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Biomedical subjects

P Unger

Publications and source records attributed to P Unger.

At least 19 recordsLinked to original sources
PubMed1991

Intravenous diltiazem versus nitroglycerin for silent and symptomatic myocardial ischemia in unstable angina pectoris.

For 18 patients consecutively admitted to the coronary care unit for unstable angina, 48-hour electrocardiographic Holter monitoring was performed after they were randomly assigned in a single-blind fashion to 1 of 2 treatment groups. The first group was treated with acetylsalicylic acid (ASA) and intravenous nitroglycerin, the second with ASA and intravenous diltiazem. All of the patients treated with nitroglycerin still had ischemic episodes after 48 hours (33% were symptomatic), in contrast with 11% of the diltiazem group (11% asymptomatic). Maximal ST-segment depressions of symptomatic and asymptomatic episodes were significantly different; and no significant increases in heart rate were observed either during the 15 seconds before ischemia began or during the ischemic episode. During the 48 hours, the diltiazem group had significantly fewer ischemic episodes (17) than did the nitroglycerin group (145). We concluded that "on-line" ST-segment observation is of prime importance for monitoring unstable angina; that the majority of the ischemic episodes associated with unstable angina are silent; and that intravenous diltiazem could be an effective pretreatment for patients who must undergo mechanical or surgical therapy.

Aged↗
PubMed1991

Endothelium-dependent effects of pentoxifylline in rat aorta.

Experiments were performed with isolated rat aortas to study the vasoactive properties of pentoxifylline, a cyclic AMP phosphodiesterase inhibitor, which is used as a hemorheologic agent in the treatment of peripheral vascular disease. In rings precontracted with phenylephrine (0.1 microM), pentoxifylline (10 nM-10 microM) induced concentration-dependent relaxations which were not modified after incubation with indomethacin (3 microM) but which were almost completely abolished after incubation with methylene blue (10 microM) or after mechanical removal of the endothelium. After incubation with pentoxifylline (10 microM) for 30 min, the concentration-response curves for endothelium-dependent relaxations to acetylcholine were shifted to the left and the serotonin-induced contractions were decreased, while the relaxations to forskolin, which are endothelium-independent and cyclic AMP-mediated, were not altered. We conclude that pentoxifylline exerts vasoactive effects that are mediated by endothelium-derived relaxing factor (EDRF), and that pentoxifylline has negligible endothelium-independent vasodilating properties. These properties of inducing or potentiating EDRF-mediated effects might contribute to the efficacy of pentoxifylline in the treatment of vascular disease.

Acetylcholine↗
PubMed1991

Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies in patients treated with the mouse monoclonal antibody 17-1A (ab1). Relation to the clinical outcome--an important antitumoral effector function?

Forty-three patients with metastatic colorectal carcinoma (CRC) were treated with the unconjugated mouse monoclonal antibody (MAb) 17-1A (ab1) only. The presence of antiidiotypic antibodies (ab2) and anti-antiidiotypic antibodies (ab3) were analyzed using an ELISA technique and a mixed hemadsorption assay respectively. Ninety-five percent (41/43) of the patients developed ab2 both of the IgM and the IgG classes. Forty-seven percent (20/43) of the patients had detectable ab3 after therapy, two of them also before administration of MAb 17-1A. Binding in vitro of ab3 (ab1) to CRC cells could be specifically inhibited by ab1. Ab3 bound to human monoclonal antiidiotypic antibodies and to a goat antiidiotypic antibody (ab2). Both these ab2 were directed against MAb 17-1A (ab1). There was a strong correlation between the presence of ab3 and the clinical outcome. Ab3+ patients survived significantly longer than those who did not develop ab3 antibodies, 80 weeks vs 38 weeks (p less than 0.001). A statistically significant correlation was found between the presence of ab3 and the anti-tumor response (CR + PR + MR + SD) (p = 0.01). Thus, induction of an antiidiotypic cascade seems to be an important antitumor effector function of MAb in the treatment of cancer patients.

Antibodies, Anti-Idiotypic↗
PubMed1991

Prevention of cyclosporine A-induced vascular toxicity by pentoxifylline.

