Mechanism of bronchodilator effect in chronic airflow limitation.

OBJECTIVE: To examine the mechanisms through which two bronchodilators (theophylline and salbutamol) influence dyspnea during daily activities. METHODS: Twenty-four patients with chronic airflow limitation participated in a multiple crossover, randomized, placebo-controlled trial. The effect of theophylline and salbutamol, alone or combined, on pulmonary function and dyspnea during daily activities was examined. Correlations of changes in forced expiratory volume in 1 second (FEV1) and maximum expiratory pressures (MIPs) (independent variables) and changes in dyspnea score during daily activities (dependent variable) were also examined. RESULTS: The two drugs proved to be beneficial the effects in general were additive rather than synergistic. The drugs improved the FEV1; theophylline significantly improved the MIPs. The correlation between the changes in FEV1 and those in dyspnea score, after adjustment for the changes in MIPs, was 0.55 (p less than 0.001). The correlation between the changes in MIPs and those in dyspnea score, after adjustment for the changes in FEV1, was 0.39 (p less than 0.001). CONCLUSIONS: Changes in airway calibre and in respiratory muscle strength play an independent and important role in dyspnea during daily activities in patients with chronic airflow limitation. Changes in airway calibre may be of greater importance.     

Monocrotaline-induced cardiopulmonary injury in rats. Modification by the neutrophil elastase inhibitor SC39026

Rats were killed after 6 weeks of continuous ingestion of the pneumotoxic alkaloid monocrotaline (2.2 mg/kg/day), the neutrophil elastase inhibitor SC39026 (60 mg/kg/day), or both. Pulmonary reactions were evaluated by light and electron microscopy. Lung endothelial function was monitored by angiotensin converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Lung hydroxyproline content was measured as an index of interstitial fibrosis. Cardiac right ventricular hypertrophy was determined by the right ventricle to the left ventricle plus septum weight ratio (RV/LV + S). Rats receiving SC39026 alone did not differ significantly from untreated control animals with respect to any of the quantitative endpoints, although rarefaction of Type I pneumocytes was observed in the electron micrographs of these animals. Monocrotaline-treated rats, in contrast, developed a significant increase in RV/LV + S, and exhibited pulmonary edema, inflammation, fibrosis, and muscularization and occlusive mural thickening of the pulmonary small arteries and arterioles. These monocrotaline-induced structural changes were accompanied by decreased lung ACE and PLA activities, and increased PGI2 and TXA2 production, and by an increase in lung hydroxyproline content. Cotreatment with SC39026 ameliorated the monocrotaline-induced pulmonary vascular wall thickening and the cardiac right ventricular hypertrophy. These data suggest that inappropriate neutrophil elastase activity contributes to monocrotaline pulmonary vasculopathy and hypertension. On the other hand, cotreatment with SC39026 had no significant effect on the severity of the monocrotaline-induced lung inflammatory reaction, the pulmonary endothelial dysfunction, or the increase in lung hydroxyproline content.     

The effect of oxytocin on basal and pethidine-induced delayed gastric emptying.

1. Continuous infusion of oxytocin (0.33 u min-1) accelerated gastric emptying of semisolid TC-99m labelled Chelex-100 resin/oatmeal in 10 healthy volunteers under basal conditions. 2. Administration of oxytocin did not change the pattern of gastric emptying delayed by pethidine. 3. The emptying pattern of semisolid has confirmed the existence of a lag phase.     

The effect of atrial natriuretic peptide on human isolated resistance arteries.

1. The action of (1-28) alpha-human atrial natriuretic peptide (ANP) was studied on human isolated resistance arteries. 2. Renal, skeletal muscle, omental and subcutaneous resistance arteries were taken from tissue removed at surgery and isometric tension responses were measured with a myograph. 3. ANP (10(-9)-10(-6) M) relaxed precontracted segments of renal and skeletal muscle arteries in a concentration-dependent manner. ANP failed to relax isolated omental or subcutaneous arteries. 4. The effect of ANP on human isolated resistance arteries varies depending on the site of origin of the artery.     

