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P B Singh

Publications and source records attributed to P B Singh.

At least 19 recordsLinked to original sources

A decade's experience with vesicovaginal fistula in India.

A retrospective analysis of 252 cases of vesicovaginal fistulae was done to analyse its etio-pathology and management in an Indian population. After a thorough evaluation, different techniques of fistula closure were used for repair and the results were listed. The main outcome measures were the etiology of the fistula, need for tissue interposition and cure rate per repair as well as the overall cure rate. We compared our results with literature and concluded that simple and small fistulae should be repaired with layered closure. All complicated fistulae should be repaired with tissue interposition or tissue graft. This is the first study from India compiling 10 years of experience on vesicovaginal fistula.

Adolescent↗

Post caesarean vesicouterine fistulae-- Youssef syndrome: our experience and review of published work.

OBJECTIVE: To analyse the incidence, symptomatology, diagnosis and therapeutic aspects of Youssef syndrome (post caesarean vesicouterine fistula), and to review relevant published work. METHODS: A retrospective study from the urosurgical unit of a tertiary care referral hospital was carried out. In a retrospective analysis of urogenital fistulae over 10 years, we identified 14 patients with uterovesical fistulae, resulting from caesarean section. All the patients were evaluated by history, physical examination, radiological tests and cystoscopy. All patients underwent transperitoneal repair of these fistulae with omental interposition. Results of surgery were evaluated by absence of cyclic haematuria, stoppage of urinary incontinence, and achievement of fertility. RESULTS: A total of 12 patients who had minimum follow up was included in the present study. The results showed that 50% of the fistulae resulted from emergency caesarean operation with 58% of patients presenting after their second caesarean section. The mean age of the patients was 19 years (range 15-29) and mean duration of symptoms was 7 months (range 3-16). Menouria and amenorrhoea were predominant presenting symptoms. The results of surgical treatment were excellent with good continence and resolution of the cyclic haematuria. Three pregnancies (37.5%) which resulted in elective caesarean section were recorded. CONCLUSION: Vesicouterine fistulae, despite being infrequent, are no longer a rare diagnosis and are most commonly secondary to lower segment caesarean section. With patient history and selected investigations diagnosis is relatively easy. The surgical repair of these fistulae is standard treatment, especially with delayed fistulae with achievement of total continence, and complete resolution of cyclic haematuria. Meticulous practice of obstetric and surgical principles during caesarean section can prevent the formation of these fistulae.

Adolescent↗

Safety and efficacy of ureteroscopic lithotripsy for ureteral calculi under sedoanalgesia--a prospective study.

OBJECTIVE: To establish the safety and efficacy of ureteroscopic lithotripsy (URSL) under sedoanalgesia. PATIENTS AND METHODS: This study was conducted at Department of Urology (Banaras Hindu University, India) among 124 patients with ureteral stones, between July 2000 and August 2003. Majority of the patients (59.68%) presented with lower ureteric calculi, 24.19% presented with upper ureteric calculi and 16.13% had middle ureteric calculi. All patients were given injection diclofenac sodium (75 mg) promethazine hydrochloride (12.5 mg) deep intramuscular 30 minutes the before procedure. Injection midazolam 0.03 mg/kg body weight slowly given intravenously immediately before the procedure for achieving sedation. Injection fentanyl 50 mcg intravenously given slowly just before introducing the ureteroscope into ureter for achieving intravenous analgesia. Patients were observed for few hours after completion of procedure and oral questions were asked as per proforma, which included tolerance, intensity of pain and percentage of pain experienced by the patients. Patients were discharged thereafter. RESULTS: 87.10% of patients opined that the procedure was acceptable. Only 4.84% opined this procedure was painful. According to present pain intensity score (PPI) in this study 79.03 patients experienced only mild pain, 11.29% cases rated procedure as discomforting, 6.45 rated procedure as distressing and only 3.23% rated as horrible procedure. As per visual analogue scale for assessment of pain 80.65 of cases rated only 20% pain score (in a scale of 0-100). 9.68% cases rated 30% and 6.45% rated 50%. Only two patients in middle ureteric group rated 100% pain. Overall success rate in fragmenting stone was 91.94, where as for lower ureteric calculi it was 97.30%; for upper and, middle ureteric calculi it was 86.66% and 80%, respectively. CONCLUSION: Ureteroscopic lithotripsy can be performed on day care basis under sedoanalgesia which is fairly tolerated by the patients with unremarkable complications and difficulty.

Adolescent↗

Serum p53 and bladder cancer: can serum p53 be used as a tumor marker?

