Harmful effects of the placebo-controlled design.
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Biomedical subjects
Publications and source records attributed to P Guillot.
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INTRODUCTION: Cutaneous dirofilariasis caused by Dirofilaria repens is a parasitic disease in dogs and cats. It is exceedingly rare in man who is an occasional host. The parasite fails to reach maturity. The true incidence of dirofilariasis is probably greater than recognized. This can be explained by the apparent benign nature of the lesions that may not warrant excision. CASE REPORT: A 12-year-old girl presented a cutaneous nodular lesion involving the forehead. Surgical excision allowed diagnosis: cutaneous dirofilariasis caused by Dirofilaria repens. The child had always stayed in mainland France. Histopathological examination showed the worm trial with inflammatory granulomatous reaction of the deep dermis. The parasite extraction allowed successful treatment. DISCUSSION: This new case of cutaneous dirofilariasis emphasizes that this parasitic disease is present in mainland France. The infection is more common in Southern France. The present report describes a pediatric case in Gironde, where it is exceedingly rare. Microscopic examination identified, and it was unusual, a male worm.
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The mutant doublefoot, Dbf, of the mouse arose spontaneously, and was shown to be inherited as an autosomal dominant, mapping 9-13 cM proximal to leaden, In, on chromosome 1 and showing no recombination with the microsatellite markers D1Mit24 and D1Mit77. In heterozygotes the phenotype includes many extra toes on all four feet, and the tibia and fibula may be reduced and bowed. The head is shortened and broad and the eyes are held half-closed, and some animals develop hydrocephalus. The tail is kinked and abnormally thick, and the soles of the feet are swollen. Growth is retarded, viability is reduced, and reproduction is impaired in both sexes. Only about 30% of males are normally fertile, and testis weights and sperm counts may be reduced, although this appears not to be the main cause of poor fertility. In females vaginal opening is delayed and oestrous cycles are irregular, although the animals appear to respond to gonadotrophic hormones. Crosses of Dbf/+ x Dbf/+ are very poorly fertile. Prenatally, Dbf/+ heterozygotes can first be recognized at 11 1/2 days gestation by abnormally broad fore limb buds. Putative Dbf/Dbf homozygotes at 12 1/2 days have similar limbs defects and also split face, due to failure of the maxillae to fuse in the midline. Some homozygotes and a few putative heterozygotes have cranioschisis. At 13 1/2 days, the heads of homozygotes tend to bulge in the frontal region and a bleb of clear fluid is visible medially. At 14 1/2 days Dbf/Dbf fetuses may have oedema and some are dead. From 15 1/2 days onwards no live Dbf/Dbf fetuses have been found. The gene maps close to the locus of Pax3, but crossovers between Dbf and Pax3 have been found, ruling out the possibility that a gain-of-function mutation in Pax3 might be involved.
The pharmacokinetics and metabolic fate of labelled compounds were investigated after intramuscular administration of 3H-radiolabelled etiproston to nine cows. Elimination was rapid (t 1/2 beta = 2.8 h). Forty-eight h after administration 92.6% of the radioactivity had been eliminated, mainly via the urinary (66% at 48 h) and faecal routes (26% at 48 h). In comparison, little elimination in milk occurred (less than 0.034% dose/l by 24 h). Radioactivity at the injection site 48 h after administration was seen in one cow (< 4.68 x 10(-5%) dose/g). No radioactivity was detected in the tissues. Urinary metabolites were purified and isolated using XAD-2 extraction and preparative HPLC in reverse and normal phases. The main urinary metabolite, identified by mass spectrometry, was the tetranor acid derivative in equilibrium with its lactone form.
Pharmacokinetic variables of spiramycin and its distribution in muscle, liver, kidney, and injection sites were studied in 18 mixed-sex 1-year-old calves to assess drug withdrawal time after 2 IM administrations of 100,000 IU of spiramycin/kg of body weight at 48-hour intervals. Presence of a compound, other than spiramycin I (ie, neospiramycin), was observed in tissues used for withdrawal time determination. High concentrations observed at the injection sites decreased slowly to maximal residue limit with half-life of 109.5 hours for neospiramycin and 77.5 hours for spiramycin. At 14 days, neospiramycin concentrations were higher in kidney than in liver and half-life was different between these 2 tissues. Two methods of withdrawal time determination were used and the part of the samples without residue detected, in the calculation, was discussed. Withdrawal time of 35 days can be proposed on the basis of average daily intake determined for spiramycin, with concentration at injection sites representing 10% of the whole muscle concentration.
Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk. However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)
Esophagus cancer surgery often becomes complicated with fistulas and above all with infections. In 50 cases, the authors relate 7 fistulas and 60 nosocomial infections among which pneumonia takes the first place. The pneumonia diagnosis has been established on the criteria of the "National Nosocomial Infection Study" and on bacteriologic samples. Those mostly isolate Gram-bacilli and streptococci. The diagnosis and etiologic factors leading to prophylactic measures are studied.
Two monozygotic female twins with linear porokeratosis of Mibelli are described. One had only minimal lesions of the right elbow. The other had a linear lesion of the right arm following Blaschko's lines. Monozygotism was established using DNA fingerprinting. A single-gene defect of variable expressivity involving the clonal development of epidermal cutaneous cells according to the lines of cutaneous embryogenesis is suspected. Dithranol and carbon dioxide laser treatment are discussed.
The pharmacokinetics of chloramphenicol were studied in sheep after 3 single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations (30 mg/kg). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After IV and SC administrations, the plasma-concentration time graphs were characteristic of a two-compartment model, and after IM administration it was characteristic of a monocompartment model. The two routes of absorption were not bioequivalent. Using the kinetic values, multidose regimens to maintain the therapeutic chloramphenicol blood level (5 micrograms/ml) were proposed: 60 mg/kg every 12 hours for 72 hours for the IM administration and 45 mg/kg administered subcutaneously according to the same regimen. A study of the chloramphenicol residues in tissues was carried out. Chloramphenicol residues remained at the injection site, and 400 hours would be necessary to obtain the level of 10 micrograms/kg. Determination of the creatinine phosphokinase serum values showed that the subcutaneous route induced less damage to muscle than the intramuscular route.
Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 micrograms/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 micrograms/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 micrograms/g (ie, lower than the generally accepted tolerance level of 2 micrograms/g).
A bioequivalence study was performed in 6 bullocks to compare intramuscular (im) and subcutaneous (sc) routes for repeated treatments with an oxytetracycline formulation. Basic pharmacokinetic parameters were determined after a 10 mg/kg intravenous administration. Bioavailabilities for both im et sc routes were close to 85%. The pharmacokinetic parameters were used to perform an analysis of variance, and to determine the 95% confidence intervals and Westlake symmetrical confidence intervals. The two routes were significantly different regarding maximum concentration. The following symmetrical confidence intervals were calculated: area under the curve (+/- 20%), minimum concentration (+/- 51.5%), period during which plasma concentration was above 1 microgram/ml (+/- 25%). The two routes were bioequivalent for the area under curve.
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The pharmacokinetic properties of a long-acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean values were a half-life of 4.1 h, a volume of distribution of 0.86 l/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10-15 micrograms/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 micrograms/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.
Chloramphenicol was administered intravenously and orally at a dose of 50 mg/kg to ten rabbits. Pharmacokinetic parameters were calculated (rate constant of terminal phase: beta = 0.21 +/- 0.09 1/h, total body clearance: Cl = 22.7 +/- 2.1 ml/min.kg, bioavailability: F = 42.5 +/- 11.9%) and were used to discuss the proposed dosage. However, caecotrophy might occur and increase absorption of chloramphenicol.
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