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Biomedical subjects

B Rouveix

Publications and source records attributed to B Rouveix.

At least 19 recordsLinked to original sources

[Clinically significant toxicity and tolerance of the main antibiotics used in lower respiratory tract infections].

The purpose of this article was not to review all reported adverse reactions of antibiotics used in the treatment of lower respiratory tract infections but rather to focus either on those which might have an impact on observance, efficacy, and resistance, or on rare but life-threatening adverse effects such as torsade de pointe. The latter are mostly predictable and prescribers should adhere to precautions and contraindications. For new antibiotics, the number of patients enrolled in phase I to III clinical trials is far to small to detect such rare adverse effects and large post registration tolerance surveys are mandatory. ss-lactams are well tolerated. The risk of anaphylactic reaction is magnified by patient reports and can be reduced by skin testing. Macrolides are well tolerated as well. The risk of cardiac toxicity should be reduced by assessing individual susceptibility and avoiding drug interactions. The tolerance to telithromycin, a new ketolide, is similar to that of macrolides. Serious toxic reactions such as convulsions, tendon rupture, torsade de pointe, and hypoglycemia are associated with the use of fluoroquinolones. Most of these adverse reactions can be often circumvented by avoiding exposure patients at risk. Quinupristin/dalfopristin can induce arthralgia and myalgia and the major adverse effects of linezolid are IMAO like reactions, reversible myelosuppression, and peripheral neuropathy. Most of the adverse antibiotic reactions are reported when precautions of use in susceptible patients are not taken into account. When they are, the safety/risk ratio is good.

Anti-Bacterial Agents↗

Classification of oral cephalosporins. A matter for debate.

There are many cephalosporins available and various ways of classifying them for clinical use. Oral cephalosporins probably need a classification of their own. This informal discussion was prompted by the appearance of the recommendations of an expert committee of the Paul Ehrlich Gesellschaft. The views of several other commentators are included. There is considerable individual variation in preference for different styles of classification depending on what the classification is for.

Administration, Oral↗

Control of staphylococcal adhesion to polymethylmethacrylate and enhancement of susceptibility to antibiotics by poloxamer 407.

We studied the antiadhesive effect of Poloxamer 407 (P407), together with modifications in the antimicrobial susceptibility of residual adherent staphylococci. Bacterial adherence was markedly inhibited (77% to more than 99.9%) whether polymethylmethacrylate was exposed to P407 before or during the adherence assay. Furthermore, residual adherent staphylococci appeared to be more susceptible to antibiotic activity, suggesting that combination of P407 with antibiotics could be a promising approach to the prevention of infection of foreign material.

Anti-Bacterial Agents↗

Controlled release of vancomycin from poloxamer 407 gels.

The purpose of this study was to investigate Poloxamer 407 25% (w/w) formulations aimed at prolonging the residence time of vancomycin, a time-dependent antibiotic, in a body site with a high infectious risk. Reversible thermal gelation of the formulations permitted their local injection in liquid form and in situ gelation as they warmed to body temperature. Neither the rheological properties of the Poloxamer matrices nor the antibacterial activity of vancomycin was altered by their combination. In vitro, the dispersed form exhibited prolonged release, with a lower diffusion coefficient of vancomycin compared to the solubilized form (4.7x10(-8) vs 2. 1x10(-7) cm(2) s(-1)131 mg l(-1) for the solubilized form), followed by lower but effective antibacterial levels for at least 8 days. Controlled-release profiles, good preservation of vancomycin activity, good tolerability in rats, and ease of administration suggest that Poloxamer 407 may be useful as a vancomycin delivery vehicle for local prophylaxis of infections, especially in prosthetic surgery.

Animals↗

[Treatment of different types of pain].

