Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension.

Pulmonary hypertension (PH) complicating chronic parenchymal lung disease, such as idiopathic pulmonary fibrosis, results in significant morbidity and mortality. Since the hypoxia-inducible factor (HIF) signaling pathway is important for development of pulmonary hypertension in chronic hypoxia, we investigated whether HIF signaling in vascular endothelium regulates development of PH related to pulmonary fibrosis. We generated a transgenic model in which HIF is deleted within vascular endothelial cells and then exposed these mice to chronic intraperitoneal bleomycin to induce PH associated with lung fibrosis. Although no differences in the degree of fibrotic remodeling were observed, we found that endothelial HIF-deficient mice were protected against development of PH, including right ventricle and pulmonary vessel remodeling. Similarly, endothelial HIF-deficient mice were protected from PH after a 4-wk exposure to normobaric hypoxia. In vitro studies of pulmonary vascular endothelial cells isolated from the HIF-targeted mice and controls revealed that endothelial HIF signaling increases endothelial cell expression of connective tissue growth factor, enhances vascular permeability, and promotes pulmonary artery smooth muscle cell proliferation and wound healing ability, all of which have the potential to impact the development of PH in vivo. Taken together, these studies demonstrate that vascular endothelial cell HIF signaling is necessary for development of hypoxia and pulmonary fibrosis associated PH. As such, HIF and HIF-regulated targets represent a therapeutic target in these conditions.

Polyflex self-expanding, removable plastic stents: assessment of treatment efficacy and safety in a variety of benign and malignant conditions of the esophagus.

BACKGROUND: Historically, esophageal fistulas, perforations, and benign and malignant strictures have been managed surgically or with the placement of permanent endoprostheses or metallic stents. Recently, a removable, self-expanding, plastic stent has become available. The authors investigated the use of this new stent at their institution. METHODS: The study reviewed all the patients who received a Polyflex stent for an esophageal indication at the authors' institution between January 2004 and October 2006. Duration of placement, complications, and treatment efficacy were recorded. RESULTS: A total of 37 stents were placed in 30 patients (14 women and 16 men) with a mean age of 68 years (range, 28-92 years). Stent placement included 7 for fistulas, 3 for perforations, 1 for an anastomotic leak, 7 for malignant strictures, and 19 for benign strictures (8 anastomotic, 1 caustic, 5 reflux, 2 radiation, and 2 autoimmune esophagitis strictures, and 1 post-Nissen gas bloat stricture). The mean follow-up period was 6 months. Stent deployment was successful for all the patients, and no complications resulted from stent placement or removal. Nine stents migrated spontaneously. Three of three perforations and three of five fistulas sealed. Only one stent was removed because of patient discomfort. One patient with a radiation stricture experienced tracheoesophageal fistulas secondary to pressure necrosis. Of 20 patients with stricture, 18 experienced improvement in their dysphagia. CONCLUSION: Self-expanding, removable plastic stents are easily and safely placed and removed from the esophagus. This has facilitated their use in the authors' institution for an increasing number of esophageal conditions. Further studies to help define their ultimate role in benign and malignant esophageal pathology are warranted.

Asian earthquake: report from the first volunteer British hospital team in Pakistan.

At 8:52 am on 8 October 2005 a massive earthquake wracked northern Pakistan and Kashmir. Various teams were sent to Islamabad and the disaster region from the UK. We discuss the types of injury patterns seen and recommend that a central register of volunteers should be created to deal with similar situations in the future.

Endoscopic retrograde cholangiopancreatography in gallstone-associated acute pancreatitis.

