Prevalence of hepatitis C virus isolate genotypes from chronically infected Lebanese patients: a hospital-based study

To assess percentages of hepatitis C virus (HCV) genotypes in infected Lebanese patients referred to St. George Hospital, Beirut, Lebanon, 77 infected cases were studied. Of those, 27 were hemodialysis patients. Genotyping was performed by nested PCR of the HCV core-region with specific primers, followed by DNA enzyme-immunoassay using HCV type and subtype-specific probes. Single genotype infections were detected in 52 patients (67.5%). In these cases, types 1, 2, 3 and 4 were detected in 19.5%, 32.5%, 5.1% and 10.4% of the cases respectively. Twenty-five (32.5%) samples showed mixed genotype infections. Single genotype distribution was significantly different among dialysis and non-dialysis patients. In the dialysis group, genotype 2 was predominant (80%, p < 0.001). In single HCV genotype-infected patients, subtype 1b was frequently detected in nondialysis cases (34.4%) whereas this genotype was found in only 5% of dialysis cases. Genotypes 5 and 6 were not detected in any of the cases studied. This pilot hospital-based study provides evidence for the diversity of HCV genotypes in the Lebanese population and establishes differences in distribution depending on the risk group.     

Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity?

Pozdzik A A, Berton A, Schmeiser H H, Missoum W, Decaestecker C, Salmon I J, Vanherweghem J‐L & Nortier J L
(2010) Histopathology 56 , 449–463 Aristolochic acid nephropathy revisited: a place for innate and adaptive immunity? Aims: The histological features of aristolochic acid nephropathy (AAN) consist of paucicellular interstitial fibrosis, severe tubular atrophy, and almost intact glomeruli with media lesions of interlobular arteries. As an early phase of interstitial inflammation preceded peritubular fibrosis in the rat model of AAN, the aim was to investigate the presence of inflammatory cells in human AAN. Methods and results: Reports of confirmed cases and case series of AAN were reviewed in terms of interstitial inflammation and found to have very conflicting results. This prompted us to search for and characterize inflammatory cells within the native kidneys provided from four end‐stage AAN patients. Prior aristolochic acid exposure was attested by the intrarenal presence of the typical aristolactam I‐derived DNA adduct. Besides the tubulointerstitial lesions usually seen in the cortex, a massive infiltration of macrophages, T and B lymphocytes was detected by immunohistochemistry in the medullary rays and in the outer medullae with some extension to the upper cortical labyrinth. Conclusions: In parallel with histological findings reported in the rat model, inflammatory cells are present preferentially in the interstitium of the medullary rays and of the outer medulllae in renal interstitium from human AAN cases, even in the terminal stages. Further studies must be undertaken to determine the respective roles of innate and adaptive immunity in the progression of AAN.     

Role of cyclooxygenase products in the regulation of vascular tone and in the endothelial vasodilator function of normal, hypertensive, and hypercholesterolemic humans.

A defective vascular activity of endothelial vasoactive substances is observed in essential hypertension and hypercholesterolemia, and is believed to participate in the vascular abnormalities characteristic of these conditions. The present study aimed to determine the role of cyclooxygenase (COX) products in the maintenance of vascular tone and in the endothelium-mediated vasodilation of healthy subjects, and to investigate their contribution to the endothelial dysfunction of essential hypertensive and hypercholesterolemic patients. The effects of intra-arterial aspirin (acetylsalicylic acid [ASA], 1, 3, and 10 mg/min) were assessed on basal forearm blood flow (strain gauge plethysmography) and on responses to acetylcholine (7.5, 15 and 30 microg/min) and sodium nitroprusside (0.8, 1.6 and 3.2 microg/min) in 24 normal, 23 hypertensive, and 24 hypercholesterolemic subjects. Basal forearm blood flow was not different among the 3 groups (p = 0.95). ASA resulted in a significant reduction of forearm blood flow from baseline in normal (p = 0.003), hypertensive (p = 0.001), and hypercholesterolemic subjects (p = 0.001), without any difference among the 3 groups (p = 0.90). ASA significantly improved the effect of acetylcholine in normal (p = 0.008), hypertensive (p = 0.008), and hypercholesterolemic subjects (p = 0.022), without significant difference among the 3 groups (p = 0.46). ASA did not significantly modify the vasodilator effect of sodium nitroprusside in any of the 3 groups. These findings suggest that in humans, vasodilator prostanoids actively contribute to the maintenance of basal vascular tone, whereas vasoconstrictor products of COX activity limit endothelium-dependent vasodilation. COX products do not appear to play a major role in the endothelial dysfunction of hypertensive or hypercholesterolemic patients.     

