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Biomedical subjects

M Bernasconi

Publications and source records attributed to M Bernasconi.

At least 37 records · Page 2Linked to original sources

Molecular cloning and characterization of a human PAX-7 cDNA expressed in normal and neoplastic myocytes.

The myogenic basic helix-loop-helix proteins are essential components of the regulatory network controlling vertebrate myogenesis. However, determined myoblasts appear in the limb buds which do not initially express any member of this transcription factor family. In a search for potential novel regulators of myogenesis, a human PAX-7 cDNA was isolated from primary myoblasts. Analysis of the DNA-binding properties of the Pax-7 paired domain revealed that it binds DNA in a sequence-specific manner indistinguishable from that of the paralogous Pax-3 protein. Each of the two proteins also binds to palindromic homeodomain-binding sites by cooperative dimerization. Both Pax-3 and Pax-7, which are known to partially overlap in their expression during development, can also efficiently form heterodimers on these sites and stimulate reporter gene transcription in transient transfection experiments which, in the case of Pax-7, is dependent on the transactivation function encoded by the C-terminal sequences. Thus, the formation of heterodimers might have important consequences for target gene recognition and regulation during development. PAX-7 was found to be weakly expressed in normal human myoblasts, while PAX-3 could not be detected in these cells at all. However, transcripts for either PAX-3 and/or PAX-7 were expressed at elevated levels in tumorigenic rhabdomyosarcoma cell lines. Hence, overexpression of these PAX genes may be involved in the genesis of myogenic tumors.

Amino Acid Sequence↗

Effects of intrinsic PEEP on pulmonary gas exchange in mechanically-ventilated patients.

The aim of the study was to assess the impact of the intrinsic positive end-expiratory pressure (PEEPi) on pulmonary gas exchange in mechanically-ventilated patients, by comparing the effects of similar levels (0.8-0.9 kPa) of positive end-expiratory pressure (PEEP) and PEEPi. Ten patients with acute respiratory failure, without chronic airway disease, were studied with three ventilatory modes: 1) intermittent positive pressure ventilation with zero end-expiratory pressure (ZEEP mode); 2) continuous positive pressure ventilation with PEEP set by the ventilator (PEEP mode); and 3) intrinsic PEEP elicited by adequate shortening of the expiratory time (PEEPi mode). Cardiorespiratory variables (e.g. respiratory compliance and resistance, arterial and mixed venous blood gases, cardiac output, pulmonary capillary pressure, oxygen delivery) were measured during each ventilatory mode. Compared to ZEEP, both PEEP and PEEPi decreased cardiac output while increasing arterial oxygen tension (PaO2). However, the improvement of PaO2 was more consistent (8 out of 10 patients), and larger (+2.1 kPa, on average, p < 0.05) with PEEP than with PEEPi (5 out of 10 patients, and +1.4 kPa, on average, NS). Since the effects of PEEP and PEEPi on ventilation, lung volume, compliance, cardiac output (QT), mixed venous oxygen tension (PvO2) and oxygen consumption (VO2) were similar, we attributed the less favourable impact of PEEPi on PaO2 to a less homogeneous distribution of PEEPi between lung units with different time constant, and hence to a more uneven distribution of the inspired gas.

Adolescent↗

Cardiovascular pressor reactivity after chronic converting enzyme inhibition.

