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Biomedical subjects

D Hager

Publications and source records attributed to D Hager.

At least 19 recordsLinked to original sources

Léri-Weill syndrome as part of a contiguous gene syndrome at Xp22.3.

We report on a mother and her 5-year old son, both with a terminal deletion of the short arm of the X chromosome. By molecular genetic analysis the breakpoint was located distal to steroid sulfatase gene. The boy manifested, due to nullisomy of this region, short stature (SHOX), chondrodysplasia punctata (ARSE), and mental retardation (putative mental retardation gene MRX 49). Short stature is present in mother and son, but both also had bilateral Madelung deformity, a key finding in the Léri-Weill syndrome. We discuss the phenotype in relationship to hitherto published cases with chromosomal aberrations and contiguous gene syndromes of Xp22.3.

Abnormalities, Multiple

Respiratory-dependent laser-Doppler flux motion in different skin areas and its meaning to autonomic nervous control of the vessels of the skin.

The aim of this study is to evaluate and quantify the respiratory dependency of cutaneous laser-Doppler flux motion in two variable innervated sites of the upper extremity (the proximal volar forearm and the fingertip) by using a computer-supported system. Various spontaneous (6-17/ min) and externally triggered (12 or 6/min) respiratory frequencies were used for comparative frequency analysis of the laser-Doppler flux signal. Further, an index (MIRSF) was determined as an indicator of the correlation between flux motion and respiration. The MIRSF is defined as the ratio of the power spectrum of the LDF signal at the specific respiratory frequency divided by the time-averaged LDF for that time period. The MIRSF enables a comparison of different intra- and interindividual flux values. A very high correlation was seen between the respiratory frequency and the MIRSF during spontaneous respiration in the skin of the proximal volar forearm; the lower the spontaneous respiratory frequency, the higher the MIRSF. However, this correlation could not be found in the results of the fingertip. The presence of a constant and therefore externally triggered respiratory frequency increased the modulations of the LDF at both measurement locations. While triggered respiration produced a decline in the taLDF of the fingertip, the taLDF of the forearm was unaffected. Considering the different innervation and hydrostatic effects the results lead to the following conclusion: the finger vessels are richly innervated with adrenoceptors which causes alpha 1-mediated vasoconstriction. In contrast to the vessels of the fingers those of the forearm seem to be under andrenergic as well as cholinergic control. Hydrostatic components appear to be more prevalent in the volar forearm site.

Adult

Medium-term effects of beta-blockade on left ventricular mechanics: a double-blind, placebo-controlled comparison of nebivolol and atenolol in patients with ischemic left ventricular dysfunction.

The aim of this study was to compare the effects on left ventricular function and exercise tolerance of a selective beta-antagonist (atenolol) with those of another selective beta 1-antagonist with vasodilator properties (nebivolol) in patients with ischemic left ventricular dysfunction but no overt congestive heart failure. Beta blockers are widely used in ischemic heart disease, but their effects on left ventricular mechanics and exercise tolerance are poorly defined in the subgroup of patients with significant systolic dysfunction but without clinical evidence of ischemia or congestive heart failure. Angiographic and symptom-limited exercise data were obtained at baseline and after an 8-10-week double-blind treatment with placebo (n = 10), 50 mg atenolol daily (n = 10), or 2.5 mg (n = 10) or 5 mg (n = 10) nebivolol daily. When compared to placebo, both atenolol and nebivolol reduced resting heart rate and improved left ventricular ejection fraction (from 33.9 to 39.2% with atenolol and from 36.5 to 40.8% with nebivolol, both P < .05) while lowering mean systolic wall stress. Only nebivolol, however, produced a parallel downward shift of the pressure-volume relationship during early diastolic filling and improved the early peak filling rate when compared to placebo (+ 10%, P < .05). When compared to baseline, maximal exercise duration increased by 7 and 13 seconds with placebo and atenolol, respectively (both NS vs baseline), and increased by 44 seconds with nebivolol (P = .0077 vs baseline). Both atenolol and nebivolol decreased maximal exercise heart rate; the reduction was more pronounced with atenolol. Prolonged beta 1-adrenoceptor blockade leads to a significant increase in left ventricular ejection fraction in patients with ischemic left ventricular dysfunction. The dissociation between the changes in resting left ventricular function and the changes in exercise duration suggests that in this clinical setting, the changes in systolic function may have less impact on functional capacity than an improvement in diastolic distensibility during the rapid filling phase.

Adrenergic beta-Antagonists

Inhaled furosemide is not effective in acute asthma.

