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Biomedical subjects

D Beaumont

Publications and source records attributed to D Beaumont.

At least 19 recordsLinked to original sources

Severe hyponatraemia: investigation and management in a district general hospital.

AIMS: To study the incidence, investigation, and management of severe hyponatraemia (serum sodium < 120 mmol/litre) over a period of six months in a district general hospital. METHODS: The laboratory computer was used to identify all inpatients who had a serum sodium concentration of less than 120 mmol/litre over a six month period. The records of these patients were reviewed for the relevant demographic, clinical, and laboratory data, in addition to diagnosis, treatment, and outcome of hospitalisation. RESULTS: Forty two patients were studied, with a female to male ratio of 2 : 1. Nine patients had central nervous system symptoms, and four of these patients died in hospital. Only 14 patients had their urinary electrolytes and/or osmolality checked. A diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was mentioned in eight patients, sometimes without checking their urinary electrolytes or osmolality. Twenty one patients died in hospital. The patients who died did not have lower serum sodium values or a higher rate of correction of hyponatraemia, but they all suffered from advanced medical conditions. CONCLUSIONS: The possible cause of hyponatraemia should always be sought and that will require an accurate drug history, clinical examination, and assessment of fluid volume, plus the measurement of urinary electrolytes and osmolality in a spot urine sample. The diagnosis of SIADH should not be confirmed without the essential criteria being satisfied. The current or recent use of diuretics is a possible pitfall in the diagnosis of SIADH. The rate of serum sodium correction of less than 10 mmol/day is probably the safest option in most cases.

Adult↗

Increase of HIV-1 subtype A in Central African Republic.

The concomitant presence of five distinct HIV-1 subtypes and of unclassified HIV-1 was reported in Bangui, Central African Republic (C.A.R.) between 1990 and 1991. This previous study was conducted in individuals belonging to the C.A.R. Armed Forces (FACA) Cohort and in patients from the University Hospital of Baugui. To follow the HIV-1 subtype distribution in Bangui over time, we conducted a cross-sectional surveillance of HIV-1 subtypes between 1987 and 1997 in three groups of individuals in Bangui: 47 men belonging to the FACA Cohort, 38 patients from the CNHUB hospital, and 51 individuals consulting the sexually transmitted diseases (STD) clinic. One hundred and ten HIV-1 were subtyped by heteroduplex mobility assay (HMA) and/or sequencing of env regions encompassing the V3 domain. By comparing the HIV-1 distribution in two time periods (1987-1991 and 1991-1996) in the FACA cohort, we observed a significant increase of subtype A from 43.7% to 83.9%. This subtype distribution does not seem specific to the FACA cohort, in that subtype A accounted for 46.7% of the HIV-1 infections in CNHUB patients in the first time period studied and for 69.6% in the second time period. In STD patients, subtype A infections were predominant in 1995 (72.7%) and 1997 (89.7%). Subtype E viruses could be identified in the second time period, but represented only between 6.5% and 21.8% of the infections in the three groups of individuals studied. Other subtypes (B, C, H) and non-classified HIV-1 in C2-V3 were detected with only a 3.2% to 9.1% frequency for each in the second time period. Phylogenetic analysis excluded infection by a single source for the individuals included in the study. Our data demonstrate an increase in the proportion of HIV-1 subtype A infections in Bangui that raises the question of a preferential transmissibility of specific HIV-1 variants.

Adult↗

Screening of vibration-induced disorders in the building industry using digital tactilometry. Results of a field study.

