Particular antihypertensive profile of amlodipine administered orally to Okamoto rats (SHRs) and NaCl-loaded salt-sensitive Dahl rats.
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Amlodipine↗
Biomedical subjects
M Frey
Publications and source records attributed to M Frey.
Protection of arterial and arteriolar wall structure by specific calcium antagonists.
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Animals↗
Effect of experimental heart failure on peripheral sympathetic vasoconstriction.
To investigate whether heart failure impairs peripheral sympathetic vasoconstriction, hindlimb vascular responses to lumbar chain stimulation (0.5-20 Hz) were studied in normal dogs and in dogs with chronic heart failure produced by rapid ventricular pacing. At lumbar chain stimulation rates of 0.5-3 Hz, hindlimb vascular responses were comparable in both groups. However, at stimulation rates of 5-20 Hz, vascular responses were significantly attenuated in the dogs with heart failure. Vascular responses to norepinephrine (0.1, 1, and 10 micrograms/min) were not altered. These findings suggest that chronic heart failure results in impaired sympathetic vasoconstriction, probably because of reduced neurotransmitter release. This abnormality may interfere with the capacity of the failing circulation to compensate for a low cardiac output and thereby intensify the severity of heart failure.
Animals↗
Restriction by nitrendipine of excessive concentration of free intracellular calcium ions in ventricular myocardium of hypertensive rats.
In earlier investigations it has been found that high arterial blood pressure of salt-sensitive DAHL rats (DAHL-S) that received a diet containing 8% NaCl could be normalized by chronic treatment with specific calcium antagonists, as for instance, nitrendipine or anipamil. Parallel measurements on heart and arterial vasculature with atomic absorption spectrometry revealed that there was a rise in absolute calcium content upon development of hypertension, whereas under the influence of nitrendipine, not only the blood pressure and heart weight but also myocardial (and arterial) tissue calcium content remained in the physiologic range. In the present study, an additional determination of the free intracellular calcium ion concentration with Ca-sensitive microelectrodes was carried out. For technical reasons, the measurements were restricted to isolated resting rat papillary muscles (stretched to optimal length in a perfusion bath of 1.5 ml at 30 degrees C in normal Tyrode solution). The impalement of the electrodes was considered adequate when the heights of Ca potential and membrane potential were constant for more than twenty minutes. In order to produce severe systemic hypertension, a group of six-week-old DAHL-S rats was fed with an 8% NaCl diet over five weeks. Another group of DAHL-S rats received additionally 150 mg/kg nitrendipine twice a day orally. Salt-resistant DAHL-R rats, also fed with an 8% NaCl diet, served as controls. The findings of this preliminary study are as follows (n = 5 in each group): (table; see text).
Animals↗
Survival of rough and smooth strains of Brucella abortus in bovine mammary gland macrophages.
Chronic bovine brucellosis is characterized by persistent infection of the mammary gland. The interaction of live Brucella abortus with bovine mammary gland macrophages was studied in vitro. Opsonization of smooth B abortus strain 2308 and rough strain 45/20 was required for phagocytosis by mammary gland macrophages. When opsonized with specific antiserum, strains 2308 and 45/20 stimulated a considerable oxidative burst when phagocytized by mammary gland macrophages. Intracellular survival rates for strain 2308 were significantly higher than those for strain 45/20. After being phagocytized, B abortus localized in phagosomes and phagolysosomes of mammary gland macrophages.
Animals↗
[Vascularized nerve transplant--theoretical advantages and disadvantages].
A survey of publications dealing with vascularized nerve grafts is given. The advantages and disadvantages are discussed by analyzing the published data. Until now the superiority of vascularized nerve grafts has not been proven by the published experimental and clinical results. This fact was underlined by the results of our own experimental investigations: In conventional nerve grafts performed on sheep it was shown that the functional results of reinnervation cannot be correlated to the degree of vascularization of the nerve graft or to number and morphology of the regenerated axons. Therefore, the indications for the clinical application of the vascularized nerve graft must be limited to the following conditions: Poorly vascularized recipient bed, thick nerve graft, unsuccessful previous conventional nerve grafting, and the necessity of vascular reconstruction at the same time.
