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D Matthias

Publications and source records attributed to D Matthias.

At least 19 recordsLinked to original sources
PubMed2004

Transdermal testosterone gel: pharmacokinetics, efficacy of dosing and application site in hypogonadal men.

OBJECTIVE: To determine the regimen that would most effectively maintain serum testosterone concentrations in treated hypogonadal men within the normal reference range of 3-11.4 microg/L. PATIENTS AND METHODS: Eighteen men aged 24-69 years with either primary or secondary hypogonadism participated in and 16 completed a randomized, six-treatment regimen, three-period (phase), three-way matrix-type crossover study. A 1% and 2% testosterone gel (CP601, Cellegy Pharmaceuticals, Inc., San Francisco, USA) was administered either once or twice daily transdermally at different body sites to determine optimal dosing, application sites, and its pharmacokinetics and tolerability in hypogonadal men. Treatments A-F included 1 g of 1% and 2% gel that was equivalent to 10 or 20 mg of testosterone, applied once or twice daily to the skin of either the thigh or the upper arm. Six men also participated in a study of 3 g of 2% gel that was equivalent to 60 mg of testosterone applied once daily, half on each thigh. Pharmacokinetic variables were calculated for testosterone for each man in each treatment period and the results analysed by anova. RESULTS: In general the higher dose regimens produced higher serum concentrations of testosterone; the 3 g/2% dose was most successful in maintaining serum testosterone within the normal reference range. The average testosterone concentration (C(avg)) was 6.52 microg/L and all men had a C(avg) of > 3.0 microg/L. The prediction of all men achieving a C(avg) of > 3.0 microg/L was 96%. The mean minimum concentration (C(min)) was 3.83 microg/L and half the patients had a C(min) of > 3.0 microg/L. Most men had serum testosterone levels within the normal reference range throughout the 24 h, and the treatment was well tolerated. CONCLUSIONS: The 3 g/2% dose applied to the skin daily resulted in serum testosterone in the normal reference range in most hypogonadal men. Dose adjustments to either a lower or higher dose should shift serum testosterone concentration to the desired range in those who do not achieve this range with this dose.

Administration, Cutaneous↗
PubMed2001

A closer look at chemotherapy errors.

Lehigh Valley Hospital and Health Network, a 700-bed tertiary care system, created a reference guide as part of its chemotherapy error prevention initiative.

Humans↗
PubMed2001

One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women.

The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 +/- 2.0 yr, 71.8 +/- 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 microg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 +/- 11.9 ng/mL) at 6 months (330.0 +/- 52.8) and 12 months (297.7 +/- 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

Affect↗
PubMed1996

Homocysteine induced arteriosclerosis-like alterations of the aorta in normotensive and hypertensive rats following application of high doses of methionine.

Following oral administration of methionine in high doses to normotensive (NR) and spontaneously hypertensive (SHR) rats, its degradation product, homocysteine (HC), which is markedly elevated in serum, exerts an angiotoxic action directed to the aorta. This is accompanied by considerable loss of endothelium and degeneration, partly with dissolution of the media cells with formation of characteristic processes of the degenerating mitochondria, and by elevated HC and cystathion (CT) values in the aortic wall. At the arterial vessels of other organs similar alterations did not occur. There are quantitative differences between NR and SHR. In SHR, serum shows higher HC and CT concentrations than in NR, and the methionine-related aortic alterations are considerably more pronounced and develop earlier, with the additional formation of connective tissue. Here, a certain dependence on the methionine dose is noted, in contrast to NR, for which the magnitude of the reaction appears to be more related to the length of time of methionine application. Additional administration of atherogenic substances (cholestane-3 beta, 5 alpha, 6 beta-triol, cholesterol, angiotensin II, cholic acid with methylthiouracil) in SHR causes an exacerbation of the methionine-related aortic alterations. Only cholestane-triol has the same effect on the aortic wall in NR and SHR, with more accentuation in SHR. Cholestane-triol has, in NR as well as in SHR, a high coincidence with methionine-induced morphological reactions including the formation of mitochondrial processes. Simultaneous application of these two substances did not cause a potentiation of the effect. High doses of cholesterol bring about aortic alterations in SHR but not in NR. Thus, in addition to the disorder of fat and carbohydrate metabolism, disturbed protein metabolism is of decisive importance as a risk factor for coronary and other vascular diseases.

Angiotensin II↗
PubMed1994

Serum erythropoietin levels in patients with solid tumours.

