Effects of combined treatment with enalapril and losartan on myocardial function in heart failure.
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Biomedical subjects
Publications and source records attributed to G Cocco.
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BACKGROUND: In patients with Ribbing's disease (RD)--a form of multiple epiphysal dystrophy--hypertension is frequent, often severe, and accompanied by a relevant cardiac dysfunction. HYPOTHESIS: This study was undertaken to evaluate the contribution of the calcium antagonist amlodipine and of the angiotensin-converting-enzyme inhibitor enalapril to blood pressure regulation by studying their effect on neurohormonal activation. METHODS: Fifty hypertensive patients with RD were studied. After a placebo run-in period of 4 to 6 weeks, patients were randomly assigned to receive either amlodipine (10 mg once daily) or enalapril (20 mg once daily) for 6 months. RESULTS: Both drugs significantly lowered blood pressure. Enalapril did not result in activation of the sympathetic system (as determined by measurement of the plasma norepinephrine level). On the other hand, the hypotensive effect of amlodipine occurred with an increase in heart rate and in the levels of plasma norepinephrine and angiotensin II. CONCLUSION: It is unclear whether amlodipine may reduce cardiac dysfunction in patients with RD.
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We report a case of acute myocardial infarction which occurred after administration of a synthetic analog of prostaglandin E2 (PGE2) for the voluntary interruption of pregnancy in a 31-year-old woman who had previously been asymptomatic, with myocardial bridging of the left anterior descending artery. The pathogenesis of the severe ischemia causing myocardial infarction and left ventricle aneurysm is quite unclear. The temporal connection is highly indicative of a causal relationship between the pharmacological effects of a synthetic PGE2 analog and coronary spasm responsible for severe ischemia. The hypothesis of endothelial dysfunction proximal to the intramyocardial artery tract and paradoxical vasoconstriction with platelet activation should be taken into consideration. A possible additional effect seems to be a horizontal coronary steal produced by the administration of PGE2 in the myocardium below the intramyocardial artery tract. It cannot be excluded that pharmacological doses of a synthetic analog of PGE2 may have inverted the vasoactive effects of the substance due to direct stimulation on the delivery of constrictive agonist factors.
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The determination of tumor markers in urine samples has been proposed as an effective diagnostic tool in bladder cancer. The aim of the present investigation was to validate in urine samples the assay of the CYFRA21.1 cytokeratin-related marker, the serum concentrations of which showed promising diagnostic utility in patients with bladder cancer. First-voided urine samples were collected from patients with different malignancies. CYFRA21.1 was assayed with a commercially available enzyme immunoassay (Boehringer Mannheim). Different centrifugation patterns, the use of different buffers and nonionic detergents, and pH variations were evaluated. We demonstrated that: (a) cells and cell debris contain a large amount of CYFRA21.1 and must be eliminated by centrifugation; (b) storage at -20 degrees C causes amorphous precipitate, which may aspecifically bind CYFRA21.1; (c) the latter behavior may be prevented by diluting fresh urine samples with phosphate buffer with nonionic detergent added; (d) pH variations within the range 4.9-8.2 do not significantly affect CYFRA21.1 assay results. Provided that samples are diluted with buffer containing nonionic detergent, the CYFRA21.1 assay showed good precision and accuracy characteristic in urine samples. We therefore propose a standard protocol for the collection of urine samples for CYFRA21.1 assay. In a preliminary clinical evaluation, CYFRA21.1 concentrations in 16 patients with primary bladder cancer were higher than in healthy subjects. In the urine collected in the follow-up of patients treated for bladder cancer, CYFRA21.1 tended to be higher in relapsed patients than in those without evidence of disease. These preliminary data induced us to extend the clinical trial to establish the actual role of this assay in routine use.
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Cardiac involvement was assessed in 14 patients with Ribbing's disease, a rare hereditary sclerosing bone dysplasia. When compared to age-, sex- and blood pressure-matched controls, the patients with Ribbing's disease had significant alterations in left ventricular systolic and diastolic function and an impaired exercise tolerance. Supraventricular and ventricular arrhythmias also tended to be more frequent in these patients than in controls. In conclusion, Ribbing's disease, initially described as a skeletal disease only, also involves the cardiovascular system. Despite its rarity, the expression of the disease is easily followed and identification of the genetic defect could shed some new light on the pathophysiological mechanisms linking hypertension, myocardial hypertrophy and diastolic dysfunction.
In a double-blind, parallel-group study, 260 patients with mild to severe essential hypertension were randomized to treatment with placebo or spirapril at 6, 12 or 24 mg once daily for 6 weeks. When blood pressures were measured at the end of the dosing interval (trough), all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures (siSBP/siDBP) which were significantly greater than those observed in placebo-treated patients. There were no relevant changes in resting heart rate in any of the study groups. At the study endpoint, the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg, 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo. In a subgroup of 122 patients, blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure. All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6-7 mmHg with placebo. The trough:peak ratios for 6, 12 and 24 mg all lay between 60% and 90% for siSBP and siDBP, indicating that most of the peak effect was maintained at trough. Spirapril was well tolerated; the adverse event profile was not different from that with placebo, and no dose-related adverse events were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Standardization of allergen provocation tests of the airways requires standardization of each of the steps involved, including standardization of the extracts used. The value of international standards is emphasized and so is the determination of a clinically relevant potency. The allergen extracts used for bronchial provocation tests must be compared with qualitatively and quantitatively clinically relevant standards using complementary immunochemical and biological methods. Ideally the same extracts should be used for diagnosis (skin test, specific IgE determinations, provocations) and treatment (immunotherapy). The importance of the biological compared with the non-biological methods is that the biological methods are established in allergenic patients in order to select a clinically relevant potency of the allergen in question, and this potency ought to be confirmed in clinical trials. Once established the biological potency of an in-house preparation can be reproduced by supplementary in vitro methods. Very few commercial allergen preparations are available which fulfil the above-mentioned criteria.
