The prevalence and characteristics of pruritus in patients with heart failure.

BACKGROUND: Pruritus (itching) can be a distressing symptom, and previous research suggests that it is common in patients with chronic heart failure (CHF). OBJECTIVES: The primary aim was to examine the prevalence of itching in patients with CHF and to compare this first to that among patients with coronary artery disease (CAD) and second to that of a normal Swedish population. The study also explored characteristics and possible causes of pruritus in patients with CHF. METHODS: In this cross-sectional prevalence study, a questionnaire was sent to 130 patients with CHF and to 130 with CAD. A total of 85 patients with CHF (65·4%) and 82 with CAD (63·1%) participated. Data were also compared with those of a previous study examining symptoms in a normal Swedish population. RESULTS: The prevalence of itching at some point during the last 3 months was 40·0% in patients with CHF and 23·2% in patients with CAD (P = 0·019). This difference was not significant after adjusting for sex, age and medication. Patients with CHF described their pruritus as more disturbing than patients with CAD. In addition, 13·6% of patients with CHF and 3·8% of persons in the normal population experienced itching every week without any rash (P = 0·001). CONCLUSIONS: Pruritus is common and sometimes disturbing in patients with CHF and warrants clinical attention. Medication should be considered as a cause of itching and may explain differences in the prevalence between patients with CHF and those with CAD. However, other causes of itching in patients with CHF should be explored in prospective studies.

Patients with lymphatic malformations who receive the immunostimulant OK-432 experience excellent long-term outcomes.

AIM: Sclerotherapy is the primary treatment for lymphatic malformations. The aim of this study was to evaluate the long-term outcome in patients with lymphatic malformations treated with the immunostimulant OK-432 as a sclerosant. METHODS: Between 1998 and 2013, we enrolled 131 of 138 eligible patients treated with OK-432 for lymphatic malformations in a retrospective study. The malformations were categorised according to the International Society for the Study of Vascular Anomalies. The outcome was assessed with a clinical examination and a questionnaire. RESULTS: The lymphatic malformations were localised to the head/neck (60%), the trunk (20%) and the extremities (6%) or involved with more than one region (14%). Patients with microcystic (10%), macrocystic (21%) and mixed lymphatic malformations (69%) underwent a median number of three, two and two injection treatments, respectively. The median age at the first injection was 3.4 years. Good or excellent clinical outcomes were seen in 70% of the patients. The number of injections, previous treatment and lesion localisation, but not time to follow-up and cyst size, predicted the clinical outcome. CONCLUSION: OK-432 treatment resulted in a successful outcome in 70% of patients with lymphatic malformations. The long-term outcome was comparable to the short-term outcome.

Membranous expression of podocalyxin-like protein is an independent factor of poor prognosis in urothelial bladder cancer.

BACKGROUND: Membranous expression of the anti-adhesive glycoprotein podocalyxin-like (PODXL) has previously been found to correlate with poor prognosis in several major cancer forms. Here we examined the prognostic impact of PODXL expression in urothelial bladder cancer. METHODS: Immunohistochemical PODXL expression was examined in tissue microarrays with tumours from two independent cohorts of patients with urothelial bladder cancer: n=100 (Cohort I) and n=343 (Cohort II). The impact of PODXL expression on disease-specific survival (DSS; Cohort II), 5-year overall survival (OS; both cohorts) and 2-year progression-free survival (PFS; Cohort II) was assessed. RESULTS: Membranous PODXL expression was significantly associated with more advanced tumour (T) stage and high-grade tumours in both cohorts, and a significantly reduced 5-year OS (unadjusted HR=2.25 in Cohort I and 3.10 in Cohort II, adjusted HR=2.05 in Cohort I and 2.18 in Cohort II) and DSS (unadjusted HR=4.36, adjusted HR=2.70). In patients with Ta and T1 tumours, membranous PODXL expression was an independent predictor of a reduced 2-year PFS (unadjusted HR=6.19, adjusted HR=4.60) and DSS (unadjusted HR=8.34, adjusted HR=7.16). CONCLUSION: Membranous PODXL expression is an independent risk factor for progressive disease and death in patients with urothelial bladder cancer.

