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Biomedical subjects

M Frey

Publications and source records attributed to M Frey.

At least 127 records · Page 7Linked to original sources
PubMed1996

Calcium antagonist drugs in hypertensive patients with angina pectoris.

Arterial hypertension frequently occurs in association with myocardial ischaemia and is an independent and significant risk factor for the development of coronary artery disease (CAD), as is left ventricular hypertrophy due to arterial hypertension. The prevalence of CAD in patients with hypertension is high, while hypertension occurs in approximately 60% of patients with CAD. Myocardial ischaemia occurs both in the presence and absence of CAD, probably as the result of limitation of coronary vasodilator capacity and reduction in coronary flow. This may occur in hypertension due to increased transmural coronary artery resistance, alterations in the vascular wall and endothelial dysfunction. Furthermore, left ventricular hypertrophy itself predisposes the heart towards ischaemia due to an increased diffusion distance between capillaries. When myocardial ischaemia occurs in hypertensive patients, 90% of all episodes are aysmptomatic. The highest incidence of ischaemic episodes appears to occur in treated elderly hypertensive men with inadequate blood pressure control (40%). Calcium antagonists exert a range of beneficial effects in hypertensive patients, including reduction of blood pressure, improvement in myocardial blood flow, regression of left ventricular hypertrophy and cardioprotection in reperfused organs. However, while vasoprotective effects have been demonstrated in animal models, beneficial effects in man are uncertain. Thus, in established coronary atherosclerosis, calcium antagonist treatment has produced only a mild reduction in the appearance of new atherosclerotic lesions.

Angina Pectoris↗
PubMed1996

Ulcerous tracheitis and mucus ball formation: a nearly fatal complication of a transtracheal oxygen catheter.

A transtracheal oxygen catheter may be superior to a nasal cannula. In particular, transtracheal oxygen therapy (TTOT) shows a 50% saving of oxygen consumption, a significant reduction of energy cost of breathing, and an improved patient compliance due to esthetic benefits and avoidance of mucosal injury by a nasal cannula. Most complications so far reported have been of minor clinical importance and could be treated easily. However, using the SCOOP technique, a serious complication has recently occurred in 1 of our patients. Soon after starting TTOT with a SCOOP-1 catheter he developed an ulcerous tracheitis and a severe tracheal obstruction by a mucus ball. To prevent further respiratory emergencies TTOT finally was stopped and the catheter replaced again by a nasal cannula. There is evidence that tracheal injury as well as the formation of mucus balls may be promoted by regular brushing the preliminary SCOOP-1 catheter which usually is left in place during the first weeks. As a result of this harmful experience, we recommend to reconsider carefully the indication for TTOT in patients with copious bronchial secretions and to avoid cleaning of the SCOOP-1 catheter with the rigid wire brush.

Aged↗
PubMed1996

Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women.

Hyperinsulinemia, a manifestation of insulin resistance, precursor of non-insulin dependent diabetes mellitus (NIDDM) and the hallmark of Syndrome X was assessed in 27 obese post-menopausal women. Insulin-like growth factor binding protein-1 (IGFBP-1), which had been shown previously to correlate inversely with insulin in animal and human studies, was evaluated as a diagnostic marker for abnormal glucose stimulated area under the curve (AUC) insulin (defined a priori as > or = 100 microU/ml). We performed analysis of variance and logistic regression to assess IGFBP-1 and other study covariates, including body mass index, blood pressure, lipids and measures of glucose and insulin in hyperinsulinemic vs. normal women and evaluated performance characteristics (sensitivity, specificity, positive and negative predictive values and accuracy rates). The mean IGFBP-1 was 6.1 ng/ml (95% confidence interval (CI) 3.1 to 8.9) for the hyper-insulinemic women compared to 33.5 ng/ml (CI 15.8 to 51.2) for normal women (P = .0027). At a cutoff point of 15ng/ml, which was selected to correspond to the lower 95% confidence limit for the normal study population, IGFBP-1 was abnormal in all 13 women with hyperinsulinemia and 4 women with normal insulin levels (sensitivity 100%, specificity 69%; positive predictive value 76%, negative predictive value 100%, diagnostic accuracy rate 85%). Logistic regression models indicated that, of all study covariates, IGFBP-1 was the best predictor variable for AUC-insulin as a binary dependent variable. These results suggest that IGFBP-1 may be a simple serum marker for hyperinsulinemia in a subpopulation of obese menopausal women.

