ACE gene insertion/deletion polymorphism has a mild influence on the acute development of left ventricular dysfunction in patients with ST elevation myocardial infarction treated with primary PCI

<p>Abstract</p> <p>Background</p> <p>We evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI).</p> <p>Methods</p> <p>A total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI.</p> <p>Results</p> <p>In comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]).</p> <p>Conclusions</p> <p>These results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.</p

ACE Inhibition and Endothelial Function: Main Findings of PERFECT, a Sub-Study of the EUROPA Trial

Background: ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction. Methods: PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months. Results: In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval −0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07). Conclusion: Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD

221st ENMC International Workshop : Foot Surgery in Charcot-Marie-Tooth disease June 10th-12th, 2016 Naarden, The Netherlands

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Laparoscopic and open surgery for pheochromocytoma

Backround Laparoscopic adrenalectomy is a promising alternative to open surgery although concerns exist in regard to laparoscopic treatment of pheocromocytoma. This report compares the outcome of laparoscopic and conventional (open) resection for pheocromocytoma particular in regard to intraoperative hemodynamic stability and postoperative patient comfort. Methods Seven patients laparoscopically treated (1997–2000) and nine patients treated by open resection (1990–1996) at the National Hospital (Rikshospitalet), Oslo. Peroperative hemodynamic stability including need of vasoactive drugs was studied. Postoperative analgesic medication, complications and hospital stay were recorded. Results No laparoscopic resections were converted to open procedure. Patients laparoscopically treated had fewer hypertensive episodes (median 1 vs. 2) and less need of vasoactive drugs peroperatively than patients conventionally operated. There was no difference in operative time between the two groups (median 110 min vs. 125 min for adrenal pheochromocytoma and 235 vs. 210 min for paraganglioma). Postoperative need of analgesic medication (1 vs. 9 patients) and hospital stay (median 3 vs. 6 days) were significantly reduced in patients laparoscopically operated compared to patients treated by the open technique. Conclusion Surgery for pheochromocytoma can be performed laparoscopically with a safety comparable to open resection. However, improved hemodynamic stability peroperatively and less need of postoperative analgesics favour the laparoscopic approach. In experienced hands the laparoscopic technique is concluded to be the method of choice also for pheocromocytoma. © Edwin et al 2001 This article is published under license to BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL

Low rate of local recurrence detection by rectoscopy in follow-up of rectal cancer

Aim: The main aim of this study was to examine the effectiveness of rectoscopy for detecting local recurrence of rectal cancer in patients following low anterior resection. Method: This was a retrospective study of 201 patients, who underwent low anterior resection for rectal or rectosigmoid cancer between 2007 and 2009 and who were followed up with rigid rectoscopy and imaging. A total of 91 patients were excluded from the analysis for various reasons, leaving 110 patients eligible for analysis. Results: A total of 613 rectoscopies were performed, and 48 biopsies taken. Six local recurrences were detected in the 110 patients, three of which were first detected by rectoscopy and three by CT. Two of the local recurrences were detected outside the follow‐up programme because of symptoms: one by rectoscopy and one by CT. Three of 613 (0.5%) rectoscopies led to detection of local recurrence. The sensitivity and specificity of rectoscopy to detect local recurrence was 0.50 and 0.93, respectively. Nineteen distant metastases were detected, and two patients had both local recurrence and distant metastasis. All local recurrences and distant metastases were detected within 48 months of surgery. Conclusion: Rigid rectoscopy is poor at detecting local recurrence. Only 3 out of 613 rectoscopies (0.5%) detected local recurrence. Due to extramural growth of some recurrences, the sensitivity is also very low. Based on our results, routine rectoscopy in the surveillance of asymptomatic patients cannot be recommended

Low rate of local recurrence detection by rectoscopy in follow-up of rectal cancer

