mixed race man: a case report.

Primary leiomyosarcoma of the testis is an extremely rare condition with only a few reported cases in the literature. None has been reported in men of Afro-Caribbean descent. This report describes the first case of a primary leiomyosarcoma in a mixed race man. Several different immunostains were used to confirm the morphological suggestion of a primary intratesticular smooth muscle tumour. Scrotal ultrasound and abdominal computed tomography imaging were used to exclude paratesticular and retroperitoneal pathology. Where reported, primary intratesticular leiomyosarcoma is described as an indolent tumour with the potential for distant metastases. Its occurrence in younger men is usually associated with anabolic steroid abuse. Although the number of reported cases is very few, radical orchidectomy followed by surveillance appears to be the treatment of choice.

Adult↗

Comparative evaluation of clinical efficacy of gallium and amalgam alloys in primary molars.

The present study was conducted to compare the clinical efficacy (marginal integrity and bulk fracture) of two alloys--Galloy (gallium based) and Aristaloy (amalgam based) in primary molars. 90 primary molars with initial caries formation were selected. 45 were restored with Galloy and 45 with Aristaloy in Class I and II preparations. They were evaluated at two-month intervals for 6 months. The results showed that Galloy performed at par with Aristaloy with regards to marginal integrity and bulk fracture. Hence Galloy can be considered as an interesting substitute in Pedodontic practice.

Adolescent↗

Transferable EST-SSR markers for the study of polymorphism and genetic diversity in bread wheat.

Nearly 900 SSRs (simple sequence repeats) were identified among 15,000 ESTs (expressed sequence tags) belonging to bread wheat ( Triticum aestivumL.). The SSRs were defined by their minimum length, which ranged from 14 to 21 bp. The maximum length ranged from 24 to 87 bp depending upon the length of the repeat unit itself (1-7 bp). The average density of SSRs was one SSR per 9.2 kb of EST sequence screened. The trinucleotide repeats were the most abundant SSRs detected. As a representative sample, 78 primer pairs were designed, which were also used to screen the dbEST entries for Hordeum vulgare and Triticum tauschii (donor of the D-genome of cultivated wheat) using a cut-off E (expectation) value of 0.01. On the basis of in silico analysis, up to 55.12% of the primer pairs exhibited transferability from Triticum to Hordeum, indicating that the sequences flanking the SSRs are not only conserved within a single genus but also between related genera in Poaceae. Primer pairs for the 78 SSRs were synthesized and used successfully for the study of (1) their transferability to 18 related wild species and five cereal species (barley, oat, rye, rice and maize); and (2) polymorphism between the parents of four mapping populations available with us. A subset of 20 EST-SSR primers was also used to assess genetic diversity in a collection of 52 elite exotic wheat genotypes. This was done with a view to compare their utility relative to other molecular markers (gSSRs, AFLPs, and SAMPL) previously used by us for the same purpose with the same set of 52 bread wheat genotypes. Although only a low level of polymorphism was detected, relative to that observed with genomic SSRs, the study suggested that EST-SSRs can be successfully used for a variety of purposes, and may actually prove superior to SSR markers extracted from genomic libraries for diversity estimation and transferability.

Bread↗

Dysregulated expression of IFN-gamma and IL-10 and impaired IFN-gamma-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection.

Cell-mediated T-helper type-1 (Th1) responses play a vital role in the immunopathogenesis of genital infections caused by herpes simplex virus 2 (HSV-2). We investigated the role of Th responses in HSV-2 infection at different disease stages by analysing the production of Th cytokines in HSV-stimulated peripheral blood mononuclear cells (PBMCs). IFN-gamma production decreased over time following a recurrence, whereas levels of IL-10, and to a lesser extent IL-2, remained elevated during this period. In addition, PBMCs from asymptomatic seropositive individuals produced high levels of IFN-gamma and low levels of IL-10, in contrast to individuals with a history of genital ulcers. Following a recurrence, virus copy number in the genital lesions decreased progressively over time, in a manner similar to IFN-gamma production by HSV-2-stimulated PBMCs. Enhanced production of IFN-gamma may modulate HSV replication and B7 expression on monocytic cells of HSV-infected individuals. In contrast to seronegative controls, IFN-gamma failed to enhance B7 expression on monocytic cells of HSV-infected individuals. In addition, monocytic cells from HSV-2-infected individuals with recurrent disease supported greater HSV replication than did those of HSV-infected asymptomatic individuals or seronegative controls. Furthermore, addition of IFN-gamma resulted in enhanced HSV replication in monocytic cells of HSV-infected individuals with recurrent disease, in contrast to the inhibition observed in HSV-seropositive asymptomatic individuals and seronegative controls. Taken together, our results suggest that dysregulated production of IFN-gamma at different disease stages and the impaired ability of monocytic cells to respond to IFN-gamma may play a role in the pathogenesis of recurrent genital herpes disease.

