Gallstone dissolution with chenodeoxycholic acid. A clinical study

Out of 95 patients with radiolucent gallstones who enrolled in a clinical study with chenodeoxycholic acid (CDC) for gallstone dissolution 75 patients with cholecystolithiasis completed 12 months of treatment. As a side effect 31% of patients reported intermittent diarrhea which did not cause cessation of therapy or missing of work. The incidence of biliary colic was markedly decreased during treatment in comparison to the rate in the year before. From more than 20 laboratory values checked before start and every 3 months during therapy only aminotransferases increased up to 3 fold in 20% of patients. gamma-GT elevated in 31% of patients before treatment improved in half of these patients during therapy. Gallstone dissolution defined as 30% or more diminution of the gallstone area on comparable x-rays occurred in 40% of patients. Analysis of factors showed that gallstones above 2 cm in diameter did not dissolve. When the dose of CDC was retrospectively related to body weight a success rate of 68% was found in the group taking more than 13 mg CDC/kg/day. The lithogenic index determined at 6 and 12 months had significantly decreased after 6 months in patients with success. This study demonstrates that medical dissolution of gallstones with chenodeoxycholic acid should be performed in patients with radiolucent stones of less than 2 cm in diameter and with a dose above 13 mg CDC/kg body weight/day. Under these conditions the success rate is above 60% accompanied by minimal side effects.     

The chlorination of 1,4-dihydroxyanthraquinone with thionyl chloride

The chlorination of 1,4-dihydroxyanthraquinone (quinizarin) using thionyl chloride yielded three different products, depending on the purity of the starting material and catalysts used. The compounds isolated were 9-chloro-10-hydroxy-1,4-anthraquinone (3a), 2,4-dichloro-1-hydroxy-anthraquinone (2) and the new compound 1-hydroxy-4-(4-hydroxy-anthraquinone-1-oxy)-anthraquinone (4a). Some acylated derivatives of 3a and of 4a are reported.     

Different inhibition patterns of tedisamil for fast and slowly inactivating transient outward current in rat ventricular myocytes

Experimental evidence increasingly implicates the beta-amyloid peptide in the pathogenesis of Alzheimer's disease. Beta-amyloid filaments dramatically accumulate in the neuritic plaques and vascular deposits as the result of the brain's inability to clear these structures. In this paper, we demonstrate that in addition to the intrinsic stability of A beta N-42, the time dependent generation of irreversibly associated A beta dimers and tetramers incorporated into A beta filaments are themselves resistant to proteolytic degradation. The presence of post-translational modifications such as isomerization of aspartyls 1 and 7, cyclization of glutamyl 3 to pyroglutamyl and oxidation of methionyl 35, further contribute to the insolubility and stability of A beta. All these factors promote the accumulation of neurotoxic amyloid in the brains of patients with Alzheimer's disease, and should be considered in therapeutic strategies directed towards the dissociation of the brain's A beta filaments.     

Alterations of autonomic cardiac control in anorexia nervosa

BACKGROUND: Interindividual differences in the structure and expression of the dopamine receptor genes affect dopamine availability and may be the genetic basis for variation in vulnerability to tobacco smoking. In this study, prevalences of polymorphisms in the TaqIA allele (A1 and A2) and the TaqIB allele (B1 and B2) of the D2 dopamine receptor gene in 157 lung cancer case patients and 126 control subjects were determined to assess whether individuals homozygous or heterozygous for the less common A1 and B1 alleles are more vulnerable to nicotine addiction. METHODS: Case and control subjects were accrued from an ongoing epidemiologic study. Blood samples were collected from them and subjected to molecular genetic analyses. Subjects were interviewed to obtain relevant information. Current and former smokers were administered a questionnaire to quantify their addiction to nicotine. RESULTS: The combined B1B2 genotypes appeared to be more prevalent in ever smokers than in never smokers among case patients (30.3% versus 13.3%; two-sided P = .233) and among control subjects (30.9% and 0%; two-sided P = .02); statistically significant differences were not observed among those with A1 genotypes. Statistically significant correlations between the presence of the A1 and B1 alleles were observed (r = .73 for case subjects and r = .76 for control subjects; two-sided P<.001). Individuals with rarer genotypes reported having been substantially younger at the time of smoking initiation (statistically significant for both A1 and B1) and having attempted to quit smoking fewer times (statistically significant for only A1). CONCLUSION: Variant alleles of the D2 dopamine receptor gene may play a role in determining nicotine addiction, although the associations between the at-risk genotypes and measures of nicotine addiction were not entirely consistent.     