As occupational physicians in the building industry, we observed among these workers a high frequency of vibration exposure, during different tasks. We intended to study vibration exposure effects on vibration perception thresholds measured by digital tactilometry in this population of construction workers. A cross-sectional field study was made, 405 subjects were examined; each of them answered a questionnaire, underwent a medical examination and performed a test measuring his vibration perception thresholds, 150 subjects constituted the reference group. A close relationship between age and thresholds among the non-exposed group was observed. A threshold normalization of age of study the 204 exposed subjects was applied. Two exposure indices allowing time dependency vibration exposure analysis were defined the present daily exposure and cumulated exposure. In the examined population, thresholds rise with the present daily exposure in hours per day for 125 Hertz, while no significant influence of cumulated exposure is apparent. It was also pointed out that subjects exposed more than one and a half hour per day have higher thresholds than reference subjects, even if they do not have any clinical neurological complaints. This results seems to indicate the infraclinical feature of the test. These results suggest that screening of hand-arm vibration exposed population should be developed using this method. As occupational physicians in the construction industry, practising in Paris and surrounding areas, the authors studied the relationship between neurological disorders measured by vibrotactile perception thresholds, and hand-arm vibration exposure, among workers. They present the results of a field study they led within their institute, in collaboration with the tested workers' firms, and with the financial participation of the French Ministry of Labour.

Adult↗

Vigabatrin in childhood epilepsy.

Sixty-six children with various types of severe drug-resistant epilepsy were entered into a long-term, dose-rising study of vigabatrin after a 4-week run-in placebo period. All the children were receiving one to three other antiepileptic drugs, the doses of which were not changed during the 6-month dose titration phase. Following the introduction of vigabatrin, 11 patients became seizure free, and 28 responded with a greater than 50% reduction in seizure frequency. The following types of epilepsy responded favorably in order of decreasing efficacy: cryptogenic and symptomatic partial epilepsy, other symptomatic generalized epilepsy, and Lennox-Gastaut syndrome. However, three of nine patients with myoclonic epilepsy showed an increase in seizure frequency. Optimal responses were found with vigabatrin doses of 40 to 80 mg/kg/day, although no significant adverse effects were noted with doses of higher than 100 mg/kg/day. Thirty-eight responders continued on vigabatrin, 19 of whom have been treated for more than 1 year, with generally good efficacy. As a result of discontinuing concomitant antiepileptics, six patients are on monotherapy with vigabatrin, four of whom are seizure free. Vigabatrin tolerability was good, with 39 of 66 children reporting no adverse effects. Hyperkinesia was reported in 17 patients (26%), and two had to drop out of the study. All these patients had a history of hyperkinesia or mental retardation. In patients in whom vigabatrin dose was reduced because of hyperkinesia, a dose increase could later be instituted without recurrence of symptoms. There was no change in neurologic examination and no drug-related abnormalities in clinical laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dose-response study of vigabatrin in children with refractory epilepsy.

Twenty children aged 2 months to 18 years were included in a dose-response study of vigabatrin as add-on therapy to preexisting antiepileptic drugs (up to two per patient). All children had severe refractory epilepsy: partial seizures with or without secondary generalization in 19, and myoclonic seizures in one. After a 2-month observation period and a 1-month add-on placebo period, a fixed dose of add-on vigabatrin was given for 2 months: 1, 1.5, or 2 g/day, according to body weight (mean dose, 60 mg/kg/day). Three patients (15%) became seizure free, and nine (45%) showed a 50% to 99% reduction in seizure frequency. In the 17 patients whose seizures were not totally suppressed, vigabatrin dose was increased for a further 2 months, and in 7 patients who still showed less than 50% reduction in seizure frequency, vigabatrin dose was increased again. Efficacy appeared unchanged by these higher doses. During a 9-month follow-up phase, no tolerance to the effects of vigabatrin was observed, with three children seizure free and 13 (65%) reporting a 50% to 99% reduction in seizure frequency. During the study, adverse effects were recorded in three children (15%), namely drowsiness, constipation, fatigue, and apathy. These effects were generally transient, being observed during the dose-modification phase and disappearing either spontaneously or on reduction of vigabatrin dose. Clinical and laboratory tolerability to vigabatrin appeared to be very good, with no patients having withdrawn from the study because of side effects. A slight reduction in red blood cell count and hemoglobin levels was noted but was of doubtful clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Therapeutic trial of vigabatrin in refractory infantile spasms.

