Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study.

The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2∙04 (95% confidence interval 1∙43-2∙91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.

Exposure to mebendazole and pyrvinium during pregnancy: a Danish nationwide cohort study.

PURPOSE: Families with children are frequently exposed to pinworm infection and treatment involves the whole family. Information on consequences of exposure during, pregnancy is limited. The aim of this study was to investigate the exposure to pyrvinium and mebendazole before, during, and after pregnancy in a Danish nationwide cohort. METHODS: From nationwide administrative registers, we identified 718,900 births in Denmark between January 1997 and December 2007 as well as maternal prescription data of anthelmintics and maternal characteristics. Redemption of a prescription for pyrvinium or mebendazole was used to identify exposure. RESULTS: 4715 women redeemed a prescription for pyrvinium or mebendazole during pregnancy; 1606 for pyrvinium, 2575 for mebendazole, and 534 for both drugs. Having >2 children compared to having no previous children was associated with exposure to pyrvinium (OR: 7.1, 95% CI: 5.8-8.7) and mebendazole (OR: 20.8, 95% CI: 17.3-24.9). CONCLUSION: 4715 pregnant women redeemed a prescription for either mebendazole or pyrvinium. We believe the exposure to be even higher since pyrvinium is also sold over-the-counter. Limited information on birth outcomes is available at present time, and considering the number of exposed pregnancies, we recommend that studies are to be undertaken to assess the safety of pyrvinium and mebendazole during pregnancy.

SU-E-I-29: Dose Rate and Image Quality Comparison Between Philips Veradius and GE OEC 9900 Elite Fluoroscopic C-Arms.

PURPOSE: The radiation dose rate and image quality were compared on GE OEC 9900 Elite Vas 8 and Philips Veradius fluoroscopic C-arms. METHODS: Plastic (PMMA) phantoms were used to simulate various thicknesses of soft tissues encountered during fluoroscopically-guided interventional procedures while aluminum and copper phantoms were used to simulate extremities of different sizes. An image quality test tool and an ionization chamber were included in the setup of each phantom. The phantoms were imaged in several fluoroscopy modes and at different dose levels. The entrance surface air KERMA rate (ESAKR) was measured for each phantom in each fluoroscopy mode. Simultaneously, the image quality was assessed by counting the number of low-contrast objects visible in the image quality test tool. For a given phantom type and thickness, the ESAKR was plotted versus the number of visible low-contrast objects to compare the dose rate required for a given level of image quality. Additionally, the mean ESAKR per number of objects was calculated and p-values were used to test for statistically significant differences between the C-arms. RESULTS: For comparable image quality with a given phantom type and thickness the ESAKR with the OEC was typically much higher than with the Veradius. One-tailed, unpaired t-tests confirm that the mean ESAKR per number of visible low-contrast objects was lower for the Veradius than for the OEC with all thicknesses of PMMA (p < 0.05). The differences for the aluminum and copper phantoms were much smaller and were not statistically significant (p-values ranged from 0.2 to 0.47). CONCLUSION: In general, the Veradius C-arm provided better low-contrast image quality during fluoroscopy, with lower ESAKR than the OEC 9900 Elite Vas 8. The differences were statistically significant only with PMMA phantoms. Funding support provided by Philips Healthcare (Bothell, WA).

Logarithmic quantitation model using serum ferritin to estimate iron overload in secondary haemochromatosis.

Nineteen children and adolescents receiving repeated transfusions and subcutaneous desferrioxamine treatment were investigated in an attempt to quantitate iron overload non-invasively. Before patients were started on desferrioxamine individual relationships were correlated for 12 to 36 months between transfused iron, absorbed iron estimated gastrointestinally, and increasing serum ferritin concentrations. Patients with inflammation, increased liver enzymes, or haemolysis were excluded from analysis. The relationship between the variables could be described by a logarithmic regression curve (y = transfused iron [plus eventually gastrointestinally absorbed iron] = iron overload = a+b log [x = serum ferritin]) for each individual patient. All patients showed close correlation (R2) between x and y (median R2 of 0.909, 0.98, and 0.92 in thalassaemia, aplastic anaemia, and sickle cell anaemia patients, respectively). When started on desferrioxamine, current serum ferritin concentrations were used to derive the iron overload from each individual regression curve. The derived estimated iron overload ranged from 0.6 g to 31 g. Left ventricular dilatation was observed in three patients with beta thalassaemia and in one patient with aplastic anaemia with median iron overload of 20.7 (14.1-31.3) g and 24.0 g respectively. Hypothyroidism was found in four patients with beta thalassaemia and one patient with aplastic anaemia with iron overload between 14.7 (6.8 and 26.1) g and 15.1 g respectively. Human growth hormone deficiency was detected in three patients with beta thalassaemia with an iron overload of 4.2 (3.5-6.8) g; all three patients had excellent desferrioxamine compliance.

