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Biomedical subjects

I Klimes

Publications and source records attributed to I Klimes.

At least 19 recordsLinked to original sources

Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVE: To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with the chronic fatigue syndrome. DESIGN: Randomised controlled trial with final assessment at 12 months. SETTING: An infectious diseases outpatient clinic. SUBJECTS: 60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome. INTERVENTIONS: Medical care comprised assessment, advice, and follow up in general practice. Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care. MAIN OUTCOME MEASURES: The proportions of patients (a) who achieved normal daily functioning (Karnofsky score 80 or more) and (b) who achieved a clinically significant improvement in functioning (change in Karnofsky score 10 points or more) by 12 months after randomisation. RESULTS: Only two eligible patients refused to participate. All randomised patients completed treatment. An intention to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients who were given only medical care (difference 47 percentage points; 95% confidence interval 24 to 69). Similar differences were observed in subsidiary outcome measures. The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy. Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone. CONCLUSION: Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment.

Adaptation, Psychological

Hereditary hypertriglyceridemic rat: a new animal model of metabolic alterations in hypertension.

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na+ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.

Animals

[The importance of diet therapy in the prevention and treatment of manifestations of metabolic syndrome X].

The authors present an account of dietetic principles in the treatment of the metabolic syndrome X (Reaven 1988). Principles valid til recently are compared with the most recent views based on experimental and clinical investigations, using molecular methods. The authors explain in detail the importance of monounsaturated and polyunsaturated fatty acids in the oil of marine fish which are important not only for reducing the blood lipid level but also to improve the insulin resistance and they reduce slightly the blood pressure.

Diabetes Mellitus, Type 2

[Cellular and molecular mechanisms of insulin resistance].

In the submitted review the authors give an account of contemporary knowledge regarding the mechanism of insulin action, including a brief account of pathological conditions associated with insulin resistance. The development of knowledge of problems of insulin resistance syndromes was always very dynamic, and due to the introduction of techniques of molecular biology and genetics at the turn of the eighties and nineties, a further very marked step forward was made. Despite this it will take some time before molecular mechanisms which will confirm (or rule out?) the etiopathogenetic importance of insulin resistance not only for diabetes but also for hypertension, dyslipidaemia, IHD will be revealed.

Humans

[Etofylline clofibrate in the treatment of diabetic dyslipidemia: results of a 6-month period of therapy].

The objective was to investigate the tolerance of ethophylline clofibrate (EPC) and its effectiveness on changes of dyslipidaemia and compensation of diabetes in type II diabetics during six-month administration of the preparation Duolip forte (Merckle). Twenty diabetics with dyslipoproteinaemia IIb and IV according to Frederickson's classification, compensated by diet alone or combined with oral antidiabetics (Glucobene, Merckle) were included in the study consecutively according to uniform basal criteria. The selected hypolipidaemic agent was administered to patients according to the following pattern: the first four weeks 1,000 mg (2 tablets in the evening) the next two weeks 1.5 tablets and then till the end of the investigation 1 tablet in the evening. In all patients treatment with EPC led to a significant reduction of the total cholesterol level (CH) at all time intervals. Changes of ApoB, ApoA1 and Lp(a) serum levels did not attain statistical significance but trends were revealed (e.g. a drop of the ApoB/ApoA1 index) which are consistent with the expected favourable action of EPC on the CH distribution in lipoproteins. The triacylglycerol (TG) serum concentration declined significantly already after one month of treatment and after identification of five patients whose TG were distributed in separate clusters the hypotriacylglycerolaemic effect of EPC persisted still three months after treatment. It may be summarized that treatment of dyslipoproteinaemia of the type II diabetics with ethophylline clofibrate (Duolip forte, Merckle) led a) to a marked reduction (13-15%) of serum cholesterol, which b) diminished (to 8-9%) but persisted still after 6 months of treatment, c) the greatest effect of EPC on the TG serum level was observed one month after treatment, d) all improvements of lipid parameters occurred without affecting the compensation of diabetes, or BMI and were not associated with any side-effects of EPC.

Clofibrate

Psychosexual problems in people with HIV infection: controlled study of gay men and men with haemophilia.

