Biomedical subjects
Publications and source records attributed to A Perruchoud.
An isolated left lower lobe was used as a left graft, during a bilateral single lung transplantation procedure, in a patient with infected fibrosis. This technique is suitable for patients with small lung volume (especially cystic fibrosis) or asymmetric retraction.
For double lung transplantation, lung volume matching is easier comparing the predicted total lung capacities of the donor and recipient and the recipient's true TLC. The major concern in the inability to close the chest when the donor lungs are too large. The technique reported of left lower lobe implantation during bilateral single lung transplantation might be of great value in patients with small lung volume.
The effects of Ca(2+)-channel blockers (amlodipine, nifedipine, nitrendipine, and verapamil) on expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.88) and low density lipoprotein receptor (LDL-R) genes stimulated by recombinant platelet-derived growth factor BB isomer (PDGF-BB) were evaluated in human skin fibroblasts. The drugs enhanced expression of the LDL-R protein on the plasma membrane of the cells; in contrast, they inhibited expression of the HMG-CoA reductase gene. In addition, PDGF-BB-dependent stimulation of transcription of c-fos mRNA was inhibited also by the Ca(2+)-channel blockers. We conclude that PDGF-BB-dependent activation of the two genes is inhibited effectively by the Ca(2+)-channel blockers, at therapeutic concentrations, although they are unable to lower systemic cholesterol levels at these concentrations; however, they do modify responses of the two genes that are involved crucially in regulation of cellular cholesterol homeostasis.
The plausible role that platelet-derived growth factor (PDGF) has in the localized pathophysiological changes that occur in the arterial wall during development of atherosclerotic lesions led us to investigate the influence of recombinant (r)PDGF isomers -AA, -AB, and -BB on the expression of low density lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase [(S)-mevalonate:NAD+ oxidoreductase (CoA-acylating), EC 1.1.1.88] genes. In addition, we clarified the role of protein kinase C (PKC) in expression of the two genes in human skin fibroblasts and vascular smooth muscle cells. The various rPDGF isoforms are distinct in their ability to activate transcription of both genes: (i) Both rPDGF-AA and -BB stimulate transcription of the LDL-R gene; in contrast, rPDGF-BB, but not -AA, activates transcription of the HMG-CoA reductase gene. (ii) All recombinant isoforms of PDGF activate transcription of the c-fos gene. (iii) While rPDGF-dependent transcription of the LDL-R gene occurs independently of PKC, transcription of the HMG-CoA reductase gene appears to involve the action of that enzyme.
HIV infects susceptible T-cell and mononuclear phagocyte targets. Unlike the dramatic changes that occur with T-cells during HIV disease, changes in monocyte and macrophage phenotype and function are qualitatively minimal. The aim of the study was to quantitatively analyze the morphology of macrophages in broncho-alveolar lavages in patients without AIDS, with AIDS, with AIDS complicated by Pneumocystis carinii and in carcinoma patients. In patients with AIDS, the nuclei of macrophages demonstrate a higher integrated optical density (2P less than 0.10), are bigger in size (2P less than 0.05) and have less notches (2P less than 0.02).
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The predictability and intraindividual variability of serum theophylline concentrations (STC) after different dosing schedules were investigated in 24 patients with chronic obstructive lung disease (COLD). Three oral regimens were compared in 3 groups of 8 randomly assigned patients. Group I:Drug A once daily in the evening; Group II: Drug A b.d.; Group III: Drug B b.d. The doses for each patient were estimated by Bayesian forecasting aiming at an STC of 10-15 mg/l. STC and FEV1 were measured on two consecutive days at steady-state. The day-to-day variability of STC was less than 20% in all three groups. The within-day fluctuation in Group I amounted to 259% (median) compared to 57% and 38% in Groups II and III, respectively. Dose adjustment by Bayesian forecasting resulted in a therapeutic STC in most patients with a b.d. regimen, whereas for the once daily dose the prediction was not satisfactory. No difference in lung function was found between the 24-h and 12-h dosing, probably because of the large intersubject variability in FEV1. Therefore, the question whether the differences in STC profile are of clinical importance in COLD can only be investigated in a larger group of patients.
To assess the interaction of the two major stress hormones epinephrine and cortisol in the regulation of leucine kinetics in man, epinephrine (50 ng/kg/min) was infused either alone or in combination with cortisol (2 micrograms/kg/min) into two groups of 6 postabsorptive normal male subjects during 180 min. Plasma leucine concentrations decreased by 28% (p less than 0.05) from baseline during epinephrine treatment (plasma levels 515 pg/ml); this was due to a decrease of leucine appearance (determined by 1-13C-leucine infusions) by 23% (p less than 0.025); leucine oxidation decreased by 29% (p less than 0.05). However, when plasma cortisol concentrations were elevated to supraphysiological levels (16.3 mumol/l) during epinephrine administration, the decreases of leucine plasma concentrations, appearance and oxidation were abolished. Plasma glucose and FFA concentrations were similarly elevated during both kinds of treatment. Since leucine appearance represents a measurement of total body protein breakdown and leucine disappearance into non-oxidative pathways reflects protein synthesis, the data indicate that plasma epinephrine concentrations during severe stress exert a protein anabolic effect in man which may counteract catabolic properties of elevated plasma cortisol.
The definition, causes and some pathophysiological aspects of acute respiratory failure are discussed and a systematic clinical workup for these patients is proposed. The clinical and functional parameters for intubation and artifical ventilation are described. Finally, some special problems of therapy in some diseases leading to acute respiratory failure are mentioned. The basic disease not only indicates the criteria for intubation but also determines modifications in ventilatory support.
