Pharmacokinetics of cilazapril in patients with renal failure.

1. The pharmacokinetics of a single 1 mg dose of cilazapril were determined in six subjects with normal renal function and in 19 uraemic patients with various degrees of renal impairment. 2. Significant decreases in systolic and diastolic blood pressure were noted in all groups of subjects between 2 and 8 h after administration of 1 mg cilazapril. 3. There was a significant correlation between ACE inhibition at 24 h and creatinine clearance (CrCL). 4. For cilazapril, Cmax and tmax were independent of creatinine clearance. AUC(24) was inversely related to CrCL and apparent plasma clearance (CL/F) was directly related to CrCL. 5. For cilazaprilat, Cmax and tmax were related to creatinine clearance. AUC(24) was inversely related to CrCl and apparent plasma clearance (CL/F) was directly related to CrCL. 6. Dialysis clearance was approximately 2 l h-1 for cilazapril and for cilazaprilat. 7. The effects of renal impairment on cilazapril and cilazaprilat kinetics were similar to those observed for other inhibitors of angiotensin-converting enzyme such as captopril, enalapril and lisinopril. 8. It may be necessary to modify doses of cilazapril for the treatment of essential hypertension in uraemic patients. When creatinine clearance was below 15 ml min-1 cilazaprilat concentrations were increased, half-lives were prolonged and ACE inhibition remained above 90% for at least 24 h. A reduced dosage is indicated for these patients. 9. In patients requiring haemodialysis, maintenance doses of 0.5 mg given after each haemodialysis session are sufficient.

[A case of acute sensory and autonomic neuropathy with regression]. / Un cas de neuropathie aiguë sensitive et végétative sévère régressive.

The authors report the case of a 24 year old man with no previous disease who presented with a severe autonomic neuropathy. This included major gastrointestinal dysfunction characterised by decreased peristalsis without distension and paralysis of the gall bladder, and orthostatic hypotension with a normal cardiac tachycardia reflex. There was an associated sensory neuropathy affecting heat sensitivity without motor dysfunction and an increased CSF protein content. The proprioceptive nerve fibre conduction was decreased but another nerve conduction was normal initially. The mesenteric plexuses examined during sigmoidectomy performed for peritonitis due to multiple bowel perforations caused by fecoliths, showed no significant changes. Peripheral nerve biopsy revealed massive rarefaction of myelinated fibres which were of small diameter, and of the unmyelinated fibres, mainly due to axonal degeneration. Only two similar cases with incomplete recovery were found in the literature. In our case, a complete recovery was observed. The cause of the condition is unknown.

[Misleading symptoms of cerebral thrombophlebitis in pregnancy and the puerperium]. / Symptomatologie trompeuse des thrombophlébites cérébrales au cours de la grossesse et du post-partum.

Four cases of cerebral thrombophlebitis, 3 of which occurred during post-partum and 1 during the first trimester of pregnancy, are reported. The symptoms were misleading, being predominantly psychiatric, with secondary appearance of an epileptic attack or motor deficit. The value of cerebral angiography is stressed in the literature.

[Syndrome of acute colonic pseudo-obstruction (Ogilvie's syndrome). Study of 13 cases]. / Le syndrome de pseudo-obstruction colique aiguë (syndrome d'Ogilvie). Etude de 13 cas.

Acute pseudo-obstruction of the colon involves acute colic distension without mechanical obstruction or stercoroma in a previously healthy colon. Our study is of 13 patients, all of whom presented a pre-existing extradigestive disorder, for which 12 were taking medication. Nine patients were treated by mechanical ventilation, and five of these had previously presented meteorism. Colic dilatation was maximal in the cecum, the diameter of which measured 9 to 14.5 cm. Two patients were treated by decompression colonoscopy, which completely cured meteorism in one case. Two patients treated by digestive aspiration died due to extra-abdominal causes. Operations were carried out on 6 patients: once for peritonitis due to cecal perforation five times for deterioration of meteorism. Five patients died due to postoperative complications. These observations show that the diameter of the cecum should be monitored daily. When it exceeds 9 cm, decompression colonoscopy must be performed. Surgery should only be envisaged when there are setbacks, due to the seriousness of the operation and the possibility of postoperative complications.

Temocillin treatment of serious infections due to gram-negative bacilli in an intensive care unit.

In a group of 27 severely ill patients in an intensive care unit, 40 infections caused by Gram-negative bacilli were treated with temocillin 2g twice daily by the direct intravenous route. The patients (17 men and 10 women) were aged from 35 to 93 years (mean 65.7 years) and 22 had severe underlying diseases. In addition, 10 of the patients were admitted to the intensive care unit following surgery; 6 had acute renal insufficiency, 5 had acute respiratory insufficiency, and 12 were suffering from infectious shock. The infections included septicaemia (19), urinary tract infection (10), respiratory tract infection (4) and biliary tract infection (4). The most frequent bacterial isolate was Escherichia coli (14), followed by Enterobacter cloacae (5), Proteus spp. (5) and Klebsiella pneumoniae (4). The initial pathogens were eliminated in 34/40 infections (85%) and the corresponding clinical cure rate was 60%, with a further 27.5% of patients being improved. In the septicaemic patients, 17/19 pathogens were eradicated from the blood, while clinically, 12 patients were cured and 5 were improved. Eight of the 10 urinary tract pathogens were eliminated, with 6 patients being clinically cured and a further 3 being improved. All of the initial pathogens in both biliary tract and respiratory tract infections were eradicated, accompanied by clinical success in 3 and 2 patients, respectively; the remaining patients were improved. Superinfection with streptococcus group D, Pseudomonas aeruginosa and Staphylococcus aureus was seen in 3 patients. The emergence of resistance to temocillin occurred in an isolate of E. coli, and also possibly in an isolate of K. pneumoniae. No adverse reactions nor abnormal laboratory values related to temocillin administration were observed and, although 7 patients died, none of the deaths were attributable to uncontrolled Gram-negative infection.

