Juvenile myoclonic epilepsy.
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Biomedical subjects
Publications and source records attributed to N Buchanan.
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Gadolinium (Gd)-DTPA enhanced magnetic resonance imaging (MRI) was performed in 15 systemic lupus erythematosus patients with past (12) or present (3) features suggesting central nervous system (CNS) involvement. Symptomatic Gd-DTPA enhancing lesions were seen in 2 patients, and immunosuppressive treatment was associated with a rapid reversal of enhancement. The pattern of enhancement was different from that usually seen in multiple sclerosis. Gd-DTPA enhanced MRI may sometimes be useful in demonstrating the activity of CNS lupus.
Mechanisms that have been suggested to underlie the abnormal ventilatory response to exercise in patients with chronic congestive heart failure (CHF) include high pulmonary pressures, ventilation-perfusion mismatching, early metabolic acidosis, and abnormal respiratory control. To evaluate the role that ventilation and gas exchange play in limiting exercise capacity in patients with CHF, data from 33 patients with CHF and 34 normal subjects of similar age who underwent maximal exercise testing were analyzed. Maximal oxygen uptake was higher among normal subjects (31.7 +/- 6 ml/kg/min) than among patients with CHF (17.7 +/- 4 ml/kg/min; p less than 0.001). The ventilatory equivalent for oxygen, expressed as a percentage of maximal oxygen uptake, was 25% to 35% higher among patients with CHF compared with normal subjects throughout exercise (p less than 0.01). A steeper component effect of ventilation on maximal oxygen uptake was observed among normal subjects compared with patients with CHF, which suggests that a significant portion of ventilation in CHF is wasted. Maximal oxygen uptake was inversely related to the ratio of maximal estimated ventilatory dead space to maximal tidal volume (VD/VT) in both groups (r = -0.73, p less than 0.001). Any given oxygen uptake at high levels of exercise among patients with CHF was accompanied by a higher VD/VT, lower tidal volume, and higher respiratory rate compared with normal subjects (p less than 0.01). Relative hyperventilation in patients with CHF started at the beginning of exercise and was observed both below and above the ventilatory threshold, which suggests that the excess ventilation was not directly related to earlier than normal metabolic acidosis. Thus abnormal ventilatory mechanisms contribute to exercise intolerance in CHF, and excess ventilation is associated with both a higher physiologic dead space and an abnormal breathing pattern. The high dead space is most likely due to ventilation-perfusion mismatching in the lungs, which is related to poor cardiac output, and the abnormal breathing pattern appears to be an effort to reduce the elevated work of breathing that is caused by high pulmonary pressures and poor lung compliance.
This study reports the nature of adverse drug reactions (ADR) occurring in 767 epilepsy clinic patients (adults and children), the drugs most commonly involved, how they were managed and the outcome of such management. One hundred and thirty four patients were found to have 155 separate ADRs. The majority appeared to be pharmacodynamic in nature, although 21 were clearly pharmacokinetic in origin and four due to drug interactions. The antiepileptic drugs (AED) perceived to be causative, in order of frequency were phenytoin, sodium valproate, carbamazepine, clonazepam, barbiturates, vigabatrin and clobazam. Management most often involved withdrawing the offending drug(s), usually replacing them with another AED. Of the 155 ADRs, 40.6% resolved totally, 27.7% showed a marked improvement, 16.1% improved, 14.8% did not change and one patient deteriorated. This study emphasizes the need to be vigilant for ADRs and demonstrates that their management is essentially clinical with some 85% of patients experiencing benefit.
Liver function tests were carried out in 206 adults and children taking anticonvulsants to ascertain the prevalence of biochemical abnormalities in asymptomatic patients. It was observed that serum gamma-glutamyl transpeptidase was elevated in 74.6% of patients, alkaline phosphatase in 29.7% and alanine aminotransferase in 25.2% of cases. These figures are similar to those previously reported in the literature and probably reflect hepatic enzyme induction by the anticonvulsants. It is suggested that there is no value in the routine performance of liver function tests in patients with epilepsy. However, such patients should be informed of the symptoms of hepatic dysfunction and asked to report for liver function tests should they have such symptoms.