Patients with malignant disease frequently develop anaemia. To investigate the role of erythropoietin (EPO) in this anaemia, serum levels were determined in patients with solid tumours. The study population consisted of 84 patients (44 males, 40 females) with solid tumours and 99 healthy control subjects, and 13/84 patients were anaemic. Serum EPO was clearly elevated in the anaemic tumour patients, but this increase was less than in patients suffering from iron deficiency anaemia. As in iron deficiency anaemia, the correlation between EPO levels and haemoglobin values was inverse. When compared to healthy control subjects, the levels of EPO in the tumour patients without anaemia were decreased. We conclude that there may be an inhibition in the expression or secretion of EPO in patients with solid tumours which, as yet, has not been further defined. Based on this, the treatment of anaemia in cancer patients with erythropoietin appears promising.

Adult↗
PubMed1987

Action of cholestane-3 beta,5 alpha,6 beta-triol on rats with particular reference to the aorta.

Cholestane-3 beta,5 alpha,6 beta-triol, administered orally to rats in different doses and for varying lengths of times, effected toxic cell damage on aortic smooth muscle cells and endothelium. Cholesterol, applied in the same doses, did not lead to appreciable alterations of the aorta. After parenteral application of lipids with simultaneous administration of cholestane-triol there were no demonstrable fat deposits in the damaged aortic wall with angiotensin II (AII) induced hypertension. Thus, there was no recognizable influence of hypertension on increased fat passage in the arterial wall, or any action of lipids to enhance the permeability of vessels. However, the hypertension had an exacerbating effect in so far as in animals with AII-induced blood pressure rise alterations of the media were more pronounced after cholestane-triol, although we were unable to rule out a primary effect of AII. A potentiation of the cholestane-triol action by simultaneous application of cholesterol demonstrated for the rabbit did not occur in rats. Blood content was lowered mostly by cholestane-triol, also by cholesterol. HDL-cholesterol was little affected; almost no influence was observed in triglycerides. The strong cytotoxic action of cholestane-triol underlines its health-damaging role. Due to its action on the aorta of the rat, despite the animal's resistance to arteriosclerosis, involvement of this cholesterol derivative in the pathogenesis of arteriosclerotic alterations can not be excluded.

Administration, Oral↗
PubMed1984

Different behaviour of normotonous and spontaneously hypertensive rats with vitamin D intoxication.

Spontaneously hypertensive rats (SHR) were found to tolerate the consequences of vitamin D intoxication much better than Wistar Kyoto rats (WKY). This is obvious from the 10-fold higher death rate of WKY rats and from the considerable differences of the tissue reactions occurring in the aorta, the cardiac muscle and the arterial vessels between WKY rats and SHR. Thus, myocardial alterations are much rarer in SHR; this holds also for the aorta calcification which is less pronounced in SHR and which is age-dependent in so far as it is almost absent from one year onward. Giant granulomas as a result of vitamin D intoxication were found in juvenile SHR at a time where they would otherwise no yet have occurred at a frequency observed in old untreated SHR. Common to both WKY rats and SHR is the formation of vascular alterations (plasmatic vasculosis) which reveal--though less pronounced with SHR--the angiotoxic action of vitamin D. For these considerable differences in the behaviour of WKY and SHR in vitamin D intoxication the different Ca-binding and transport properties of the arterial plasma membranes should be responsible, which is likely to be due to a defect in the Ca-transport mechanism of the smooth vascular muscle. The importance of these findings for the use of vitamin D intoxication in arteriosclerosis research as well as for studies on the pathogenesis of permeability disorders and alterations of the arterial vascular system is pointed out.

Aging↗
PubMed1983

[Autoradiographic analysis of proliferative processes in the arterial terminal vascular system in experimental hypertension].

The participation of various vascular wall cells in the proliferation process and their distribution in the arterial terminal vascular bed were investigated by 3H-thymidine autoradiography in rats during an acute angiotensin hypertension. The results show that both the proliferative pattern and the distribution of labeled cells have distinct differences according to the functional importance and the histologic structure of the vessels. A common feature of all vascular parts is the enhancement of the proliferation of smooth muscle cells. In particular, the proliferation is increased in the arterioles, suggesting a structural adaptation to the raised vascular tonus. The strongly altered endothelium of peripheral vessels show a retarded reparative cell proliferation. This implies a considerable risk factor for the development of an arteriosclerosis in the circulatory periphery.

Acute Disease↗
PubMed1983

[Functional and structural vascular reactions following intermittent administration of angiotensin in spontaneously hypertensive rats].

