Impact of variation in ADRB2, ADRB3, and GNB3 genes on body mass index and waist circumference in a Brazilian population.

The potential effect of variants in three catecholaminergic pathway genes (ADRB2, ADRB3, and GNB3) on obesity-related traits was investigated in an European-derived Brazilian population. Three-hundred and thirty-five individuals were screened for the ADRB2 Arg16Gly and Gln27Glu, ADRB3 Trp64Arg, and GNB3 814G-->A and 825C-->T polymorphisms using PCR-based methods. The association of the polymorphisms with quantitative variables was tested separately in each sex by analysis of covariance using general linear models, including age as a covariate. Only the ADRB2 Arg16Gly polymorphism was associated with higher body mass index and waist circumference. This association was restricted to the male sample. As the number of studies increases, it becomes clear that the genetic bases of obesity are complex, with sex-specific effects a playing an important role in its etiology. In the context of this European-derived population, the ADRB2 gene accounts for a significant part of obesity-related phenotypes in males.     

Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type I carbohydrate chain.

Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have screened a series of 11 monoclonal antibodies directed to these cells and found that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8 did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control, MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1 activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not affect their adhesion. The effect of MBr8 was also tested in an experimental system in vivo. As described previously, radiolabeled HT29 cell retention in the lung of nude mice was increased in animals given IL-1. MBr8 administration to nude mice or pretreatment of tumor cells with it inhibited this effect. These data suggest that cell adhesion to ELAM-1 might be mediated by different, cell type specific, sugar ligands.     

Potentiation of acute opioid-induced respiratory depression and reversal of tolerance by the calcium antagonist nimodipine in awake rats

Summary The interaction between sufentanil, a -opioid agonist, and the Ca²⁺ antagonist nimodipine on respiration and on the development of opioid tolerance in awake rats has been analyzed. Our previous work demonstrated that chronic treatment with nimodipine together with sufentanil increases the analgesic potency of the opioid 50 fold. Therefore, we have investigated whether the opioid-induced respiratory depression is potentiated in parallel with the analgesia. Ventilation was measured by the whole body plethysmographic method. In naive rats, sufentanil (10–80 g/kg) consistently induced a dose-dependent respiratory depression. Pretreatment with nimodipine (200 g/kg) potentiated this effect but to a lesser extent than it potentiated analgesia. After chronic administration of the opioid (2 g/h, 7 days) tolerance was manifested as a reduction in both the area under the time course curve and in the maximum effect. Nimodipine (1 g/h) administered concurrently with sufentanil for 7 days counteracted the tolerance to respiratory depression but no additional potentiation was observed. These results demonstrate that the interaction between nimodipine and sufentanil is not limited to antinociception but also exends to respiratory depression. However, compared with analgesia, the clinical relevance of a potential increase in opioid-induced respiratory depression by nimodipine may be negligible.Correspondence to: M. A. Hurlé at the above address     

Calcium channel modulation by dihydropyridines modifies sufentanil-induced antinociception in acute and tolerant conditions

Summary The study was aimed at elucidating the possible participation of l-type Ca²⁺ channel in the acute analgesic effect of an opiate and the development of tolerance to this action. Sufentanil, a selective p agonist, and two dihydropyridines, the Ca²⁺ antagonist nimodipine and the Ca²⁺ agonist Bay K 8644, were selected. The tail-flick test was used to assess the nociceptive threshold. In naive rats, nimodipine (200 g/kg) potentiated the analgesic effect of sufentanil reducing the ED₅₀ from 0.26 to 0.08 g/kg. Similar results were observed with its (–)-enantiomer Bay N 5248, while the (+) enantiomer Bay N 5247 was ineffective. Tolerance to the opiate was induced by chronic subcutaneous administration of sufentanil with minipumps (2 g/h, 7 days). In these conditions the dose-response curve to sufentanil was displaced to the right and the ED₅₀ was increased to 1.49 g/kg. In tolerant rats, nimodipine preserved its potentiating ability and prevented the displacement to the right of the sufentanil dose response-curve (ED₅₀ = 0.48 g/kg). When nimodipine was pumped (1 g/h, 7 days) concurrently with sufentanil, the development of tolerance to the opioid was not disturbed. However, the expression of tolerance was abolished and even the effect of acutely administered sufentanil was markedly potentiated (ED₅₀ = 0.03 g/kg). Similar experiments were performed with Bay K 8644. In naive rats, Bay K 8644 at a low dose (20 g/kg) that behaves as a calcium agonist, antagonized the analgesic effect of sufentanil (ED₅₀ = 0.58 g/kg), whereas at a high dose (200 g/kg) it potentiated this action (ED₅₀ = 0.15 g/kg). In tolerant rats, Bay K 8644 (20 g/kg) preserved its antagonizing ability inducing a displacement to the right of the sufentanildose-response curve (ED₅₀ = 4.2 g/kg). When Bay K 8644 was pumped (1 g/h, 7 days) concurrently with sufentanil, it enhanced the expression of tolerance to the opiate (ED₅₀ = 3.8 g/kg). These results suggest that the calcium fluxes through the l-type channel in neurones are functionally linked to the activation of the opiate receptor: the blockade of the channel increased the potency of sufentanil, whereas its activation reduced the potency of the opiate. In chronic experiments, DHPs concurrently administered with sufentanil did not affect the development of tolerance to the opiate. However, nimodipine prevented the expression of this phenomenon. Even more, the animals became hypersensitive to the opiate suggesting that the adaptative mechanisms induced by chronic opiate could be affected by chronic nimodipine.This work was supported by grants from Universidad de Cantabria-Caja Cantabria (1988) and Bayer AG, Wuppertal, FRGPredoctoral Fellow: Fondo de Investigaciones Sanitarias de la Seguridad Social.Send offprint requests to: M. A. Hurlé at the above address     

