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Biomedical subjects

Michael Weber

Publications and source records attributed to Michael Weber.

88 records · Page 5Linked to original sources
PubMed2002

Progesterone inhibits human infragenicular arterial smooth muscle cell proliferation induced by high glucose and insulin concentrations.

INTRODUCTION: Diabetes mellitus is a significant risk factor for atherosclerotic peripheral vascular disease. Hyperglycemia and hyperinsulinemia, as encountered in patients with type II diabetes, have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation, a paramount feature in atherosclerosis. Female sex hormones, such as estrogen, have been suggested to inhibit VSMC proliferation. However, the role of progesterone, particularly in patients with diabetes mellitus, has not been examined. Therefore, we studied the effect of progesterone on VSMCs exposed to various concentrations of glucose and insulin. METHODS: Human infragenicular VSMCs isolated from the tibial arteries of five male patients with diabetes undergoing lower extremity amputation were used. Immunocytochemical studies with confocal microscopy were performed for progesterone receptor identification in these VSMCs. Cells were grown to subconfluence, followed by exposure to deprived media with various glucose (100 and 200 mg/dL) and insulin (no insulin and 100 ng/mL) concentrations. Cells were then additionally exposed to physiologic progesterone (10 ng/mL, progesterone group) and compared with a no-progesterone group. Cell count and methyl-(3)H-thymidine incorporation were used to determine cellular proliferation. Cell count with hemocytometry was performed on day 6. DNA synthesis as reflected through methyl-(3)H-thymidine incorporation was measured at 24 hours. RESULTS: Immunocytochemical studies with confocal microscopy showed cytosolic progesterone receptors. The no-progesterone group showed a significant rise in cell count (P <.05) at all concentrations of glucose or insulin compared with the control group containing 100 mg/dL glucose concentration. The no-progesterone group also showed a significant rise in thymidine incorporation (P <.05) in the 100 mg/dL glucose-100 ng/mL insulin group and the 200 mg/dL glucose-100 ng/mL insulin group compared with the 100 mg/dL glucose group. In the cell count studies, progesterone significantly inhibited cellular proliferation in several settings. All cell groups cultured with insulin or an elevated glucose concentration showed a significant (P <.05) antiproliferative effect when exposed to progesterone. With thymidine incorporation, progesterone showed a similar antiproliferative effect in cells stimulated with glucose or insulin. CONCLUSION: Significant reductions in cell proliferation as determined with both cell count and thymidine incorporation suggest that progesterone is an inhibitor of VSMC proliferation induced by our in vitro models of hyperglycemia and hyperinsulinemia. Therefore, progesterone may have a protective role against the atherosclerotic changes associated with type II diabetes.

Aged↗
PubMed2001

Short dementia questionnaire for assessing the severity of cognitive impairment in patients with dementia.

This paper describes the Short Dementia Questionnaire (SDQ), a psychometric test that provides an initial assessment of the severity of cognitive impairment in patients with dementia. This test requires minimal effort on the part of the assessor and places little strain on the patient. For several years now, a preliminary form of the test has been used for large-scale screening of dementia patients in nursing homes within clinical drug trials. This test is short, inexpensive and largely standardized in regard to implementation, even without the usual intensive training. This paper focuses in particular on the structure and implementation of the test. The item and scale parameters relevant for the evaluation of its field of application are presented, and finally, the results of an initial validation study are reported. These results show that the test procedure is a good predictor of severity scores in frequently used, more extensive tests for grading the severity of dementia. (c) 2001 Prous Science. All rights reserved.

Journal Article↗
PubMed1999

O-Alkylated Derivatives of 1,3,5-Triamino-1,3,5-trideoxy-cis-inositol: Triamine Ligands with Unexpectedly High Affinity toward Divalent Transition- and d(10)-Metal Ions.

