Development and validation of the EUROFORGEN NAME (North African and Middle Eastern) ancestry panel.

Inference of biogeographic origin is an important factor in clinical, population and forensic genetics. The information provided by AIMs (Ancestry Informative Markers) can allow the differentiation of major continental population groups, and several AIM panels have been developed for this purpose. However, from these major population groups, Eurasia covers a wide area between two continents that is difficult to differentiate genetically. These populations display a gradual genetic cline from West Europe to South Asia in terms of allele frequency distribution. Although differences have been reported between Europe and South Asia, Middle East populations continue to be a target of further investigations due to the lack of genetic variability, therefore hampering their genetic differentiation from neighboring populations. In the present study, a custom-built ancestry panel was developed to analyze North African and Middle Eastern populations, designated the 'NAME' panel. The NAME panel contains 111 SNPs that have patterns of allele frequency differentiation that can distinguish individuals originating in North Africa and the Middle East when combined with a previous set of 126 Global AIM-SNPs.

Inference of biogeographical ancestry across central regions of Eurasia.

The inference of biogeographical ancestry (BGA) can provide useful information for forensic investigators when there are no suspects to be compared with DNA collected at the crime scene or when no DNA database matches exist. Although public databases are increasing in size and population scope, there is a lack of information regarding genetic variation in Eurasian populations, especially in central regions such as the Middle East. Inhabitants of these regions show a high degree of genetic admixture, characterized by an allele frequency cline running from NW Europe to East Asia. Although a proper differentiation has been established between the cline extremes of western Europe and South Asia, populations geographically located in between, i.e, Middle East and Mediterranean populations, require more detailed study in order to characterize their genetic background as well as to further understand their demographic histories. To initiate these studies, three ancestry informative SNP (AI-SNP) multiplex panels: the SNPforID 34-plex, Eurasiaplex and a novel 33-plex assay were used to describe the ancestry patterns of a total of 24 populations ranging across the longitudinal axis from NW Europe to East Asia. Different ancestry inference approaches, including STRUCTURE, PCA, DAPC and Snipper Bayes analysis, were applied to determine relationships among populations. The structure results show differentiation between continental groups and a NW to SE allele frequency cline running across Eurasian populations. This study adds useful population data that could be used as reference genotypes for future ancestry investigations in forensic cases. The 33-plex assay also includes pigmentation predictive SNPs, but this study primarily focused on Eurasian population differentiation using 33-plex and its combination with the other two AI-SNP sets.

The relationship between metformin therapy and sleep quantity and quality in patients with Type 2 diabetes referred for potential sleep disorders.

AIMS: Given that sleep disorders are known to be related to insulin resistance, and metformin has favourable effects on insulin resistance and on ventilatory drive, we sought to determine whether metformin therapy was related to sleep variables in a group of patients with Type 2 diabetes. METHODS: We performed a retrospective, observational study of our centre's database for patients referred for potential sleep disorders and then compared metformin-treated patients with those not treated with the drug. All study patients had undergone the same standard polysomnographic procedure. A multivariate analysis was performed to establish whether or not there was an independent relationship between metformin use and sleep variables (after adjusting for age, gender, BMI, neck circumference, cumulated risk factors and insulin use). RESULTS: We studied 387 patients (mean ± sd age: 58.4 ± 10.8 years), of whom 314 had been treated with metformin. Total sleep time and sleep efficiency were higher in metformin-treated patients than in patients not treated with metformin [total sleep time: 6 h 39 min vs. 6 h 3 min, respectively (P = 0.002); sleep efficiency: 77.9 ± 12.3 vs. 71.5 ± 17.2%, respectively (P = 0.003)]. These differences persisted after adjustment for covariates and were observed even although metformin users had a higher BMI than did non-users (median 37.5 vs. 34.8 kg/m(2) ; P = 0.045). CONCLUSION: We showed that metformin therapy is associated with a longer sleep duration and better sleep efficiency. Randomized clinical trials are needed to confirm metformin's favourable effect on sleep quality and quantity.

[Drug's administration via feeding tubes: evaluation of practices in an intensive care unit of a Tunisian hospital]. / Administration des médicaments par sonde de nutrition entérale : évaluation des pratiques dans un service de réanimation médicale d'un hôpital tunisien.