Infantile spasms usually start during the first year of life and constitute one of the most difficult types of epilepsy to treat. They carry a very poor prognosis for both epilepsy and mental development. Seventy children, including 47 infants, with intractable infantile spasms were entered into an open study with vigabatrin as add-on therapy to the usual anticonvulsant treatment. All were resistant to previous treatments, including corticosteroids (43 patients), carbamazepine, benzodiazepines, and sodium valproate. Two children withdrew from the study because of intolerance to vigabatrin (hypotonia or hypertonia) before evaluation of efficacy could be made. Of the remaining 68 children, 29 (43%) showed complete suppression of spasms. Forty-six children had a greater than 50% reduction in spasms. The best response was observed in those with tuberous sclerosis (12/14 compared with 12/18 with symptomatic infantile spasms of other origin and 22/36 with cryptogenic infantile spasms). Following the initial response to treatment of these patients (n = 68), a long-term response was confirmed in 75% of children with symptomatic infantile spasms and 36% of children with cryptogenic infantile spasms. In eight children, all other anticonvulsant medication could be definitively withdrawn. Tolerability appeared excellent, with 52 of 70 patients reporting no side effects. Somnolence, hypotonia, weight gain, excitation, and insomnia were the most common problems at the beginning of the study and were usually transient. Given the poor prognosis of this type of childhood epilepsy, vigabatrin appears to be a very interesting advance in the management of drug-resistant infantile spasms.

Adolescent↗

Pharmacokinetics of the individual enantiomers of vigabatrin (gamma-vinyl GABA) in epileptic children.

1. The pharmacokinetics of the enantiomers of vigabatrin were investigated after oral administration of a single 50 mg kg-1 dose of the racemate to two groups of six epileptic children (I: 5 months-2 years, II: 4-14 years). 2. The mean (+/- s.d.) values of maximum plasma concentration and area under the plasma concentration-time curve of the R(-) enantiomer were significantly higher than those of S(+) vigabatrin in both groups: R(-) Cmax: 21 +/- 6.6 (I)-41.3 +/- 13.9 (II) vs S(+) Cmax: 13.9 +/- 4.5 (I)-23.8 +/- 12.2 (II) mg l-1; R(-) AUC: 106 +/- 28.5 (I)-147 +/- 34 (II) vs S(+) AUC: 90.9 +/- 27.9 (I)-117 +/- 26 (II) mg l-1 h. In group I, the half-life of the R(-) isomer was significantly shorter than that of the S(+) isomer; in group II, the half-lives were comparable. 3. For the R(-) enantiomer the area under the curve, and the elimination half-life increased linearly with age. 4. During chronic administration (50 mg kg-1 vigabatrin racemate twice a day for 4 days), the morning trough plasma drug concentrations did not increase.

Adolescent↗

Protein turnover in malnourished elderly subjects: the effects of refeeding.

A primed constant-rate infusion of L-(l-14C)-leucine was used to assess protein flux, synthesis, and breakdown in a group of malnourished elderly subjects (n = 9) and a group of age-matched healthy elderly control subjects (n = 9). No significant differences between the two groups were observed in measures of protein metabolism. Four out of six malnourished subjects, restudied after a period of dietary replenishment, showed non-significant increases in protein synthesis and breakdown. Plasma insulin concentrations were significantly suppressed (p less than 0.05) and plasma growth hormone and cortisol concentrations significantly elevated (p less than 0.05) in the malnourished subjects before and after refeeding compared with the healthy elderly controls.

Age Factors↗

Effects of long term vigabatrin on somatosensory evoked potentials in epileptic patients.

1. Vigabatrin has proved to be a very effective antiepileptic in clinical trials, with excellent long term tolerability. 2. The purpose of this study was to test the central nervous system (CNS) safety of the drug during long term clinical use, due to the existence of species-dependent intramyelinic oedema in animal toxicology studies. 3. Somatosensory evoked potentials were recorded repeatedly over a mean period of 11 months, in 54 adult patients with refractory epilepsy who received vigabatrin as add-on therapy to their current antiepileptic regime. 4. There was no suggestion throughout the study that vigabatrin could lead to a prolongation of neuronal conduction times within the CNS pathways. 5. The results are consistent with previous studies of somatosensory, visual and brainstem auditory evoked potentials in patients. In view of the results observed in the dog, where increases in central latencies of somatosensory evoked potentials were clearly apparent, these data provide strong reassurance about the neurological safety of vigabatrin in the treatment of epileptic patients.

