Clinical toxicology: 'bones' of contention.
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Comment↗
Biomedical subjects
F Daly
Publications and source records attributed to F Daly.
The Scottish Heart and Arterial Risk Prevention (SHARP) survey of cardiovascular risk: regional differences.
The objective was to explore variation in cardiovascular risk profiles within the Scottish workforce over different regions of Scotland by a planned review of survey data of workplaces throughout Scotland, surveyed between December 1991 and March 1996. The subjects sampled were 19,400 men and women aged between 18 and 70, who were in work and apparently healthy at the time of screening. The results showed that the regions of Scotland may be distinguished through particular risk factors and also by using a single summary score (the SHARP risk score). Overall the Perth and Kinross region tops the league for cardiovascular risk (with the main contributing factors being smoking and high blood pressure); regions of least risk are Inverness-shire and Edinburgh. There are statistically significant differences to be discerned in the regional distribution of cardiovascular risk within the working population of Scotland.
Cardiovascular Diseases↗
Pharmacokinetics and pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2 diabetes.
AIMS: Gliclazide pharmacokinetics and pharmacodynamics were assessed in 9 Caucasians and 10 Australian Aborigines with uncomplicated type 2 diabetes. METHODS: Subjects were on a stable dose of 80 mg gliclazide twice daily, took 160 mg on the morning of study and had a standard breakfast. No further gliclazide was given over the next 48 h. Regular blood samples were drawn for serum glucose, insulin and gliclazide assay. Gliclazide was measured using h.p.l.c. Noncompartmental analysis was used to describe primary data. A multicompartment model incorporating entero-hepatic recirculation was fitted to group mean serum gliclazide profiles. RESULTS: The Caucasians were older than the Aborigines (mean +/- s.d. age 53.4 +/- 12.2 vs 40.3 +/- 6.9 years, P < 0.05) but had similar diabetes duration, body mass index and glycated haemoglobin. Noncompartmental analysis revealed no between-group differences in gliclazide kinetics. Post-breakfast serum glucose and insulin responses were also similar apart from a longer time to maximum concentration (tmax) for glucose amongst the Aborigines (2.6 +/- 0.4 vs 2.2 +/- 0. 3 h in Caucasians; P = 0.024). Gliclazide tmax exhibited a skewed unimodal distribution and was not associated with gliclazide maximum concentration, or glucose or insulin responses. Most patients had a serum gliclazide profile suggestive of enterohepatic recirculation and/or biphasic absorption. Model-derived estimates of the extent of putative enterohepatic recirculation were 30% and 20% of dose in Caucasians and Aborigines, respectively. CONCLUSIONS: Gliclazide is equally effective in Caucasian and Aboriginal diabetic patients. The pharmacokinetics of oral gliclazide appear more complex than previously thought. Gliclazide pharmacodynamics are unrelated to rate and extent of absorption, consistent with a threshold concentration for hypoglycaemic effect.
Adult↗
Results of a survey of cardiovascular risk factor prevalence amongst health care workers. The Executive Committee of SHARP--(Scottish Heart and Arterial Risk Prevention).
Summary analyses of screening data were used to ascertain the cardiovascular risk profile in a sample of health care workers in Scotland. A sample of NHS staff (298 women and 78 men) were screened during visits to Perth Royal Infirmary (PRI) in 1996 and 1997. Comparisons were made within subsets and with previous screening studies. Health care workers have been a neglected component of the workforce for receiving education about risk factors. The high prevalence of smokers found in this sample should be a cause for concern.
Adult↗
Vascular risk factor profiles in the first phase of the Scottish Heart and Arterial Risk Prevention (SHARP) Survey, 1991-1996.
BACKGROUND: The SHARP survey data comprises personal information, family history, lifestyle and risk factor prevalence for 19,400 men and women sampled from the Scottish working population between 1991 and 1996. The purpose of the survey was the achievement of a clearer understanding of coronary risk factor prevalence in the working population of Scotland; the education of that population through counselling and advice; and a clearer appreciation of an individual's risk factor profile as a predictor for future events. In this paper a selection of attributes is explored for the information they yield about the characteristics of an apparently healthy population. Comparisons are drawn with earlier studies. METHODS: A mobile risk factor screening unit toured workplaces throughout Scotland and recorded information on age, sex, occupation, social class, personal and family history, smoking, alcohol and salt consumption, body mass index, blood pressure, glucose and total cholesterol. RESULTS: The variation in measured levels for common risk factors in a sample of apparently healthy Scottish people shows substantial differences from the measured variation in an unstratified survey. CONCLUSIONS: Across all conventional coronary risk factor measurements, working Scottish people are uniformly "more healthy" than the general population. A comparison of trend with age for male and female smokers and non-smokers in cholesterol level shows no difference between smokers and non-smokers; a similar comparison for body mass index and weight shows some consistent differences but without statistical significance.
Adolescent↗
Olanzapine overdose mimicking opioid intoxication.
