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Biomedical subjects

I Thomson

Publications and source records attributed to I Thomson.

At least 19 recordsLinked to original sources

Primary and preschool immunisation in Grampian: progress and the 1990 contract.

OBJECTIVE: To examine changes in immunisation performance in Grampian region after the introduction of the 1990 contract for general practitioners. DESIGN: Retrospective descriptive study using data held on the Grampian immunisation record system's computer. SETTING: All 95 general practices in Grampian region (313 general practitioners). PATIENTS: All children in the primary immunisation and preschool booster age groups. This formed two groups of children for each of the four calendar quarters of 1990 and first three quarters of 1991 analysed as (a) those aged 2 years on the first day of the relevant quarter and (b) those aged 5 years on the first day of the relevant quarter, with an average population of 6600 and 6400 respectively. MAIN OUTCOME MEASURE: Percentage immunised by practice. RESULTS: For primary immunisation the number of practices achieving immunisation rates of at least 95% increased from 29 (31%) to 76 (81%), and practices achieving 90% rates rose from 69 (73%) to 87 (93%). For preschool boosters, the number of practices achieving at least 95% immunisation rates increased from 22 (23%) to 61 (64%). By the end of September 1991, 76 (80%) practices were achieving at least 90% levels compared with 36 (39%) at the beginning of 1990. Since the beginning of 1989 the proportion of immunisations not given by general practitioners declined from 14% to 2%. CONCLUSIONS: Primary and preschool immunisation rates for preschool children in Grampian showed a sustained improvement during 1990 and consolidation in 1991. Although overall trends were unchanged, 18 months after the introduction of the 1990 contract only one practice failed to meet lower target levels of 70% for both primary and preschool immunisation. By September 1991 more than three out of four practices had reached levels of at least 95% for primary immunisation.

Child, Preschool

Cataract surgery.

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Cataract Extraction

Inhibition of bovine adrenocortical steroidogenesis by benzodiazepines: a direct effect on microsomal hydroxylation or an inhibition of calcium uptake?

We have previously reported that benzodiazepines inhibit microsomal steroid hydroxylases. We have now studied their effects at much lower drug concentrations and have also addressed the suggestion that benzodiazepines alter cellular calcium metabolism. We investigated the in-vitro effects of midazolam on microsomal steroid hydroxylation by measuring basal and ACTH-stimulated cortisol and 17 alpha-hydroxyprogesterone (17-OHP) synthesis. Threshold inhibition of basal cortisol production was achieved by 3.4 mumol midazolam/l while ACTH-stimulated production required 13.6 mumol/l. This was accompanied by a biphasic response of 17-OHP production, rising to a maximum at 13.6 mumol midazolam/l for basal and 6.8 mumol midazolam/l for ACTH-stimulated synthesis suggesting a preferential inhibitory effect on 21-hydroxylase activity at < 6.8 mumol/l and additional effects on 17 alpha-hydroxylation at higher drug concentrations. This explains the inhibition of ACTH-stimulated cortisol synthesis by midazolam (50% inhibitor dose (IC50) 22 mumol/l). Using 21-deoxycortisol as substrate, we have demonstrated that midazolam is a competitive inhibitor of 21-hydroxylase (inhibitory constant (KI) 35 mumol/l). Both midazolam and diazepam inhibited K(+)-stimulated aldosterone synthesis, with IC50 values of 1.2 mumol/l and 0.8 mumol/l respectively, which are far lower than those observed for ACTH-stimulated cortisol synthesis. With 11 beta-hydroxyprogesterone as substrate, the KI for the inhibition of aldosterone synthesis by midazolam was 54 mumol/l. Potassium stimulates aldosterone biosynthesis at least partly by changing intracellular free calcium levels. To investigate possible antagonistic effects of benzodiazepines on calcium metabolism, we measured 45Ca uptake in the presence of midazolam.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone

Dantrolene inhibits adrenal steroidogenesis by a mechanism independent of effects on stored calcium release.

