The Anglo-Scandinavian Cardiac Outcomes Trial: blood pressure-lowering limb: effects in patients with type II diabetes

OBJECTIVE: To compare the effects of two antihypertensive treatment strategies for the prevention of coronary heart disease and other cardiovascular events in the large subpopulation (n=5137) with diabetes mellitus in the blood pressure-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial. METHODS: Patients had either untreated hypertension or treated hypertension. For those with type II diabetes mellitus, inclusion criteria required at least two additional risk factors. Patients were randomized to amlodipine with addition of perindopril as required (amlodipine-based) or atenolol with addition of thiazide as required (atenolol-based). Therapy was titrated to achieve a target blood pressure of less than 130/80 mmHg. RESULTS: The trial was terminated early due to significant benefits on mortality and stroke associated with the amlodipine-based regimen. In patients with diabetes mellitus, the amlodipine-based treatment reduced the incidence of the composite endpoint--total cardiovascular events and procedures--compared with the atenolol-based regimen (hazard ratio 0.86, confidence interval 0.76-0.98, P=0.026). Fatal and nonfatal strokes were reduced by 25% (P=0.017), peripheral arterial disease by 48% (P=0.004) and noncoronary revascularization procedures by 57% (P<0.001). For the other endpoints included in the composite, the endpoint differences were less clear including coronary heart disease deaths and nonfatal myocardial infarctions (the primary endpoint), which were reduced nonsignificantly by 8% (hazard ratio 0.92, confidence interval 0.74-1.15). CONCLUSION: In the large diabetic subgroup in the blood pressure-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial, the benefits of amlodipine-based treatment, compared with atenolol-based treatment, on the incidence of total cardiovascular events and procedures was significant (14% reduction) and similar to that observed in the total trial population (16% reduction).     

The role of endothelium in factor Xa regulation: the effect of plasma proteinase inhibitors and hirudin

The role of endothelium in the inhibition of human factor Xa was studied in a plasma environment. Human factor Xa can bind to and function on bovine aortic endothelium in a manner similar to that of bovine factor Xa. Approximately 70% of the bound factor Xa is subject to inhibition by plasma proteinase inhibitors, and the remaining 30% is irreversibly bound as part of a 125 Kd membrane-associated complex not subject to proteolytic degradation. The proportion reversibly bound and its rate of release do not alter with changes in calcium, citrate, heparin, or active proteinase inhibitor concentrations. The principal plasma proteinase inhibitor of human factor Xa was antithrombin III, which accounted for 60% to 65% of factor Xa released from endothelium, with alpha 1-proteinase inhibitor inactivating 20% to 25% and alpha 2- macroglobulin approximately 15%. All of the reversibly bound factor Xa was identified in complex with one of these three proteinase inhibitors. The thrombin active-site inhibitor hirudin was found to markedly accelerate the displacement of reversibly bound factor Xa from the endothelium and to associate specifically with factor Xa without a loss of activity toward chromogenic substrates, perhaps accounting for a novel mechanism of anticoagulation.     

Localization of Left Atrial Ganglionated Plexi in Patients with Atrial Fibrillation

Background. The intrinsic cardiac autonomic nervous system (ICANS), which forms a neural network, has been shown to be a critical element responsible for the initiation and maintenance of atrial fibrillation (AF). We developed a technique to localize and ablate the ganglionated plexi (GP), which serves as the "integration centers" of the ICANS.
Method. The four major atrial GP are localized by delivering high frequency stimulation (HFS; 20 Hz, 10–150 V, 1–10 ms pulse width) to atrial tissue where GP are presumed to be located. Sites showing a parasympathetic response, which is arbitrarily defined as ≥50% increase in mean R-R interval during AF, was assigned as a GP site. Radiofrequency current is then applied to that site to eliminate the parasympathetic response. All patients received ablation of the four major atrial GP, followed by pulmonary vein antrum ablation.
Results. Our preliminary results showed that all the four major atrial GP can be identified in the vast majority of patients. The parasympathetic response can be eliminated by applying radiofrequency current. In the first 83 patients, the percent of patients free of symptomatic AF or atrial tachycardia after a single ablation procedure was 80% at 12 months and 86% at a mean follow-up of 22 months.
Conclusion. These results indicate additional benefits of GP ablation to PV antrum ablation and improvement with time, particularly ≥ 12 months after ablation. We postulate that this late benefit may result from destruction of the autonomic neurons in the GP that cannot regenerate.     