The emergency medicine training needs of rural general practitioners

This study aimed to identify the emergency medicine training needs of rural general practitioners (GPs) in the catchment area of the Hunter Rural Division of General Practice. The GPs were surveyed using a questionnaire in which they were asked about their confidence levels in a number of specific emergency medicine skills, and about the areas of emergency medicine that they saw as priorities for upskilling. More than a third of GPs who were responsible for on-call work at the hospital indicated that they had low levels of confidence in a number of their emergency medicine skills, in particular skills relating to paediatric emergencies, cardiovascular emergencies, and respiratory emergencies. These emergency medicine domains were also seen as high priorities for upskilling by the majority of the respondents. The study shows that rural doctors need the opportunity to access emergency medicine training that provides upskilling not only in the management of clinical problems, but also in practical procedures.     

An assessment of abdominal fatty tissue distribution in obese children. A comparison between echography and computed tomography

PURPOSE: Computed tomography (CT) and, more recently, ultrasound (US), have proved excellent tools for quantifying adipose tissue distribution. Body fat distribution is an important factor in the treatment of obesity and its complications. We investigated the correlation between CT and US measurements in pediatric obesity. MATERIAL AND METHODS: Forty obese children and adolescents aged 4.1-14.8 years were submitted to CT and US. Intra-abdominal, subcutaneous and total body fat were calculated (in cm2), with the CT image analysis software. The rectus muscle-spine and rectus muscle-aorta distances, as indicative of visceral fat thickness, were measured on US images with(out) compression. The distance between skin-fat and fat-rectus muscle interfaces was measured as subcutaneous fat thickness. We also compared US-CT findings with other morphometric variables--i.e., patient's (ideal) body weight and skin fold measures. RESULTS: At US, the rectus muscle-aorta and rectus muscle-spine distances ranged 2.4-7.5 cm (mean: 4.47 cm) and 3.6-8.9 cm (mean: 5.79 cm), respectively. The skin-rectus muscle distance ranged 1.2-7.5 cm (mean: 3.14 cm). A statistically significant correlation was found between the CT measurement of visceral fat and the aorta-rectus muscle and rectus muscle-spine distances (r = 0.80 and 0.74, respectively). The US measurements of subcutaneous fat were correlated with CT subcutaneous fat area (r = 0.82). No correlation was found between overweight, as calculated by body mass index, and CT or US fat. CONCLUSION: Our findings indicate that US is as useful as CT in evaluating body fat distribution in pediatric obesity.     

Lymphocytic hypophysitis. Case report

Lymphocytic hypophysitis is a very unusual disease typically observed in the peripartum period but found also in non-pregnant women or in men. We report the case of a 50-year-old woman with a five-year history of erithema nodosus for which was treated with variable doses of steroids. One year before admission the patient began to complain of headache, amenorrhea and rapidly progressive hypopituitarism. Magnetic resonance imaging showed an expanding sellar mass with homogeneous contrast enhancement while lacking the hyperintense signal of posterior lobe. The MRI findings and the history of autoimmune disease raised the suspicion of hypophysitis. The growth of the lesion and its unresponsiveness to the prolonged steroid therapy made surgery, which is both diagnostic and therapeutic, mandatory. The pathogenesis, diagnosis and management of this unusual clinical condition are discussed.