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Biomedical subjects

J Mumford

Publications and source records attributed to J Mumford.

At least 19 recordsLinked to original sources

Effect of long-term vigabatrin therapy on selected neurotransmitter concentrations in cerebrospinal fluid.

Ten patients, suffering from drug-resistant complex partial seizures were treated for a period of up to 3 years with vigabatrin (Sabril). Vigabatrin is a novel antiepileptic agent, whose action is based on the inhibition of gamma-aminobutyric acid (GABA) aminotransferase, the enzyme responsible for the catabolism of the neurotransmitter GABA. Samples of lumbar cerebrospinal fluid were obtained from the patients prior to commencing vigabatrin therapy, and thereafter at 6 months, 1 year, 2 years, and up to 3 years following the initiation of vigabatrin treatment. The influence of vigabatrin on the cerebrospinal fluid concentrations of free and total GABA, homocarnosine, homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol, as well as of the drug itself, was assessed. All patients demonstrated a clinical response to vigabatrin, and the drug was well tolerated over the entire observation period. Mean (+/- SD) reduction of seizure frequency was 65% +/- 23% (range, 26% to 100%) when comparing the end of the treatment period to the previgabatrin baseline. The cerebrospinal fluid concentrations of both free and total GABA and of the dipeptide homocarnosine showed approximately 2- to 5-fold increases over baseline values, with free GABA and homocarnosine being the more sensitive variables. Cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were not altered in a significant manner over the observation period. These findings support the concept that the effects of vigabatrin are restricted to an effect on GABA catabolism and do not extend to the neurotransmitters dopamine and norepinephrine. Clinical efficacy and elevation of GABA and homocarnosine concentration were sustained over the period of observation.

Adult

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

Randomized controlled pilot study of vigabatrin versus carbamazepine monotherapy in newly diagnosed patients with epilepsy: an interim report.

At present, 34 patients aged 15 to 63 years with newly diagnosed epilepsy have been randomly assigned to vigabatrin (n = 17) or carbamazepine (n = 17). Evaluation of clinical data, neuropsychological assessment, quantitative spectral electroencephalogram (EEG), and somatosensory- and visual-evoked potentials at baseline and after a 3 months' maintenance phase are presented for 12 patients on vigabatrin and for 11 patients on carbamazepine. Among these patients, retention rate in the maintenance phase of the study is 75% for vigabatrin patients (two noncompliant patients and one nonresponder dropped out) followed up for a mean of 11 months (range, 5 to 16 months). The retention rate for carbamazepine is 100% for the 11 patients, followed up for a mean of 9 months (range, 3 to 17 months). Patients receiving vigabatrin showed significant improvements in sustained concentration and tasks requiring flexible mental processing after the 3-month maintenance period, compared to baseline. In the carbamazepine group, there was improvement only in delayed list recall, and in contrast, errors in visuomotor tasks requiring processing increased significantly. Patients on carbamazepine demonstrated slowed occipital mean frequencies, but vigabatrin treatment was not associated with any significant quantitative EEG changes. Significant prolongation of somatosensory-evoked potential N19 latencies was seen with both carbamazepine and vigabatrin.

Adolescent

Long-term evaluation of once daily vigabatrin in drug-resistant partial epilepsy.

The purpose of this study was to evaluate on an open basis the long-term efficacy and safety of vigabatrin in drug-resistant partial epilepsy as add-on therapy, administered on a once daily basis. Thirty-five patients entered the study. Twenty patients (57%) responded to therapy and are still on drug. This efficacy is in agreement with that seen in double-blind controlled studies on twice daily dose schedules. There did not appear to be any loss of efficacy with continued treatment at this dose regimen in patients responding favourably to the drug. The once daily dosing schedule was well tolerated and side effects were usually mild and always reversible. Vigabatrin seems to be a valuable therapeutic addition for patients with partial seizures resistant to standard anti-epileptic drugs.

Adolescent

Effects of vigabatrin on evoked potentials in epileptic patients.