Biomarkers↗
PubMed1996

[Local efficiency of percutaneous radiotherapy in lung cancer. Analysis of 215 repeated bronchoscopies in relation to applied radiation dosage].

PURPOSE: During a locoregional radiotherapy with curative attempts of lung cancer patients bronchoscopic examinations with biopsies and/or cytologic lavages were repeated to assess the accuracy of limiting the total dose to 60 Gy. In order of the applied dose macroscopic changements of the endoluminal tumor and microscopic elimination should be made out. The correlation between macro- and microscopical regression should allow a statement about reliability of single results. The clinical course and a conventional thoracic X-ray examination seemed to be a to large-meshed screen to evaluate the effect at the end of therapy. The aim was to improve the criterias of success and to adapt and optimize the radiation dose individually. PATIENTS AND METHODS: The prospective, together with the pneumologists, defined treatment concept included the repetition of bronchoscopic evaluations after the application of 60 Gy and 80 Gy. These radiation doses from 60 Gy up to 80 Gy have been given with a shrinking-field technique to the mediastinum and the primary. In order to record statistically the optical tumor changements we were urged to create a so-called bT-score. The structure of this score was orientated towards the periphery of the tracheobronchial tree. RESULTS: Hundred and forty-four patients with endoscopically and histologically verified bronchogenic carcinomas were treated. On the subjects 215 re-bronchoscopies accomplished with biopsies were performed and allowed to analyze the macro- and microscopical behavior under treatment. A histological/cytological elimination of tumor was achieved after 60 Gy in 35.1%, after 80 Gy in 62.3%. Macroscopically no tumor was visible after 60 Gy in 43.6%, after 80 Gy in 82%. A correlation between identical micro- and macroscopical observations was only seen in 61%, respectively in 71%. CONCLUSIONS: The escalation of the radiation dose from 60 Gy up to 80 Gy with shrinked fields could increase the local tumor sterilization rate by 1.8 times from 35.1% to 62.3%. The refining and completion of usually known parameters by endoscopical and histological examinations seems to be an acceptable way to define individual radiation doses. The quality of the performed therapy can be better determined. A predestination of the total dose to a limit of 60 Gy does not ensure a macro- and microscopical elimination of the tumor and may be inferior to an individually adaptation of the dose.

Adenocarcinoma↗
PubMed1996

[Surgical development in free flaps as exemplified by repair of tissue defects of the skull].

At the time of the introduction of microvascular techniques to reconstructive surgery twenty years ago, priority was given to the free groin flap for coverage of large and problematic defects of the skull. At that time, we reported about our surgical concepts (Frey et al., 1981). In the meantime, our concept of soft-tissue reconstruction in the skull region by microvascular free flaps has evolved during the past fifteen years. The favoring of the free latissimus dorsi-muscle flap and its coverage with split-thickness skin grafts is due to the following advantages: Muscle tissue with its excellent vascularisation solves defect problems even under extremely difficult local conditions. The large diameter of the vessels of the flap and the long, anatomically constant vascular pedicle guarantees safety of this operative procedure. The dimensions and thickness of the free muscle flap can be nicely adapted to the convex surface of the skull. The surface of the muscle flap is covered with split thickness skin grafts and demonstrates resistance to chronic mechanical stress and shows good aesthetic appearance.

Adolescent↗
PubMed1995

Crystal structure of the nickel-iron hydrogenase from Desulfovibrio gigas.

The X-ray structure of the heterodimeric Ni-Fe hydrogenase from Desulfovibrio gigas, the enzyme responsible for the metabolism of molecular hydrogen, has been solved at 2.85 A resolution. The active site, which appears to contain, besides nickel, a second metal ion, is buried in the 60K subunit. The 28K subunit, which coordinates one [3Fe-4S] and two [4Fe-4S] clusters, contains an amino-terminal domain with similarities to the redox protein flavodoxin. The structure suggests plausible electron and proton transfer pathways.

