Effect of Calcitonin on the Alcohol Drinking of Rats

Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20 IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n = 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross-over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10-day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment x Day interactions (p < 1E-10 and p = 6E-7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of YadA, Ail, and Lipopolysaccharide in Serum Resistance of Yersinia enterocolitica Serotype O:3

Complement attack is a host strategy leading to elimination of pathogens. Yersinia enterocolitica expresses several potential complement resistance factors: the outer membrane proteins YadA and Ail as well as lipopolysaccharide (LPS). To study the contribution of these factors to the survival of Y. enterocolitica serotype O:3 in nonimmune human serum, we constructed 23 mutant strains of Y. enterocolitica O:3 expressing different combinations of YadA, Ail, LPS O antigen, and LPS outer core. Survival of bacteria was analyzed in normal serum (with functional classical, lectin, and alternative complement activation pathways) and EGTA-Mg-treated serum (only alternative pathway functional). Kinetic killing tests revealed that the most potent single-serum resistance factor needed for long-term survival was YadA; Ail was also indispensable, but it provided short-term survival and delayed the bacterial killing. On the contrary, the LPS O antigen and outer core, when in combination with YadA, Ail, or both, had a minor and often negative effect on serum resistance. Bacteria in the exponential phase of growth were more resistant to serum killing than stationary-phase bacteria. After exposing bacteria to EGTA-Mg-treated serum, O antigen could prevent deposition of covalently bound C3b on bacteria at 3 min of incubation, even as a single factor. At later time points (15 and 30 min) it had to be accompanied by YadA, Ail, and outer core. In normal serum, the bacteria were less resistant to C3b deposition. However, no direct correlation between the C3 deposition pattern and bacterial resistance was observed.     

Acute Kidney Injury Following Aortic Valve Replacement in Patients Without Chronic Kidney Disease

BackgroundThe data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD.MethodsThis registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. For sensitivity analysis, propensity-score matching between TAVR and SAVR was performed.ResultsThe study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P < 0.001, multivariable analysis: odds ratio, 0.29, 95% confidence interval [CI], 0.20-0.41; matched 5.9% vs 19.0%, P < 0.001). Patients with AKI had significantly increased 5-year mortality compared with those without AKI (unmatched 36.0% vs 19.1%, log-rank P < 0.001; matched 36.3% vs 24.0%, log-rank P < 0.001). The adjusted hazard ratios for 5-year mortality were 1.58 (95% CI, 1.20-2.08) for AKI grade 1, 3.27 (95% CI, 2.09-5.06) for grade 2, and 4.82 (95% CI, 2.93-8.04) for grade 3.ConclusionsTAVR in patients without CKD was associated with a significantly less frequent incidence of AKI compared with SAVR. AKI significantly increased the risk of 5-year mortality after either TAVR or SAVR, and increasing severity of AKI was incrementally associated with 5-year mortality.     

Local daily temperatures,thermal seasons,and suicide rates in Finland from 1974 to 2010

Objectives

Suicide peaks in late spring and October are still seen in Finland among many countries. Weather factors have been suggested as explanations for these peaks, although with inconsistent results. Since the exact timing of these peaks varies each year, the length of daylight and changes in it seem inadequate as an explanation. We hypothesized that ambient temperature and the timing of thermal seasons might associate with suicide rate.

Methods

Suicide rates from three areas across Finland (N = 10,802) were analyzed with Poisson regression in six different models against variables calculated from the local ambient daily temperature, diurnal temperature range, and the duration from the onset of thermal seasons. Separate models for men and women were constructed.

Results

The temperature change over 5 days associated with the suicide rate of men in Helsinki region, or in other words, the lower the suicide rate was, the higher the temperature decrease had been. For women, the results were more inconsistent.

Conclusions

Our study is in line with some earlier studies which imply that impairment of thermoregulation might exist among suicide victims.     

Off-pump versus on-pump coronary artery bypass surgery in patients aged 80 years and older: institutional results and meta-analysis

Patients aged ≥80 years are at high risk of adverse events after coronary artery bypass grafting. This study was performed to evaluate whether off-pump coronary artery bypass surgery (OPCAB) is superior to conventional surgery (CCAB) in these high-risk patients. The outcome of 185 patients aged ≥80 years who underwent OPCAB or CCAB at our institution was reviewed and a meta-analysis on this issue was performed. Similar immediate postoperative results were observed after OPCAB and CCAB at our institution, despite significantly different operative risk (mean logistic EuroSCORE, OPCAB 20.3% vs CCAB 13.4%, P = 0.003). Among 56 propensity score matched pairs a trend toward lower postoperative stroke (0%, 95% CI 0–0 vs 3.6%, 95% CI 0–10.0, P = 0.50) was observed after OPCAB. No significant differences were observed in the other outcome end points. Five-year survival was 81.0% after OPCAB and 78.1% after CCAB (P = 0.239). Pooled analysis of eight studies including 3416 patients showed a significantly higher risk of postoperative stroke after CCAB (pooled rates: 4.2%, 95% confidence interval (95% CI) 2.4–7.1 vs 1.5%, 95% CI 0.9–2.5, risk ratio (RR) 2.15, 95% CI 1.17–3.96, P = 0.01). A trend toward higher immediate postoperative mortality was observed after CCAB (15 studies including 4409 patients, pooled rates: 6.5%, 95% CI 5.2–8.0 vs 5.6%, 95% CI 4.2–7.4, RR 1.29, 95% CI 0.86–1.93, P = 0.21). Generic inverse variance analysis showed similar intermediate survival after CCAB and OPCAB (RR 1.31, 95% CI 0.85–2.01, P = 0.22). At 2 years, survival was 82.8% (95% CI 76.4–89.2) after CCAB and 88.3% (95% CI 82.9–93.7) after OPCAB. Current results indicate that OPCAB compared with CCAB in patients aged ≥80 years is associated with significantly lower postoperative stroke and with a trend toward better early survival. However, suboptimal quality of the available studies, particularly the lack of comparability of the study groups, prevents conclusive results on this controversial issue.     

