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Biomedical subjects

N Brion

Publications and source records attributed to N Brion.

At least 55 records · Page 3Linked to original sources
PubMed1987

Comparative efficacy of cefotiam, cefmenoxime, and ceftriaxone in experimental endocarditis and correlation with pharmacokinetics and in vitro efficacy.

To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three cephalosporins, cefotiam, cefmenoxime, and ceftriaxone, in a rabbit model of experimental Escherichia coli endocarditis after 4 days of treatment. The MBCs of cefotiam, cefmenoxime, and ceftriaxone for the E. coli strain were 0.5, 0.125, and 0.06 microgram/ml, respectively. Killing curves at 10 times the MBC were similar for the three cephalosporins. In serum, the elimination half-life of ceftriaxone was twice as much as the elimination half-life of cefotiam or cefmenoxime (2.8 +/- 0.45 versus 1.4 +/- 0.25 or 1.3 +/- 0.4 h, respectively). Ceftriaxone was much more effective than cefotiam. The bacterial titer in the vegetations (log10 CFU per gram of vegetation) was 7.56 +/- 1 with cefotiam and 2.41 +/- 2.6 with ceftriaxone, as their concentrations were 18 and 466 times higher, respectively, than their MBCs. Although ceftriaxone and cefmenoxime exhibited a similar rate of killing and percentage of protein binding, ceftriaxone was more effective than cefmenoxime at the same regimen of 15 mg/kg twice a day (3.08 +/- 1.1 versus 4.82 +/- 3.2 log10 CFU/g of vegetation). When antibiotic was given as a single daily injection of 30 mg/kg, the antibacterial effect persisted for ceftriaxone, but not for cefmenoxime. The longer elimination half-life and the higher local concentration/MBC ratio of ceftriaxone explained these results. The bacterial titer measured 24 h after the fourth injection of 30 mg of ceftriaxone per kg confirmed that this regimen prevented regrowth of bacteria. These results suggest that the local antibiotic level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed between the drugs in vivo. They also demonstrate that, provided that the dose is sufficient, a long-acting broad-spectrum cephalosporin may be effective in severe gram-negative infections, even when given at relatively long dosing intervals, in contrast with a rapidly cleared drug with the same intrinsic activity.

Animals↗
PubMed1986

[Is systematic syphilis serology still useful in a department of internal medicine? A one-year prospective study using a diagnostic and therapeutic decision algorithm].

During one year syphilis serology was systematically studied, using the TPHA and VDRL tests, in each of the 1,279 patients hospitalized in an Internal Medicine department. In all cases diagnosis and treatment were analyzed by means of a decision algorithm. Only 37 patients were found to have one or both serological tests positive. No evolutive syphilis was observed, and none of these positive tests was contributive to the diagnosis of another disease. Only 14 patients received a specific antibiotic treatment on the grounds that their positive test confirmed a late asymptomatic syphilis. We conclude that systematic syphilis serological tests are not useful in an Internal Medicine department, except in some patients epidemiologically at high risk of syphilis.

Algorithms↗
PubMed1986

Penetration of pefloxacin in human heart valves.

Pefloxacin concentrations were measured by HPLC in serum, subcutaneous tissue, heart muscle and heart valves of 41 patients receiving a one hour infusion of 800 mg iv 4, 8, 12, 18, or 24 h before open heart surgery for prosthetic cardiac valve insertion. In all but three of the 46 valvular samples, pefloxacin concentrations were higher than the mode MIC of Staphylococcus, Enterobacteriaceae and Pseudomonas microorganisms causing infections following open heart surgery. Pefloxacin therefore has good penetration of heart valves and is present for up to 24 h. It could be considered as a useful drug in the prophylaxis of cardiac surgery and in therapy of bacterial endocarditis due to susceptible micro-organisms.

Adolescent↗
PubMed1986

[Treatment of systemic scleroderma with D-penicillamine. Results in 14 patients treated for more than a year].