In order to find out whether after repeated intermittent treatment with angiotensin-II (A-II) the hypertrophically and hyperplastically altered vascular walls show the same adaptation as with normotensive rats (NR), investigations were performed on 44 male 16-week-old spontaneously hypertensive rats (SHR) (Okamoto-Aoki). In three repeated series daily doses of 0.15 mg depot A-II, the lowest blood pressure effective dose attended by vascular and organic reactions, were applied for 5 days. We found that the functional reactivity of the arterial vascular system in SHR was retained after repeated intermittent administration of A-II despite the hypertrophically hyperplastic processes. This was equally true for the structural reactivity as shown by the occurrence of equal vascular alterations following each new injection series as those which appeared after the first administration of A-II. Thereafter, no structural adaptation of the arterial vascular system occurred in the SHR. The extensive A-II induced vascular alterations did not lead in SHR to additional sustained increase in blood pressure. On discontinuation of A-II treatment the A-II-induced vascular alterations reconverted within a month, even after repeated intermittent A-II treatment, despite the existence of high blood pressure. They are thus reversible. A similar remission is observed also with the A-II-induced myocardial alterations. It thus becomes obvious that, with maintained reactivity of the vascular walls against A-II and with an existing hypertension, R-A-S stimulating factors obviously are able to induce structural alterations at the arterial vessels.

Angiotensin II↗
PubMed1981

[Functional and structural behavior of the cardiovascular system of normotonic and spontaneously hypertensive rats following chemical sympathectomy and angiotensin administration].

The non-cleared influences of the sympathetic nervous system [sN] on structural reactions of SHR and on the direct cardiac effects of AII and the structural vascular behavior were investigated. In 67 spontaneously hypertensive rats (Okamoto-Aoki) and 55 normotonic Wistar rats (NR) the blood pressure behaviour, the structural vascular and organ reactions and the noradrenaline (NA) content of the myocardium were examined with an intact sympathetic nervous system as well as after its almost complete elimination by chemical sympathectomy with 6-hydroxy-dopamine (6-OH-DA). Moreover, the functional and structural responsiveness of the arterial vessels of sympathectomized animals to angiotensin II administrations was investigated. 6-OH-DA in the dosage applied, induces during its time of action in NR a smaller, in SHR a larger decrease of blood pressure and, presumably induced by intense NA-depletion of the myocardium, myocardial alterations. Despite extensive AII-induced alterations of the already early hypertrophically-hyperplastically changed vascular wall, the structural and functional responsiveness of the arterial vascular system was maintained even after sympathectomy, and the sensitivity of the SHR to AII remained. For maintaining hypertension, the cooperation of structural and functional influences is necessary, as is indicated by the reduction of blood pressure in sympathectomized SHR and its regular return to the daily initial values of normotonic animals under additional AII administration. Besides the vascular alterations contributing to the exacerbation of the hypertension, here the sNS is of essential importance. For obtaining a total pressure effect of AII the sNS obviously has not necessarily to be intact, though its activity state can influence the responsiveness of the arterial vascular system to AII. The reduction of the sympathicotonus by sympathectomy seems to have a protective effect on the development of AII-induced structural vascular alterations; in contrast to the myocardium in SHR, in which it induces an exacerbation and an increase in the AII-induced myocardial alteration. These findings obtained from rats are supposed to be important also for the essential hypertension in man. By maintaining the functional responsiveness of the arterial vascular system, antihypertensives which react with the different parts of the sNS cab become effective while structural alterations of the vascular wall can be influenced, too. The possibility of the simultaneous development of myocardial alterations should be taken into special consideration.

Angiotensin II↗
PubMed1981

[Functional and structural reactivity of the arterial vascular system to angiotensin II in spontaneously hypertensive rats].

In 55 spontaneously hypertensive rats (SHR) (Okamoto/Aoki) and 63 normotensive Wistar rats (NR) receiving Angiotensin-II, hypertrophically-hyperplastically altered vessels of SHR were tested for their functional and structural reactivity and compared with the behaviour of the arterial vascular system at essential hypertension of man. After 5 days of treatment with 0.15 and 0.02 mg depot-Angiotensin II (A-II) SHR showed an increase in systolic and, with 0.15 mg A-II, even in diastolic blood pressure and bradycardia. At either A-II dosage, plasmatic vasculoses were found at the arterioles and small arteries both in SHR and similarly treated NR, though in higher frequency and in a larger quantity in SHR, as it was the case also with myocardial alterations. Although in the arterial vessels in SHR there developed already primary hypertrophically-hyperplastic wall alterations, A-II application led to functional and structural reactions. Consequently, an additional vasoconstrictor stimulus does not lead in SHR to a process comparable with essential hypertension in man, but merely to reversible, acute vasculopathies.

Angiotensin II↗
PubMed1980

Pathomorphological reactions of myocardium and intramural vessels of rats in the course of hypertension induced by depot angiotensin. Autoradiographic, light and electron microscopic investigations.

