Set-up and routine use of a database of 10 555 genotyped blood donors to facilitate the screening of compatible blood components for alloimmunized patients

Background and Objectives  Large-scale genotyping of blood donors for red blood cell and platelet antigens has been predicted to replace phenotyping assays in the screening of compatible blood components for alloimmunized patients. Although several genotyping platforms have been described, novel procedures and processes are needed to perform genotyping efficiently and to maximize its benefits for blood banks.
Materials and Methods  Here we describe the processes and procedures developed to introduce large-scale genotyping in our routine operations.
Results  Preliminary cost–benefit analysis indicated that genotyping must target frequent blood donors (> 3 donations/year) to be efficiently used. A custom-designed computer application was developed to manage the whole project. It selects frequent donors among recent donations, prints coded labels to identify blood samples sent to the external genotyping laboratory, and stores genotyping results. It can search for donors compatible for any combination of the 22 genotyped antigens as well as consult the current inventory for the presence of the corresponding blood components. The phenotype of recovered components is confirmed by standard serology techniques prior to shipment to hospitals.
Conclusion  Since October 2007, 10 555 blood donors have been genotyped. The database is used on a regular basis to find compatible blood components with a genotype–phenotype concordance of 99·6%.     

Effects of androgens on adipocyte differentiation and adipose tissue explant metabolism in men and women

Objective To examine the effects of aromatizable or nonaromatizable androgens on abdominal subcutaneous (SC) and omental (OM) adipose tissue lipid metabolism and adipogenesis in men and women. Design and subjects Primary organ and preadipocyte cultures were established from surgical samples obtained in men (n = 22) and women undergoing biliopancreatic diversions (n = 12) or gynaecological surgeries (n = 8). Cultures were treated with testosterone, dihydrotestosterone (DHT) and methyltrienolone (R1881). Measurements Heparin‐releasable lipoprotein lipase (HR‐LPL) activity, glycerol release, adiponectin secretion, glycerol‐3‐phosphate dehydrogenase activity and lipid accumulation were measured. Results In organ cultures from men, DHT had a statistically significant inhibitory effect on HR‐LPL activity in the OM compartment. Testosterone significantly inhibited HR‐LPL activity in SC and OM cultures. In women, high DHT concentrations tended to inhibit HR‐LPL activity in OM cultures. Minor androgenic effects were observed for basal and isoproterenol‐stimulated lipolysis as well as adiponectin release in men. On the other hand, adipocyte differentiation was significantly and dose‐dependently inhibited by DHT, testosterone and R1881 in SC and OM cultures from both sexes. These effects did not differ according to adipose tissue depot but appeared to be more pronounced in women than in men. Conclusions Androgens slightly decreased HR‐LPL activity in adipose tissue organ cultures, but markedly inhibited adipogenesis in SC and OM primary preadipocyte cultures in both sexes. Androgenic effects on adipose tissue in men vs. women may not differ in terms of direction but in the magnitude of their negative impact on adipogenesis and lipid synthesis.     

Antenatal diagnosis of ovarian cysts: natural history and therapeutic implications

A retrospective study from 1980 to 1990 shows 29 ovarian cysts in 27 patients diagnosed by prenatal ultrasound performed between 28 and 38 weeks of gestation. Ten patients underwent surgery, 17 patients were observed with serial ultrasound. Delayed good quality sonograms after spontaneous resolution of the cyst in a selected group of 7 patients showed restoration of a normal ovarian anatomy. The size of the cyst and/or its sonographic characteristics are the 2 main factors for deciding a conservative or a surgical management.Presented at the ESPR meeting in Munich 1990. Selected for publication by an International Group of the ESPRThe surgical aspects of this series will be discussed in more details in the Journal of Pediatric Surgery, Brandt et al. (in press)     

Molecular enzymology underlying regulation of protein phosphatase-1 by natural toxins