The authors review the theoretical bases for the treatment of systemic scleroderma (SS) by D-penicillamine (DP). They then present a review of the papers published over the last 20 years on the subject. Although Rodnan's team has conducted studies against a control series and the majority of published works have concluded on the effectiveness of this treatment, there has not been any randomised prospective study, to date, to clearly demonstrate this effectiveness. The authors report a series of 14 patients with SS treated for a mean of 2 years with 900 mg/day of DP. DP seemed to be effective on the cutaneous lesions in 12 of the patients treated at a maximum of 3 years after the frank onset of the disease. Treatment failed in 2 patients who were only treated late in the disease. Objective results were obtained on the pulmonary lesion, but they are more difficult to interpret. 5 patients had to interrupt DP treatment because of intolerance. Tiopronine was tried in 4 of these patients with 3 interpretables follow-ups. This agent was well tolerated and effective in 2 of these 3 patients.

Adult↗
PubMed1986

[Diffusion of trimethoprim and sulfamethoxazole into the pleural fluid].

The level of Trimethoprim (TMP) and of Sulfamethoxazole (SMZ) in the fluid of both pleural effusion and plasma was determined in 7 patients on the first day of treatment consisting of two daily doses of 160 mg TMP and 800 mg SMZ. In 4 subjects, the levels were determined again on the third (J3) and fifth day of treatment (J5). Thus with TMP the ratio of pleural/plasma drug levels rose progressively from the first day of treatment to attain by 12 hours a mean value of 0.79 +/- 0.16; subsequently it stayed at about the same level for day 3 (J3) and day 5 (J5). As for SMZ, the ratio of the pleural plasma drug level reached a maximum at 8 hours on the first day of treatment (0.53 +/- 0.12) then rose progressively on day 3 (J3 0.58 +/- 0.06) and on day 5 to 0.71 (+/- 0.08). The levels of TMP in the pleural fluid were below those which are usually described in bronchial secretions. On the other hand those of SMZ are appreciably raised.

Drug Combinations↗
PubMed1985

Renal disposition of gentamicin, dibekacin, tobramycin, netilmicin, and amikacin in humans.

The tubular disposition of five aminoglycosides was studied in humans to establish a possible relationship between tubular reabsorption and the nephrotoxicity that has been described in the literature. Thirty-three healthy male volunteers received a continuous intravenous infusion of isotonic saline with inulin, followed 1 h later by inulin plus gentamicin, dibekacin, tobramycin, netilmicin, or amikacin (1 mg/kg per h) or amikacin (4 mg/kg per h) over a period of 2 h. Brain-stem-evoked response audiometry was performed both before and at the end of each infusion. The latency of wave V remained constant whichever antibiotic was considered. The glomerular filtration rate did not vary significantly during the infusion of each drug. The percent fractional excretion was 79 +/- 6, 81 +/- 22, 85 +/- 5, and 99 +/- 9 for gentamicin, dibekacin, tobramycin, and netilmicin, respectively, and 83 +/- 4 and 124 +/- 13 for amikacin at concentrations of 1 and 4 mg/kg per h, respectively. Net balance and renal clearance were similar for the five aminoglycosides when administered at a rate of 1 mg/kg per h. With gentamicin only, fractional excretion was correlated with the urinary flow rate. We can conclude that (i) gentamicin, generally considered the most nephrotoxic agent, had the highest degree of net reabsorption; (ii) netilmicin exhibited a net zero tubular balance; (iii) amikacin had different patterns of tubular disposition according to the dose, i.e., reabsorption at 1 mg/kg per h and secretion at 4 mg/kg per h, raising the hypothesis of a saturable process of reabsorption; and (iv) these differences in tubular reabsorption could account at least in part for the known different nephrotoxic potentials of these five aminoglycosides in humans.

Adult↗
PubMed1985

Effects of urinary pH on renal interactions between probenecid and cefsulodin in rabbits.

The effect of urinary pH on renal interaction of cefsulodin and probenecid was tested in rabbits. Probenecid was reabsorbed in acidic urine (fractional excretion [FE] = 8 +/- 4%) and secreted in alkaline urine (FE = 492 +/- 258%). Renal excretion of cefsulodin alone was not affected by the urinary pH (FE = ca. 100%). In acidic urine, probenecid significantly reduced tubular secretion of cefsulodin (FE = 74 +/- 8%). An inverse pattern was observed in alkaline urine (FE = 122 +/- 18%).

Animals↗
PubMed1984

Gentamicin, netilmicin, dibekacin, and amikacin nephrotoxicity and its relationship to tubular reabsorption in rabbits.