Case-Control Studies↗

Prospective evaluation and comparison of the direct agglutination test and an rK39-antigen-based dipstick test for the diagnosis of suspected kala-azar in Nepal.

The diagnosis of visceral leishmaniasis (kala-azar) remains difficult in rural endemic areas and practical and reliable tests are badly needed. Two serological tests, the Direct Agglutination Test (DAT) and an rK39-antigen-based dipstick test, were compared to parasitological diagnosis in a group of 184 patients presenting at a tertiary care centre in south-eastern Nepal with a history of fever > or = 14 days and splenomegaly; 139 patients had a parasitologically proven kala-azar and 45 patients had a negative parasitological work-up. The rK39 dipstick showed a sensitivity of 97% and a specificity of 71%. The DAT was up to 99% sensitive with a low cut-off titre (1:400) but its specificity did not exceed 82% even with a high cut-off titre (1:51 200). Both tests could be used for screening suspect patients in endemic areas. However, their use as confirmatory tests should be restricted to situations where the proportion of kala-azar among clinical suspect patients is high. The rK39 dipstick is cheaper and easier to use than the DAT and could be used widely provided that both its performance and production remain stable.

Adult↗

Identifying under-performing surgeons.

OBJECTIVE: To estimate the likelihood of poor surgical results being explained by chance rather than under-performance. METHODS: The 30-day mortality rates after radical cystectomy for bladder cancer were analysed theoretically. Surgical competence was defined as a mortality rate of 4%, excellence as 2% and under-performance as 8%, 12%, 20% or 40%. Four scenarios were explored for surgeons of different competence: first, the sample size required to show that a given level of under-performance is very unlikely to be due to chance; second, the likelihood of two or more consecutive deaths in a series of cases; third, the likelihood of clustering of deaths, defined as two deaths in five or in 10 cases; and last, the likelihood of outstanding surgical results (i.e. no deaths) being achieved in small cohorts by surgeons of differing competence. RESULTS: For surgeons with a mortality rate of 8%, 12%, 20% or 40%, the sample sizes needed to prove under-performance are 211, 65, 21 and seven, respectively. For consecutive deaths, 0.4% of excellent, 1.4% of competent and 21% of surgeons with a mortality rate of 12% will experience two or more consecutive deaths in the next 10 cases. For clustered deaths, 1% of excellent, 5% of competent and 23% of seriously under-performing surgeons (mortality rates > or = 12%) will experience two deaths in their next 10 cases. Lastly, for the likelihood of outstanding results, only 3.6% of surgeons with an 8% mortality rate and < 1% of surgeons with a mortality rate > or = 12% will experience no deaths over 40 consecutive cases. CONCLUSIONS: Very large cohorts are needed to confirm even significant under-performance. Consecutive deaths are very unlikely events for competent surgeons. Clustered deaths (two deaths in 10 cases) are very unlikely events for excellent surgeons but plausible for competent ones. Analysis of consecutive/clustered deaths is limited by low statistical sensitivity; only up to a quarter of seriously under-performing surgeons are identified. No deaths in 40 consecutive cases implies competence.

Clinical Competence↗

Association between leptin receptor gene polymorphisms and early-onset prostate cancer.

OBJECTIVE: To report a case-control study examining the relationship between polymorphisms in the leptin receptor (OBR) gene and the development of young-onset prostate cancer, because epidemiological studies report that prostate cancer risk is associated with animal fat intake, and thus we investigated if this association occurs via this genetic mechanism. PATIENTS, SUBJECTS AND METHODS: The Lys109Arg (OBR1) and Gln223Arg (OBR2) polymorphisms in the coding region of OBR were studied in blood DNA from 271 patients with prostate cancer aged < 56 years at diagnosis and 277 geographically matched control subjects. Cases were collected through the Cancer Research UK/British Prostate Group Familial Prostate Cancer Study. Blood DNA was genotyped using the polymerase chain reaction and a restriction enzyme digest. RESULTS: There was no statistically significant association between the OBR genotype and prostate cancer risk; men homozygous for 109Arg genotype had a slightly increased risk for prostate cancer, with a relative risk (95% confidence interval) of 1.36 (0.65-2.85), and those homozygous for the 223Arg allele had some reduction in prostate cancer risk, at 0.82 (0.58-1.26), but neither was statistically significant. CONCLUSION: This case-control study showed no significant association between leptin receptor gene polymorphisms and the risk of young-onset prostate cancer, suggesting that genetic variations in OBR are unlikely to have a major role in the development of early-onset prostate cancer in the UK.

