Acute cholecystitis managed in a rural surgical department

ObjectivesTo define the outcome over a prolonged period of an unselected cohort of patients presenting with acute cholecystitis (AC) to a 560 bed rural hospital in Israel.Design, setting and participantsRetrospective case series analysed from a single referral centre between 2006 and 2015. Separated into Group 1 managed by emergent cholecystectomy, Group 2 treated with antibiotics and delayed cholecystectomy, Group 3 treated with percutaneous cholecystostomy (PC) and selected delayed cholecystectomy and Group 4 managed entirely conservatively with no subsequent cholecystectomy.Methods Assessment of complication rates: in-hospital and delayed cause-specific morbidity and mortality along with conversion rates and the risk of intraoperative stone spillage. Results Of 321 patients hospitalized for AC, there were 50 in Group 1, 68 in Group 2, 59 in Group 3 and 98 in Group 4. Group 3 were older with more comorbidities and when coming to surgery had more open conversions. Intraoperative stone spillage was more common in Groups 2 and 3. The length of hospital stay was greater for Groups 1 and 3. Of the Group 4 cases, 63.2 per cent remained asymptomatic over a median follow-up of 78 months. Of those with recurrent biliary symptoms, 58.3 per cent were ASA Grade III/IV with 25/36 late deaths 80 per cent of which were from non-biliary causes. ConclusionIn the management of AC, early cholecystectomy is favored with non-operative approaches like PC drainage or antibiotic treatment alone being reserved for frailer comorbid cases. The absolute need for subsequent cholecystectomy is not supported by this series and requires further investigation

Effect of leptin on intestinal re-growth following massive small bowel resection in rat

Recent evidence suggests that the adipose tissue-derived cytokine leptin (LEP) is involved in modulation of growth and differentiation of normal small intestine. The purpose of the present study was to evaluate the effects of parenteral LEP on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, SBS-rats underwent a 75% small bowel resection, and SBS-LEP-rats underwent bowel resection and were treated with LEP given subcutaneously at a dose of 20 μg/kg, once daily, from day 3 through 14. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height and crypt depth in jejunum and ileum), enterocyte proliferation and enterocyte apoptosis were determined on day 15 following operation. Ileal tissue samples were taken for detection of bax and bcl-2 gene expression using RT-PCR technique. Statistical analysis was performed using the non-parametric Kruskal–Wallis ANOVA test, with P< 0.05 considered statistically significant. Treatment with subcutaneous LEP resulted in a significant increase in jejunal (17%, P< 0.05) and ileal (13%, P< 0.05) bowel weight, jejunal (10%, P< 0.05) and ileal (25%, P< 0.05) mucosal weight, jejunal (26%, P< 0.05) and ileal (38%, P< 0.05) mucosal DNA, ileal (25%, P< 0.05) mucosal protein, jejunal (41%, P< 0.05) and ileal (21%, P< 0.05) villus height, jejunal (37%, P< 0.05) crypt depth, and jejunal (24%, P< 0.05) and ileal (21%, P< 0.05) enterocyte proliferation compared to SBS-animals. Enterocyte apoptosis increased significantly after bowel resection in jejunum and ileum compared to sham animals and was accompanied by an increased bax gene expression and a decreased bcl-2 gene expression in ileal samples. SBS-LEP rats showed a trend toward a decrease in enterocyte apoptosis in ileum and a mild decrease in bax gene expression compared to SBS-untreated animals. In conclusion, in a rat model of SBS parenteral LEP stimulates structural intestinal adaptation. Increased cell proliferation and decreased cell death via apoptosis may be responsible for this increased cell mass.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47175/1/383_2005_Article_1572.pd

The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans

Atherosclerosis remains a major cause of death in the developed world despite the success of therapies that lower cholesterol and BP. The intermediate-conductance calcium-activated potassium channel KCa3.1 is expressed in multiple cell types implicated in atherogenesis, and pharmacological blockade of this channel inhibits VSMC and lymphocyte activation in rats and mice. We found that coronary vessels from patients with coronary artery disease expressed elevated levels of KCa3.1. In Apoe–/– mice, a genetic model of atherosclerosis, KCa3.1 expression was elevated in the VSMCs, macrophages, and T lymphocytes that infiltrated atherosclerotic lesions. Selective pharmacological blockade and gene silencing of KCa3.1 suppressed proliferation, migration, and oxidative stress of human VSMCs. Furthermore, VSMC proliferation and macrophage activation were reduced in KCa3.1–/– mice. In vivo therapy with 2 KCa3.1 blockers, TRAM-34 and clotrimazole, significantly reduced the development of atherosclerosis in aortas of Apoe–/– mice by suppressing VSMC proliferation and migration into plaques, decreasing infiltration of plaques by macrophages and T lymphocytes, and reducing oxidative stress. Therapeutic concentrations of TRAM-34 in mice caused no discernible toxicity after repeated dosing and did not compromise the immune response to influenza virus. These data suggest that KCa3.1 blockers represent a promising therapeutic strategy for atherosclerosis