Incontinence after lateral internal sphincterotomy

PURPOSE: This study was designed to evaluate the anatomic and functional consequences of lateral internal sphincterotomy in patients who developed anal incontinence and in matched controls. METHODS: The study includes 13 patients with anal incontinence after lateral internal sphincterotomy and 13 controls who underwent the same operation and were continent and satisfied with the results of the procedure. Patients underwent clinical evaluation, anorectal manometry, pudendal nerve terminal motor latency testing, and endoanal ultrasonography. RESULTS: Sphincterotomies were longer in incontinent patients (75vs. 57 percent), but the resting pressure and length of the high-pressure zone were not different between groups. Surprisingly, maximum voluntary contraction was higher in incontinent patients than in continent controls (136vs. 100 mmHg). Rectal sensation and pudendal nerve terminal motor latency were similar in both groups. The defect in the internal sphincter was wider in incontinent patients than in continent controls (17.3vs. 14.4 mm), but these differences were not statistically significant. The thickness of the internal sphincter measured by endoanal ultrasound was identical in both groups, but the external sphincter was thinner in incontinent patients both at the site of the sphincterotomy (6.8vs. 8.1 mm) and in the posterior midline (7.1vs. 8.6 mm). CONCLUSIONS: Anal incontinence after lateral internal sphincterotomy is directly related to the length of the sphincterotomy. Whether secondary to preoperative sphincter abnormality or the result of lateral internal sphincterotomy, the external sphincter is thinner in incontinent patients than in continent controls.Read at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.     

Shelf-price agreements: the next frontier in competitive bidding for coronary intervention supplies.

In an attempt to further reduce operating costs, in 2004 our institution embarked on a novel approach in which we defined the price to be paid for interventional cardiology supplies and challenged vendors to meet that price. The results suggest that this strategy can further reduce supply costs while maintaining collaborative relationships with vendors.     

Three cases of autoimmune hepatitis in HIV-infected patients

Autoimmune hepatitis (AIH) is an uncommon liver disease that has previously been reported only 4 times in HIV-infected patients. Our report describes 3 new cases of AIH, 2 probable, and 1 definite. Two of these cases developed while the patient was virologically suppressed on antiretroviral therapy. Liver biopsy findings were critical in establishing the diagnosis of AIH. Because abnormal liver function tests in HIV-positive patients are often ascribed to antiretroviral medications and/or comorbid conditions, AIH may be underdiagnosed in this population. These cases underscore the value of liver biopsy in evaluating hepatitis of unclear etiology in HIV-positive patients. The clinical course of these cases also suggests that standard immunosuppressive therapy for AIH remains the optimal treatment regimen, even in HIV-positive patients.     

Reversible regional wall motion abnormalities on exercise technetium-99m-gated cardiac single photon emission computed tomography predict high-grade angiographic stenoses

OBJECTIVES: We sought to determine the level of angiographic stenosis at which reversible regional wall motion abnormalities (RWMA) are present on exercise stress technetium-99m (Tc-99m)- gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and whether assessments of stress and rest RWMA add incremental diagnostic information. BACKGROUND: Stress and rest gated SPECT MPI enables the detection of post-exercise stunning. Although some studies have correlated RWMA to the severity of MPI defects, only one previous study correlated RWMA on gated MPI to angiographic findings. However, this correlation excluded patients with rest perfusion defects and did not involve gating of rest images. METHODS: One hundred patients undergoing angiography within six months of exercise stress Tc-99m (sestamibi)-gated SPECT MPI (in the absence of interim cardiac events or revascularization) were recruited. Images were acquired 15 to 30 min after stress and interpreted without knowledge of the Duke treadmill score, left ventricular ejection fraction and angiographic data. RESULTS: The sensitivity of reversible RWMA for angiographic stenoses >70% was 53%, with a specificity of 100%. The presence of reversible RWMA was able to stratify patients with angiographic stenoses of 50% to 79% and 80% to 99% with a high positive predictive value. A good correlation was noted between the presence of reversible RWMA and the coronary artery jeopardy score (R = 0.49, p < 0.0001). Multivariate analysis showed that the post-stress RWMA, Duke treadmill and reversible RWMA scores were significant predictors of angiographic severity. CONCLUSIONS: Post-stress and reversible RWMA, as shown by exercise stress Tc-99m-gated SPECT MPI, are significant predictors of angiographic disease and add incremental value to MPI for the assessment of angiographic severity.     

