Search PubMed⌕ Search

Biomedical subjects

C Carbon

Publications and source records attributed to C Carbon.

At least 145 records · Page 8Linked to original sources
PubMed1995

A reappraisal of quinolone tolerability. The experience of their musculoskeletal adverse effects.

The experience of the rheumatological adverse effects of fluoroquinolones should be helpful for both toxicologists and epidemiologists. In the case of fluoroquinolone-related arthropathy, the paediatric clinical experience seems to support the possible use of newer derivatives like ciprofloxacin in children who really need it. This therapeutic attitude is still contradictory to the labelling of fluoroquinolones. Inversely, there has been an important time-lag between the first reports of fluoroquinolone-related tendinopathies and the official recognition of this unusual toxic phenomenon. This delay, along with the widespread use of fluoroquinolones, makes it difficult to return to more reasonable prescribing guidelines for these very useful and effective anti-microbial compounds. The reasons why potentially serious adverse effects of fluoroquinolones were not anticipated before their commercialisation may be related to the lack of adequate in vitro and in vivo models, and the unexpectedness of the events. When it occurs, fluoroquinolone-induced arthropathy is most frequently benign, and heals without sequelae. The prognosis is not so favourable in the case of fluoroquinolone-related tendinopathy, which carries an important risk of immediate or secondary tendon rupture. Increasingly, fluoroquinolones are being prescribed for benign infections of the urinary or bronchopulmonary tracts. Sometimes, they are even used for antimicrobial prophylaxis before surgical or endoscopic procedures. We believe that for any prescription, the risk/benefit ratio of the fluoroquinolones should be carefully considered, since better tolerated, less expensive drugs can usually be prescribed. Clear information dedicated both to physicians and patients regarding the cautions for use and possible adverse effects of fluoroquinolones would help reduce the risk and severity of adverse reactions. This is especially important for phototoxicity, tendinopathy and cardiovascular adverse effects. As underlined by Ball and Tillotson in this issue, the future clinical use of the fluoroquinolones will be determined by the balance between the antibacterial efficacy and adverse effects of these agents. The adverse reactions affecting the musculoskeletal system provide a good example of this dilemma. Given the absence of an adequate model of tendinopathy and the poor predictivity of animal manifestations in arthropathy and cartilage lesions in humans, careful monitoring of patients during phase II and III trials and, more importantly, long term pharmacovigilance during the postmarketing period, are still strongly warranted.

Age Factors↗
PubMed1995

[Contribution of the experimental model of bacterial endocarditis].

Bacterial endocarditis is a difficult to cure infection, due to poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response which could cooperate with antibiotic action. The contribution of animal models to a better understanding of the pathophysiology of the infection and to definition and improvement of therapeutic regimens of endocarditis in humans, remains of great importance due to the difficulties encountered in clinical trials. The advantage of the experimental model is that besides the fact that is closely simulates the characteristics of the infection in humans, it provides clear endpoints which allow statistical comparisons among different therapeutic regimens. The animal model has definitively established that bactericidal therapy is warranted and that in vitro susceptibility tests, especially those evaluating the killing rate, have a good predictive value on therapeutic outcome. Two main aspects are discussed for their relevance to human therapy and represent our recent contribution: (i) the kinetics of antibiotic diffusion into vegetations, with special reference to data obtained with autoradiography; and (ii) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis. This animal model has also helped to define the importance of antibiotic dosing strategies to achieve in vivo synergism and to outline the predictive value of some drug pharmacokinetic and dynamic properties on the in vivo response to therapy.

Animals↗
PubMed1995

[Assessment of the role of enterocyte ion exchange in the intestinal absorption of amoxicillin, based on a study of the interaction with amiloride].

Intestinal dipeptide carrier system has been shown in vitro to be involved in intestinal absorption of betalactam antibiotics. Given that efficiency of this transport system depends on a pH gradient (extracellular pH < intracellular pH) at the brush-border membrane of enterocytes, we assessed the effects of amiloride, a known inhibitor of the Na-H exchange, on the bioavilability of oral amoxicillin in eight normal volunteers. Following a single 10 mg oral dose of amiloride, the absolute bioavailability of oral amoxicillin turned out to decrease by 27% (p < 0.01). The extent of reduction of oral amoxicillin AUC appeared to significantly correlate (p = 0.005) with the extent of decrease in potassium renal excretion but not with variations in antibiotic renal clearance under amiloride effect. Such patterns seem to confirm in vivo the role of the Na-H exchange in betalactam absorption and to suggest the underlying regulatory function of intracellular Na concentration, the latter depending on the (NaK)-ATPase activity.

