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Biomedical subjects

M Muratori

Publications and source records attributed to M Muratori.

At least 19 recordsLinked to original sources
PubMed1997

Protein tyrosine kinase, mitogen-activated protein kinase and protein kinase C are involved in the mitogenic signaling of platelet-activating factor (PAF) in HEC-1A cells.

We have recently demonstrated that the phospholipid platelet-activating factor (PAF) mediates an autocrine proliferative loop in the endometrial adenocarcinoma cell line HEC-1A. In the present study we investigated the signaling pathways involved in PAF-mediated increase of proliferation in these cells. In particular, we studied the effect of PAF on protein tyrosine phosphorylation and mitogen-activated protein kinase (MAPK) activity, as well as the effect of protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibition on PAF-induced increase of c-fos gene expression and thymidine incorporation in HEC-1A cells. We found that PAF induced a rapid, time- and dose-dependent increase of tyrosine phosphorylation of a subset of proteins of 42, 44, 78, 99, and 150 kDa molecular weight. We also found that PAF increased tyrosine phosphorylation and activity of p42 MAPK, suggesting the involvement of this important intermediary enzyme in the proliferative effect of PAF. The effect of PAF on c-fos gene expression was not prevented by pre incubation with the PTK inhibitors genistein or methyl-2,5-dihydroxycinnamate, whereas was strongly affected by PKC down regulation after long term incubation with PMA or by PKC inhibition with sangivamycin. We also found that genistein and methyl 2,5-dihydroxycinnamate decreased both basal and PAF-stimulated [3H]thymidine uptake in these cells. Similar results were obtained with PD 098059, a specific inhibitor of MAP kinase cascade. PAF-stimulated [3H]thymidine uptake was also prevented by PKC down regulation after long term exposure to PMA and PKC inhibition with the two inhibitors sangivamycin and bis-indolylmaleimide. In conclusion, our results indicate that PAF-induced mitogenesis in HEC-1A cells is mediated by the activation of multiple signaling pathways, involving PTK, MAPK, and PKC activation.

Adenocarcinoma↗
PubMed1997

Use of cabergoline in the long-term treatment of hyperprolactinemic and acromegalic patients.

Cabergoline (Cab), a very potent and long-lasting dopaminergic compound, was administered to 26 women with pituitary microprolactinoma [mean serum PRL levels: 124.8 +/- 11.3 micrograms/l (+/- SE), range 62-300 micrograms/l] and 3 patients with GH-secreting pituitary adenoma (2 with associated PRL hypersecretion) for 12 and 24 months, respectively. In microprolactinomas, a stable normoprolactinemia was achieved in 96.1% of cases: in 13 women (50%) with the lowest dose of the drug (0.5 mg/week), and in other 12 patients (46.1%) with increasing doses up to 3 mg/week. All the oligomenorrheic/amenorrheic women, except one, restored regular and ovulatory menses. Two patients became pregnant. Pituitary abnormalities at high resolution-CT (HR-CT) scan disappeared in 13 of 19 patients (68.4%) after 12 months of therapy and this feature persisted in 8/13 cases (61.5%) 12 months after drug withdrawal. During Cab discontinuation (range: 3-60 months), mean serum PRL levels remained significantly lower than the basal ones. Six of 25 women are still without therapy. In 2 patients, normoprolactinemia persisted up to 38 and 60 months, respectively. Cab treatment was re-instituted in 13 patients because of the recurrence of hyperprolactinemia. Five patients were lost at follow up. In all the acromegalic patients, Cab (1-3 mg/week) normalized serum GH, IGF-I and PRL levels. A clear improvement in clinical symptoms was observed in all patients, but neuroradiological improvement in only one. Cab therapy was very well tolerated, as only seven patients complained of mild and transient side-effects and none had to stop treatment. In conclusion, Cab is an effective, safe, and well tolerated dopaminergic compound for the treatment of hyperprolactinemic disorders and the control of the clinical and hormonal features of dopamine-sensitive acromegalic patients.

Acromegaly↗
PubMed1997

Relation between exercise-induced left ventricular wall motion abnormalities and coronary artery disease in hypertensive patients: effects of blood pressure normalization.

