PubMed HealthSearch

Biomedical subjects

M Roland

Publications and source records attributed to M Roland.

At least 19 recordsLinked to original sources

Factors affecting iontophoretic mobility of metoprolol.

The effect of different factors on the iontophoretic transport of metoprolol was analyzed. In vitro experiments were first performed in a diffusion cell with a cellophane membrane. Comparison of different pH, buffers, and ionic strengths in the donor compartment showed that higher iontophoretic transport was obtained with phthalate buffer (0.01 M) at pH 3. When the current density increased, the flux of metoprolol also increased. A decrease in drug concentration or an increase in viscosity slowed down the iontophoretic transport of metoprolol. The fluxes of metoprolol through hairless rat skin were strongly enhanced compared with passive diffusion. Direct current seemed to be more efficient than pulse current. When the on:off ratio of the pulse current was reduced, the flux also decreased.

Algorithms

Macrophage activation by polymeric nanoparticles of polyalkylcyanoacrylates: activity against intracellular Leishmania donovani associated with hydrogen peroxide production.

Nanoparticles of polyalkylcyanoacrylates (PACA) can be useful carrier for the targeting of antileishmanial drugs into macrophages and also possess significant antileishmanial activity by themselves. No significant difference in antileishmanial activity could be detected between nanoparticles of five PACAs with differing alkyl side chains, suggesting that the main degradation products of PACA are not involved in their antileishmanial action. The effect of polyisohexylcyanoacrylate (PIHCA) on the induction of the respiratory burst in a macrophage-like cell line (J774G8) was assessed in non-infected macrophages and in macrophages infected with amastigotes of Leishmania donovani infantum, by measuring nitroblue tetrazolium (NBT) reduction and hydrogen peroxide production. Phagocytosis of PIHCA nanoparticles led to a respiratory burst, which was more pronounced in infected than in uninfected macrophages. The production of reactive oxygen intermediates associated with the respiratory burst was inhibited by addition of superoxide dismutase and catalase to the cell suspensions. The addition of catalase to the culture medium together with PIHCA nanoparticles significantly reduced the antileishmanial activity of PIHCA. Moreover PIHCA nanoparticles did not induce interleukin-1 release by macrophages. It is suggested that the antileishmanial action of PIHCA and other PACA nanoparticles results from the activation of respiratory burst in macrophages.

Animals

Drug targeting with polyalkylcyanoacrylate nanoparticles: in vitro activity of primaquine-loaded nanoparticles against intracellular Leishmania donovani.

The efficacy of primaquine-loaded polyisohexylcyanoacrylate (PIHCA) nanoparticles was evaluated using J774G8 macrophage-like cells infected with Leishmania donovani: as an in vitro model of visceral leishmaniasis. The in vitro antileishmanial activity of primaquine-loaded nanoparticles showed a 21-fold increase in ED50 compared with free primaquine. Although unloaded PIHCA nanoparticles also exhibited a significant anti-leishmanial effect, the loaded nanoparticles showed a synergistic effect compared with a mixture of unloaded nanoparticles and free primaquine at equivalent concentrations. Primaquine release and isohexanol production were evaluated in a lysosomal fraction; the correlation of both with protein concentration and the rapid drug release indicate the processes are associated with an enzymatic degradation. The results indicate that PIHCA and other polyalkylcyanoacrylates may be useful for targeting drugs at intracellular Leishmania, and that the unloaded carrier itself could be of interest in experimental chemotherapy of leishmaniasis.

Animals

Comparison of nephrotoxicities of different polyoxyethyleneglycol formulations of amphotericin B in rats.

