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Biomedical subjects

N Buchanan

Publications and source records attributed to N Buchanan.

At least 19 recordsLinked to original sources
PubMed2001

Glucuronidation of prodrug reactive site: isolation and characterization of oxymethylglucuronide metabolite of fosphenytoin.

BACKGROUND: This investigation was undertaken to identify the structure of a novel immunoreactive metabolite derived from fosphenytoin that has been hypothesized previously as present in sera from renally impaired patients receiving this prodrug. METHODS: The metabolite was isolated from uremic sera using solid-phase extraction and HPLC. Structural analysis was performed using HPLC-tandem mass spectrometry, nuclear magnetic resonance (NMR), deuterium exchange, and chemical derivatization. Immunoreactivity was evaluated using a fluorescence polarization immunoassay. RESULTS: The metabolite had a parent ion at m/z 457 in the negative-ion mode and fragmented to yield the m/z 251 of phenytoin, as well as other mass fragments of phenytoin. Mass fragments associated with glucuronic acid were also present. The chromatographic peak corresponding to this metabolite demonstrated immunoreactivity sufficient to lead to falsely increased reported values for phenytoin immunoassays. The observed immunoreactivity was also proportional to the relative concentration of the metabolite in collected fractions. Analysis by NMR indicated the presence of phenyl groups with chemical shifts identical to those of phenytoin, as well as the presence of a methylene bridge, which was consistent with the same methylene bridge present on the phosphate ester of fosphenytoin. Comparative analysis of serum samples from renally impaired patients receiving phenytoin vs fosphenytoin using multiple reaction monitoring quantification demonstrated that this metabolite was associated with fosphenytoin administration. CONCLUSIONS: A unique immunoreactive oxymethylglucuronide metabolite derived from fosphenytoin has been isolated from sera from uremic patients receiving this prodrug.

Chromatography, High Pressure Liquid↗
PubMed2000

Health policy and eye care services in Jamaica.

PURPOSE: To test the hypothesis that access to and amount of eye care services in Jamaica are inadequate and that this is related to insufficient eye care personnel and legal limitations on optometric practice in Jamaica. METHODS: An eye care provider survey, a consumer survey, and a literature search were used for data collection. The consumer sample consisted of 500 subjects (aged 16 to 84 years or older) recruited from a stratified random sample of food markets in Jamaica. The provider sample consisted of 10 ophthalmologists and 10 optometrists, randomly selected from licensing rosters. Adequacy of amount of eye care services was measured by comparing the frequency of eye examinations in Jamaica with professional practice guidelines. Access was measured by the eye provider to population ratio compared with calculated need for adequate care. RESULTS: Only 38.6% of the study population had received an eye examination within 3 years and only 23.4% reported having eye examinations at least once every 3 years. Over 43% had never received an eye examination. The total eye care provider/population ratio was only 2.04/100,000 and only 1.32/100,000 when optometrists are excluded. CONCLUSION: Access to and amount of eye care services are severely inadequate in Jamaica. Outdated optometric laws governing the activities of eye care professionals compounds the problem.

Adolescent↗
PubMed1997

Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies.

Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies. All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.

Adult↗
PubMed1996

A double-blind, placebo-controlled crossover study of vigabatrin 2 g/day and 3 g/day in uncontrolled partial seizures.

The efficacy and tolerability of vigabatrin as add-on therapy was assessed in patients with uncontrolled partial seizures. Ninety-seven patients entered this seven-centre, double-blind, placebo-crossover study. Vigabatrin (2 g or 3 g) or placebo was administered daily. Vigabatrin was well-tolerated and did not cause clinically significant adverse drug effects when added to established anticonvulsant therapy. No significant differences were observed between dose groups for the overall incidence of adverse events, although drowsiness and visual disturbances (diplopia, ataxia, visual abnormalities) showed a dose-related increase with vigabatrin treatment. The results of this study indicate that vigabatrin, given in a daily dose of either 2 g or 3 g is significantly more effective than placebo in reducing seizure frequency among patients with partial seizures.

Adolescent↗
PubMed1996

Lamotrigine: clinical experience in 200 patients with epilepsy with follow-up to four years.

This open, clinical study describes the use of lamotrigine in 200 adults and children with drug resistant epilepsy. Lamotrigine was used largely as add-on therapy and outcome was assessed by the patients, parents and carers and the physician in terms of reduction of seizure frequency, drug side-effects and improvement in quality of life. Of the 200 patients, 70 (35%) were rendered seizure free. Lamotrigine was especially helpful in resistant primary generalized epilepsy, complex partial seizures, mixed seizures subsequent to brain damage, Lennox-Gastaut syndrome and in complex partial seizures which secondarily generalized. Fifty-three patients ceased lamotrigine; 30 due to lack of effect, and 13 due to side-effects. Lamotrigine is a very useful antiepileptic medication of a "broad spectrum' nature being effective in primary generalized epilepsy and partial seizures as add-on therapy. The side-effect profile is good with most side-effects being avoidable.

Adolescent↗
PubMed1996

The use of lamotrigine in juvenile myoclonic epilepsy.

Lamotrigine (LTG) was used in 12 patients with juvenile myoclonic epilepsy (JME) who either had sodium valproate (VPA) side effects or did not wish to take VPA. Five patients are now fully controlled on LTG monotherapy. Side-effects were corrected by VPA withdrawal or reduction except for severe weight gain. In three patients it was not possible to withdraw VPA due to the re-emergence of myoclonus, suggesting LTG-VPA synergism. Two patients had successful pregnancies whilst taking LTG. Lamotrigine is a useful alternative in the management of JME.

Adolescent↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