In hypertension, several factors disturb coronary circulation and the metabolic reserve of the heart. This study was undertaken to test whether in hypertensive patients global and regional left ventricular (LV) function is related during exercise to the presence of significant coronary stenosis and whether lowering of coronary perfusion pressure through rapid normalization of the diastolic pressure may modify the dynamics of the left ventricle. Thirty-five patients with mild to moderate hypertension undergoing coronary angiography for the evaluation of chest pain were included in the study; upright bicycle exercise echocardiography tests were performed without therapy and 1 day later 1 h after sublingual administration of nifedipine. LV ejection fraction and regional wall motion scores were evaluated and compared at baseline, peak exercise, immediate postexercise, and recovery phases in each test through digital on-line storing of echocardiographic images. Twenty-one patients had normal coronary arteries (group 1) and 14 significant coronary stenoses (group 2); age, gender, heart rate, blood pressure, left ventricular diameter and mass index, and ejection fraction were similar in the two groups. At peak exercise LV ejection fraction slightly increased in group 1, whereas it slightly decreased in group 2 (both during the test without therapy and after nifedipine administration). All patients in group 1 had normal left ventricular wall motion during exercise; 13 of 14 patients in group 2 had LV wall motion abnormalities at peak exercise. Nifedipine did not produce any effect on LV regional wall motion in group 1, but it induced significant changes in LV regional wall motion in seven patients in group 2. Changes in LV wall motion between the two test groups were related to the number of the stenotic coronary vessels: the normal exercise test before and after therapy and the two normalized tests after nifedipine administration were in fact observed in patients with one-vessel disease, whereas worsening or changes in the site of ischemia were observed only in patients with multivessel disease. Regional and global left ventricular dynamics during exercise is mainly dependent on the existence of significant coronary artery disease. Rapid decrease of blood pressure does not alter the regional dynamics of the left ventricle during exercise in patients without coronary artery disease, but it may induce normalization, worsening, or changes in the site of wall motion abnormalities in hypertensives with significant coronary stenoses.

Aged↗
PubMed1997

Treatment of macroprolactinoma with cabergoline: a study of 85 patients.

OBJECTIVE: Cabergoline is now established as an effective and well-tolerated treatment for prolactinoma. However, there are relatively few published data on the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore reviewed the efficiency and safety of cabergoline in the treatment of patients with prolactin-secreting macroadenomas treated on a compassionate basis. STUDY DESIGN AND PATIENTS: Eighty-five patients with prolactin-secreting macroadenomas were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty-five patients (32 intolerant, 16 resistant) had been treated previously with other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300 micrograms/I and tumour maximum diameters were between 11 and 42 mm. MEASUREMENTS: Serum prolactin, visual fields if initially abnormal, occurrence of menses or return of libido and potency, blood chemistry and adverse events were assessed at 1 month and then at 3-month intervals during treatment. Pituitary computed tomography or magnetic resonance imaging was usually repeated at 3 months and 1 year, then yearly, in most patients (n = 62). RESULTS: Normalization of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20 de novo patients, 17 had prolactin normalized and the remainder had at least 75% reduction. Disappearance of tumour image was found in eight of 62 evaluable patients (12.9%) and reduction of the largest diameter by at least 25% in another 33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo patients the success rate was 82.3%. Fifteen of 21 patients who failed to show tumour shrinkage had previously demonstrated resistance/intolerance to other prolactin-lowering treatments. Of the 12 patients with visual field defects at baseline, six normalized and two showed an improvement. Menses resumed during cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was reported by seven of eight evaluable men. Adverse events were recorded in 24.7% of cases, four of whom (4.7%) discontinued treatment. CONCLUSIONS: Although the present data were not obtained in a formal study we conclude that cabergoline is an effective and well-tolerated treatment for macroprolactinoma patients.

Adolescent↗
PubMed1996

Fluoroscopic functional evaluation of bileaflet prostheses: effect of different intraoperative valve orientation.