INTRODUCTION: Drugs' administration via feeding tubes is a potential source of iatrogenic events for the intensive care patients because of the problem of not adapted galenic forms. OBJECTIVES: We analyzed the prescriptions of patients with enteral feedings to determine if the galenic forms were compatible with administration via feeding tubes. We also observed and analyzed the methods of drugs passage by nurses. PATIENTS AND METHODS: We analyzed 30 prescriptions of patients with enteral feedings in the intensive care unit of Habib Bourguiba Sfax hospital, by a prospective and exhaustive way. We also, observed and evaluated the practices of preparation and administration of drugs to these patients via feeding tube by nurses. RESULTS: Only 12% of drugs were liquids. Eighty-eight percent of the drugs were pulverised and capsule open before administration. The galenic form was not in conformity for 20% of drugs because of the prohibition to crushing tablet or opening capsule (gastroresistant form was dissolved), or because of the administration of a parenteral form (risk of irritation). Among 78 drugs administered by 10 different nurses, the time between passage of the drug and enteral nutrition were not respected for 59% of the observations. The drugs were managed in mixture for 90% of the observations. The gloves were not worn in 80% of observations. No rinsing is made between consecutive administrations and before administration. CONCLUSION: This study shows that it is possible to reduce risk of administration errors in the intensive care unit and to facilitate the administration of drug via feeding tube by prescribing liquid oral form or soluble solid oral form. It also shows the need for cooperation with the pharmacist in order to adapt the galenic forms and to redact protocol of administration.

The use of intravenous catheterisation with a rest period is useful for determination of plasma cortisol levels but not plasma prolactin levels.

OBJECTIVE: The use of an intravenous catheter with a rest period has been recommended to avoid false-positive results for hyperprolactinaemia and false-negative results for hypocortisolaemia. We tested the relevance of this recommendation. DESIGN: Plasma cortisol and prolactin levels were determined before (T-15) and after a 15-min rest period (T0) in 119 patients, 38 males (M) and 81 females (F). 52 of the 119 patients were known (K; 30 females and 22 males) and 67 unknown (UK; 49 females and 18 males) to the unit. RESULTS: Prolactin was lower after rest in women (12.3+/-22.7 ng/l vs 11.7+/-22.5 ng/ml, P=0.03), but not in men (6.2+/-4.5 ng/ml at T-15 vs 5.8+/-3.2 ng/ml at T0, P=0.09), in the UK subgroup (10.6+/-20.7 ng/ml at T-15 vs 10.1+/-20.9 ng/ml at T0, P=0.06) and in the K subgroup (10.1+/-16.7 ng/ml at T-15 vs 9.7+/-15.8 ng/ml at T0, P=0.08). None of the patients with prolactin levels higher than 20 ng/ml at T-15 diminished its prolactin value below this cut-off value. Plasma cortisol levels were lower after rest in women (17.9+/-5.9 microg/dl at T-15 vs 16.5+/-6.1 microg/dl at T0, P<0.0001), in the UK subgroup (18+/-6.1 microg/dl at T-15 vs 16.6+/-6.4 microg/dl at T0, P=0.0003) but not in men (18+/-4.4 microg/dl at T-15 vs 17.5+/-5.8 microg/dl at T0, P=0.47) and in the K subgroup (17.8+/-4.6 microg/dl at T-15 vs 17+/-5.4 microg/dl at T0, P=0.13). At T0, 3.3% and 15% of patients presented values below the cut-off value of 10 microg/dl (276 nmol/l) and 17 microg/dl (470 nmol/l), respectively. CONCLUSION: These results don't justify intravenous catheterisation with a rest period for plasma prolactin determination in contrast with plasma cortisol determination.

Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects.

