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High-affinity goat antibodies and Fab fragments (Ka = 1.1 x 10(10) M(-1) specific to colchicine were prepared to study their effect on colchicine pharmacokinetics in rabbits. First, colchicine disposition kinetics were investigated in four control rabbits after administration of 0.1 mg/kg i.v. Total and free plasma and urine colchicine were assayed by specific radioimmunoassay. The mean elimination half-life of total plasma colchicine was 16 +/- 2.9 h. Colchicine has a large volume of distribution (8.8 +/- 1.8 l/kg) and a low systemic clearance (114.6 +/- 3.4 ml.h-1.kg-1). Renal clearance represented 30.7 +/- 1.9% of total body clearance. The free plasma colchicine fraction was 70% after equilibrium dialysis. Second, 1.5 h after injection of 0.1 mg/kg colchicine, four rabbits were infused over 0.25 h with colchicine-specific Fab fragments at a half-stoichiometrically equivalent dose compared to the colchicine dose. Within 15 min after Fab infusion, total colchicine concentrations increased 10- to 16-fold. Mean area under the plasma concentration-time curves increased 20-fold compared to controls. The free plasma fraction decreased to an undetectable level over a period of 2 h. The Fab fragment administration also produced, respectively, a 24- and 17-fold decrease in the volume of distribution and systemic clearance. Colchicine recovered in urine was significantly higher than in the control group: 44.7 +/- 2.3 and 30.9 +/- 2% of the dose, respectively (P less than .05). These data suggest that high-affinity colchicine-specific Fab fragments can sequestrate and extract colchicine from tissues to the vascular compartment with subsequent colchicine excretion by the renal route.

High-affinity Fab fragments (2 x 10(10) M-1) specific to colchicine were produced to evaluate their potency in reversing murine colchicine intoxication. Intraperitoneal injection of a 4.46 mg/kg colchicine dose was lethal for 100% of mice. 1.5 h after colchicine administration, a group of 10 mice was treated with colchicine-specific Fab fragments at a half-stoichiometrical dose compared to the colchicine dose by intravenous and intraperitoneal routes. 70% of the Fab-infused mice survived (P less than 0.01). This high efficiency of colchicine-specific Fab fragments in reversing acute murine colchicine toxicity suggests that Fab fragments would be an efficient antidote for the treatment of human colchicine poisoning.

A patient developed fulminant hepatic failure 48 h after the ingestion of T 61, a veterinary euthanasia drug which contains both general and local anesthetics, a neuromuscular blocking agent, and dimethylformamide (DMF) as a solvent. This is the first report of such severe hepatic manifestation in T 61 poisoning, the most common symptoms of which are early coma and respiratory failure due to the anesthetic and the neuromuscular blocking agent. In a very few cases mild and transitory symptoms of hepatic insufficiency have been observed. In this case the fulminant hepatic failure was due to the high dose (0.6 ml/kg) ingestion of DMF.

From a retrospective series of 162 patients hospitalized for an acute intoxication including the taking of benzodiazepine, the different aspects of this intoxication are looked into. This intoxication is, at the present time, the most frequent among those due to drugs, and the benzodiazepine responsible in most cases are oxazepam, chlorazepate and diazepam. When benzodiazepine are taken alone, in most cases, these intoxications are without troubles or responsible for moderate consciousness troubles. Troubles are over all due to associated toxic drugs, without ethanol seeming to increase considerably the seriousness of troubles. Plasmatic dosages of its compounds are difficult to explain and the levels are discordant with the symptomatology. Particularly, some levels, among the highest, are found in patients having no troubles.

Subacute lead encephalopathy due a chronic poisoning was present in a 6 year-old child. Neurologic features (coma, seizures, CSF abnormalities) began after 2 weeks of vomiting, abdominal pain and constipation. Diagnosis was confirmed by studies of porphyrin metabolism. Lead poisoning following pica in childhood has rarely been reported in France. Its pathogenesis, main features, diagnosis and treatment are reviewed.

