Short-term impact of a 4-week intensive cardiac rehabilitation program on quality of life and anxiety-depression.

INTRODUCTION: Cardiac rehabilitation programs are well recognized as being essential to the comprehensive care of patients with cardiovascular disease and chronic heart failure. These programs aim at reducing cardiovascular risks, promoting healthy lifestyle behaviours and compliance as well as limiting disability and increasing quality of life (QoL) of cardiac patients. PURPOSE: To evaluate the impact of a 4-week cardiac rehabilitation program on physical parameters and several aspects of the QoL of cardiac patients. METHODS: A cohort of 101 cardiac patients (men: 70%) mean age 65±12 years (mean±SD) participated in a cardiac rehabilitation program. Before and after the 4-week cardiac rehabilitation program, the study recorded and assessed the patients' physical parameters such as weight, body mass index (BMI), waist circumference and effort tolerance as well as QoL using different questionnaires: SF-36 Health Survey (SF-36), Hospital Anxiety and Depression Scale (HAD) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The patients' physical parameters (BMI and waist circumference) decreased by 3%, while effort tolerance increased by 25% (P<0.0001). Furthermore, for all patients, the PSQI, HAD and physical and mental SF-36 scores improved significantly (P<0.0001). The different SF-36 subscales' scores did also increase after the program (P<0.0001). CONCLUSION: Despite a modest weight loss and reduction in waist circumference, a 4-week cardiac rehabilitation program (short-term) seems to be sufficient for improving patients' physical state and mental well-being.

Venlafaxine occupation at the noradrenaline reuptake site: in-vivo determination in healthy volunteers.

Venlafaxine, a serotonin and noradrenaline reuptake inhibitor, is an effective antidepressant at doses of 75 mg p.o. daily and above. Preclinical and healthy volunteer studies have demonstrated that venlafaxine is more potent at the serotonin than at the noradrenaline reuptake site, with noradrenergic blocking effects being observed at doses >75 mg p.o. in man. We used the Multiple Organs Coincidences Counter and [11C] meta hydroxy ephedrine (MHED) to test whether significant occupation of cardiac sympathetic neurones was achieved in man in vivo after the acute administration of venlafaxine 75 mg p.o. in nine healthy volunteers. MHED is a tracer which binds at the noradrenaline reuptake site. This study demonstrates that the [11C]MHED signal is significantly reduced after the administration of venlafaxine 75 mg p.o. thus showing that noradrenaline reuptake blockade is observable at this dose. This effect is predominantly seen in volunteers who received > 1 mg/kg venlafaxine.

Effects of 7 years of growth hormone replacement therapy in hypopituitary adults.

Short-term studies of GH replacement in adult hypopituitarism have usually demonstrated beneficial effects on body composition and circulating lipids, with neutral or occasionally adverse effects on glucose tolerance. Fasting hyperinsulinemia has been reported. GH effects on cardiac function have been variable. The effects of long-term GH therapy, taking into account the consequences of increasing age, are not fully known. Thirty-three hypopituitary, initially middle-aged adults were studied over a 7-yr period; 12 patients took GH therapy (mean, 0.7 mg daily) continuously (group A); 11 took GH for only 6-18 months, a minimum of 5 yr previously (group B); and 10 patients never received GH therapy (group C). Other pituitary replacement was maintained. Effects on anthropometry, body composition (by bioimpedance analysis, total body potassium, and dual energy x-ray absorptiometry), circulating lipids, glucose and insulin concentrations, cardiac 2-dimensional and Doppler echocardiography, and exercise tolerance were assessed before and after the treatment period. Continuous GH therapy had no significant effect on body weight, but it prevented the increase in waist circumference and waist to hip ratio that occurred in the patients without GH substitution (waist to hip ratio, group A, 0.87+/-0.08 at baseline, 0.85+/-0.09 at 7 yr; group B, 0.89+/-0.11 at baseline, 0.94+/-0.11 at 7 yr; P < 0.005 for GH effect; group C, 0.87+/-0.10 at baseline, 0.92+/-0.10 at 7 yr; P < 0.005 for GH effect). A GH-induced decrease in subscapular skinfold thickness was also observed. By bioimpedance analysis, GH therapy caused an increase in total body water and fat-free mass, and a decrease in the percent body fat. Although changes occurred with time in all groups, no significant additional GH therapy effects were observed on glucose tolerance, insulin concentrations, lipid levels, cardiac dimensions, echocardiographic diastolic function, or exercise tolerance. In conclusion, prolonged GH substitution in middle-aged hypopituitary adults causes a sustained improvement in body composition. Other benefits, e.g. on lipid levels and exercise tolerance, were not apparent at 7 yr when comparisons were made with GH-untreated hypopituitary controls. Potentially adverse effects on glucose tolerance and insulinemia did not develop with prolonged GH therapy.

The prevalence of hepatitis B and C in HIV-positive Greek patients: relationship to survival of deceased AIDS patients.

