Efficacy and dosing of antidotes applied to Daphnia intoxicated by nerve agent tabun

A new assay with Daphnia, which can be used as a time, cost, and human effort-saving tool in the development of effective antidotes against organophosphate intoxications, is presented. Five concentrations of atropine (antimuscarinic anticholinergics) as well as a reactivator (trimedoxime) were tested to define the optimal dosage. Various reactivators (trimedoxime, obidoxime) were used to examine difference in effectivity of treatments. The most effective dose of trimedoxime corresponded to the 75% of its EC(50)(24) value, i.e. 77.85mgl(-1). The most effective dose of atropine corresponded to the 25% of its EC(50)(24) value, i.e. 104.70mgl(-1). The most effective treatment was a combined atropine-obidoxime treatment, followed by the combined atropine-trimedoxime treatment, the atropine only and the obidoxime only treatments. The efficacy of the trimedoxime only treatment was doubtful. The surprisingly high efficacy of obidoxime in the obidoxime only treatment indicates that some oximes might act in daphnids not just as reactivators but also by some other mechanisms.     

Mixed medullary and follicular cell carcinoma of the thyroid in a 71-year-old man with history of malignant melanoma.

BACKGROUND: Mixed medullary-follicular carcinoma of the thyroid with a pleomorphic pattern is a rare malignant epithelial tumor characterized by clinical and immunohistochemical features of follicular and parafollicular thyroid cells. Different molecular mechanisms for mixed thyroid tumors have been suggested. CASE REPORT: We describe a 71-year-old man with a history of malignant melanoma with mixed medullary-follicular thyroid carcinoma. Cytology results of a fine needle aspiration biopsy were suspicious of a thyroid carcinoma. The patient underwent a total thyroidectomy for a solitary thyroid nodule in the right lobe. No lymph node metastases were present. Histopathology and immunohistochemistry revealed a mixed medullary and follicular cell carcinoma that showed characteristic patterns and calcitonin and thyroglobulin positivities in many of the tumor cells. The tumor was not associated with multiple endocrine neoplasia type 2. Detection of RET proto-oncogene point mutations in risk exons 10, 11, 13, 14, 15, and 16 was negative. Two polymorphisms, one in exon 11 G691S (GGT-->AGT) and another in exon 15 S904S (TCC-->TCG) were detected. CONCLUSIONS: A mixed differentiated thyroid tumor is a diagnostic challenge with fine needle aspiration. Definitive diagnosis remains the domain of histology because of the necessity of topographic information. The origins of this rare tumor entity are unclear. The possible association with the uncommon polymorphism G691S of the RET proto-oncogene is discussed.     

Long‐term follow‐up of Wilson Disease: natural history,treatment, mutations analysis and phenotypic correlation

Background and aims: Wilson disease (WD) is an inherited disorder of copper metabolism. When treated, the outcome can be excellent, although the long‐term survival has yet to be well documented. The aim of this study was to describe the long‐term outcome of a cohort of patients with WD and to assess those factors affecting the phenotypic manifestation of WD. Methods: The presence of mutations to the ATP7B gene, the clinical manifestations, treatments and the long‐term outcomes were analysed retrospectively in 117 patients with WD (59 men and 58 women, aged at evaluation 38.5 ± 11, range 16–63 years). Results: Fifty‐five patients with a neurological presentation, 51 patients with a hepatic presentation and 11 asymptomatic patients were followed up for an average of 15.1 ± 10 years (median 12 years, range 1–41 years). The H1069Q ATP7B gene mutation was the most frequent genetic variant (54.3%); the frequency of this mutation did not differ between patients with either the hepatic or the neurological presentation (P=0.099). d ‐penicillamine or zinc salts (81 and 17% respectively) were used for treatment, and three patients underwent liver transplantation. The majority of symptomatic patients became asymptomatic, or improved, during the follow‐up (82% patients with hepatic presentation, 69% with neurological presentation). The long‐term survival of patients with WD did not differ from that of the general Czech population (P=0.95). Conclusions: Long‐term follow‐up shows a satisfactory response in the great majority of adequately treated patients with WD and survival coincides with that of the general population.     

The ribosomal basis of Diamond-Blackfan Anemia: mutation and database update

Diamond-Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. DBA exhibits an autosomal dominant pattern of inheritance with incomplete penetrance. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. Experimental evidence supports the hypothesis that DBA is primarily the result of defective ribosome synthesis. By means of a large collaboration among six centers, we report here a mutation update that includes nine genes and 220 distinct mutations, 56 of which are new. The DBA Mutation Database now includes data from 355 patients. Of those where inheritance has been examined, 125 patients carry a de novo mutation and 72 an inherited mutation. Mutagenesis may be ascribed to slippage in 65.5% of indels, whereas CpG dinucleotides are involved in 23% of transitions. Using bioinformatic tools we show that gene conversion mechanism is not common in RP genes mutagenesis, notwithstanding the abundance of RP pseudogenes. Genotype-phenotype analysis reveals that malformations are more frequently associated with mutations in RPL5 and RPL11 than in the other genes. All currently reported DBA mutations together with their functional and clinical data are included in the DBA Mutation Database.     

Natural history of recessive inheritance of DMT1 mutations

DMT1 deficiency causes microcytic hypochromic anemia due to decreased erythroid iron utilization. Anemia is present from birth. Transferrin saturation is high and serum ferritin is mildly elevated, despite liver iron overload. DMT1 deficiency must be considered in the differential diagnosis of microcytic hypochromic anemia observed in the newborn period.     

An assessment of predictive value of the biophysical profile in women with preeclampsia using data from the fullPIERS database

IntroductionPre-eclampsia is associated with increased risk to both the mother and fetus. Effective monitoring of the fetal condition is essential to the management of women with pre-eclampsia. The biophysical profile (BPP) is one monitoring tool available to clinicians.Aims and ObjectivesTo compare the BPP test with cardiotocography/non-stress test (CTG/NST) alone for their ability to predict fetal acidemia at birth or a composite adverse perinatal outcome among women with preeclampsia and to estimate the effect of BPP assessment on mode of delivery and birth outcome.MethodsSecondary analysis of a prospective cohort of women with preeclampsia. The predictive ability of the tests was assessed based on sensitivity, specificity, positive and negative likelihood ratios (LR+, LR?). Women assessed with the BPP were compared with matched controls not assessed with the BPP to determine the odds of Cesarean delivery or adverse perinatal outcomes after adjustment for potential confounders.ResultsFive out of 89 women (5.6%) had an abnormal BPP; 18 out of 89 (20.2%) had an abnormal CTG/NST. Fetal acidemia was diagnosed in 13 fetuses (14.6%); composite adverse perinatal outcome in 68 fetuses/infants (76.4%). Both tests had relatively poor predictive performance for both outcomes (LR+ between 2.50 and 3.90 and LR? between 0.64 and 0.93). Assessment with the BPP was positively associated with fetal acidemia (adjusted OR 4.84; 95% CI 1.33–17.66).ConclusionThe BPP and CTG/NST alone were poor predictors of perinatal outcome in this cohort; multiple tests should be considered when assessing fetal risk in women with preeclampsia.