Administration, Oral↗
PubMed1995

Overview of the efficacy of isepamicin in the adult core clinical trial programme.

The efficacy of once-daily administration of isepamicin in hospitalized adult patients has been assessed in a multinational clinical trails programme. Following a small phase II programme, the phase III programmed assessed four main indications: lower respiratory tract infections (including nosocomial pneumonia), urinary tract, intra-abdominal and skin and soft tissue infections. The phase III trials were open, prospective, multicentre studies in which 1443 patients were randomised to receive either isepamicin (n = 1005) or amikacin (n = 438). The daily dose of isepamicin was dependent on the severity of infection (8 or 15 mg/kg once daily) while all patients received amikacin 7.5 mg/kg twice daily. A study of patients with nosocomial pneumonia had an additional treatment arm of isepamicin 7.5 mg/kg twice daily. The aminoglycosides were combined with other antimicrobial agents in accordance with current clinical practice depending on the site and severity of the infection and the type of organism isolated. Overall, clinical cure or improvement response rates of the isepamicin and amikacin regimens were comparable, ranging from 76-95% in the intent-to-treat population. Lower clinical response rates (62-63%) was observed in severely ill patients with nosocomial pneumonia in both the isepamicin and amikacin treatment groups. In the efficacy population, organism elimination rates of 90% were achieved with isepamicin and amikacin. Therefore, in adult patients with a wide range of infections requiring aminoglycoside therapy, once-daily dosing with isepamicin is as effective as twice- daily dosing with amikacin.

Abdomen↗
PubMed1994

[Streptococcus pneumoniae bacteremia and HIV infection. Retrospective study of 41 episodes in 30 patients].

OBJECTIVES: Pulmonary infections and bacteraemia, essentially due to Streptococcus pneumoniae and Haemophilus influenzae, are frequently reported in patients infected with the human immunodeficiency virus (HIV). We retrospectively analyzed episodes of bacteraemia in HIV-infected patients to determine whether supplementary risk factors could be ascertained and whether it would be advisable to propose vaccination. METHODS: From June 1986 to February 1992, 41 episodes of bacteraemia in 30 HIV-infected patients were observed in 7 different wards. Data on age, sex, risk group, Centers for Disease Control classification, CD4 counts and clinical outcome were recorded. RESULTS: There were 18 males and 12 females, mean age 34 years (range 26-67 years) in CDC class II (n = 11), III (n = 5) and IV (n = 16). There were 17 intravenous drug users (56.6%). There were 8 heterosexuals (26%), 3 homosexuals or bisexuals (n = 3) and 2 patients infected after blood transfusions (6%). All the heterosexual patients were of black-African or Carabean ethnic origin. Mean CD4 count was 239 mm3 (range 2-1148) during the episode of bacteraemia which occurred during an upper respiratory tract infection in 96% of the patients. Recurrent episodes were observed in 7 patients. Outcome of the infectious episode was favourable in 35/41 cases after antibiotic therapy. Six patients (all CDC class IV) died during the episode of bacteraemia. CONCLUSIONS: These observations showed that intravenous drug use and black-African ethnic origin are supplementary risk factors for S. pneumoniae infection in HIV-infected patients. The frequency of upper respiratory tract infections in these patients suggests that anti-S. pneumoniae vaccination should be evaluated further.

AIDS-Related Opportunistic Infections↗
PubMed1994

[New infectious risks].

New infectious risks have been identified or better elucidated in the last few years. The concept of infectious risks implies: a receptive host; or more or less pathogenic agent, inducing pathologic phenomena with variable facility, depending the receptivity of the host; and individual or community environmental factors (risk of accidental and massive contact with a pathogenic agent). These new risks are linked to: 1. the appearance of new or newly identified pathogenic agents, and the periodic changes in the pathogenic strength of some microorganisms, modifying the epidemiology of some infections; 2. changes in host receptivity (immunodepression, either acquired or linked to aggressive therapy which leads to prolonged survival of receptive patients); 3. environmental modifications (spread of resistant pathogenic bacteria, for example, presently the tuberculosis bacillus; declining socioeconomic conditions; reduced efficacy of community measures for prevention); 4. exposure to new risks linked to progress in diagnostic and therapeutic techniques (invasiveness of medical treatments, new treatment techniques, transplantations, implantation of foreign materials, transfusions). These phenomena illustrate the constant change in infectious risks and the need for a multidisciplinary approach to the problem and its effects.

