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Biomedical subjects

P Timmermans

Publications and source records attributed to P Timmermans.

10 recordsLinked to original sources
PubMed1998

Evaluation in vivo of the endothelial function of the native gastroepiploic artery.

The endothelial function of a coronary bypass graft is an important aspect, contributing not only to its patency but to its functional performance. To evaluate this aspect in vivo, we studied 16 patients who underwent selective catheterization of the native gastroepiploic artery (GEA). Quantitative angiography of the GEA was performed at baseline, after 2 minutes' infusion of acetylcholine in three ascending doses, and after 2 mg isosorbide dinitrate injection directly into the GEA. Mean GEA diameter was 2.02 +/- 0.38 mm at baseline. We observed dose-dependent vasodilation during acetylcholine infusion: The mean diameter increased slightly to 2.11 +/- 0.32 mm (+6%, not significant) with the second dosage and, more significantly, with the highest dosage, to 2.32 +/- 0.33 mm (+18%, p < 0.001). More important vasodilation was observed after administration of nitrates (+36%, p < 0.001). We found no difference between patients with and without coronary artery disease and no relationship with risk factors for atherosclerosis. A positive correlation was seen between the vasodilation observed after nitrate administration and the highest dose of acetylcholine (r = 0.728, p = 0.002). In conclusion, the GEA demonstrates a notable vasodilatory response to nitrates (non-endothelium-dependent) and a dose-related dilator response to acetylcholine, reflecting preserved endothelial function. This sensitivity should affect favorably the hemodynamic performance of grafts performed with GEA, as well as these grafts' long-term patency rate.

Acetylcholine↗
PubMed1998

A novel angiotensin II binding site in murine tissues.

A novel binding site for angiotensin II has been identified in certain murine tissues. This site, denoted ATm, is distinct from both the AT1 and AT2 sites, as well as the various atypical sites that have been described. The site has a low affinity for angiotensin II (100 nM) and is not blocked by losartan, PD123177 or saralasin. The site shows structural specificity for angiotensin II since both angiotensin III and angiotensin II (1-7) failed to inhibit the binding. Numerous standard drugs, including various receptor blockers, enzyme inhibitors and therapeutic agents, showed no affinity for the site. In murine tissues the site is associated with active tissue generation, as found in spleen, placenta and growing tumors, but its occurrence appears to be rare outside of the mouse.

Amino Acid Sequence↗
PubMed1998

Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure.

Losartan (COZAAR) is the prototype of a new class of potent and selective angiotensin II (AII) type 1 (AT(1)) receptor antagonists with the largest published preclinical and clinical data base. Since all of the AII antagonists are selective for the AT(1) receptor, these drugs should exhibit similar cardiovascular effects. However, since the pharmacokinetic/pharmacodynamic profiles of these agents and their degree of affinity for the AT(1) receptor differ, it is likely that differences in clinical profiles between these drugs exist and will require investigation. Losartan (parent compound), has moderate affinity for the AT(1) receptor (competitive inhibition). Losartan is well-absorbed orally as an active drug and is rapidly converted via oxidation in the human liver to a more potent metabolite (designated E3174) with an affinity 20- to 30-times greater for the AT(1) receptor (non-competitive inhibition). E3174 has a half-life of 6 - 9 h; elimination is via renal and hepatic routes. Antihypertensive and, in heart failure patients, haemodynamic activity is observed over a 24 h period with once daily dosing. Over 6 million patients have been treated for hypertension with continued excellent tolerability. Clinical experience in heart failure is growing, and recent data suggest an improved survival with losartan versus captopril, a drug from the angiotensin-converting-enzyme inhibitor class with proven benefit in this population. The current comprehensive losartan clinical end-point programme (4 large scale morbidity/mortality trials) should provide evidence regarding the efficacy of direct blockade of the AT(1) receptor with losartan compared to standard therapy: 1) The Losartan Heart Failure Survival Study - ELITE II, 2) The Losartan Post-Myocardial Infarction Survival Study - OPTIMAAL, 3) The Losartan Hypertension Survival Study - LIFE and 4) The Losartan Renal Protection Study - RENAAL.

Journal Article↗
PubMed1996

Regulation of arachidonic acid metabolism, aromatase activity and growth in human breast cancer cells by interleukin-1beta and phorbol ester: dissociation of a mediatory role for prostaglandin E2 in the autocrine control of cell function.