Animals↗
[Radiotherapy of locally recurring colorectal tumors. Prognostic factors, follow-up diagnosis and results].
From 1979 through April, 1985, 74 patients were treated by percutaneous irradiation for local recurrences of colorectal carcinomas. The treatment consisted of a contralateral irradiation up to a dose of 40 Gy and a small-volume boost up to 60 to 66 Gy. In case of progressive remote metastases, the treatment was finished at 50 Gy. 53 patients received a dose of 50 Gy or more and were followed for at least six months. The decisive prognostic parameter was the presence of remote metastases when the recurrence appeared (n = 32). The median survival was six months, in patients without remote metastases at this moment it was 15 months. A complete or considerable relief of pain was obtained in 78%; it continued for a median period of 8.5 months, although most of the patients showed a new local tumor progression after an interval of three to 26 months. Computed tomography showed only small regressions or, in most cases, unchanged volumes of the tumors.
Aged↗
Rubredoxin from Desulfovibrio gigas. A molecular model of the oxidized form at 1.4 A resolution.
The crystal structure of rubredoxin from the sulfate-reducing bacterium Desulfovibrio gigas has been determined at 1.4 A resolution (1 A = 0.1 nm) by X-ray diffraction methods; starting with a model of the isostructural rubredoxin from Desulfovibrio vulgaris. Refinement of the molecular model has been carried out by restrained least-squares techniques and Fourier series calculations. The present model includes a formyl at the N-terminal end and 121 possible sites for solvent molecules with full or partial occupancy, which corresponds to the modeling of nearly all the solvent medium. The crystallographic R factor against the data with 10 A greater than d greater than 1.4 A with F greater than 2 sig(F), is 0.136; and R = 0.140 when all the data are considered. The estimated average root-mean-square (r.m.s.) error on the positional parameters is about 0.12 A. The overall structural features of this molecule are close to those of the two highly refined rubredoxins from Clostridium pasteurianum and D. vulgaris. Superposition of these two molecules on the rubredoxin from D. gigas shows in both cases an overall r.m.s. deviation of 0.5 A for the atoms in the main-chain and of 0.4 A for the atoms in the side-chains that make up the hydrophobic core. The iron atom is co-ordinated to four cysteine sulfur atoms forming an almost regular tetrahedron, with Fe-SG distances ranging from 2.27 A to 2.31 A and angles varying from 103 degrees to 115 degrees. The intramolecular hydrogen-bonding pattern is quite comparable to those found in other proteins refined at high resolution. All the polar groups are involved in hydrogen bonds: intramolecular, intermolecular or with solvent molecules. The main structural differences from the other rubredoxins are in the nature and the distribution of some of the charged residues over the molecular surface. The possible influence of several structural factors on the intramolecular and intermolecular electron transfer properties such as the NH...SG bonds, the solvent exposure of the redox center, and the aromatic core is discussed. The conservation, during evolution, of a ring of acidic residues in the proximity of the FeSG4 center suggests that this ring may be implicated in the recognition processes between rubredoxins and their functional partners.
Desulfovibrio↗
Crystallization, preliminary X-ray study and crystal activity of the hydrogenase from Desulfovibrio gigas.
Hydrogenase (EC 1.12) from Desulfovibrio gigas is a dimeric enzyme (26 and 62 (X 10(3) Mr) that catalyzes the reversible oxidation of molecular hydrogen. Single crystals of hydrogenase have been produced using the hanging drop method, with either PEG (polyethylene glycol) 6000 or ammonium sulfate as precipitants at pH 6.5. X-ray examination of the crystals indicates that those obtained with ammonium sulfate are suitable for structure determination to at least 3.0 A resolution when synchrotron radiation Sources are used (1 A = 0.1 nm). The crystals are monoclinic, with space group C2, and cell dimensions a = 257.0 A, b = 184.7 A, c = 148.3 A and beta = 101.3 degrees, and contain between four and ten molecules per asymmetric unit. The enzyme can be reactivated within the crystals under reducing conditions without crystal damage.
