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Biomedical subjects

N Buchanan

Publications and source records attributed to N Buchanan.

At least 19 recordsLinked to original sources

Juvenile myoclonic epilepsy: diagnosis, management and outcome.

OBJECTIVES: To study delay in diagnosis, seizure control, seizure-provoking factors, suitable medications and drug side effects in patients with juvenile myoclonic epilepsy. DESIGN: Telephone and personal interview of patients and review of their clinical notes. PARTICIPANTS AND SETTING: Thirty-six patients attending an epilepsy clinic at a tertiary referral hospital. RESULTS: There was a substantial delay in the diagnosis of juvenile myoclonic epilepsy because the symptom of early-morning myoclonus was not specifically sought. Sodium valproate is the drug of choice, producing absolute seizure control in 63% of cases (19/30). Most patients with poor seizure control had provoked seizures only, emphasising the importance of lifestyle in management. Half of the patients taking sodium valproate experienced side effects, such as weight gain. Lamotrigine is the most suitable alternative. CONCLUSIONS: Juvenile myoclonic epilepsy is a common, under-recognised form of epilepsy which is best treated with sodium valproate. If side effects occur, lamotrigine should be used.

Adolescent

Trypanosoma brucei: inheritance of kinetoplast DNA maxicircles in a genetic cross and their segregation during vegetative growth.

The inheritance of maxicircle DNA was determined using a polymorphic EcoRI restriction site in the maxicircle variable region. In 11 hybrid progeny from a genetic cross of two stocks of Trypanosoma brucei, 7 progeny apparently inherited maxicircles uniparentally from either parent, in agreement with the results from previous studies, but in 4 progeny inheritance was biparental. Three subclones from 2 of these 4 progeny were made, and in these the maxicircles of only one parental type were detected. These data are considered in terms of a simple model whereby half the maxicircle genomes are inherited from each parent into progeny at meiosis with subsequent stochastic segregation at each mitotic division. This model generates a quantitative prediction as to the period of time required for fixation of inheritance to a uniparental pattern which provides a reasonable fit to the experimental data. These results provide an explanation as to why previous studies have shown that maxicircles are (apparently) inherited uniparentally: the kinetoplast is a unitary organelle inherited faithfully at cell division, but the maxicircles that it contains are best considered as a population that divides stochastically. Consideration of the model also explains why maxicircle populations are homogeneous.

Animals

The efficacy of lamotrigine on seizure control in 34 children, adolescents and young adults with intellectual and physical disability.

This study reports the use of lamotrigine, largely as add-on therapy, in 34 children, adolescents and adults with brain damage and resistant seizures. Seventy-four percent of the patients showed a greater than 50% improvement in seizure control with 35% becoming seizure free. This improvement in seizure control was associated with an enhanced quality of life in 65% of the patients as assessed by improved alertness, mobility, speech and independence. It was possible to reduce 36% of the pre-existing antiepileptic drugs and the side effect profile of lamotrigine was very good. It is proposed that lamotrigine may be a particularly useful antiepileptic drug in this particular group of patients.

Activities of Daily Living

Juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy is a relatively common, though under diagnosed, form of epilepsy that commences in adolescence. The distinguishing symptoms, diagnosis and medical management are discussed.

Adolescent

Lamotrigine: clinical experience in 93 patients with epilepsy.

This open study reports the use of lamotrigine in 93 adults and children with drug resistant epilepsy. Lamotrigine was used predominantly as add-on therapy and outcome was assessed by the patient, parents and carers and the physician in terms of reduction of seizure frequency, drug side effects, and importantly with this drug, improvement in quality of life. Twenty five of the 93 patients (26.9%) studied were rendered seizure free with the addition of lamotrigine to their therapy. This was especially the case for patients with complex partial seizures, generalised seizures secondary to brain damage, primary generalised epilepsy and the Lennox Gastaut syndrome. Quality of life improvements were especially striking in patients with seizures secondary to brain damage and in the Lennox Gastaut Syndrome. Twenty eight patients ceased lamotrigine, 13 due to lack of effect and the remainder due to side effects. Lamotrigine is a potentially very useful anti-epileptic medication in persons with complex partial seizures, but also in primary generalised epilepsy, the Lennox Gastaut syndrome and especially in those individuals who have seizures subsequent to brain damage.

