Complex urethral disruptions: In pursuit of a successful reconstruction

OBJECTIVES: We analyzed the methods and outcomes of urethroplasty in men with complex urethral disruptions. METHODS: The medical records of 40 men with complex urethral disruptions were analyzed. Surgical methods were individualized according to stricture location, severity and length of the stricture, bladder neck characteristics and presence of complicating factors. Patients were divided into four groups based on the above characteristics. RESULTS: End-to-end urethroplasty performed in six patients with short bulbar strictures (<3 cm) was successful in all. Elaborated perineal repair was performed in 10 patients with intermediate (3-6 cm) strictures with or without complicating factors. Elaborated perineal repair with urethral substitution was performed in nine patients with long segment stricture (>6 cm). Abdominal transpubic repair was successfully applied to patients with rectourethral fistula or lacerated bladder neck. Success rate of anastomotic urethroplasty was 95% while over all success rate was 85%. CONCLUSION: Guidelines for urethral reconstruction of complex urethral disruptions are predicated on stricture length, location, bladder neck characteristics and associated complicating factors. End-to-end urethroplasty with stricture excision is highly reliable for short strictures for which previous operative repair have failed. Elaborated perineal repair is extremely versatile for intermediate and longer strictures with associated complicating factors. Abdominal transpubic urethroplasty is effective for patients with rectourethral fistula or lacerated bladder neck.     

Duodenogastric reflux after choledochoduodenostomy

Duodenogastric reflux (DGR) has been implicated in several disease processes. The present study was carried out to document the incidence and evaluate the clinical significance of DGR after choledochoduodenostomy (CDD). A total of 13 patients who had undergone cholecystectomy with a standard side-to-side CDD for choledocholithiasis or chronic pancreatitis were studied by symptom evaluation, scintigraphy, endoscopy, and gastric mucosal histology at least 6 months after surgery. The scintigraphic findings were then compared with those of 10 patients who had undergone cholecystectomy alone. Only two patients (15%) had mild dyspeptic symptoms. The incidence of DGR after CDD was 69% compared to 20% in the cholecystectomy alone group (P < 0.05). In the majority of patients the DGR was only mild to moderate and the severity correlated well with the degree of endoscopic gastritis, but not with the clinical symptoms or histological findings. These results indicate that while CDD is associated with a high incidence of DGR, its occurrence does not produce significant clinical symptoms.     

Thymopentin and splenopentin as immunomodulators

Splenopentin (SP-5, Arg-Lys-Glu-Val-Tyr) and thymopentin (TP-5, Arg-Lys-Asp-Val-Tyr) are synthetic immunomodulating peptides corresponding to the region 32–34 of a splenic product called splenin (SP) and the thymic hormone thymopoietin (TP), respectively. TP was originally isolated as a 5-kDa (49-amino acids) protein from bovine thymus while studying effects of the thymic extracts on neuromuscular transmission and was subsequently observed to affect T cell differentiation and function. TP I and II are two closely related polypeptides isolated from bovine thymus. A radioimmunoassay for TP revealed a crossreaction with a product found in spleen and lymph node. This product, named splenin, differs from TP only in position 34, aspartic acid for bovine TP and glutamic acid for bovine splenin and it was called TP III as well. Synthetic pentapeptides (TP-5) and (SP-5), reproduce the biological activities of TP and SP, respectively. It is now evident that various forms of TPs were created by proteolytic cleavage of larger proteins during isolation. cDNA clones have been isolated for three alternatively spliced mRNAs that encodes three distinct human T cell TPs. The immunomodulatory properties of TP, SP, TP-5, SP-5 and some of their synthetic analogs reported in the literature have been briefly reviewed.     

Development of Press-Coated,Floating-Pulsatile Drug Delivery of Lisinopril

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.     

HIV‐infected CD4+ T Cells Use T‐bet‐dependent Pathway for Production of IL‐10 Upon Antigen Recognition

Interleukin (IL)‐10 has been implicated in persistence of pathogens in a number of chronic infections. Infected CD4+ cells upon reactivation with HIV antigens were also shown to produce IL‐10, which might contribute to their persistence. Hence, it is crucial to determine mechanisms regulating IL‐10 production after activation with HIV antigens for devising effective blocking strategies. In this study, ERK‐, T‐bet‐ and FoxP3‐dependent pathways were evaluated for their possible roles in IL‐10 production by infected CD4+ cells after reactivation with HIV Env. Intracellular and secreted IL‐10 levels were determined by flow cytometry and Bioplex assay after treating PBMCs with PD98059, tipifarnib and cyclosporin A for blocking of ERK‐, T‐bet‐and FoxP3‐dependent pathways, respectively. Baseline levels of T‐bet, pERK were higher in P24+ CD4+ cells as compared to uninfected CD4+ cells, which increased further after activation with Env. Inhibition of T‐bet resulted in 2.3‐fold reduction of IL‐10 expression whereas ERK and FoxP3 inhibition failed to cause suppression of IL‐10 expression. Conversely, IL‐10 secreted by PBMCs was inhibited maximally after ERK inhibition suggesting its role in regulation of cytokine secretory pathway. IFN‐γ was found to be suppressed after treatment with inhibitors of all these pathways. Thus, the study highlighted need for IL‐10 blockade along with the use of antigens for therapeutic vaccinations or latency reversal and identified the T‐bet‐dependent pathway as an important pathway regulating IL‐10 production by infected CD4+ cells. However, simultaneous blockade of IFN‐γ precludes use of inhibitor of this pathway as an IL‐10 blocking strategy.     