Accurate assessment of pain is the key to appropriate analgesia. This necessitates not only an understanding of the organic component, but also a comprehension of the role played by the mental, social and spiritual dimensions in the individual patient's suffering. It implies that the entire care team must be involved in pain management. The nature of a patient's pain is one predictor of the response to treatment. It is mainly characterized by its location, intensity, extent, timing and type (excessive nociception, neurogenic, or mixed), the circumstances in which it appears, and any accompanying signs. The choice of analgesic for treating pain due to excessive nociception was greatly facilitated by the introduction of the WHO three-step approach. Better knowledge of the pharmacological and pharmacokinetic properties of the different analgesics has contributed to increase their efficacy and tolerability. Certain types of pain of neurogenic origin respond poorly to both opiate and non opiate analgesics. They can be treated with other drugs whose mechanisms of action in pain relief are not fully understood. They include the following; antidepressants (amitriptyline, nortriptyline, desipramine and doxepine); anticonvulsants (carbamazepine, phenytoin, valporic acid and clonazepam); antiarrhythmic agents (lidocaine, mexiletine, flecainide and tocainide). The unwanted effects of these different treatments, together with psychological disturbances induced by the underlying disease, can call for the use of antiemetics, laxatives, spasmolytics, glucocorticoids and psychotropic agents (anxiolytics, neuroleptics and antidepressants). Finally, in many cases, better pain relief is obtained by combining drug-based therapy with other interventions such as radiation therapy, neurosurgery, and psychological/behavioral approaches. All these means must be chosen and used according to each individual patient's needs. Pain must be considered as a disease that can and must be eliminated or at least attenuated.

Analgesics, Non-Narcotic↗

[Drugs for respiratory tropism and pregnancy].

The pharmokinetics of drugs used to treat lung disease in pregnant women undergo changes due to the physiological variations induced by pregnancy. Dosage must therefore be adapted; increased doses are often required for the treatment of severe lung infections. Most drugs used for lung disease have a teratogenic potential and thus carry a risk for the fetus. Drugs used for asthma usually present little risk for the fetus. Administration by inhalation is particularly well adapted as it limits systemic diffusion. Excessively high doses can however lead to neonatal toxicity. Penicillins, cephalosporins and erythromycin have been shown to be well tolerated and are the choice antibiotics. Aminoglycosides require careful monitoring due to the risk of renal and auditory toxicity. Fluoroquinolones, sulfamides and tetracyclines should be avoided. Available data on recent compounds such as the new macrolides (azithromycin, clarithromycin) are too limited for recommending their use during pregnancy. In case of resistant tuberculosis, it is sometimes necessary to prescribe a second choice anti-tuberculosis drug with known or suspected fetal toxicity.

Anti-Asthmatic Agents↗

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: a scintigraphic study.

Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.

Administration, Oral↗

The effect of drugs on the mortality of mice inoculated with Friend leukaemia virus or toxoplasma gondii.

Infection and tumors provoke substantial changes accompanied with the disbalance of many neuroendocrine factors which in their summarizing effects influence the life span of animals. Our previous results showed enhanced mortality after one injection of morphine in association with Friend leukaemia virus infection. The aim of this study was to examine the effects of some other opioids (pethidine and pentazocine) and an acetylcholine esterase inhibitor neostigmine on the survival of animals under two conditions: (1) Friend leukaemia virus infection which mostly depressed immune functions, and (2) Toxoplasma gondii infection which in general enhanced the immune status. In contrast to our previous observation with morphine, the mortality induced by single doses of pethidine (150 mg/kg) or pentazocine (50-75 mg/kg) was unchanged during the Friend leukaemia virus infection. A single injection of neostigmine (0.42 or 0.56 mg/kg) was significantly more lethal in DBA-2 mice infected with Friend leukaemia virus. Neostigmine in doses of 0.33 and 0.4 mg/kg caused death in 46 % and 57 %, respectively, of animals infected with Toxoplasma gondii which was significantly higher in comparison with only 8 % and 12.5 % in control groups. Pethidine (150 mg/kg) killed 70 % of Toxoplasma gondii infected animals and even 90 % of non-infected mice. Thus, the Friend leukaemia virus and Toxoplasma gondii infections increased toxicity only of some drugs which may, at least partly, be associated with altered immune status during infection and involvement of the cholinergic system.