The ligands all-cis-2,4,6-trimethoxycyclohexane-1,3,5-triamine (tmca) and all-cis-2,4,6-tribenzoxycyclohexane-1,3,5-triamine (tbca) were prepared almost quantitatively by using [Ni(taci)(2)](2+) (taci = 1,3,5-triamino-1,3,5-trideoxy-cis-inositol) as precursor, where Ni(2+) acted as a very efficient protecting group for the nitrogen donors. The structure of tmca in solution was investigated by NMR spectroscopy. A strongly solvent-dependent conformational equilibrium was observed. In CD(3)CN, a chair conformation with three axial amino groups formed exclusively, whereas in D(2)O, the conformation with three equatorial amino groups predominated. This effect, as well as conformational changes in the course of stepwise protonation, is discussed in terms of hydrogen bonding effects. The crystal structure of H(3)tmca(3+) exhibits a chair conformation with three equatorial ammonium groups and three axial methoxy groups. The trihydrochloride hydrate crystallizes in the monoclinic space group P2(1)/n, a = 11.057(5) Å, b = 9.960(6) Å, c = 14.671(6) Å, beta = 93.79(3) degrees, Z = 4 for C(9)Cl(3)H(26)N(3)O(4). A variety of bis complexes [M(tmca)(2)](2+) (M = Ni, Cu, Zn, Cd) and [M(tbca)(2)](2+) (M = Ni, Cu) were prepared and they were isolated as solid, crystalline trinitrate or trichloride salts. Crystal data: [Ni(tmca)(2)](NO(3))(2).4H(2)O, triclinic, space group P&onemacr;, a = 8.919(11) Å, b = 9.293(9) Å, c = 9.942(11) Å, alpha = 96.73(9) degrees, beta = 100.66(9) degrees, gamma = 101.95(9) degrees, Z = 1 for C(18)H(50)N(8)NiO(16); [Cu(tmca)(2)](NO(3))(2), tetragonal, space group P&fourmacr;2(1)c, a = 13.017(6) Å, c = 15.985(10) Å, Z = 4 for C(18)CuH(42)N(8)O(12); [Ni(tbca)(2)](NO(3))(2).MeCN.H(2)O, monoclinic, space group P2(1)/c, a = 12.930(8) Å, b = 19.324(10) Å, c = 22.724(14) Å, beta = 97.21(5) degrees, Z = 4 for C(56)H(71)N(9)NiO(13). The formation constants of [M(tmca)](2+) and [M(tmca)(2)](2+) were determined by means of a series of potentiometric titration experiments. A comparison of the taci complexes with the corresponding tmca complexes revealed an unexpected increase of stability for the latter. This increase is more than 2 orders of magnitude for the 1:1 complexes and about 5 orders of magnitudes for the 1:2 complexes. Possible reasons for this unexpected increase in stability are discussed.

Journal Article↗
PubMed1995

The Antihypertensive Properties of the Angiotensin-Converting Enzyme Inhibitor Moexipril Given Alone or in Combination with a Low Dose of a Diuretic.

The antihypertensive characteristics of the angiotensin-converting enzyme inhibitor moexipril were evaluated in 413 patients with baseline setting diastolic blood pressures between 95 and 114 mm Hg. The study was double blind, with patients randomized to placebo or to differing doses of moexipril alone or in combination with a low dose of hydrochlorothiazide. Compared with placebo, moexipril 3.75 mg daily was not different, but single daily doses of 7.5, 15, and 30 mg were significantly more effective (as measured at trough, approximately 24 h after dosing) in decreasing the diastolic blood pressuring during an 8-week treatment period. The dose-response relationship indicated that no additional blood-pressure-lowering effect occurred above 15 mg daily. Hydrochlorothiazide 12.5 mg was not significantly more effective than placebo, but the combinations of the diuretic with moexipril doses of 3.75, 7.5, and 15 mg all produced significant antihypertensive actions. Interestingly, the 3.75-mg moexipril--hydrochlorothiazide combination was equally as efficacious as the higher doses. The combinations were all more effective than their respective moexipril and hydrochlorothiazide monotherapies. There were no meaningful laboratory changes except for decreased potassium concentrations in the patients on diuretic alone; this effect was attenuated in the low-dose moexipril combination. Only 14 of the 413 patients who entered the double-blind study period (3%) discontinued treatment because of adverse experiences. Thus, moexipril is a well-tolerated drug that has clear antihypertensive efficacy as a single agent in once-daily doses of 7.5--30 mg. When combined with hydrochlorothiazide 12.5 mg, it is effective in daily doses as low as 3.75 mg.