Adult↗

Common peroneal nerve palsy after lateral unicompartmental knee arthroplasty.

Unicompartmental knee arthroplasty is now being used more commonly to treat single compartment disease of knee, with very encouraging results. We report on a rare case of common peroneal nerve palsy; 8 years after lateral unicompartmental knee arthroplasty. This palsy was caused by pressure on the common peroneal nerve, due to posterior migration of tibial component.

Arthroplasty, Replacement, Knee↗

Repeating the measurement of prostate-specific antigen in symptomatic men can avoid unnecessary prostatic biopsy.

OBJECTIVES: To report the 2-year clinical and biochemical follow-up of symptomatic men who had a high prostate-specific-antigen (PSA) level, for whom our policy has been to avoid biopsy in those with a normal repeat PSA, as minimizing negative prostate biopsies is an important goal in managing men with a high PSA, where the decision for biopsy based on one high value may be inappropriate. PATIENTS AND METHODS: In all, 101 men (median age 72 years, range 47-85) referred to a urology department over 1 year with a PSA level above the age-specific reference range (but < 50 ng/mL) had a repeat PSA measurement. Those with a normal PSA and a normal digital rectal examination (DRE) were not biopsied. Their follow-up included a symptom review, DRE and PSA measurements. RESULTS: Of the 101 men, 67% presented with LUTS, 11% with symptoms of urinary infection, 8% with haematuria and 9% for screening. In 35 patients the repeat PSA level was normal; in three of these 35 prostate cancer was diagnosed after biopsy because of an abnormal DRE, three were lost to follow-up and one died from unrelated causes. Thus 28 patients were available for review at 2 years. In 23 (82%) the PSA remained within the normal range. In 66 of the 101 men the repeat PSA was abnormal. Cancer was diagnosed in 28 and the remaining 36 with no cancer were managed by PSA review; 30 were reviewed at 2 years and in half of them the PSA level returned to normal. CONCLUSIONS: In symptomatic men referred with a raised PSA level and who have a normal DRE and normal repeat PSA, prostatic biopsy can be safely avoided.

Aged↗

Characterization of Salmonella enterica serotype newport isolated from humans and food animals.

Salmonella enterica serotype Newport isolates resistant to at least nine antimicrobials (including extended-spectrum cephalosporins), known as serotype Newport MDR-AmpC isolates, have been rapidly emerging as pathogens in both animals and humans throughout the United States. Resistance to extended-spectrum cephalosporins is associated with clinical failures, including death, in patients with systemic infections. In this study, 87 Salmonella serotype Newport strains were characterized by pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility testing and examined for the presence of class 1 integrons and bla(CMY) genes. Thirty-five PFGE patterns were observed with XbaI, and three of these patterns were indistinguishable among isolates from humans and animals. Fifty-three (60%) Salmonella serotype Newport isolates were identified as serotype Newport MDR-AmpC, including 16 (53%) of 30 human isolates, 27 (93%) of 29 cattle isolates, 7 (70%) of 10 swine isolates, and 3 (30%) of 10 chicken isolates. However, 28 (32%) Salmonella serotype Newport isolates were susceptible to all 16 antimicrobials tested. The bla(CMY) gene was present in all serotype Newport MDR-AmpC isolates. Furthermore, the plasmid-mediated bla(CMY) gene was transferable via conjugation to an Escherichia coli strain. The transconjugant showed the MDR-AmpC resistance profile. Thirty-five (40%) of the isolates possessed class 1 integrons. Sequence analyses of the integrons showed that they contained aadA, which confers resistance to streptomycin, or aadA and dhfr, which confer resistance to trimethoprim-sulfamethoxazole. One integron from a swine isolate contained the sat-1 gene, which encodes resistance to streptothricin, an antimicrobial agent that has never been approved for use in the United States. In conclusion, Salmonella serotype Newport MDR-AmpC was commonly identified among Salmonella serotype Newport isolates recovered from humans and food animals. These findings support the possibility of transmission of this organism to humans through the food chain.

Animals↗

Pancreatitis leading to thrombotic thrombocytopenic purpura in systemic lupus erythematosus: a case report and review of literature.