BACKGROUND: Early endoscopic retrograde cholangio-pancreatography with or without endoscopic sphincterotomy (ERCP+/-ES) has been advocated to reduce complications in patients presenting with a severe attack of gallstone-associated acute pancreatitis (GAP). However, a recent trial has reported contradictory results. Importantly, patients with acute cholangitis were excluded suggesting it may be a major confounding factor affecting previous studies. OBJECTIVES: To assess the effectiveness of early ERCP+/-ES compared to conservative management stratified according to severity of disease, concealment of randomisation, acute cholangitis and bilirubin level in the reduction of mortality, morbidity, length of hospitalisation and cost in adults suspected of having GAP. SEARCH STRATEGY: We searched - Cochrane Library (Issue 4 2003), Medline (1966-2004), EMBASE (1980-2004) and LILACS. 'Grey literature' was sought by looking at cited references and hand searched to identify further relevant trials. Conference proceedings of United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were also hand searched. SELECTION CRITERIA: Randomized controlled trials (RCT) of adult patients, from 15 years old or greater, presenting with gallstone-associated acute pancreatitis (GAP) comparing ERCP +/- ES versus Conservative management within 72 hours of admission. DATA COLLECTION AND ANALYSIS: Data were assessed for quality independently by two reviewers. Wherever appropriate, results were pooled together and sub-grouped by predicted severity of disease. Fixed and random effects models were applied. Sensitivity analysis was performed to test the fragility of results. MAIN RESULTS: Three trials, involving 511 patients, met inclusion criteria. The test for heterogeneity yielded statistically non-significant results (p-value 0.1 to 0.63) suggesting all comparisons were above the established threshold for combinability (p<0.1). Fixed effect and random effect meta-analyses gave identical results. Early ERCP +/- ES was associated with non-significant effect on reduction of mortality in predicted mild (OR = 0.62, 95% CI = 0.27 to 1.41) and severe GAP (OR = 0.62, 95% CI = 0.27 to 1.41). Reduction in complications was non-significant in predicted mild (OR = 0.89, 95% CI = 0.53 to 1.49), but significant in severe GAP (OR = 0.27, 95% CI = 0.14 to 0.53). There was insufficient evidence to draw any conclusions about hospital stay and cost. REVIEWERS' CONCLUSIONS: Odds of having complications are reduced in predicted severe disease by early ERCP +/- ES. This effect was however, non-significant in predicted mild disease and for reduction of mortality in either predicted mild or severe disease. These results are controlled for confounding due to associated acute cholangitis and are robust for clinical and statistical heterogeneity.

Recurrent rectal carcinoma treated with high dose rate intraluminal brachytherapy.

A 65 years old man with recurrent rectal cancer was treated with remote afterloading High Dose Rate Intraluminal Brachytherapy (HDRILB). After eight weeks of HDRILB there was complete regression of the tumor. Bleeding per rectum and pain in the perineum were greatly improved. He died of myocardial infarction after 41 months of treatment with HDRILB. The treated lesions were incomplete remission at the time of death. The procedure was well tolerated. The only treatment-associated toxicity was grade 2 proctitis, which was treated conservatively. HDRILB can be used as one of the treatment options in patients with recurrent rectal cancers who have undergone previous abdominal surgery and external beam irradiation, as exhibited in our limited experience.

Low-salt bowel cleansing preparation (LoSo Prep) as preparation for colonoscopy: a pilot study.

BACKGROUND: Currently available colon cleansing preparations are often poorly tolerated. AIM: To evaluate the efficacy of a low-volume, low-salt preparation for colonoscopy. METHODS: This was a pilot study in patients scheduled for colonoscopy. The preparation consisted of 34 g of magnesium citrate and four bisacodyl tablets the day before the procedure, and one bisacodyl suppository on the morning of the procedure. RESULTS: Twenty patients (age range, 49-81 years; all males) were entered into the study. There were no significant side-effects associated with the preparation. All rated the taste as 'tolerable or better'. The examination was considered to be adequate, with no limitations, in 17 patients (85%), and was scored as good to excellent (no solid stool) in 11 (55%), acceptable (small amounts of solid stool) in six (30%) and poor in three (15%: two in-patients and one out-patient). Importantly, two of the failures then received a standard polyethylene glycol preparation and again failed to show adequate colon preparation. CONCLUSIONS: This pilot study showed that the low-salt colon cleansing preparation was an effective alternative preparation for colonoscopy.

Expression of inducible nitric oxide synthase contributes to the development of pancreatitis following pancreatic ischaemia and reperfusion.

BACKGROUND: Inducible nitric oxide synthase (iNOS) activity is increased in experimentally induced acute pancreatitis. Increased expression of this isoform of nitric oxide synthase has been demonstrated in several organs subjected to ischaemia-reperfusion injury. The present experiment investigated the expression of iNOS and the effect of selective iNOS inhibition in pancreatic ischaemia-reperfusion. METHODS: Wistar rats (n = 40) were randomly and equally assigned to four groups. Groups 2 and 4 underwent 60 min of total pancreatic ischaemia followed by 6 h of reperfusion (I-R). Groups 1 and 3 underwent sham operation. The selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) was administered to groups 3 and 4. Expression of iNOS was examined by immunohistochemistry. Other investigations included measurement of serum amylase activity and pancreatic wet : dry weight ratio, and histopathological examination. RESULTS: Eight of ten rats in group 2 (I-R only) expressed iNOS but none of the ten animals in group 1 (sham laparotomy) did so. Group 4 (I-R + L-NIL) animals had significantly lower serum amylase levels and wet : dry weight ratios than those in group 2 (I-R only). Microscopic evidence of pancreatic injury was present only in rats in group 2 (I-R only). CONCLUSION: Expression of iNOS during reperfusion following pancreatic ischaemia contributes significantly to the development of acute pancreatitis.