Fluoroscopy is a reliable, easy, and readily available technique to follow-up prosthesis functioning after heart valve surgery. The different orientation given to the prosthesis may represent a limitation of the technique accounting for unsatisfactory results in 10% to 40% of the cases. The aim of the study was to evaluate whether and to what extent different intraoperative valve orientation influence feasibility and accuracy of postoperative fluoroscopic evaluation of bileaflet prostheses. We prospectively evaluated 90 patients who had aortic, mitral, and/or tricuspid valve replacement with Sorin Bicarbon or CarboMedics bileaflet prostheses. Fifty percent of the patients in each group were randomly assigned to receive prostheses oriented in a perpendicular or a parallel position with respect to the ventricular septum. Fluoroscopic evaluation was considered appropriate when the prosthesis' "tilting disk" projection was obtained. The valve's hemodynamic performance was investigated through Doppler study. A proper fluoroscopic evaluation was rapidly (15 +/- 5 seconds) achieved in all patients with the former orientation, whereas it was impossible to obtain it in 8 of 20 (40%), 19 of 20 (95%), and 4 of 5 (80%) of patients with the latter orientation. In the remaining patients extremely angulated, uneasy projection was often required to get a correct fluoroscopic image. The Doppler study showed a similarly favorable hemodynamic performance regardless of valve orientation. Prosthesis orientation crucially affects the rate of success of the fluoroscopic evaluation. The orientation perpendicular to the ventricular septum greatly facilitates the postoperative feasibility and accuracy of fluoroscopy, and it is not detrimental to the valve's hemodynamic performance. This valve orientation may provide a better fluoroscopic window whenever a valve dysfunction is suspected.

Aortic Valve↗
PubMed1995

How the two sides of the heart adapt to graded impedance to venous return with head-up tilting.

OBJECTIVES: The study sought to probe whether the adaptation of the right ventricle to reduced preload may influence that of the left ventricle (interdependence) and whether and how this mechanism contributes to maintain an adequate pump function. BACKGROUND: A study like this requires that subjects be normal, restraint of venous return be gradual, systolic function and diastolic filling and dimensions of either ventricle be monitored. METHODS: Of 30 healthy men (mean [+/- SD] age 35 +/- 7 years) studied with Doppler echocardiography, 20 were studied in the supine position and after 20 degrees, 40 degrees and 60 degrees tilting for 10 min; the remaining 10 subjects were also studied at the same levels of tilting for 45 min. RESULTS: At 20 degrees, heart rate, blood pressure and stroke volume were steady; the diastolic right ventricular area was reduced (p < 0.001); and the end-diastolic dimension of the left ventricle did not vary. Tilting at 40 degrees and 60 degrees increased heart rate and diastolic pressure, decreased systolic pressure and stroke volume and reduced the diastolic dimensions of both ventricles. At any tilting level, right and left peak early inflow velocities (E) were decreased, peak late velocities (A) were unchanged, and E/A ratios were reduced, suggesting that the atrial-ventricular pressure difference was diminished bilaterally and that the atrial contribution to ventricular filling was maintained. Tachycardia at 40 degrees and 60 degrees tilting was not associated with enhancement of left ventricular fiber fractional shortening or mean velocity of shortening for any corresponding end-systolic wall stress; changes in heart rate also did not correlate with those in fiber fractional shortening and velocity of shortening. The adaptive responses to the same degrees of tilting for a duration of 45 min were comparable to those at 10 min. CONCLUSIONS: With moderate restraint of venous return, the left ventricle maintains filling and output in response to a reduction in right ventricular diastolic volume, which increases left ventricular compliance (interdependence), and to the pulmonary blood reservoir, which compensates for an immediate decrease in right ventricular stroke volume. The decreased lung blood volume would facilitate right ventricular ejection, resulting in a normal stroke output despite the reduced preload. Thus, mechanical adjustments fully compensate for moderate reduction of venous return. A more severe reduction requires chronotropic support for the maintenance of cardiac output. With prolongation of tilting time to 45 min, adaptive mechanisms do not become exhausted in normal persons.

Adaptation, Physiological↗
PubMed1994

Calcium modulates the cyclin D1 expression in a rat parathyroid cell line.

