Beta-fibrinogen gene polymorphism (C148-->T) is associated with carotid atherosclerosis: results of the Austrian Stroke Prevention Study.

Polymorphisms at the beta-fibrinogen locus have been shown to be associated with plasma concentration of fibrinogen and coronary heart disease. The effect of the genetic heterogeneity of fibrinogen on carotid atherosclerosis has not been determined so far. We examined the influence of the C148 --> T polymorphism on carotid disease in a large cohort of middle-aged to elderly subjects without evidence of neuropsychiatric disease. This polymorphism is located close to the consensus sequence of the interleukin-6 element and may represent a functional sequence variant. The genotype of 399 randomly selected, neurologically asymptomatic individuals, aged 45 to 75 years, was determined by denaturing gradient gel electrophoresis. Carotid atherosclerosis was assessed by color-coded duplex scanning and was graded on a five-point scale ranging from 0 (=normal) to 5 (=complete luminal obstruction). The C/C, C/T, and T/T genotypes were noted in 226 (56.6%), 148 (37.1 %), and 25 (6.3%) individuals, respectively. The T/T genotype group demonstrated higher grades of carotid atherosclerosis than did the C/C and C/T genotypes (P=.003). Logistic regression analysis created a model of independent predictors of carotid atherosclerosis that included apolipoprotein B (odds ratio [OR], 1.17/10 mg/dL), age (OR, 2.46/10 years), lifetime tobacco consumption (OR, 1.03/1000 g), presence of the beta-fibrinogen promoter T/T genotype (OR, 6.17), plasma fibrinogen concentration (OR, 1.05/10 mg/dL), and cardiac disease (OR, 1.80). These data suggest that the beta-fibrinogen promoter T/T148 genotype represents a genetic risk factor for carotid atherosclerosis in the middle-aged to elderly.

[Prevalence and risk factors in the population of Graz (Austrian Stroke Prevention Study)]. / Prävalenz von Risikofaktoren in der Grazer Bevölkerung (Austrian Stroke Prevention Study).

The Austrian Stroke Prevention Study recruited 1960 randomly selected subjects aged 50 to 75 years during a 3-year period of enrollment. The response rate of the study was 32.4%. A telephone interview with 200 randomly selected non-responders yielded no differences to responders regarding the frequency of major vascular risk factors known to the subjects. Besides demographics, the study assessed arterial hypertension, diabetes mellitus, cardiac disease, smoking, a complete lipid status including the apolipoprotein-E genotype, serum fibrinogen and anticardiolipin antibodies as well as various natural antioxidants such as vitamins A, C, E and beta-carotene. Arterial hypertension, diabetes mellitus, cardiac disease and hypercholesterolemia > 200 mg/dl were strikingly common and occurred in 38%, 7.6%, 32% and 76%, respectively. Suboptimal plasma concentrations of vitamin A, E, and beta-carotene were noted in 77.2%, 56.1% and in 53.2% of study participants. The rate of treatment of major risk factors known to the subjects prior to study entry were 60.3% and 70% for arterial hypertension and diabetes mellitus, but only 37.1% and 6.3% for cardiac disease and hypercholesterolemia > 250 mg/dl. Diet was commonly used to treat diabetes but was almost neglected in the treatment of other vascular risk factors. These data provide an orientation on the prevalence of risk factors and the use of primary preventive measures for stroke treatment in our community.

Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery.

Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia.

[Correlation between late potentials, left ventricular function and coronary heart disease]. / Korrelation zwischen Spätpotentialen, Linksventrikulärer Funktion und koronarer Herzkrankheit.

By signal averaging it is possible to registrate late, fragmented low amplitude signals (late potentials, LP's) from the bodysurface 26 patients (21 males, 5 females) with a mean age of 57 years were investigated by signal averaging, Holter-monitoring and cardiac catheterization. 11 patients had a dilative cardiomyopathy (group A), 10 patients a coronary heart disease (group B), 5 of them with an ejection fraction greater than 50%, 5 of them with a reduced ejection fraction, whereas the control-group with 5 patients (group C) showed no coronary stenosis or reduced ventricular function, 6 out of 11 patients with dilative cardiomyopathy showed LP's; all of these with Lown IVb had LP's. In 2 patients with coronary heart disease and good left ventricular function late potentials were found, and in all 5 patients with disturbed left ventricular function. The control-group revealed no late potentials although 4 patients had Lown IVa or more in Holter-ECG. In conclusion, late potentials show a good correlation to malignant ventricular ectopic beats in patients with dilative cardiomyopathy and coronary heart disease, especially when the left ventricular function is reduced.

4'-O-tetrahydropyranyl-doxorubicin in advanced breast cancer: a phase II study.

In a phase II study, 35 patients with advanced breast cancer were treated with 4'-O-tetrahydropyranyl-doxorubicin (THP-DXR) (70 mg/m2 i.v. on day 1); treatment was repeated every 3 weeks. Eight patients had failed prior chemotherapy for advanced disease. A total of 34 patients were evaluable for response. After a median of 10 treatment courses (range, 3-15), objective tumor response was seen in 59% (20 of 34 patients) (95% confidence limits, 42%-75%). In all, 17 partial remissions and 3 complete remissions were observed; stable disease occurred in 13 patients. The median duration of response was 42+ weeks (range, 21 - 77+ weeks). The dose-limiting side effects were leukopenia (26 patients, WHO grade III-IV) and thrombocytopenia (9 patients, WHO grade II-IV). Nausea/vomiting was experienced by 34 patients; in 18, it reached WHO grade II-III. Other treatment-related side effects included alopecia (WHO grade II-III) in 26 patients and stomatitis and diarrhea (WHO grade I-III) in 9 patients. At cumulative doses of THP-DXR of at least 700 mg/m2 (range, 700-1,050 mg/m2), no signs of congestive heart failure were observed. We conclude that THP-DXR is effective for first- and second-line chemotherapy in advanced breast cancer and that side effects are manageable.

[Redilatation with the trefoil balloon catheter in 2 patients with a high degree of aortic stenosis]. / Redilatation mit dem Trefoil-Ballonkatheter bei 2 Patienten mit hochgradiger Aortenstenose.

Percutaneous transluminal balloon valvuloplasty (PTBV) is successfully applied in the treatment of calcified aortic stenosis. However, results following redilatation have not yet been dealt with in the literature. This method was successfully used in two patients (62a m/70a f) suffering from severe sclerotic aortic stenoses. Redilatation was undertaken in the first case after one month and after four in the second. A second redilatation by balloon catheter was done upon request of the patients after a further nine months. Following this third dilatation both patients suffered from femoral thrombosis which was treated surgically in the second case, while in the first local thrombolysis was done. In the management of the first patient valve replacement had to be performed four months after the last dilatation due to renewed complaints, while the second patient showed no evidence of recurrence within three months after the last dilatation.