The muscle relaxant dantrolene has been widely used in signal transduction studies as an inhibitor of intracellular calcium release. However, in vivo studies have shown that the drug may inhibit steroidogenesis by a mechanism which is distinct from its effects on calcium mobilization. Using freshly isolated cells and mitochondria from the outermost regions of bovine adrenal cortex we have shown that dantrolene (0.2 mM) significantly inhibits steroid synthesis stimulated by either angiotensin II (AII) or by addition of various precursors. Our results suggest that dantrolene inhibits the rate-limiting steps of adrenocortical steroidogenesis, i.e. the intramitochondrial conversion of cholesterol to pregnenolone (for both aldosterone and cortisol) and the conversion of corticosterone to aldosterone (for aldosterone), by a mechanism independent from its known effects on calcium release. A possible alternative mechanism may involve direct inhibition of cytochrome P450-dependent hydroxylation reactions.

18-Hydroxycorticosterone

Autonomic mechanisms underlying intraocular pressure changes during insulin-induced hypoglycaemia in normal human subjects: effects of pharmacological blockade.

1. A fall in intraocular pressure is induced by acute hypoglycaemia in humans. The role of the autonomic nervous system in mediating this response was investigated in 24 normal volunteers in whom hypoglycaemia was induced with intravenous soluble insulin, under four experimental conditions: (1) control (n = 6), (2) non-selective alpha-adrenoceptor blockade (phentolamine) (n = 6), (3) non-selective beta-adrenoceptor blockade (propranolol) (n = 6) and (4) cholinergic blockade (atropine) (n = 6). Intraocular pressure was measured by using an applanation tonometer. In 12 subjects intraocular pressure was measured during each type of pharmacological blockade of similar duration without induction of hypoglycaemia, to assess the effects of individual antagonists. 2. In the control study intraocular pressure fell during hypoglycaemia from 15 +/- 1.0 to 10 +/- 1.3 mmHg (P less than 0.01) 10 min after the autonomic reaction. beta-Adrenoceptor blockade caused a reduction in intraocular pressure from 15 +/- 1.1 to 9 +/- 1.0 mmHg (P less than 0.001) before the administration of insulin, and when hypoglycaemia was induced intraocular pressure decreased further to 7 +/- 1.0 mmHg (P less than 0.05, compared with immediately before insulin). A decrease in intraocular pressure of similar magnitude was observed with propranolol alone (16 +/- 1.0 to 10 +/- 1.0 mmHg, P less than 0.05). 3. Cholinergic blockade had no immediate effect on intraocular pressure, and the reduction in intraocular pressure during hypoglycaemia was of similar magnitude to that observed during the control study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Hypoglycaemia unawareness in type 1 diabetes: a lower plasma glucose is required to stimulate sympatho-adrenal activation.

To investigate the relationship between awareness of symptoms and the autonomic reaction of hypoglycaemia, acute hypoglycaemia was induced with intravenous insulin (2.5 mU kg-1 min-1) in diabetic and non-diabetic subjects, all of whom had normal cardiovascular autonomic function tests. Three groups were studied: (1) nine patients with Type 1 diabetes with loss of awareness of hypoglycaemia; (2) eight patients who had normal awareness of hypoglycemia, matched for duration of diabetes and blood glucose control; (3) eleven non-diabetic volunteers. The onset of the acute autonomic reaction was identified objectively by the sudden and rapid responses of heart rate and sweating. Cognitive function and hypoglycaemia symptom scores were estimated serially. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia. In the 'unaware' diabetic patients, onset of the reaction occurred at a significantly lower plasma glucose (1.0 +/- 0.1 mmol l-1) than in the 'aware' diabetic patients (1.6 +/- 0.2 mmol l-1) (p less than 0.05) or in the non-diabetic control group (1.4 +/- 0.1 mmol l-1) (p less than 0.05). Obvious neuroglycopenia was observed only in the 'unaware' diabetic group and developed when plasma glucose had declined to approximately 1.4 +/- 0.1 mmol l-1, and thus preceded the reaction (p less than 0.02 vs the autonomic threshold). The maximal rise in plasma adrenaline was of similar magnitude in all three groups but a lower plasma glucose was required to stimulate this hormonal response in the 'unaware' patients, in whom the plasma adrenaline concentration was lower at the time of the reaction. Thus, the plasma glucose at which activation of the autonomic reaction was observed was lower in the diabetic patients with unawareness of hypoglycaemia.

Adrenal Glands

Effects of adrenergic blockade on serum potassium changes in response to acute insulin-induced hypoglycemia in nondiabetic humans.

