Meta-analysis of drop-out rates in randomised clinical trials, comparing typical and atypical antipsychotics in the treatment of schizophrenia.

OBJECTIVE: To assess antipsychotic medication in the treatment of schizophrenia, based on trial drop-out rates. METHOD: The studies included were randomised controlled trials that compared any of the four clinically best-established atypical antipsychotics (quetiapine, olanzapine, risperidone or clozapine) against either of two typical antipsychotics regarded as the gold standard (haloperidol or chlorpromazine). RESULTS: Meta-analysis indicated less risk of all-cause patient withdrawal from atypical medication trials where dosage was flexible, in both the short, relative risk (RR) 0.70 (95% CI 0.64-0.76), P<0.00001, and long term, RR 0.72 (0.65-0.80), P<0.00001. Similar results were observed for withdrawal due to adverse events, RR: 0.54 (0.41-0.72), P<0.0001. Nevertheless, the favourable effects of atypical medication disappeared in trials relying on fixed dosage. CONCLUSIONS: We detected a significant positive effect in terms of the outcome of treatment discontinuation for atypical versus typical medication, though only where the use of flexible rather than fixed doses (closer to an experimental control situation) was possible.     

Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32

Some MCP SNP and aHUS-associated MCP mutation     

Limiting behaviour during the hydroperoxide ion generation in a flow alkaline fuel cell

A comparative study of an O₂-diffusion cathode and a H₂-diffusion anode has been performed to ascertain the limiting processes, when they are combined in a flow alkaline fuel cell with hydroperoxide ion generation. The linear sweep voltammograms and the impedance diagrams of both electrodes show large differences. The cathode reaction is charge transfer-controlled up to current densities of at least 1 A cm^?2, whereas the dissociative adsorption, charge transfer and diffusion of H₂ appear to limit the anode reaction. The anode, with limiting current densities of about 90 and 150 mA cm^?2 for 1.0 and 6.0 M KOH, respectively, then clearly controls the hydroperoxide ion production in the fuel cell. Diffuse reflectance infrared Fourier transform spectroscopy and X-ray photoelectron spectroscopy reveal that, the carbon of the H₂-diffusion anode does not undergo significant oxygen functionalisation during hydroperoxide ion generation in the fuel cell.     

Genetic analysis of seven Mediterranean families with multiple endocrine neoplasia type 2A

OBJECTIVE   Genetic analysis is now essential for the accurate screening of families with multiple endocrine neoplasia type 2 (MEN2). We present the genetic analyses by both haplotype and direct RET proto-oncogene mutation analysis in seven Mediterranean MEN 2A families and have compared these results with biochemical screening tests and pathological examinations.
DESIGN  Total DNA was extracted from leucocytes. Linkage analysis was performed using five RFLP systems from three loci that flank the MEN2A locus (FNRB, RBP3, D10S15). RET proto-oncogene analysis was carried out by automatic DNA sequencing and adequate digestion of PCR amplified products for exons 10 and 11. Screening for medullary thyroid carcinoma or C-cell hyperplasia was performed by the pentagastrin provocation test. Adrenal medullary function was assessed by measurements of 24-hour urinary excretion of catecholamines and their metabolites. Serum calcium and phosphate measurements were the initial screen for hyperparathyroidism. Serum PTH was determined only if hyperparathyroidism was suggested by the former determinations.
PATIENT   Genetic study was performed in 59 individuals (39 at risk) from seven kindreds of Mediterranean origin with MEN 2A.
RESULTS   Diagnosis by linkage analysis was not possible in 30% of individuals at risk, but RET proto-oncogene analysis identified all these individuals. Mutations of the RET proto-oncogene were detected in exon 10 (codon 618) in one MEN 2A kindred and in exon 11 (codon 634) in the others. The results of direct analysis were concordant with linkage studies in each case. Three individuals from different MEN 2A kindreds, who were subsequently shown not to be gene carriers, had false positive pentagastrin stimulation tests.
CONCLUSION   Biochemical tests can be replaced by direct DNA mutation analysis as the first line screening test in order to identify gene carriers of MEN 2A.     