Inhalation challenge with lysine acetylsalicylate (L-ASA) is often used to diagnose aspirin-induced asthma. The aim of this study was to evaluate the specificity and safety of performing L-ASA inhalation challenge with a dosimeter. Twenty-four subjects entered the study: ten ASA-sensitive asthmatic patients, seven non-ASA-sensitive asthmatic patients, and seven normal control subjects. The investigation was performed on two consecutive days. On day 1 a dosimeter inhalation test with methacholine was performed to establish the provocation dose (PD20). On day 2, patients underwent the L-ASA inhalation test, whereby increasing doses of L-ASA (from 1 to 32 mg cumulative dose) were inhaled using a dosimeter and a dose response curve was constructed. In subjects negative to the top dose, an additional oral dose of 500 mg of aspirin was administered to exclude aspirin sensitivity not revealed with the inhaled drug. The ten ASA-sensitive asthmatic patients developed early reactions within 30 minutes of PD20 administration. Recovery time from induced bronchoconstriction varied from two to three hours to six hours or longer resulting in an "early prolonged reaction." The response was limited to airways. No clear late reactions were observed. There was no correlation between PD20 with methacholine and PD20 with L-ASA. The L-ASA challenge was negative in the seven non-ASA-sensitive asthmatic patients and in the seven normal control subjects. In conclusion the dosimeter method is sensitive, specific, and safe for the detection of aspirin-induced asthma.
Diaphragmatic injuries due to blunt trauma are steadily related to a high mortality. Their diagnosis may be difficult, due to the lack of specific symptoms and, more frequently to the high incidence of coexisting lesions which can mask the clinical appearance. This work presents the main aspects of ten cases admitted to the Emergency Surgery Division of Cagliari (USL 21), during the last seven years, with a review of the literature.
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The new beta-adrenoceptor partial agonist cicloprolol acts as a beta-agonist at normal levels and as a beta-antagonist at high levels of adrenergic discharge. Treatment with cicloprolol should protect the heart against excessive stimulation, while providing a baseline level of sympathetic drive. The clinical interest of such a profile is, however, not yet established in heart failure. Accordingly this study examined the safety of oral cicloprolol, a step necessary before undertaking efficacy comparison with other compounds recently proposed to treat heart failure. Twenty-five patients were studied. Cicloprolol was given once a day for 2 weeks in a crossover double-blind placebo-controlled design. Follow-ups were obtained at baseline and at the end of each period. At baseline all patients had clear evidence of heart failure. Cicloprolol did not affect resting heart rate and blood pressure, but it reduced significantly peak exercise heart rate and peak rate-pressure product. The effect was especially significant in patients with sinus rhythm. The drug did not induce bradycardia or arrhythmias. Resting and exercise ejection rate were not affected. Cicloprolol improved the quality of life and the work capacity of 5 of 12 patients with congestive failure due to ischemic etiology. Side effects were few and similar with placebo and cicloprolol. Thus, short-term administration of cicloprolol is safe in moderate heart failure.
Twenty-two patients with stable cardiac disease drove into a radar trap while having an ambulatory electrocardiogram. All patients reported cardiac symptoms, heart rate increases, and appearance of repetitive ventricular arrhythmias. Myocardial ischemia was observed in some patients. Being caught while car speeding under the stresses of daily life may induce potentially dangerous cardiac effects. The data confirm the effects of stress and adrenergic tone on ventricular arrhythmias.
This report describes the successful surgical treatment of a ruptured aneurysm of the left gastroepiploic artery. These aneurysms represent a very small fraction of visceral aneurysms.
Azelastine, a phthalazinone derivative, is a new potent, long acting, orally active anti-allergic compound with particularly strong H1-histamine receptor antagonistic effects which has been proven to possess in vitro and in vivo a number of anti-inflammatory properties. The aim of the present study was to investigate whether azelastine would be able to prevent and/or reverse the seasonal increase in non-specific bronchial responsiveness to methacholine in pollen allergic patients. Twelve atopic patients (5 males, mean age 31 years), skin positive exclusively to grass and/or Parietaria pollen extract, with rhinitis and mild asthma occurring in the spring for at least two years previously, were studied. After a 2 week run-in period, oral azelastine, 4 mg twice daily, or placebo, was given for 2 weeks from the start of the pollen season, according to a randomized, double-blind design. After 2 weeks, the treatments were crossed over. During both the run-in and study periods, patients recorded rhinitis and asthma symptoms, additional antihistamine and bronchodilator drugs taken and peak expiratory flow measurements. A methacholine inhalation test was carried out on four occasions in each patient: before the run-in period, before the start of the treatment, and at the end of the two 2 week treatment periods. Azelastine significantly reduced rhinitis symptoms and the need for antihistamine drugs, whereas asthmatic symptoms, use of bronchodilator drugs, peak flow recordings and bronchial responsiveness to methacholine were unaffected by the treatment. Compliance level and adverse side-effects were not significantly different between active treatment and placebo. In the final subjective evaluation of the two treatments, eight out of 12 patients preferred azelastine.(ABSTRACT TRUNCATED AT 250 WORDS)