OBJECTIVE: To determine the possible role of adrenergic mechanisms in mediating the fall in serum potassium concentration after intravenous injection of insulin. RESEARCH DESIGN AND METHODS: Eighteen nondiabetic male volunteers, divided into three groups of six subjects, comprised the study. Hypoglycemia was induced by a bolus of short-acting insulin (0.15 U/kg body wt). Six subjects were studied in control conditions, six during alpha-adrenergic blockade with phentolamine, and six during beta-adrenergic blockade with propranolol. RESULTS: In the control group, there was an immediate fall in serum potassium from 4.0 +/- 0.1 to 3.6 +/- 0.1 mM at baseline + 15 min. After the onset of acute hypoglycemia, potassium decreased further in the control group, reaching a lowest concentration of 3.3 +/- 0.1 mM. In the propranolol group, the late decrease in potassium was inhibited, and there were no further changes in serum potassium. During alpha-blockade, there was an exaggerated fall to 2.6 +/- 0.1 mM at 30 min after the onset of hypoglycemia. CONCLUSIONS: The later fall in serum potassium, which occurs after the onset of hypoglycemia, is probably mediated by stimulation of beta-adrenoreceptors, whereas coincidental stimulation of alpha-adrenoreceptors opposes this fall in potassium and may prevent the development of severe hypokalemia in response to acute hypoglycemia.

Adrenergic Fibers

Use of computerised records to ensure optimum measles vaccination.

Measles immunisations in Grampian were studied using the computerised Grampian Immunisation Record System. Records of children who were shown to have been immunised under 12 months of age were re-checked. This served as an audit of Grampian Health Board's centralised computer system and General Practice records, and as an educational exercise for the health professionals involved.

Forms and Records Control

The effects of acute insulin-induced hypoglycaemia on renal function in normal human subjects.

The effects of acute insulin-induced hypoglycaemia on renal function were studied in 8 normal male subjects. Plasma glucose (mean (SE) fell from 4.6(0.2) to 1.3(0.2) mmol l(-1), the nadir being coincident with the acute autonomic reaction, and returned to the basal value over the following 120 min. Glomerular filtration rate declined from 118(6) to 95(4) ml min-1 at the glucose nadir (p less than 0.01), and during the recovery phase returned to 118(7) ml min-1 (NS compared with basal). Renal plasma flow fell from 625(38) to 485(27) ml min-1 (p less than 0.01), rising to 545(46) ml min-1 during recovery from hypoglycaemia (NS compared with basal). Following hypoglycaemia, urinary excretion of sodium and dopamine were reduced significantly, but the albumin excretion rate was unchanged. Plasma concentrations of adrenaline, noradrenaline, angiotensin II, and plasma renin activity increased in response to hypoglycaemia. These acute changes in renal function are probably caused by sympatho-adrenal activation and secretion of catecholamines, but other hormones, such as angiotensin II, may be contributory.

Albuminuria

Repair of a false aneurysm of the aortic arch.

A 66-year-old man having previously undergone repair of aneurysms of the ascending, transverse and infrarenal aorta, presented with a large false aneurysm of the aortic arch. Successful repair of the aneurysm was achieved under a state of profound hypothermia and circulatory arrest. The patient remains well and free from aortic aneurysmal disease two years after surgery.

Aged

Relationship between crystallin mRNA expression in retina cells and their capacity to re-differentiate into lens cells.

Differentiating vertebrate embryo tissues pass through a stage when they have the potential for several pathways of differentiation, some of them revealed only by experimental manoeuvres. As differentiation proceeds, the potential for alternative pathways becomes progressively restricted and is eventually lost. We have investigated the molecular basis for this phenomenon, using the chick embryo retina, which has a potential for differentiation into lens cells. This potential requires special conditions for its manifestation; it declines during development and is finally lost before hatching. Lens protein (crystallin) mRNA is expressed in early embryo retina: its levels decline in parallel with the decline in lens-forming potential. There is also evidence of an ontogenic change in post-transcriptional regulation. Such a relationship between heterologous mRNA and heterologous differentiation potential may be of general application.

Animals

Cyanide exposure in fires.

The toxic hazard from cyanide produced in fires was assessed in casualties and in firemen exposed to the fire atmosphere. The levels of cyanide and its principal metabolite, thiocyanate, were measured in blood samples from fireman, non-fetal and fatal casualties, and from controls. Although firemen did not differ significantly from controls, casualities showed significant elevation of blood-cyanide, and in a small proportion of fatalities blood-cyanide reached toxic levels.

Cyanides