Adult

Pregnancy in granulomatous vasculitis.

OBJECTIVE: To study the fetal and maternal outcome of pregnancy in patients with granulomatous vasculitis. METHODS: Four pregnancies in two patients with Wegener's granulomatosis (WG) and one patient with Churg-Strauss syndrome (CSS) were identified and followed in our specialised clinic for pregnancy and connective tissue diseases. RESULTS: Three pregnancies ended with live babies and one with intrauterine death at 25 weeks of gestation. One WG patient remained in remission throughout pregnancy and the other experienced severe activity at 12 weeks. The CSS patient was in remission during her first pregnancy, but the disease flared severely in the second. CONCLUSIONS: Pregnancy in patients with granulomatous vasculitis requires preconceptual planning, careful clinical management, and vigorous treatment of active disease.

Adult

Clonazepam withdrawal in 13 patients with active epilepsy and drug side effects.

We report the end result of clonazepam (CZP) withdrawal in 13 patients with significant side effects felt to be due to CZP. The present observations supplement the recent report in Seizure by Chataway et al., in proposing a safe CZP withdrawal rate of 0.2 mg/day. Eight of the patients had withdrawal seizures, five had withdrawal symptoms and four patients had no withdrawal problems at all. Ultimately all the patients came off CZP, mainly quite rapidly (3-30 days) with the initial side effects regressing totally in 11 patients.

Adolescent

Vigabatrin use in 72 patients with drug-resistant epilepsy.

OBJECTIVE: To determine the efficacy of a new anti-epileptic medication vigabatrin in adults and children with drug-resistant epilepsy. DESIGN AND SETTING: An open, uncontrolled study in a tertiary referral clinic setting with vigabatrin used as add-on therapy. SUBJECTS: All persons with intractable epilepsy, predominantly with complex partial seizures, with or without secondary generalization. MAIN OUTCOME MEASURES: Outcome was assessed by the patient and physician in terms of reduction of seizure frequency and severity balanced against drug side effects. RESULTS: Of 72 patients studied, seven are seizure-free and a total of 41/72 (57%) continue to take vigabatrin as they are deriving benefit therefrom. The results were most striking in patients with complex partial seizures with, or without, secondary generalization (65.6 and 60.9% ongoing treatment, respectively). Most of the 31 patients who ceased taking vigabatrin did so due to a lack of effect, but 9/31 did so because of adverse events: behavioural change, increased seizure frequency and oedema. CONCLUSIONS: Vigabatrin has a definite role to play in the management of persons with intractable complex partial seizures where standard anti-epileptic therapy has failed to achieve control.

Adolescent

Trypanosoma brucei: characterization of protein kinases that are capable of autophosphorylation in vitro.

Autophosphorylation by protein kinases has been implicated as an important control mechanism in signal transduction and growth regulatory pathways in mammalian cells. We have set out to investigate whether any such autophosphorylating protein kinase activities can be found in Trypanosoma brucei. In order to do this, we have developed a system for characterizing such protein kinase activities using an in vitro assay. This assay was carried out by fractionation of trypanosome lysates using isoelectric focusing gel electrophoresis followed by incubation of the gel in gamma 32P-labelled nucleotide triphosphate and subsequent autoradiography. We have identified two classes of autophosphorylating protein kinase activities. In the first class all were dependent on ATP as the phosphate donor substrate and were all found to have a molecular size of 60 kDa. Differences in the activity of these protein kinases were observed between the bloodstream and procyclic life-cycle stages. Furthermore, the addition of mammalian epidermal growth factor to bloodstream stage lysates stimulated an additional activity. The second class of autophosphorylating protein kinases utilized GTP as the phosphate donor and were all found to be 90 kDa in size. Stage-specific differences were also observed in the activity of these protein kinases.