Journal Article↗
PubMedDate not supplied

Chrono: a community-based hypertension trial of a chronotherapeutic formulation of verapamil.

An open-label, multicenter, dose-titration study evaluated 2,556 patients with stage I or II essential hypertension (untreated or previously treated with one antihypertensive agent) to assess the effect of a chronotherapeutic formulation of verapamil (Verelan PM) designed to provide maximum plasma concentrations in the midmorning hours. After starting with 200 mg/d at bedtime, the dose of Verelan PM was titrated to a maximum of 400 mg/d at 4-week intervals to achieve a target blood pressure (BP) <140/90 mm Hg using morning BP measurements. In 85.3% of patients, a diastolic blood pressure (DBP) response to less than 90 mm Hg or a 10-mm Hg decline from baseline DBP was achieved. The systolic BP response (<140 mm Hg or 10% decline from baseline) was attained in 76.9% of patients. Blood pressure was controlled in 62.6% of patients with Verelan PM monotherapy. Upward titration of Verelan PM from 200 to 400 mg nearly doubled the DBP response rate (45.8% to 85.3%). This chronotherapeutic formulation of verapamil was well tolerated in this community trial.

Adult↗
PubMedDate not supplied

Characterization of hepatocellular tumors: value of mangafodipir-enhanced magnetic resonance imaging.

PURPOSE: To assess the value of mangafodipir trisodium-enhanced MR imaging for characterization of hepatocellular lesions. MATERIALS AND METHODS: Magnetic resonance images of 41 patients with 48 histopathologically proven hepatocellular lesions (20 cases of focal nodular hyperplasia [FNH], 4 adenomas, 15 hepatocellular carcinomas [HCCs], 7 regenerative nodules, and 2 others) were retrospectively studied. Magnetic resonance imaging was performed on a 1.5-T unit (Vision, Siemens, Erlangen, Germany; ACS-NT, Philips, Best, The Netherlands) using T2-weighted, fat-saturation, turbo spin echo imaging and T1-weighted gradient echo imaging before and 20 minutes after infusion of 5 micromol/kg mangafodipir (Amersham Health, Oslo, Norway). Qualitative analysis by 4 blinded independent readers included assessment of unenhanced images and, in a second step, assessment of unenhanced and contrast-enhanced images together. Lesions were classified as benign or malignant using a 5-point scale, and readers made a specific diagnosis. RESULTS: For characterization of hepatocellular lesions, mangafodipir-enhanced imaging was significantly superior to unenhanced imaging (P < 0.05). On receiver operating characteristic analysis, the area under the curve was 0.768 (95% confidence interval: 0.633-0.903) for unenhanced images and 0.866 (95% confidence interval: 0.767-0.966) for evaluation of unenhanced and contrast-enhanced images together (P < 0.05). Analysis of enhancement patterns aided in characterization and classification of tumors. CONCLUSION: Administration of mangafodipir improves the differentiation between adenoma or HCC and "nonsurgical" lesions (FNH or regenerative nodules). The accuracy for arriving at a specific diagnosis is higher when unenhanced and mangafodipir-enhanced images are considered together than for unenhanced MR images alone.

Adenoma, Liver Cell↗
PubMedDate not supplied

The Losartan Intervention for Endpoint Reduction (LIFE) trial-have angiotensin-receptor blockers come of age?

The Losartan Intervention for Endpoint Reduction trial is one of several end-point trials that are now available with angiotensin-receptor blockers. This trial compared two regimens-losartan-based therapy to atenolol-based therapy-in 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy. In the instance of each of these therapeutic groups, hydrochlorothiazide add-on therapy was permitted as per protocol. Although blood pressures were comparably reduced in both the losartan and the atenolol-based treatment groups, stroke rate was notably less in the losartan-treatment group. The 1195 patient diabetic cohort in this trial also experienced a substantial reduction in total and cardiovascular mortality favoring losartan. An additional finding in this trial was that new-onset diabetes developed 25% less frequently in the losartan-treated group. The results of this trial are both interesting and relevant to what is an expanding use of angiotensin-receptor blockers in the hypertensive population.

Angiotensin Receptor Antagonists↗