High resolution of human lactate dehydrogenase: new multiple forms and potential tumor markers.

Human lactate dehydrogenase (LDH) was investigated by ultrathin-layer polyacrylamide gel isoelectric focusing (IEF). In serum, approximately 15 bands and in lyzates of erythrocytes approximately 20 bands were detected. Known LDH isoenzymes (identified by markers) appeared in the zymograms as follows: LDH-1 as a single or double band, LDH-2 as a single band in serum and in the marker, and as a double band in hemolyzate, LDH-3 as a double band, and LDH-4 and LDH-5 each as a single band. LDH-1 was partly inactivated, probably due to deamidation in the acidic range of the pH gradient. Potential LDH tumor markers were detected in different tumor cytosols.

Automated determination of serum (plasma) and urine iron: a comparative investigation of chromogens improved tripyridyltriazine micromethod.

Four different, well known colour reagents for iron determination were tested in a citrate buffer at pH 2.0 under the same automated standard conditions and compared with a manual reference method on human serum and plasma samples. Specific results were obtained only with the chromogen tripyridyl-s-triazine. A micromethod was developed, which is generally well suited for automated, direct serum iron determinations, with respect to good flow properties, simple reagent composition, high reagent stability, rapid colour development, stable colour complex and high specificity. This method was run on either a Gilford System 203 S, Gilford Impact 400 or a Greiner G-400 analyser and adapted to the Technicon SMAC II, Technicon RA 1000, Eppendorf Epos and Abbott Spectrum automated systems. The tripyridyl-s-triazine method permits the determination of ferrioxamine iron in urine after a simple sample pretreatment.

Crohn's disease activity: assessment by factor VIII coagulation proteins.

Twenty-eight patients (mean age 13.5 years) with proven Crohn's disease were examined for factor VIII coagulation activity (VIII:C), factor VIII-related antigen (VIII R:Ag), and factor VIII-related ristocetin cofactor activity (VIII R:RCF). The factor VIII coagulation proteins were correlated with disease activity index according to van Hees and were compared with inflammatory parameters such as erythrocyte sedimentation rate, c-reactive protein, and orosomucoid. Among the factor VIII proteins, factor VIII-related protein (VIII R:Ag) correlates best with van Hees disease activity index, orosomucoid, c-reactive protein, and erythrocyte sedimentation rate (p less than 0.001 for all parameters). Since acute phase proteins are produced by liver cells, whereas VIII R:Ag is synthesized by endothelial cells, we postulate that this coagulation factor is highly sensitive in reflecting the inflammatory process in the intestine.

Mass screening for glucose-6-phosphate dehydrogenase deficiency: improved fluorescent spot test.

New data on the reliability of the fluorescent spot test are presented. Improvements in the assay were established. Newborn mass screening for glucose-6-phosphate dehydrogenase (G-6-PD, EC 1.1.1.49) deficiency was performed with dried blood samples on filter paper (Guthrie-cards). Females, known to be heterozygote for G-6-PD deficiency were detected at a rate of approximately 30-70%, depending on the storage conditions of the samples. False positive results in male hemizygotes were eliminated.

Glucose-6 phosphate dehydrogenase deficiency: an easy and sensitive quantitative assay for the detection of female heterozygotes in red blood cells.

Different methods for the quantitative determination of glucose-6-phosphate dehydrogenase (G-6-PD) were compared and one of them found to be highly precise. Maleimide inactivation of 6-phosphogluconate dehydrogenase (PGD) was investigated. It was shown that this inactivation is time-dependent and causes loss of assay precision. The most precise method was adapted to lysates of red blood cells from females, known to be heterozygote for G-6-PD deficiency and from non-deficient males and females. Heterozygote gene carriers were detected at a rate of 97.0%.

High excretion of beta-aminoisobutyric acid in patients with ketoacidosis.

High concentrations of beta-aminoisobutyric acid (BAIBA) were found to be present in the urine from patients with ketoacidosis. The R-form was always the dominating isomer of BAIBA. The finding is discussed, and it is suggested that the mechanism might be a derangement in the degradation of valine.