Acetylcholine↗

Effects of two oral erythromycin ethylsuccinate formulations on the motility of the small intestine in human beings.

Fourteen-membered macrolides are known to produce alterations in digestive tract motor activity; these include the induction of strong gastric contractions and a decrease in the motility of the small intestine. The aim of the study was to compare the effects of two different formulations of erythromycin ethylsuccinate (EE) on duodenojejunal motility. Compared with the more commonly used crystalline formulation of EE (CEE), the amorphous formulation (AEE) has previously been described to have greater bioavailability and to induce significantly fewer gastrointestinal side effects when given at therapeutic and what have been considered to be equivalent oral doses (i.e., CEE, 1,000 mg every 12 h; AEE, 500 mg every 12 h). In a crossover double-blind study, duodenojejunal manometric recordings were performed for 10 volunteers treated with placebo, CEE at 1,000 mg, or AEE at 500 mg. Recordings for each volunteer were obtained for a fed period after a standard dinner and then for a nocturnal fasting period. When compared with the placebo, CEE significantly decreased the motility index of the duodenum during the 30 min after the peak serum erythromycin concentrations, shortened the duration of the fed state, and had no effect during the fasting state. In contrast, AEE did not significantly modify any motility parameter. Because AEE produced significantly lower concentrations in serum than CEE, these results do not necessarily imply that the two formulations of EE act differently on the motility of the small intestine.

Administration, Oral↗

[Effects of morphine on murine infection with Friend retrovirus].

The immunomodulatory effects of opiates can modify host defenses against infection. We investigated the mechanisms involved in these effects by studying the influence of morphine on the pathogenesis of murine Friend retrovirus infection. The response to this opiate varied greatly according to the treatment schedule. Daily intra-peritoneal administration of morphine (50 mg/kg) for 16 to 27 days attenuated pathological manifestations in infected animals without modifying the mortality rate. The protective effect increased proportionately with the duration of treatment, and depended on the time of treatment initiation relative to inoculation. Naloxone (10 mg/kg/day i.p.) inhibited the morphine-induced decrease in both splenomegaly and viral titer. Mifepristone--a glucocorticoid receptor inhibitor--had no significant effect on the morphine-induced attenuation of splenomegaly. The influence of the infection on acute morphine toxicity was also analysed, using a non lethal dose in noninfected mice (200 mg/kg). Susceptibility to morphine increased in parallel to the development of the infection, with mortality rates ranging from 20% on D14 to 90% on D21. Simultaneous administration of naloxone (20-100 mg/kg) reduced the mortality rate and postponed death. Administration of mifepristone, terfenadin, phentolamine or propranolol did not modify mortality at the used doses. These findings show that the influence of morphine on the development of Friend virus infection in mice depends on the conditions of administration. The transient protective effect seen in certain conditions of administration seems to be due essentially to the direct effects of morphine on its specific receptors.

Adjuvants, Immunologic↗

Effects of morphine on the pathogenesis of murine Friend retrovirus infection.