Genotypes of Helicobacter pylori obtained from gastric ulcer patients taking or not taking NSAIDs.

OBJECTIVE: Whether Helicobacter pylori infection and use of nonsteroidal antiinflammatory drugs (NSAIDs) are independent risk factors for ulcerogenesis remains unclear. We undertook this study to evaluate H. pylori isolates from gastric ulcer patients to determine whether the genotype of the infecting isolate could be correlated with the use or nonuse of NSAIDs. METHODS: Fifty-two patients presenting with gastric ulcer and infected with H. pylori were included; 26 patients were taking NSAIDs or aspirin (ASA) regularly at the time of ulcer diagnosis. Polymerase chain reaction (PCR) was employed to assess the presence and mosaicism of the following H. pylori genes: cagA, vacA, iceA, and picB. RESULTS: We found no statistical differences in the presence of these genes in H. pylori isolates from gastric ulcer patients taking or not taking prescription NSAIDs or ASA. A 297-bp fragment of the cagA gene was detected in 96% of the isolates from the NSAID and ASA users and 100% from the non-NSAID users (p = 1.0). A larger and more variable region of the cagA gene was detected more frequently among the isolates from non-NSAID users than those from NSAID users (p = 0.05). Ninety-two percent of the isolates were identified as vacA genotype s1. The dominant vacA subtype was s1b, 76.9% and 65.4% in isolates from non-NSAID-taking or NSAID-taking patients, respectively (p = 0.4). iceA1 genotype was not correlated with gastric ulcer as this allele was only detected in 17.3% of all isolates. CONCLUSIONS: No significant differences in the presence of the candidate virulence genes vacA, cagA, picB, or iceA were detected in isolates from gastric ulcer patients taking prescription NSAIDs or ASA, compared with those not taking these drugs, indicating that single gene presence does not allow discrimination of isolates that may be important in NSAID-induced ulcerogenesis. A variable region of the cagA gene was more frequently detected in isolates from patients not taking NSAIDs or ASA, suggesting that this gene may be modified by NSAID- or ASA-related factors or that certain strains may be selected for in patients taking these medications.

Houseflies are an unlikely reservoir or vector for Helicobacter pylori.

The route of transmission of Helicobacter pylori from individual to individual remains undefined. It has recently been reported that the domestic housefly, Musca domestica, when fed pure cultures of H. pylori, was able to harbor the organism in its midgut for up to 30 h (P. Grubel, S. Hoffman, F. K. Chong, N. A. Barstein, C. Mepani, and D. R. Cave, J. Clin. Microbiol. 35:1300-1303, 1997). Our investigation examined whether houseflies could acquire H. pylori from fresh human feces. Domestic houseflies (40 flies/group) were exposed for 24 h to feces from an H. pylori-positive volunteer, feces from an H. pylori-negative volunteer, or feces from an H. pylori-negative volunteer to which a known amount of viable H. pylori had been added. At various intervals, flies were sacrificed and the midguts were excised, homogenized, and plated in duplicate onto selective horse blood agar plates. All plates were incubated under microaerobic conditions at 37 degreesC for 14 days. Emergent colonies presumptive of H. pylori were picked and tested biochemically to confirm the identity as H. pylori. H. pylori was not recovered from houseflies fed human feces either naturally infected or artificially infected with H. pylori. These results suggest that the domestic housefly is not a vector for transmission or a reservoir for H. pylori infection.

A simple alternative technique of orchiopexy for high undescended testis.

Medial displacement of the testicular vessels constitutes an important principle for a successful operation for high undescended testis. Prentiss's manoeuvre involving division of the fascia transversalis attempts to achieve this objective but has not found favour with surgeons because it is more invasive. A simple alternative procedure of rerouting the testicular pedicle behind the fascia transversalis is described. The technique has been reported earlier and this paper aims to illustrate the steps with the help of intraoperative photographs. This method serves as a fixation procedure owing to the 'button-hole' effect of a small pathway and may be combined with other techniques of scrotal fixation such as formation of a dartos pouch and suturing.

TRAUMATIC ARTERIOVENOUS COMMUNICATION PRESENTING 36 YEARS AFTER INITIAL INJURY.

A 59-year-old man who had sustained multiple pelvic fractures 36 years ago recently developed progressive neurological deficits. His symptoms suggested an arteriovenous (AV) malformation of the spinal cord. This report details the steps taken in locating the fistula angiographically and in performing a preliminary temporary obliteration using an intra-arterial catheter balloon. After appropriate studies were carried out, the fistula was successfully excised. Immediate improvement in the peripheral circulation resulted, along with progressive ablation of the neurological deficits. A review of the literature has not revealed a similar case.