Autoradiographic, light and electron microscopic investigations on the effect of depot angiotensin on the hearts of rats suggested that the myocardium and the intramural vessels reacted with an activation of the mesenchymal and DNA metabolism already 3 hrs, after the injection of depot angiotensin. The reactions in the capillaries and small arterioles were dominating. Degenerative alterations could be found in the cardiac muscle cells only 9 hrs. after injection and culminated in infarction-like necroses and intensive mesenchymal proliferation after the 4th A II injection. Despite further daily applications of A II the degenerative and necrotic myocardial alterations will extensively diminish until the 14th day of experiment, while the mesenchymal activation and the enhanced DNA synthesis in the vessels remained unchanged. Thus an initial stage with the development of disseminated muscle fibre necroses and infarction-like alterations and a stage of compensatory adaptation may be distinguished in the heart after depot angiotensin injections.

Angiotensin II↗
PubMed1977

[Pathomorphological reactions and noradrenalin content of the heart after administration of depot angiotensin in trained and untrained rats].

A 14-days' training of rats designed to adapt the animals to the procedure of blood-pressure measurement caused in the myocardium a decrease, in serum an increase in noradrenaline ( NA) content. The latter remained unchanged following 3 days of treatment with 2.5 mg depot angiotensin II (AII) but decreased by more than one-half in the myocardium of untreated animals, and increased in serum. Despite the considerable difference in myocardial NA content and blood-pressure behaviour, both trained and untrained rats showed the same morphological reactions following administration of A II. These myocardial alterations which largely correspond to the so-called epinephrine myocarditis should not therefore be due solely to NA action; rather, the involvement of A II should be considered also.

Adaptation, Physiological↗
PubMed1976

Ultrastructural investigation of peripheral arterial vessels in the cortex of rats with experimental hypertension.

The peripheral arterial blood vessels in the cerebrum of 36 experimental animals and 9 controls were studied by electron microscopy. In 5 rats of these renal hypertension was produced (the animals were sacrificed 3 to 15 days following the second operation). 24 animals were treated with depot angiotensin (0.02 to 2.5 mg/daily) for 3 hr up to 40 days, and 7 rats were neurotized for 1 to 41/2 months. The alterations of the cerebral vessels were distinctly different within these 3 models already in the early reactions. Thus, even in the first 14 days of the experiment with renal and angiotensinogenic hypertension alterations were observed that did never occur in the neurotized rats. There were always observed disturbances in permeability of the cerebral vessels, but they were never followed by such heavy wall insudations as usually noticed in the splanchnic vessels. The less frequent occurrence of hemorrhages and malacic processes in the rat brain is ascribed aside from the physiological properties of the brain supply, to genetic factors and the absence of arteriosclerotic burden to the vascular wall in the non-dietetically pretreated experimental animals.

Angiotensin II↗
PubMed1976

[Studies on the blood pressure effects of various high doses of angiotensin II in depot form in rats under defined conditions].

Daily s.c. injections of 0.02--10.0 mg angiotensin in depot form for 14 days caused in rats, under defined conditions, pronounced dose-dependent effects, with an unusual tolerance to the drug being observed. The behaviour of the systolic and diastolic blood pressure and heart rate allowed to define 4 dose ranges. In the lowest dose range of 0.02 mg angiotensin-II a lasting borderline hypertension with only straight-line changes of diastolic blood pressure and bradycardia were observed. The doses of 0.15--1.25 mg angiotensin-II caused a continual blood pressure rise and led, between day 4 and 6 of the experiment, to a pronounced lasting resistance high-pressure without appreciable changes in heart rate. The strongest resistance high-pressure, which occurred as early as on day 3, with pronounced tachycardia was achieved with a dose of 2.5 mg angiotensin-II. Higher doses produced pronounced tachycardia but no significant effects on blood pressure. The varying dose-dependent effects of depot angiotensin are discussed, and the possibility is pointed out to study by the angiotensin-II hypertension model various mechanisms of a long-time hypertensive dysregulation.

Angiotensin II↗
PubMed1976

[Angiotensin-induced hypertension in pigs].

In pigs receiving up to 14 days daily injections of depot angiotensin, repeated daily bloody measurements of the blood pressure at the carotid artery proved unsuitable because of ensueing septic processes, in contrast to the unbloody measurement at the caudal artery. The depot angiotensin, despite the use of preparations with varying content of angiotensin-II and carrier solution, caused immediately after the injections a very strong maximal rise in systolic and diastolic blood pressure that occurred also with longer periods of the experiment; this rise gradually diminished in the course of the day but remained mostly in the hypertonic range and showed daily initial values above normal. The pig proved to be much more sensitive to angiotensin than the rat, for instance. Despite the proved vasoconstricting action of angiotensin, light-microscopic alterations at the vessels, kidneys, and the myocardium could not be observed. Part of the arterioles showed an increased wall thickness in animals killed on the 8th and 15th day of the experiment. The differences in the pathomorphological and blood pressure behaviour from the rat are discussed. The first experimental results qualify the pig as an experimental animal for comparative hypertension studies.

Angiotensin II↗