We have used a rat epithelial parathyroid cell line (PT-r) to study the expression and regulation of D-type cyclins. In PT-r cells the cyclin D1 gene is the most abundantly expressed, being transcribed in at least two mRNAs whose levels oscillate during the cell cycle. We also screened a cDNA library prepared from PT-r cells with the human cyclin D1 probe and isolated its rat homologue. Cyclin D2 and D3 mRNAs are both represented in PT-r cells but the former one is only barely detectable. Moreover, the oscillation of cyclin D3 transcript is slightly delayed when compared to cyclin D1 and D2. Since extracellular calcium inhibits parathyroid cell proliferation, we looked for the effect of the ion on the expression of cyclin D genes in PT-r cells. Increasing amounts of calcium in the incubation medium reduced the expression of rat cyclin D1 and D2. The effect appears to be cell-specific and probably mediated through the inhibition of mitogenic signalling pathways.

Amino Acid Sequence↗
PubMed1994

Platelet-activating factor mediates an autocrine proliferative loop in the endometrial adenocarcinoma cell line HEC-1A.

We investigated the synthesis and biological effects of platelet-activating factor (PAF) in the human endometrial cancer cell line HEC-1A. We found that HEC-1A cells actively synthesize and release PAF, as demonstrated by both [3H]acetate incorporation into PAF and gas chromatography-mass spectrometry studies. HEC-1A cells not only synthesize but also respond to PAF. Indeed, in fura-2-loaded cells, PAF stimulates [Ca2+]i increase with a median effective concentration of 5.6 nM. Furthermore, PAF induces a time-dependent expression increase of the nuclear protooncogene c-fos with a median effective concentration of 130 nM and stimulates DNA synthesis (median effective concentration, 700 nM). All of these effects are inhibited by the PAF receptor antagonist L659,989. Radioligand binding studies indicated the presence of two populations of PAF receptors with affinity constants in the nanomolar and micromolar range. Since the PAF antagonist per se inhibits DNA synthesis and cell proliferation, we suggest that PAF supports an autocrine growth circuit in HEC-1A cells. On the contrary, in the uterine leiomyosarcoma cell line SK-UT-1, which does not express specific binding sites for PAF, neither this phospholipid nor its receptor antagonist affect DNA synthesis. Our results provide evidence for the existence of an autocrine proliferative loop involving PAF in the endometrial cancer cell line HEC-1A.

Acetyl-CoA C-Acetyltransferase↗
PubMed1994

Platelet-activating factor in human endometrium.

Platelet-activating factor (PAF) is a phospholipid actively produced by human endometrium and deeply involved in the processes of ovoimplantation and labor. We recently found that PAF represents a new autocrine growth factor for a human adenocarcinoma cell line, HEC-1A. Indeed, biologically active PAF is synthesized by HEC-1A cells, under progesterone control. In HEC-1A cells, PAF regulates intracellular calcium concentration ([Ca2+]), DNA synthesis and expression of early oncogenes. All these effects are blocked by the receptor antagonist L659,989. However, while nanomolar concentrations of PAF mobilize [Ca2+], only micromolar concentrations affect cell growth, suggesting heterogeneity of PAF receptors or signaling. Two distinct populations of PAF receptors are present in HEC-1A cells, which bind PAF in nanomolar and micromolar concentrations, respectively. Since HEC-1A cells are producing elevated concentrations of PAF and micromolar concentrations of the PAF antagonist L659,989 inhibit cell proliferation, an autocrine role for PAF is suggested in HEC-1A cells.

Adenocarcinoma↗
PubMed1994

Pericardial effusion after cardiac surgery: incidence, site, size, and haemodynamic consequences.

