Should plasma from female donors be avoided? A population‐based cohort study of plasma recipients in Sweden from 1990 through 2002

BACKGROUND: Plasma from female donors has been implicated in the sometimes fatal complication known as transfusion‐related acute lung injury. In studies of patients in intensive care units, worsened gas exchange of the lungs has also been attributed to female plasma. Despite a lack of population‐based evidence, policies have already been introduced to exclude female donor plasma. STUDY DESIGN AND METHODS: Short‐term mortality after plasma transfusion was investigated using data from the Scandinavian Donations and Transfusions (SCANDAT) database. A cohort of 92,565 patients in 30 Swedish hospitals were followed for 14 days after their first plasma transfusion. The relative risk (RR) of death in recipients of female plasma compared to recipients of only male plasma was estimated from Poisson regression. RESULTS: Recipients had median age 70 years, received a mean of 4.4 plasma units, and had an overall 14‐day mortality of 8.43%. Sixty‐eight percent were exposed to female plasma, with a 14‐day mortality of 8.85% compared to 7.53% in the nonexposed group. After adjustment for potential confounding factors, the RRs were 1.16 (confidence interval [CI], 1.06‐1.27) and 1.32 (CI, 1.17‐1.49) for those receiving 3 to 4 and 5 or more units of female plasma, respectively. Risk estimates were increased in an analysis of deaths with a concomitant discharge diagnosis involving the respiratory or circulatory system or an adverse reaction. CONCLUSIONS: This large population‐based cohort study of unselected patients suggests that transfusion of plasma from female donors confers a short‐term survival disadvantage on recipients.     

In vivo and in vitro characterization of [18F]-FE-(+)-DTBZ as a tracer for beta-cell mass

IntroductionThe positron emission tomography (PET) tracer 9-[¹⁸F]fluoroethyl-(+)-dihydrotetrabenazine ([¹⁸F]-FE-(+)-DTBZ) is a potential candidate for quantifying beta-cell mass in vivo. The purpose was to investigate in vitro and in vivo utility of this tracer for the assessment of beta-cell mass.MethodsThree pigs were intravenously administered [¹⁸F]-FE-(+)-DTBZ and examined by PET/computed tomography. Binding parameters were estimated by kinetic modeling. In vitro k_D and B_max were determined by saturation binding studies of endocrine and exocrine human tissue homogenates. In vitro pancreatic uptake was determined by tissue autoradiography with pancreases from patients with types 1 (T1DM) and 2 diabetes mellitus (T2DM) and healthy controls.Results[¹⁸F]-FE-(+)-DTBZ had a k_D of 3.5±1.0 nM, a B_max of 382±108 fmol/mg protein and a specificity of 89±1.8% in islet homogenates. The total exocrine uptake was lower and 65% was nondisplaceable. No uptake difference was observed in pancreatic tissue slices from patients with T1DM, T2DM or healthy controls. The in vivo porcine pancreatic uptake reached a peak of standardized uptake value (SUV) of 2.8 with a low distribution volume ratio in all animals. Moderate to high tracer uptake was identified in the bile system and in bone.Conclusions[¹⁸F]-FE-(+)-DTBZ binds to vesicular monoamine transporter 2 (VMAT2) with high specificity in pure islet tissue in vitro. However, there is high nondisplaceable binding to exocrine tissue. In addition, in vivo tracer metabolism and dehalogenation result in severe underestimation of porcine pancreatic VMAT2 expression and BCM. The results do not support [¹⁸F]-FE-(+)-DTBZ as a suitable tracer for in vivo beta-cell imaging.     