Relationship between in vivo first-order intestinal absorption rate constant and the membrane permeability clearance

An attempt was made to explore the quantitative relationship between the intestinal absorption data obtained from in vivo studies and in situ perfusion studies. The time course of the fraction remaining to be absorbed of L-glucose, erythritol, and urea in the small intestine following the intrajejunal administration to rats was described by a one-compartment model. Thus derived first-order intestinal absorption rate constants (ka) obtained from the in vivo studies in rats were compared with the membrane permeability clearances (CLa,m) estimated in a single-pass perfusion system. Not only were ka and CLa,m in the same increasing order of L-glucose less than erythritol less than urea, but also the operational luminal volumes given as CLa,m/ka were in agreement with the in vivo luminal volume of jejunum estimated by an inulin dilution method. This result suggests that the in vivo intestinal absorption rate (or ka) can be correlated with the intestinal membrane permeability (or CLa,m) by taking the in vivo luminal volume into account.     

Disposition and hypoglycaemic action of glipizide in diabetic patients given a single dose of nifedipine

Summary Adrenaline, when administered in dental local anaesthetic solutions, significantly reduces the plasma potassium concentration in young healthy adults. This effect occurs within 10 min of extravascular injections into the maxillary buccal sulcus and may influence the choice of local anaesthetic solution for patients receiving kaliuretic diuretics.     

Studies on stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-fat and high-cholesterol diet--effects of salt intake on serum lipoprotein and apolipoprotein metabolism

Recently, food intake in Japan has been characterized by an increase in fat intake, especially animal-fat intake and the maintenance of excess salt (sodium chloride) intake. It is generally accepted that the increase in fat intake is closely related to atherosclerosis, and excess salt intake is a high risk factor for the development of hypertension and cerebrovascular lesions. So far, in almost all reports, the increase in fat intake and excess salt intake have been studied independently, and there have been few reports on the combined effects of these two factors. Taking the above things into consideration, it would seem to be very interesting to investigate the effect of excess salt intake on lipid metabolism. In this paper, we studied the effects of excess salt intake on lipoprotein and apolipoprotein metabolisms, using stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Kyo: Wistar rats (WKY) as model animals. The results obtained were as follows: A significant increase in the concentration of serum total cholesterol (TC) was observed in SHRSP and WKY, when the rats were given a regular diet (CE-2, Clea Japan Inc.) and 1% sodium chloride solution (1% NaCl) as drinking water for 4 weeks. This was accompanied by a tendency toward increases in the concentrations of serum apolipoproteins in both strains. These results suggest that excess salt intake could accelerate the production of serum total lipoproteins in SHRSP and WKY, when the rats are fed a regular diet. Next, 1% NaCl and a high-fat and high-cholesterol diet (HFC diet) were simultaneously given to SHRSP and WKY for 6 weeks. The effects of simultaneous administration on lipoprotein and apolipoprotein metabolisms were compared with those of HFC feeding. One percent NaCl did not markedly affect hypercholesterolemia in WKY, while it induced more marked hypercholesterolemia in SHRSP that was associated with extreme elevations of serum TC and the atherogenic index (A.I.). This deleterious effect of 1% NaCl in SHRSP was due to drastic elevations of cholesterol contents in the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fractions. This was also associated with marked increases in apo B contents in the VLDL, IDL and LDL fractions and significant increases in apo E contents in the VLDL and IDL fractions. These results indicate that 1% NaCl induced much larger increases in serum atherogenic beta-lipoproteins in SHRSP.(ABSTRACT TRUNCATED AT 400 WORDS)     

Orthotopic liver transplantation in children

Between 1-1-1982 and 1-1-1988 52 children with an end-stage liver disease were evaluated to determine whether orthotopic liver transplantation (OLT) would be appropriate. 24 children were accepted as candidates in the long term. Twelve were not accepted as potential recipients. The parents of 3 decided not to accept OLT as treatment for their children. Two children died before a suitable donor liver was available, so that OLT was carried out in 11 children. Two of these children needed a second transplant. In 3 children only a part of a donor liver was transplanted. Shortage of donor livers of small size is partly alleviated by using a part of a larger liver. The underlying diseases of the transplanted children were cryptogenic cirrhosis (1x), biliary atresia with a hepatoportoenterostomy (8x) and cirrhosis following neonatal hepatitis (2x). Ten children with OLT are clinically and physically well. Postoperatively a primary graft dysfunction occurred in one child. He was retransplanted. The median waiting time for a donor liver was 5 months. The timing for OLT has to take this in account. In treating children with end-stage liver disease (partial) OLT should be considered.