OBJECTIVE: To evaluate the incidence, characteristics, and haemodynamic consequences of pericardial effusion after cardiac surgery. DESIGN: Clinical, echocardiographic, and Doppler evaluations before and 8 days after cardiac surgery; with echocardiographic and Doppler follow up of patients with moderate or large pericardial effusion after operation. SETTING: Patients undergoing cardiac surgery at a tertiary centre. PATIENTS: 803 consecutive patients who had coronary artery bypass grafting (430), valve replacement (330), and other types of surgery (43). 23 were excluded because of early reoperation. MAIN OUTCOME MEASURES: Size and site of pericardial effusion evaluated by cross sectional echocardiography and signs of cardiac tamponade detected by ultrasound (right atrial and ventricular diastolic collapse, left ventricular diastolic collapse, distension of the inferior vena cava), and Doppler echocardiography (inspiratory decrease of aortic and mitral flow velocities). RESULTS: Pericardial effusion was detected in 498 (64%) of 780 patients and was more often associated with coronary artery bypass grafting than with valve replacement or other types of surgery; it was small in 68.4%, moderate in 29.8%, and large in 1.6%. Loculated effusions (57.8%) were more frequent than diffuse ones (42.2%). The size and site of effusion were related to the type of surgery. None of the small pericardial effusions increased in size; the amount of fluid decreased within a month in most patients with moderate effusion and in a few (7 patients) developed into a large effusion and cardiac tamponade. 15 individuals (1.9%) had cardiac tamponade; this event was significantly more common after valve replacement (12 patients) than after coronary artery bypass grafting (2 patients) or other types of surgery (1 patient after pulmonary embolectomy). In patients with cardiac tamponade aortic and mitral flow velocities invariably decreased during inspiration; the echocardiographic signs were less reliable. CONCLUSIONS: Pericardial effusion after cardiac surgery is common and its size and site are related to the type of surgery. Cardiac tamponade is rare and is more common in patients receiving oral anticoagulants. Echo-Doppler imaging is useful for the evaluation of pericardial fluid accumulations after cardiac surgery. It can identify effusions that herald cardiac tamponade.

Adolescent↗
PubMed1994

Prolactin responsiveness to peptide histidine methionine-27 in normal subjects and hyperprolactinemic patients.

In order to verify whether synthetic peptide histidine methionine (PHM-27) is able to induce serum prolactin (PRL) rise in normal subjects and to investigate its effect on PRL secretion in hyperprolactinemic conditions, PHM-27 (100 micrograms i.v. over 60 min at a rate of 3.3 micrograms/min) was given to 6 normal subjects and 11 hyperprolactinemic women, and serum PRL levels were measured before and at intervals up to 120 min after beginning the infusion. On a separate occasion, a saline infusion was administered to all these subjects as a control test. In normal subjects, PHM-27 caused PRL to increase from 7.8 +/- 1.4 micrograms/l (mean +/- SE) to 13 +/- 2.1 micrograms/l (p < 0.05), the peak occurring at 30 min, whereas it did not significantly modify serum PRL levels in 11 patients with prolactin-secreting adenomas. We also observed a significant difference of serum PRL pattern during PHM infusion when compared to saline in normal subjects. In contrast, in hyperprolactinemic states, PRL curves were similar in both tests. Continuous infusion of PHM-27 was very well tolerated and caused no important adverse events. These data suggest that PHM, like vasoactive intestinal peptide, can participate in the regulation of PRL release under physiological conditions and that the unsignificant PRL increase in PRL-secreting tumors may reflect abnormalities of the PRL secretion mechanism in these pathological states.

Adolescent↗
PubMed1994

[Multiplane transesophageal echocardiography for the monitoring of cardiac surgery].

Multiplane transesophageal echocardiography (TEE) allows visualization of the heart and great vessels through an infinite number of imaging planes and improves the diagnostic capabilities of mono and biplane TEE. This study was undertaken to test whether MTEE is a useful intraoperative monitoring method during cardiac surgery. Intraoperative multiplane TEE was performed in 200 patients (mean age 56 +/- 19 years) as a part of the routine clinical care. We systematically acquired cardiac images from the gastric fundus (short and long axes of the ventricles), lower esophagus (four-chamber, two-chamber, and long axis), upper esophagus (13 views concerning the aorta, pulmonary artery, left and right atrium, systemic and pulmonary veins, coronary arteries, right ventricular outflow tract), and searched for complete views of the thoracic descending aorta. All views analyzed in the preoperative (immediately before cardiopulmonary bypass), intraoperative and postoperative phases evaluating: the angle between current and 0 degree at which each view was obtained; the success rate of each view; the usefulness of the different views in providing essential additional clinical information compared to 0 degrees and 90 degrees of the traditional biplane TEE. Most views of the heart and great vessels were visualized in oblique planes, and other views were significantly improved thanks to slight angle corrections. Multiplane TEE was particularly useful in the preoperative and postoperative phases of aortic dissection (11 cases), mitral valve repair (13 cases), left ventricular aneurysmectomy (9 cases), right atrial thrombosis (1 case), positioning of left ventricular hemopump (2 cases), mitral-aortic endocarditis (3 cases), bleeding from proximal suture of an aortic heterograft (1 case).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Control of pulmonary vasomotility in congestive heart failure.