Crystallography↗
Future directions in the use of calcium antagonists.
There are several reasons to expect that the use of calcium antagonists to treat cardiovascular disease will continue to spread. The scope of indications for existing calcium antagonists is expanding; new calcium antagonists with more selective organ affinity are being developed and these drugs may be given over the long term for prophylaxis against hypertension and for vasoprotection. In all probability, the long-term prophylactic use of calcium antagonists offers the most promise. The long-term effects of calcium antagonists for treating hypertension as well as for preventing vascular damage due to calcinosis and sclerosis will be discussed.
Animals↗
New aspects of excitation-contraction coupling in cardiac muscle: two types of Ca++ entry promotion with and without involvement of cyclic AMP and Mg++ ions.
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Action Potentials↗
Perspectives of radiotherapy.
The 5 years' survival rate of all cancer patients is 35-45%. In that survival rate radiotherapy takes part in 15%. By further development of radiological methods and techniques radiotherapy gains significance in the recent time. Optimizing radiation planning and tactics, all modern imaging techniques are applied consequently. The radiotherapist must be able to asses their immanent specifity which should remain object of the radiological training, even if separated into therapy and diagnostics. Dose distribution is calculated by computer; three-dimensional planning is done in tumors of the mediastinum, oesophagus carcinoma and paraaortic lymphomas. Critical description of radiation techniques, results, problems and prognoses are given by results in tumors of the epipharynx and gastric cancer. After-loading, done until now only in gynaecological tumors, is performed in recurrences of pharyngeal tumors by individually shaped applicators. Reducing the number of therapy failures as well as possible, the application of higher tumor doses, new kinds of rays as neutrons and combinations with physical and chemical methods is outlined. Modifications of radiation volumes are discussed, especially the irradiation of the complete abdomen in ovarian cancer, the irradiation of the complete body surface by electrons in mycosis fungoides, and the total body irradiation prior to autologue bone marrow transplantation. Modifications of fractionation are shown in short-time radiation of bone metastases and single-time radiation of brain lesions. Low penetrating electron therapy facilitates intraoperative single-time irradiation. Because of higher biological efficiency neutrons and heavy ions allow to irradiate low sensible tumors or recurrences embedded in fibrotic tissue respectively. The combination with hyperthermia yields good results in tumors of the head and neck with better local response and total remissions of 59%. There are potentials in synchronising with chemotherapeutics. Remissions of different duration were achieved in 190 patients. Because of neutrotoxicity there are still problems in applicating radiosensitizers. New methods are applied treating endocrine active tumors by labelled hormone precursers.
Brachytherapy↗
[Comparative study of primary and secondary management of flexor tendon injuries].
In 1974 a replantation service started at the authors' department. Before that time the treatment of flexor tendon injuries was mainly performed secondarily. Therefore, the authors had the opportunity to compare patients after primary and secondary surgery. In 52 primarily and 22 secondarily treated patients the technique of Kleinert was used. Following issues were investigated: functional results, decrease of grip strength, influence of early mobilization on sensibility restoration in cases of nerve injury, relation between sensitivity to cold and vessel and nerve injuries, duration of physiotherapy and disability. The damage of only one finger might lead to decrease of grip strength. Primary surgery was superior to secondary surgery. Early mobilization in cases of additional nerve injuries did not affect sensibility restoration. Poor sensibility increased the chance of cold sensitivity. The duration of physiotherapy and of disability depended on the need for second procedures such as tenolysis which was more common in the group of secondarily treated patients.
