Basal and exercise-induced neuroendocrine activation in patients with heart failure and in normal subjects

BACKGROUND: Neuroendocrine activation is a pathophysiological response and an important prognostic marker in patients with chronic heart failure (CHF). Although chronic activation is well described, data on the responsiveness of the hormone systems are more limited. Most previous studies have looked at activation during maximal exercise, whereas we believe that activation at a submaximal level might be more pathophysiologically relevant. AIM: To compare exercise-induced neurohormonal activation between CHF patients and normal subjects using the same relative and submaximal workload. Subjects: Twenty-three newly-diagnosed CHF patients and 18 age- and gender-matched healthy subjects were exercised at two workloads, which were calculated to correspond to 50 and 75% of each individual's heart rate response. RESULTS: In CHF patients, baseline levels of ANP, BNP, AVP, PRA and ET-1 were elevated compared to healthy subjects. Exercise induced an increase in ANP, A and NA in both CHF patients and in normal subjects, however BNP was only increased in CHF patients and not in normal subjects. CONCLUSION: When CHF patients exercise at the same relative and submaximal level as age-matched healthy subjects, the relative increases in ANP, A and NA were similar, however, BNP levels only increased in the CHF group.     

Interaction of thyroid-stimulating antibodies with the human thyrotrophin receptor.

Thyroid-stimulating antibodies (TSAb) were found to inhibit the binding of labelled thyrotrophin (TSH) to thyroid membranes in a dose-dependent manner and this effect was localized in the Fab part of the TSAb molecule. Analysis of the binding data suggested that TSAb and TSH bound to the same receptor site. Production of cyclic AMP by the thyroid membranes was stimulated by TSAb and TSAb-Fab with a similar time course to that observed with TSH. Kinetic studies indicated that the binding of TSAb to the thyroid membranes was not rate-limiting in the process of stimulation of cyclic AMP production.     

Lewis blood type frequency in patients with primary Sj?gren's syndrome. A prospective study including analyses for A1A2BO, Secretor, MNSs, P, Duffy, Kell, Lutheran and rhesus blood groups

Seventy-five patients in two randomly selected groups (N = 40 plus 35) with primary Sj?gren's syndrome were tested for Lewis, A1A2BO, secretor, MNSs, P, Duffy, Kell, Lutheran and rhesus blood group antigens. The results were compared with the frequencies in a control group and in the general population. The Lewis blood group frequency differed (p less than 0.05) from that of the general population, due mainly to an increased Le(a-b-) frequency. Similar immuno-haematological findings have not been reported earlier in patients with rheumatological diseases. If confirmed by other centres, the results may be of importance for our understanding of the immunological mechanisms of chronic inflammatory connective tissue diseases.     

Pattern of platelet-associated immunoglobulin (classes and IgG subclasses) in childhood immune thrombocytopenic purpura

Platelet-associated Ig classes and IgG subclasses were studied by a semiquantitative platelet ELISA test in 17 children with immune thrombocytopenic purpura (ITP). An elevation of PAIg was found in 94% of the children. In nearly all cases increased amounts of PAIgG of subclass G1 was seen, and in half of the cases increased amounts of PAIgM were also seen. No statistical difference in the composition of PAIg classes and PAIgG subclasses in acute and in chronic ITP was found. However, a correlation of increased amount of PAIgG3 and very low platelet count (20 x 10(9)/l) was observed.     

Connective tissue growth factor with a novel fibronectin binding site promotes cell adhesion and migration during rat oval cell activation

Oval cell activation, as part of the regenerative process after liver injury, involves considerable cell-matrix interaction. The matricellular protein, connective tissue growth factor (CTGF), has been shown to be critical for oval cell activation during liver regeneration following N-2-acetylaminofluorene/partial hepatectomy. To understand the mode of action of CTGF during this process, N-terminal CTGF was used as bait to screen a yeast two-hybrid complementary DNA library specific for regenerating livers with massive oval cell presence. Fibronectin (FN), a prominent component of hepatic extracellular matrix (ECM), was found to specifically bind to a new site on CTGF. In addition to module IV, this study showed that module I of CTGF was sufficient for binding to FN in both solid-phase in vitro binding assays and immunoprecipitation. Immunofluorescent staining revealed a dynamic ECM remodeling characterized by an FN-concentrated provisional matrix during oval cell-aided liver regeneration. Abundant CTGF protein was colocalized with FN in the provisional matrix. When expressed as recombinant proteins and immobilized on plastic surfaces, modules I and IV of CTGF were selectively adhesive to thymus cell antigen 1-positive (Thy1(+)) oval cells, stellate cells, and sinusoidal endothelial cells but not to hepatocytes. The adhesion of these two modules on Thy1(+) oval cells required heparan sulfate proteoglycan and integrin alpha(5)beta(1). Recombinant CTGF promoted an integrin alpha(5)beta(1)-dependent migration but not proliferation on Thy1(+) oval cells. CONCLUSION: Modules I and IV enabled the linkage of CTGF to FN and activated hepatic cells. Through these bindings, CTGF on the FN-concentrated provisional matrix promoted cell adhesion and migration, thereby facilitating oval cell activation.     

Contraception for women with diabetes mellitus

Planned pregnancy is mandatory in women with diabetes, and their need for contraception is essential. Basically, the same methods can be used as in women without diabetes, but a number of specific conditions have to be considered when guiding these women, as we discuss in this review. Unfortunately, the field is limited in studies in certain areas, especially considering contraception for women with type 1 diabetes and late diabetic complications and women with type 2 diabetes. Thus, in the real clinical world, the choice of contraceptive often will be a kind of compromise, balancing pro and cons for the different available methods.     

Neurohormones as markers of right- and left-sided cardiac dimensions and function in patients with untreated chronic heart failure

BACKGROUND: It is now well accepted that neuroendocrine activation is of pathophysiological and prognostic importance in patients with chronic heart failure (CHF). We hypothesized that the different neuroendocrine factors reflect different aspects of the cardiac dysfunction in CHF patients and that neuroendocrine profiling could be of value. In order to study this, we investigated the relationship between hormones and cardiac dimensions and function of both the right and left ventricle. METHODS: Twenty-three patients with newly diagnosed, untreated CHF were included. Right (RVEF) and left ventricular ejection fractions (LVEF) and volumes were measured by means of first-pass and equilibrium radionuclide ventriculography. RESULTS: LVEF was 0.29 (range: 0.11-0.55). Two-thirds of the patients had dilated left ventricles with volumes above upper reference limit. Right ventricular ejection fraction was normal in all subjects as well as right ventricular volumes. Likewise, on average, the lung transit time (LTT) was normal. Brain natriuretic peptide (BNP) significantly correlated with LVEF, left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI). Adrenaline correlated significantly with both right ventricular end-diastolic volume index and right ventricular end-systolic volume index. Lung transit time correlated with atrial natriuretic peptide (ANP) and BNP (only ANP in multivariate analysis). CONCLUSIONS: (1) BNP reflects the LVEF as well as diastolic and systolic dimensions; (2) adrenaline reflects the right ventricular systolic and diastolic dimensions; and (3) ANP reflects the lung transit time. We conclude that "neuroendocrine profiling" may potentially be of diagnostic and therapeutic use.