No abstract

Abnormalities of the autonomic nervous system are known to be of prognostic significance in chronic heart failure (CHF). The prognostic value of positron emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not been explored previously. We retrospectively studied the survival data of 46 NYHA class II-III CHF patients (mean LVEF 35% +/- 8%) who had undergone carbon-11 hydroxyephedrine (11C-HED) studies at the Turku PET Centre between August 1992 and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46 patients and coronary artery disease with at least one prior myocardial infarction in the remaining 33. Data on causes of death and heart transplantation were collected, and the statistically significant predictors of prognosis were analysed using Cox's proportional hazards regression. During the mean follow-up period of 55 +/- 19 months, 11 deaths occurred and two patients underwent heart transplantation successfully. Eleven end-points were classified as cardiac (nine sudden cardiac deaths and two deaths due to progressive heart failure) and two as non-cardiac. When divided into two groups based on the median of 11C-HED retention (mean 0.184 +/- 0.061, median 0.183), eight end-points (death or cardiac transplantation) were reached in the group with 11C-HED retention below the median and three in the group with 11C-HED retention above the median (P < 0.02). In proportional hazards regression analysis, only peak oxygen uptake (peak VO2), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that 11C-HED PET provides independent prognostic information in patients with CHF.

A double-blinded, placebo-controlled cross-over trial was carried out with 27 hypercholesterolemic men with coronary heart disease. During the 6-week treatment period lovastatin (60 mg/day) decreased fasting serum LDL cholesterol by 45%, LDL phosphorus by 38% and apoB by 33%. Ubiquinol content diminished by 13% as measured per LDL phosphorus. When LDL was oxidized ex vivo with AMVN both LDL ubiquinol and a-tocopherol were exhausted faster after lovastatin treatment compared to placebo, by 24% (P < 0.005) and 36% (P < 0.0001), respectively. Lag time in copper-induced oxidation of LDL decreased by 7% (P < 0.01). This suggests diminished antioxidant-dependent resistance of LDL to the early phase of oxidative stress.© 1997 Federation of European Biochemical Societies.

A b s t r a c tWe evaluated the Sysmex UF-100 urine flow cytometer (TOA Medical Electronics, Kobe, Japan) The development of automated blood cell analyzers has prompted several attempts to produce similar devices for urinalysis. The first commercially available instruments were the Yellow IRIS (International Remote Imaging Systems, Chatsworth, CA) in the United States' and the Sysmex UA series (TOA Medical Electronics, Kobe, Japan) in Japan. 2Demands for a higher level of automation and satisfactory differentiation of specific urine particles have been the driving forces for improvement.We evaluated a second-generation urine flow cytometer, the Sysmex UF-100 (TOA Medical Electronics) by comparing its performance with chamber counting of Sternheimerstained noncentrifuged specimens and with conventional bacterial cultures on cystine-lactose-electrolyte-deficient (CLED) agar plates. Routine reflectometric test strip measurements and morphologic analyses based on the Finnish recommendations 3 were also performed for comparison. The characterization of formed elements with the UF-100 analyzer is based on flow cytometry of particles doublestained for DNA and membranes; particle identification involves measurement of forward-scattered light intensity and fluorescent light intensity, and the widths of these signals. Conductivity of the sample is measured before it enters the flow cell to adjust a constant electrical current in the flow cell for the impedance measurement. The final differentiation is accomplished with multiparametric algorithms (adaptive cluster analysis). A quantitative report is given for RBCs, WBCs, (large) epithelial cells, bacteria, and casts. Additional information flags are provided to indicate the presence of inclusional casts (granular or cellular casts),

Ž. Purpose: Impaired insulin sensitivity has been linked with chronic heart failure CHF . Exercise has a beneficial effect on insulin sensitivity in healthy subjects. It is used also as an adjunctive therapy in patients with CHF. We studied the effect of Ž . randomized treatment with celiprolol, a vasodilating ␤ -adrenoceptor antagonist, 200 mg once daily n s 20 or placebo 1 Ž . ns11 on serum lipid levels and insulin sensitivity in patients with CHF. In addition, all subjects participated in a 6-month exercise training protocol. Thirteen subjects in the celiprolol and eight subjects in the control group were on additional ␤ -adrenoceptor antagonist as part of their tailored CHF therapy. Insulin sensitivity was determined using the hyperinsu-1 Ž . linemic euglycemic clamp test diabetic subjects excluded, n s 11 for the celiprolol group and n s 8 for the placebo group .Ž . Ž . Ž . Results: Insulin sensitivity index ISI increased by 33% P-0.05 in the celiprolol group and by 17% NS in the control w Ž . x group. The mean increase in the whole group was 20% from 68.2" 11.5 to 81.7" 10.7 mlrminrkg mUrl , P-0.05 . No Ž change was found in the total cholesterol level. HDL cholesterol levels increased by 12% from 0.98" 0.05 to 1.10" 0.05 . Ž . mmolrl, P-0.005 , and HDLrtotal cholesterol and HDLrLDL cholesterol ratios by 15% and 16%, respectively P -0.005 . Ž . The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group P-0.05 . At baseline ISI Ž . Ž . correlated with maximal oxygen uptake r s 0.65, P-0.0001 and body mass index r sy0.55, P-0.001 . The change in ISI Ž . correlated weakly with the improvement in muscle exercise capacity r s 0.53, P-0.05 . Conclusions: Insulin sensitivity and serum lipid levels may be favorably affected by exercise training in subjects with mild-to-moderate CHF. Celiprolol, a vasodilating ␤1-selective adrenoceptor antagonist, potentiates this effect. ᮊ

