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Biomedical subjects

D Breton

Publications and source records attributed to D Breton.

At least 19 recordsLinked to original sources

LC-UV and LC-MS evaluation of stress degradation behaviour of avizafone.

It has been known for many years that benzodiazepine compounds effectively antagonize seizures induced by organophosphorous nerve agents. In the event of poisoning, a combination of three drugs is commonly used: an anticholinergic drug (e.g. atropine), an oxime used as cholinesterase reactivator (e.g. pralidoxime or HI-6) and an anticonvulsant (i.e. benzodiazepine). Most of anticholinergics and oximes are freely soluble in water, whereas many benzodiazepines are not. However, a water-soluble prodrug form of diazepam, avizafone, has been adopted by French armed forces for the immediate treatment of nerve agent seizure. The degradation behaviour of this new drug was investigated under different stress degradation conditions (hydrolytic, oxidative, photolytic and thermal) as recommended by International Conference on Harmonization. Successful separation of the active pharmaceutical ingredient from decomposition products formed under stress conditions was achieved using liquid chromatography. The method was validated with respect to specificity, linearity, precision and accuracy.

Chemistry, Pharmaceutical↗

Chiral separation of atropine by high-performance liquid chromatography.

The separation and quantitation of the enantiomers and also the determination of the enantiomeric purity are now current and indispensable tasks for the pharmaceutical analysis. Among the various techniques, liquid chromatography remains the best modality owing to several advantages. High speed, sensitivity, and reproducible results make LC the method of choice in almost all laboratories. Phases that contain alpha1-acid glycoprotein as chiral selector are suitable for separation of charged and uncharged enantiomers with widely different structure. Atropine is widely used as parasympatolytic, anticholinergic and antiemetic drugs. It is one of the preferred antidote for immediate management of toxicity associated with nerve agents. Stereoselective separation was achieved with a prepacked alpha1-acid glycoprotein column without any derivatization procedure. The liquid chromatography system is coupled to mass spectrometry with an atmospheric pressure chemical ionization interface in the positive-ion mode. The chromatographed analytes are detected in selective ion monitoring after optimisation using factorial experimental design. Small amount of enantiomeric composition can be evaluated either by MS or by UV spectrometry (less than 5%).

Atropine↗

[In vitro studies of factors possibly influencing the performance of latex condoms].

Male condoms are undoubtedly the best protection against sexually transmitted diseases. The French Military Health Service buys condoms from civilian manufacturers using a public purchasing process. This process includes strict technical analysis that allows selection of the best supplier. In addition each batch of condoms delivered to French armed forces undergoes quality testing in the laboratory of the Armed Services Central Pharmacy before being distributed to troops. Despite these strict control measures, several isss remain unclear. One issue involves the shelf life of condoms stored in warm humid tropical conditions. Another issue involves the effect of lubricants on condom quality. The purpose of this report is to describe a study designed to gain insight into these two issues. This study was conducted by the Armed Services Central Pharmacy in colaboration with the Procuremnt and Central Establishment Directorate. Findings showed that stage conditions have no negative effects on the intrinsic physico-chemial properties of condoms supplied by two different manufacturers. Conversely use of inadequate lubricants (alimentary or cosmetic compounds) appeared to have extremely deleterious effects on condom quality. Laboratory tests showed that lubricants composed mainly of fatty acids dramatically decreased the effectiveness of condoms.

Condoms↗

[Vagal hyperreactivity and sudden infant death. Study of 15 families].

Prone sleep position is obviously the main risk factor for sudden infant death. Other risk factors, such as vagal overactivity particularly in the familial form, are still discussed. We here report 15 families characterized by the coexistence of vagal overactivity and sudden infant death. At least, 1 child for each family had documented [Holter or occulo-cardiac reflex (OCR)] vagal overactivity. In 5 families 2 children were affected; in 2 families 3 children were affected and in 1 family 4 children were affected. Sudden death occurred in the elderly of the family in 8 cases, in the twin in 3 cases, in the 2nd in 3 cases and in the 5th child in 1 case. Within the 15 families, at least 1 parent had experienced vagally-induced fainting or syncope in 10 cases. Familial pattern of vagal overactivity is underlined. Possible links between vagal overactivity, risk factor for suddden death and sudden death are discussed. We suggest an Holter-ECG and OCR follow-up for sudden infant death siblings with history of familial vagal overactivity (3 examinations during the 1st year of life, at 1, 3 and 9 months).

Electrocardiography, Ambulatory↗

[Sustained ventricular tachycardia in older children. Spontaneous regression in 3 cases].