Prostaglandin E2 (PGE2) levels are elevated in malignant human breast tissue. However, the cellular mechanisms regulating this arachidonate metabolism and the autocrine influence PGE2 production may have on breast cancer cell growth and function are unclear. In the present study, we have investigated the effects of 2 putative cyclo-oxygenase inducers, interleukin-1beta (IL-1beta) and the protein kinase C agonist 12-O-tetradecanoyl-phorbol-13-acetate (TPA), on PGE2 production, growth and aromatase activity in the MDA MB 231 breast cancer cell line. TPA stimulated a dose-dependent increase in PGE2 production, inhibited cell growth and stimulated aromatase activity. Although IL-1beta alone had no effect on any of these breast cancer cell functions, the cytokine greatly potentiated PGE2 production in the presence of TPA. Similarly, growth inhibition and aromatase stimulation in response to TPA were both further enhanced by IL-1beta treatment. Indomethacin and dexamethasone both prevented PGE2 production in response to IL-Ibeta and TPA but had no effect on the anti-proliferative action of the cytokine and phorbol ester. While indomethacin had no effect on induction of aromatase activity by IL-1beta and TPA, dexamethasone exhibited a temporally biphasic action. Dexamethasone alone stimulated aromatase activity and demonstrated a permissive action on aromatase stimulation by IL-1beta and TPA. However, pre-treatment of cells with dexamethasone prevented subsequent induction of aromatase activity by IL-1beta and TPA. Our study describes a novel synergistic interaction in response to protein kinase C activation and IL-1beta during the regulation of arachidonate metabolism, cell growth and aromatase activity in human breast cancer cells. We conclude that the cyclooxygenase pathway does not play a mediatory role during the inhibition of cell growth and the induction of aromatase activity by IL-1beta and TPA.

Arachidonic Acid↗
PubMed1993

Post traumatic myocardial infarction.

We report the history of a young man who developed an acute anterolateral myocardial infarction secondary to blunt chest trauma in an automobile accident. Arteriography demonstrated that the patient had sustained a left anterior descending artery tear and a coronary-ventricular fistula from the first septal branch. Different pathogenetic mechanisms with their specific complications and diagnostic features are discussed.

Adult↗
PubMed1988

Angina pectoris and coronary artery disease in severe aortic regurgitation.

A consecutive series of 198 patients (148 men and 50 women, mean age 51 years, range 18 to 76) with pure, isolated, severe aortic regurgitation was retrospectively studied to determine the prevalence of angiographically significant coronary artery disease (CAD) and its relation to angina pectoris and coronary risk factors. Significant CAD (coronary diameter stenoses greater than 50%) was found in 28 patients (14%). Typical angina was present in 18% and atypical chest pain in 16%. Angina alone had a sensitivity of 57% to detect significant CAD. The predictive accuracy of a positive history of angina was 46% and that of a negative test 93%. By using multivariate logistic regression, a risk score could be calculated that increased the sensitivity to 74% at equal specificity. Almost 40% of the total population had a risk score of less than -2.9 (only 1 patient in this group had CAD). It is concluded that coronary arteriography can safely be omitted in many patients with severe aortic regurgitation if they have no symptoms of myocardial ischemia or risk factors known to increase its incidence.

Angina Pectoris↗
PubMed1982

Interaction of staphylococcal protein A in enzyme-linked immunosorbent assays for detecting staphylococcal antigens.

ELISA procedures for detecting staphylococcal antigens may be subject to interference by reactions between staphylococcal protein A (SPA) and IgG molecules. It was found that rabbit IgG reacted with SPA, both in the native state and after conjugation with peroxidase. Sheep IgG, however, did not react with SPA if conjugated with peroxidase. Peroxidase conjugated SPA reacted with rabbit IgG but not with sheep IgG. These results demonstrate that the source of IgG used in an ELISA system is of major importance to correct quantitation of staphylococcal antigens.

Animals↗
PubMed1981

[A simple method for the detection of staphylococcal enterotoxin type B in vanilla custard using the ELISA (author's transl)].

The ELISA for the detection of staphylococcal enterotoxin type B (SEB) was employed to demonstrate SEB in Dutch Vanilla custard. Due to the sensitivity of the ELISA the extraction procedure, which is necessary when the Ouchterlony test is used, can be abbreviated to a great extent. Two successive extractions at pH 7.4 and pH 4.5 followed by a concentration (1:20) was sufficient to detect 0.1 mcg SEB in 100 g custard.

Enterotoxins↗
PubMedDate not supplied

Chronotropic incompetence: a case report.

Chronotropic incompetence is generally defined as an inadequate heart rate response to exercise, but manifestations can vary. The incidence depends on underlying cardiac pathology and, to a lesser degree, on the cut-off value of the predicted heart rate during exercise. Different pathologies induce chronotropic incompetence. Its presence indicates an adverse outcome and is strongly correlated with coronary artery disease. Treatment consists of rate-responsive pacemakers; dual-sensor, adaptive pacemakers are superior to single-sensor, rate-augmenting pacemakers. This case report illustrates the negative effect of chronotropic incompetence on daily activities and its amelioration by implantation of a rate-responsive pacemaker. (c)2001 by CHF, Inc.

Journal Article↗