Testosterone-induced relaxation of coronary arteries: activation of BKCa channels via the cGMP-dependent protein kinase.

Androgens are reported to have both beneficial and detrimental effects on human cardiovascular health. The aim of this study was to characterize nongenomic signaling mechanisms in coronary artery smooth muscle (CASM) and define the ionic basis of testosterone (TES) action. TES-induced relaxation of endothelium-denuded porcine coronary arteries was nearly abolished by 20 nM iberiotoxin, a highly specific inhibitor of large-conductance, calcium-activated potassium (BK(Ca)) channels. Molecular patch-clamp studies confirmed that nanomolar concentrations of TES stimulated BK(Ca) channel activity by ∼100-fold and that inhibition of nitric oxide synthase (NOS) activity by N(G)-monomethyl-L-arginine nearly abolished this effect. Inhibition of nitric oxide (NO) synthesis or guanylyl cyclase activity also attenuated TES-induced coronary artery relaxation but did not alter relaxation due to 8-bromo-cGMP. Furthermore, we detected TES-stimulated NO production in porcine coronary arteries and in human CASM cells via stimulation of the type 1 neuronal NOS isoform. Inhibition of the cGMP-dependent protein kinase (PKG) attenuated TES-stimulated BK(Ca) channel activity, and direct assay determined that TES increased activity of PKG in a concentration-dependent fashion. Last, the stimulatory effect of TES on BK(Ca) channel activity was mimicked by addition of purified PKG to the cytoplasmic surface of a cell-free membrane patch from CASM myocytes (∼100-fold increase). These findings indicate that TES-induced relaxation of endothelium-denuded coronary arteries is mediated, at least in part, by enhanced NO production, leading to cGMP synthesis and PKG activation, which, in turn, opens BK(Ca) channels. These findings provide a molecular mechanism that could help explain why androgens have been reported to relax coronary arteries and relieve angina pectoris.

Endoscopist-directed administration of propofol: a worldwide safety experience.

BACKGROUND & AIMS: Endoscopist-directed propofol sedation (EDP) remains controversial. We sought to update the safety experience of EDP and estimate the cost of using anesthesia specialists for endoscopic sedation. METHODS: We reviewed all published work using EDP. We contacted all endoscopists performing EDP for endoscopy that we were aware of to obtain their safety experience. These complications were available in all patients: endotracheal intubations, permanent neurologic injuries, and death. RESULTS: A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified. Endotracheal intubations, permanent neurologic injuries, and deaths were 11, 0, and 4, respectively. Deaths occurred in 2 patients with pancreatic cancer, a severely handicapped patient with mental retardation, and a patient with severe cardiomyopathy. The overall number of cases requiring mask ventilation was 489 (0.1%) of 569,220 cases with data available. For sites specifying mask ventilation risk by procedure type, 185 (0.1%) of 185,245 patients and 20 (0.01%) of 142,863 patients required mask ventilation during their esophagogastroduodenoscopy or colonoscopy, respectively (P < .001). The estimated cost per life-year saved to substitute anesthesia specialists in these cases, assuming they would have prevented all deaths, was $5.3 million. CONCLUSIONS: EDP thus far has a lower mortality rate than that in published data on endoscopist-delivered benzodiazepines and opioids and a comparable rate to that in published data on general anesthesia by anesthesiologists. In the cases described here, use of anesthesia specialists to deliver propofol would have had high costs relative to any potential benefit.

Gastroenterologist-directed propofol: an update.

Gastroenterologist directed propofol has been proven safe in more than 220,000 published cases. Administration of low doses of opioid and/or benzodiazepine ("balanced propofol sedation") is the safest format for gastroenterologist directed propofol. Specific training is needed to undertake gastroenterologist directed propofol administration.

Does obesity confer an increased risk and/or more severe course of post-ERCP pancreatitis?: a retrospective, multicenter study.

BACKGROUND: Pancreatitis is the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). Recent studies have suggested that obesity may serve as a prognostic indicator of poor outcome in non-ERCP-induced acute pancreatitis. However, to our knowledge, no one has ever investigated the potential association of obesity and ERCP-induced pancreatitis. Thus, the purpose of our study was to determine whether obesity conferred an increased risk and/or more severe course of post-ERCP pancreatitis. METHODS: A 160 variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study, evaluating whether prophylactic corticosteroids reduces the incidence of post-ERCP pancreatitis. Body mass indices (BMIs) were available on 964 of the 1115 patients from the original study. A BMI > or = 30 kg/m2 was defined as obese (World Health Organization) and used as a cutoff point in this study. BMIs were analyzed in a retrospective fashion to determine whether obesity confers an increased risk and/or more severe course of post-ERCP pancreatitis. Data were collected before the ERCP, at the time of procedure, and 24 to 72 hours after discharge. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis. RESULTS: Nine hundred sixty four patients were enrolled in the study. Pancreatitis occurred in 149 patients (15.5%) and was graded as mild in 101 (67.8%), moderate in 42 (28.2%), and severe in 6 (4.0%). The patients were categorized by BMI (kg/m2) using the following breakdowns: BMI < 20, 20 to < 25, 25 to < 30, and > or = 30, as well as BMI < 30 or > or = 30. The groups were similar with respect to the patient and procedure risk factors for post-ERCP pancreatitis except the group with BMI > or = 30 had a higher frequency of females, were younger, had less frequent chronic pancreatitis, a lower number of pancreatic duct injections, and fewer patients received more than 2 pancreatic duct injections. Of the patients with a BMI < 30, 119 (16.4%) developed post-ERCP pancreatitis compared with 30 (12.5%) of those with a BMI > or = 30 (P=0.14). There was no association between the presence of obesity and the severity of pancreatitis (P=0.74). Patients with a BMI < 20, 20 to < 25, 25 to < 30, and > or = 30 had a similar incidence of post-ERCP pancreatitis. CONCLUSIONS: Obesity did not seem to confer an increased risk for ERCP-induced pancreatitis. A statistically significant association between obesity and the severity of ERCP-induced pancreatitis was not apparent.