In addition to inhibiting the formation of angiotensin II, chronic converting enzyme inhibition may affect other blood pressure modulating factors. The influence of an 8 week treatment phase with cilazapril on the activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, the pressor reactivity to infused angiotensin II or norepinephrine, the chronotropic response to isoproterenol, and body sodium and plasma atrial natriuretic peptide concentrations was assessed in 11 normal subjects and 12 patients with essential hypertension. As compared to a 4 week placebo phase, cilazapril decreased arterial pressure in both study groups (from 124/83 +/- 9/6 to 114/77 +/- 9/5 mm Hg and from 143/102 +/- 13/7 to 137/96 +/- 10/10 mm Hg; P less than .025); exchangeable sodium (-158 mmol and, respectively, -104 mmol) and upright plasma aldosterone (-24% and -15%) also tended to fall. Heart rate, the chronotropic response to posture or isoproterenol, plasma norepinephrine levels, the concentration/pressor response curve to norepinephrine, plasma atrial natriuretic peptide concentration, plasma angiotensin II and the responses of blood pressure or plasma aldosterone to angiotensin II were unchanged after 8 weeks of cilazapril. Plasma renin activity increased (+175% to +650%). These findings indicate that the blood pressure lowering effect of cilazapril in the stable phase of pharmacological intervention is not associated with modifications of sympathetic-dependent pressor reactivity or beta-adrenergic sensitivity. Plasma angiotensin II concentration and angiotensin II-dependent pathways including the pressor and aldosterone responsiveness to angiotensin II are also unchanged.

Adolescent↗

Dose-response effects and time course of effects of inhaled fenoterol on respiratory mechanics and arterial oxygen tension in mechanically ventilated patients with chronic airflow obstruction.

To investigate the dose-response relationship and the time course of the effects of fenoterol (a selective beta 2-adrenergic agonist) on respiratory function in mechanically ventilated patients with acute respiratory failure due to exacerbation of chronic airflow obstruction (CAO), seven consecutive acutely ill patients were studied within 3 days of the onset of mechanical ventilation. Airflow, airway pressure, and changes in lung volume were measured with the transducers of the 900 C Servo Ventilator, the last by electronic integration. The end-expiratory lung volume (EELV), the intrinsic positive end-expiratory pressure (PEEPi), the static respiratory compliance (Cstrs), maximum and minimum respiratory resistance (Rrsmax and Rrsmin), and arterial oxygen tension (PaO2), were measured under control conditions (all patients were receiving aminophylline infused at a constant rate) 5, 15, and 30 min after administration of 4 ml aerosolized saline solution and 5, 15, and 30 min after inhalation of 0.4, 0.8, and 1.2 mg fenoterol. After the last dose, measurements were repeated at 60, 120, and 180 min. We found that, on average, while saline did not cause any significant change in respiratory mechanics, a low dose (0.4 mg) of inhaled fenoterol was followed by a rapid (5 min) and significant decrease in Rrsmax (-33%), Rrsmin (-28%), EELV (-34%), and PEEPi (-44%), with a slight but not significant further fall with higher doses. However, changes were short-lasting, and by 2 h after the end of administration were no longer significant. PaO2 dropped significantly on average, with a maximum mean fall of 15 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

[Pheochromocytoma diagnosed during quinapril therapy].

A hypertensive diabetic woman, who was resistant to any pharmacological therapy, underwent to check for secondary hypertension. The treatment with the particularly active ACE inhibitor quinapril failed but it suggested a procedure for a fast differential diagnosis of disease.

Adrenal Gland Neoplasms↗

[Chronic gastritis. A study of 151 cases diagnosed using gastric biopsy].

With the aim to detect a correlation between endoscopic aspects and histological features of chronic gastritis, the Authors have analysed retrospectively a series of 151 cases where endoscopic alterations were likely due to chronic gastritis and in all cases multiple biopsies were performed. A possible correlation between endoscopy, histology and occurrence of intestinal metaplasia has been carefully evaluated. Only in chronic atrophic gastritis a certain relationship between endoscopic features and histologic diagnosis was detectable: in the same cases a high incidence of intestinal metaplasia was found as well, independently from the severity of endoscopic and/or histologic aspects. The Authors discuss the controversial problems in terminology and endoscopic definition of chronic gastritis.

Adolescent↗

Doxofylline and respiratory mechanics. Short-term effects in mechanically ventilated patients with airflow obstruction and respiratory failure.