Angiogenesis and lymphangiogenesis in stage 1 germ cell tumours of the testis

OBJECTIVE: To determine whether angiogenesis can be used as an additional prognostic indicator in patients with stage 1 germ cell tumours of the testis. PATIENTS AND METHODS: Paraffin sections were assessed immunohistochemically from 51 patients with clinical stage 1 germ cell tumours of the testis (28 seminoma, 23 teratoma) treated by orchidectomy and surveillance only. Sections were analysed for microvascular density (MVD), and expression of the angiogenic factors vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). In addition, in the seminoma cases the presence of mRNA for the lymphangiogenic factor VEGF-C was examined by in situ hybridization, and its corresponding receptor VEGFR-3 by immunohistochemistry. RESULTS: Teratoma specimens had a significantly higher mean (range) MVD (85, 26-163; P < 0.01) than both seminoma (37, 16-91) and four normal specimens (26, 18-30). Teratoma specimens also had significantly higher VEGF expression than both seminoma and normal specimens (P < 0.01). Despite these differences between groups, and indeed individual tumours, there was no significant correlation between MVD and VEGF, or between either MVD or VEGF and relapse-free survival. TP expression was significantly greater in tumours than in normal specimens (P < 0.02) but with very little inter-tumour variation. VEGF-C mRNA and VEGFR-3 protein were detected in a third to a half of cases, with expression mostly around endothelial vessels. CONCLUSIONS: The marked differences between normal testis and tumours implicate angiogenesis in the biology of germ cell tumours of the testis. In addition, the detection of factors involved in lymphangiogenesis in some seminomas, tumours which initially metastasize primarily to lymph nodes, indicate that although not prognostic in this study, further studies are warranted in both these areas in the search for further prognostic indicators and therapeutic targets.     

The effect of sodium cromoglycate eyedrops compared to the effect of terfenadine on acute symptoms of seasonal allergic conjunctivitis.

A multicentre, group comparative open study was carried out on 68 patients to compare the effects of 2% sodium cromoglycate eyedrops and an oral antihistamine, terfenadine, on acute symptoms of seasonal allergic conjunctivitis. The study was continued for one week after the onset of acute symptoms. Both medications were equally efficient in reducing symptoms during the first hour of observation. During the one-week follow-up both medications reduced symptoms to a low level, and both medications were equally effective for allergic symptoms, except that terfenadine was more effective in reducing the watering of eyes.     

Use of blood products and risk of stroke after coronary artery bypass surgery

Background

The impact of blood transfusion on the development of post-operative stroke after coronary artery bypass grafting (CABG) is not well established. We, therefore, investigated this issue.

Materials and methods.

Complete data on peri-operative blood transfusion were available for 2,226 patients who underwent CABG in three Finnish hospitals.

Results

Stroke occurred post-operatively in 53 patients (2.4%). Logistic regression showed that pre-operative creatinine (OR 1.003, 95% CI 1.000–1.006), extracardiac arteriopathy (OR 2.344, 95% CI 1.133–4.847), pre-operative atrial fibrillation (OR 2.409, 95% CI 1.149–5.052), and the number of packed red blood cell units transfused (OR 1.121, 95% CI 1.065–1.180) were significantly associated with post-operative stroke. When the various blood product transfusions instead of transfused units were included in the multivariable analysis, solvent/detergent treated plasma (Octaplas^®) transfusion (OR 2.149, 95% CI 1.141–4.047), but not red blood cell transfusion, was significantly associated with postoperative stroke. Use of blood products ranging from no transfusion (stroke rate 1.6%) to combined transfusion of red blood cells, platelets and Octaplas^® was associated with a significant increase in post-operative stroke incidence (6.6%, adjusted analysis: OR 1.727, 95% 1.350–2.209). Patients who received >2 units of red blood cells, >4 units of Octaplas^® units and >8 units of platelets had the highest stroke rate of 21%. CART analysis showed that increasing amount of transfused Octaplas^®, platelets and history of extracardiac arteriopathy were significantly associated with post-operative stroke.

Conclusions

Transfusion of blood products after CABG has a strong, dose-dependent association with the risk of stroke. The use of Octaplas^® and platelet transfusions seem to have an even larger impact on the development of stroke than red blood cell transfusions.