Longitudinal study of bronchial hyperreactivity using the carbachol test with school children

STUDY DESIGN: Bronchial hyperresponsiveness of 476 schoolchildren (10.8 +/- 2.3 years) was studied three times at 12 months' intervals. The cumulative dose of 400 micrograms carbachol was applied in 50 + 50 + 100 + 200 micrograms steps. A fall of FEV1 of at least 15% was regarded as positive reaction. The test was save, as no severe obstruction was observed, only three children withdrew because of unpleasant cough. RESULTS: Reactivity was observed in 19.1, 10.0, and 5.2% of children at the occasion of the first, second and third test (sensitivity/specificity for prevalence of physician diagnosed asthma: 70/83, 35/91, and 24/96%, respectively). Reactivity was age dependent (7-11 years: 35%, 12-16 years: 18%), not influenced by sex, and the relative risk to be reactive was 1.9 in children 2-3 weeks after a respiratory tract infection. CONCLUSION: For epidemiological purposes carbachol provocation test--like other unspecific bronchial provocation tests--is inappropriate as a single test to classify individuals as asthmatics.     

The serine chemoreceptor from Escherichia coli is methylated through an inter-dimer process

Covalent modification of receptors is a widespread phenomenon in signal transduction. In the chemosensory system of Escherichia coli, the reversible methylation of certain glutamic acid residues in the cytoplasmic domain of receptor homodimers mediates adaptation to stimuli. Here we report that the serine receptor is methylated by an inter-dimer process. Methyltransferase bound to one subunit in a serine receptor homodimer was found to catalyze the addition of methyl groups to a receptor subunit in an adjacent dimer in the membrane. These results demonstrate a role for inter-dimer interactions in transmembrane signaling.     

Wave Equation Numerical Resolution: A Comprehensive Mechanized Proof of a C Program

We formally prove correct a C program that implements a numerical scheme for the resolution of the one-dimensional acoustic wave equation. Such an implementation introduces errors at several levels: the numerical scheme introduces method errors, and floating-point computations lead to round-off errors. We annotate this C program to specify both method error and round-off error. We use Frama-C to generate theorems that guarantee the soundness of the code. We discharge these theorems using SMT solvers, Gappa, and Coq. This involves a large Coq development to prove the adequacy of the C program to the numerical scheme and to bound errors. To our knowledge, this is the first time such a numerical analysis program is fully machine-checked.     

Architectural Support for Fault Tolerance in a Teradevice Dataflow System

The high parallelism of future Teradevices, which are going to contain more than 1,000 complex cores on a single die, requests new execution paradigms. Coarse-grained dataflow execution models are able to exploit such parallelism, since they combine side-effect free execution and reduced synchronization overhead. However, the terascale transistor integration of such future chips make them orders of magnitude more vulnerable to voltage fluctuation, radiation, and process variations. This means dynamic fault-tolerance mechanisms have to be an essential part of such future system. In this paper, we present a fault tolerant architecture for a coarse-grained dataflow system, leveraging the inherent features of the dataflow execution model. In detail, we provide methods to dynamically detect and manage permanent, intermittent, and transient faults during runtime. Furthermore, we exploit the dataflow execution model for a thread-level recovery scheme. Our results showed that redundant execution of dataflow threads can efficiently make use of underutilized resources in a multi-core, while the overhead in a fully utilized system stays reasonable. Moreover, thread-level recovery suffered from moderate overhead, even in the case of high fault rates.