To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the vascular toxicity of cyclosporine A (Cx), three groups of rats were studied in parallel. The first group received daily injections of Cx (20 mg/kg intramuscularly) and pentoxifylline (80 mg/kg intraperitoneally) for 7 days, the second group was treated with Cx only, and the third group served as control (vehicle treatment). Cx serum levels were similar in groups 1 and 2. In thoracic aortic rings isolated from Cx group (group 2), the concentration-response curves to phenylephrine were potentiated: there was a significant leftward shift (p less than 0.001 vs. control) in the EC50 values and an increase in the maximal responses (p less than 0.05). After mechanical removal of the endothelium or inhibition of endothelium-derived relaxing factor formation (incubation with NG-monomethyl-L-arginine, L-NMMA), this enhanced responsiveness to phenylephrine persisted. In preparations from the same group (group 2), the endothelium-dependent relaxations to acetylcholine (ACh) were decreased whereas the endothelium-independent relaxations to nitroprusside (NTP 0.01-10 nM) and forskolin (1 nM) were slightly attenuated but without changes in the maximal response. In the group cotreated with Cx and PTX (group 1), the responses to ACh, NTP, and forskolin were not different from controls whereas the greater responsiveness to phenylephrine was only partially attenuated. In vivo cotreatment with PTX may prevent the endothelial dysfunction and the functional changes in smooth muscle cells induced by Cx.

Acetylcholine↗
PubMed1991

Hemodynamic response to molsidomine in patients with ischemic cardiomyopathy tolerant to isosorbide dinitrate.

Unlike nitrates, molsidomine is able to relax vascular smooth muscle without depending on the availability of sulfhydryl groups. To assess the clinical relevance of this property, the hemodynamic effects of a 24-h i.v. infusion of molsidomine were studied in 14 patients with ischemic cardiomyopathy rendered tolerant to i.v. isosorbide dinitrate. In order to determine the role of neurohormonal activation, six of these patients were studied in the presence of an angiotensin-converting enzyme (ACE) inhibitor (enalapril, 5 mg, b.i.d.) (group 2). Six patients out of eight in group 1 (without ACE inhibition) and all patients in group 2 responded to molsidomine with a marked reduction of pulmonary artery wedge pressure (PAWP) (49% +/- 5 and 50% +/- 4 versus baseline value, respectively). However, the reduction of PAWP in group 1 was no longer significant at 12 h, and at 24 h the loss of the peak effect reached 67% +/- 7. On the contrary, PAWP remained persistently reduced in group 2 (loss of peak effect, 20% +/- 3 at 24 h, p less than 0.005). In addition, a significant decrease in hematocrit and increase in epinephrine occurred in group 1 but not in group 2. These results suggest that both the absence of dependence on sulfhydryl groups and the blockade of neurohormonal reactions are needed to avoid nitrate tolerance.

Aged↗
PubMed1991

S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas.

The absence or presence of S100-positive sustentacular cells has been previously shown to be correlated with benign and malignant pheochromocytomas and paragangliomas. We evaluated a total of 17 malignant and recurrent or locally aggressive adrenal pheochromocytomas for their quantity of sustentacular cells. An absence of sustentacular cells was demonstrated in the majority of malignant cases, while the locally aggressive or recurrent group usually contained an abundance of these cells. However, in one malignant case a constant moderate number of sustentacular cells in the primary site and in two sequential metastases was found. We conclude that the absence of sustentacular cells in pheochromocytomas may indicate a lesion with a greater potential for metastasis and that sustentacular cells, when they are present in a malignant pheochromocytoma, are an integral part of the tumor.

Adolescent↗
PubMed1990

Alpha-adrenergic coronary constriction in effort angina.

In order to assess the role of alpha-adrenergic coronary tone in exercise-induced ischemia, 23 patients with chronic stable angina underwent, after coronary angiography, a symptom-limited supine exercise test on a cyclo-ergometer. After recovery, either phentolamine (for the first nine patients) or indoramin (for the following nine patients) was directly injected into the most diseased vessel at identical doses (2 mg over 5 min). In the remaining 5 patients, a placebo was injected. Immediately thereafter the same exercise (identical workloads and exercise duration) was repeated. During exercise 1, heart rate (HR), mean blood pressure, and cardiac index increased by 51%, 23% and 33% in the phentolamine group, and by 45%, 15%, and 33% in the indoramin group. After intracoronary injection of phentolamine or indoramin, control values (including pulmonary artery wedge pressure (PA wedge] at rest did not change significantly. During exercise 2, HR, mean blood pressure, and cardiac index increased in a similar way; however, the increase in PA wedge was less pronounced (p less than 0.01 in the phentolamine group and p less than 0.05 in the indoramin group). ST-segment depression at the end of exercise 2 was significantly smaller for identical workloads and double products in the phentolamine group: 1.5 +/- 0.3 mm vs 2.5 +/- 0.3 mm (p less than 0.01). However, these changes did not reach a statistical significance in the indoramin group: 1.7 +/- 0.2 mm vs 2.0 +/- 0.1 mm (NS). ST/HR slope in exercise 2 decreased by 51% (p less than 0.01) in the phentolamine group and by 34% (p less than 0.05) in the indoramin group. In the placebo group, exercise 2 was identical to exercise 1 and the ST/HR slopes were quite reproducible. These results show a less severe ischemic response after intracoronary alpha-blockade. Therefore, our results argue for a role of alpha-adrenergic coronary tone in exertional angina. The relatively higher efficiency of phentolamine vs indoramin suggests that alpha 2-adrenergic mechanisms contribute to the inappropriate coronary vasoconstriction during exercise in these patients.