To assess the short-term effects of a methylxanthine (doxofylline) on respiratory mechanics in mechanically ventilated patients with airway obstruction and respiratory failure, nine consecutive patients were examined within three days from the onset of mechanical ventilation. Flow, changes in pulmonary volume, and Paw were measured using a ventilator (Servo 900C). End-expiratory and end-inspiratory airway occlusion was performed to measure PEEPi, Cstrs, Rrsmax, and Rrsmin. Measurements were performed before and at 5, 15, and 30 minutes after an intravenous loading dose of doxofylline (5 to 6 mg/kg). We found that doxofylline determined, on the average, a marked decrease in respiratory resistance (Rrsmax and Rrsmin, -27.2 percent and -36.5 percent, respectively) without significant changes in Cstrs and Pmax. The PEEPi, reflecting pulmonary dynamic hyperinflation, was also significantly decreased by doxofylline (-41 percent, on the average). The Pmax was not reliable for evaluation of a single patient, since changes in the elastic pressure can offset changes in the resistive one. No patient experienced significant side effects due to doxofylline. We conclude that (1) the effects of therapy can be assessed noninvasively at bedside in critically ill patients; (2) doxofylline is a rapid and efficient bronchodilator in mechanically ventilated patients with ARF and airflow obstruction; and (3) the decrease in the respiratory resistance and PEEPi, associated with an improved mechanical efficiency of the respiratory muscles at a lower pulmonary volume, can provide better conditions for the patient-ventilator interaction and for weaning.

Bronchodilator Agents↗

[Amiodarone prophylaxis of ventricular tachycardia in ischemic cardiopathy].

Sustained ventricular tachycardia (VT) in coronary heart disease (CHD) represents a major risk factor for sudden death. The Authors evaluated the prophylactic efficacy of the chronic administration of amiodarone (A) on this arrhythmia and simultaneously the trend of ventricular extrasystole during the antiarrhythmic treatment. Twenty-three patients were examined, 17 with post-infarction cardiopathy and 6 with mixed angina. They showed either 1 or more episodes (2 patients) of sustained VT involving hemodynamic difficulties. The ejection fraction (EF) ranged between 20 and 45% average (35.2 +/- 9). All patients underwent a basal 24 hour ECG 3 days after the VT cardioversion, and every 6 months. All subjects took A orally for a period ranging from 7 to 67 months (average 23.04 +/- 14) at the dose of 800 mg/day 7 for days, and then 200 or 400 mg/day according to the presence or absence of ventricular extrasystoles (VE) greater than or equal to 30/hr and/or Lown's class (L) greater than or equal to 3. No patients died suddenly during the follow-up; 6 of them died for causes other than arrhythmia. Four of them showed only 1 sustained VT relapse after a period of 6 to 11 months. Two of these 4 patients showed a persistent increase of the number of VE and L-class while, in the remaining 2 patients, the number of VE remained substantially unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure.

The purpose of this study was noninvasive assessment of respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure (ARF). To this end, flow, change in lung volume, and airway pressure were measured at the proximal tip of the endotracheal tubes in twenty nine critically ill unselected patients. Eleven had acute exacerbation of chronic obstructive pulmonary disease (COPD), 8 had adult respiratory distress syndrome (ARDS) and 10 had ARF of various etiologies. Static compliance (Cst,rs), 'intrinsic' PEEP (PEEPi), as well as minimum and maximum resistance (Rrs,min and Rrs,max, respectively) were obtained with end-inspiratory and end-expiratory airway occlusions. We found that: (1) PEEPi was present in all patients with COPD (up to 11.4 cmH2O) and it was not uncommon in patients with ARF without history of chronic airway disease (up to 4.1 cmH2O). (2) Without correction for PEEPi average Cst,rs was not significantly different between ARDS and COPD patients, whereas the average corrected compliance was significantly lower in ARDS patients. (3) Substantial frequency-dependence of resistance was exhibited not only by COPD patients, but also by ARDS patients.

Adult↗