Causality↗
PubMed1994

Effect of the platelet activating factor antagonist BN52021 in rabbits: role in gentamicin nephrotoxicity.

Platelet activating factor (PAF) is an ubiquitous phospholipid that acts as a mediator of numerous pathophysiological conditions, including drug nephrotoxicity. Aminoglycosides are potent antibiotics but their use is limited by their nephrotoxic potential. We assumed that PAF could participate in inducing gentamicin nephrotoxicity, and we used the PAF antagonist BN52021 to test this hypothesis. We studied renal glomerular and tubular function by clearance techniques and renal histology in four groups of New Zealand male rabbits treated for 7 days with isotonic saline, BN52021, gentamicin, or gentamicin + BN52021. BN52021 alone reduced only fractional excretions (FE) of sodium and chloride, without modifying the other parameters studied. Renal histology was not altered. Gentamicin reduced glomerular filtration rate and renal plasma flow. Free water clearance was not modified. Sodium, potassium, chloride, calcium, and magnesium FEs were raised. Renal histology showed a massive and diffuse tubular necrosis. BN52021 did not modify gentamicin glomerular, tubular, or histopathological alterations. These data suggest that PAF might physiologically affect tubular function in New Zealand male rabbits, increasing sodium and chloride excretions, and in a minute manner, potassium, calcium, and magnesium excretions. Under our experimental conditions, there was no evidence for a role of PAF in gentamicin nephrotoxicity.

Animals↗
PubMed1994

Animal models of endocarditis.

Bacterial endocarditis is a difficult infection to cure, due to poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the lesion, and absence of adequate host-defense cellular response which could cooperate with antibiotic action. The contribution of animal models to a better understanding of the pathophysiology of the infection and to definition and improvement of therapeutic regimens of endocarditis in humans remains of great importance due to the difficulties encountered in clinical trials. The advantage of the experimental model is that besides the fact that it closely simulates the characteristics of the infection in humans, it provides clear endpoints which allow statistical comparisons among different therapeutic regimens: number of bacteria per gram of tissue, frequency of emergence of resistance, positivity of blood cultures, death vs. survival rates, and percentage of relapses after treatment has been stopped. All these parameters are more sensitive and more easy to study than in humans. The animal model has definitively established that bactericidal therapy is warranted and that in vitro susceptibility tests, especially those evaluating the killing rate, have a good predictive value on the therapeutic outcome. Two main aspects are discussed for their relevance to human therapy: (i) the kinetics of antibiotic diffusion into vegetations, with special reference to data obtained with autoradiography; and (ii) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis, including the clinical consequences of these two parameters with respect to antibiotic dosing regimens and length of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Evaluation of a rabbit model for osteomyelitis by high field, high resolution imaging using the chemical-shift-specific-slice-selection technique.

The rabbit model of osteomyelitis introduced by C.W. Norden, based on injection of an infecting solution (Staphylococcus aureus, sodium morrhuate) into the tibia, was studied at 4.7 Tesla with a time-efficient chemical shift selective imaging technique, Chemical Shift Specific Slice Selection (C4S). The evolution of the disease over several weeks was followed on water-selective, fat-selective, and sum images obtained simultaneously with this imaging sequence. Experiments were performed either on different groups of rabbits at different times after infection with subsequent sacrifice of the animal and microbiological analysis of the infected tibia or on the same group of animals imaged several times after infection. Associated analysis of the water and fat selective images revealed marrow modifications very early (Day 5 after inoculation) demonstrating the high sensitivity of the employed imaging technique. Later on, bone modifications were best identified on the sum images. Additional experiments performed on animals injected with a noninfecting solution containing only sodium morrhuate showed however that the sclerosing agent alone can yield images similar to those produced by infection at early stages after inoculation. Therefore, the Norden model would not be suitable for monitoring quantitatively outcome of therapy by magnetic resonance imaging. It is however well adapted for the evaluation and optimization of MRI techniques or protocols intended to detect early changes of bone marrow produced by septic or aseptic infarct.

Adipose Tissue↗
PubMed1994

The impact of a comprehensive multi-dimensional geriatric assessment programme on duration of stay in a French acute medical ward.

