Explorative two-locus linkage analysis suggests a multiplicative interaction between the 7q32 and 16p13 myoclonic seizures-related photosensitivity loci

In traits suspected to be governed by at least two loci, linkage analysis incorporating the joint action of both loci may improve the power to detect linkage, increase the precision of estimating locus positions and provide insight into the underlying etiological mechanism. Recently, we mapped two susceptibility loci for epilepsy-related photosensitivity (or photoparoxysmal response, PPR) at regions 7q32 (PPR1) and 16p13 (PPR2) in PPR families with prominent myoclonic seizures background (MS-related PPR). To follow-up these results and evaluate interaction effects between these regions, we conducted two-locus (2L) linkage analyses using parametric and non-parametric methods. The 2L linkage was calculated under a multiplicative (MULT) epistasis model, encompassing models where each locus is necessary but not sufficient for MS-related PPR and a heterogeneity (HET) model, encompassing models in which each locus is by itself sufficient but not necessary for MS-related PPR expression. We found maximal 2L linkage under the (MULT) model, which was significantly better than the 2L linkage under the (HET) model (P = 0.001). The 2L analyses gave no increase in power to detect linkage over the single-locus analyses nor did they improve location estimates at PPR1 and PPR2, as expected under a best-fit 2L (MULT) model in an affecteds-only analysis. Our findings suggest that the genes underlying the PPR1 and PPR2 susceptibility loci may have similar functions or act in the same biochemical pathway.     

Validation of local venous sampling within the at risk left anterior descending artery vascular bed in the canine left ventricle

The validity of using blood sampled from the anterior interventricular vein (AIV), anatomically located within the myocardium perfused by the left anterior descending (LAD) coronary artery, to represent venous drainage originating from the LAD vascular territory was studied in eight anaesthetised, open chest dogs. The LAD was cannulated and perfused from a blood reservoir isolated from the systemic circulation. To determine the presence of blood from non-LAD sources that appears in the AIV sample, 51Cr-labelled red blood cells were injected into the left atrium and distributed in the systemic circulation while the LAD was perfused by non-radioactive blood. The percentage spillover of red blood cells from non-LAD sources into the AIV drainage was determined under control, reduced LAD flow, ischaemia, and reperfusion conditions as 100 X (AIV chromium content/arterial chromium content). Spillover of red blood cells into AIV blood samples averaged only 1.5(1.3)% under control conditions and increased insignificantly to 8.6(3.5)% during reduced LAD flow. During ischaemia red blood cells in AIV blood increased insignificantly to 98.3(5.0)% but decreased to 1.9(1.3)% after reperfusion. Studies in five dogs with microspheres showed that a portion of this admixture from non-LAD sources originated from precapillary nutritional collateral or overlapping blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulation of eosinophil production in vitro by eosinophilopoietin and spleen-cell-derived eosinophil growth-stimulating factor

Eosinophilopoietin (EPP) was previously characterized by the ability to stimulate eosinophil production in vivo, but these studies could not ascertain whether EPP had a direct effect on the bone marrow or acted indirectly by causing release of eosinophilopoietic activity by other tissues. The present studies demonstrate that EPP stimulates eosinophil growth in liquid culture of mouse bone marrow in vitro. The timing of stimulation by EPP in vivo and in vitro were parallel, with maximal eosinophil growth after 48 hr. Moreover, EPP appears similar to, and possible identical with, the eosinophil growth-stimulating substance (EO-GSF) released by antigenic stimulation of immune nonadherent spleen cells. Both EPP and EO-GSF are of low molecular weight, both produce stimulation of eosinophil growth with identical kinetics, and both produced similar dose-response curves in the liquid culture system.     

Multinational medical support to operations: challenges, benefits and recommendations for the future

This paper considers the strategic aspects of medical support to military operations as delivered through multi-national collaboration. The military medical services are in essence a people organisation; the purpose of the organisation is primarily to support the people engaged in military operations, and also the people providing healthcare to them. Increasingly, supporting the latter also includes preparation for the ethical dilemmas that they will face. Providing health advice and healthcare on operations is now usually undertaken on a multinational basis, in order to generate sufficient medical capacity to meet the requirement with assets of the appropriate (and NATO mandated) capability. This will be an enduring feature, particularly in light of increasing costs of providing high quality healthcare and the operational and logistic challenges of delivering this capability in adverse environments, and in the context of medical personnel being a limited resource. The key to overcoming the challenges, often the result of the "people issues" such as cultural differences, is to recognise the value that the inherent diversity of multinational healthcare provision brings. The benefit is realised through sharing best practice, and the lessons from challenges met, as well as through burden sharing, and to understand that challenges are most commonly the result of misunderstandings, such as those inherent in language differences. The advice for those bringing a multinational team together includes considering the implications of culture (noting differences in national and military perspectives, and in medical processes such as clinical governance), to ensure effective communication, and to utilise feedback to confirm understanding. It is important not to prejudge or denigrate others. Share information and knowledge, provide positive reinforcement when things go well, and recognise that there will inevitably be challenges and use these as an opportunity to learn. Above all, the personal touch builds a culture within the multinational team that transcends national culture; celebrating success breeds success and thus optimal outcome for patients.     

Shape response of human erythrocytes to altered cell pH

Alteration of red blood cell (RBC) pH produces stomatocytosis (at low pH) and echinocytosis (at high pH). Cell shrinkage potentiates high pH echinocytosis, but shrinkage alone does not cause echinocytosis. Mechanisms for these shape changes have not been described. In this study, measured dependence of RBC shape on cell pH was nonlinear, with a broad pH range in which normal discoid shape was maintained. Transbilayer distribution of phosphatidylcholine and phosphatidylserine, measured by back-extraction of radiolabeled lipid, was the same in control and altered pH cells. Possible roles of pH- titratable inner monolayer phospholipids were examined by assessing pH- dependent shape in cells in which their levels had been perturbed. In metabolically depleted cells and calcium-treated cells, which have altered levels of phosphatidic acid, phosphatidylinositol-4-phosphate, and/or phosphatidylinositol-4,5-bisphosphate, low cell pH was stomatocytogenic and high cell pH was echinocytogenic, as in control cells. Thus, neither change in membrane lipid asymmetry nor normal levels of the pH-titratable inner monolayer lipids is necessary for cell pH-mediated shape change.     

Left heart volume characteristics following ventricular septal defect closure in infancy.

Left ventricular and left atrial volume, left ventricular ejection fraction, and left ventricular muscle mass were determined preoperatively and postoperatively in 13 patients who underwent surgical closure of ventricular septal defects in the first two years of life. Left ventricular end-diastolic volume and systolic output averaged 255 +/- 19% (+/- SEM) and 240 +/- 19% of normal, respectively, before operation but fell to within normal limits postoperatively. Left ventricular ejection fraction was normal preoperatively (100 +/- 4% of normal) and remained so after correction (106 +/- 3%, NS). Left ventricular mass was mildly elevated at the preoperative catheterization (271 +/- 21%) and decreased significantly following repair (P less than 0.001). However, the postoperative left atrial volume (147 +/- 14%) remained abnormal (P greater than 0.05). These data suggest that when early surgical closure of a ventricular septal defect is necessary because of failure of medical management, good results with regard to postoperative left ventricular size and function can be expected.     

Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial.

STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.