The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.

Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.

Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline.     

Comparison of loop diuretics in patients with chronic renal insufficiency

Furosemide and bumetanide share a number of characteristics including reduced natriuretic effects in azotemic patients. It has been presumed that this condition affects each drug equally. Previous studies, however, suggest dissimilar pathways of delivery to their sites of action. Though not rigorously tested, this potential disparity might cause them to differ when used in azotemia. We, therefore, assessed the pharmacokinetic and pharmacodynamic characteristics of intravenously administered furosemide and bumetanide in ten adult patients with stable, chronic renal insufficiency (mean creatinine clearance = 14.1 +/- 2.0 ml/min/1.73 m2) in a randomized, cross-over study during controlled sodium intake. Our goals were to assess differences in diuretic effectiveness and in so doing to determine the dose required to produce a maximal response. The mean diuretic doses of 172 and 4.3 mg for furosemide and bumetanide, respectively (ratio = 40:1) were sufficient to produce a maximum response. Despite similarities in maximal fractional excretion of sodium (18.2 +/- 2.6% with furosemide vs. 19.4 +/- 4.5% with bumetanide, P = 0.687) demonstrating an equal tubular responsiveness to both drugs, overall response as quantified by cumulative natriuresis in the initial eight hour period was 52% greater with furosemide (108 +/- 17 vs. 71 +/- 7 mEq; P = 0.042). The difference in total excreted sodium was accounted for by a preserved nonrenal clearance of bumetanide (113 +/- 12 compared to 53 +/- 5 ml/min for furosemide, P = 0.001) which resulted in relatively less bumetanide in serum available to be delivered into the urine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trends and district variations in the hospital care of childhood asthma: results of a regional study 1970-85.

Trends and district variations in the pre-hospital and hospital care of children aged 0-14 years admitted with acute asthma were surveyed in all 13 districts of a health region by examining case notes for 1970, 1978, and 1985. From 1970 to 1985 there was a substantial increase in admissions and some reduction of hospital stay. Over this time adrenergic drugs remained the most frequently used treatment with a large shift towards selective beta2 agonists administered by nebulisation. Use of corticosteroids fell in the under 5s with a decrease in the parenteral route of administration but rose in the 5-14 age group with an increase in the oral route of administration. There was an increase the use of oral xanthines but this was outweighed by falls in the use of suppositories and in parenteral administration. The use of antibiotics became less frequent and that of sedatives and antihistamines fell to almost nil. There were also important changes in other aspects of management, notably an increase in the use of lung function tests (from 3% to 70%) and falls in the use of chest radiographs, blood tests, bacteriology, and physiotherapy. In nearly all aspects of management there were significant and often very extreme variations in practice between districts, which were unlikely to be explained by differences in morbidity. These variations would be a suitable focus for medical audit, with the aim of establishing which treatment regimens have the best outcome and avoiding unnecessary cost and discomfort. Because early hospital drug treatment is closely related to the type of treatment given before admission such audit activities would need to include general practitioners.     

Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver

The ability to identify, isolate, and transplant progenitor cells from solid tissues would greatly facilitate the treatment of diseases currently requiring whole organ transplantation. In this study, cell fractions enriched in candidate epithelial progenitor cells from the rat pancreas were isolated and transplanted into the liver of an inbred strain of Fischer rats. Using a dipeptidyl dipeptidase IV genetic marker system to follow the fate of transplanted cells in conjunction with albumin gene expression, we provide conclusive evidence that, after transplantation to the liver, epithelial progenitor cells from the pancreas differentiate into hepatocytes, express liver-specific proteins, and become fully integrated into the liver parenchymal structure. These studies demonstrate the presence of multipotent progenitor cells in the adult pancreas and establish a role for the liver microenvironment in the terminal differentiation of epithelial cells of foregut origin. They further suggest that such progenitor cells might be useful in studies of organ repopulation following acute or chronic liver injury.