Amino Acid Sequence↗
PubMed1995

Losartan in heart failure. Hemodynamic effects and tolerability. Losartan Hemodynamic Study Group.

BACKGROUND: The aim of the present study was to assess the short- and long-term effects of multiple doses of the angiotensin II receptor antagonist losartan in heart failure. METHODS AND RESULTS: A multicenter, placebo-controlled, oral, multidose (2.5, 10, 25, and 50 mg losartan once daily) double-blind comparison in patients with symptomatic heart failure and impaired left ventricular function (ejection fraction < 40%). Invasive 24-hour hemodynamic assessment was performed after the first dose and after 12 weeks of treatment. Clinical status and tolerability of treatment with losartan over the 12-week period were also evaluated. One hundred fifty-four patients were enrolled, of which 134 met the protocol criterion of baseline pulmonary capillary wedge pressure > or = 13 mm Hg. During short-term administration, systemic vascular resistance (SVR) (largest reduction against placebo of 197 dyne.s-1.cm-5 at 4 hours) and blood pressure fell significantly with 50 mg, lesser decreases were seen with 25 mg, and no discernible effects were seen with 2.5 and 10 mg. After 12 weeks of treatment, similar effects were seen on SVR and blood pressure (maximal fall in SVR against placebo, 318 dyne.s-1.cm-5 at 5 hours with 50 mg). In addition, pulmonary capillary wedge pressure fell with 2.5, 25, and 50 mg (largest reduction against placebo of 6.3 mm Hg at 6 hours with 50 mg), cardiac index rose with 25 and 50 mg, and heart rate was lower with all active treatment groups. Active treatment was well tolerated, and excess cough was not reported. CONCLUSIONS: This study showed that oral losartan administered to patients with symptomatic heart failure resulted in beneficial hemodynamic effects with short-term administration, with additional beneficial hemodynamic effects seen after 12 weeks of therapy. Clear effects were seen with both 25 and 50 mg, with the greatest effect seen with 50 mg.

Aged↗
PubMed1995

Expression of a cytochrome P450 gene family in maize.

Maize seedlings, like seedlings of many other plants, are rich in cytochrome P450 (P450) enzyme activity. Four P450 genes (CYPzm1-4), isolated from a seedling-specific cDNA library, are characterized by a transient and seedling-specific expression pattern. The maximum steady state mRNA levels are reached at 3 days in root and at 7 days in shoot tissue, respectively. All four genes belong to one gene family and are closely related to the CYP71 family of plant P450 genes, which includes the enzymes of the ripening avocado fruit (CYP71A1) and eggplant hypocotyls (CYP71A2, A3, A4). The expression of these related P450 genes in monocot and dicot plants indicates that these enzymes play a significant role in plants; however, the in vivo enzyme functions are unknown. The divergence of the four members of the maize gene family is sufficiently high to account for different substrate and/or reaction specificity. Although the general expression pattern of the four genes is identical, the maximum steady-state mRNA levels vary in different maize lines. In situ hybridisation reveals the highest mRNA levels in the coleoptile, the first developed leaflets, the ground tissue of the nodular complex, and in the cortex and pith of the region of cell division in the root. The mapping of the maize CYPzm genes shows that, as in animals, P450 genes of the same family can be clustered. The presence of the CYPzm gene cluster in maize argues for generation of distinct plant P450 gene families by gene duplication.

Amino Acid Sequence↗
PubMed1995

Progression and regression by verapamil of vitamin D3-induced calcific medial degeneration in coronary arteries of rats.