1. Somatosensory (SEP) brainstem auditory (BAEP) and visual (VEP) evoked potentials were determined before and after add-on administration of vigabatrin (GVG) in patients with epilepsy. 2. At pre-treatment assessment SEP and BAEP parameters were usually found to be within normal limits, while P100 latencies of the VEP were abnormally prolonged in a considerable proportion of patients. 3. In a double-blind, placebo-controlled trial in 22 patients GVG (1-3 g day-1 stratified according to body weight) given for 7 weeks did not modify any of the evoked potential parameters evaluated. 4. Eighteen patients were evaluated prospectively at regular intervals during long-term GVG (2-4 g day-1) therapy with a mean follow up of 24 months (range 13-42 months). SEP, BAEP and especially VEP parameters showed some interindividual variability, but the within patient variation was relatively small. No consistent important changes were seen in association with GVG, although a possible trend towards a shortening of BAEP latencies and P100 latencies was observed. 5. The relevance of these findings with respect to GVG safety is discussed.

Adolescent

Home air nicotine levels and urinary cotinine excretion in preschool children.

We examined the extent of correlation between home air nicotine levels and urine cotinine/creatinine ratios (CCR) in 27 children who attended a research day care program where they were not exposed to environmental tobacco smoke (ETS) during the daytime hours. Average concentrations of nicotine in home air were determined by active air sampling during the evening and night hours on 2 consecutive days. Urine samples for cotinine and creatinine determinations were collected before, during, and after the two sampling periods. In addition, four sequential weekly urine samples for CCR were obtained from study children to determine the extent to which single determinations of CCR were representative for individual children. Fifteen children resided in homes with smokers, and 12 did not. Urine CCR consistently distinguished most exposed and unexposed children. However, three exposed children had urine CCRs that clustered routinely around the criterion CCR (30 ng/mg cotinine-creatinine) that best distinguished exposed and unexposed children. In children exposed to ETS in the home, there was a significant correlation between average home air nicotine levels and the average logarithm of urine CCR the two mornings after the home air monitoring periods (r = 0.68; p = 0.006). In study children, urine CCRs were remarkably stable over the 1-month observation period. Rank correlation coefficients for sequential weekly determinations of CCR were consistently greater than r = 0.88; p less than 0.0001.

Child, Preschool

The problems of people in long-term psychiatric day care. An introduction to the Camberwell High Contact Survey.

The aims of the Camberwell High Contract Survey (CHCS) were to develop and test a systematic needs assessment procedure and use it to evaluate the services provided to long-term users of day centres and sheltered residential accommodation (excluding hospital wards). This paper describes the background to the study, the sample of 145 attenders and their characteristics, their clinical and social problems and the care provided for them.

Adolescent

Anatomy of the thenar branch of the median nerve.

The gross and interfascicular anatomy of the terminal portion of the thenar (or recurrent median) nerve was defined by a microdissection of 20 fresh-frozen cadaveric hands. The traditionally described pattern of one main thenar trunk with three terminal branches, one each to the abductor pollicis brevis, opponens pollicis, and flexor pollicis brevis muscles, was observed in nine specimens (45%). One main trunk with two terminal branches (one branch to the abductor and one to the opponens, but no branch to the flexor) was seen in six specimens (30%). The remaining five specimens (25%) exhibited four other terminal patterns with either two, three, or four branches off the main trunk. In 15 specimens (75%), a previously undescribed "accessory thenar nerve" (ATN) arose from either the first common digital nerve (25%) or the radial proper digital nerve to the thumb (50%). The ATN innervated the flexor pollicis brevis.

Hand

Single-radial-immunodiffusion potency tests of inactivated influenza vaccines for use in man and animals.

Single-radial-immunodiffusion (SRD) provides a sensitive and reproducible in vitro assay for haemagglutinin (HA) concentration in inactivated influenza vaccines. The use of SRD for human influenza vaccine standardization and application for equine and avian influenza vaccines is discussed. In clinical trials, vaccine HA concentration measured by SRD has been shown to be directly related to antibody responses and to protection against challenge. The use of SRD may considerably reduce the usage of animals for potency testing of veterinary influenza vaccines.

Animals

A single-radial haemolysis technique for measurement of antibody to influenza virus neuraminidase in equine sera.

A modified single-radial-haemolysis (SRH) test for measurement of antibody to influenza virus neuraminidase (NA) is described. The test requires treatment of sheep erythrocytes with butanol to increase sensitivity. In comparative assays, SRH was found to be more sensitive than the conventional neuraminidase-inhibition test. The SRH test was reproducible, specifically measured antibody to influenza NA and was easy to use. SRH antibody responses in ponies vaccinated with bivalent equine influenza vaccine were shown to be vaccine dose-related but were lower in magnitude and shorter in duration than comparable anti-haemagglutinin responses.