We report significant central nervous system depression and the previously unreported phenomenon of pupillary constriction after acute overdose of olanzapine (Zyprexa) in 4 patients. Phase 2 trials describe a typically benign course in overdose, and published abstracts note a wide spectrum of clinical effects with supratherapeutic ingestion of olanzapine. Our patients demonstrated profound central nervous system depression, and 2 required advanced airway support. All 4 patients recovered with supportive care. Olanzapine should be added to opioid and alpha(2)-adrenergic agonist intoxication in the differential diagnosis of the patient with depressed mental status and miosis.
Adult↗
Heart and arterial disease risk factors measured in an office workforce: changes from 1993 to 1996. The Scottish Heart and Arterial Risk Prevention Group (SHARP).
Screening for cardiovascular risk factor prevalence was arranged in an office workforce in Scotland with two screenings taking place three years apart, in order to measure and attempt to modify individual risk factor profiles, and in order to explore the nature and extent of any changes. There were some increases over time for both sexes, with increased tobacco usage for men, significant increases in diastolic blood pressure for both sexes and a significant increase in mean cholesterol levels for women. A separate analysis was restricted to those individuals screened on both occasions and sought to explore the effect of personal counselling and advice: in fact there were significant increases in tobacco usage for women, with more starting smoking than stopping, and for both sexes there were significant rises in cholesterol levels and increases in body mass index for many individuals. There was significantly increased use of wine and spirits by both sexes.
Adult↗
Severe falciparum malaria with hyperparasitaemia treated with intravenous artesunate.
We report a 57-year-old man with falciparum malaria contracted in Kenya who presented with a three-day history of symptoms. Despite prompt treatment with quinine and artesunate and rapid clearing of the parasitaemia, he developed multiple complications and died 28 days after presentation. This case illustrates the potential for malaria to be fatal despite appropriate treatment and is one of the first reports of the use of artesunate in a hospital in a developed country.
Antimalarials↗
Deliberate self-poisoning, unemployment and public health.
The purpose of the present investigation was to explore further the known relationship between deliberate self-poisoning and social deprivation. Each individual who attended one of Cork city's three casualty departments following an act of deliberate self-poisoning in 1988 was examined. The place of residence (ward) of each city resident patient was established. The social status of the city's 34 wards was estimated using a number of indices obtained from the 1981 and 1986 census reports and social service records. A comparison was made between the 1988 self-poisoning rate for each ward and the rate found in a 1982 study of the city. Correlations between self-poisoning rate and seven social deprivation indices were found to be significant. Multiple regression, factor, and partial correlation analyses were carried out to examine more closely the interrelationships between the social deprivation indices. With respect to explaining the variation in the self-poisoning rate, unemployment alone performed almost as well as all of the indices together and as well as the factors derived using factor analysis. The correlation between unemployment and self-poisoning rate remained highly significant when the other related variables were controlled for. However, at fixed levels of unemployment, these variables were found to be independent of the self-poisoning rate. It is suggested that whereas clinical intervention may benefit the individual, deliberate self-poisoning as an issue requires a public health approach for its resolution.
Adolescent↗
The 'dawn phenomenon' in adolescents with insulin dependent diabetes mellitus: possible contribution of insulin-like growth factor binding protein-1.
OBJECTIVE: Insulin resistance increases during adolescence, and is exaggerated in patients with insulin dependent diabetes mellitus (IDDM). A relative deficiency of insulin-like growth factor-I (IGF-I) may contribute to this increased insulin requirement. Two mechanisms have been proposed: (a) increased GH secretion, caused by failure of IGF feedback control, leading to increased insulin resistance and (b) lack of insulin-like action of the IGFs which is reinforced by high plasma levels of IGFBP-1, an inhibitor of IGF action. The contribution of these two mechanisms to the 'dawn phenomenon' is assessed. DESIGN: The two possible mechanisms were studied during the dawn rise of glucose in pubertal adolescent patients with IDDM. Two overnight studies were performed in each subject. Patients remained on the same insulin regimen throughout. SUBJECTS: Twenty-two diabetic adolescent subjects, aged (mean +/- SEM) 14.0 +/- 0.4 years, duration of IDDM 7.9 +/- 0.8 years, were recruited. Pubertal status was: group 1 (breast stage 1-2; testicular volume < 4-8 ml) 3 male and 4 female, group 2 (breast stage 3; testicular volume 10-12 ml) 0 male 4 female, group 3 (breast stage 4-5; testicular volume 15-25 ml) 4 male and 7 female. Height standard deviation score (mean +/- SD) (-0.02 +/- 0.99) and daily insulin dose (50.4 +/- 3.1 U/day) did not change between studies. There were no differences in HbA1 (study A 11.26 +/- 0.45%, study B 