The immunomodulatory effects of opiates can modify host defenses against infection. We investigated the mechanisms involved in these effects by studying the influence of morphine on the pathogenesis of murine Friend retrovirus infection. The response to this opiate varied greatly according to the treatment schedule. Daily intraperitoneal administration of morphine (50 mg/kg) for 16 to 27 days attenuated pathological manifestations in infected animals without modifying the mortality rate. The protective effect increased proportionately with the duration of treatment and depended on the time of treatment initiation relative to inoculation. Naloxone (100 mg/kg/day i.p.) inhibited the morphine-induced decrease in both splenomegaly and viral titer. Mifepristone--a glucocorticoid receptor inhibitor--had no significant effect on the morphine-induced attenuation of splenomegaly. The influence of the infection on acute morphine toxicity was also analyzed using a nonlethal dose in noninfected mice (200 mg/kg). Susceptibility to morphine increased in parallel to the development of the infection, with mortality rates ranging from 20% on day 14 to 90% on day 21. Simultaneous administration of naloxone (20-100 mg/kg) reduced the mortality rate and postponed death. Administration of mifepristone, terfenadin, phentolamine or propranolol did not modify mortality at the doses used. These findings show that the influence of morphine on the development of Friend virus infection in mice depends on the conditions of administration. The transient protective effect seen in certain conditions of administration appears to be due essentially to the direct effects of morphine on its specific receptors.

Animals↗

Pharmacological basis of immunotherapy in autoimmune diseases.

The clinical development of immunomodulatory agents for the treatment of autoimmune diseases is an arduous process. This can be explained by the fact that the true pathogenic mechanism of the disease(s) is unknown. Moreover, the properties and pharmacokinetic profile of these immunomodulatory agents are different from other classic therapeutic compounds. The aim of this brief review is to discuss a number of general aspects of the clinical pharmacology of i.v. immune globulin as well as more recent immunotherapeutic approaches such as anti-cytokine therapy, which are currently being applied in the immunotherapy for neurologic and rheumatic autoimmune disorders such as myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and rheumatoid arthritis. A better understanding of the interaction of the therapeutic compound and the host immune response, the knowledge of its kinetic profile, and the development of surrogate markers of clinical efficacy should help in designing randomized and blinded clinical trials that will ultimately determine the optimal therapeutic regimen.

Adjuvants, Immunologic↗

Synergistic activity of azithromycin and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis.

The efficacy of azithromycin administered alone or combined with pyrimethamine or sulfadiazine was examined in a murine model of acute toxoplasmosis. Outbred Swiss mice acutely infected with tachyzoites of the virulent RH strain were treated for 10 days from day +1 postinfection. The efficacy of each regimen was assessed in terms of survival rates and sequential titration of parasites in blood, brain, and lungs by using a tissue culture method. Administration of azithromycin at 300, 150, or 75 mg/kg of body weight per day resulted in prolonged survival relative to that of untreated controls; sequential examination of parasite burden showed early eradiaction of Toxoplasma gondii from the lungs, whereas dissemination to the brain was not prevented. A remarkable synergistic effect was observed when azithromycin (150 mg/kg/day) was administered in combination with pyrimethamine or sulfadiazine at noncurative dosages, i.e., 12.5 and 200 mg/kg/day, respectively. In mice treated with azithromycin plus sulfadiazine and azithromycin plus pyrimethamine, parasite burdens in blood and organs, relapses after cessation of therapy, and mortality were all markedly reduced relative to mice treated with any of the agents alone. These results show that azithromycin, which is remarkably active on pulmonary Toxoplasma infection, significantly potentiates the curative effect of sulfadiazine or pyrimethamine.

Animals↗

Opiates and immune function. Consequences on infectious diseases with special reference to AIDS.