Adenosine Triphosphate

Analysis of a new genetic cross between two East African Trypanosoma brucei clones.

Two clones of East African Trypanosoma brucei, with distinct homozygous isoenzyme patterns for one of three enzymes examined, were cotransmitted through the tsetse fly vector Glossina morsitans centralis. Flies with mature infections were individually fed on mice and the subsequent bloodstream from populations analysed for the presence of hybrid trypanosomes by isoenzyme analysis. Several combinations have previously been detected using this approach (Schweizer, Tait & Jenni, 1988; Sternberg et al. 1989). Four clones were isolated from one of the hybrid-containing populations. They showed a hybrid phenotype, as would be expected for the F1 progeny in a diploid Mendelian system. The analysis of the progeny clones, using two gene probes which detect restriction fragment length polymorphisms between the two parental stocks, showed that alleles had segregated at each locus and given rise to three different non-parental combinations of alleles in the hybrid progeny. Characterization of the hybrid progeny clones by PFGE (pulsed field gradient gel electrophoresis) revealed that all progeny clones were recombinant for the intermediate size chromosomes. From the analysis of the segregation of the larger chromosomes, marked by PGK (phosphoglycerate kinase) and CP (cysteine protease) gene probes, it was inferred that the progeny clones did not result from a direct fusion of diploid cells. Results with the PGK probe fit into a classical system with meiosis and subsequent fusion of the nuclei to form diploid progeny. On the other hand, blots with the CP probe as well as some of the ethidium bromide stained PFGE gels revealed the existence of non-parental size chromosomes in some of the hybrid progeny. This phenomenon was observed previously (Gibson, 1989) and further investigation is required to elucidate the mechanism.

Africa, Eastern

Increase in blood lactate during ramp exercise: comparison of continuous and threshold models.

Controversy persists regarding the mechanism underlying the lactate threshold. It has recently been argued that there is in fact no "threshold" and that blood lactate increases as a continuous function during exercise (Hughson J. Appl. Physiol. 62:1975-1981, 1987). In comparing continuous and threshold models, questions have been raised regarding the ramp rate, data sampling, and the mathematical models employed (Morton J. Appl. Physiol. 67:885-888, 1989). To address some of these concerns, we evaluated 61 subjects (mean age 45 +/- 15), who underwent maximal ramp treadmill tests with the ramp rate individualized such that test duration was approximately 10 min for each subject. The relationship between changes in blood lactate and oxygen uptake were evaluated using a modification of the log-log transformation model described by Beaver (J. Appl. Physiol. 59:1936-1940, 1985) and a continuous exponential plus constant model described by Hughson et al. (J. Appl. Physiol. 62:1975-1981, 1987). Model fitting, using mean squared error (MSE) and coefficient of determination (CD) for each method were as follows: [table: see text] The modified log-log model had a better fit as indicated by the lower MSE and higher CD, suggesting the change in lactate was better described by this model. However, the differences were so slight as to suggest: 1) a meaningful difference does not exist between the two; or 2) these methods may not be capable of detecting a difference, if one exists.

Adult

Effects of sublingual nitroglycerin on the gas exchange response to exercise in stable angina pectoris.

To quantitate changes in gas exchange variables that occur after administration of sublingual nitroglycerin in patients with stable angina pectoris, a randomized double-blind 2-period crossover study was performed with continuous expired gas exchange analysis and progressive exercise using individualized ramp treadmill protocols. Significant reductions in minute ventilation and respiratory rate were observed at 5 minutes of exercise during nitroglycerin therapy. Gas exchange variables i.e., minute ventilation, carbon dioxide production and oxygen uptake were significantly increased at the onset of angina after nitroglycerin administration. When techniques for optimizing the assessment of cardiopulmonary function were used, significant improvements in gas exchange variables were demonstrated in stable angina pectoris after administration of sublingual nitroglycerin.

Administration, Sublingual