Extensively described since Gallvardin's reports, the electrical features of salves of ventricular tachycardia in an apparently healthy heart are now well known. The usual benign nature of this arrhythmia is acknowledged, seldom contradicted by isolated clinical cases. Although chronicity is the rule in young adults, there have been a few publications concerning the natural history of these tachycardias in the paediatric age group. The authors report three cases of episodic sustained ventricular tachycardia in older children, presenting at an average of 7 years of age (range 5 to 9 years) and followed up for an average of 7 years (range: 5.5 to 9 years). These three children were treated for an average of 4.5 years (range: 3 to 5.5 years). All treatment was finally withdrawn when stable permanent sinus rhythm without ventricular extrasystoles was restored and confirmed over an average period of 2 years (range 10 months to 3.5 years), an average of 4 (range 3 to 7) successive normal Holter recordings at several months' interval. The outcome in children to spontaneous regression after several years would seem to make radiofrequency ablation more dangerous than useful given the benign nature of the arrhythmia and its good response to pharmacological intervention.

Adult↗

[Non-toxic Corynebacterium diphtheriae septicemia with endocarditis in an earlier healthy adult. First case and review of the literature].

Corynebacterium diphtheriae septicaemia is rarely encountered, usually in very particular situations: children with severe congenital heart disease or after heart surgery. Rare cases have been reported in immunodepressed adults or drug addicts. We observed a case in a formerly healthy 41-year-old woman who was hospitalized for fever unresponsive to bacampicillin. In this patient, no portal of entry could be identified; there was no history of past surgery nor drug abuse. The patient was not immunodepressed and HIV serology was negative. The last anti-diphtheria vaccination had been given at the age of 12 years. Corynebacterium diphtheriae var. metis was identified on five blood cultures. The in vitro Elek test revealed that the strain was non-toxic. Echocardiography did not show any signs until the fourth examination performed 1 month after onset of fever and 15 days after initiating effective adapted antibiotic treatment with amoxicillin-clavanic acid. Mitral vegetations with grade 2 regurgitation completely regressed after 5 weeks of treatment. After 5 months of follow-up, the patient is in good health and no mitral damage has been observed. This is to our knowledge the first case report of Corynebacterium diphtheriae in a formerly healthy adult. In the literature 12 other cases in adults all concerned immunodepressed subjects or drug abusers. The question is raised as to whether Corynebacterium diphtheriae is undergoing mutation. The germ could persist as a commensal host and explain a certain number of the recent observations in drug abusers and immunodepressed patients.

Adult↗

[Convulsions and neonatal hypoparathyroidism revealing maternal hyperparathyroidism].

BACKGROUND: Severe prolonged hypocalcemia may occur in neonates whose parathyroid hormone production has been blocked by maternal hyperparathyroidism. This report describes such a case. CASE REPORT: A 7 day-old girl was admitted suffering from dyspnea and repeated convulsions that had continued for 2 days. Her birthweight was 3,500 g and her height 50 cm. Her mother had been given an iron preparation and calcium during pregnancy. Clinical examination of the newborn at birth revealed a cleft palate and micrognathia. The baby had been given milk-formula plus ergocalciferol, 1,200 IU/day. At admission, the baby was hypotonic. Her serum total calcium was 1.27 mmol/l; total proteins 61 g/l; ionized calcium 1.1 mmol/l; phosphorus 2.14 mmol/l; intact PTH 21 pg/ml (N = 10-65) and 25(OH)D 8 ng/ml (N = 8-30). She was given intravenous calcium gluconate (1 g/m2/d), diazepam (0.5 mg/kg) rectally, intravenous phenobarbital (20 mg/kg) but intravenous phenytoin was needed to stop clinical and electrical seizures. Her blood calcium was normalized 5 days later. Her mother, who was clinically normal, had: total serum calcium: 2.72 and 2.77 mmol/l; total proteins: 71 g/l; phosphorus: 0.85 mmol/l; intact PTH: 73 pg/ml; 25(OH)D: 6 ng/ml; Ultrasonography showed an adenoma of the right parathyroid. Further studies on the baby showed no signs of Di George syndrome. CONCLUSION: Neonatal hypocalcemia always requires investigation of both the infant and mother. Measurements of vitamin D metabolites and intact PTH are required to recognize maternal hyperparathyroidism.

Female↗

[Toxicity of fire smoke. Apropos of 2 pediatric cases].

BACKGROUND: Smoke inhalation is one of the main cause of respiratory problems in fire-related accidents. CASE REPORTS: Case 1. A girl, aged 11 months, was found in her apartment 15 minutes after the start of accidental fire. She was in a stage I coma with cyanosis and covered with soot. She was placed on oxygen and given hydroxocobalamin. Aggravation of respiratory problems led to mechanical ventilation. Tracheobronchoscopy showed deposits of soots with moderate burnt lesions. Intubation was discontinued 12 hours later, but the child remained oxygen-dependent, with persistent tracheobronchitis, despite steroid therapy for 2 weeks. Case 2. Another girl, aged 4 1/2 years, was found in the same room as the preceding patient. She was also covered with soot, and in a coma (Glascow score = 11). She was intubated, placed on mechanical ventilation, and given hydroxocobalamin. Tracheobronchoscopy revealed similar changes to those seen in the preceding patient. Despite repeated tracheobronchial washings and steroid therapy, respiratory problems persisted with thoracic distension and pneumothorax. Mechanical ventilation was discontinued 16 days later but at 5 1/2 years, this child still has dyspnea and has developed bronchiectasis. CONCLUSION: Bronchopulmonary changes can be a severe complication of smoke inhalation during fires, and require early mechanical ventilation and repeated tracheobronchoscopy.