The protein serine/threonine phosphatases constitute a unique class of enzymes that are critical for cell regulation, as they must counteract the activities of thousands of protein kinases in human cells. Uncontrolled inhibition of phosphatase activity by toxic inhibitors can lead to widespread catastrophic effects. Over the past decade, a number of natural product toxins have been identified that specifically and potently inhibit protein phosphatase-1 and 2A. Amongst these are the cyanobacteria-derived cyclic heptapeptide microcystin-LR and the polyether fatty acid okadaic acid from dinoflagellate sources. The molecular mechanism underlying potent inhibition of protein phosphatase-1 by these toxins is becoming clear through insights gathered from diverse sources. These include: 1. Comparison of structure-activity relationships amongst the different classes of toxins. 2. Delineation of the structural differences between protein phosphatase-1 and 2A that account for their differing sensitivity to toxins, particularly okadaic acid and microcystin-LR. 3. Determination of the crystal structure of protein phosphatase-1 with microcystin-LR, okadaic acid and calyculin bound. 4. Site-specific mutagenesis and biochemical analysis of protein phosphatase-1 mutants. Taken together, these data point to a common binding site on protein phosphatase-1 for okadaic acid, microcystin-LR and the calyculins. However, careful analysis of these data suggest that each toxin binds to the common binding site in a subtly different way, relying on distinct structural interactions such as hydrophobic binding, hydrogen bonding and electrostatic interactions to different degrees. The insights derived from studying the molecular enzymology of protein phosphatase-1 may help explain the different sensitivities of other structurally conserved protein serine/theonine phosphatases to toxin inhibition. Furthermore, studies on the binding of structurally diverse toxins at the active site of protein phosphatase-1 are leading to a clearer understanding of potential enzyme-substrate interactions in this important class of cell regulatory proteins.     

Helical CT with CT angiography in assessing periampullary neoplasms: identification of vascular invasion

PURPOSE: To determine the accuracy of helical computed tomography (CT) with CT angiography in identifying vascular invasion by periampullary neoplasms and to assess the added value of CT angiography. MATERIALS AND METHODS: Sixty-nine patients suspected of having periampullary neoplasms were examined. Images from dual phase helical CT with CT angiography were compared with surgical findings in 36 patients. Arterial and venous invasion were assessed separately. Accuracy, positive predictive value (PPV), and negative predictive value (NPV) were determined for CT alone and for CT supplemented with CT angiography. RESULTS: The accuracy, PPV, and NPV of helical CT with CT angiography in identifying venous invasion was 92% (33 of 36 patients), 86% (12 of 14 patients), and 95% (21 of 22 patients), respectively. When transverse CT images alone were analyzed, accuracy decreased to 69% (25 of 36 patients) (P =.005); PPV and NPV were 63% (five of eight patients) and 71% (20 of 28 patients), respectively. When identifying arterial invasion, the accuracy of CT with CT angiography and of CT alone was 86% (31 of 36 patients). PPV and NPV also were identical at 71% (five of seven patients) and 90% (26 of 29 patients), respectively. CONCLUSION: CT angiography significantly increases the ability to identify venous invasion when compared with CT alone but does not improve detection of arterial invasion.     

Outbreak of head pediculosis during SFINCSS-99 isolation experiment

This short case report presents the development and treatment of a head lice outbreak during a space simulation experiment. The confinement experiment was conducted from July 1999 to March 2000 at the State Research Center of the Russian Federation Institute for Biomedical Problems in Moscow. Following a symptom period of up to 9 wk before diagnosis and treatment, 3 wk of treatment were required to remove all nits from those infected. Recommendations are made with regard to prevention of such infections during space missions. Treatment altered performance and comfort of crews, took time out of other duties, and even affected relations between crewmembers. The case is made for the development of a public health agenda in space research and medical space programs.     

Recruitment of Montreal women of very low socioeconomic status for a randomized clinical study

Studies show that it is difficult to recruit women of low socioeconomic status as clinical research participants. Such an objective was attained though as our results demonstrate in an evaluative study of a program implemented to lower the percentage of low birthweight in four CLSCs of the Island of Montreal between 1994 and 1996. The global recruitment strategy enabled us to reach 56.2% of our goal in 1994 and 77.4% in 1996. Two conclusions can be drawn from this result: the effectiveness of the three methods of recruitment varied according to each participating CLSC, and the global strategy, combined with the mobilization of community resources, was successful in enrolling women of low socioeconomic status.     

Salbutamol disposition and dynamics in conscious rabbits: influence of the route of administration and of the dose.

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 micrograms/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 micrograms/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 micrograms/kg), total plasma clearance was 82 +/- 5 ml/min per kg, apparent volume of distribution was 5.0 +/- 0.5 l/kg, and terminal half-life was 41 +/- 2 min. Similar values were estimated when 120 micrograms/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80 +/- 0.19, 0.48 +/- 0.22, and 0.78 +/- 0.46 mmol/l, and for the second group, maximal decrement was 1.31 +/- 0.37, 0.70 +/- 0.24, and 0.84 +/- 0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po > it > iv.(ABSTRACT TRUNCATED AT 250 WORDS)