OBJECTIVES: To determine the prevalence of hepatitis viruses B (HBV) and C (HCV) co-infections in HIV-infected patients and the overall impact of these co-infections on deceased AIDS patients survival. METHODS: One hundred and eighty-one patients (159 males, 22 females) infected with HIV, attending an academic AIDS unit in Athens, Greece, constituted the study population. The study population consisted of 124 homo/bisexual men, 34 heterosexuals, 12 intravenous drug users (IDU) and 11 blood transfusion recipients. Virological markers tested for HBV infection included HBsAg, anti-HBs and total anti-HBc by enzyme-linked immunoassays. Detection of HCV antibodies was carried out by third generation enzyme-linked immunoassay, and repeatedly positive samples were further tested by a supplemental enzyme-linked immunoassay; only sera reactive by both methods were considered to be HCV-positive. RESULTS: The prevalence of HBV markers was 67.4%: 71.8% in homo/bisexuals, 35.3% in heterosexuals, 91.7% in IDUs and 90.9% in blood transfusion recipients (P = 0.00004). The prevalence of HCV antibodies was 13.8%: 8.1% in homo/bisexuals, 8.8% in heterosexuals, 58.3% in IDU and 45.5% in blood transfusion recipients (P<0.000001). The prevalence of HCV antibodies was not significantly higher in homo/bisexuals than in heterosexuals (P= 0.8). Coinfection with HBV or HCV, or both, did not influence the survival of deceased AIDS patients (n = 73). CONCLUSIONS: HBV infection was equally prevalent among homo/bisexuals and IDU with HIV infection, whereas HCV infection was more prevalent in IDU than in homo/bisexuals with HIV infection. The prevalence of HCV infection was equal among heterosexuals and homo/bisexuals, indicating that if sexual transmission of HCV occurs, homo/bisexuals are not at greater risk than heterosexuals. Finally, the survival of deceased AIDS patients was not affected by the presence of HBV and HCV co-infections.

Desipramine binding to noradrenaline reuptake sites in cardiac sympathetic neurons in man in vivo.

Noradrenergic reuptake blockade is a recognised mechanism of antidepressant action, but the extent of the blockade necessary for therapeutic effect is not known and plasma levels do not provide a guide to therapy. We report a method to assess noradrenaline reuptake blockade in vivo in man using [11C]meta-hydroxyephedrine and the multiple organs' coincidences counter. Eight healthy volunteers had two scans, one with tracer alone and one after preloading with desipramine 50-75 mg p.o. In all subjects, there was an increased washout rate of the radioligand from the heart following preloading (t=4.38; P<0.003) as well as a decrease of the area under the [11C]meta-hydroxyephedrine time activity curve (t=7. 4; P=0.001). In one subject who had three doses of desipramine, the increase in washout rate was dose-dependent. In conclusion, [11C]meta-hydroxyephedrine in the multiple organs' coincidences counter gives a valid, low radiation method to assess noradrenergic reuptake blockade in the clinic.

Sulfone-linked paracyclophanes via macrocyclic aromatic thioethers: synthetic and structural investigations.

Reaction of 4,4'-sulfonylbis(benzenethiol) with 4,4'-dichlorodiphenylsulfone under pseudo-high-dilution conditions leads to macrocyclic thioethersulfones [-S-Ar-SO2-Ar-]n (Ar = 1,4-phenylene). These include a highly strained [1+1] cyclodimer (n = 2), a cyclotrimer resulting from thioetherexchange reactions, and a [2+2] cyclotetramer which can adopt two entirely different conformations in the crystalline state, one having molecular D2d ("tennis-ball-seam") symmetry. The same type of reaction is successful using 4,4'-thiobis(benzenethiol) instead of 4,4'-sulfonylbis(benzenethiol) and affords macrocycles with a higher ratio of thioether to sulfone linkages. Exhaustive oxidation of macrocyclic thioethersulfones with hydrogen peroxide affords a series of sulfone-linked paracyclophanes, [-Ar-SO2-]4, [-Ar-SO2-]6, [-Ar-SO2-]8 and [-Ar-SO2-]12. Single crystal X-ray analysis reveals [Ar-SO2-]4 to be a near-perfect square box, whilst the cyclic hexamer [-Ar-SO2-]6 adopts a much more irregular conformation. and [-Ar-SO2-]8 displays a "double-box" structure clearly related to that of [Ar-SO2-]4.

[Chromatography of thrombin and antithrombin III on biospecific silochromes]. / Khromatohrafiia trombinu ta antytrombinu III na biospetsyfichnykh sylokhromakh.

It was shown that the seaweed sulfopolysaccharides Furcellaria and Phyllophora--furcellaran and phyllophoran--are the competitive inhibitors of thrombin-induced fibrinogen clotting. Biospecific adsorbents for thrombin and antithrombin III (AT III) isolation were synthesized with heparin, phyllophoran and furcellaran as ligands on aminopropylsilochrome and this proteins sorption characteristics on this sorbents in comparisons with heparin-cellulose and heparin-sepharose were investigated. Possible application of the synthesized adsorbents both for thrombin, AT III purification from blood products and for alpha-thrombin, beta and gamma-thrombin separation are discussed.

A new human (psycho)pharmacology tool: the multiple organs coincidences counter (MOCC).

We describe a novel instrument which is capable of measuring the uptake of radioligand in human organs in vivo with the administration of very small doses of positron-emitting radioligands. This technique readily detects the displacement or reduced uptake of radioligand when a competitive agonist or antagonist is administered. This system provides no tomographic information, but the small radioactive doses involved mean that investigations can be repeated at regular intervals and that female volunteers can also participate. We administered [(11) C]flumazenil, [(11)C]diprenorphine, [(11)C]meta -hydroxyephedrine (MHED) and [(11)C]RTI 55 to healthy male volunteers and performed control, pre-loading and displacement experiments. These demonstrate the feasibility of using this technique to investigate benzodiazepine and opiate receptor occupancy, as well as occupancy at dopamine, noradrenaline and serotonin (5-HT) re-uptake sites. This method is likely to be useful in pharmacokinetic/pharmacodynamic experiments, in drug development and discovery and in the development of novel imaging radioligands.