[Lung diseases complicating acute poisoning with psychotropic drugs]. / Pneumopathies compliquant les intoxications aiguës par les drogues psychotropes.

474 patients admitted in ICU between 1976 and 1981 were retrospectively analysed. Pneumonia (P) was assessed by condensation on chest X ray. P developed in 14,3%. 24 hours after admission 77,6% of P had appeared. Initial location was unilateral in 79,4% with predilection to the inferior half of the right lung. Fever was almost constant (89,5%). Promoting factors were observed: delay between ingestion and admission, vomiting and tracheobronchial embarrassment, coma depth. Recovery was simple in 83,3%. Among the 14 deads, 6 died because only of p, in 4 other P was aggravating. Duration in ICU was much longer when P was present (9 +/- 8,1 days) than when P was absent (2,5 +/- 2,1) p less than 0,001.

[Contribution of the determination of soluble antigens to the diagnosis of Streptococcus pneumoniae pneumopathies]. / Apport de la recherche d'antigène soluble au diagnostic des pneumopathies à Streptococcus pneumoniae.

We studied the diagnostic value of the detection of soluble pneumococcal antigens by counter-immunoelectrophoresis (ES) in patients with pneumonia. Pneumococcal antigens were detected in blood, urine and pleural fluid. 59 patients were distributed into 3 groups: (Group 1) - 19 patients with a non-pneumococcal, but bacteriologically-proven pneumonia, (Group 2)-32 patients with a bacteriologically confirmed pneumococcal pneumonia, (Group 3)-8 patients with a non-bacteriologically proven pneumonia, but with pneumococcal antigens. No Group 1 patients had pneumococcal antigens. In Group 2 pneumococcal antigens were present in 15 cases. The sensitivity of ES in the detection of soluble pneumococcal antigens (APS) in the blood, urine and pleural fluid during pneumococcal pneumonias was 57.5%. There was a diagnostic benefit when compared to bacteriological analysis alone of 20%. We believe that ES is a useful complementary examination to classical bacteriology.

Pattern of respiration in patients recovering from barbiturate overdose.

Ventilation has been recorded in seven patients who were unconscious following self-poisoning. Measurements were obtained on admission to the hospital and repeated daily until the patients regained consciousness. On admission, recordings were characterized by a low minute ventilation as a result of a low tidal volume in spite of a high frequency of respiration. During the period of recovery tidal volume and minute ventilation increased, whereas frequency decreased. The modifications observed during recovery were the reverse of those noted during the induction of anaesthesia wih barbiturates in man. However, these modifications differ from those observed during induction of anaesthesia in cats. Consequently, as far as respiratory control is concerned, models elaborated in animals cannot be extrapolated to deeply anaesthetized human subjects.

[Budd-Chiari syndrome with massive thrombosis of the subdiaphragmatic venous system and major fibrinopenia (author's transl)]. / Syndrome de Budd-Chiari avec thrombose massive du système veineux sous-diaphragmatique et fibrinopénie majeure.

A 32-year-old patient without previous medical history died within three weeks of acute Budd-Chiari syndrome with massive thrombosis of the subdiaphragmatic venous system. No definite cause could be elicited. The course of the disease was complicated by anuria attributed to hepotorenal syndrome. Laboratory tests demonstrated major fibrinopenia. Detailed study of the haemostatic system was suggestive of hepatic failure associated with consumption coagulopathy of obscure origin.

Phospholipase and prophospholipase activities in bronchoalveolar lavage fluid in severe acute pulmonary disease with or without ARDS.

Bronchoalveolar lavages were performed in 21 patients undergoing mechanical ventilation: Group I: coma due to sedative overdose (11 cases), without pulmonary impairment, serving as control group; Group II: severe acute pulmonary disease without ARDS (5 cases); Group III: patients with ARDS (5 cases). In the recovered fluid we measured: total proteins (P) and phospholipids (PL), phospholipasic (PLase) and prophospholipasic (PPLase) activities. In ARDS group, considerable increase of P, (p less than 0.001), and a doubling of PL (p less than 0.02) was found. Total PLase activity was present in all three groups, with a higher mean level in Group III (p less than 0.01). PPLase activities were low or undetectable in four patients of this group. PLase/PL ratio was increased in acute respiratory insufficiency, with or without ARDS, suggesting an increase of surfactant catabolism. The decrease of this ratio when pulmonary function improved, or its increase after deterioration suggest that it is related to changes of surfactant.