The aim of this study was to find the correlation between serum p53 and carcinoma of the bladder and to investigate whether serum p53 protein can be used as a tumor marker for p53 gene alteration. The study included patients with carcinoma of the bladder and controls. Serum p53 protein estimation was done with an ELISA kit. There were 23 patients with superficial and 17 with invasive carcinoma. The median serum p53 was 31.5 U/ml in superficial and 41 U/ml in invasive cancer. This was significantly higher than the mean value (16.4 U/ml) of controls. Serum p53 rises in patients with carcinoma of the bladder and correlates with the grade of the disease . It can therefore be used as a tumor marker for bladder cancer.

Biomarkers, Tumor↗

Mucocutaneous lesions in transplant recipient in a tropical country.

Dermatological manifestations are common in renal transplant patients, but differ markedly with ethnic group and geographical location. We studied mucocutaneous lesions in 54 renal allograft recipients (related donors = 30; unrelated donors = 24) living in tropical atmospheres. Their gender was 50 males, and 4 females ranging in age between 15 and 63 years (mean = 37.84 years). The mean duration of follow-up was 124 months (range = 4 to 173 months). All patients received kidneys from living donors and were kept on immunosupression with mean daily doses of prednisolone, azathioprine, and cyclosporine of 10.2 mg, 68.6 mg, and 252 mg, respectively. The mean trough concentration of cyclosporine was 185 ng/mL. The mucocutaneous lesions were divided into four groups: drug-induced (n = 24, 44.4%), fungal (n = 18, 33.3%), viral (n = 9, 16.6%), and bacterial (n = 10, 18.5%). Cushingoid features, gum hypertrophy, and hypertrichosis were seen in 7 (12.9%) patients. Steroid acne was seen in three cases. Pityriasis versicolor was the most common (20.3%) fungal infection of the skin. In addition, Tinea unguium and mucocutaneous candidiasis were noted in four and three cases respectively. Herpes virus infection (Herpes zoster 5; Herpes simplex 2) was noted in 7 (12.9%) cases. Chicken pox at 5 years posttransplant and cutaneous vasculitis associated with cytomegalovirus disease at 6 months posttransplant were seen in one case each. We have not seen warts in our patients. Pyogenic bacterial infection of skin in the form of abscess (n = 6), cellulitis (n = 3), and pyoderma (n = 1) were observed in 10 (18.5%) patients. Thus, drug-induced mucocutaneous side effects and skin fungal infections are the most common dermatological manifestations among renal transplant recipients living in a tropical country.

Adolescent↗

Povidone iodine and dextrose solution combination sclerotherapy in chyluria.

OBJECTIVES: To evaluate the effectiveness of combination (povidone iodine and 50% dextrose) renal pelvic instillation sclerotherapy (RPIS) as a minimally invasive therapy for chyluria resistant to conservative treatment. METHODS: A total of 50 patients with chyluria and hematochyluria (28 men and 22 women) were included in the study. Initially, all were offered conservative antifilarial drug therapy and dietary fat restriction. Intravenous urography was done in all cases to document normal renal functional status. In the patients in whom chyluria persisted after 3 weeks of conservative therapy, cystoscopic lateralization was done and a 5F open-ended ureteral catheter was positioned under local anesthesia. The same was left attached to a 16F Foley catheter for 3 days of RPIS. A solution of 5 mL of 5% povidone iodine and 5 mL of 50% dextrose was instilled twice a day with the patient in the Trendelenburg position for 3 days. In cases of bilateral efflux, the dominant side was treated first. The opposite side was subjected to a similar instillation sclerotherapy schedule after 6 weeks if chyluria persisted. RESULTS: Of the 50 patients, only 4 responded to conservative therapy. The remaining 46 patients underwent combination RPIS. The mean follow-up was 24 months. Complete remission of chyluria or hematochyluria occurred in 40 (87%) and persisted in 6 patients (13%). Of the 6 patients in whom symptoms persisted, 2 developed chyluria on the side opposite the one treated with RPIS. Another 2 patients developed recurrence on the same side after remaining asymptomatic for 6 months after RPIS. All four of these patients subsequently underwent chylolymphatic disconnection and nephropexy (two open and two laparoscopic) with a successful outcome. The final 2 patients with persistent symptoms were lost to follow-up. CONCLUSIONS: Combination sclerotherapy using a 5% povidone iodine and 50% dextrose solution is a safe and cost-effective minimally invasive therapy for chyluria refractory to conservative treatment.

Adult↗

Messenger RNA electroporation is highly efficient in mouse embryonic stem cells: successful FLPe- and Cre-mediated recombination.

