Biomedical subjects
Publications and source records attributed to S Lamotte-Barrillon.
M. tuberculosis infection of a total hip prosthesis was observed in two patients. Clinical and bacteriological diagnostic features are described, as well as the two possible physiopathological mechanisms involved: activation of a chronic local lesion or blood dissemination. Combined medical and surgical treatment results in effective clinical and functional recovery.
We studied the effects of furosemide on the disposition of cefazolin and gentamicin in rabbits. The following points were investigated: protein binding (PB) by ultracentrifugation in vitro; renal excretion and distribution in extravascular fluid (EF) obtained from s.c. tissue cages in vivo. Single i.m. injections of cefazolin (30 mg/kg) and gentamicin (1.5 mg/kg) alone or in combination with furosemide (0.5, 1 and 5 mg/kg) were made. After furosemide injection, blood and EF levels of gentamicin significantly decreased. Cefazolin blood levels were unchanged. Cefazolin appeared in EF earlier and at higher levels, up to 4 hr after furosemide injection, than when administered alone. Late cefazolin EF levels (8 and 12 hr) were reduced. All these effects were furosemide dose-dependent. Furosemide, in vitro, decreased cefazolin PG from 80 to 50%, whereas PB of gentamicin remained minimal (0--4%). Furosemide significantly increased the renal excretion of cefazolin and gentamicin without any effect on the glomerular filtration rate. A competitive effect of furosemide on the PB of cephradin and netilmicin was also demonstrated in vitro and in vivo. Our studies outline two kinds of interaction between furosemide and antibiotics. With protein-bound drugs, furosemide induced a competitive reduction of PB responsible for earlier EF diffusion and increased glomerular filtered load, but also induced an increased renal excretion by a tubular process. The latter was the only one induced by furosemide on unbound drugs (gentamicin).
Isolated neuropathies of 5th cranial nerves are rare apart from primary facial neuralgia. A case is reported, in which Raynaud's syndrome was also present, that enabled a diagnosis of mixed connective tissue disease to be established. The authors underline the importance of undertaking complete immunological investigations in order to decide whether there is a particular type of systemic disease present, which could be responsible for these special types of trigeminal nerve disorders.
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We compared the penetration of five aminoglycosides into interstitial fluid (IF). IF was obtained in rabbits from Silastic tissue cages. Intramuscular injections were made: 1.5 mg/kg per dose for gentamicin (G), tobramycin (T), sisomicin (S), and netilmicin (N) and 7.5 mg/kg per dose for amikacin (A). Serum levels and IF concentrations were studied for 12 h after a single injection. IF levels were also compared in a six-injection study (one injection every 8 h). Peak serum levels were significantly higher with A than with G, T, S, and N, which gave similar concentrations. In IF, G gave the highest levels 1 h after the first injection. At 4 and 8 h, the concentrations achieved with G and A were similar but significantly greater than those achieved with T, S, and N. Twelve hours after a single injection, N gave higher IF levels than the other drugs except A. In the six-injection study, the IF levels of G and A reached 4.6 +/- 1.5 and 5.27 +/- 1.1 microgram/ml, respectively, at 48 h. S and N gave identical concentrations (2.07 +/- 0.25 and 2.42 +/- 0.42 microgram/ml, respectively). T induced the lowest levels (1.17 +/- 0.30 microgram/ml). Thus, in this rabbit model, the IF concentrations achieved with G and A were above the minimal inhibitory concentrations for most susceptible strains. Possible relations between IF aminoglycoside concentrations and therapeutic efficiency or toxicity are pointed out but deserve further studies.
An animal model in which antibiotic concentrations can be meausred in intersittial fluid (IF) withdrawn from subcutaneous tissue cages has been used. Although the physiological significance of IF is not well established, this model allowed the comparison of 1) two pharmacological forms of the same drug (bacampicillin and ampicillin were compared after a single oral dose; and 2) drugs of the same group in a single i.m. injection study and in a cumulative effect study. These data provide new criteria for clinical choice of antibiotics. A rapid penetration into IF can be explained by a low degree of serum protein binding, but a highly bound drug is not restricted to the intravascular space. In this animal model we have also shown that an 0.25 h i.v. infusion of cephalothin induced higher IF levels than an i.v. bolus injection and an 1 h i.v. infusion. Using a single i.v. bolus injection of various cephalosporins, we have shown that a two open compartment model cannot explain both serum and IF data. Sustained late IF levels suggested the hypothesis of a deep compartment.
The combined study of animal experimental findings and clinical trials indicates the minimal effect on renal function of a combination of Cefalotin with aminoglycosides. Nevertheless, whilst the published cases of renal insufficiency are often difficult to analyse with regard to the exclusive responsibility of antibiotic therapy, it seems that strict attention to dose and frequency of administration is essential when this combination is prescribed and that regular surveillance of renal function is necessary, above all with prolonged treatment. The renal toxicity of aminoglycosides more recent than Gentamicin has not yet been fully explored, the same applying to their use in association with Cefalotin.
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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.
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The authors report 25 cases of infection following total hip replacement and individual factors are analysed. The role of immunological abnormalities is discussed. They distinguish early infection due to the operative conditions from late infection where individual factors are the most important. A few preventive measures are proposed, they emphasise the necessity of a large scale study of factors favouring late infection.
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Eosinophil leukemia is still an uncertain entity owing to the lack of specific markers for malignancy. The authors report a case with increased serum vitamin B12 and intravascular coagulation, and discuss the value of these two abnormalities as functional markers.
The authors report 18 cases of Clostridium perfringens infection and discuss the main clinical and etiological aspects apart from gynecological forms and those usually requiring intensive care. Pathological foci, digestive infection and the problem of bacteremia are discussed together with appropriate treatment.
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