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Pefloxacin, a new fluoroquinolone, was given to 10 volunteers in single 400-mg oral doses repeated at 12-h intervals during 7 days. Serum, saliva, and feces samples were collected before and at appropriate intervals after the initiation of treatment. Drug concentrations were determined by bioassay. Qualitative and quantitative analyses of the saliva and fecal floras were performed. Mean concentrations in saliva (3.46 micrograms/ml on day 1 and 7.54 micrograms/ml on day 7) were closely related to levels in serum. High concentrations of pefloxacin were found in the feces (645 micrograms/g on day 8). No modification of oral flora was observed. In the fecal flora, members of the family Enterobacteriaceae were eliminated between days 2 and 8. The alterations in streptococci and anaerobic flora were not significant; Bacteroides fragilis was more resistant to pefloxacin after treatment. Clostridium difficile was not detected, and there was no overgrowth by yeasts. No side effects were observed.

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We associated HPA 23 (inhibitor of the reverse transcriptase) to cyclosporin A (CSA) for two homosexual patients with positive HIV serology, who had a peripheral thrombocytopenia resistant after alone CSA treatment. HPA 23 was given for 15 days at a dose of 4 mg/kg/day in a 24 hours continuous perfusion. The circulating tungsten blood concentration was about 4.4 micrograms/ml (between 3 and 8.4 micrograms/ml). Even if HPA 23 has frequently been responsible of thrombocytopenia at a dose superior than 2 mg/kg/day and in spite of any CSA activity in single treatment, this association shows a significant platelets increase. But thrombocytopenia reappeared a week after the stay of HPA 23 treatment. So, it is possible that HPA 23 might have, at this circulating blood concentration, an antiviral activity in vitro. In this hypothesis there might be a relation between antiviral replication and autoimmune disorders and, at least, CSA might oppose against the thrombocytopenia induced by HPA 23.

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An acute infectious disease with predominant pulmonary symptoms, Q fever, may become chronic as hepatitis or, more frequently, endocarditis. We report 3 cases of Q fever endocarditis. In 2 of these patients endocarditis developed on cardiac valve prosthesis. The 3 patients have been under doxycycline for more than a year, and their condition is satisfactory. A review of the literature provides additional data on the epidemiological, aetiological, clinical, biological and therapeutic aspects of this rare type of endocarditis. It is recommended to look for chronic Q fever in all cases of endocarditis with negative blood cultures.

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Nine subjects (5 women) aged between 17-66 years, with hydrocephalus were studied. An external ventricular drain was introduced for diagnostic purposes. Cerebro-spinal fluid (CSF) and plasma samples were obtained at suitable intervals after 1 h infusion of 400 mg pefloxacin. In plasma, pefloxacin Cmax was 8.54 +/- 1.53 (mean +/- S.E.M.) mg/l, at the end of infusion, whereas N-desmethyl pefloxacin concentration was 0.17 +/- 0.03 mg/l. The metabolite accounted for only 2% of plasma levels of pefloxacin. In CSF, pefloxacin Cmax was 2.97 +/- 0.32 mg/l, 5-6 h after the start of infusion, whereas N-desmethyl pefloxacin Cmax varied between 0.1-0.2 mg/l. Apart from the 1 h sample, the CSF/plasma ratio of pefloxacin was 60% which is similar to the unbound fraction of pefloxacin in plasma. The apparent half-life (T1/2) of transfer of pefloxacin from plasma to CSF was 1.26 +/- 0.18 h, assuming a first order process, while the apparent elimination T1/2 in CSF was 13.40 +/- 1.76 h, which is similar to the elimination T1/2 found previously in plasma, thus accumulation of pefloxacin in CSF is unlikely. With the present dosage regimen, CSF quickly attains therapeutic levels of pefloxacin.