Adolescent↗

Vigabatrin in the treatment of epilepsy in children.

1. This study presents the results of the preliminary screening of vigabatrin as add-on therapy in an open, non-controlled multicentre study in children with refractory epilepsy. 2. There were 135 children, with an age range of 2 months-12 years. Main seizure type was partial in 42%, generalized in 29%, Lennox-Gastaut syndrome in 19% and West syndrome in 10%. 3. Vigabatrin was added onto current antiepileptic treatment in an initially recommended dose of 40-80 mg kg-1 day-1. However, the doses were frequently increased when tolerance allowed it, and the final mean dose used was 87 mg kg-1 day-1 (27-600). 4. A 75% to 100% reduction in seizure frequency was observed in 25% of patients (11 patients became seizure free) and 50 to 75% decrease in a further 13%. Efficacy was better in partial seizures, with good to excellent results in 49% of patients. The use of high doses, above 100 mg kg-1 day, was not associated with greater efficacy in this preliminary study. 5. No side effects were reported in 79% of patients. Agitation and insomnia were observed in 8.8% and somnolence in 6%. Other adverse events included ataxia (2.2%), nausea (2.2%) and increased appetite (1%). A moderate and transient decrease in haemoglobin was reported in six patients from the same centre; these patients were all receiving very high doses of vigabatrin (250 to 600 mg kg-1 day-1). 6. Vigabatrin thus appears to be a safe antiepileptic drug that may be effective in the treatment of severe epilepsy in children.

Adolescent↗

Efficacy and safety of vigabatrin in the long-term treatment of refractory epilepsy.

1. The long term safety and efficacy of vigabatrin has been studied in 254 patients with refractory epilepsy (82% with partial seizures) in 23 different clinics in eight European countries. 2. This was an open multicentre study in which patients who had experienced a significant benefit from vigabatrin and had continued to take the drug for 1 year or longer were eligible for evaluation. The mean duration of therapy in the 254 patients was 22.7 months; 72 patients received vigabatrin for more than 2 years. 3. Patients were severely affected by epilepsy with a median monthly seizure frequency of 15.7 despite taking an average of 2.2 antiepileptic drugs. On vigabatrin, the median seizure frequency was about 35% of baseline, remaining stable over time despite a 10% reduction in the number of concurrent medications. 4. The lack of tachyphylaxis to the antiepileptic effect of vigabatrin is shown by the small number of patients who discontinued for insufficient efficacy (11%), two thirds of them during the first 6 months of follow-up. Maintenance of efficacy is also clearly demonstrated by analysis of 2 year and 3 year cohorts of patients. 5. Clinical and biological tolerability was excellent. There was a very low rate of drop out for adverse events (1.6%). Adverse events, mainly sedation, irritation and weight gain were mostly mild and transient. 75% of patients reported no adverse event at all. 6. Safety evaluation included serial neurological, ophthalmological and general examinations: no new abnormal clinical feature or adverse event emerged with long term therapy.

Adolescent↗

Lack of effect of terfenadine on theophylline pharmacokinetics and metabolism in normal subjects.

The pharmacokinetics of oral theophylline (250 mg) and the production of its metabolites (3-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid) were studied before and after the administration of oral terfenadine (120 mg twice daily for 16 days) in 10 healthy volunteers. Comparison of volumes of distribution, elimination half-lives, areas under the plasma concentration-time curves, plasma clearance of theophylline and elimination of theophylline metabolites indicated that terfenadine had no significant effect on theophylline pharmacokinetics and metabolism.

Adult↗

Effects of long-term vigabatrin on somatosensory-evoked potentials in epileptic patients.