Adult↗
PubMed1990

Effects of in vivo SIN1 treatment on nitrovasodilator relaxation and on EDRF-mediated responses in rat aorta.

SIN1 (the active metabolite of molsidomine), nitroglycerin, and endothelium-derived relaxing factor (EDRF) produce vasodilation by activation of soluble guanylate cyclase. Therefore, prolonged exposure to SIN1 might affect not only the responses to SIN1 itself and to nitroglycerin but also to EDRF. In vivo treatment of rats consisted of subcutaneous injections of either SIN1 (60 mg/kg) for the treated group or placebo for the control group, twice daily for 3 days. Thoracic aortas from the treated group were threefold and sixfold less sensitive to nitroglycerin and SIN1, respectively. The endothelium-dependent relaxations to acetylcholine were, nevertheless, similar in both groups. Moreover, the concentration-response curves to phenylephrine, which are known to be modulated by the endothelium, were similar in both groups. In addition, incubation with methylene blue (10 microM for 30 min), which blocks the vasodilator action of EDRF, potentiated in the same way the contractions to this alpha-adrenergic agonist. The increase in resting tone induced by methylene blue incubation was also equivalent in the two groups. The present results show that SIN1 treatment for several days in rats is associated with slight tolerance development not only to SIN1 itself but also to nitroglycerin, while the endothelial function remains operative. We conclude that the mechanisms involved in the activation of guanylate cyclase by SIN1 and nitroglycerin are probably different than those of EDRF-mediated responses.

Animals↗
PubMed1990

[The treatment of carcinoma in situ of the breast].

In reference to a series of 36 in situ breast carcinomas, the current therapeutic possibilities are considered: 8 lobular carcinomas in situ (LCIS) and 28 ductal carcinomas in situ (DCIS) were diagnosed between January 1985 and July 1988. These are infraclinical forms in 80% of the cases, representing 20% of the breast carcinomas treated during the same period of time. The natural history of carcinomas in situ is presented; LCIS rarely evolve toward an invasive carcinoma and they should not be considered as risk factors. DCIS evolve, after biopsy, toward an infiltrating ductal carcinoma in 26 to 28% of the cases. Axillary node invasion is present in 3% of the cases. After diagnostic biopsy of a LCIS, a subcutaneous mastectomy with prosthetic reconstruction will be offered only if there are bilateral foci or diffuse microcalcifications. Supervision will be recommended in all other cases. The results of the mastectomy-node excision procedure are well known for the LCIS: less than 5% recurrence and a mortality under 1.5%. The current tendency goes toward a limited surgical act: axillary dissection is discussed for small LCIS; lumpectomy is more and more advocated with long-term results still not well known; in case of lumpectomy, two prospective trials are currently in progress in the world, in order to assess the efficacy of radiotherapy.

Adult↗
PubMed1990

Mass concentration of creatine kinase MB isoenzyme and lactate dehydrogenase isoenzyme 1 in diagnosis of perioperative myocardial infarction after coronary bypass surgery.

Recent advances in methodology allow the mass concentration of creatine kinase MB isoenzyme (CK-MB), and of lactate dehydrogenase isoenzyme 1 (LD1) to be determined quickly and easily as routine, emergency tests. We evaluated these tests as diagnostic criteria of perioperative myocardial infarction (PMI) after coronary bypass surgery. These tests were compared with the usual measurements of CK-MB activity by immunoinhibition and LD1 by electrophoresis and with other biological markers of myocardial infarction such as total CK, total LD, and aspartate aminotransferase. Sixty-one patients who underwent coronary bypass grafting were followed pre- and postoperatively by enzyme determinations and electrocardiography; a subgroup was monitored by myocardial scintigraphy. CK-MB mass appeared to be the best marker of PMI during the first 48 h, although LD1 was the marker of choice from days 2 to 4.

