Zur Geschichte der Glaucom-Iridectomie

Ohne Zusammenfassung     

Dual-source-Computertomographie des Herzens

In a newly developed dual-source computed tomography system (DSCT) the relation of heart rate and image quality and the possible advantages of the system’s superior temporal resolution in the evaluation of left ventricular parameters as compared to results of cardiac magnetic resonance imaging (MRI) were assessed. Coronary CT angiography was performed using a DSCT (Somatom Defintion, Siemens Medical Solutions, Forchheim, Germany) in 21 patients (mean age 62±8; 15 male, 6 female). Image quality of the coronary arteries, the heart valves, and the left ventricular myocardium was assessed using a three-point grading scale. Ten of these patients also underwent cardiac MRI for the assessment of left ventricular function, using a SSFP (steady-state free precession) sequence. Left ventricular ejection fractions (LV-EF), the end-systolic volumes (ESV), and the end-diastolic volumes (EDV) were measured employing MRI and DSCT datasets. The image quality ratings for the coronary arteries at the optimal reconstruction interval were diagnostic even in patients with high heart rates (1.42±0.49). Analysis of global LV function using DSCT quantified from CTA datasets showed a good correlation with results of cardiac MRI [EF: r=0.75 (p=0.01); ESV: r=0.72 (p=0.19); EDV: r=0.71 (p=0.02)]. The dual-source CT system offers robust image quality of the coronary arteries, independent of the heart rate, and provides combined diagnostic imaging of coronary arteries, the heart valves, the myocardium, and the global left ventricular function.     

The Role of Instructional Set on Alcoholic Performance

This study was conducted to determine whether alcoholic and control subjects respond differently to manipulations that either enhance personal involvement (PI) or reduce negative affect (R, relaxation) on tests of neuropsychological function. In Phase 1, 48 male alcoholics and 36 male control subjects completed neuropsychological tasks under standard instructional sets. In Phase 2, subjects completed equivalent forms of these tests under one of three randomly assigned conditions; the PI condition in which subjects were encouraged to identify specific ways of improving their performance, the R condition in which subjects participated in a short relaxation exercise designed to reduce anxiety, or a No Treatment (NT) condition in which no attempt to manipulate the subjects' involvement or affect was made. Alcoholics were inferior to controls in both Phase 1 and Phase 2 [Fs (1,82) > 5.03, ps < 0.03]. The experimental manipulation differentially affected measures of negative affect and effort in the predicted direction. There were no group x condition interactions. Alcoholic and control subjects responded comparably to the experimental manipulations. This investigation, in combination with others using related manipulations, reinforces the hypothesis that alcohol-related cognitives dysfunction reflects an underlying deficit in brain states.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.