Colorectal cancer screening: a guide to the guidelines.

The best known guidelines for colorectal cancer screening in the United States are those of the US Multisociety Task Force on Colorectal Cancer, the American Cancer Society, the United States Preventive Services Task Force, the American College of Gastroenterology, and the American Society of Gastrointestinal Endoscopy. Screening is currently endorsed for both average-risk and high-risk persons by all guideline groups. Some guidelines offer a menu of options for average-risk persons, from which patients and physicians can select according to their perceptions and values regarding effectiveness, risk, and upfront costs. The alternative approach of colonoscopy as the preferred strategy simplifies discussions with patients and better reflects current trends in procedure use in the United States. For patients who refuse invasive testing, fecal occult blood testing is available. Quantitative fecal immunochemical tests offer promise for improved performance compared with guaiac testing. Radiographic screening has declined, although double contrast barium enema still remains an option in some guidelines. Computed tomographic colonography remains under active consideration but is not yet endorsed by any of the guidelines. High risk is still based primarily on family history, and the guidelines are fairly consistent in adjusting screening modality and intervals according to family history.

Colon polyp retrieval after cold snaring.

BACKGROUND: The removal of small colon polyps by cold snare transection without electrocautery effectively eliminates polyps, and anecdotal reports indicate a low risk of bleeding and perforation. Concerns about using cold snaring have centered on the risk of immediate bleeding and the difficulty in retrieving the polyp. The objective was to determine the retrieval rates of polyps after cold snaring after two different methods of resection and retrieval. METHODS: Consecutive polyps were identified by a single colonoscopist who chose the technique of polypectomy (hot snare, cold snare, or cold forceps). If cold snaring was chosen, an independent observer assigned the polyp to method A (cold resection of polyp without tenting and then suction of the transected polyp into a trap) or method B (ensnare the polyp, pull it into the colonoscope channel, and then transect it while suctioning). The size and the approximate location of all polyps were recorded and all collected specimens were sent separately for histologic examination. Results Of 519 consecutively encountered polyps, 400 were removed by cold snare: 197 were assigned to method A and 203 to method B. The mean size of polyps that were cold snared was 3.5 mm. The mean time to remove and to retrieve polyps with method A was 14.5 seconds (n = 58) and with method B was 18.1 seconds (n = 60) ( p = 0.03). There were no complications from cold snaring. The rate of successful retrieval with method A was 100% (197 of 197 polyps) and with method B was 98% (199 of 203 polyps) ( p = 0.04). CONCLUSIONS: Cold snare removal of colon polyps is associated with a high polyp retrieval rate. Each of two methods of polyp retrieval was effective. Snare transection without tenting of the polyp, followed by suctioning of the specimen off the polyp site, was more efficient, though the difference in efficiency was minimal. Difficulty or failure to retrieve polyps should not be a concern with regard to cold snare polypectomy.

170 degrees wide-angle colonoscope: effect on efficiency and miss rates.

BACKGROUND: Small polyps are routinely missed during colonoscopy even with careful examination. AIM: To determine and compare endoscopic efficiency and polyp miss rate between a prototype 170 degrees wide-angle (WA) colonoscope and a standard (S) colonoscope. METHODS: Two consecutive same-day colonoscopies were performed in 50 patients with intact colons. The patients were randomized to undergo the first colonoscopy with either the prototype WA 170 degrees angle of view colonoscope or an S adult 140 degrees angle of view colonoscope. RESULTS: The mean time for insertion was 2.09 (1.09) min versus 2.53 (1.47) min (p= 0.002) for the WA colonoscope and the S colonoscope, respectively. Similarly, the mean time for examination during withdrawal was shorter with the WA colonoscope (4.98 (0.94) vs 5.74 (1.12) min; p < 0.0001). The mean insertion time for the second examination was shorter than the insertion time for the first examination, irrespective of the colonoscope (p= 0.006). However, the withdrawal times were not significantly different between the first and second examinations (p= 0.11). The miss rate for all polyps with the WA colonoscope (19%) was similar to the miss rate with the S colonoscope (27%; p= 0.19). The miss rates for adenomas with the WA (10/33; 30.3%) and the S scope (15/50; 30%) were similar (p= 0.98). CONCLUSIONS: The use of the WA colonoscope was associated with a reduction in insertion time to the cecum, as well as examination time during withdrawal. No evidence was found that the accuracy of the two colonoscopes differs.

Fecal-based DNA assays: a new, noninvasive approach to colorectal cancer screening.

Stool-based DNA testing is a new, noninvasive method of colorectal cancer screening. Because it is easier to use and more sensitive than fecal occult blood testing, physicians may be more likely to recommend it, and patients may be more apt to comply. Although it is expensive, initial assessments show it to be cost-effective.