The impact of a multi-dimensional geriatric assessment (MDGA) programme on the reorientation of the elderly person at discharge is described. One hundred and six elderly persons from a hospital catchment area identified for its poor level of social services, poor living conditions and high prevalence of dependency were allocated to either an experimental or control group. The experimental group was given the multi-dimensional assessment in the first three days of admission while the control group was subject to the usual hospital procedures. The study shows that the provision to the medical staff of easily obtained information relating to the individual's level of dependency and living conditions, in conjunction with recommendations for possible post-discharge placement, significantly reduced prolongation of stay due to non-medical reasons, albeit without a measurable impact on the whole duration of hospital stay.

Activities of Daily Living↗
PubMed1994

The intestinal elimination of ciprofloxacin in the rat.

The transepithelial intestinal elimination of ciprofloxacin was studied in a rat model. Two jejunal and one ileal segment, along with their intact blood supplies, were isolated and continuously perfused. Following a single parenteral administration of 25 mg/kg ciprofloxacin, the drug in amounts of 1.97 +/- 0.70, 1.88 +/- 0.99, and 1.44 +/- 0.77 micrograms/cm2 of mucosal surface was recovered over 90 min from the proximal and distal jejunal loops and the ileal loop, respectively, reaching a calculated fraction of 6%-7% of the dose eliminated in the entire small intestine. The rate of intestinal elimination related linearly to the parenteral dose. In the proximal jejunum, however, doses > 25 mg/kg were not accompanied by a concomitant increase in the eliminated fraction, suggesting a saturable transport process. Parenterally administered probenecid, amoxicillin, and nifedipine and changes ranging from 6.0 to 8.5 in the pH of the perfusates did not alter transepithelial elimination. This pathway of elimination of ciprofloxacin may play an important role in curing intestinal infections.

Amoxicillin↗
PubMed1994

Investigation of the potential role of Enterococcus faecalis in the pathophysiology of experimental peritonitis.

Two nonfatal models of peritonitis differing by the duration and the severity of the disease were studied in rats by implantation of Escherichia coli and Bacteroides fragilis with or without increasing concentrations of Enterococcus faecalis. Results were evaluated at 3 or 6 days after inoculation. The highest enterococcal concentrations (10(9) cfu/mL) enhanced the severity of the infection, evident by increased emaciation, increased peritoneal counts of E. coli and B. fragilis, and increased frequency of E. coli and B. fragilis bacteremia compared with enterococcus-free animals. Six therapeutic regimens (low-dose amoxicillin + low-dose gentamicin, high-dose amoxicillin + high-dose gentamicin, pefloxacin, ornidazole, pefloxacin + ornidazole, imipenem + gentamicin) were tested. All treatments failed to eradicate E. faecalis except the combination pefloxacin + ornidazole, which achieved a significant reduction of local bacterial counts and suppressed bacteremia. Enterococcus played an important role in the mechanisms of bacterial synergy in experimental peritonitis. However, eradication of enterococcus did not seem possible by conventional antienterococcal therapy.

Abscess↗
PubMed1994

Activity of isepamicin and selection of permeability mutants to beta-lactams during aminoglycoside therapy of experimental endocarditis due to Klebsiella pneumoniae CF104 producing an aminoglycoside acetyltransferase 6' modifying enzyme and a TEM-3 beta-lactamase.

The pharmacokinetics and efficacy of isepamicin were compared with those of amikacin and gentamicin in a rabbit model of endocarditis due to Klebsiella pneumoniae CF104 producing beta-lactamase TEM-3 and aminoglycoside acetyltransferase AAC(6')-IV. Only isepamicin and gentamicin, alone or combined with ceftriaxone, were effective as determined by titration of viable bacteria in vegetations. Variants highly resistant to ceftriaxone without change in MICs of aminoglycosides were isolated at the end of each therapeutic regimen except with the most effective one (ceftriaxone plus gentamicin). Examination of the bacterial outer membrane proteins as well as the 50% inhibition of the beta-lactamase activity in intact and sonified cells suggested a permeability defect as being responsible for the increased MICs of ceftriaxone. The activity of isepamicin was superior to that of amikacin against the TEM-3-AAC(6')-IV-producing strain. The combination of gentamicin plus ceftriaxone was the most effective regimen in terms of efficacy and prevention of emergence of resistant strains. Suboptimal aminoglycoside monotherapy might be responsible for selection of permeability mutants to beta-lactams.

Acetyltransferases↗