Animals

A discriminant-function analysis of screening tests for excessive drinking and alcoholism.

Because a previous study among 385 psychiatric admissions had shown each of three rapid interviews to be far superior to each of nine laboratory tests in screening for excessive drinking and alcoholism, the separation of patients with these drinking patterns from normal drinkers was reexamined by the more sophisticated technique of discriminant analysis. It was thus possible to determine where there was overlap in the information provided by some tests in contrast to "new information" provided by others and whether the arbitrary cut-off points of the normal ranges of the laboratory tests were contributing to their poor sensitivity. Discriminant analysis again confirmed the good performance of the rapid interviews, particularly the Brief Michigan Alcoholism Screening Test and the Reich interview, but it also identified glutamate dehydrogenase (GDH) as the best of the laboratory tests and of comparable efficacy to the rapid interview for the group of excessive drinkers. By comparison, gamma-glutamyl transpeptidase and mean corpuscular volume performed poorly. Using the whole range of results rather than a single cut-off point for discriminant analysis did not alter the relative performance of the screening tests. The optimum combination of tests was that of the Reich interview and the GDH, achieving 100% sensitivity for excessive drinking and alcoholism without any decline in the specificity or predictive value of a positive test result.

Adult

The standardization of inactivated equine influenza vaccines by single-radial immunodiffusion.

Single-radial-immunodiffusion (SRD) assays were used for measuring the haemagglutinin (HA) antigen content of equine influenza vaccines containing the virus strains A/equine/Prague/56 (H7N7) and A/equine/Miami/63 (H3N8). Three bivalent aqueous vaccines and one bivalent adjuvanted vaccine were standardized by SRD to contain graded amounts of HA antigen activity. The SRD reaction was influenza subtype specific and was not influenced by the presence of adjuvant in vaccine.

Animals

Studies with inactivated equine influenza vaccine. 1. Serological responses of ponies to graded doses of vaccine.

Serological responses to three bivalent aqueous equine influenza vaccines of different potency and an adjuvanted bivalent vaccine containing inactivated A/equine/Prague/56 (H7N7) and A/equine/Miami/63 (H3N8) viruses, were examined in seronegative ponies. Potencies of the vaccines, measured by single-radial-diffusion tests, ranged from 4 to 56 micrograms of haemagglutinin (HA) antigen activity/virus strain per dose. Serological responses to vaccination were examined by haemagglutination-inhibition (HI) and single-radial-haemolysis (SRH) tests. Four weeks after a primary dose, HI responses to both vaccine viruses were barely detectable; after a second dose the HI responses to A/Miami/63 virus were low or undetectable but HI responses to A/Prague/56 virus were higher (17/20 ponies with titres greater than or equal to 1:16). In contrast SRH tests revealed dose-related antibody responses to both virus strains after one and two vaccine doses; levels after the second dose were 2- to 5-fold higher than after the primary dose. Highest post-vaccination antibody titres were obtained with the adjuvanted vaccine which contained 2- to 4-fold less antigen (13-23 micrograms HA) than the most potent aqueous vaccine. Post-vaccination antibody reacted well in SRH tests with recent antigenic variants of equine influenza virus. A remarkable finding was the high rate of decline in antibody, detected by HI or SRH tests, following one or two doses of vaccine. Even in animals with the highest post-vaccine antibody levels 2-4 weeks after a booster dose, antibody levels had declined to low or indetectable levels 14 weeks later. The low antibody titres detected at 14-32 weeks after vaccination were nevertheless vaccine dose-related.

Animals

Studies with inactivated equine influenza vaccine. 2. Protection against experimental infection with influenza virus A/equine/Newmarket/79 (H3N8).

Forty ponies immunized with inactivated virus vaccine containing A/equine/Miami/63 (H3N8) virus and six unvaccinated, seronegative ponies were experimentally challenged with a representative of recent equine H3N8 virus isolates, A/equine/Newmarket/79. All unvaccinated ponies became infected as judged by virus excretion, febrile responses and antibody responses, but only two of the vaccinated ponies were fully protected. Pre-challenge antibody levels to A/Newmarket/79 virus detected by single radial haemolysis (SRH) correlated well with the degree of clinical protection but the levels required for complete protection (SRH zones greater than 65 mm2) were high. The importance of these results in relation to conventional vaccination procedures against equine influenza is discussed.

Animals