Direct quantification of ethyl glucuronide in clinical urine samples by liquid chromatography-mass spectrometry

Ethyl glucuronide is a minor metabolite of ethanol, and its presence in urine can be used as a laboratory test to detect recent alcohol intake, even for some time after the ethanol is no longer measurable. A simple analytical procedure was developed based on direct injection of urine diluted with a deuterated internal standard into an electrospray liquid chromatographic-mass spectrometric (LC-MS) system. A novel LC system using a porous graphite column (Hypercarb) enabled an isocratic elution with retention times of 5-6 minutes. The intra- and inter-assay coefficients of variation were 2-12%, and the measuring range was 0.1-1,500 mg/L (0.45-6,750 micromol/L). Ethyl glucuronide was found to be stable in urine for more than 4 days at room temperature, and no artifactual formation was observed on storage of urine samples fortified with 1% ethanol. Ethyl glucuronide was not detected in urine samples collected after abstinence from alcohol. Intake of a very low amount (7 g) of ethanol produced ethyl glucuronide values up to 8.4 mg/L after 4 hours and was still detectable at 6 hours. When the method was applied for routine screening of 252 clinical urine samples (range, 0-1,240 mg/L), it fulfilled the need for a simple and reliable assay to be used in the evaluation of urinary ethyl glucuronide as a routine test of recent alcohol intake.     

Chromatographic screening for zopiclone and metabolites in urine using liquid chromatography and liquid chromatography-mass spectrometry techniques

Zopiclone is a benzodiazepine-like hypnotic that was believed not to have any abuse potential. Nevertheless, during the past few years there have been an increasing number of reports on the abuse and misuse of zopiclone. Despite this, methods for screening analysis in urine are lacking. To investigate whether UV detection would be possible to use for this purpose, a liquid chromatography method with ultraviolet detection for analyzing zopiclone and its urinary metabolites was developed, with liquid chromatography-mass spectrometry for confirmation. The method was used for analyzing samples from subjects receiving methadone. The limits of detection were approximately 100 ng/mL in control urine samples and 500 ng/mL in urine samples from subjects receiving methadone. However, due to the high background in these patients' urine, a single therapeutic dose was impossible to detect.     

Heat sterilization of peritoneal dialysis solutions influences ingestive behavior in non-uremic rats

BACKGROUND: The appetite inhibitory effect of glucose-based peritoneal dialysis (PD) solutions may be due to glucose as such, or the hyperosmolality of the PD solution, or an effect of glucose degradation products (GDPs) formed in the PD solution during heat sterilization. This was studied in an experimental appetite model in rat. METHODS: The effect of different experimental PD solutions on ingestive behavior was investigated in non-uremic rats equipped with an implanted intraoral (i.o.) cannula through which a 1 mol/L sucrose solution was infused during tests. The amount of intake was recorded at 30 min after rats were infused intraperitoneally (IP) with 30 mL of different solutions. This method allowed an accurate and reproducible analysis of i.o. intake. The experimental PD solutions tested included (1) glucose based PD solutions with different glucose concentrations, sterilized by heat or microbiological filter, (2) glucose- and mannitol-based PD solutions with the same osmolality, sterilized by heat or microbiological filter; and (3) glucose based PD solutions, using different pH values (pH 3.0, pH 5.5 or pH 7.4) during heat sterilization. RESULTS: Following IP infusion of solutions, (1) the i.o. intake was significantly inhibited by glucose based, heat sterilized PD solutions and the degree of appetite suppression was related to the concentration of dialysate glucose in a dose-dependent way; (2) the i.o. intake was significantly less suppressed by filter sterilized than by heat sterilized glucose-based solutions; (3) the i.o. intake was significantly less following the IP infusion of glucose-based than following the mannitol-based heat sterilized solutions; however, i.o. intake did not differ between the glucose-based and mannitol-based filter sterilized solutions; and (4) furthermore, the degree of suppression of i.o. intake induced by glucose-based PD solutions was influenced by the pH value during heat sterilization. The lower the pH of the PD solution during heat sterilization, the higher the i.o. intake. CONCLUSIONS: The IP infusion of glucose-based heat-sterilized PD solutions inhibited food intake in this experimental appetite model, and the degree of suppression depended on the concentration of dialysate glucose and the pH of the solution during heat sterilization. The results suggest that GDPs formed during heat sterilization may exert a more adverse effect than glucose itself on ingestive behavior, and that a reduction of the concentration of GDPs in the PD solution using filter sterilization or a low pH value in the PD solution during heat sterilization may improve food intake.     