Cholesterol crystals in biliary microlithiasis

A recent study put forward the hypothesis that microlithiasis may represent an early stage in the development of biliary calculi. It is an established fact that cholesterol crystals are the product of an inevitable stage in the sequence leading to gallstone formation. To test the hypothesis stated above ten patients affected by gallbladder cholesterol microlithiasis (CM) were examined in the lipid composition of the bile, the cholesterol saturation index and the presence of cholesterol crystals being calculated. The results were compared with those of 14 patients affected by pigment microliths, 24 with larger stones (LS) and ten control patients. The cholesterol saturation index was above one in all CM patients, whereas in some LS patients the gall-bladder bile was not supersaturated. Cholesterol crystals were observed in the gallbladders of all CM patients and seven LS patients. These results would seem to provide support for the hypothesis of microcalculi as being "young stones", with the bile of CM patients maintaining the conditions leading to gallstone formation.     

Which are the best biological markers of the antiphospholipid syndrome?

The diagnosis of antiphospholipid syndrome (APS) requires the presence of both clinical and biological features. Due to the heterogeneity of anti-phospholipid antibodies (aPL) the laboratory approach for their detection includes clotting-based tests for lupus anticoagulant (LA) as well as solid-phase assays for anticardiolipin antibodies (aCL). In addition, as it has been shown that autoimmune aPL recognize epitopes on phospholipid (PL)-binding plasma proteins, assays detecting antibodies to beta 2-glycoprotein I (beta 2-GPI) or prothrombin have been developed. The association between venous or arterial thrombosis and recurrent fetal loss with the presence of conventional aPL (LA and/or aCL) has been confirmed by many studies. The LA and IgG aCL at moderate/high titre seem to exhibit the strongest association with clinical manifestations of the APS. Several reports indicate that LA is less sensitive but more specific than aCL for the APS. Assays against PLs other than CL as well as the use of mixtures of PLs have been proposed to improve the detection of APS-related aPL. Concerning antibodies to PL-binding proteins (detected in the absence of PLs), there is evidence that anti-beta 2-GPI are closely associated with thrombosis and other clinical features of the APS. Moreover, these antibodies may be more specific in the recognition of the APS and in some cases may be present in the absence of aPL detected by standard tests. Many issues are still under debate and are discussed in this review, such as the problems of standardization of anti-beta 2-GPI assays, detection of the IgA isotype of aCL and anti-beta 2-GPI, the coagulation profiles of LA in the recognition of the thrombotic risk and the association of particular markers with subsets of patients with APS.     

Embryo transfer under ultrasound guidance improves pregnancy rates after in-vitro fertilization

Between October 1998 and January 1999, we examined the influence of ultrasound guidance in embryo transfer on pregnancy rate in 362 patients from our in-vitro fertilization (IVF)-embryo transfer programme. These patients were prospectively randomized into two groups: 182 had ultrasound-guided embryo replacement, and 180 had clinical touch embryo transfer. There were no statistically significant differences between the two groups with respect to age, cause of infertility and in the characteristics of the IVF cycle. The pregnancy rate was significantly higher among the ultrasound-guided embryo transfer group (50%) compared with the clinical touch group (33.7%) (P < 0.002). Furthermore, there was also a significant increase in the implantation rate: 25.3% in the ultrasound group compared with 18.1% in the clinical touch group (P < 0.05). In conclusion, ultrasound assistance in embryo transfer significantly improved pregnancy and implantation rates in IVF.     

WFS1 mutations in Spanish patients with diabetes mellitus and deafness

Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disorder characterised by early onset diabetes mellitus and progressive optic atrophy, as well as other clinical features such as deafness, diabetes insipida, renal tract abnormalities and diverse psychiatric illnesses. A gene responsible for WS was identified in 4p16.1 (WFS1). It encodes a putative 890 amino acid transmembrane protein expressed in a wide spectrum of tissues. Recently, a new locus for WS has been located on 4q22-24, providing additional evidence for the genetic heterogeneity of this syndrome. We have studied the presence of WFS1 variants in three groups of individuals: patients with diabetes mellitus, patients with deafness and patients with both conditions. A fourth group of healthy subjects was used as control. We have identified a total of 18 nucleotide changes in the WFS1 gene: three mutations and 15 polymorphisms. Six of these changes were previously undescribed. Four of the 15 polymorphisms studied among the patients group present statistical differences in the allelic and genotypic distribution when comparing affected vs control groups.