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment.

BACKGROUND AND AIMS: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. METHODS AND RESULTS: Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI ≤24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2), respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height(2.7), higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m(2) higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05). CONCLUSIONS: In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

Von Willebrand factor predicts major bleeding and mortality during oral anticoagulant treatment.

AIMS: Oral anticoagulation (OAC), predominantly with warfarin, is an effective treatment to prevent thromboembolic events. Serious bleeding is a frequent and feared treatment complication. In this longitudinal cohort study of OAC-treated patients, we aimed to evaluate the relationship between von Willebrand factor (VWF) levels and risk of bleeding complications, cardiovascular mortality and all-cause mortality. METHODS AND RESULTS: A total of 719 patients receiving warfarin treatment were observed for a mean duration of 4.2 years. All bleeding complications causing hospitalization were registered and classified into clinically relevant bleeding (CRB) and major bleeding. Ischaemic stroke, peripheral arterial embolism, myocardial infarction, and death were also recorded. We identified 113 cases of CRB and 73 of major bleeding. In total, 161 deaths occurred during follow-up with cardiovascular disease identified as the cause of death in 110 patients. Patients in the highest tertile of VWF had a significantly increased risk of bleeding complications: hazard ratio (HR) 2.53 (95% CI 1.41-4.56) for major bleeding and HR 2.19 (95% CI 1.38-3.48) for CRB. VWF, expressed either in tertiles or as a continuous variable, showed a significant association with cardiovascular mortality (HR 1.68, 95% CI 1.40-2.01) and all-cause mortality (HR 1.77, 95% CI 1.52-2.05). In multivariate Cox regression analysis, the findings remained significant after adjusting for age, high-sensitivity C-reactive protein and creatinine. CONCLUSIONS: Patients with high levels of VWF had an increased risk of bleeding complications, cardiovascular mortality and all-cause mortality during OAC treatment. Our findings imply that the use of VWF as a risk marker for thromboembolic events is complicated by the association of VWF with bleeding complications.

Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy.

AIMS/HYPOTHESIS: High levels of serum heat shock protein 27 (sHSP27) have been associated with distal symmetric polyneuropathy in patients with type 1 diabetes. Our objective was to investigate the association between sHSP27, neuropathic signs and nerve function in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes. METHODS: Participants were recruited consecutively from the population-based Västerbotten Intervention Program (NGT, n = 39, IGT, n = 29, and type 2 diabetes, n = 51) and were matched for age and sex. sHSP27 levels were measured and nerve conduction studies were performed (peroneal and sural nerves). z Scores for each nerve conduction measure were calculated and compiled into a composite z score for the leg. Neuropathy disability score (NDS) was used to assess neuropathic signs. RESULTS: Patients with diabetes had significantly lower sHSP27 levels (geometric mean sHSP27 206 pg/ml, 95% CI 142, 299) than those with IGT (geometric mean sHSP27 455 pg/ml, 95% CI 319, 650, p < 0.05) and controls (geometric mean sHSP27 361 pg/ml, 95% CI 282, 461, p < 0.05). Participants with few signs of neuropathy (first tertile, NDS ≤2) had significantly higher sHSP27 levels (geometric mean sHSP27 401 pg/ml, 95% CI 310, 520) than participants with many signs (third tertile, NDS ≥7) (geometric mean sHSP27 192 pg/ml, 95% CI 128, 288, p = 0.007). The highest sHSP27 tertile was associated with better nerve function, adjusted for age, sex, statin medication and HbA(1c) (OR 2.51, 95% CI 1.25, 5.05, p < 0.05). CONCLUSIONS/INTERPRETATION: High sHSP27 levels were associated with better nerve function and fewer neuropathic signs in NGT, IGT and type 2 diabetes.

Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer.

BACKGROUND: This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC). PATIENTS AND METHODS: Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0. RESULTS: ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B). CONCLUSIONS: Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.

Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up.

There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m(2)) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer.

Metabolic control in diabetic subjects in three Swedish areas with high, medium, and low sales of antidiabetic drugs.