Global perspectives in breast milk contamination: infectious and toxic hazards

Breast milk is the natural and optimal food for infants. In addition to meeting nutritional needs, breast milk provides numerous immunologic, developmental, psychologic, economic, and practical advantages. It is postulated that breast-feeding may also be related to the prevention of some adult health problems such as diabetes and coronary heart disease. Malnutrition among infants and young children, which remains one of the most severe global public health problems, is among the main reasons that the World Health Organization (WHO) so strongly supports breast-feeding. However, WHO recognizes the growing concern expressed by scientists, health professionals, environmentalists, and mothers about the potential risks posed by the presence of toxicants and infectious agents in breast milk. In this paper we review the main infectious hazards (tuberculosis, hepatitis B, and human immunodeficiency virus) and selected chemical hazards (tobacco, persistent contaminants) and the activities undertaken by WHO. We conclude that in cases where there is a high degree of pollution from chemical sources occurring simultaneously in a bacterially contaminated environment, the choice is not simply between polluted breast milk and risk-free substitutes. Rather, informed choice is based on assessing the known and unknown risks of artificial feeding versus the unknown, but potential, risks of chemical contamination of breast milk. Clearly, the possible toxicity of compounds requires further investigation. Of much greater importance, however, are effective measures to protect the environment for the entire population by controlling the use of these toxic products. Current scientific evidence does not support altering WHO's global public health recommendation of exclusive breast-feeding for 6 months followed by safe and appropriate complementary foods, with continued breast-feeding, up to 2 years of age or beyond.     

A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale)

Objective: To construct an observer's rating scale sensitive to change for measuring severity and treatment outcome in fibromyalgia (FM) and chronic fatigue syndrome (CFS) patients. Methods: A selection of items from the Comprehensive Psychopathological Rating Scale (CPRS) were repeatedly rated and used as outcome measure of a 24-week treatment study. In the study 100 women, fulfilling the criteria for both FM and CFS, received intermittent injections of a staphylococcus toxoid or placebo. Nine CPRS-items with high baseline incidence (cutoff 70%) were extracted and validated against global ratings and the Fibromyalgia Impact Questionnaire (FIQ). The fibromyalgia and chronic fatigue syndrome rating scale (the FibroFatigue scale) was thereafter formed based upon the extracted items and three supplemented ones. The interrater reliability was tested in 27 consecutive patients of both sexes. Results: The FibroFatigue scale is an observer's rating scale with 12 items measuring pain, muscular tension, fatigue, concentration difficulties, failing memory, irritability, sadness, sleep disturbances, and autonomic disturbances (items derived from the CPRS) and irritable bowel, headache, and subjective experience of infection (new items). There was a statistically significant correlation between the CPRS-extracted items and global ratings as well as with the FIQ. The interrater reliability of the new scale was excellent (correlation coefficient .98), irrespective of the patients' gender. Conclusion: The FibroFatigue scale seems to be a reliable and valid measuring instrument with capacity to monitor symptom severity and change during treatment of FM/CFS patients.     

Epidemiological investigation of a food-borne gastroenteritis outbreak caused by Norwalk-like virus in 30 day-care centres

In March 1999, an outbreak of gastroenteritis occurred affecting 30 day-care centres served by the same caterer. A retrospective cohort study was performed in 13 randomly selected day-care centres to determine the source and mode of transmission. Electron microscopy and PCR were used to verify the diagnosis. The overall attack rate (AR) was 37% (195/524): 30% in children and 62% in adults. Modified by the age of the patient, eating pumpkin salad served on 1 March was associated with becoming an early case (odds ratio = 3.9; 95% confidence interval 1.8-8.8). No significant association was found between food consumption and becoming a late case. The primary food-borne AR was 27% and the secondary AR was 14%. The same genotype of Norwalk-like virus was found in 5 cases and in 1 ill and 1 asymptomatic food-handler. Contamination by 1 of the food-handlers seems the most likely route of spread of the virus and underlines the importance of strict hygienic routines.