OBJECTIVES: Although the existence of a deep compartment for metformin has long been hypothesized, there is still little direct information concerning metformin distribution in individual tissues in man. The only available study involves chronic metformin therapy. In that study, the measurement of metformin in erythrocytes provided a reliable indicator of metformin distribution and of potential accumulation. To determine the kinetics of metformin in plasma and in erythrocytes after acute oral administration, we performed the present study in healthy subjects after a single oral dose of metformin and compared the pharmacokinetics parameters in erythrocytes to those in plasma. METHODS: Six nondiabetic participants took the study dose of 850 mg metformin at 8: 00 AM after a non-standardized breakfast (i.e., as recommended in clinical practice). Blood samples were collected for metformin measurement in plasma and in erythrocytes at 0, 1, 2, 3, 4, 6, 9, 24, 33, 48, 57, and 72 h. RESULTS: Maximum metformin concentration was attained at 3.0 +/- 0.3 h in plasma and 4.7 +/- 0.5 h in erythrocytes. This difference was not significant. Metformin concentrations peaked at a maximum almost 6 times higher in plasma than in erythrocytes (1.7 +/- 0.1 and 0.3 +/- 0.0 mg/l, respectively). However, because the elimination half-life of metformin was much longer in erythrocytes (23.4 +/- 1.9 h vs. 2.7 +/- 1.2 h), there was no difference in area under the curve between plasma and erythrocytes. The distribution volume (plasma) was calculated to be 146 +/- 11 l. Plasma and erythrocytes concentration-time curves showed that metformin was not detectable in plasma 24 hours after the oral administration, while it remained detectable in erythrocytes up to 48 hours. Metformin concentrations crossed approximately 13 hours after having reached their maximum values in plasma, approximately 16 h after metformin intake. CONCLUSION: Having demonstrated the rapid elimination of metformin from plasma and its slow disappearance from erythrocytes, the presents results should contribute to adjustment of metformin dosage to renal function, assessment of drug compliance, and retrospective analysis (when blood samples are drawn with delay) of the link between metformin and development of lactic acidosis. Most importantly, the present findings should help to ascertain the optimal dosage of metformin, particularly in elderly patients.

[Percutaneous mitral commissurotomy. 5-year results]. / La commissurotomie mitrale percutanee. Resultats a 5 ans.

Long-term results of percutaneous mitral commissurotomy were evaluated in 410 patients with mean age of 31 years (18 to 68 years). 48% of patients had mean thickened leaflets, 35% had calcified valves and 17% had flexible leaflets and subvalvular apparatus. Procedure was performed with a double balloon in 57% and with Inoue's balloon in 43% patients. A good immediate results was obtained in 77% of patients. A good result was defined as a mitral valve area > or = 1.5 cm2 without mitral regurgitation. Clinical follow-up concern 378 patients. The actuarial 5 years rate were 84% in our serie, without surgery or new percutaneous mitral commissurotomy and good functional results (NYHA class I or II) were 71%. Valvular anatomy, immediate results (mitral valve area), history of mitral commissurotomy, old patients, atrial fibrillation can influence strongly the results.

Hydatid cyst of the heart located in the interventricular septum.

Cardiac hydatosis is a rare condition, and the localization of a hydatid cyst within the interventricular septum is exceptional. A 61-year-old man found to have a hydatid cyst of the interventricular septum is reported. Presenting manifestations were congestive heart failure and signs suggestive of an aortic valvulopathy. Diagnosis was made by Doppler echocardiography and confirmed by magnetic resonance imaging. The cyst was approached surgically by right ventriculotomy. Despite a technically successful intervention without rupture of the cyst or appearance of a conduction delay, the patient died on the 20th postoperative day because of acute respiratory distress syndrome complicating infectious pneumonia.

[Percutaneous implantation under local anesthesia of an implantable automatic defibrillator: report of the first Tunisian case]. / Implantation percutanée sous anesthesie locale d'un defibrillateur automatique implantable: a propos du premier cas Tunisien.

We report the case of a 58 years old male affected by a severe relapsing ventricular tachycardia despite a well administered anti arrhythmic therapy. Etiology is an arrhythmogene right ventricular dysplasia. Considering the severity of this arrhythmia we proceed to percutaneous implantation of an automatically implantable defibrillator under local anesthesia. Evolution was favorable with a follow-up of 3 months.

[Oral-dental health status in patients with infectious endocarditis]. / Etat bucco-dentaire chez des patients atteints d'endocardite infectieuse.

Mouth and dental examination is a systematic act in the etiologic follow up of an infectious endocarditis. Our study concerned 42 patients collected during 5 years period, starting july 1995 until July 2000, in the dental medical service of Hedi Chaker university hospital of Sfax oriented by the cardiovascular diseases service looking for a buccodental entry of bacteria. Our patients group is divided into 25 men and 17 women of 36.1 years mean age. Dental or parodontal lesions were observed in 25 patients. Panoramic X-rays showed periapical lesions of granuloma or cystic type in 15 patients. Among the etiological factors encountered we noticed dental acts accomplished without antibioprophylaxis and dental bacterial collection medically treated without extraction. Buccodental lesions were a frequent cause of the infectious endocarditis in 59.5% of the patients studied in this report, and were due more to defectious hygienic conditions than to a disabled dental act.

