The prevalence of peripheral arterial disease and medial arterial calcification in patients with chronic renal failure: requirements for diagnostics

BACKGROUND: Knowledge of the prevalence of peripheral arterial disease (PAD) in patients with chronic renal failure (CRF) is limited because of a lack of uniformity in disease definition and recognition. Furthermore, little is known of the prevalence of medial arterial calcification (MAC) in patients with CRF. Our goal is to study the prevalence of PAD and MAC defined by ankle brachial index (ABI) or toe brachial index (TBI) measurements in a Finnish population of patients with CRF consisting of predialysis and dialysis patients, as well as renal transplant recipients. METHODS: We examined 136 patients with CRF and 59 control subjects. Fifty-nine of the patients with CRF had moderate to severe predialysis CRF, 36 patients were on dialysis treatment, and 41 were renal transplant recipients. Mean age of patients was 51.9 +/- 11.5 years, and 39 patients (29%) had diabetes. ABI and TBI were measured by means of photoplethysmography. The definition of PAD required an ABI value of 0.90 or less, a TBI value of 0.60 or less, or a previous positive lower-extremity angiogram result. ABI values of 1.3 or greater or incompressible arteries at ankle level indicated MAC. The presence of claudication was determined by an interview. RESULTS: Prevalences of PAD on this study were 22.0% in patients with predialysis CRF, 30.6% in patients on dialysis treatment, 14.6% in renal transplant recipients, and 1.7% in the control group (P = 0.001). Prevalences of MAC were 23.7%, 41.7%, 23.1%, and 3.4% (P < 0.001), respectively. Only 9 patients had claudication, and 6 of those patients had PAD. CONCLUSION: Both asymptomatic PAD and MAC are common in patients with CRF. Therefore, we recommend the use of both ABI and TBI measurements in the evaluation of PAD in patients with CRF.     

Serotonin 5-HT2C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments.

Selective serotonin reuptake inhibitors (SSRIs) bind directly to various neurotransmitter receptors. The clinical effects of SSRIs appear gradually during weeks of treatment, suggesting a role for adaptive changes in neurotransmitter receptors. Most clinically used antidepressants, e.g. fluoxetine, bind to 5-HT2C receptors. When administered chronically, many antidepressants elicit adaptive regulation of 5-HT2C receptors. The present study was conducted in order to determine the effects of acute and chronic fluoxetine and citalopram treatments on the density and function of 5-HT2C receptors in the rat choroid plexus. Acute and chronic treatments followed by phosphoinositide (PI) hydrolysis assays and quantitative receptor autoradiography were performed. Acute (single-dose) treatment with neither drug significantly affected basal or 5-HT-stimulated PI hydrolysis, but acute citalopram (20 mg/kg) treatment increased both agonist and antagonist binding to 5-HT(2C) receptors. Chronic (14 days) citalopram treatment (20 mg/kg) increased the maximal PI hydrolysis response by 40%, but fluoxetine lacked this effect. The present data suggest that sensitisation of 5-HT2C receptor-mediated intracellular signal transduction may play a role in the effects of citalopram. In contrast, fluoxetine treatment does not functionally sensitise 5-HT2C receptors. Thus, functional 5-HT2C receptor sensitisation is not a common effect of antidepressants, but the differential effects may explain some of the pharmacodynamic differences seen with these drugs, especially upon repeated administration.     

Exposure of pancreatic islets to different alkylating agents decreases mitochondrial DNA content but only streptozotocin induces long-lasting functional impairment of B-cells.

Pancreatic B-cells exposed in vivo or in vitro to streptozotocin (SZ), the N-nitrosourea derivative of glucosamide, present a long-lasting impairment in the production and release of insulin while other cell functions are better preserved. This functional impairment is associated with a defective mitochondrial function. To further study the mechanisms behind SZ actions, mouse pancreatic islets were exposed in vitro to SZ (1.5 mM) or to different concentrations of methyl methanesulfonate (MMS; 2, 4 and 6 mM). The effect of the aglucone moiety of SZ, nitroso-N-methylurea (NMU; 2, 4 and 6 mM) was also tested. Islets were either studied immediately after exposure to the drugs (day 0) or after six days in culture following toxin treatment (day 6). On day 0 the islets showed a decrease in the NAD + NADH content, decreased glucose oxidation rates and an impaired insulin release in response to glucose. Six days after exposure to SZ there was still impaired glucose oxidation and insulin release, and decreased islet insulin mRNA and insulin content, but the NAD + NADH content was again similar to the control group. On the other hand, islets which survived for 6 days in culture following exposure to either MMS or NMU were able to regain normal B-cell function. The mouse islets exposed to SZ, NMU and MMS showed on day 6 a 30-40% decrease in the content of the mitochondrial DNA encoded cytochrome b mRNA and a 60-70% decrease in total mitochondrial DNA, as evaluated by dot and Southern blot analysis. Only SZ decreased the insulin mRNA content whereas both MMS and NMU decreased the glucagon mRNA content. As a whole, the data obtained indicate that SZ, NMU and MMS induce damage to the mitochondrial genome, and this may contribute to the B-cell dysfunction observed after SZ treatment. It is conceivable that the glucose moiety of SZ may direct the methylation to other intracellular sites besides the mitochondrial DNA, thus explaining the different functional responses of islets following exposure to SZ and NMU.     