11.09 +/- 0.42%). METHODS: The subjects were admitted for the two studies 0.3 +/- 0.03 years apart. Blood samples were taken via an indwelling cannula every 20 minutes between 1900 and 0700 h. MEASUREMENTS: GH was assayed every 20 minutes, IGFBP-1, glucose and free insulin every hour and IGF-I at 0700 h. GH, IGFBP-1, IGF-I and free insulin were measured by radioimmunoassay. IGFBPs were also analysed by Western ligand blotting techniques. GH profiles were analysed by Pulsar and results compared by paired Student's t-test. The relations between the dawn rise in glucose and the changes in IGFBP-1, GH and free insulin were examined by multiple linear regression analysis. RESULTS: Serum IGFBP-1 levels rose overnight in the two studies (study A, from 9 +/- 1 at 2200 to 59 +/- 9 micrograms/l at 0700 h; study B, from 10 +/- 1 at 2100 to 64 +/- 14 micrograms/l at 0700 h) whilst insulin levels fell from 47 +/- 5 at 2200 to 16 +/- 2 mU/l at 0700 h (study A) and from 45 +/- 5 at 2000 to 14 +/- 2 mU/l at 0700 h (study B). Glucose levels fell from 16.0 +/- 1.0 to 9.3 +/- 0.9 mmol/l at 0400 h, and then rose to 11.9 +/- 1.1 mmol/l at 0700 h during study A, and from 13.4 +/- 1.3 to 10.1 +/- 1.1 mmol/l at 0400 h and then rose to 13.5 +/- 1.0 mmol/l at 0700 h during study B. There were no differences in GH secretion between studies (mean GH levels (mean +/- SD) (study A, 15.7 +/- 6.6 mU/l; study B, 16.2 +/- 7.1 mU/l; correlation within subjects between studies r = 0.77, P < 0.001), sum of GH peaks (study A, 189.9 +/- 90.3 mU/l; study B, 185.8 +/- 100.2 mU/l; r = 0.57, P = 0.006)). Mean GH levels varied with pubertal stage (group 1, 12.1 +/- 1.5 mU/l; group 2, 23.3 +/- 2.1 mU/l; group 3, 15.3 +/- 1.2 mU/l). Serum IGF-I levels were not different (study A, 203 +/- 12 micrograms/l; study B, 218 +/- 13 micrograms/l). REGRESSION ANALYSIS: The change in plasma glucose between 0200 and 0700 h in both studies related to free insulin, IGFBP-1 and the sum of the GH levels over the preceding hour (log glucose = 7.87 + 5.32 log IGFBP-1 (P = 0.0001) - 5.05 log free insulin (P = 0.0001) - 1.44 log GH (P = 0.004); R2 = 72%). Mean overnight GH levels did not predict the morning rise in plasma glucose. CONCLUSION: The morning rise of IGFBP-1 and plasma glucose appear to be related in this group of subjects with IDDM and this was a consistent finding in the two studies. This relation was additive to the effect of insulin deficiency.
Adolescent↗
More on combination antidepressant therapy.
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Adult↗
A randomized controlled trial of fall prevention strategies in old peoples' homes.
BACKGROUND: Falls are a major cause of morbidity in old age. A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective. This study set out to examine the preventability of falls in older people living in institutional care. OBJECTIVE: To evaluate the effectiveness of falls risk factor assessment/modification and seated balance exercise training in reducing falls among elderly people living in residential care. METHODS: 133 residents with a mean age of 84+/- (SD) 6.8 years were allocated at random by home to receive either a 6-month falls risk factor assessment/modification and seated balance exercise training programme (n = 77) or 6 months of reminiscence therapy (n = 56). The risk factors targeted were postural hypotension, polypharmacy, visual acuity, and ambient lighting levels. Falls risk factor assessments and recommendation for modifications were performed at baseline in the intervention group and assessments repeated at 6 months. Functional reach, reaction time, timed up-and- go, grip strength, spinal flexibility, and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a 'blind' observer. Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period. RESULTS: Only 90 of 133 (67.7%) residents completed the 6-month intervention period, and 84 (63.2%) completed the 7- to 12-month falls-monitoring follow-up period. Both prevalence of postural hypotension (p = 0.0005) and poor visual acuity (p = 0.04) were reduced in the intervention group. There was no difference between the groups in the number of falls sustained, the risk of falling [odds ratio 0.45 (95% CI 0.19-1.14)], or in the risk of recurrent falling [odds ratio 1.07 (95% CI 0.40-2.97)]. No significant differences were found between the groups with regard to change in other outcome measures. CONCLUSIONS: The high drop-out rate reduced the power of this study to detect any effect of the interventions used. It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed standing. Further research is required to identify effective fall prevention strategies for elderly people in residential settings.
Accidental Falls↗
Suicide levels in Cork City 1987/1991.
This study investigates the level of suicide in Cork City during the 5-year period 1987/1991. Both male and female crude rates were higher than the corresponding national levels. The male/female ratio was 2.3:1, which is consistent with established findings. Vulnerability to suicide is most pronounced in 20-39 year old males and females in the 40-59 age category. There was some evidence of an increased risk of suicide among single elderly males; otherwise marital status was not a significant factor. A positive association was noted between unemployment and suicide rate for males. Drowning was used as the method of suicide by approximately half the male and female sub-groups; this was followed by hanging in the case of males and overdosing among females. However all suicide cases under 20 years of age used hanging.
Adolescent↗