OBJECTIVE: The relationship between use of antidiabetic drugs and metabolic control was studied in Swedish diabetic populations in areas with high (Gotland), medium (Tierp), and low (Skellefteå) sales of antidiabetic drugs. RESEARCH DESIGN AND METHODS: The study population consisted of 405 drug-treated diabetic subjects aged 50-74 yr. In all three areas, glyburide comprised approximately 75% of the oral treatment. RESULTS: In accordance with sales, Gotland was found to be a heavy-use area, characterized by a high prevalence of insulin treatment (43%), combination therapy with sulfonylureas and biguanide (28%), and high prescribed daily doses (PDDs) of glyburide (15.5 +/- 0.8 mg) compared with other areas. In Skellefteå, 38% were on insulin, 4% were on combination therapy, and the PDD of glyburide was 7.1 +/- 0.6 mg. In Tierp, 27% were on insulin, 26% were on combination therapy, and the PDD of glyburide was 11.4 +/- 0.7 mg. In Gotland, both men and women had significantly lower HbA1c levels, regardless of treatment mode, and a tendency to be more overweight compared with the area with the least pharmacological intensity (Skellefteå). CONCLUSIONS: In the three diabetic populations, good metabolic control, defined as an HbA1c level of less than 7% and acceptable weight control (body mass index less than 27 for men and less than 25 for women), was achieved among only 16% in Gotland, 17% in Skellefteå, and 12% in Tierp.

Apoptosis, proliferation, and sex hormone receptors in superficial parts of human endometrium at the end of the secretory phase.

Apoptosis with one regulator, Bcl-2, and proliferation with the marker Ki-67 were studied in 75 endometrial biopsies representing superficial parts of endometrium from 35 regularly menstruating women premenstrually and menstrually. Hormonal withdrawal was studied in serum samples and potentiated in epithelium by the decreasing 17beta-estradiol and progesterone receptor scores 4 days premenstrually. The apoptotic index increased 2 days before the onset of menstruation and peaked on the second menstrual day. The high apoptotic index together with low proliferation in endometrial epithelium at the end of the menstrual cycle are similar to the involution process seen in other hormone-dependent organs. In stroma, the apoptotic index increased later, at the onset of menstruation, and the increase was lower than that in epithelium. The Ki-67 index increased during the last 3 days of the secretory phase, parallel with an increasing progesterone receptor score and decreasing Bcl-2 staining, and peaked at the onset of menstruation. The findings in stroma concur with high proliferation at the end of the menstrual cycle and high cell turnover during menstruation, suggesting the participation of stroma in the renewal process of endometrium.

Endurance physical activity, diet and fibrinolysis.

The impact of long-term, heavy exercise on recently established cardiovascular/thromboembolic risk factors of the fibrinolytic system, tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) in relation to food composition was studied. Twenty healthy men, aged 18-55 years participated in a 14-day skiing tour through the Swedish mountains, carrying a pack load of 30 kg, and spending each night in self-dug igloos (ambient temp -10 degrees to -25 degrees C), and were randomized to 2 food regimens having 30 or 40 energy percent of fat. Individual records were kept of all consumed food. Citrated plasma was obtained before and after 1 and 2 weeks of exercise: tPA release was assessed by a 10 min venous occlusion (VO) test. At baseline, daily dietary fiber intake correlated negatively with PAI-1 activity. Already after the first week of the skiing tour there were significant drops in PAI-1 activities, cholesterol and triglycerides. The tPA mass concentrations also dropped, both before and after VO, but tPA activities were unchanged, as were von Willebrand factor (vWF) levels. These changes were related mainly to the expenditure of energy, calculated from the food consumption, and appeared to be mediated through changed insulin sensitivity and decreased body fat mass. The energy percent of fat in the food had no differential impact. The effects receded a few weeks after cessation of the endurance exercise. Thus, endurance physical activity improves the fibrinolytic risk factor profile by reducing PAI-1 while leaving tPA activity unaffected, independently of food composition. A low dietary fiber intake appears to be associated with higher PAI-1 activities at baseline.

Left ventricular wall stresses and wall stress-mass-heart rate products in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint reduction in hypertension.