Development of efficient short-term gene transfer technologies for embryonic stem (ES) cells is urgently needed for various existing and new ES cell-based research strategies. In this study, we present a highly efficient, nonviral non-DNA technology for genetic loading of mouse ES cells based on electroporation of defined mRNA. Here, we show that mouse ES cells can be efficiently loaded with mRNA encoding a green fluorescent reporter protein, resulting in a level of at least 90% of transgene expression without loss of cell viability and phenotype. To show that transgenes, introduced by mRNA electroporation, exert a specific cellular function in transfected cells, we electroporated stably transfected ES cell lines with mRNA encoding FLPe or Cre recombinase proteins in order to excise an FRT- or LoxP-flanked reporter gene. The results, as determined by the disappearance and/or appearance of a fluorescent reporter gene expression, show that FLPe and Cre recombinase proteins, introduced by mRNA electroporation, efficiently exert their function without influence on further culture of undifferentiated ES cell populations and their ability to differentiate towards a specific lineage.

Animals↗

Filarial chyluria: long-term experience of a university hospital in India.

BACKGROUND: Filariasis is an endemic problem in various Indian states. We evaluated the results of long-term follow up (10-20 years) of patients with filarial chyluria. METHODS: We conducted a retrospective analysis of 160 patients treated for filarial chyluria who presented to the Banaras Hindu University Hospital from 1982 to 1992. Eighty-four patients (52.5%) were treated using diethylcarbamazine (DEC) and a fat restricted diet and 76 patients (47.5%) underwent surgery. To examine the long-term effects of filarial chyluria we analysed data on post-treatment recurrence, weight gain, dietary freedom, chyluria free period and a number of other associated factors. RESULTS: Previous history of filariasis or its complication was documented in 19% of patients. In 71% of cases, cystoscopy showed that chylous efflux was predominant in the left ureteric orifice. The long-term remission rate was 62% in the conservatively managed group (DEC + fat restricted diet), whereas 90% of patients in the operated group were cured. Postoperative recurrence rate was 10%. There was more weight gain and dietary freedom along with a longer chyluria free period in the operated group relative to the conservatively managed group. CONCLUSIONS: Definitive surgical ablation of lymphatic urinary fistula is better than conservative medical management because it has a higher success rate, more dietary freedom and, therefore, better patient acceptability.

Adolescent↗

Exposure of infants to outdoor and indoor air pollution in low-income urban areas - a case study of Delhi.

Indoor air pollution is potentially a very serious environmental and public health problem in India. In poor communities, with the continuing trend in biofuel combustion coupled with deteriorating housing conditions, the problem will remain for some time to come. While to some extent the problem has been studied in rural areas, there is a dearth of reliable data and knowledge about the situation in urban slum areas. The microenvironmental model was used for assessing daily-integrated exposure of infants and women to respirable suspended particulates (RSP) in two slums of Delhi - one in an area of high outdoor pollution and the other in a less polluted area. The study confirmed that indoor concentrations of RSP during cooking in kerosene-using houses are lesser than that in wood-using houses. However, the exposure due to cooking was not significantly different across the two groups. This was because, perhaps due to socioeconomic reasons, kerosene-using women were found to cook for longer durations, cook inside more often, and that infants in such houses stayed in the kitchen for longer durations. It was observed that indoor background levels during the day and at nighttime can be exceedingly high. We speculate that this may have been due to resuspension of dust, infiltration, unknown sources, or a combination of these factors. The outdoor RSP levels measured just outside the houses (near ambient) were not correlated with indoor background levels and were higher than those reported by the ambient air quality monitoring network at the corresponding stations. More importantly, the outdoor levels measured in this study not only underestimated the daily-integrated exposure, but were also poorly correlated with it.

Adult↗

Artificial neural networks in predicting optimum renal stone fragmentation by extracorporeal shock wave lithotripsy: a preliminary study.