Vigabatrin (gamma vinyl GABA, GVG) has been shown to be an effective antiepileptic agent. GVG specifically and irreversibly inhibits GABA-transaminase (GABA-T). Long-term animal toxicology studies have demonstrated that GVG can induce nonprogressive, reversible intramyelinic edema in central white matter tracts. The response to GVG varies among species, with rodents being the most dramatic and monkeys showing an equivocal effect even at high doses. The response in dogs is marked and measurable. The detection of these subtle findings requires the use of sophisticated technology. Evoked potentials are becoming reliable and sensitive tools in clinical neurology. This study, involving 54 patients for 11 months, was undertaken to assess the effect and safety of GVG in humans with refractory epilepsy. No data from this investigation indicate prolongation of neuronal conduction time in CNS pathways, suggesting that this agent is safe in humans.

Adolescent↗

Attenuation of hyperventilation-induced bronchospasm by terfenadine: a new antihistamine.

The effect of terfenadine, a selective H1-receptor antagonist devoid of central nervous system side effects, was evaluated on hyperventilation-induced bronchospasm in 11 adult subjects with asthma in a double-blind, placebo-controlled, crossover study. Increases in specific airway resistance (SRaw) were induced by isocapnic hyperventilation with dry air on two occasions, 7 days apart. Before the tests, the subjects received oral terfenadine (120 mg, twice daily) or placebo for 3 days with the last dose administered 3 hours before the test. Baseline SRaw and spirometric values (vital capacity and FEV1) were similar for the two tests. Terfenadine yielded a significant (p less than 0.001) parallel shift to the right of the stimulus (hyperventilation)-response (SRaw) curve; 100% increases in SRaw occurred at ventilation rates of 44 L/min after placebo treatment and 64 L/min after terfenadine treatment. These data suggest that histamine release plays a role in hyperventilation-induced bronchospasm despite the fact that increase in plasma histamine has not been found in this situation, in contrast to exercise-induced bronchospasm.

Adolescent↗

Evaluation of the antimuscarinic activity of atropine, terfenadine and mequitazine in healthy volunteers.

1 The anticholinergic effects of atropine and two antihistamines (terfenadine and mequitazine) were investigated vs placebo in a double-blind study. 2 Salivary secretion, basal pupil diameter, pilocarpine (0.25%) induced miosis and heart rate were determined in eight healthy volunteers, seven male and one female, aged between 23 and 35 years. Each volunteer received all four separate courses of treatment: i.e. terfenadine 60 mg or mequitazine 5 mg twice daily for 3 days, and one single dose on the day of the trial; for the placebo or atropine courses they received the placebo twice daily during 3 days and, on the morning of test day, either the placebo again or atropine 1 mg. Pupillary diameter was measured under standardized conditions using a pupil gauge (Smith and Nephew Pharmaceuticals Ltd). 3 Atropine significantly reduced salivary output (-2.25 +/- 0.36 ml from control values of 4.17 +/- 0.42 ml, P less than 0.001) and heart rate (-9.7 +/- 3.7 beats min-1 from 77.5 +/- 2.7, P less than 0.05). These maximal effects were observed 3 h after atropine dosing for salivary secretion and 1 h for heart rate. Atropine did not affect basal pupil diameter or pilocarpine-induced miosis. 4 Mequitazine and terfenadine did not affect salivary flow, heart rate or pilocarpine-induced miosis. 5 Terfenadine and mequitazine had no anticholinergic effect in these tests involving a limited number of subjects.

Adult↗

[Administration of terfenadine in a single dose: comparison to standard treatment, as a double blind study, in patients presenting with allergic rhinitis].

This double-blind, randomized multicentre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily.

Benzhydryl Compounds↗

[Ambulatory surgery in pediatrics. The value of caudal anesthesia].

Ambulatory surgery appears to minimize lasting psychological upset in children. Patients must be properly selected. It is essential that the children and their parents should have a visit with an anaesthetist prior to the patient's admission. Laboratory investigations should be prescribed at that time after questioning and examining the patient. Caudal anaesthesia is a useful regional technique for postoperative pain relief in children. Sacral canal puncture is carried out after the induction of general anaesthesia. Only a light state of general anaesthesia is required. The local anaesthetic mixture is made of equal volumes of 1% lidocaine and 0.5% bupivacaine without adrenaline. Rapid awakening, early feeding and pain relief increase reliability and comfort.

Ambulatory Surgical Procedures↗