The study compared two homogenous series of attempted suicide with barbiturates: 1012 patients from November 1967 to July 1969, and 327 patients in 1977. During these ten years there was a 10% decrease in the incidence of barbiturate intoxications to the benefit of intoxications with benzodiazepines. A similar trend was seen in the use of medium - or long - acting barbiturates alone as compared with association with other drugs. There also was a remarkable shortening of the delay in admission to hospital: 66% of the patients were admitted within 6 hours of poisoning in 1977, as against 56% in 1967-69) to 1% (3 deaths out of 327 cases in 1977).

Coburn's differential equation for the uptake of carbon monoxide by hemoglobin and two particular types of solution of this equation were considered and the solutions verified for a group of healthy adults consisting of 73 nonsmoking pedestrians or car passengers exposed to low levels of carbon monoxide as experienced in the city of Lyon. The CO levels at the breathing level and the walking speed of the subjects was continually measured, and the carboxyhemoglobin levels determined at the beginning and the end of each test journey. The values of all the other relevant parameters were also determined. The half-life of carboxyhemoglobin was studied as a function of the degree of activity, the age, the sex and the height of the subjects. Finally a mathematical model was set up to represent a periodic uptake of CO which made it possible to estimate the variations in the carboxyhemoglobin level for any subject during a period of a day or a week without any need to know the initial level.

Thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LH-RH) have been measured by radioimmunoassay in individual human hypothalamic nuclei. A significant lateralization has been found for TRH in the ventromedial, dorsal and paraventricular nuclei, with higher concentration in the left side. In contrast LH-RH values did not differ between the left and the right side. This finding represents an additional example of cerebral specialization and the first report of lateralized peptide distribution in the human hypothalamus.

Over a 2-year period (1981-1982), blood alcohol levels were measured in 1371 post-mortem examinations performed at the medico-legal Institute of Lyon. These levels were higher in men, in subjects who died between 9 p.m. and 3 a.m., in corpses found in water and in subjects killed by a fall or in a fire. Among the 4 main types of death (homicide, suicide, accident and natural death), those by homicide had the highest, and those by suicide the lowest blood alcohol concentrations.

After having looked at which was the value and the scientific extent of experiments on a healthy man, the authors show in which conditions this type of experiment can be considered as ethical. Two points are important in order to admit this ethical character: the necessity of the experiment and the existence of a collective benefit. Then, the juridical outline of these experiments is debated and the authors remind: --that medicinal products are experimented on the healthy man, --that there are texts which make official the acts offering risk, with collective benefit exclusively, --that a law imposes experiments for non-medicinal products. Finally, the types of responsibilities which could be looked at in case of experiment on a healthy man, with collective benefit, are debated.

The characteristics of benzodiazepine binding sites (distribution, number, affinity) were defined on frozen sections of suicide's hippocampus (death by hanging) labeled with 3H flunitrazepam and compared to data previously obtained on control brains. The study was carried out qualitatively by autoradiography (distribution) and quantitatively by a biochemical technique (number and affinity). As a whole, the characteristics of BZD binding sites were not modified in relation to controls, except for a very slight decrease in affinity of subtype I.

The prevention of neonatal hyperbilirubinemia by phenobarbital is widely used in many countries. However, dose and period of administration vary according to authors, as the dose-effect relation is not known and since little research in pharmacokinetics of phenobarbital has been done so far. In the present study we compared the effect on serum bilirubin of a single injection of 10 mg/kg body weight and of a prolonged administration of 10 mg/kg/day during 3 days in premature and full-term newborn infants. The single injection had the same effect as the prolonged administration, provided it was given within 12 h after birth.

Investigation of post mortem neurobiochemical changes is an important field in biological psychiatry which allows analyses of the analogies between peripherical markers and the central neurochemical processes they represent. Our study discusses the pathological neuroanatomy (collection and conservation of the anatomical specimens) and clinical criteria (selection of an evaluation and diagnostic scale, analysis of results of retrospective clinical interviews: "the psychological autopsy"). We also discuss the many methodological issues which arise in interpretations of these correlations. We wish to encourage others to apply a standardized methodology to these scientific studies of post mortem neurochemical parameters and retrospective clinical diagnosis.