OBJECTIVE: To assess the ability of artificial neural networks (ANNs) to predict optimum renal stone fragmentation in patients being managed by extracorporeal shock wave lithotripsy (ESWL). PATIENTS AND METHODS: The study included 82 patients with renal stones who were being treated by ESWL. Data (input and output values) from 60 patients in whom there was optimum fragmentation of stones by ESWL were used for training the ANN. These data mainly included the 24-h urinary variables, the radiological features of the stone disease and the ESWL settings used. The predictability of the trained ANN was tested on 22 subsequent patients, by supplying the input variables of the 22 patients into the trained ANN and recording the output values (predicted values). After subjecting these patients to ESWL, the actual results (observed values) were recorded. The predicted and the observed values were then compared. RESULTS: In the 22 patients in whom predictability was tested, the trained ANN predicted optimum fragmentation at < or = 13 000 shocks/stone (as per study protocol) in 17 and optimum fragmentation at> 13 000 shocks/stone in the other five. In the 17 patients (test set) where the trained ANN had predicted optimum fragmentation at < or = 13 000 shocks/stone, the optimum fragmentation was at that value, although the predicted and observed values were not identical. The overall correlation between the predicted and the observed values was 75.5% (correlation coefficient 0.7547) in these 17 patients. Of the other five patients, none had optimum fragmentation at < 13 000 shocks/stone, as predicted by the trained ANN, giving complete accuracy for this factor. CONCLUSION: This was a pilot study, i.e. an initial attempt to use an ANN in this regard, and although there were few patients, such that it is not possible to make final recommendations, the overall predictability was approximately 75%. An encouraging outcome of the study was that the trained ANN identified patients unlikely to benefit from ESWL. Using a larger dataset and identifying more significant variables, while eliminating inputs with a negative effect, the efficiency and utility of this ANN can probably be enhanced and in future it might be possible to predict stone fragmentation with reasonable accuracy.

Humans↗

Histones H3/H4 form a tight complex with the inner nuclear membrane protein LBR and heterochromatin protein 1.

We have recently shown that heterochromatin protein 1 (HP1) interacts with the nuclear envelope in an acetylation-dependent manner. Using purified components and in vitro assays, we now demonstrate that HP1 forms a quaternary complex with the inner nuclear membrane protein LBR and a sub-set of core histones. This complex involves histone H3/H4 oligomers, which mediate binding of LBR to HP1 and cross-link these two proteins that do not interact directly with each other. Consistent with previous observations, HP1 and LBR binding to core histones is strongly inhibited when H3/H4 are modified by recombinant CREB-binding protein, revealing a new mechanism for anchoring domains of under-acetylated chromatin to the inner nuclear membrane.

Acetylation↗

Binding of heterochromatin protein 1 to the nuclear envelope is regulated by a soluble form of tubulin.

We have previously shown that the mouse heterochromatin protein 1 homologue M31 interacts dynamically with the nuclear envelope. Using quantitative in vitro assays, we now demonstrate that this interaction is potently inhibited by soluble factors present in mitotic and interphase cytosol. As indicated by depletion and order-of-addition experiments, the inhibitory activity co-isolates with a 55-kDa protein, which binds avidly to the nuclear envelope and presumably blocks M31-binding sites. Purification of this protein and microsequencing of tryptic peptides identify it as alpha2/6:beta2-tubulin. Consistent with this observation, bona fide tubulin, isolated from rat brain and maintained in a nonpolymerized state, abolishes binding of M31 to the nuclear envelope and aborts M31-mediated nuclear envelope reassembly in an in vitro system. These observations provide a new example of "moonlighting," a process whereby multimeric proteins switch function when their aggregation state or localization is altered.

Amino Acid Sequence↗

M31 and macroH2A1.2 colocalise at the pseudoautosomal region during mouse meiosis.

Progression through meiotic prophase is associated with dramatic changes in chromosome condensation. Two proteins that have been implicated in effecting these changes are the mammalian HP1-like protein M31 (HP1beta or MOD1) and the unusual core histone macroH2A1.2. Previous analyses of M31 and macroH2A1.2 localisation in mouse testis sections have indicated that both proteins are components of meiotic centromeric heterochromatin and of the sex body, the transcriptionally inactive domain of the X and Y chromosomes. This second observation has raised the possibility that these proteins co-operate in meiotic sex chromosome inactivation. In order to investigate the roles of M31 and macroH2A1.2 in meiosis in greater detail, we have examined their localisation patterns in surface-spread meiocytes from male and female mice. Using this approach, we report that, in addition to their previous described staining patterns, both proteins localise to a focus within the portion of the pseudoautosomal region (PAR) that contains the steroid sulphatase (Sts) gene. In light of the timing of its appearance and of its behaviour in sex-chromosomally variant mice, we suggest a role for this heterochromatin focus in preventing complete desynapsis of the terminally associated X and Y chromosomes prior to anaphase I.

Animals↗

Chemosensation and genetic individuality.