OBJECTIVE: Left ventricular (LV) hypertrophy on echocardiogram (ECG) strongly predicts coronary heart disease events, but the mechanisms linking increased LV mass to ischemic vascular events is uncertain. DESIGN: Variables related to myocardial oxygen demand were compared among normotensive adults and patients with mild and more severe hypertension, and among groups of moderately hypertensive patients with target organ damage in relation to gender, LV geometry and LV systolic function. SETTING: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, in which hypertensive patients with ECG LV hypertrophy (Cornell voltage-duration product, > 2440 mm x ms and/or SV1 + RV(5-6) > 38 mm) were randomized to > or = 4 years double-blinded treatment with losartan or atenolol. PATIENTS/PARTICIPANTS: A total of 964 LIFE participants enrolled in an echocardiographic substudy, and groups of 282 employed hypertensive and 366 apparently normal adults. INTERVENTIONS: None. MAIN OUTCOME MEASURES: ECG LV parameters contributing to myocardial oxygen demand (wall stresses, LV mass, heart rate and wall stress-mass-heart rate products). RESULTS: In both women and men, stepwise increases from reference subjects to employed hypertensives to LIFE patients were observed for LV wall stresses, mass and stress-mass-heart rate products. LIFE men patients had slightly higher wall stresses and significantly higher triple products than women. Wall stresses were increased in patients with normal LV geometry, eccentric or concentric hypertrophy; triple products were about three and two times normal with eccentric and concentric hypertrophy, with smaller increases in other geometric groups. Patients with decreased LV fractional shortening had two times normal end-systolic stresses and three or four times normal triple products; smaller increases in stresses and triple products occurred with decreased LV midwall function. CONCLUSIONS: Hypertensive patients with ECG LV hypertrophy have increased LV wall stresses and stress-mass-heart rate products, suggesting a contribution of high myocardial oxygen demand to increased risk in such patients. Particularly high stresses and triple products were associated with echocardiographic LV hypertrophy, and subnormal LV chamber and midwall function.

Endothelial haemostatic factors may be associated with mortality in patients on long-term anticoagulant treatment.

The aim of the present study was to test if long-term mortality could be predicted by endothelial derived haemostatic variables in a population with high morbidity due to thromboembolic disease. Plasma samples were drawn from 212 out-patients treated with oral anticoagulants, at the beginning of the study, and analyzed for mass concentration of tissue plasminogen activator (tPA) and its inhibitor (PAI-1), and von Willebrand factor. In the course of 3.8-year follow-up 45 patients died, including 38 vascular deaths. We found that all-cause mortality was significantly associated with increased levels of vWF and tPA. For vascular mortality there was a significant association with all three haemostatic variables (tPA, PAI-1, vWF). For vWF there was a 3-fold increase in total and vascular mortality in the highest quartile compared to the lowest quartile. There were 27 vascular deaths in the group of patients with a tPA-value above the median compared to 11 in those with a tPA below the median. In multivariate Cox regression analysis (including: age, sex, smoking habits, body mass index, diabetes mellitus, hypertension, tPA, PAI-1, and vWF), vWF and smoking were independently significantly associated with all-cause mortality, and tPA and age with vascular mortality. Endothelial derived haemostatic variables are predictors of total and vascular mortality in patients treated with oral anticoagulants.

Apoptosis, proliferation, and hormone receptors in endometrial carcinoma: results depending on methods of analysis.

Apoptosis and proliferation were studied in 29 endometrial adenocarcinomas of the endometrioid type and characterized by the immunohisto-chemical pattern of estrogen receptor (ER) alpha and progesterone receptor (PR) expression. Intratumoral heterogeneous distribution of both ER and PR as well as of the proliferation marker Ki-67 was studied and quantified. Both density and heterogeneity of the two steroid receptors and Ki-67 varied, depending on the histological malignancy grade (grades 1-3, or G1-3); interestingly, however, the apoptotic index (Ai) was in the same range for all grades. Receptor staining was evaluated by three different methods: i) counting the percentage of stained cells (staining index), according to stereological principles; ii) the mixed method, a combination of the staining index results and ranking staining intensity; and iii) a superficial and rapid visual scoring. The three methods gave equal results. Apoptotic cells and bodies were generally scattered in the endometrial carcinoma but more frequently observed adjacent to necrotic foci. Bcl-2, known as anti-apoptotic factor, showed no correlation to apoptotic index, Ki-67 expression, ER, or PR. Overexpression of p53 was seen in two tumors of grade 3. In a detailed study of intra-tumoral microfoci performed on consecutively taken tissue sections, a higher staining index of both ER and PR was found in the areas of maximal proliferation compared with the areas of minimal proliferation in tumors of grades 1-2, but not in G3 tumors. Other covariations were also found when non-specified areas were studied. The Ki-67 index was both higher and more heterogeneous in G2-3 tumors than in G1 tumors. Our results indicate that there is an increasing discrepancy between cell death and cell proliferation with progressing tumor grade, which may contribute to the differences in tumor aggressivity.