There is an increasingly body of evidence, obtained both in vitro and in vivo, showing that exogenous opioids have a variety of effects on cells of the immune system. The consequence is that opiates at pharmacological concentrations suppress cell-mediated immunity, as reflected by depressed T-dependent antibody production by B lymphocytes, altered T lymphocyte functions such as proliferation, delayed-type hypersensitivity, graft-versus-host responses and decreased cytotoxic NK cell activity. The macrophage/monocyte oxidative burst and phagocytosis are also impaired, effects probably mediated by various opioid receptor types as they are blocked or reversed by naloxone, an opioid antagonist. Other possible mechanisms of interaction remain to be elucidated: exogenous opioids can act on neurons of the central nervous system, thereby activating the neuroendocrine system with a subsequent increase in serum glucocorticoid levels. Another potential link between the central nervous system and lymphoid tissue is the sympathetic nervous system, via which opioid-induced activation could result in noradrenergic inhibition of the immune system. The clinical consequences of these suppressive effects on the immune system are seen in the striking increase in the incidence of infections in intravenous opioid addicts. The advent of AIDS and the identification of intravenous drug abusers as a critical risk group have propelled interest in this area. Data obtained both in vitro and in vivo with various experimental models shows that morphine increases susceptibility to bacterial and viral infections, the latter effect possibly being related to a depressive effect of opioids on gamma-interferon levels. The dosage and time of administration strongly influence the results: it appears that chronic opioid treatment in vivo induces a state of immune tolerance, with normal resistance to viral infections, whereas short or single administration has a detrimental effect. In the former context, other factors such as a morphine-induced increase in CD4+ cell numbers may tend to enhance the infectivity of HIV-infected subjects.

AIDS-Related Opportunistic Infections↗

Anti-Toxoplasma effects of dapsone alone and combined with pyrimethamine.

The efficacy of dapsone alone or combined with pyrimethamine against Toxoplasma gondii was investigated experimentally. For in vitro studies, a sensitive immunoassay was used for assessment of Toxoplasma growth in tissue cultures; dapsone was found to have a significant inhibitory effect at a concentration of 0.5 micrograms/ml in the cultures, and the 50% inhibitory concentration was estimated to be 0.55 micrograms/ml. When pyrimethamine and dapsone were combined, an important synergistic effect which was associated with morphological alterations of the parasites was observed. In vivo studies were performed in a murine model of acute toxoplasmosis in which a tissue culture method was used to estimate the parasite burden in the blood, lungs, and brains of infected mice. Dapsone alone, which was administered at 100 mg/kg/day for 10 days from day 1 after infection, was unable to prevent parasite dissemination and only delayed the time to death of treated mice compared with the time of death of untreated controls. When dapsone and pyrimethamine (18.5 mg/kg/day) were administered in combination from day 4 after infection, parasites were cleared from blood and organs within 6 days, but relapses were observed 15 days after the cessation of therapy. When treatment was started at day 1 after infection, 100% of mice survived and relapses were not observed, suggesting a good efficacy of this combination for preventive therapy.

Animals↗

Activities of lung NADPH-cytochrome C-reductase and of cytochrome P-450 peroxidase during the protection of rat from hyperoxic injury by polyriboinosinic acid-polyribocytidilic acid.

Rats exposed to normobaric oxygen received a single i.p. injection of 2.5 mg/kg of poly I: poly C at various times (-120 to +36 h) before and after the beginning of oxygen exposure. Hyperoxic lung damage and modifications in cytochrome P-450 system components were evaluated. Our results confirmed the protective effect of poly I: poly C on rats exposed to oxygen, reducing the lung edema and the mortality. This effect was only observed when poly I: poly C was injected 48 or 36 h before the beginning of oxygen exposure. Although oxygen exposure per se decreased the total level of lung cytochrome P-450, poly I: poly C per se induced a deeper decrease to levels similar in air- or oxygen-exposed rats. Poly I: poly C did not modify the NADPH-cytochrome c reductase level nor the cytochrome P-450 peroxidase activity in air-exposed rats. The oxygen exposure induced a decrease of these two enzymes, either in the absence or in the presence of poly I: poly C, except when poly I: poly C was injected 48 or 36 h before the beginning of oxygen exposure, times at which poly I: poly C restored the enzymatic values measured in rats exposed to air. Because the times of injection of poly I: poly C were those at which the protective effect was observed, it suggested that the protective effect of poly I: poly C against oxygen toxicity was associated with a lack of oxygen-induced decrease of both the lung NADPH-cytochrome c reductase level and the lung cytochrome P-450 peroxidase activity.

Animals↗