An Updated Critical Analysis of the Treatment Strategy for Newly Diagnosed High-grade T1 (Previously T1G3) Bladder Cancer

Context

High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as “T1G3.”

Objective

To review the current literature on the management of T1G3 BCa and to provide recommendations for its treatment.

Evidence acquisition

A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1996 and 9 January 2009 was performed using the Medical Subject Headings “T1G3” or “T1” and “Bladder cancer.” Articles relevant to the treatment of T1G3 BCa were retained.

Evidence synthesis

The diagnosis of T1G3 disease is difficult because pathologic staging is often unreliable and because of the risk of significant understaging at initial transurethral resection (TUR) of bladder tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing approach, intravesical BCG should be given as induction with maintenance dosing. Immediate or early radical cystectomy (RC) should be offered to all patients with recurrent or multifocal T1G3 disease, those who are at high risk of progression, and those failing BCG treatment.

Conclusions

Both bladder preservation and RC are appropriate options for T1G3 BCa. Risk stratification of patients based on pathologic features at initial TUR or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.     

A Critical Analysis of Orthotopic Bladder Substitutes in Adult Patients with Bladder Cancer: Is There a Perfect Solution?

Context

Orthotopic bladder substitute (OBS) has been popularized over the past 2 decades as a diversion following radical cystectomy for invasive bladder cancer. Various reports, mostly single-center experiences, are published on patients with OBS.

Objective

This study reviews the literature regarding indications, postoperative care, complications, quality-of-life measures, as well as functional and oncologic outcomes that have been published on patients with OBS.

Evidence acquisition

An English-language literature review of the Medline database (1990 to January 2010) of published data on patients with OBS following radical cystectomy for bladder cancer was undertaken. Articles that included surgery for noncancer etiology were excluded.

Evidence synthesis

Indications and patient selection criteria have significantly widened over the past 2 decades. Comparable oncologic data have been reported between patients with OBS versus other diversions. Secondary urethral tumors seem less common in patients with OBS compared with those with conduits or continent cutaneous diversions. Durable daytime and nocturnal continence is achieved in 85–90% and 60–80%, respectively. Continence is inferior in elderly patients with OBS. Urinary retention remains significant in the female patients, ranging from 25% to 50%. Complications including electrolyte disturbances, altered sensorium and drug metabolism, mucus retention, rupture, urinary tract infections, and upper tract deterioration are reviewed.

Conclusions

Indications for OBS following radical cystectomy in patients with invasive bladder cancer have significantly widened over the past 2 decades. An OBS should be offered to both male and female patients in the absence of contraindications. Good long-term functional and oncologic outcomes can be achieved in patients with OBS treated in high-volume institutions by experienced surgeons with specific knowledge in the field. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.     

Mass casualty incidents with multiple burn victims: Rationale for a Swiss burn plan

Introduction

Mass casualty incidents involving victims with severe burns pose difficult and unique problems for both rescue teams and hospitals. This paper presents an analysis of the published reports with the aim of proposing a rational model for burn rescue and hospital referral for Switzerland.

Methods

Literature review including systematic searches of PubMed/Medline, reference textbooks and journals as well as landmark articles.

Results

Since hospitals have limited surge capacities in the event of burn disasters, a special approach to both prehospital and hospital management of these victims is required. Specialized rescue and care can be adequately met and at all levels of needs by deploying mobile burn teams to the scene. These burn teams can bring needed skills and enhance the efficiency of the classical disaster response teams. Burn teams assist with both primary and secondary triage, contribute to initial patient management and offer advice to non-specialized designated hospitals that provide acute care for burn patients with Total Burn Surface Area (TBSA) <20–30%. The main components required for successful deployments of mobile burn teams include socio-economic feasibility, streamlined logistical implementation as well as partnership coordination with other agencies including subsidiary military resources.

Conclusions

Disaster preparedness plans involving burn specialists dispatched from a referral burn center can upgrade and significantly improve prehospital rescue outcome, initial resuscitation care and help prevent an overload to hospital surge capacities in case of multiple burn victims. This is the rationale behind the ongoing development and implementation of the Swiss burn plan.