Insulin sensitivity, insulin action, and fibrinolysis activity in nondiabetic and diabetic obese subjects.

Because inconsistencies occur with regard to the relative contribution of insulin to the hypofibrinolysis characteristic of obesity and diabetes, we explored the relationship between insulin and fibrinolysis, assessing both insulin sensitivity and insulin action. Seventeen markedly obese subjects (body mass index [BMI], 34.0+/-1.6 kg/m2; 12 nondiabetic and five diabetic) were studied using the three-step euglycemic-hyperinsulinemic clamp technique. Since the circadian rhythm of the fibrinolytic system may obscure a true effect of insulin, variations in fibrinolysis parameters observed during the glucose clamp were compared with those occurring spontaneously because of the circadian rhythm. Compared with six normal-weight subjects (BMI, 21.0+/-0.9 kg/m2), all obese subjects exhibited basal hyperinsulinism (fasting plasma insulin, 16.0+/-1.4 v 9.8+/-1.3 microU/microL, P < .001; fasting plasma C-peptide, 1.4+/-0.2 v 0.5+/-0.2 ng/mL, P < .001), hypofibrinolysis (euglobulin lysis time [ELT], 378+/-29 v 222+/-31 minutes, P=.01; tissue plasminogen activator [tPA] antigen, 7.8+/-0.9 v 4.2+/-0.5 ng/mL, P=.04; plasminogen activator inhibitor type 1 [PAI-1] activity, 22.2+/-2.5 v3.9+/-0.6 AU/mL, P=.004), and marked insulin resistance (M value, ie, the maximal glucose disposal rate, 9.1+/-0.6 v 18.6+/-0.8 mg/(kg x min), P < .001). The M value correlated inversely with tPA antigen (r=-.46, P=.05). During insulin infusion, values for fibrinolysis parameters decreased, but were not different compared with variations due to the circadian rhythm. In conclusion, our findings together with previously reported data reinforce the idea that chronic hyperinsulinism is linked to hypofibrinolysis, but insulin does not seem to acutely regulate the fibrinolysis system.

[Chronic cor pulmonale caused by hydatid embolism complicating hepatic hydatid cyst]. / Coeur pulmonaire chronique par embolies hydatiques compliquant un kyste du foie.

An hydatid cyst of the left lobe of the liver, associated with right heart failure, was diagnosed in a 61-year-old man presenting with dyspnoea. Doppler echocardiography combined with cardiac catheterization demonstrated the presence of pulmonary precapillary hypertension. Pulmonary perfusion scintigraphy with Technetium-labelled albumin microspheres demonstrated multiple pulmonary embolisms, leading to a diagnosis of postembolic chronic cor pulmonale. Due to the absence of thrombophlebitis and ultrasound signs of an intracaval hydatid membrane, floating at the level of the cyst of the left lobe of the liver, the diagnosis of parasitic postembolic chronic heart pulmonale, due to fistulization of an hepatic hydatid cyst into the inferior vena cava, was established. Only chemotherapy was proposed in this patient due to dissemination of the hydatid material in the lungs.

[Right coronary-ventricular fistula. Diagnosis and course. Apropos of 2 cases]. / Fistule coronaro-ventriculaire droite. Diagnostic et évolution. A propos de deux cas.

The authors report two cases of coronary-right ventricular fistulas diagnosed in a 7-month-old infant and a 9-year-old girl. The discovery of the heart disease was incidental in both cases, following detection of a low continuous murmur. Doppler ultrasonography established the diagnosis, which was confirmed by haemodynamic studies and coronary angiography. The left anterior descending artery was involved in both cases and the recipient cavity was the right ventricle. The first patient was cured by early operation with distal ligation of the artery. In the second patient, the natural course was complicated by aneurysmal dilatation of the coronary artery. The authors recall the value of colour Doppler ultrasound in the noninvasive diagnosis, especially of the recipient cavity by colour Doppler and the need to rapidly treat coronary fistulas to prevent the development of complications reported after an average age of 20 years.

Relationship between insulin sensitivity and circulating sex hormone-binding globulin levels in hyperandrogenic obese women.