Numerous studies have shown that there are measurable behavioural consequences that can result from the olfactory recognition of alleles borne at the major histocompatibility complex (MHC). These consequences include simple individual recognition, disassortative mate preference, discrimination of kin from non-kin and whether a pregnancy is carried to term. Such a system, which can influence the reproductive behaviour of a species, will have profound effects on its genetic constitution and survival. The likely mechanism responsible for the production of MHC-related odours involves soluble MHC molecules that carry allele-specific odoriferous molecules from the blood via the kidneys into the urine, from where they are released into the environment. The ability of soluble MHC molecules to signal genetic individuality in this way may have evolved before the appearance of an acquired immune system in our immediate ancestors, the protochordates.

Animals↗

The gene and pseudogenes of Cbx3/mHP1 gamma.

The HP1 class of chromobox (Cbx) genes encode an evolutionarily conserved family of proteins involved in the packaging of chromosomal domains into a repressive heterochromatic state. The murine Cbx5, Cbx1 and Cbx3 genes encode the three mouse HP1 proteins, mHP1 alpha, -beta and -gamma respectively. Here, we report the cloning of the mouse Cbx3/HP1 gamma gene and the chromosomal localisation of Cbx3 and three Cbx3-related pseudogenes. The Cbx3 structural gene is located on mouse Chromosome 6, close to the Hoxa cluster. Two Cbx3 processed pseudogenes are separated by just 300 bp and are arranged in a head-to-tail configuration on Chromosome 13 while a third pseudogene is found on mouse Chromosome 4. The genomic intron-exon arrangement of Cbx3 is different from the conserved organisation of three other mammalian HP1 genes, Cbx1 (mHP1 beta), CBX3 (hHP1 gamma), and Cbx5 (mHP1 alpha) in that Cbx3 lacks an intron that is present in the others.

Amino Acid Sequence↗

Dynamic associations of heterochromatin protein 1 with the nuclear envelope.

To study the dynamics of mammalian HP1 proteins we have microinjected recombinant forms of mHP1alpha, M31 and M32 into the cytoplasm of living cells. As could be expected from previous studies, the three fusion proteins were efficiently transported into the nucleus and targeted specific chromatin areas. However, before incorporation into these areas the exogenous proteins accumulated in a peripheral zone and associated closely with the nuclear envelope. This transient association did not occur when the cells were treated with deacetylase inhibitors, indicating an acetylation-inhibited interaction. In line with these observations, recombinant HP1 proteins exhibited saturable binding to purified nuclear envelopes and stained the nuclei of detergent-permeabilized cells in a rim-like fashion. Competition experiments with various M31 mutants allowed mapping of the nuclear envelope-binding site within an N-terminal region that includes the chromodomain. A His(6)-tagged peptide representing this region inhibited recruitment of LAP2beta and B-type lamins around the surfaces of condensed chromosomes, suggesting involvement of HP1 proteins in nuclear envelope reassembly.

Acetylation↗

The murine heterochromatin protein M31 is associated with the chromocenter in round spermatids and Is a component of mature spermatozoa.

In mature sperm the normal nucleosomal packaging of DNA found in somatic and meiotic cells is transformed into a highly condensed form of chromatin which consists mostly of nucleoprotamines. Although sperm DNA is highly condensed it is nevertheless packaged into a highly defined nuclear architecture which may be organized by the heterochromatic chromocenter. One major component of heterochromatin is the heterochromatin protein 1 which is involved in epigenetic gene silencing. In order to investigate the possible involvement of heterochromatin protein in higher order organization of sperm DNA we studied the localization of the murine homologue of heterochromatin protein 1, M31, during chromatin reorganization in male germ cell differentiation. Each cell type in the testis showed a unique distribution pattern of M31. Colocalization to the heterochromatic regions were found in Sertoli cells, in midstage pachytene spermatocytes, and in round spermatids in which M31 localizes to the centromeric chromocenter. M31 cannot be detected in elongated spermatids or mature spermatozoa immunocytologically, but could be detected in mature spermatozoa by Western blotting. We suggest that M31, a nuclear protein involved in the organization of chromatin architecture, is involved in higher order organization of sperm DNA.

Animals↗

Mammalian chromodomain proteins: their role in genome organisation and expression.

The chromodomain is a highly conserved sequence motif that has been identified in a variety of animal and plant species. In mammals, chromodomain proteins appear to be either structural components of large macromolecular chromatin complexes or proteins involved in remodelling chromatin structure. Recent work has suggested that apart from a role in regulating gene activity, chromodomain proteins may also play roles in genome organisation. This article reviews progress made in characterising mammalian chromodomain proteins and emphasises their emerging role in the regulation of gene expression and genome organisation. BioEssays 22:124-137, 2000.

Amino Acid Sequence↗