Adult↗
PubMed1990

[Tomographic aspects of the temporomandibular joint (TMJ). Comparative study of 30 subjects with rheumatoid arthritis and 30 normal subjects].

From a prospective study, two populations are compared: 30 Healthy subjects with 30 subjects suffering from rheumatoid arthritis. Two conclusions are statistically significant: --The temporo-mandibular joint is affected like the other joints in the rheumatoid arthritis, --the lesions are often bilateral. Two radiographic aspects, are most often observed: the erosion and the lacuna.

Arthritis, Rheumatoid↗
PubMed1989

Study of ridazolol on isolated canine and human coronary arteries.

Experiments were performed on isolated canine and human coronary arteries to study the alpha- and beta-adrenolytic properties of ridazolol. On canine coronary arteries precontracted with prostaglandin F2 alpha 2 microM and pretreated with phentolamine 1 microM, ridazolol competitively antagonized the isoproterenol-induced relaxations, with a pA2 value of 8.5 (7.8-9.1). Thereafter the alpha-adrenolytic activity of ridazolol was assessed on these same canine coronary vessels. Ridazolol activity was compared with that of prazosin on dose-response curves to norepinephrine in the presence of cocaine (30 microM) and propranolol (3 microM). Schild plots for both drugs gave straight lines, with slopes not different from unity. The pA2 value was 7.1 (6.8-7.3) for ridazolol and 8.1 (7.9-8.4) for prazosin. In another set of experiments the alpha-adrenolytic activity of ridazolol was compared on canine and human coronary arteries. A submaximal contraction with norepinephrine (10 microM) was first assessed in the presence of propranolol 3 microM. The addition of ridazolol 3 microM significantly decreased the norepinephrine (10 microM)-induced contractions of both preparations. However, the inhibition was more pronounced on canine coronary arteries. In conclusion, ridazolol is a potent beta-adrenergic antagonist with moderate alpha-adrenolytic activity. The weaker inhibition of the norepinephrine-induced contraction observed in human preparations suggests the presence of a heterogeneous population of postjunctional alpha adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1989

Comparison of responses to acetylcholine and serotonin on isolated canine and human coronary arteries.

Canine and human coronary arteries were studied in organ baths to compare the responses to acetylcholine and serotonin in the two species. The human coronary rings were isolated from seven patients without cardiac disease (mean age 15 years, range 7-20). In one set of experiments canine and human preparations were incubated with phentolamine, propranolol and ketanserin (all at 1 mumol.litre-1 concentration) and precontracted with prostaglandin F2 alpha (PGF2 alpha 1-2 mumol.litre-1). Acetylcholine (0.1-10 mumol.litre-1) and serotonin (0.1-100 mumol.litre-1) relaxed canine preparations dose dependently, the maximum responses (expressed as % of depression of PGF2 alpha response) being 84 (SEM 6)% (n = 9) and 51(5)% (n = 6) respectively. In the same experimental conditions, acetylcholine and serotonin failed to relax the human coronary rings (n = 11) while substance P and bradykinin induced relaxations of 72(4)% (n = 11) and 66(7)% (n = 11) of PGF2 alpha response respectively. In another set of experiments, dose-contraction curves were constructed for acetylcholine or serotonin (in presence of phentolamine and propranolol). On human rings with endothelium, methylene blue (10 mumol.litre-1), a non-specific inhibitor of endothelium derived relaxing factor (EDRF), potentiated these dose-contraction curves: markedly for serotonin, the EC50 decreasing from 1.2(0.2) to 0.22(0.08) mumol.litre-1 (n = 11, p less than 0.01) with a significant increase in the maximal response); and slightly for acetylcholine, EC50 decreasing from 0.84(0.11) to 0.40(0.13) mumol.litre-1 (n = 10, p less than 0.05) without significant change in the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Acute disseminated intravascular coagulation after percutaneous balloon aortic valvuloplasty in a cirrhotic patient.

We report the case of a 71-year-old man presenting a histologically proven liver cirrhosis with compensated disseminated intravascular coagulation and calcified aortic stenosis. This coagulation disorder became clinically and biologically severe during or soon after percutaneous balloon aortic valvuloplasty. In a cirrhotic patient with compensated disseminated intravascular coagulation, the procedure can induce life-threatening bleeding disorders.

Acute Disease↗