HIV infection can be associated with major psychological and social disturbance. Psychosexual problems would be expected to arise in the context of the infection, in view of the contribution that sexual behaviour can make to the acquisition and spread of HIV infection. Here the results of a study of the psychosexual consequences of HIV infection in gay men and men with haemophilia are presented, with the inclusion of data from control groups. Sixteen HIV-positive and 23 HIV-negative gay men, and 20 HIV-positive and 24 HIV-negative men with haemophilia with sexual partners were studied. HIV infection was found to be associated with the greater risk of development of sexual dysfunction in seropositives, in particular in relation to ejaculatory difficulties, both delayed ejaculation in the case of gay men and men with haemophilia, and premature ejaculation in the case of men with haemophilia. Possible aetiological mechanisms are considered, including the possibility of organic disease. The findings are of relevance to those involved in the care of people with HIV infection.

Adult

Dietary fish oil and olive oil improve the liver insulin receptor tyrosine kinase activity in high sucrose fed rats.

In order to shed light on the possible beneficial effect of dietary unsaturated fatty acids on insulin binding, the effect of fish oil and olive oil administration on insulin binding, autophosphorylation and tyrosine kinase activity of partially purified liver insulin receptors were investigated. These data were confronted with the parameters of sugar and lipid metabolism (blood glucose, insulin and triglycerides), with liver plasma membrane fluidity and fatty acid composition. High sucrose feeding resulted in the elevation of blood glucose and triglyceride level, while the supplementation of animals with fish oil reduced that of triglycerides and olive oil that of insulin. Any significant changes between experimental groups were not detected either in insulin binding to partially purified liver insulin receptor nor in receptor autophosphorylation. However, the insulin stimulated tyrosine kinase activity towards an exogenous substrate (poly(Glu,Tyr)) was decreased by about 50% in the receptors solubilized from liver membranes of sucrose fed rats. Increased dietary intake of fish oil or olive oil restored the activity of insulin tyrosine kinase towards control values, half maximal effect being obtained at similar insulin concentration in all groups. Such improvement might be due to the induced increase of membrane fluidity by unsaturated fatty acids, and/or to the decrease of insulinemia.

Animals

Modulation of the hypolipidemic effect of fish oil by inhibition of adipose tissue lipolysis with acipimox, a nicotinic acid analog.

To assess the possible benefits of combined hypolipidemic therapy (acipimox+marine fish oil) on lipid and lipoprotein metabolism, male Wistar rats were fed for 14 days a high sucrose diet (70 cal% sucrose) alone or a high sucrose diet supplemented with acipimox (0.2 g/100 g diet) and/or fish oil (1 ml orally daily; 30 wt% of n-3 PUFA). Feeding a high sucrose diet increased (control: 61 +/- 6 vs HS: 110 +/- 8 nmol.min-1.mg-1, p < 0.001) the activity of acetyl CoA carboxylase in the liver, this was normalized by fish oil but not acipimox alone (HS+FO: 68 +/- 4; HS+ACI: 95 +/- 4; HS+ACI+FO: 71 +/- 2 nmol.min-1.mg-1). Increased triglyceride concentration in serum and muscle tissue (m. soleus and heart) of high sucrose-fed animals was suppressed equally by fish oil, acipimox, and/or both. The cholesterol-lowering effect of fish oil was also present in the liver (p < 0.005). The cholesterol-lowering action of acipimox was accompanied by the accumulation of cholesterol in the liver (p < 0.005), whereas the combination of acipimox+fish oil did not change the liver cholesterol content. After fish oil the LDL binding capacity of liver plasma membranes was increased 1.6-fold (p < 0.001). LDL receptor activity was significantly decreased in HS+ACI group (p < 0.05), but remained unchanged in HS+FO+ACI-fed animals. In summary, (a) the hypotriglyceridemic effect of fish oil in high sucrose-induced HTG is due to its inhibitory effects at the level of fatty acid synthesis; (b) decreased triglyceride production and output from the liver prevent triglyceride accumulation in muscle tissue; (c) the cholesterol-lowering action of acipimox but not fish oil was accompanied by an accumulation of cholesterol in the liver; (d) the latter phenomenon may be due to the opposite effects of both drugs on cholesterol catabolism via hepatic LDL receptors.

Acetyl-CoA Carboxylase

Muscle GLUT 4 protein levels and impaired triglyceride metabolism in streptozotocin diabetic rats. Effect of a high sucrose diet and fish oil supplementation.

Our data indicate that (a) the existence of a defect in the clearance of circulating TG and persistence of muscle TG deposition in the high sucrose-fed neonatal streptozotocin diabetic rat, which (b) can only be partially corrected by raised dietary n-3 PUFA intake. (c) Skeletal muscle of STZ type II-like diabetic rats contains about 40% less glucose transporters, and (d) this situation cannot be changed by any of the dietary treatments employed. (e) These findings indicate that muscle TG accumulation may have no direct relation to glucose transport in muscle.