Efficacy and tolerability of a new antipsychotic compound (risperidone): results of a pilot study.

Risperidone is a new benzisoxazole derivative displaying a very potent serotonin antagonism and a potent dopamine antagonism in pharmacological studies. These properties suggest the hypothesis that risperidone may exert antipsychotic effects and be superior to classic neuroleptics in its beneficial effects on negative and affective symptoms and its low extrapyramidal side-effect propensity. In an open pilot study 13 patients suffering from acute schizophrenic psychosis were treated with risperidone within an individually adapted dose range from 1 to 10 mg per day. A good antipsychotic efficacy could be demonstrated in 6 of the 8 patients who completed the trial. Risperidone was very well tolerated. The substance possesses a low EPS-inducing profile. Future research has to test the suggested advantage of risperidone over other neuroleptic drugs and its performance in the treatment of chronic schizophrenic patients.     

Incidence of multiple sclerosis in Hordaland, western Norway: a fluctuating pattern

The incidence of multiple sclerosis (MS) was studied in the county of Hordaland, western Norway. A significant increase in incidence in the period 1958-1987, a decline followed by a gradual increase in mean age at onset, geographic differences in time trends and a biphasic pattern revealed by a birth cohort analysis support the theory of real time-space fluctuations in the incidence of MS over time.     

Early development of the olfactory and terminalis systems in baleen whales

The development of the olfactory and terminalis systems was studied in tissue from eight embryonic and early fetal specimens belonging to three species of baleen whales. In contrast to toothed whales, baleen whales, particularly in these ontogenetic stages, are much less specialized in nasal organ morphology. The nasal cavity and peripheral olfactory system are well developed and do not show signs of reduction. However, as in toothed whales, there is no trace of a vomeronasal organ or nerve. The terminalis neuroblasts can already be distinguished from the olfactory material in the embryonic period, and they form compact masses medial and caudal to the developing olfactory bulb. As in most prenatal toothed whales, there are two large intrameningeal terminalis ganglia. These are connected with the telencephalic wall by central rootlets and with the septal mucosa by fiber bundles running through the level of the future cribriform plate. Clusters of terminalis neuroblasts also lie near the septal mucosa and along the peripheral terminalis fiber bundles. The functional implications of the olfactory and terminalis systems in whales are discussed.     

Type 2 diabetes heredity and nutrient intake. A dietary history assessment in non-obese normoglycaemic men

The impact of type 2 diabetes heredity on nutrient intake was studied, by means of dietary histories, in 51 normoglycaemic, non-obese men, aged 54-59 years; 29 with familial aggregation of type 2 diabetes, and 22 with no such family history. The average daily intake of energy, macronutrients and minerals was almost identical in the two groups. Mean energy intake was approximately 2400 kcal/d, about 15 per cent of the energy deriving from protein, 35 per cent from fat, 45 per cent from carbohydrate and 5 per cent from alcohol. The average daily intake or dietary fibre was approximately 17 g, or 7 g/1000 kcal. Mean daily sodium and potassium intake, estimated from food sources, was about 3000 and 4000 mg, respectively. The findings provide no support for the existence of any relationship between type 2 diabetes heredity and dietary habits or nutrient intake.     

Inhibition of platelet aggregation following chronic in vivo treatment of rats with nicotine: prevention by simultaneous application of propranolol

Platelet aggregability is known to be enhanced and platelet-survival time shortened in smokers when compared with nonsmokers. Up to now it is unknown which of the substances in tobacco smoke are responsible for these effects. To evaluate a possible role of nicotine, rats were chronically treated with the alkaloid (10 mg/kg/day), continuously released from subcutaneously implanted osmotic minipumps. Surprisingly, after 8 weeks, platelet sensitivity toward the aggregating stimulus adenosine 5'-diphosphate (ADP) was markedly reduced. The mean ADP concentration required to induce half the maximum rate of aggregation (EC50) was 0.88 mumol/L in nicotine-treated animals, as compared with 0.67 mumol/L in controls (p less than 0.002). Platelet aggregability remained normal when the rats were treated simultaneously with nicotine and the beta blocker propranolol (3.5 mg/kg/day); for these animals, the mean EC50 for ADP was 0.73 mumol/L. These results are suggestive of a catecholamine-mediated action of nicotine. However, neither the basal levels of cAMP in platelet-rich plasma, nor the cAMP levels attained after stimulation of platelet adenylate cyclase with prostaglandin E1 (PGE1), were affected by 8 weeks of treatment with nicotine or nicotine plus propranolol. No effect on platelet aggregation was observed when the rats were treated with nicotine for only 2 weeks, or when nicotine or nicotine plus cotinine were added to platelet-rich plasma in vitro in concentrations equal to those attained in vivo after 8 weeks. Thus, prolonged application of nicotine in vivo caused an inhibition of ADP-induced rat platelet aggregation presumably mediated by beta-catecholaminergic stimulation of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)