Aim: The main aim of this study was to examine the effectiveness of rectoscopy for detecting local recurrence of rectal cancer in patients following low anterior resection. Method: This was a retrospective study of 201 patients, who underwent low anterior resection for rectal or rectosigmoid cancer between 2007 and 2009 and who were followed up with rigid rectoscopy and imaging. A total of 91 patients were excluded from the analysis for various reasons, leaving 110 patients eligible for analysis. Results: A total of 613 rectoscopies were performed, and 48 biopsies taken. Six local recurrences were detected in the 110 patients, three of which were first detected by rectoscopy and three by CT. Two of the local recurrences were detected outside the follow‐up programme because of symptoms: one by rectoscopy and one by CT. Three of 613 (0.5%) rectoscopies led to detection of local recurrence. The sensitivity and specificity of rectoscopy to detect local recurrence was 0.50 and 0.93, respectively. Nineteen distant metastases were detected, and two patients had both local recurrence and distant metastasis. All local recurrences and distant metastases were detected within 48 months of surgery. Conclusion: Rigid rectoscopy is poor at detecting local recurrence. Only 3 out of 613 rectoscopies (0.5%) detected local recurrence. Due to extramural growth of some recurrences, the sensitivity is also very low. Based on our results, routine rectoscopy in the surveillance of asymptomatic patients cannot be recommended

Risk factors, mortality trends and cardiovasuclar diseases in people with Type 1 diabetes and controls : A Swedish observational cohort study

Background Historically, the incidence of cardiovascular disease and mortality in persons with Type I diabetes (TID) has been increased compared to the general population. Contemporary studies on time trends of mortality and cardiovascular disease are sparse. Methods In this observational study, TID persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141). Incidence rates from 2002 to 2019 were estimated with respect to mortality and cardiovascular disease in persons with TID overall and when stratified for prevalent cardiovascular and renal disease relative to controls. Findings Mean age in persons with TID was 32.4 years and 44.9% (20,446/45,575) were women. Age- and sex-adjusted mortality rates declined over time in both groups but remained significantly higher in those with TID compared to controls during 2017-2019, 7.62 (95% CI 7.16; 8.08) vs. 2.23 (95% CI 2.13; 2.33) deaths per 1,000 person years. Myocardial infarction, heart failure and stroke decreased over time in both groups, with persistent excess risks in the range of 3.4 -5.0 times from 2017 to 2019 in those with TID. TID persons &amp;gt;= 45 years without previous renal or cardiovascular complications had standardized mortality rates similar or even lower than controls 5.55 (4.51; 6.60) vs.7.08 (6.75; 7.40) respectively in the last time period. Interpretation Excess mortality persisted over time in persons with TID, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on individualized treatment is needed to dose the gap in mortality for individuals with TID. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.Funding Agencies|ALF-agreement; Novo Nordisk Foundation; Swedish Heart and Lung Foundation</p

Declining intracellular T-lymphocyte concentration of cyclosporine A precedes acute rejection in kidney transplant recipients

BACKGROUND. We investigated cyclosporine A (CsA) concentrations at the site of action, inside T-lymphocytes, to evaluate its applicability as a new supplementary therapeutic drug monitoring method after renal transplantation. METHOD. In this prospective single-center study, 20 kidney transplant recipients, mean age 54 (range 21-74) years, on CsA-based immunosuppression were included within 2 weeks posttransplant and followed for 3 months. Nine patients also had one full 12-hour pharmacokinetic profile performed. T-lymphocytes were isolated from 7 ml whole blood using Prepacyte and intracellular CsA concentrations were determined using a validated liquid chromatography double mass spectrometry method. RESULTS. Seven patients (35%) experienced acute rejections (all biopsy verified) during the first three months posttransplantation. Intracellular CsA concentrations tended to decline 1 week prior to acute rejection and the decrease was significant (-27.1±14.6%, P=0.014) three days before the rejection episodes were recognized clinically. In addition, the intracellular CsA area under the curve 0-12 measured during stable phase was 182% higher in the rejection-free patients (P=0.004). There was no difference between patients experiencing rejection and the rejection-free patients with respect to CsA C2-levels, dose (mg/kg), human leukocyte antigen mismatch, donor age, recipient age, or ABCB1 genotyping. CONCLUSION. Intracellular CsA T-lymphocyte concentrations declined significantly 3 days prior to a rejection episode and there was a general lower intracellular exposure of CsA in recipients experiencing rejection. Intracellular measurement of CsA therefore seems to have a potential to further improve individualization of therapeutic drug monitoring. Larger studies are needed to elucidate the role for intracellular T-lymphocyte measurements in ordinary clinical care, for both CsA and other immunosuppressive drugs. © 2008 Lippincott Williams & Wilkins, Inc