The aim of this work was to examine the effect of an insulin infusion on SHBG levels as well as the relationship between SHBG levels and insulin sensitivity. Acute insulin infusion was used with the insulin-glucose clamp technique. The subjects were 14 consecutive well-characterized hyperandrogenic non-diabetic obese women without biological and echographic symptoms of polycystic ovary syndrome. Adiposity and fat distribution were assessed respectively by the body mass index (BMI: 38.7 +/- 1.6 kg/m2) and by the waist hip ratio (WHR: 0.91 +/- 0.01). Hyperandrogenism was evidenced by hirsutism and serum testosterone greater than 2.8 nM. Circulating SHBG levels were determined in the fasting state by RIA. Insulin sensitivity was assessed using the euglycemic hyperinsulinemic glucose clamp technique with three incremental doses of insulin. Seven non-obese non-hyperandrogenic subjects (BMI: 21.0 +/- 0.6 kg/m2) served as controls for the study of the insulin resistance state. Because of supraphysiological insulin infusion rates (40, 100, and 350 mU/min.m2, each dose for 2 h), insulin sensitivity was mainly studied at peripheral level. We calculated the Km, i.e. the ED50 of the dose-response curve, the glucose disposal rate, and the maximal glucose disposal rate per U insulin (M/I). The hyperandrogenic obese subjects exhibited marked insulin resistance. SHBG levels, although already in the lower half of normal in the basal state, decreased from 34.8 +/- 3.4 nmol/l to 29.7 +/- 3.3 nmol/l (P = 0.001; normal values are 18-83 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Metformin effects on peripheral sensitivity to insulin in non diabetic obese subjects.

Using the euglycaemic insulin-clamp technique we examined the effects of one-month metformin treatment on peripheral glucose utilization in non diabetic obese subjects. Two groups of obese subjects were studied in comparison with untreated lean women. Group 1 (n = 6) experienced weight loss (BMI: 32.6 +/- 1.7 vs 34.8 +/- 1.6 kg/m2, p < 0.05) but not group 2 (n = 7; BMI before and after treatment: 34.6 +/- 3.2 and 34.8 +/- 3.1 kg/m2). After a continuous insulin infusion of 40, 100, and 350 mU/m2/min we estimated the tissue sensitivity to insulin by the determination of Km, the glucose disposal (M), and the amount of glucose metabolized per U insulin (M/I ratio). After the metformin treatment the mean Km decreased by 31% in group 1 (p < 0.05) but not significantly in group 2; M and M/I were not modified in the two study groups. In conclusion, in non diabetic obese subjects, metformin seems not to affect peripheral insulin-mediated glucose metabolism unless there is weight loss.

[Female obesity: testosteronemia is positively correlated with peripheral insulin resistance]. / Obésité féminine: la testostéronémie est postivement corrélée à l'insulinorésistance périphérique.

Hyperinsulinemia and hyperandrogenemia are frequent in obese women. The aim of this study is to examine the relationship between the degree of insulin resistance and plasma androgens, and the role of android obesity. We studied 16 obese (BMI = 39.3 +/- 1.6 kg/m2) premenopausal non diabetic women (age = 28.2 +/- 1.4 years). The peripheral insulin sensitivity was determined during an euglycemic insulin clamp study. Serum total testosterone (TT), free testosterone (FT), androstenedione (A) were measured in each women. We compared these results to those of 5 control subjects (BMI = 20 +/- 1 kg/m2). Insulin resistance was more severe in the obese women than in the control subjects: Vmax = 9.1 +/- 0.5 mg/kg/mm vs 19.1 +/- 1.0 mg/kg/mn (p < 0.01) and Km = 152.2 +/- 13.9 microU/ml vs 42.6 +/- 5.8 microU/ml (p < 0.01). Significant positive correlations were demonstrated in the obese women between Km and both total testosterone (r = 0.74; p < 0.01) and free testosterone (r = 0.52; p < 0.05). There was no correlation between Km and Androstenedione. The waist to hip ratio (WHR) differentiated two groups of age--and weight-matched obese women; Gr 1:10 upper body obese women (WHR = 0.90 +/- 0.10; BMI = 39.0 +/- 1.9 kg/m2); Gr 2: 6 lower body obese (WHR = 0.77 +/- 0.02; BMI = 40.0 +/- 3.1 kg/m2. Insulin resistance was more severe in the Gr I: Km = 174 +/- 17 microU/ml, than in the Gr 2: Km = 101 +/- 8 microU/ml (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)