Carbon Monoxide Poisoning↗

Relative diagnostic value of cerebrospinal fluid kappa chains in MS: comparison with other immunoglobulin tests.

We used receiver operating characteristic (ROC) curve analysis to determine the relative performance of different CSF IgG parameters as diagnostic markers for multiple sclerosis. We quantitated CSF and serum IgG and albumin to determine an IgG albumin ratio, IgG index, Tourtellotte's synthesis rate, and Schuller's formula; CSF free kappa light chains were measured by radioimmunoassay. We compared a group of patients with clinically definite MS with a group of patients with a variety of other neurologic diseases. Tourtellotte's formula, IgG albumin ratio, IgG index, and free kappa chains distinguished the MS group from the comparative group of patients. ROC curve analysis demonstrated that CSF free kappa light chains were more closely linked to MS than the other measures. Multiple logistic regression analysis demonstrated no advantage of adding any single IgG measure or combination of measures to free kappa light chain analysis. Our results strongly suggest that free kappa light chains in CSF are the single best quantitative assay to support a clinical diagnosis of MS.

Humans↗

The GABA-agonist progabide for spasticity in multiple sclerosis.

Thirty-two patients with spasticity due to multiple sclerosis were entered into a randomized, double-blinded, placebo-controlled crossover trial of the gamma-aminobutyric acid agonist, progabide. Each patient was treated with a maximum of 45 mg/kg of progabide during each of two four-week treatment periods, separated by a two-week washout. Twenty-five participants completed the study; seven failed to complete the study due to adverse events. Progabide was associated with lessened spasticity. There was no loss of motor power associated with progabide. The physician, patients, and study nurse coordinator all declared preferences for progabide for treatment of spasticity. Ten participants (40%) chose to remain on progabide in an open, long-term follow-up protocol. Seven serious adverse events occurred. One consisted of fever and weakness without infection; the other six consisted of elevated aspartate aminotransferase and alanine aminotransferase levels, four of which were asymptomatic. All adverse events resolved entirely when the drug was stopped. Progabide is an effective antispastic agent and its antispastic effect is not accompanied by increased motor weakness. The use of the drug, however, is associated with a high incidence of adverse events, which will likely limit progabide's therapeutic usefulness.

Adult↗

[Recording and data processing of electrical signals of the specific atrioventricular conduction pathways in man].

Signals of the electrical activity of the specific atrioventricular conduction pathways were recorded with an unipolar lead to obtain an exact time reference. The amplifier used had special characteristics: high gain settings (up to 300,000), very low noise levels, and wide filter range (2 Hz - 1,600 Hz). The low amplitude of the signals under study, of the order of a microvolt, and the wide filter range of the amplifier necessitated placing the patient in a Faraday cage. The signals recorded on magnetic tape were treated by a system of analysis for signal treatment. The method of averaging was used to extract the signal from background noise especially that arising from somatic muscle. The amplitude of the Hisian signal was much larger than that usually obtained with other methods. The intervals were determined with precision of the order of 1 millisecond. Frequential analysis of the signals gave another representation of the information contained in the time signals. This new representation seems to give better discrimination of the different zones of activation of the specific atrioventricular conduction pathways.

Adult↗

[Coronary by-pass operations in diabetic and non-diabetic patients with angina. Results of 102 coronary arteriographies (author's transl)].

The results of coronary arteriography were compared in 102 patients (55 non-diabetics and 47 diabetics) with angina. The lesions noted an arteriography were more severe in the diabetic patients: more frequent stenosis in the common trunk and three branches, and present in greater numbers (more than 4 in more than a half of the patients), with only a moderate proximal bed in 65% of the cases. By-pass operations can only be performed, therefore, in 32% of these patients as against 54% for the non-diabetic anginal patients. The operative risk also appears to be increased (1 death and 6 complications in 10 by-pass operations). It was also demonstrated that with similar lesions of the common trunk, the diabetics have radiological signs of a greater incidence of cardiomegaly and generalized hypokinesia of the left ventricle than non-diabetics. By-pass operations are impossible in about 85% of patients because of ischemic signs or evidence of necrosis in the ECG recordings of diabetic patients with angina.

Adult↗