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Biomedical subjects

N Brion

Publications and source records attributed to N Brion.

69 records · Page 4Linked to original sources

Recovery of acetylsalicylic acid and indalpine (LM 5008) after buccal partitioning.

The recoveries were compared of acetylsalicylic acid (ASA) and indalpine (1) after buccal absorption in three trained human volunteers. Recovery of the poorly lipid soluble ASA was less than 1% at pH 5 or 8, while that of the lipid soluble I was 19% and 13% at pH 5 and 8 respectively. This difference in recovery may represent a difference in their storage within the buccal mucosa dependent on their different lipid solubilities.

Absorption↗

[Cryptic miliary tuberculosis. Two case-reports (author's transl)].

The term cryptic miliary tuberculosis designates a particular form of hematogenous tuberculosis in which the usual diagnostic criteria, especially the roentgenographic ones, are lacking. Two cases are reported. Initial clinical manifestations were prolonged fever, poor general condition, low blood pressure, low serum sodium, mild hepatic biological disorders, and myocarditis. No other radiological or biological features, suggestive of tuberculosis were found. In the first patient, the various visceral tuberculous localizations occurred under specific treatment, although the latter was otherwise effective. In the second patient, they were identified by pathological examination. The incidence of these occult forms of tuberculosis, where diagnosis is often established too late, and sometimes only postmortem, is not negligible. This possibility must be borne in mind in severe infectious conditions without obvious etiology, particularly when the following features are present : inadequate secretion of ADH, which often indicates latent encephalitic and meningitic involvement where CSF anomalies may be incomplete or lacking ; leucopenia or pancytopenia ; biological hepatic anomalies ; exceptionally, such as in the two cases described, cardiac involvement. Among diagnostic procedures, liver biopsy is of the utmost importance. Mere diagnostic presumption is sufficient to warrant initiation of antituberculous therapy. This ensures survival and, paradoxically, allows delayed overt clinical manifestations to develop.

Acute Disease↗

[Disseminated actinomycosis presenting with multiple subcutaneous abscesses (author's transl)].

The case report describes a patient hospitalized for multiple subcutaneous abscesses who presented a four-year history of recurrent skin lesions and a fifteen-year history of non specific bronchopulmonary infections requiring segmental resection. The diagnosis of actinomycosis, A. israeli species, was established by culture of surgical drainage material from a thoraco-abdominal wall abscess. Muscle and bone involvement of the right thigh was subsequently demonstrated. There was no evidence of pulmonary infection at the time of hospitalization. Treatment with Penicillin G was curative. A review of the literature is presented together with a summary of thirteen reported cases. Although disseminated actinomycosis has become very rare since the introduction of antibiotic therapy, patients share similar features and a common clinical pattern which are highly evocative of the disease. All patients described had preceding pleuropulmonary disease, characteristically chronic. Evolution of cutaneous lesions was subacute or chronic. In all cases, there was significant delay (months to years) between the initial appearance of skin lesions and subsequent diagnosis. In most cases, actinomycosis had not been suspected. Diagnosis was usually established by isolation and identification of the micro-organism in cultures of purulent material obtained from cutaneous lesions. Despite the probability of hematogenous disease dissemination, pleuro-pulmonary foci were only rarely demonstrated. Prolonged antibiotic therapy was curative in all treated cases.

Abscess↗

Penetration of cefazolin, cephaloridine, and cefamandole into interstitial fluid in rabbits.

We compared the penetration of three cephalosporins into interstitial fluid. Interstitial fluid was obtained in rabbits from Silastic tissue cages. Cefazolin, cephaloridine, and cefamandole were administered by the intramuscular route (30 mg/kg per injection). Peak blood levels and interstitial concentrations were studied after a single injection. Interstitial levels were also compared in a three-injection study (one injection every 12 h) and in a cumulative effect study (six injections), in which the interval between injections was established for each drug on the basis of its common therapeutic use. After a single injection, cephaloridine activity was detected more rapidly and attained higher levels than the other two drugs within the first 4 h. However, 2 h after the third injection, cefazolin levels in tissue fluid were higher than with cephaloridine. Cefamandole consistently gave the lowest interstitial levels. With all three drugs, detectable concentrations were present in interstitial fluid at a time when no detectable antibiotic was found in serum. In the six-injection study, the interstitial levels obtained with cefazolin were significantly higher than those observed with the other drugs. Our data suggest that cefazolin is a drug of choice due to its high extravascular levels.

Animals↗

Pulsed estrogen therapy: pharmacokinetics of intranasal 17-beta-estradiol (S21400) in postmenopausal women and comparison with oral and transdermal formulations.

