Βeta-fibrinogen gene promoter A -455 allele associated with poor longterm survival among 55-71 years old Caucasian women in Finnish stroke cohort.

BACKGROUND: Women die of stroke more often than men. After menopause, the incidence of ischemic stroke increases rapidly. Elevated fibrinogen levels and smoking have been associated with an increased risk of stroke. In gene-cluster haplotype analyses, the beta-fibrinogen (FGB) promoter -455 G/A polymorphic locus was most strongly associated with elevated plasma fibrinogen levels. We investigated whether the FGB -455 G/A polymorphism and smoking might interact with sex on longterm survival of acute stroke sufferers. METHODS: The Stroke Aging Memory (SAM) cohort comprising 486 consecutive stroke patients (55-85 years, 246 men, 240 women) subjected to clinical and MRI examination was followed over 12.5 years. During this period 347 (71.4%) patients died. The genotypes of the FGB -455 G/A polymorphism were determined by PCR. RESULTS: The FGB -455 G/A polymorphism genotype distributions were 64.7%, 32.1%, and 3.2% for GG, GA, and AA, respectively. During the follow-up, the FGB -455 A + genotype did not associate with survival, nor was there any genotype-by-smoking interaction on poor outcome in the total study population. However, women aged 55-71 years who carried the FGB -455 A-allele showed worse survival regardless of smoking status compared to non-smoking FGB -455 GG homozygotes (non-smokers, crude HR = 5.21, 95% CI: 1.38-19.7; smokers, crude HR = 7.03, 95% CI: 1.81-27.3). This association persisted in adjusted analyses. No such association was observed for women in the oldest age-group, nor among men. CONCLUSION: The A + genotype of the FGB -455 G/A polymorphism associated with poor survival among 55-71 years old Caucasian women in the Finnish stroke cohort.

Cerebral small vessel disease and kidney function predict long-term survival in patients with acute stroke.

BACKGROUND AND PURPOSE: Cerebral small vessel disease reflected by white matter lesions (WMLs) in MRI and kidney function reflected by estimated glomerular filtration rate (eGFR) is closely associated in patients without stroke. We studied whether eGFR and WMLs predict long-term survival in patients with acute stroke. METHODS: After exclusion of patients with low eGFR (N=5 [1.3%]; <30 mL/min/1.73 m(2)), consecutive patients with acute stroke (N=378) subjected to MRI and serum creatinine determination were included in the study and prospectively followed-up up to 12 years. RESULTS: Of the patients, 71.2% had died during the follow-up, 152 (40.2%) had moderate (eGFR <60 mL/min/1.73 m(2)), and 226 (59.8%) had normal or mildly impaired eGFR (>or=60 mL/min/1.73 m(2)). Of the patients, 108 (28.6%) had mild, 68 (18.0%) had moderate, and 202 (53.4%) had severe WMLs. In logistic regression analysis adjusted with age and sex, eGFR <60 mL/min/1.73 m(2) was associated with severe WMLs (relative risk 2.77, 95% CI 1.10 to 6.98, P=0.030). In Cox regression survival analysis adjusted with significant covariates, eGFR <60 mL/min/1.73 m(2) (1.30, 95% CI 1.00 to 1.68, P=0.047) and severe WMLs (hazard ratio 1.32, 95% CI 1.02 to 1.71, P=0.033) were associated with poor survival, whereas they were not independent from each other. In further analyses, presence of either eGFR >or=60 mL/min/1.73 m(2) or only mild to moderate WMLs, or both, was associated with improved survival compared with all other combinations. CONCLUSIONS: Cerebral small vessel disease is closely associated with kidney function in patients with acute stroke. Cerebral small vessel disease and kidney function are closely associated predictors of poor poststroke survival.

Depression-executive dysfunction syndrome relates to poor poststroke survival.