Vitamin D3-induced mural calcification represents an animal model for investigating experimental calcium (Ca) overload and calcification of arterial walls. In this study, long-term progression of calcific degeneration in coronary arteries of rats after one intoxication with vitamin D3 was examined, as well as possible regression of preestablished mural Ca overload with the Ca antagonist verapamil. Sprague-Dawley rats were treated with one intramuscular (i.m.) overdose of vitamin D3 [300,000 IU/kg body weight (b.w.)]. Oral verapamil therapy (100 mg/kg/day b.w. for 24 weeks) was initiated 14 days after the vitamin D3 intoxication. Arteriosclerotic alterations were verified by microchemical analyses of tissue Ca and of cholesterol contents with atomic absorption spectroscopy (special graphite tube technique) and gas chromatography, respectively, and by standard histological techniques. Serum lipids were determined by sequential ultracentrifugation. Between week 3 and week 26 after the vitamin D3 injection, a progressive Ca incorporation from 448.8 +/- 110 to 1,310 +/- 166.3% of control values (i.e., coronary Ca content in 32-week-old untreated control rats = 100%) was observed, associated with calcific morphological lesions, and reactive intimal plaque formation. Verapamil prevented this progression and induced a regression of preestablished mural Ca overload. Therefore, the coronary Ca content after 24 weeks of verapamil treatment amounted to only 146.3 +/- 53.8% of controls. The data indicate that an initial calcific lesion of coronary arteries may serve as crystallization nucleus for advancing Ca overload and morphological alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Which changes occur in nerve grafts harvested with a nerve stripper? Morphological studies].

A histological and morphometric study was undertaken in order to evaluate the alterations in sural nerves harvested for nerve grafting using a nerve stripper. In 19 nerves biopsies were taken from the proximal and/or the distal end of the stripped nerve graft. Cross sections were examined for alterations of the perineurium and the myelin sheaths. In four nerves alterations within the perineurium were found, which affected 37% of the endoneural cross-sectional area on the average. In all specimens, the perineurial sheath was seen to be intact. The results of the present study suggest that harvesting of a nerve graft using a stripper does not cause major injuries to the graft and therefore successful neurotization of the graft should not be impaired.

Humans↗
PubMed1994

Crystal structure of the ferredoxin I from Desulfovibrio africanus at 2.3 A resolution.

The crystal structure of the ferredoxin I from the sulfate-reducing bacterium Desulfovibrio africanus (DaFdI) has been solved and refined by X-ray diffraction. The crystals are orthorhombic with a = 96.6 A, b = 58.1 A, and c = 20.7 A, space group P2(1)2(1)2, and two ferredoxin molecules per asymmetric unit. The initial electron density map has been obtained by combining phasing by molecular replacement methods, anomalous scattering, and noncrystallographic averaging. The final crystallographic R factor is 0.182 with 10-2.3 A resolution data. In parallel, the amino acid sequence was redetermined. This showed that DaFdI contains 64 residues (instead of 61) including one free cysteine, one histidine, and one tryptophan in the C-terminal part of the molecule. The current molecular model includes the two molecules of the asymmetric unit, 67 water molecules, and one sulfate ion. The DaFdI overall folding very closely resembles that of ferredoxins of known structure. Comparisons with the single cluster ferredoxins from Desulfovibrio gigas and Bacillus thermoproteolyticus show that the presence or the absence of a disulfide bridge does not significantly affect the folding of the other half of the molecule, including the characteristic alpha-helix of the single cluster ferreddoxins. Like other ferredoxins or analogs, the [4Fe-4S] iron--sulfur cluster presents, at 2.3 A resolution, a cubane-like geometry. By contrast, its immediate environment is different as it includes, besides the four cysteic sulfur ligands, the sulfur atom of the free cysteine. This sulfur atom, which is buried within the protein, is in van der Waals contact with one labile sulfur of the cluster and one liganded cysteic sulfur. The association of a [4Fe-4S] cluster with one free cysteic sulfur is similar to that previously found in both X-ray structures of Azotobacter vinelandii and Peptococcus aerogenes [Stout, C. D. (1989) J. Mol. Biol. 205, 545-555; Backes, G., et al. (1991) J. Am. Chem. Soc. 113, 2055-2064]. Chemical sequence analysis suggests that this characteristic [4Fe-4S] cluster sulfur environment is widely distributed among ferredoxins.

Amino Acid Sequence↗
PubMed1994

Water structure associated with proteins and its role in crystallization.

X-ray or neutron diffraction studies have shown, at the atomic level, that water molecules occupy well determined sites inside or at the surface of biological macromolecules. These water molecules are constitutive of biomolecules and play a crucial role in their structural and functional properties. Upon crystallization some water molecules are either desolvated or involved in crystal packing. The role of water in determining crystal packing has been experimentally confirmed by several X-ray analyses.

Journal Article↗