The management of heart failure in Sweden.

Heart failure is a major concern to health care providers in Sweden due to its increasing prevalence and the rising health care costs. Heart failure affects more than 160000 Swedes, approximately 2% of the population. The costs for the management of heart failure have been calculated to be approximately SEK 2.500 million (Euro 275 million) which is 2% of the total health care budget. Most heart failure patients are managed by primary care physicians but hospitalisation is common and heart failure is the most common cause for hospitalisation in patients over 65 years of age. National diagnostic and treatment guidelines are not completely adhered to. Echocardiography is performed in a little more than 30% of patients in primary care probably due to poor access. In hospitals echocardiography is more easily available and routinely used for diagnosis. Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers appear to be under prescribed. Nurse-led heart failure clinics are being widely established in an attempt to curtail costs and improve management.

Termination of a separate (proprioceptive?) cuneothalamic tract from external cuneate nucleus in monkey.

The termination of a pathway recently discovered in monkey, from the external cuneate nucleus (ECN) to the thalamus, has been investigated with the degeneration method. A previous HRP study showed that the projection is crossed. The ECN fibers terminate a wedge-shaped zone located dorsally in the rostral half of the contralateral nucleus ventralis posterolateralis (VPL). This zone occupies the dorsolateral corner of the forelimb division of the VPL. The main cuneate nucleus also projects to this zone, most of which has the cytoarchitectonic characteristics of Olszewski's VPLc24. The ECN pathway may be phylogenetically recent, and it may be a direct route for proprioceptive information to the cerebral cortex.

Effects on fibrinolytic activity of corn oil and a fish oil preparation enriched with omega-3-polyunsaturated fatty acids in a long-term study.

In addition to their beneficial effects in reducing platelet responsiveness, it has been a matter of controversy whether polyunsaturated fatty acids impair the fibrinolytic system or not. In a double-blind, parallel clinical trial, 40 subjects were randomized to treatment with 6 g/day of corn oil, or to 6 g/day of a fish oil preparation, enriched with omega-3-polyunsaturated fatty acids (2.0 g/day of omega-3-PUFA). Clinical and fibrinolytic variables were measured before and after 5 months of treatment. In the corn oil group, plasminogen activator inhibitor (PAI-1) decreased significantly but in the cod liver oil group, PAI-1 remained unchanged. Activities and mass concentrations of tissue plasminogen activator (t-PA) were unchanged in both groups. It is concluded that, in the doses given here, both these preparations have small or no effects on the fibrinolytic system.

Shifting the distribution of risk: results of a community intervention in a Swedish programme for the prevention of cardiovascular disease.