Pharmacokinetics of estradiol and estrone were assessed in postmenopausal women receiving S21400, a novel 17beta-estradiol formulation administered by nasal route; the results were compared with those obtained with oral and transdermal routes. Thirty six women received three treatments: a specified dose of 17beta-estradiol (100, 300 or 450 microg) given once and as 2 doses, 12 h apart, using three parallel dose groups in a randomised, crossover study. Thereafter, a reservoir patch (50 microg/day of 17beta-estradiol) or a tablet of 2 mg micronised 17beta-estradiol were randomly administered. Plasma concentrations of estradiol and estrone were measured by radioimmunoassays. Following intranasal dosing, estradiol was rapidly absorbed with plasma concentrations reaching maximal values (approximately 1400 pg/ml with a single 300 microg dose) after 10-30 min and returning within 12 h to levels of untreated postmenopausal women. Systemic exposure to estradiol was dose proportional and independent of the treatment regimen. Moreover, the dose of 300 microg gave an estimated 24 h systemic exposure to exogenous estradiol close to that of the 50 microg/day reservoir patch or the 2 mg tablet. The mean estrone to estradiol ratio was similar and 4-fold lower than those with the patch and the tablet, respectively. In conclusion, by this new route for estrogen replacement therapy, the nasal route, the pharmacokinetics of estradiol as S21400 were linear and displayed a 'pulsed' kinetic profile, different from those obtained with the usual routes of administration.

Administration, Cutaneous↗

[Metastatic colorectal cancer: new therapeutics].

NEED FOR NEW CHEMOTHERAPEUTIC AGENTS: The use of 5-FU in combination with leucoverin (LV) in the treatment of advanced colorectal cancer has consistently provided antitumoral response. The antitumoral activity of the 5-FU/LV combination is associated with inhibition of thymidylate synthetase, an essential enzyme in pyrimidine de novo biosynthesis of thymidilates as precursors of DNA synthesis. However, dose-limiting toxicities and the limited impact on survival point to the need to develop new drugs and approaches to improve therapeutic efficacy and survival. CLINICAL RESULTS: In advanced colorecal cancer, clinical results have confirmed the therapeutic efficacy of direct and indirect thymidylate synthetase inhibitors. Promising new agents: 5-FU prodrugs and inhibitors of dihydropyrimidine dehydrogenase (DPD) are promising chemotherapeutic agents with good oral bioavailability which can be combined with other drugs (leucoverin) with acceptable toxicity. Oxaliplatin and topoisomerase inhibitors such as irinotecan (CPT-11) have demonstrated activity in previously treated and newly diagnosed patients. COMBINATIONS: The best combination between DNA interaction drugs based on potentiation of DNA damage induced by thymidylate synthetase inhibitors and inhibition of DNA repair by DNA interactions remains to be evaluated.

Antimetabolites, Antineoplastic↗

[Diffusion of minocycline in pulmonary tissue].

The penetration of minocycline into lung tissue was evaluated in 14 patients about to undergo excision of the lung for cancer. The patients received minocycline orally in doses of 100 mg twice a day for 3 days, the 100 mg in the morning of the operation day. Minocycline concentrations were measured in plasma samples taken before surgery and in the lung tissue resected. The mean tissue/plasma concentration ration was 3.17 +/- 0.41 (range: 1.5 to 7.48). The same ratios were obtained in peritumoral and tumoral tissues. These results indicate that minocycline penetrates well into tissues.

Adenocarcinoma↗

Effects of six beta-blockers on the isolated guinea-pig trachea.

The effects of six beta-blocking agents (propranolol, metoprolol, atenolol, pindolol, medroxalol and labetalol) selected on the basis of their intrinsic sympathomimetic properties, membrane-stabilizing activities and selectivity for beta 1-adrenoceptors were investigated on the isolated guinea-pig trachea. Tracheal spirals were either allowed to remain under resting tension or were precontracted with histamine 2 X 10(-6) M or 2 X 10(-5) M. Pindolol, medroxalol and labetalol exerted a moderate relaxant effect on tracheal muscle. This effect was inhibited by propranolol, but not significantly modified by indomethacin. Propranolol and metoprolol exerted a moderate contracturant effect on the preparations. The effect was inhibited by indomethacin but not by FPL 55712. Atenolol had no effect on tracheal muscle. This in vitro study provided data concerning two properties of beta-blockers--intrinsic sympathomimetic and membrane-stabilizing activities--which are involved in the bronchomotor response to these drugs in vivo.

Adrenergic beta-Antagonists↗

[Chronic hepatopathy and progressive systemic sclerosis. Frequency of association with Gougerot-Sjögren's disease. A report on six new cases (author's transl)].

Six patients with scleroderma (Barnett's type I and II) associated with hepatopathy are reported. Primary biliary cirrhosis was confirmed in four cases and was probably present in one case, while cirrhosis of unknown origin was present in the sixth patient. The outcome was fatal in two cases. Salivary secretions were reduced in all six cases, and a diagnosis of Gougerot-Sjögren's disease was confirmed in four patients. The frequency with which this triple association has been reported suggests that its incidence has been underestimated.

Adult↗