罗马Ⅲ:新的标准

功能性胃肠病（functional gastrointestinal disorders）是胃肠病学领域中一个常见而重要的疾病类别。人群中功能性胃肠病患者人数众多，功能性胃肠道症状的发生率亦很高。这一情况不仅使医疗服务和药品费用支出上升．直接导致卫生保健成本增高，更存在因患者误工而带来的间接损失。因此，我很荣幸受邀为《胃肠病学》杂志撰写这篇文章，以进一步提高中国临床医师对功能性胃肠病重要性的认识。     

Notch signaling controls multiple steps of pancreatic differentiation

Multiple cell types of the pancreas appear asynchronously during embryogenesis, which requires that pancreatic progenitor cell potential changes over time. Loss-of-function studies have shown that Notch signaling modulates the differentiation of these progenitors, but it remains unclear how and when the Notch pathway acts. We established a modular transgenic system to heritably activate mouse Notch1 in multiple types of progenitors and differentiated cells. We find that misexpression of activated Notch in Pdx1-expressing progenitor cells prevents differentiation of both exocrine and endocrine lineages. Progenitors remain trapped in an undifferentiated state even if Notch activation occurs long after the pancreas has been specified. Furthermore, endocrine differentiation is associated with escape from this activity, because Ngn3-expressing endocrine precursors are susceptible to Notch inhibition, whereas fully differentiated endocrine cells are resistant.     

Anti-inflammatory modulation of chronic airway inflammation in the murine house dust mite model

Asthma affects 300 million people worldwide and continues to be a major cause of morbidity and mortality. Disease relevant animal models of asthma are required for benchmarking of novel therapeutic mechanisms in comparison to established clinical approaches. We demonstrate that chronic exposure of mice to house dust mite (HDM) extract results in allergic airway inflammation, that can be significantly attenuated by therapeutic intervention with phosphodiesterase 4 inhibition and corticosteroid treatment. Female BALB/c mice were administered intranasally with HDM (Dermatophagoides pteronyssinus) extract daily for five weeks, and therapeutic intervention with anti-inflammatory treatment (dexamethasone 1 mg/kg subcutaneous once daily, prednisolone 10mg/kg orally twice daily, fluticasone 3, 10 and 30 microg intranasally twice daily, roflumilast 10 mg/kg orally twice daily and intranasally 10 and 30 microg twice daily) was initiated after three weeks of exposure. Chronic HDM extract exposure resulted in significant airway inflammation, demonstrated by bronchoalveolar lavage cell infiltration and lung tissue inflammatory gene expression by TaqMan low density array. Chronic steroid treatment significantly inhibited these parameters. In addition, roflumilast caused a significant reduction in airway inflammatory cell infiltration. We have demonstrated that chronic HDM-induced allergic inflammation can be significantly ameliorated by steroid treatment, and that phosphodiesterase 4 inhibition modulates inflammatory cell infiltration. Therefore, the murine HDM model may be a useful tool for evaluating new targets for the treatment of asthma.     

Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia

Allogeneic hematopoietic stem cell transplantation is the only curative therapy for myelodysplasia (MDS). To identify factors influencing transplantation outcome, we studied 452 recipients of HLA-identical sibling transplants for MDS from 1989 to 1997, reported to the International Bone Marrow Transplant Registry. Patients with treatment-related MDS or unclassified MDS were excluded. Median age was 38 years (range, 2-64 years). Sixty percent had refractory anemia with excess blasts (n = 136) or with excess blasts in transformation (n = 136). Conditioning regimens included total body irradiation in 199 (44%) cases. Marrow was T-cell depleted for 58 (13%) transplants. Cumulative incidences of neutrophil engraftment, grades II-IV acute graft-versus-host disease (GVHD), and chronic GVHD were 91% (95% confidence interval [CI], 88%-93%), 36% (95% CI, 31%-40%), and 39% (95% CI, 33%-44%), respectively. Three-year transplantation-related mortality (TRM), relapse, disease-free survival, and overall survival rates were 37% (95% CI, 32%-42%), 23% (95% CI, 19%-27%), 40% (95% CI, 36%-45%), and 42% (95% CI, 37%-47%), respectively. Multivariate analyses showed that young age and platelet counts higher than 100 x 10(9)/L at transplantation were associated with lower TRM and higher disease-free and overall survival rates. Relapse incidence was higher in patients with high percentages of blasts in the marrow at transplantation or presentation, with high International Prognostic Scoring System scores at diagnosis, and with T-cell-depleted transplants. These findings indicate that transplantation from an HLA-identical sibling offers the possibility of long-term, disease-free survival to patients with MDS. Best candidates are younger patients with a low percentage of blasts and preserved platelet counts.     

The life cycle of the steroidogenic acute regulatory (StAR) protein: from transcription through proteolysis

The Steroidogenic Acute Regulatory (StAR) protein is a mitochondrial protein required for the transport of cholesterol substrate to the P450scc enzyme located in the inner mitochondrial membranes of steroid producing cells. This study suggests that the acute regulation of the rodent StAR gene in the ovary is mediated by two factors, C/EBPbeta and GATA-4. Once translated, the StAR precursor protein is either imported into the mitochondria, or it is rapidly degraded in the cytosol. We predicted that in order to perpetuate StAR activity cycles, imported StAR should turn over rapidly to avoid a potentially harmful accumulation of the protein in sub-mitochondrial compartments. Pulse-chase experiments in metabolically labeled cells showed that: (a) the turnover rate of mature mitochondrial StAR protein (30 kDa) is much faster (t(1/2) = 4-5 h) than that of other mitochondrial proteins; (b) dissipation of the inner membrane potential (-delta psi) by carbonyl cyanide m-chlorophenylhydrazone (mCCCP) accelerates the mitochondrial degradation of StAR; (c) unexpectedly, the mitochondrial degradation of StAR is inhibited by MG132 and lactacystin, but not by epoxomicin. Furthermore, StAR degradation becomes inhibitor-resistant two hours after import. Therefore, these studies suggest a bi-phasic route of StAR turnover in the mitochondria. Shortly after import, StAR is degraded by inhibitor-sensitive protease(s) (phase I), whereas at later times, StAR turnover proceeds to completion through an MG132-resistant proteolytic activity (phase II). Collectively, this study defines StAR as a unique protein that can authentically be used to probe multiple proteolytic activities in mammalian mitochondria.     

Assessment of communication skills in family medicine

Objective

To assess the communication and interviewing skills of incoming residents and provide formative feedback to residents early in their training.

Design

New residents completed a 15-minute objective structured clinical examination (OSCE) assessing communication skills and a 12-question, self-administered content quiz at the start of their residency. Each resident was directly observed by a family physician in the OSCE and provided with 15 minutes of structured feedback, with an opportunity for questions and discussion. The entire process remained private and did not affect summative evaluations.

Setting

Family medicine residency training program at the University of Alberta in Edmonton.

Participants

First-year family medicine residents.

Main outcome measures

Residents’ scores on the OSCE and the content quiz; residents’ rating of the usefulness of the assessment and the likelihood it would lead to practice change.

Results

A total of 61 residents (93.8%) completed the skills assessment (50 Canadian graduates, 11 international graduates). The mean score for the content quiz was 20.6 out of a total possible score of 24. Resident scores ranged from 8 to 24. The mean score on the OSCE practice interview was 21.1 out of 30, with a range of 13 to 29. Learner feedback indicated that the skills assessment was useful (4.68 out of 6) and would lead to a change in practice (4.43 out of 6).

Conclusion

The introductory communication OSCE and quiz offer new residents an opportunity to gauge their baseline skill level, become aware of program expectations early in their training, and garner specific suggestions in a nonthreatening environment. This tailored approach helps orient residents while taking into account their previous experiences.