The objective of this study was to ascertain the perceptions of people with epilepsy about their condition. Nine hundred and eight questionnaires were sent to members of epilepsy associations, with a 45% response rate, and 625 questionnaires were sent to neurologists for their patients to complete, with a response rate of 16.5%. The results reinforce and extend previous observations that there is an ongoing need for educating health care professionals and persons with epilepsy about the condition. Matters pertaining to driving, the unpredictability of seizures, lack of employment and cognitive difficulties were of major concern to the respondents. The present data also highlighted the vexed relationship between stress and seizure control, which needs to be further investigated. These data should be of value to doctors and other health care professionals in their dealings with people with epilepsy. It should also provide epilepsy associations with data upon which they might be able to plan education services.
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The many different approaches to exercise testing have hindered the consistent interpretation of hemodynamic, electrocardiographic, and ventilatory gas exchange responses. One of the most influential approaches is the choice of the exercise protocol. Recent data suggest that the protocol can have an important impact on test sensitivity, the reason for test termination, the ST/HR slope calculation, the interpretation of gas exchange responses, and the accuracy with which oxygen uptake is predicted from work rate. Recent recommendations for optimizing the test have focused on the test duration, reducing the increments in work rate, and individualizing the test relative to the purpose of the test and the subject tested. We describe a treadmill test which considers these recommendations for optimizing exercise testing.
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To evaluate the effects of different methods of detection, exercise modes, protocols, and reviewers on oxygen uptake (VO2) at the ventilatory threshold (ATge), 17 men with heart disease (mean age 59 +/- 6 years) and six healthy men (mean age 60 +/- 11 years) underwent six exercise tests on different days. Each subject performed three treadmill tests (Bruce, Balke, and ramp) and three bicycle ergometer tests (50 W/stage, 25 W/stage, and ramp) in random order. The ventilatory threshold was determined for each of the six exercise tests by three independent, blinded reviewers by means of graphic plots of three commonly used methods of determination: (1) changes in the ventilatory equivalents for VO2 and VCO2, (2) changes in end-tidal oxygen and carbon dioxide pressures, and (3) the intersection of the slope of VCO2 and VO2 (V slope). The largest variability in the ATge was observed with changes in the exercise protocol. The greatest absolute (ml/min) and percentage differences in oxygen uptake at the ATge as a result of changes in protocol, method of determination, and observers were 336 (36%), 125 (12%), and 70 (7%), respectively. The overall intraclass correlation coefficient for VO2 at the ATge among the three reviewers was 0.60 and among the three protocols was 0.85 (p less than 0.01). The V slope method of detection had consistently good agreement among reviewers and was least affected by the protocol. The variance in the ATge (excluding intersubject and error variance) accounted for by differences in protocol, method, and reviewer was 82%, 14%, and 4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
We have previously described a system for characterising the relationships between trypanosome stocks of the T.brucei group based on Southern blotting with repetitive DNA probes followed by cluster analysis of resultant banding patterns (G. Hide et al. Molec. Bioch. Parasitol. 39, 213-226, 1990). In this study, we extend this analysis to examine the relationships between trypanosome stocks isolated from major sleeping sickness foci in Zambia, Kenya, and Uganda. We show that the trypanosome strains responsible for disease in Zambia are quite distinct from those sampled from the Kenya/Uganda foci. Furthermore, the human serum resistant stocks isolated from the Kenya/Uganda foci which were isolated from man (or from animals) were found to form a tight group in the cluster analysis, while stocks isolated from nonhuman sources in the same area or stocks from elsewhere were found in separate groups. Thus, the human infective trypanosome strains found in these foci may have common origins and have, perhaps, arisen by clonal selection from a common source.