Acetyl-CoA Carboxylase

Effect of dietary fish oil on 2-deoxy-D-3H glucose uptake in isolated adipocytes of rats fed various diets.

High sucrose diet-induced insulin resistance and mild glucose intolerance are associated with decreased insulin binding to isolated adipocytes and reduced insulin action in adipose tissue. Enhanced dietary intake of omega-3 polyunsaturated fatty acids (n-3-FA) counteracts these disorders. To provide more information on the possible role of membrane-related glucose transport processes, basal and insulin-stimulated 2-deoxy-D-3H glucose uptake was evaluated in isolated adipocytes obtained from rats on various dietary regimens. For 2 weeks animals were fed three different isocaloric (18 cal% proteins, 19 cal% fat, and 63 cal% carbohydrate) diets: (1) a standard rat chow (B), (2) a high sucrose diet (S, 63 cal% sucrose), or (3) an S diet supplemented with marine fish oil (S + FO, Martens, 30 wt% of n-3-FA). High dietary n-3-FA intake resulted in a significant decline in both basal (0.05 +/- 0.01 pmol/10(6) fat cells; mean +/- SEM) and insulin-stimulated (10(-6) M) (0.20 +/- 0.01) glucose uptake when compared with the control (basal: 0.12 +/- 0.02; insulin: 0.35 +/- 0.02) and/or the S group (basal: 0.18 +/- 0.03; insulin: 0.43 +/- 0.03), indicating decreases in insulin responsiveness and sensitivity (ED50: B: 0.03 +/- 0.01; S: 0.03 +/- 0.01; S + FO: 0.73 +/- 0.2 nM; p < 0.01 for S + FO vs B and S + FO vs S). Fish oil supplementation induced an increase in adipocyte size (B: 69 +/- 1.6; S: 70 +/- 2.5 and S + FO: 76 +/- 2.2 microns; B: S + FO p < 0.05) and a decrease in plasma membrane microviscosity (B: 4.08 +/- 0.3; S: 5.39 +/- 0.5; S + FO: 3.10 +/- 0.3; p < 0.05). Rates of basal and insulin-stimulated glucose uptake did not correlate with plasma membrane microviscosity; however, a negative relation to fat cell size was found (r = -0.484; p < 0.05). On the other hand, a positive correlation between both basal (r = 0.504; p < 0.05) and insulin-stimulated (10(-6) M, r = 0.640; p < 0.02) glucose uptake and blood glucose levels was observed. In conclusion, these data (a) suggest a less important role of diet-induced changes in plasma membrane microviscosity for glucose uptake in adipose tissue, and (b) leave unclear the mechanism of why dietary fish oil decreases the sensitivity of glucose uptake to insulin in isolated rat adipocytes.

Adipose Tissue

Effect of a low salt diet on blood pressure and vasoactive hormones in the hereditary hypertriglyceridemic rat.

In hereditary HTG rats, basal systolic blood pressure using tail-cuff sphygmomanometry was significantly higher (122.1 +/- 2.1 mm Hg; n = 16) than that in NTG animals (107.1 +/- 1.52; n = 16). A low salt diet did not influence blood pressure in NTG rats during the consecutive 4 weekly periods. However, in the second week blood pressure in HTG rats rose significantly in both the control rats on a normal salt diet and those on a low salt diet (132.5 +/- 1.89, n = 8, and 132.6 +/- 1.93, n = 8). No further changes were registered in the third and fourth week in control HTG rats. On the other hand, blood pressure fell significantly in HTG rats on a low salt diet in the third week in comparison with the second week (119.5 +/- 3.2, n = 8), and it increased again in the fourth week (123.0 +/- 2.35, n = 8). Hormones in plasma were determined at the end of the experiment. Plasma levels of norepinephrine were not influenced by differences in salt intake and were significantly higher by about 45% in HTG than in NTG animals. The lowest concentration of corticosterone in plasma was found in control HTG rats (1.2 +/- 0.2 vs 4.6 +/- 0.8 micrograms/100 ml in control NTG rats). Nevertheless, corticosterone concentration increased in HTG rats on a low salt diet at comparable values found in NTG rats on a low salt diet (3.1 +/- 0.8 vs 4.3 +/- 1.5). Plasma renin activity and plasma aldosterone concentrations were not different in the NTG and HTG groups and were uninfluenced by the diets (Table 1). We conclude that the elevated blood pressure in HTG rats and its variations during the experiment may reflect more pronounced sympathetic activity in HTG rats rather than blood pressure dependency on different salt intake.

Aldosterone