Alpha-1-antitrypsin deficiency in a large sibship.

We studied alpha 1-antitrypsin deficiency in a large family of 10 siblings: 3 subjects had PiZZ phenotype, but only 1 had emphysema; 2 subjects had no respiratory complaint. The patient with emphysema was a heavy smoker. According to the literature, this case suggests that, in PiZZ phenotype, emphysema appears earlier and is more severe if the patients smoke.

Evolution of pulmonary haemodynamics in COLD patients under long-term oxygen therapy.

The North-American Trial (NOTT) and the British MRC study clearly indicated that long-term oxygen therapy (LTO) increases the survival rate of patients with severe chronic obstructive long disease (COLD), but O2 must be given for more than 15 h/24 h. At present OT is largely prescribed in COLD patients whose (stable) PaO2 less than or equal to 55 mmHg. The pulmonary haemodynamic effects of OT are still a matter of debate. The first studies, in 1967, indicated that continuous O2 for 6-8 weeks could markedly improve pulmonary hypertension (PH). In the MRC study there was no change in pulmonary artery mean pressure (PAP) in patients receiving O2 for more than 15 h/day, whereas patients not receiving O2 exhibited a progressive increase of PH. In the NOTT study there was a modest but significant improvement of PAP after 6 months in those patients receiving "continuous OT" (in fact greater than 18 h/day), but not in patients receiving only nocturnal OT. In our own study, we found that OT could reverse the progression of PH in COLD patients. In 16 carefully studied patients, PAP increased from 23.3 +/- 6.8 to 28.0 +/- 7.4 mmHg (p less than 0.01) before the initiation of OT (mean duration of follow-up = 48 months) and then decreased to 23.9 +/- 6.6 mmHg (p less than 0.05) during OT (mean duration of follow-up = 31 months). The average yearly change in PAP was +1.5 mmHg before OT, and -2.1 mmHg under OT and the difference was highly significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease.

In 175 patients with chronic obstructive lung disease (157 chronic bronchitic and 18 emphysematous patients) exhibiting moderate to severe airway obstruction (mean FEV1/vital capacity = 40.2 +/- 11.1%), cumulative survival rates calculated by the actuarial method were compared in subgroups according to the initial level of mean pulmonary artery pressure, pulmonary volumes, and arterial blood gases. Patients were catheterised between 1968 and 1972 and were followed for at least five years. The results emphasise the high prognostic value of PAP since survival rates after four and seven years were significantly lower in the subgroup with PAP greater than 20 mmHg (2.7 kPa). Certain other parameters ("driving" pressure across the pulmonary circulation, FEV1 and Paco2) appear to be equally good at predicting survival as PAP in these obstructed patients. The effect of age should be taken into account in prognostic studies such as ours since survival rates were significantly lower in patients over 60 years of age. In 64 patients who underwent a second right heart catheterisation at least three years after the first (average delay: 5.5 +/- 2 years), the prognostic value of changes in PAP, arterial blood gases, and pulmonary volumes was studied but with the exception of Pao2 was unremarkable. Further studies are needed in this field.

[The prognostic significance of pulmonary arterial hypertension in chronic obstructive airway disease (author's transl)]. / Signification pronostique de l'hypertension artérielle pulmonaire dans les bronchopneumopathies chroniques obstructives.

In 175 cases of chronic obstructive airway disease (most often chronic bronchitis) with severe ventilatory deficit in the majority of cases, the prognostic value of mean pulmonary arterial pressure (PAP) and other respiratory function parameters (FEV1, blood gases) was studied by calculation of survival rates using the actuarial method. The patients were cathetherised between 1968 and 1972 and the maximum period of follow-up is 10 years. The results demonstrated the definite prognostic value of PAP : 4 and 7 year survival rates were markedly different according to whether initial PAP was above or below 20 mmHg. However other haemodynamic (motor pressure through the pulmonary circulation) and non-haemodynamic (FEV1, PaCO2) parameters also would appear to be as useful as PAP in predicting survival in such patients. The prognosis is particularly bad in patients with severe pulmonary arterial hypertension (PAP greater than 30 mmHg). In this type of study, it is essential to bear in mind the influence of age. Survival rates differed significantly according to whether the subjects were over 60 years in age initially.