Nephropathy is a major cause of premature morbidity and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM). The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) is a genetic determinant of plasma ACE levels. Recent studies have found I/D polymorphism of the ACE gene to be associated with nephropathy in NIDDM. This association has not been evaluated in prospective studies. We, therefore, studied the relationship between ACE gene I/D polymorphism and diabetic albuminuria and glomerular filtration rate (GFR) in 83 NIDDM patients followed up for 9 years. At baseline, 29% (24 of 83) of the diabetic patients had an increased (>30 mg/24 h) urinary albumin excretion rate (UAER) and the prevalence of albuminuria at the 9-year examination was 35% (29 of 83). During the follow-up period, systolic blood pressure (p = 0.044), prevalence of hypertension (p < 0.01), and fasting blood glucose levels (p < 0.01) increased, while high-density lipoprotein cholesterol (p < 0.01) decreased. The declines of GFR during the follow-up period were 8.5, 14.1, and 16.3% within genotype groups of II, ID, and DD, respectively (p values for decreases: NS for II, <0.001 for ID, and <0.001 for DD). Patients with the DD genotype tended to have a steeper decrease of GFR, but the change was not statistically significant between the genotype groups. The increases of UAER during the follow-up period were 35.1, 8.3, and 122.4% within genotype groups of II, ID, and DD, respectively, but p values for all increases were not significant. Parallel to GFR, patients with the DD genotype tended to have a steeper increase of UAER, but the change was not statistically significant between the genotype groups. There were no differences in the ACE genotype distribution and allele frequencies between the patients with or without albuminuria either at follow-up or in cross-sectional settings. In conclusion, this 9-year follow-up study does not support the hypothesis that the ACE I/D polymorphism is a major genetic marker of diabetic nephropathy in NIDDM patients.

The study was undertaken to evaluate the development and association of parameters related to the metabolic syndrome during celiprolol treatment. Hyperinsulinemic euglycemic clamp and independent oral glucose tolerance tests (OGTT) were performed on 25 nondiabetic patients with controlled hypertension and dyslipidemia. The tests were carried out during the patients' previous antihypertensive monotherapy (beta- or Ca-blocker, or an ACE inhibitor), and after 6 and 12 months of celiprolol treatment. About one third of patients were randomized to a control group in which treatment was kept unchanged. Insulin sensitivity index (ISI), measured by the euglycemic clamp test, increased 35% in the celiprolol group at 6 months and remained at that level at 12 months, independent of the previous treatment (p = 0.03, compared to the change in the control group). During a 2 hour OGTT, incremental glucose area under the curve (AUC) decreased from 4.5 to 1.9 hr x mmol/l during 6 months of celiprolol treatment, and decreased further to 1.5 hr x mmol/l at 12 months (p < 0.001). Insulin AUC decreased from 113 to 72 hr x mU/l, and decreased further to 68 hr x mU/l (p < 0.01). All insulin parameters in OGTT were highly significant (p < 0.0001) and inversely associated with ISI. Insulin AUC had the best linear correlation with ISI (r = -0.682, p < 0.0001). Glucose parameters in OGTT correlated only weakly and inversely with insulin sensitivity. From the fasting serum lipids, triglycerides showed an inverse (p < 0.001) and HDL a weak (p < 0.05) positive association with ISI. Four out of 20 metabolic, clinical, and demographic parameters proved to be independently significant predictors for ISI in multiple regression analysis. These were insulin AUC, fasting insulin levels, triglyceride values, and age. The coefficient of determination in this four-parameter linear model was 69%. In this preliminary, observer-masked trial with a limited control group, celiprolol improved the impaired insulin sensitivity and glucose tolerance of dyslipidemic hypertensive patients. A fairly predictive model can be formulated to evaluate the peripheral insulin sensitivity of hypertensive patients with suspected metabolic syndrome using OGTT with serum insulin determinations.

Repeated group education applied as an economically feasible part of specialist care had only small positive effects on patients' risk factors. There was a significant, but transient, increase in the resistance of LDL against oxidation. However, effective lipid lowering drug treatment is indicated for most coronary artery bypass patients rather than repeated health education alone.