Adolescent↗
State of the art of implanted multichannel devices to mobilize paraplegics.
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Adult↗
Renal failure due to lymphomatous infiltration of the kidneys. Report of three new cases and review of the literature.
Three new cases of renal failure due to lymphomatous infiltration of the kidneys are described and the clinical features of 14 similar patients in the literature are reviewed. The diagnosis of renal failure secondary to lymphomatous infiltration was made by ruling out other causes of renal failure and demonstrating prompt improvement in renal function after systemic chemotherapy or local irradiation of one or both kidneys. Histiocytic lymphoma was the most common underlying disease. In the setting of diffuse lymphoma with other causes of renal failure reasonably excluded, radiographic demonstration of enlarged kidneys without obstruction suggests the need for intensive combination chemotherapy in most cases.
Aged↗
Antihypertensive and arterial anticalcinotic effects of calcium antagonists.
In vascular smooth muscle (as in myocardial fibers), a transmembrane supply of calcium ions is required for active tension development. In consequence, calcium antagonists possess a wide scope of action against practically all types of vasoconstrictor or spastic responses of arterial smooth muscle cells. Calcium antagonists are the drugs of choice for the treatment of coronary, pulmonary, cerebral or mesenteric artery spasms. Other clinically important targets of calcium antagonists are the systemic resistance vessels that rapidly dilate, which explains why calcium antagonists are increasingly used for the treatment of acute hypertensive crises as well as for antihypertensive long-term therapy. In physiologic experiments, calcium antagonists normalize the blood pressure of spontaneously hypertensive rats, neutralize various vasoconstrictor agents (if they act via promotion of transmembrane calcium influx), and greatly reduce the sensitivity of the systemic arteries and arterioles to mechanical stimuli, which can produce additional vasoconstriction, if a rise in intraluminal pressure stretches the vascular wall (Bayliss effect). Calcium antagonists also prevent noxious arterial calcium overload in animals. In the human arterial walls, at an advanced age, pathogenic degrees of calcium accumulation are reached and probably play an important role in both the development of hypertension and of arteriosclerotic lesions. Hypertensive rats exhibit progressive arterial calcium overload that responds well to the calcium antagonists nifedipine, nimodipine, nisoldipine and nitrendipine, as well as to verapamil.
Aging↗
Long-term performance of polyurethane pacing leads: mechanisms of design-related failures.
Environmental stress cracking has been identified as a crack propagating mechanism in polyurethane-insulated, heart pacemaker leads, which is directly related to specific lead design parameters. Lead designs imposing excessive stress on the polyurethane insulation through an interference fit between the coil and polymer have demonstrated insulation failures. Conversely, low-stress designs have shown virtually no insulation problems. The higher-stress designs have used organic solvents to facilitate coil placement during manufacturing, which may result in lowering the polymer's ability to resist the higher stress. In addition, a specific silver-containing coil wire composition has been found to galvanically corrode upon body fluid intrusion into the lead, ionizing the silver. These ions interact with the polyurethane polymer resulting in the loss of polymer strength. All polyurethane lead failures to date have been specific to high stress and/or chemical interaction. Leads using low-stress designs and nonreactive coil wire compositions continue to demonstrate a positive clinical experience.
Animals↗
[Value of conventional tomography and computer tomography in therapy-resistant diseases of the paranasal sinuses].
The informational value of conventional tomography as primary diagnostic method is pointed out in diseases of nasal sinuses resistant to therapy. 5 cases demonstrate the additional information gained by CT-differentiation of soft tissue structures, intraorbital and intracranial expansion. In 78.4% of the examined group of 51 patients conventional tomography allowed the diagnosis of a process limited to the nasal sinuses, further evidence by CT could be omitted. In 11 patients examined by CT additionally, the expansion of the process was defined more precisely and the assumed intraorbital and intracranial growth confirmed.
Adolescent↗