Although enhanced sympathetic tone is a well-known component of the autonomic imbalance of heart failure, its influence on pulmonary vasomotility is undefined. We investigated the pulmonary circulation in 12 patients with congestive heart failure in NYHA functional class III and in a control group of 10 normal subjects. Sympathetic influence on pulmonary vessels was studied through adrenergic activation by the arithmetic test and the cold pressor test. A rubber balloon was distended in the inferior vena cava to reduce transpulmonary flow and its influence on vascular tone. In normal individuals the arithmetic test caused pulmonary vasodilation, probably because of the mechanical effect of a largely enhanced flow: in fact, caval obstruction unmasked a neurogenic vasoconstrictor response to the arithmetic test by simply reducing the amount of cardiac output increase. In patients with heart failure, cardiac output and pulmonary arteriolar resistance remained steady during the arithmetic test, no matter what the condition of the venous return was. The cold pressor test was always a vasoconstrictor stimulus, but only in normal subjects was vasoconstriction potentiated by reducing, with caval obstruction, transpulmonary flow and its vasodilatory influence. From these data an attenuation of the sympathetic influence on pulmonary vessels in congestive heart failure seems to be likely. This might be explained as the result of modifications of pulmonary vessels rather than of reduced sympathetic excitability since circulating catecholamine levels varied to similar extents in the two groups during the tests. In congestive heart failure interstitial edema and vascular wall imbibition might increase pulmonary vessel tone and decrease vascular receptor availability. Lower reactivity to sympathetic stimuli, particularly to the vasoconstrictor ones, would ensue.

Adult↗
PubMed1993

Sustained cardiac diastolic changes elicited by ultrafiltration in patients with moderate congestive heart failure: pathophysiological correlates.

OBJECTIVE: To investigate the pathophysiological (cardiac function and physical performance) significance of clinically silent interstitial lung water accumulation in patients with moderate heart failure; to use isolated ultrafiltration as a means of extravascular fluid reabsorption. DESIGN: Echocardiographic, Doppler, chest x-ray evaluations, and cardiopulmonary tests at baseline, soon after ultrafiltration (veno venous extracorporeal circuit), and four days, one month, and three months later. SETTING: University institute of cardiology. SUBJECTS: 24 patients with heart failure due to idiopathic dilated cardiomyopathy or ischaemic myocardial disease with sinus rhythm and ejection fraction less than 35%. Twelve were randomised to ultrafiltration and 12 were taken as controls. MAIN OUTCOME MEASURES: Left ventricular systolic function (from ultrasonography); Doppler evaluation of mitral, tricuspid, and aortic flow and echo-Doppler determination of cardiac output; radiological score of extravascular lung water; right and left ventricular filling pressures; oxygen consumption at peak exercise and exercise tolerance time in cardiopulmonary tests. RESULTS: Soon after ultrafiltration (1976 (760) ml of fluid removed) the following was observed: a reduction in radiological score of extravascular lung water (from 15(1) to 9(1)) and of right (from 7.1 (2.3) to 2.3 (1.7) mm Hg) and left (from 17.6 (8.8) to 9.5 (6.4) mm Hg) ventricular filling pressures; an increase in oxygen consumption at peak exercise (from 15.8 (3.3) to 17.6 (2) ml/min/kg) and of tolerance time (from 444 (138) to 508 (134) s); a slight decrease in atrial and ventricular dimensions; no changes in the systolic function of the left ventricle; a reduction of the early to late filling ratio in both ventricles (mitral valve from 2 (2) to 1.1 (1.1)); (tricuspid valve from 1.3 (1.3) to 0.69 (0.18)) and an increase in the deceleration time of mitral and tricuspid flow, reflecting a redistribution of filling to late diastole. Variations in the ventricular filling pattern, lung water content, and functional performance persisted for three months in all cases. None of these changes was detected in the control group. CONCLUSIONS: Reduction of interstitial lung water was probably the mechanism whereby ultrafiltration modified the pattern of filling of the two ventricles and improved functional performance.