Association between a prolonged corrected QT interval and outcomes in patients in a medical Intensive Care Unit

Introduction:

Patients admitted into a medical Intensive Care Unit (ICU) have varying illnesses and risk factors. An electrocardiogram (ECG) is a useful tool to assess the cardiac status. The aim of the study was to determine the prevalence of QT prolongation of the ECG in patients admitted to a medical ICU in a tertiary hospital, to assess outcomes in terms of mortality, cardiovascular events, and duration of ICU stay.

Materials and Methods:

Prospective observational study, 6 months duration, assessing the prevalence of prolonged corrected QT interval (QTc) at admission into a medical ICU. A QTc calculated by Bazett''s formula, of >440 ms for males and >460 ms for females was considered prolonged. Details of illness, clinical and lab parameters were monitored.

Results:

The total number of patients screened was 182. There was a high prevalence of prolonged QTc (30%) on admission to the ICU. This reduced to 19% on day 3 (P = 0.011). In patients with a prolonged QTc the odds ratio of adverse outcome from ICU was 3.17 (confidence interval [CI]: 1.52–6.63) (P = 0.001) and of adverse outcome for hospital stay was 2.27 (CI: 1.11–4.66) (P = 0.014). In the study, 35% of all patients received drugs with QT prolonging action. Of patients with a prolonged QTc at admission 18 (35%) received a QT prolonging drug.

Conclusions:

We found that prolonged QTc is common (30%) in our medical ICU at admission and a large proportion (35%) received drugs capable of prolonging QT interval. These patients with QTc prolongation have a higher odds ratio for adverse outcomes.     

Sensitivity and specificity of rapid HIV testing of pregnant women in India

OBJECTIVE: Efforts to prevent HIV transmission from mother to infants in settings like India may benefit from the availability of reliable methods for rapid and simple HIV screening. Data from India on the reliability of rapid HIV test kits are limited and there are no data on the use of rapid HIV tests for screening of pregnant women. METHODS: Pregnant women attending an antenatal clinic and delivery room in Pune agreed to participate in an evaluation of five rapid HIV tests, including (a) a saliva brush test (Oraquick HIV-1/2, Orasure Technologies Inc.), (b) a rapid plasma test (Oraquick HIV-1/2) and (c) three rapid finger prick tests (Oraquick HIV-1/2; HIV-1/2 Determine, Abbott; NEVA HIV-1/2 Cadila). Results of the rapid tests were compared with three commercial plasma enzyme immunoassay (EIA) tests (Innotest HIV AB EIA, Lab systems/ELISCAN HIV AB EIA, UBI HIV Ab EIA). RESULTS: Between September 2000 and October 1, 2001, 1258 pregnant women were screened for HIV using these rapid tests. Forty-four (3.49%) of the specimens were HIV-antibody-positive by at least two plasma EIA tests. All of the rapid HIV tests demonstrated excellent specificity (96-100%). The sensitivity of the rapid tests ranged from 75-94%. The combined sensitivity and specificity of a two-step algorithm for rapid HIV testing was excellent for a number of combinations of the five rapid finger stick tests. CONCLUSION: In this relatively low HIV prevalence population of pregnant women in India, the sensitivity of the rapid HIV tests varied, when compared to a dual EIA algorithm. In general, the specificity of all the rapid tests was excellent, with very few false positive HIV tests. Based upon these data, two different rapid HIV tests for screening pregnant women in India would be highly sensitive, with excellent specificity to reliably prevent inappropriate use of antiretroviral therapy for prevention of vertical HIV transmission.     

Left atrial spindle cell sarcoma - Case report

Primary spindle cell sarcoma of the left atrium is an extremely rare tumour. Surgical excision is the mainstay of treatment since it responds poorly to chemotherapy or radiotherapy. In spite of all the treatment, the prognosis remains poor due to inadvertent delay in diagnosis, few therapeutic options and propensity to metastasize. We present a 47-year-old male who underwent a surgical excision of a left atrial mass in February 2010. It was proved to be a high-grade spindle cell sarcoma on histopathology. He presented again in October 2010 with recurrence of the tumour for which he was re-operated. However, the tumour recurred again within one month, to which the patient succumbed.     

A study of clinical presentation and delays in management of acute myocardial infarction in community

To assess the medico social demographics of acute myocardial infarction (AMI) in our community we studied 609 patients presenting between January 2008 to December 2008 with a detailed questionnaire in four centres of UP. Medical attention was sought late (> 6 hours) in 316 (51.6%), thrombolysis was obtained in 45.2% (275) and presentation was atypical in 16.3% (99). 36.2% (221) had pre-monitory symptoms of which 68% (150) ignored the same while of 32% (71) who did seek medical attention 47.9% (37) were brushed away as non-cardiac in origin. 20.3% (46/226) of hypertension, 23.2% (43/185) of diabetes and 83.4% (91/109) of hyperlipidaemia was diagnosed post event. We conclude that at least half of patients with AMI do not get definitive therapy, at least one in 10 patients do not have the classical symptoms, reasonable proportion are unaware of their risk factors, and a good majority have pre-monitory symptoms which get overlooked.