Course of pulmonary hemodynamics in patients with chronic obstructive pulmonary disease.

Eighty-five patients with chronic obstructive pulmonary disease, mainly chronic bronchitis (71 patients), who had arterial hypoxemia and moderate to severe obstruction of the airways underwent at least two right cardiac catheterizations in a clinical steady state, with a delay of three years or more between the first and the last catheterization. The average delay was 60 +/- 19 months (range, 36 to 119 months). Patients were regularly examined (quarterly clinical and functional checkups). The changes in pulmonary hemodynamic data were small. In the group of 53 patients with an initial mean pulmonary arterial pressure of 20 mm Hg or less, this pressure varied from 15.4 +/- 3.1 to 18.3 +/- 6.6 mm Hg (P less than 0.001); in the group of 32 patients with an initial mean pulmonary arterial pressure greater than 20 mm Hg, this pressure varied from 27.7 +/- 6.0 to 31.0 +/- 9.3 mm Hg (P less than 0.05). The mean pulmonary arterial pressure increased by 5 mm Hg or more in only 28 patients. In these patients with hemodynamic "worsening," the final arterial oxygen pressure (PaO2) was lower and the final arterial carbon dioxide tension was higher than in the remaining patients. A significant negative correlation (r = -0.39; P less than 0.001) was observed between changes in PaO2 and mean pulmonary arterial pressure. There was a generally good agreement between the course of pulmonary hemodynamics (mean pulmonary arterial pressure), on the one hand, and the clinical, radiologic (transverse diameter of the heart), and electrocardiographic evolution, on the other hand. In the 33 patients who died, a relatively long survival was observed after the first episode of right-sided heart failure or after ascertaining pulmonary hypertension.

Hormonal stimulation of intestinal brush border enzymes release.

The rat small bowel was perfused in vivo and ex vivo in the absence of biliary and pancreatic secretion. Intraluminal release of sucrase, alkaline phosphatase, aminopeptidases and enterokinase was significantly increased after administration of pentagastrin, caerulein and glucagon at doses ranging between 1 pg and 10 microgram. This suggests that there is a direct hormonal stimulation of the intestinal mucosa. This effect might at least partly be mediated through cyclic AMP since dibutyryl derivates of this cyclic nucleotide exerted a significant stimulatory effect on intraluminal release of proteins, sucrase and enterokinase, although the pattern of enzyme was quite different from the effect produced by the three peptides.

Prostaglandins E1 and E2 stimulate release of intestinal brush border enzymes.

Rat small bowel was perfused in vivo and ex vivo in the absence of biliary and pancreatic secretion. Intraluminal release of sucrase, alkaline phosphatase, aminopeptidase and enterokinase was significantly increased after administration of PG E1 and E2 1 and 5 microgram/kg. This suggests a direct stimulation of the intestinal mucosa, which might be mediated through cyclic AMP; dibutyryl cAMP significantly stimulates intraluminal release of proteins, sucrase and enterokinase.

Ex vivo vascular perfusion of the isolated rat small bowel. Importance of the intestinal brush border enzyme-release in basal conditions.

The vascular perfusion of the whole isolated intestine of the rat with homologous non-diluted blood is compared with classical in vivo experiments. During a 2 1/2-hour perfusion procedure no significant difference was noted between the two experimental schedules as far as haemodynamic, histological, mechanical and/or electrical activities of the gut are concerned. However, striking changes in the intestinal brush border enzyme output within the lumen appear between ex vivo and in vivo experiments. The early increase of intraluminal intestinal sucrase, already after the 95th min of perfusion indicate clearly the existence of a subcellular damage even not detectable by other tests of viability. Therefore, it is suggested that release of brush border enzymes might represent an interesting criterion of viability of in vitro or ex vivo preparations.