The aim of the present study was to assess whether amphotericin B (AmB)-Myrj 59, AmB-polyoxyethyleneglycol 24 cholesterol (PC), and AmB-Synperonic A50 (SA50) were less nephrotoxic than AmB-deoxycholate (DC). Rats were treated with the different AmB formulations (10 mg/kg of body weight) intraperitoneally or with the surfactants alone. A group of control rats receiving the vehicle was also examined. After 6 days of daily intraperitoneal injections of AmB-DC, decreased body weight and glomerular filtration rate as well as increased degree of diuresis, uremia, microalbuminuria, and N-acetyl-beta-D-glucosaminidase excretion in urine were noted. Urinary excretion of potassium and sodium was also decreased in AmB-DC-treated rats. Most of these effects were more pronounced with AmB-PC and AmB-SA50. In contrast, AmB-Myrj 59 was less nephrotoxic than AmB-DC. Indeed, after 6 days of treatment with AmB-Myrj 59, the natriuria, kaliuria, albuminuria, and glomerular filtration rates were unchanged compared with those of controls. Moreover, the body weight loss and uremia increase of the rats treated by AmB-Myrj 59 were less than those of the rats treated with the commercial preparation. Among the surfactants, only PC was toxic for the rats. The intrinsic toxicity of PC and the higher systemic exposure to AmB could contribute to increased toxicities of AmB-PC and AmB-SA50, respectively. AmB-Myrj 59 was less nephrotoxic than AmB-DC at equivalent areas under the plasma concentration-time curves. These preliminary results suggest that this formulation could be a good alternative to the commercial product.

Amphotericin B

Boneline: evaluation of an initiative to improve communication between specialists and general practitioners.

In response to a previous study of GPs' and consultants' satisfaction with orthopaedic outpatient referrals, orthopaedic surgeons at Doncaster Royal Infirmary made themselves available for telephone consultations with general practitioners (GPs) at advertised times. This service, called 'Boneline', was used infrequently, though the GPs who did use it found it valuable, and reported that a number of referrals had been avoided by speaking to the consultant. There was, however, no significant change in the rate at which requests for out-patient appointments were received during the six months of Boneline's operation. Opportunities for improving telephone communication between GPs and consultants are discussed.

Communication

The influence of Myrj 59 on the solubility, toxicity and activity of amphotericin B.

The effect of Myrj 59 (a polyoxyethyleneglycol derivative of stearic acid) on amphotericin B (Am B) solubility, toxicity and activity has been investigated. We showed that Myrj 59 could solubilize the antibiotic. Moreover, it also decreased and abolished the haemolytic activity of the drug by increasing the resistance of the red blood cells and impairing the interaction of Am B with the cellular membrane cholesterol, but it did not modify the in-vitro antifungal activity of the drug. On the other hand, Myrj 59 did not decrease the acute in-vivo toxicity of the drug (LD50 and nephrotoxicity). In a previous study we have shown that a polyoxyethleneglycol derivative of cholesterol could solubilize Am B and was able to decrease the in-vitro and in-vivo toxicity of the antibiotic without altering its in-vitro antifungal activity. The results of the present study suggest that the cholesterol moiety of the surfactant is not necessary to decrease the in-vitro lytic activity of the drug but could play a role in the reduction of the in-vivo toxicity.

Amphotericin B

Perimenopausal women's views on taking hormone replacement therapy to prevent osteoporosis.

OBJECTIVE: To find out perimenopausal women's views on taking hormone replacement therapy to prevent osteoporosis. DESIGN: Semistructured postal questionnaire survey; the questionnaire was enclosed with a letter to explain the purpose of the study and to give patients some information about hormone replacement therapy and osteoporosis. SETTING: Mixed social class, urban general practice with 12,000 registered patients. PATIENTS: All women aged 50, 51, or 52 were selected from the age-sex register; 102 women were identified and 84 (87%) replied to the questionnaire. MAIN OUTCOME MEASURES: Response rates to questions on interest in taking hormone replacement therapy, the importance of preventing osteoporosis, and worries about side effects of the treatment. RESULTS: More than three quarters of the respondents (65) were interested in taking hormone replacement therapy to prevent osteoporosis, but 48 of them would have liked further information. Sixty four women thought that it was very important to prevent osteoporosis. More than half of the respondents (51) were worried about side effects of the treatment, but only 15 women thought that continued menstruation would be a major disadvantage. CONCLUSIONS: There is considerable interest among perimenopausal women in taking hormone replacement therapy to prevent osteoporosis. The resource implications for primary care in meeting this interest are substantial.

Attitude to Health

Tissue distribution of doxorubicin associated with polyisohexylcyanoacrylate nanoparticles.