Pancreatitis is a well-established but unusual complication of thrombotic thrombocytopenic purpura (TTP). It is also an unusual complication of systemic lupus erythematosus (SLE). However, TTP occurring as a consequence of acute pancreatitis in a patient with SLE has never been reported. We report a 24-year-old African American woman with active systemic lupus (SLE) who developed thrombotic thrombocytopenic purpura (TTP) following an episode of acute pancreatitis. The TTP was manifested by low-grade fever, microangiopathic hemolytic anemia, renal insufficiency, altered mental status, seizures and thrombocytopenia. The patient was initially treated with pulse corticosteroids with inadequate response and subsequently with daily plasmaphresis, leading to full remission. This case represents first report of pancreatitis leading to TTP in a patient with systemic lupus erythematosus.

Adult↗

Hypothyroidism alters the expression of Bcl-2 family genes to induce enhanced apoptosis in the developing cerebellum.

Thyroid hormone (TH) deficiency results in delayed proliferation and migration of cerebellar granule cells. Although extensive cell loss during the development of the cerebellum under hypothyroid conditions is known, its nature and its mechanism are poorly understood. Bcl-2 family gene expression is known to determine the fate of cells to undergo apoptosis. We evaluated the effect of hypothyroidism on Bcl-2 family gene expression in the developing rat cerebellum. Electrophoresis and Western blotting were used to analyze DNA fragmentation and expression of DNA fragmentation factor (DFF-45), Bcl-2, Bcl-xL and Bax genes respectively. In the hypothyroid condition, extensive DNA fragmentation and enhanced cleavage of DFF-45 were seen throughout development (postnatal day 0 to day 24) and adulthood whereas they were absent in the euthyroid state. The anti-apoptotic genes Bcl-2 and Bcl-xL were down-regulated and the pro-apoptotic gene Bax was expressed at higher levels compared with the euthyroid state. These results suggest that normal levels of TH prevent cerebellar apoptosis to a large extent, whereas hypothyroidism not only increases the extent but also the duration of apoptosis by down-regulating the anti-apoptotic genes and maintaining a high level of the pro-apoptotic gene Bax.

Animals↗

Hypothyroidism alters mitochondrial morphology and induces release of apoptogenic proteins during rat cerebellar development.

Thyroid hormone (TH) deficiency leads to extensive apoptosis during cerebellar development, but the mechanism still remains unclear. Different signals also converge on mitochondria during apoptosis to induce the release of apoptogenic proteins that activate proteolytic cascade through specific enzymes called caspases. Here we studied the effect of hypothyroidism on alterations in mitochondrial structure and translocation of apoptogenic molecules during rat cerebellar development. Structural analysis of mitochondria was studied by electron microscopy. The translocation of apoptogenic molecules was analyzed by Western blotting. TH deficiency led to vacuolization, enlargement and decrease in the number of cristae. The majority of the proapoptotic molecule, Bax, was localized in mitochondria under hypothyroid conditions whereas a limited presence of Bax was detected in the euthyroid state. Translocation of cytochrome c, apoptosis-inducing factor (AIF) and second mitochondrial-derived activator of caspases (SMAC) from mitochondria to cytosol was detected primarily in early developmental stages in the hypothyroid condition. These experimental results demonstrate that TH maintains mitochondrial architecture and inhibits the release of apoptogenic molecules to prevent excess apoptosis during cerebellar development.

Animals↗

4-oxa-1-azabicyclo[3.2.0]heptan-7-one derivatives as anti-tumor agents.

A series of naturally occurring and synthetic novel oxapenam (4-oxa-1-azabicyclo[3.2.0] heptan-7-one) derivatives with their antitumor activity and the structure-activity relationship among this class of compounds is reported. Among the synthetic 4-oxa-1-azabicyclo[3.2.0]heptan-7-one having an ester, amide, ether derivatives of hydroxy group at C-3 position exhibited either no activity or reduced the antitumor activity in vitro. The 3-amino acid 4-oxa-1-azabicyclo[3.2.0]heptan-7-one derivatives showed better antitumor activity than naturally occurring 4-oxa-1-azabicyclo[3.2.0]heptan-7-one derivative G0069A. The trans isomers exhibited superior stability and activity over the cis isomers at the 3- and 5-position. Some of these compounds showed strong cytotoxicity against P388 and KB cells with IC(50) value ranging from 0.004 to 0.6 micro g/ml and they did not show any cross resistance against ADR, 5-FU and VCR resistant cell lines in vitro. Of these, 3-hydroxy methyl, 3-(2-amino-2-carboxy-1-benzyloxy ethyl) and 3-(2-amino-2-carboxy ethyl) 4-oxa-1-azabicyclo[3.2.0] heptan-7-one inhibited 71-84% in vivo tumor growth of colon 26 and S-180 cells subcutaneously implanted into mice at a varying dose between 0.625-15 mg/kg/day depending upon the compounds and the tumor cell lines.

Animals↗