Diabetes mellitus in Danish cystic fibrosis patients: prevalence and late diabetic complications

Lanng S, Thorsteinsson B, Lund-Andersen C, Nerup J, Schiatz PO, Koch C. Diabetes mellitus in Danish cystic fibrosis patients: prevalence and late diabetic complications. Acta Pzdiatr 1994;83: 72–7. Stockholm. ISSN 0803–5253.
The prevalences of impaired glucose tolerance (IGT), diabetes mellitus and late diabetic complications were studied in all Danish cystic fibrosis (CF) patients. A total of 311 CF patients were identified with an estimated ascertainment rate above 98%. Glucose tolerdnce was classified in 278 (89%) patients: the prevalences of IGT and diabetes mellitus were 13.7% (38 patients) and 14.7% (41 patients), respectively, with no sex differences. The prevalence of diabetes mellitus increased with age but not with the severity of CF as compared with age- and sex-matched non-diabetic CF patients. Diabetes was diagnosed at a median age of 20 years (range 3–40 years) and the duration of diabetes was 1.7 years (0.1–17 years). Twenty-eight of the diabetic patients (70%) were trcated with insulin, on average 20 (4–90) IU per day. Late diabetic complications were identified in 4 patients (10%) with a duration of diabetes mellitus of 1–17 years: background retinopathy (2 patients), diabetic nephropathy (1 patient), microalbuminuria (1 patient) and neuropathy (2 patients). Thus diabetic CF patients are probably not less prone to develop late diabetic complications than patients with other types of diabetes of equally long duration and comparable glycemic control.     

Improving family and community health in eastern Europe--the lifecycle approach at WHO

There are great differences in the health status of young children in the European Region. Central Asia and the Caucasus are the worst-off areas. After reviewing under-five mortality in the eight countries of this part of Eastern Europe, a new WHO strategy to improve child survival is presented. Adopted in late 2005, the strategy has four main principles: a lifecycle approach, youth participation, equity and intersectoral collaboration.     

Infantile colic and the role of trait anxiety during pregnancy in relation to psychosocial and socioeconomic factors

AIMS: A study was undertaken to assess the impact of psychological, psychosocial and socioeconomic factors on the risk of having a child with infantile colic. METHODS: Psychosocial and psychological factors were assessed by self-administered questionnaires in the 17th, and by telephone interviews in the 35th-37th pregnancy weeks; infantile colic occurrence was assessed by telephone interviews at infant age 5 weeks; subjects were 1,099 mother-infant dyads. RESULTS: High trait anxiety increased the colic risk; OR 2.04 (95% CI: 1.16, 3.59), and so did affirming a perceived risk of spoiling young infants with too much physical contact; OR 1.77 (1.07, 2.91). In the final step of a multivariate model, not cohabiting with the child's father was the factor with the strongest association with colic; OR 3.48 (1.38, 8.77). Analyses of effect modification showed that high education seemed to protect from the influence of high trait anxiety. Young women were particularly high in trait anxiety, and being exposed to both these risk factors seemed to act synergistically on the risk of having a colicky infant; OR 2.41 (1.12, 5.18). CONCLUSIONS: Psychological and psychosocial factors were found to be significantly related to an increased risk for infantile colic, and these factors interacted with age, parity, social support, and educational level in a complex manner. Even though no single most important psychosocial risk factor was identified, the findings lend support to the strategy of offering special attention in terms of information and support in the maternal healthcare system to very young women, women who do not cohabit with the father, and women with high trait anxiety.