Aged↗
PubMed1993

Modification of exercise performance by sharp reduction of blood pressure. A study in patients with uncomplicated hypertension.

We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.

Anaerobic Threshold↗
PubMed1990

Effects of erdosteine on sputum biochemical and rheologic properties: pharmacokinetics in chronic obstructive lung disease.

Erdosteine is a new thioderivative endowed with mucokinetic, mucolytic, and free-radical-scavenging properties. This study evaluated (in a double-blind design vs. placebo) its efficacy on biochemical and rheologic properties of sputum and on some indices of respiratory function in chronic patients with chronic bronchitis (10 per group), while receiving basic treatment with a controlled-release theophylline preparation. The pharmacokinetics of erdosteine and theophylline were also studied. We found that a 2 week treatment with erdosteine (300 mg 3 times daily) was able to reduce significantly (p less than 0.05) the sputum apparent viscosity, fucose content, and macromolecular dry weight (MDW) with no statistically significant influence on sputum elasticity, DNA, albumin, total proteins, total IgA, lactoferrin, and lysozyme content. The treatment caused a significant increase in the following ratios: total IgA/albumin, lactoferrin/albumin, and lysozyme/albumin. The pharmacokinetics of erdosteine, its metabolites, and theophylline were the same after 1 or 14 days of treatment, evidence both of absence of an enzymatic induction and of an accumulation process. Further confirmation that there was no interference between erdosteine and theophylline was obtained from the data available on the group of patients receiving only theophylline, since its plasma levels and related pharmacokinetic parameters were identical to those obtained in patients receiving both drugs. In conclusion, 2 weeks of therapy with erdosteine reduced the marker of mucus glycoproteins (fucose) in patients with chronic bronchitis but did not interfere with the pharmacokinetics of xanthine derivatives. We also suggest that the significant increment in the IgA/albumin ratio might be related to a sum of other local effects such as reduction of the inflammatory process and enhancement of the humoral defense mechanism.

Bronchitis↗
PubMed1990

Osteocalcin levels in patients with microprolactinoma before and during medical treatment.

Osteocalcin (OC) concentration, a specific index of bone formation, was measured in 29 female patients with microprolactinoma (serum prolactin, PRL: 105 +/- 10.9 ng/ml; mean +/- SE). Mean OC levels were significantly lower than in controls (1.7 +/- 0.2 vs 5.1 +/- 0.3 ng/ml; p less than 0.001), being below the normal range in 28 out of 29 patients. All patients were treated with dopaminergic agents (dihydroergocriptine, bromocriptine or cabergoline). After treatment mean serum PRL levels were significantly reduced (12 +/- 3.1 ng/ml; p less than 0.001), a full normalization being obtained in 26 patients. There were no significant differences in both basal and after treatment PRL levels among patients treated with different drugs, although a greater PRL decrease was induced by cabergoline. Serum OC levels significantly increased after 12 month therapy (4.7 +/- 0.6 ng/ml, p less than 0.001), a normal concentration being reached in 14 of 29 cases. During treatment there were no significant differences in serum estradiol and PRL concentrations between patients who normalized or not their OC levels, while the reduction in PRL levels with respect to baseline was more pronounced in the former group. The absolute increase in OC levels positively correlated with serum PRL decrements (p less than 0.01). It is noteworthy that serum OC normalized in 1/10 patients during dihydroergocriptine, 3/8 during bromocriptine and 10/11 during cabergoline. Four patients, previously treated with dihydroergocriptine and bromocriptine without normalizing OC and PRL levels, underwent a second course of therapy with cabergoline and then normalized OC concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