BACKGROUND: The aim of this study was to investigate the influence of poststroke depression and executive dysfunction on long-term survival after acute stroke. METHODS: A total of 257 consecutive acute ischemic stroke patients were included in the study and followed up to 12 years. Depression was diagnosed 3 months after stroke in 99 patients (38.5%). FINDINGS: In Kaplan-Meier analysis, there was no difference in survival of patients with and without poststroke depression (8.7 versus 8.3 years). Instead, patients with both depression and executive dysfunction had shorter median survival than patients with neither depression nor executive dysfunction (6.6 versus 10.3 years). Comparison between all patients with executive dysfunction and patients without it, not regarding depressive status, showed that executive dysfunction in itself was strongly associated with poor poststroke survival (6.4 versus 10.6 years). In stepwise Cox regression proportional hazards analysis adjusted with covariates, poststroke depression with executive dysfunction (hazard ratio [HR] 1.63) and advanced age (HR 1.11) remained as independent predictors of poor long-term survival. INTERPRETATION: The authors' well-defined poststroke cohort with long-term follow-up indicates that in poststroke depression, the depression-executive dysfunction syndrome is the predictor of poor long-term survival rather than depression in itself.

Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis-dependent mechanism.

AIM: In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis. EXPERIMENTAL DESIGN: Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax. RESULTS: Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In. CONCLUSION: The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis.

Complications in antireflux surgery: national-based analysis of laparoscopic and open fundoplications.

HYPOTHESIS: Longer experience of surgeons has reduced the rate of complications in antireflux surgery. DESIGN: Comparison of the rate of serious complications between open and laparoscopic fundoplication in Finland at the national level. SETTING: University teaching hospital. PATIENTS: From January 1, 1992, to December 31, 2001, 10 846 fundoplications were performed in Finland. Of these, 3987 (37%) were open and 6859 (63%) were laparoscopic. MAIN OUTCOME MEASURES: Administrative databases provided the number of fundoplications, the rate of severe complications, and the mortality. Medical records allowed for evaluation of the nature and cause of severe complications of laparoscopic and open fundoplications. RESULTS: From January 1, 1992, to December 31, 2001, hospital mortality was significantly lower after laparoscopy (P = .01). In comparable groups, surgical mortality or the overall rate of serious complications did not differ. The rate of serious complications decreased after both open surgery (P = .01) and laparoscopic surgery (P = .03). After laparoscopy, patients made claims for injuries more often (P = .003) and had a higher rate of dysphagia (P < .001). In all of the patients with severe dysphagia or fundic perforations after laparoscopy, the short gastric vessels were not divided. Furthermore, 1 open fundoplication and 22 laparoscopic fundoplications had to have reoperations performed owing to dysphagia, mostly involving technical failure. CONCLUSIONS: At the national level, the first 10-year experience of laparoscopic fundoplication reduced the rate of serious complications. The complications largely were technical failures related to the lack of a standardized surgical technique.

Incomplete circle of Willis and right axillary artery perfusion.

BACKGROUND: The aim of our anatomic study was to assess whether the commonly used method of perfusion through the right axillary artery is sufficient in providing uniform distribution of blood to both hemispheres of the brain in patients undergoing surgery of the aortic arch. We considered that critical arteries to examine are anterior and left posterior communicating arteries of the circle of Willis because the absence or insufficiency of either one would drastically endanger perfusion to the left hemisphere of the brain. The existence and the diameters of these arteries were studied. METHODS: The material was collected as a part of normal forensic medicine autopsies. The anatomy of the cerebral arteries of 87 deceased individuals was assessed by angiography and permanent silicone casts. A new classification was created for this study. According to a recent observation in the literature we defined the minimum threshold of arterial diameter that allows cross flow to be 0.5 mm. We also repeated analyses using 1 mm as a threshold, which has also been recommended. RESULTS: In our material 22% of the anterior communicating arteries and 46% of the left posterior communicating arteries were missing. In this anatomic population the perfusion to the left hemisphere might have been insufficient in 14% of the patients at a threshold of 0.5 mm and in 17% at a threshold of 1 mm. CONCLUSIONS: When the right axillary artery is used for perfusion, the circulation to the contralateral hemisphere seems to be good for most patients undergoing operations of the aortic arch, but additional means of brain protection are still needed.