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We report 3 cases of rickettsial hepatitis observed in the Lyon area which were secondary to boutonneuse fever. The temperature was elevated and clinical signs were an often painful hepatomegaly and digestive disorders. These signs are only indicative when accompanied by atypical pneumonopathy or exantherma. Indeed, if the inflammatory syndrome is clear, hepatic function is little perturbed. Diagnosis is sometimes influenced by the epidemiological situation, and depends on serologic tests and histological evidence of granulomatous hepatitis (2 of the 3 cases here). The successful antibiotic treatment shows that patients presenting febrile granulomatous hepatitis should be tested for rickettsiosis.

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40,749 RP, a pyridyl-2-tetrahydrothiophene derivative is known to be a potent gastric antisecretory agent in animals and man. In 27 healthy volunteers in four double-blind cross-over studies, this activity has been examined against basal and pentagastrin stimulated gastric acid secretion. The effect of a single oral dose of 2 mg/kg was still present after 12, 24 and 48 h. The effect of 1 mg/kg was definitely increased after treatment for 7 days as compared to a single dose of 1 mg/kg.

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40 749 RP, an N-methyl-2-(2-pyridyl)-2,3,4,5-tetrahydro-2-thiophene carbothioamide derivative, is already known as a potent gastric antisecretory agent in animals and in man. In order to determine its duration of action, its activity was investigated on Histalog-stimulated gastric acid secretion in 6 healthy volunteers. The efficacy of a 2 mg/kg dose, compared with that of placebo, was potent, and remained the same when the drug was ingested 6 h before stimulation instead of 1 h. The duration of action of 40 749 RP is therefore longer than 6 h.

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The authors discussed the malign form of lymphomatoid granulomatosis on the basis of two cases and consider the possible role of an aerocontaminant which is usually responsible for the extrinsic allergic type of alveolitis. A detailed biochemical and cytological study of the alveolar fluid from one of these patients is presented in parallel with immunofluorescent histology and electron microscopy of the lung. The observed biochemical abnormalities in the alveolar fluid could be superimposed on those formed in certain types of hypertensive lung disease. On the other hand the cytology was different, the cytofluorimetric technique revealed a mononuclear cell population rich in RNA whose role in the genesis of the disease of malign nature are discussed. The hypothesis of a hypersecretion of IgA by this malign process is raised by immunofluorescent studies of the lung. The role of IgA in lymphomatoid granulomatosis and bird fanciers lung is discussed in the light of recent work on pigeon IgA.

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The pharmacokinetics and bioavailability of diacetolol, the principal metabolite of acebutolol, were studied in 6 healthy subjects. Plasma concentrations were determined following a single intravenous injection of diacetolol 100 mg and three oral doses of diacetolol 100, 400 and 800 mg, in random order. The average oral bioavailability of diacetolol was F: 0.302 +/- 0.052 (100 mg), 0.363 +/- 0.052 (400 mg) and 0.426 +/- 0.068 (800 mg); the differences are not significant. The mean plasma half-life of the terminal phase, 7.94 +/- 0.26 h after intravenous administration, was significantly higher than after oral administration 12.27 +/- 1.00 h (100 mg), 12.82 +/- 1.59 h (400 mg) and 13.05 +/- 13.05 +/- 1.22 h (800 mg) (p less than 0.02 to 0.05); the mean urine half-lives of the terminal phase were not significantly different. Renal clearance of diacetolol 10.2 +/- 0.81 . h-1 represented about wo-thirds of total body clearance 15.9 +/- 1.21 . h-1. The results suggest either a first-pass effect or incomplete absorption of diacetolol after oral administration.

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Cementum regeneration on exposed dentinal root surfaces of replanted teeth not subjected to replantation. The implication was that secondary reattachment of replanted teeth was largely dependent on the status of supporting alveolar tissues. The role of the replant appeared essentially passive, reacting as a substrate for cementum deposition that may be more or less acceptable to the regenerating periodontal tissues as dictated by the extraoral history. Although the pattern of cementum deposition was unaltered by replantation, the quantity of new cementum deposited on exposed dentin did appear to be affected by pulpal treatment; thus, an indication was given that survival of replanted teeth may be influenced by pulpal procedures.

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