The role of the tubular reabsorption of aminoglycosides in nephrotoxicity was considered. The tubular reabsorption rate, fractional reabsorption, and net balance, expressed as the excreted to infused aminoglycoside ratio, were concomitantly studied in male rabbits by continuous infusion of gentamicin, netilmicin, dibekacin, and amikacin. Aminoglycoside nephrotoxicity was evaluated by creatinine levels in serum and pathological renal damage after 14 days of a low- or high-dose regimen, comprising either eight, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (4 mg/kg) or amikacin (16 mg/kg); twelve, hourly intramuscular injections of gentamicin, netilmicin, or dibekacin (15 mg/kg) or amikacin (60 mg/kg); or injections of saline for the control group. Aminoglycosides exhibited three degrees of tubular reabsorption: gentamicin had the highest, netilmicin had the lowest, and dibekacin and amikacin had intermediate degrees of reabsorption. Nephrotoxicity associated with alteration in renal histology was observed with gentamicin and, to a lesser extent, with dibekacin in the high-dose regiment. No nephrotoxicity was noted with netilmicin or amikacin compared with the control group. Concentrations of the aminoglycosides in renal cortex and serum were not predictive of renal toxicity. Except for amikacin, which appeared to exhibit the lowest intrinsic renal toxicity, nephrotoxicity was correlated with the tubular reabsorption of each aminoglycoside. It was concluded that aminoglycoside renal toxicity can be determined by two major factors: importance of transport into tubular cells and intrinsic intracellular toxicity.

Amikacin↗
PubMed1984

Renal disposition of ceftazidime illustrated by interferences by probenecid, furosemide, and indomethacin in rabbits.

Excretion of ceftazidime (C), a new cephalosporin antibiotic, has been reported to occur unexpectedly through glomerular filtration only, without being significantly affected by probenecid. We investigated renal tubular disposition of C in rabbits by calculating its rates of fractional excretion, net tubular secretion, and absolute excretion. During continuous intravenous infusion of C, 3 mg of furosemide (F), 15 mg of probenecid (P), or 2 mg of indomethacin (I) per kg was injected intravenously as a bolus. Equilibrium dialysis showed that the percentage of C bound to serum proteins (14 +/- 5%) was not altered by F, P, or I. Fractional excretion of C was 94 +/- 22, 65 +/- 21, 182 +/- 36, and 98 +/- 3% for the drug given alone and after injection of F, P, and I, respectively. For 15 min after P injection, we observed net tubular secretion of C (404 +/- 276 micrograms/min). The C absolute excretion rate was significantly reduced by I compared with the absolute excretion rate for the control (405 +/- 104 versus 696 +/- 157 micrograms/min). We conclude that (i) C undergoes bidirectional transport in the nephron, revealed by the effects of F and P, with a nil net C balance; (ii) F and P have opposite unexpected effects on tubular handling of C, possibly due to competition for C secretion processes; (iii) I reduces C excretion solely by decreasing its glomerular-filtered load; and (iv) tubular handling of C differs from that of previously studied cephalosporins.

Animals↗
PubMed1983

[From serum pharmacokinetics to extravascular pharmacokinetics of antibiotics. Importance of protein binding].

Serum and urinary concentrations of antibiotics are not predictive of their extravascular distribution. Data from an animal model giving access to an extravascular fluid have demonstrated the effects of protein binding on the extravascular diffusion of cephalosporins. A high percentage of protein binding delays extravascular distribution and facilitates accumulation from repeated doses. Moreover, strongly bound drugs may reduce the number of protein-bound cephalosporin molecules by competing for binding sites and interfere with the extravascular distribution of these antibiotics without modifying their serum levels.

Animals↗
PubMed1983

[Late recurrence of Horton's disease with sicca syndrome].

The authors report the case of an eighty-three-year-old woman with giant-cell arteritis who experienced recurrence five years after the withdrawal of corticosteroids which had been given for four consecutive years. This recurrence, demonstrated by arterial biopsy, was accompanied with Sjögren disease proven upon histological examination. With reference to this case-report, the various possible courses of protracted giant-cell arteritis are discussed; relapses occurring more than one year after therapy is discontinued are exceptional.

Aged↗