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Biomedical subjects

M Gugger

Publications and source records attributed to M Gugger.

81 records · Page 5Linked to original sources

Low plasma concentrations of ionized calcium in patients with asthma.

It has been suggested that calcium homeostasis is abnormal in the vascular smooth muscle of hypertensive patients and in the bronchial smooth muscle in asthmatics. We have found the mean baseline concentration of plasma ionized calcium to be significantly lower both in 12 asthmatics with exercise-induced asthma (EIA) [1.16 +/- 0.01 (SE) mmol/l, P less than 0.001] and in 20 asthmatics without EIA (1.16 +/- 0.01; P less than 0.001) compared with 42 healthy subjects (1.24 +/- 0.01). The mean concentrations of plasma ionized calcium were not significantly different in asthmatics with and without EIA when measured either before treadmill exercise, during the last seconds of this exercise, or 10 or 20 min after exercise but were significantly lower than in another seven healthy subjects who undertook the same exercise protocol. Total plasma calcium concentrations in the three exercising groups were not significantly different at any point in time. The results suggest that in bronchial asthma an alteration of calcium metabolism may be important, but they also suggest that there is no simple relationship between the plasma ionized calcium concentration and acute exercise-induced bronchoconstriction.

Asthma↗

Breathing pattern and eye movement density during REM sleep in humans.

Changes in the density of eye movement during rapid eye movement (REM) sleep are associated with changes in ventilation and ventilatory response in animals. Recent data in patients with chronic obstructive pulmonary disease suggest that periods of frequent eye movements may be associated with hypoxemia during REM sleep. We have therefore investigated the association between eye movements and ventilation and ventilatory pattern in 10 normal men. Expired ventilation was measured using a pneumotachograph attached to a valved face mask with a dead space of 50 ml and incorporating a peripheral CO2 leak detector. Ventilation was reduced (p less than 0.02) in all stages of sleep compared with that during wakefulness, with no difference between the level of ventilation in each sleep stage (awake, 7.18 +/- 0.43 SEM; Stage 2, 6.47 +/- 0.43; Stage 3/4, 6.45 +/- 0.52; REM sleep, 6.55 +/- 0.47 L/min). During REM sleep, eye movements (EMs) were associated with rapid shallow breathing. Dividing REM into 20-s epochs with or without EMs, EMs were associated with a raised breathing frequency (no EMs, 14.4 +/- 0.4 breaths/min; EMs, 15.8 +/- 0.5 breaths/min; p = 0.01), reduced tidal volume (0.49 +/- 0.03 L; 0.41 +/- 0.03 L; p less than 0.01), and reduced minute ventilation (6.87 +/- 0.45 L; 6.27 +/- 0.51 L; p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Steady-state concentration of cotinine as a measure of nicotine-intake by smokers.

Measurement of plasma cotinine, the major metabolite of nicotine, is usually done to determine nicotine-intake in smokers. Cotinine is used instead of nicotine because it has a much longer half-life than the mother substance and its plasma concentrations are therefore less dependent on the exact times of blood sampling. However, the linearity of the relationship between nicotine-intake and cotinine level in plasma has never been proven. Therefore cotinine was measured in 6 healthy volunteers infused over 4 days with several doses of nicotine i.v. up to 480 micrograms/kg/day. Cotinine concentrations in plasma were shown to be linearly and directly related to nicotine intake. The concentration of cotinine showed little variation during and for up to 2 h after the last dose of nicotine. Therefore, cotinine can be used as an epidemiological marker of nicotine intake if it is measured around the time of the last cigarette of the day.

Adult↗

Effects of the calcium antagonist tiapamil on pulmonary gas exchange in patients with chronic obstructive pulmonary disease who receive salbutamol.