As previous studies have suggested that inhaled furosemide may have a protective effect against certain types of provocative challenges in asthmatic subjects, we investigated the role of furosemide in treating acute asthma exacerbations. Twenty-four patients (n = 24) with acute asthma were entered into the study on presenting to the emergency department. They were blindly randomized to receive one of three drug regimens: (1) inhaled furosemide (40 mg) (n = 8); (2) inhaled metaproterenol (15 mg) (n = 7); or (3) the combination of furosemide (40 mg) and metaproterenol (15 mg) (n = 9). We measured FEV1 at entry (time 0) and 15, 30, 45, and 60 min after inhalation of the individual drugs or the combination from a face mask nebulizer. At entry, the three groups did not differ significantly in age (mean +/- SEM = 37.6 +/- 3.6, 38.5 +/- 3.6, and 41.0 years, respectively; p = 0.770), baseline FEV1 (1.01 +/- 0.27, 1.04 +/- 0.27, and 1.25 +/- 0.14 L, respectively; p = 0.620), or theophylline levels (2.87 +/- 1.8, 7.39 +/- 2.8, and 5.29 +/- 2.6 micrograms/ml, respectively; p = 0.498). Pretreatment and posttreatment potassium levels were similar among the three groups. Inhalation of furosemide alone resulted in a 14.9 +/- 10.5 percent change in FEV1 percent from baseline, which was not statistically significant. In contrast, metaproterenol alone resulted in a 42.9 +/- 15.2 percent increase in FEV1 percent (F ratio = 6.226; p = 0.0028). The combination of furosemide and metaproterenol resulted in a change in FEV1 percent that was not statistically different compared with metaproterenol alone (FEV1 percent = 41.9 +/- 12 percent). No significant adverse effects occurred in any of the groups.

Acute Disease

Effect of short-term infusion of sodium nitroprusside on mortality rate in acute myocardial infarction complicated by left ventricular failure: results of a Veterans Administration cooperative study.

Eight hundred twelve men with presumed acute myocardial infarction and left ventricular filling pressure of at least 12 mm Hg participated in a randomized double-blind placebo-controlled trial to assess the efficacy of a 48-hour infusion of sodium nitroprusside. The mortality rates at 21 days (10.4 per cent in the placebo group and 11.5 per cent in the nitroprusside group) and at 13 weeks (19.0 per cent and 17.0 per cent, respectively) were not significantly affected by treatment. The efficacy of nitroprusside was related to the time of treatment: the drug had a deleterious effect in patients whose infusions were started within nine hours of the onset of pain (mortality at 13 weeks, 24.2 per cent vs. 12.7 per cent; P = 0.025) and a beneficial effect in those whose infusions were begun later (mortality at 13 weeks, 14.4 per cent vs. 22.3 per cent; P = 0.04). Nitroprusside should probably not be used routinely in patients with high left ventricular filling pressures after acute myocardial infarction. However, the results in the patients given late treatment suggest that those with persistent pump failure might receive sustained benefit from short-term nitroprusside therapy.

Aged

Characterization of cells of amniotic fluids by immunological identification of intermediate-sized filaments: presence of cells of different tissue origin.

Antibodies against intermediate-sized filaments, of the prekeratin or vimentin type, were used to investigate the presence of these filaments by indirect immunofluorescence microscopy in cultured and non-cultured amniotic fluid cells, in frozen sections of the placenta and in isolated cells of the amniotic epithelium. Two major classes of cells can be cultured from amniotic fluids, namely cells of epithelial origin containing filaments of the prekeratin type and cells of different origin which contain filaments of the vimentin type but are negative when tested with antibodies to epidermal prekeratin. The presence of prekeratin type filaments correlates with the morphology of colonies of amniotic fluid cell cultures in vitro as classified by Hoehn et al. (1974). Cells of E-type colonies are shown to be of epithelial origin. In contrast our data indicate a different origin of almost all cells of F-type colonies and of the large majority of cells of AF-type colonies. Cells of epithelial origin and positively stained with antibodies to epidermal prekeratin are occasionally scattered in F-type colonies and in variable percentages (up to 30%) in AF-type colonies. Surprisingly, cryostat sections of the amniotic epithelium and isolated groups of amniotic cells showed positive reactions with both antibodies to vimentin and prekeratin. The possibility that amniotic cells may be different from other epithelial cells in that they contain both types of filaments simultaneously already in situ is presently under investigation.

Adult

Legionnaires' disease following cardiac transplantation.

The first two cases of Legionnaires' disease in heart transplant patients are reported. Of interest in these cases were culture of the organism from sputum, diagnosis by percutaneous lung aspiration, bronchopleural fistula formation in the first case, which was then successfully treated with multiple-tube thoracostomies, early cavitation of lesions in both cases after the start of antibiotic therapy, positive direct fluorescent antibody staining from transtracheal aspirate 42 days after starting appropriate antibiotic therapy in the first case, apparent superiority of intravenous erythromycin therapy in the first case, and survival of both patients. Our laboratory isolated and identified the organism in both cases.

Adult

Mutation affecting thermostability of sigma subunit of Escherichia coli RNA polymerase lies near the dnaG locus at about 66 min on the E. coli genetic map.

The Escherichia coli strain, ts-rnp5, originally described in 1975 by G. D. Burdick and H. Berger, is shown to possess an RNA polymerase (RNA nucleotidyltransferase) sigma subunit with an activity 4--6 times less thermostable at 45 degrees than sigma from wild-type strains. This defect remains associated with the sigma polypeptide through a variety of purification stages, including renaturation of sigma after its elution from sodium dodecyl sulfate/polyacrylamide gels. The mutation responsible for decreased thermostability of sigma, called rpoD1, cotransduces with dnaG and therefore is located at about 66 min of the E. coli genetic map.

Chromosome Mapping