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90 out of 202 lung cancer patients hospitalized for preoperative investigations were scheduled for radical surgery. 15 patients were not operated on because of insufficient lung function data. The operation was performed in 75 patients. The complication rate was 11% and mortality 8%. 7 out of 8 patients who subsequently developed severe complications had fulfilled the criteria for lung resection only after intensive antibronchitic treatment. Nearly all the survivors showed the predicted preoperative minimal lung function values after the operation. The limit of 1000 ml for postoperative FEV1 is justified, since patients with these or larger functional reserves nearly all had a favourable early and late postoperative course, and also because lung function values continuously deteriorate in chronic obstructive lung disease.
The effect of three different doses of somatostatin on splanchnic blood flow (SBF) and on arterial plasma insulin, glucagon and glucose was determined. 125, 250 and 500 microgram/h of somatostatin was infused during 60 minutes in 3 groups of 6 patients undergoing arterial-hepatic-venous catheterization; no patient had clinical evidence of metabolitic or hepatic disease. Continuous infusion of 125 microgram/h somatostatin was without significant effect on SBF, whereas 250 microgram/h resulted in a mean 28% reduction of SBF (p less than 0.05). Doubling the dose to 500 microgram/h affected SBF similarly (21% reduction of SBF). In contrast, administration of all three doses of somatostatin suppressed the circulating insulin and glucagon levels significantly. In a recent report somatostatin had been administered in a dose of 250 microgram/h to control gastric ulcer hemorrhage. The present studies demonstrate that this dose results in a significant reduction of SBF which cannot be further depressed by increasing the dose.
The dose-response relationship of the new bronchodilator Clenbuterol (NAB 365, Boehringer Ingelheim) was tested in 12 patients with chronic obstructive lung disease. Clenbuterol is a beta-2-sympathicomimetic, from a series of substituted phenylethanolamines, and it is characterised by good absorption and prolonged action after systemic administration. The action of four different doses of Clenbuterol inhalation solution (6, 12, 24, and 48 microgram corresponding to 2, 4, 8 and 16 drops of a 0.006% solution) was assessed after a single inhalation on 4 successive days. The parameters monitored were bronchial resistance and FEV. The effect of all four doses was the same, both in respect of improvement in FEV and of decrease in bronchial resistance. The increase in expiratory volume and the decrease in bronchial resistance lasted for 6 h. The results show that for inhalation therapy Clenbuterol is a potent, selective bronchodilator, which is largely free of sideeffects. It has still to be determined whether a maximal effect could be achieved with a lower dose 6 microgram.
Thoracoscopy is a method involving little discomfort for the patient but of high diagnostic effectiveness for pleural alterations. A histological diagnosis was established in 56 cases out of a total of 60 pleural effusions of unknown origin. In 10 pleural or pleuropulmonary diseases, anatomical classification was possible in all cases. In cases of pneumothorax (21 patients) the bronchopleural fistula could very often be seen and closure by detaching of pleural adhesions or cauterization was possible. These manipulations are usually followed by insufflation of sterile talcum powder through the thoracoscope. Suspicion of ruptured diaphragm due to accident was easily and quickly verified. No complications occurred in our 100 thoracoscopic examinations.
The treatment of spontaneous pneumothorax is still controversial. To evaluate pleural drainage with a chest tube the therapeutic results in 73 patients with benign pneumothorax were reviewed. Benign spontaneous pneumothorax treated with a thick chest tube size Charrière 18-22 disappeared within an average of only 6.6 days. On the other hand, the high recurrence rate of 24% after the initial pneumothorax and 37% after the first recurrence is comparable with the results of conservative management in other pneumothorax series in the literature. Small pneumothorax without severe symptoms should therefore be supervised conservatively on an outpatient basis. The more extended forms of pneumothorax should be treated with thick chest tubes. Failure of therapeutic effect, second ipsilateral relapse or the first contralateral pneumothorax are indications for parietal pleurectomy.
Previous reports dealing with cardiac herniation following intrapericardial pneumonectomy illustrate the critical and often lethal hemodynamic sequelae of this complication. In the case presented here, the first and nearly exclusive sign of cardiac herniation after left-sided pneumonectomy with extensive resection of the pericardium was systemic arterial hypoxemia. Subsequent investigations suggested inter-atrial right-to-left shunt in the presence of a patent foramen ovale, caused by slight right-ventricular outflow obstruction with consecutively reversed pressure relationships at atrial level. This explanation was supported by the operative findings, and reversibility was achieved by pericardial reconstruction with parietal pleura. When the patient died 8 months later due to general progression of a mucoepidermoid carcinoma, autopsy confirmed a large patent foramen ovale.
The effects of smoking and inhalation of carbon monoxide on the systolic time intervals and blood pressure were examined in ten healthy smokers with a mean age of 24.3 years. Each subject smoked a low-nicotine cigarette with a ventilated filter (0.1 mg nicotine, 1.1 vol percent CO), and a high-nicotine plain cigarette (2.6 mg nicotine, 4.5 vol percent CO), as well as a cigar in random sequence and in a standardized way. Cigar smoke was not inhaled. The product heart rate x blood pressure was increased and the left ventricular ejection time index (LVETc) prolonged following smoking the high-nicotine cigarette, whereas changes after smoking the low-nicotine cigarette and the cigar were not as pronounced. These changes are presumably caused by nicotine-induced catecholamine release. Inhalation of CO did not affect cardiac performance acutely as shown by unchanged systolic time intervals. When a high-nicotine cigarette was smoked after the subject received a beta blocker, a significant prolongation of the pre-ejection period index (PEPc) occurred as a result of the increased afterload. Thus, the effects of catecholamines on parameters of myocardial contractility (PEPc, PEP/LVET) were presumably offset by the increased afterload. We conclude that the acute hemodynamic changes of smoking in healthy subjects depend upon the amount of nicotine absorbed.