STUDY OBJECTIVE: To examine the impact of a systematic risk factor screening and counselling carried out by family physicians and family nurses within the larger framework of a community intervention programme for the prevention of cardiovascular disease (CVD). DESIGN: Quasi-experimental study comparing trends in an intervention area with those in a reference area. SETTING: A Northern Sweden municipality (5500 inhabitants) constituted the intervention area while the Northern Sweden region (510,000 inhabitants) served as the reference area. PARTICIPANTS: All 30, 40, 50, and 60 year old inhabitants were invited each year from 1985 to 1992. Among 2046 eligible 1893 participated (92.5%), which formed eight independent cross sections. One cross section, 1986, was re-surveyed forming a panel. MAIN RESULTS: In the cross sections, mean total cholesterol was reduced from 7.09 to 6.27 mmol/l for men (p < 0.001) and from 7.13 to 5.89 mmol/l for women (p < 0.001) and mean systolic blood pressure from 132.2 to 123.7 mm Hg for men (p < 0.05) and from 129.2 to 122.0 mm Hg for women (p < 0.001) during the eight years. Body mass index (BMI) increased from 25.6 to 26.2 for men (p < 0.05) and from 25.0 to 25.5 for women (NS). A corresponding reduction in cholesterol and blood pressure (for women) occurred in the panel, while BMI was unchanged. The risk for CVD, using the Framingham equation, was estimated to be reduced overall by 19% (p = 0.0021) when comparing early cross sections (1985/86) with the later cross sections (1990/91). CONCLUSIONS: It was concluded that a long term community based CVD prevention programme that combines population and individual strategies can substantially promote a health shift in CVD risk in a high risk rural population. The individual attention and evaluation provided by the health provider survey seem to accelerate, but not increase the amount of, risk reduction.

Impact of valvular regurgitation on left ventricular geometry and function in hypertensive patients with left ventricular hypertrophy: the LIFE study.

Mild-to-moderate aortic and mitral regurgitation are frequently detected by echocardiogram in asymptomatic hypertensive patients. Our goal was to assess the prevalence and impact of mild-to-moderate mitral and/or aortic regurgitation on left ventricular (LV) structure and function in patients with hypertension and LV hypertrophy (LVH). Hypertensive patients with ECG LVH enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy were evaluated. Among 939 patients with needed LV measurements and Doppler data, 242 had mild (1+) valvular regurgitation, and 51 patients had moderate (2+ or 3+) regurgitation of one or both valves. In analyses adjusting for gender, patients with mild mitral and/or aortic regurgitation had larger LV internal dimensions (5.25 vs 5.33 cm, P<0.05), higher LV mass indexed for body surface area (122 vs 125 g/m(2), P<0.05) or height(2.7) (55.4 vs 57.3, P<0.05), and larger left atrial diameter. Patients with moderate regurgitation of one or both valves had larger LV chambers (5.25 vs 5.9 cm, P<0.001), greater mean LV mass (232 vs 248 g, P<0.001) and LV mass indexed for body surface area or height(2.7), and higher Doppler stroke volume. Patients with moderate valvular regurgitation also had a higher prevalence of LVH due to an increased prevalence of eccentric LVH. There were no differences among groups defined by the presence and severity of valvular regurgitation in cardiac output, total peripheral resistance, or pulse pressure/stroke volume, indicating that the observed inter-group differences in LV geometry were not due to differences in the haemodynamic severity of hypertension. Hypertensive patients with mild-to-moderate mitral or aortic valvular insufficiency have additional LV structural and functional changes that may affect prognosis.

Progesterone androstenedione testosterone and clinical characteristics in endometrial carcinoma.

Serum concentrations of progesterone (P), androstenedione (A) and testosterone (T) were measured in 128 postmenopausal women with endometrial adenocarcinoma. The correlations between these hormones were studied and related to such clinical parameters as: stage, histopathology, age, gynaecological history, body mass index and related diseases. In previous studies we have shown the relations between oestron (E1) and oestradiol (E2) serum concentration and clinical parameters. A clear correlation was seen between E1 and E2. Both E1 and E2 also strongly correlated with BMI. In this study androstenedione is found to correlate with E1 and E2, p less than 0.03 and p less than 0.02 resp. Progesterone and E1 were correlated, p less than 0.01, but not P and E2. Testosterone correlated with E1, p less than 0.002, E2, p less than 0.003 and A, p less than 0.02. None of the hormones P, A or T correlate with BMI. Androstenedione and age, and A and menopausal years showed a negative correlation, p less than 0.01 for both. Testosterone correlated with menopausal years, p less than 0.03; and correlated negatively with years of menstruation, p less than 0.03. These results do not support the hypothesis that A is the exclusive precursor for conversion to E1 in fat tissue. The correlation between P and E1 could indicate a relation to steroids higher up in the synthesis chain. The influence of P, A and T on the investigated clinical factors can not be strong, since correlations are virtually missing.