Patients with chronic obstructive pulmonary disease (COPD) and cardiovascular diseases are frequently given combination therapy with a beta 2-agonist and a calcium antagonist. Each drug is known to increase ventilation-perfusion inequalities. It was our aim to define the effects of their combination on lung function and on pulmonary gas exchange in eight subjects with COPD but partially reversible airway obstruction. Sixty minutes after placebo or 450 mg tiapamil, subjects inhaled 0.2 mg salbutamol. There was no significant effect of tiapamil on specific airway conductance and the forced expiratory volume in 1 second before or after the inhalation of salbutamol. Blood was drawn 30, 55, 80, and 100 minutes after placebo or tiapamil dosing. After placebo the mean (+/- SD) arterial oxygen tension (Pao2) fell from 67.1 +/- 7.3 to 64.4 +/- 5.5 mm Hg and the mean alveolar-arterial oxygen tension difference (AaDo2) rose from 34.6 +/- 8.4 to 40.5 +/- 6.8 mm Hg. After tiapamil the mean Pao2 fell from 68.7 +/- 7.3 to 66.4 +/- 5.8 mm Hg and the mean AaDo2 rose from 35.1 +/- 6.8 to 38.7 +/- 7.4 mm Hg. The changes in Pao2 were not significant. The increase in AaDo2 after placebo was significant, but that after tiapamil was not. We conclude that the combination of the calcium antagonist tiapamil and the bronchodilator salbutamol is safe with respect to lung function in COPD. There is no evidence that tiapamil increases beta 2-agonist-induced impairment in pulmonary gas exchange.

Adult↗

[Young syndrome. Chronic sino-pulmonary infection and infertility].

Young's syndrome is a combination of chronic sinopulmonary infections and obstructive azoospermia in men. Cystic fibrosis and the "immotile cilia syndrome" must be ruled out. The most important methods in differential diagnosis are determination of sweat chloride and sodium levels, investigation of cilia ultrastructure and analysis of semen samples. A case of Young's syndrome in a 42-year-old patient is reported.

Adult↗

beta blockade with pindolol: differential cardiac and renal effects despite similar plasma kinetics in normal and uremic man.

Cardiac and renal effects (measured as the reduction in exercise-induced tachycardia and PRA, respectively) and circulating drug concentrations after acute beta blockade with intravenous pindolol were compared between seven normal volunteers and six patients with terminal renal failure. Kinetic parameters were similar in both groups (total body clearance, 450 mg/min), indicating enhanced extrarenal elimination in patients. For any given drug concentration, however, the uremic patients responded to beta blockade with a greater decrease in pulse rate than did normal volunteers (P less than 0.001). Moreover, in the same group, the decrease of PRA was more marked (from 13.3 to 5.7 vs. 3.3 to 1.9 ng/ml/hr) and lasted longer (8 hours and more vs. 2 hours). Plasma aldosterone remained unchanged. These data reveal an increased dependency of both heart rate and renin release on beta adrenergic-mediated mechanisms in uremic man. They also show that kinetic findings in normal subjects cannot always be extrapolated to predict kinetic behavior in disease, and that similar kinetics do not imply similar effectiveness.

Adult↗

Alterations of cell cycle regulators are less frequent in advanced non-small cell lung cancer than in resectable tumours.

Prognosis of lung cancer is related to stage of disease at time of diagnosis. In this study we examine alterations of pathways governing the cell cycle, in particular pRb-cyclinD1-p16 alpha and p53-p14ARF, in a series of NSCLC (n=92) at different stages at diagnosis. Using immunohistochemistry, we assessed the expression of the retinoblastoma protein (pRb), cyclin D1, p16 alpha, p53 and p14ARF. Tumours in stage I-IIIA (resectable) were more likely to have alterations in the pRb-cyclinD1-p16 alpha pathway than tumours in advanced stage (IIIB-IV) (90% versus 63%, P=0.002). pRb and p14ARF were more frequently downregulated in resectable tumours (P< or =0.03), and cyclin D1, p16 alpha, and p53 were altered at a similar frequency in resectable and advanced tumours. In 12 patients, metastatic sites (5 lymph node, 3 bone, 2 brain and 2 gastrointestinal metastases) were available for comparison with the primary tumour: 19 altered protein expressions were found to be concordant, six additional alterations (in 4 patients) were found in the metastases only, especially in lymph node metastases (3 patients). Compared with normal protein expression, both pathway alterations were associated with a longer survival (P=0.02). In a multivariate analysis (Cox regression) this difference was not maintained after adjustment for age, stage and tumour differentiation. Cyclin D1 was the sole protein with independent prognostic value in resectable tumours: the relative risk of local relapse was 4.7 in tumours without cyclin D1 overexpression (P=0.02, Cox regression analysis). No protein studied had a predictive significance for response after chemotherapy in non-resectable tumours. These results demonstrate a strong correlation between stage and pathway alterations, cell cycle regulators being less likely altered in advanced NSCLC. Tumours with defects in these control pathways tend therefore to remain localised and to metastasize at a later phase in tumour development. This finding might be an explanation for distinct biological behaviour (e.g. chemotherapy response) of resectable versus advanced disease.

Aged↗