Epidemiology and clinical pattern of hepatitis delta virus infection in Pakistan

BACKGROUND AND AIMS: The global epidemiology of hepatitis delta virus (HDV) infection is changing. This study was performed to determine the epidemiology and clinical impact of hepatitis delta in Pakistan. METHODS: Countrywide data was collected from 1994 to 2001. A total of 8721 patients were tested for hepatitis delta antibody. A subset of 97 hepatitis delta antibody reactive inpatients with chronic liver disease were compared to 97 patients admitted with liver disease due to hepatitis B alone. RESULTS: Of the 8721 patients tested, 1444 (16.6%) were reactive for hepatitis delta antibody. Most were males (87.4%, P < 0.001) and younger (mean age 31 years, P < 0.001) compared to HDV non-reactive patients. Prevalence of delta infection was highest in the rural (range 25-60%) compared to the urban population (range 6.5-11%). Analysis of the inpatient data showed that delta infected patients had significantly less severe clinical liver disease and a trend towards lesser development of hepatocellular carcinoma compared to delta negative patients. CONCLUSIONS: (i) HDV infection is present in 16.6% of hepatitis B infected patients in Pakistan, most commonly in younger males living in rural areas; and (ii) delta virus infected patients have less severe clinical liver disease compared to delta negative, hepatitis B patients.     

Decision-making for lung resection in patients with empyema and collapsed lung due to tuberculosis

OBJECTIVE: Collapsed lung with associated empyema is a different clinical entity from destroyed lung . A low perfusion rate of the diseased lung is usually considered an indication for pneumonectomy in patients undergoing thoracotomy for tuberculosis. Such a criterion may not adequately reflect the functional capacity of the underlying parenchyma when the lung is collapsed. METHODS: One hundred twenty-seven patients underwent thoracotomy for tuberculosis at our hospital between 1998 and 2003. Among these, 5 (4%) patients who had a collapsed lung for more than 3 months and pleural infection were the subjects of this study. Surgery was considered after at least a 3-month course of regular antituberculous treatment. Despite no perfusions in 2 patients and 8%, 10%, and 15% perfusion rates for the remaining 3 patients, decortication alone was intentionally performed, and any kind of resectional operation was avoided. RESULTS: The lung gradually filled the hemithorax between 5 and 12 days after surgery in 4 patients. The remaining patient required a thoracomyoplasty 8 weeks after the initial operation. Repeated perfusion scans 1 and 2 years after decortication continued to show no perfusion in patients who had had no preoperative perfusion. All patients were symptom free on regular follow-up between 10 months and 4.5 years. CONCLUSIONS: It seems that the outcome is unpredictable in terms of lung expansion after decortication, which is a relatively simple procedure compared with other surgical options. We think that the risk of rethoracotomy is acceptable, considering the devastating complications and high mortality rates of resectional surgery in the treatment of such patients.     

Examining microcirculation improves the angiosome theory in explaining the delay phenomenon in a rabbit model

Topographic and temporal changes in circulation were studied with laser Doppler flowmetry in rabbit dorsal skin flaps comprised of three vascular territories. The reduced caliber vessels along the dorsal median line, rather than the vessels interconnecting the thoracodorsal and deep circumflex iliac vascular trees, behaved as true choke vessels. The authors found an increased proximal circulation lasting for 48 to 72 hr. This coincided with the reported rapid phase of choke vessel dilatation. The increase in distal circulation began after postoperative day 3, coinciding with the resolution of proximal hyperemia but not with the earlier prominent vasodilatation. Secondary elevation of the flaps at 3 weeks did not disturb the homogeneous distribution of circulation and did not cause a hyperemic response at postoperative 24 hr. Based on these findings, the authors postulate that the same mechanisms may underlie the rapid choke vessel dilatation and microvascular dilatation observed at 48 to 72 hr postoperatively. Surgical delay may work not only by diminishing the resistance to blood flow along the flap, but also by diminishing the steal effect of increased proximal microcirculation, which characterizes this period, over the distal circulation.     

In vivo proteomic analysis of cytokine expression in laser capture-microdissected urothelial cells of obstructed ureteropelvic junction procured by laparoscopic dismembered pyeloplasty

BACKGROUND AND PURPOSE: Ureteropelvic junction obstruction (UPJO) is defined as an impediment to urinary flow from the renal pelvis into the ureter. The exact cause remains an enigma despite investigations along embryologic, anatomic, and histologic lines. Our goal was to investigate in vivo the expression profile of cytokines in hyperplastic urothelial cells as a means of determining the source of UPJO. MATERIALS AND METHODS: Cellular proteomes of matched normal and hyperplastic urothelial cells were analyzed by laser capture microdissection (LCM) and tissue microdissection and human cytokine proteomic chips. All specimens (N = 9) were surgically obtained from patients undergoing laparoscopic dismembered pyeloplasty and were immediately embedded in O.C.T. solution and flash-frozen in liquid nitrogen. Tissue sections (6 microm) were mounted on uncoated glass slides using a cryostat, fixed in 70% ethanol, stained with hematoxylin and eosin, and sequentially dehydrated in ethanol and xylene. Typically, paired samples of normal and hyperplastic urothelial cells were procured on separate caps from serial sections of each specimen by the Arcturus PixCell II LCM system using 3000 laser pulses and a spot diameter of 30 microm. Total proteins were harvested and quantitated. Differential expression profile analysis of 43 cytokines in normal and hyperplastic cells were performed using human protein chips. Briefly, the membranes were initially probed with protein (150 ng) from normal or hyperplastic cells and sequentially reacted with a cocktail of biotinylated cytokine antibodies and horseradish peroxidase-conjugated streptavidin. The membranes were developed using enhanced chemiluminescence and analyzed by densitometry. RESULTS: Comparative densitometric analysis revealed twofold to fourfold upregulation of growth-related oncogene alpha (GRO-alpha), interleukin (IL)-1alpha, interferon (INF)-gamma, IL-8, tumor necrosis factor (TNF)-alpha, RANTES, and macrophage inflammatory protein-1beta (MIP-1beta) and twofold to fourfold downregulation of transforming growth factor (TGF)-beta and IL-10 in hyperplastic urothelial cells compared with paired control cells. CONCLUSIONS: We here report the efficient application of LCM and proteomic array chips for expression profile analysis of cytokines in vivo. Because the etiology and pathogenesis of UPJO are still fragmentary, the marked heterogeneity of the observed cytokine alterations reported here may be of significance. Further studies are required to elucidate the functional significance of the differentially expressed cytokines in the pathogenesis of the disease.     

The upregulation of CC chemokine receptor 7 and the increased migration of maturing dendritic cells to macrophage inflammatory protein 3beta and secondary lymphoid chemokine is mediated by the p38 stress-activated protein kinase pathway

Using the p38 stress-activated protein kinase (p38SAPK) inhibitor, SB203580, increased responsiveness of monocyte-derived dendritic cells (MoDCs) to secondary lymphoid chemokine (SLC) and macrophage inflammatory protein 3beta (MIP3beta), following lipopolysaccharide-induced MoDC maturation, was shown to be mediated by the p38SAPK pathway. This was due to the complete abrogation of upregulation of CC chemokine receptor 7, the receptor for MIP3beta/SLC. Once mature, MoDCs utilized both the p38SAPK and phosphoinositide-3 kinase pathways to migrate in response to SLC or MIP3beta. These findings have implications for the mechanism of action of p38SAPK inhibitors, currently in use in clinical trials for patients with autoimmune diseases.