The body distribution of i.v. doxorubicin depends mainly on the physicochemical characteristics of the molecule. However, entrapment of that cytostatic drug inside polyalkylcyanoacrylate nanoparticles has been shown to modify its distribution profoundly in the mouse. Polysiohexylcyanoacrylate nanoparticles loaded with [14C]-doxorubicin were studied in comparison with free drug, with emphasis on their distribution pattern in mouse tissue after i.v. administration. An autoradiographic study showed that most of the radioactivity was found in the reticuloendothelial system as soon as a few minutes after i.v. administration of the doxorubicin-loaded nanoparticles. Quantitative determinations by liquid scintillation counting in fresh tissue (spleen, heart, kidneys, liver, lungs, bone marrow) and blood samples confirmed these observations. When the drug was linked to nanoparticles, doxorubicin blood clearance was reduced during the first few minutes after administration, whereas heart and kidney concentrations were substantially decreased. Assays of doxorubicin and doxorubicinol by a specific HPLC analytical method gave results very similar to those obtained by scintillation counting.

Animals

Antimicrobial prophylaxis in elective colorectal surgery and appendicitis.

The purpose of this presentation is to evaluate the role of anaerobic and aerobic microorganisms in postoperative infections after colorectal surgery and appendicitis, and to evaluate when antimicrobial agents should be administered prophylactically in conjunction with these operations. In one multicenter study, prophylactic regimens against anaerobic and aerobic microorganisms were compared for durations of one and three days after colorectal surgery. In another multicenter study, the effect of a regimen against anaerobes used alone or in combination with an agent against aerobes in one preoperative dose were compared. The different types of operations had different potential for postoperative infections. An antimicrobial agent against anaerobic microorganisms given as one preoperative dose may suffice in surgery on the upper part of the colon, but a combination with an agent against aerobic bacteria is recommended in rectal surgery. The effectiveness of agents against anaerobic and aerobic bacteria in preventing postoperative infections after appendectomy in cases of gangrenous or perforated appendicitis without general peritonitis were compared in another study. This concluded that an agent against anaerobes is recommended when the appendix is gangrenous or perforated.

Anti-Bacterial Agents

Randomized controlled trial of an educational booklet for patients presenting with back pain in general practice.

A randomized controlled trial was used to evaluate an educational booklet on back pain for patients presenting to five group practices during one calendar year. The booklet had no immediate effect on consultations for back pain, but in the period from two weeks to one year after presentation significantly fewer patients in the group receiving the booklet consulted with back pain (35.6%) than in the control group (42.2%) (P less than 0.05). There were no significant differences between the booklet and control groups in certified absence from work owing to back pain. Referral to hospital, referral to physiotherapy, admissions to hospital and laminectomies were all less common in the booklet group. The reduction in the combined referral rate to physiotherapy and hospital, and the reduction in laminectomy rate almost reached statistical significance at the 5% level. In replying to a questionnaire sent one year after entry to the study 94.1% of respondents in the booklet group said that they had read the book, 84.0% said that they found it useful, and 68.0% said that they still had a copy. Scores on a 15-item test of knowledge about back pain were significantly higher in the group of patients who had received the booklet than in the control group. The results suggest that the booklet had some effect in altering both the knowledge and behaviour of patients with back pain. The provision of an educational booklet was a method of giving information which was appreciated by both patients and doctors.

Adult

[Primary health services, financing and research].

The capitation method of payment is presently used in five health centres in Belgium, in accordance with the 1963 health insurance law. The position of this experience in the field of primary health care, with its direct impact on concrete and subjective dimensions, implies that its evaluation, even quantitative, should rely on action research methodology. Action-research includes concern for change and involvement of concerned actors with the objectives and the field of the research. The study protocol developed by the Federation of Health Centres is presented. It proposes the parameter "mean total cost by insured person". Presently the study does not progress; reason for this are examined.

Capitation Fee

Are referrals by general practitioners influenced by the availability of consultants?

To investigate variations in the number of outpatients seen in different NHS regions of Great Britain data on numbers of outpatients, number of consultants per 100,000 population, mortality, and prescribing rates were analysed for four specialties: medicine, thoracic medicine, psychiatry, and dermatology. The number of outpatients seen was strongly associated with the provision of consultants in all four specialties and only weakly associated with need for outpatient services as measured by standardised mortality ratios and mean numbers of prescriptions per patient issued by general practitioners. Interpretations of differences in referral rates need to take into account variations in the supply of specialists as a factor that may influence the referral behaviour of general practitioners.

Catchment Area, Health