To compare the hemodynamic and gas exchange responses of ramp treadmill and cycle ergometer tests with standard exercise protocols used clinically, 10 patients with chronic heart failure, 10 with coronary artery disease who were asymptomatic during exercise, 11 with coronary artery disease who were limited by angina during exercise and 10 age-matched normal subjects performed maximal exercise using six different exercise protocols. Gas exchange data were collected continuously during each of the following protocols, performed on separate days in randomized order: Bruce, Balke and an individualized ramp treadmill; 25 W/stage, 50 W/stage and an individualized ramp cycle ergometer test. Maximal oxygen uptake was 16% greater on the treadmill protocols combined (21.4 +/- 8 ml/kg per min) versus the cycle ergometer protocols combined (18.1 +/- 7 ml/kg per min) (p less than 0.01), although no differences were observed in maximal heart rate (131 +/- 24 versus 126 +/- 24 beats/min for the treadmill and cycle ergometer protocols, respectively). No major differences were observed in maximal heart rate or maximal oxygen uptake among the various treadmill protocols or among the various cycle ergometer protocols. The ratio of oxygen uptake to work rate, expressed as a slope, was highest for the ramp tests (slope +/- SEE ml/kg per min = 0.80 +/- 2.5 and 0.78 +/- 1.7 for ramp treadmill and ramp cycle ergometer, respectively). The slopes were poorest for the tests with the largest increments in work (0.62 +/- 4.0 and 0.59 +/- 2.8 for the Bruce treadmill and 50 W/stage cycle ergometer, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
The inheritance of variant surface antigens in Trypanosoma brucei has been determined by identifying variable antigen types (VATs) in each of two cloned parental stocks and then examining the presence and abundance of these VATs in hybrid progeny produced when these stocks undergo genetic exchange during co-transmission through tsetse flies. Nine VATs have been identified from the repertoire of the parental stock STIB 247L and 5 VATs have been identified from the parental stock STIB 386AA; the identified VATs were exclusive to each stock. Their inheritance was elucidated using two assays. In the first, repertoire antisera (RAS) containing antibody specificities to many different VATs were raised in rabbits to the 2 parental stocks and 6 progeny clones. The presence of VAT-specific antibodies in these RAS was then determined by antibody-dependent complement-mediated lysis. In the second assay, the 2 parental stocks and 4 hybrid progeny clones were each independently transmitted through tsetse flies and VATs observed using VAT-specific antisera in indirect immunofluorescence of metacyclic trypanosomes and in bloodstream forms of fly-bitten mice. The results from both assays showed that (1) both metacyclic- and bloodstream-VATs were inherited into the progeny, (2) each hybrid progeny clone contained some VATs from both parents, (3) hybrids did not express all the VATs from either parent, (4) there was little apparent pattern as to which VATs had been inherited and which had not and (5) the VAT repertoires of the hybrid progeny appeared to be larger than those of the parents. In addition, two results indicated that control of VAT expression remains unaltered after genetic exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Paracetamol is one of the most common drugs that children accidentally ingest. Unlike the situation in adults, death and hepatotoxicity in children from paracetamol poisoning are exceedingly uncommon events. A review of the literature has revealed only seven deaths and fourteen cases of hepatotoxicity in children, with most of the cases resulting from chronic poisoning and not acute poisoning. 2. Children may be less prone to paracetamol hepatotoxicity because of developmental differences in the drug's metabolism and its pathways of detoxification. In the therapeutic setting of treatment of fever and pain in children, paracetamol is regarded as a drug with a higher therapeutic index, and as such, there seems to be little concern with strict adherence to dosage regimes. 3. Scrutiny of the above paediatric cases associated with chronic paracetamol poisoning suggests that the margin of safety of frequent therapeutic doses of paracetamol in infants and young children to be a lot lower than previously appreciated. This review highlights the need to re-evaluate the safety of paracetamol in the context of chronic therapy in infants and young children.
A patient with a 15-year history of urticarial vasculitic rashes and chronic vasculitic skin ulceration has been followed at our Connective Tissue Disease Clinic for the past five years. Serum complement levels have been persistently normal. She has been unresponsive to a variety of medications including steroids, dapsone and hydroxychloroquine. She had a dramatic response to colchicine 500 micrograms daily with total clearing of the urticarial vasculitic rash.
The purpose of this study was to observe the effects of methadone exposure in utero, with special reference to maternal and neonatal methadone concentrations and neonatal withdrawal. Two groups of mother-infant pairs were studied. In the first group, serum methadone concentrations were determined in infants at 1, 6 and 24 h after delivery. In the second group, blood was obtained at 24, 48, 72 and 96 h after birth. There was no correlation between neonatal serum levels and the intensity of withdrawal symptoms. There was no relationship between maternal methadone dose at delivery or maternal serum levels and neonatal methadone levels. The results of this study may be complicated by the prenatal exposure of the neonates to other drugs of abuse apart from methadone.