Carotid endarterectomy in New Zealand.
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Endarterectomy, Carotid↗
Biomedical subjects
I Thomson
Publications and source records attributed to I Thomson.
EVA dosimetry in manned spacecraft.
Extra Vehicular Activity (EVA) will become a large part of the astronaut's work on board the International Space Station (ISS). It is already well known that long duration space missions inside a spacecraft lead to radiation doses which are high enough to be a significant health risk to the crew. The doses received during EVA, however, have not been quantified to the same degree. This paper reviews the space radiation environment and the current dose limits to critical organs. Results of preliminary radiation dosimetry experiments on the external surface of the BION series of satellites indicate that EVA doses will vary considerably due to a number of factors such as EVA suit shielding, temporal fluctuations and spacecraft orbit and shielding. It is concluded that measurement of doses to crew members who engage in EVA should be done on board the spacecraft. An experiment is described which will lead the way to implementing this plan on the ISS. It is expected that results of this experiment will help future crew mitigate the risks of ionising radiation in space.
Animals↗
Recurrent varicose veins: patterns of reflux and clinical severity.
Duplex scanning was used to determine patterns of recurrent varicose veins in 264 limbs and to relate these to clinical factors. All limbs had previously undergone sapheno-femoral ligation in the groin. A recurrent sapheno-femoral junction was present in 172 (65.2%). Incompetence was found in long or short saphenous veins in 232 limbs (87.9%), perforators in 176 (66.7%), and deep veins in 156 (59.1%). Residual long saphenous veins were present in 43.4% and 73.6% of limbs that were with and without stripped long saphenous veins, respectively. An incompetent thigh perforator was present in 14.0% and 15.3% of these two groups, respectively. Multiple sites of incompetence were observed in the majority (75.4%). In general, no particular reflux pattern in the groin was related to an increased incidence of ulceration. However, ulceration was more frequent in limbs with deep reflux to knee or below-knee levels. None of those with isolated reflux in the groin that was unrelated to the common femoral vein had ulceration. The pattern of reflux was unrelated to striping or non-striping of the long saphenous veins and the time since initial surgery. A history of deep vein thrombosis was invariably associated with some degree of deep reflux. A system of recurrent patterns in the groin is described for the purpose of surgical audit. In 15.1%, recurrence was attributed with some confidence to inadequate surgery. These results indicate that the pattern of recurrence is highly variable and often with multiple sites of incompetence. In a few instances, the pattern of recurrence was associated with specific clinical factors. A full work-up including duplex scanning is recommended.
Aged↗
A two-center study evaluating the hemodynamic and pharmacodynamic effects of cisatracurium and vecuronium in patients undergoing coronary artery bypass surgery.
OBJECTIVE: To determine the hemodynamic and pharmacodynamic effects of rapid bolus administration of cisatracurium compared with vecuronium. DESIGN: A randomized, prospective, double-blind study. SETTING: Tertiary-care university hospitals. PARTICIPANTS: Seventy-nine adult patients with diagnosed coronary artery disease (CAD). INTERVENTION: Elective coronary artery bypass graft surgery (CABG). MEASUREMENTS AND MAIN RESULTS: Patients were randomly divided into four groups. Patients received a rapid bolus of two or four times the 95% peak depression of twitch (ED95) of either cisatracurium (groups 1 and 2) or vecuronium (groups 3 and 4). Three minutes after a midazolam induction, all patients received a rapid bolus administration of either study drug. Maintenance of anesthesia was with a standardized propofol-sufentanil-oxygen anesthetic. Patients were monitored with radial and pulmonary artery catheters and electromyography. End points of the study were hemodynamic stability at induction, after bolus administration of study drugs, and after intubation; the quality of intubating conditions; drug interventions to correct hemodynamic instability; the onset, duration, and recovery of neuromuscular function; and drug cost. Mean arterial pressure (MAP) and heart rate (HR) decreased in a similar proportion in all four groups after induction while, following study drug administration, MAP and HR did not change significantly. Both cisatracurium groups required more boluses to maintain neuromuscular block, but spontaneous recovery rates were faster. Both agents, but cisatracurium to a lesser degree, showed increased duration with repeated maintenance doses. Both agents afforded good to excellent intubating conditions, but the cost of cisatracurium was significantly less. CONCLUSION: The authors conclude there is no evidence of a hemodynamic difference between the two neuromuscular blocking drugs (NMBDs). There are some clinical and cost advantages in favor of cisatracurium.
Adolescent↗
Stimulation of aldosterone secretion by benzodiazepines in bovine adrenocortical cells.
Previous studies have indicated that peripheral benzodiazepine receptor (PBR) ligands inhibit aldosterone secretion in isolated adrenal zona glomerulosa cells although positive responses have been demonstrated in other steroidogenic tissues. In the present study, aldosterone secretion was measured in bovine cells after 6 days of primary culture. At this time, basal aldosterone secretion was very low and cells appeared less sensitive to the steroidogenic effects of extracellular [K+] (maximal response required K+ concentration > 32 mmol/L) but were sensitised to angiotensin II (maximal response achieved with 3 nM) when compared with previous studies with freshly isolated cells. Diazepam concentration in the range 0.1 nM to 1 microM increased basal aldosterone secretion, an effect which was not enhanced by pre-treatment with diazepam. The effects were small compared with those of angiotensin II or K+. Over the same concentration range, diazepam also potentiated the stimulatory effects of sub-maximally effective concentrations of angiotensin II. When cells were treated with high-density lipoprotein (HDL-3) as a source of cholesterol, diazepam and the PBR ligands Ro5-4864 and PK11195 also stimulated aldosterone secretion at nanomolar concentrations. In addition, the conversion of added 11-deoxycorticosterone (DOC) to aldosterone was increased by nanomolar concentrations of diazepam and Ro5-4864 but inhibited by high micromolar concentrations of these drugs (100 microM). We conclude that adrenocortical responses to PBR ligands are complex. At high concentrations, inhibitory effects involving competition for steroidogenic enzymes and calcium channel blockage predominate. At low concentrations, an enhancement of basal, angiotensin-II and cholesterol-dependent aldosterone synthesis is revealed which may involve a PBR-mediated mitochondrial uptake of cholesterol and DOC.
Adrenal Cortex↗
A clinic based survey of blindness and eye disease in Cambodia.
AIMS: To survey the spectrum of eye disease presenting to rural eye clinics in Cambodia. METHODS: A total of 1381 patients seen consecutively at 13 eye clinics were examined and the findings recorded. RESULTS: 231 (16.7%) were bilaterally blind (visual acuity < 3/60 in both eyes); 263 (19%) were unilaterally blind, and 169 (12%) had low vision (visual acuity < 6/18 in the better eye). Cataract was the commonest cause of visual loss in all three categories and was responsible respectively in 69%, 40%, and 55% of each group. Trachoma was diagnosed in 13% of patients. Thirty three of them needed lid surgery for trichiasis. CONCLUSION: With the difficult practical and political situation in Cambodia there seems little prospect of making substantial inroads into the backlog of avoidable blindness in the near future.
Adolescent↗
Regulation of adrenocortical steroidogenesis by benzodiazepines.
Benzodiazepines affect steroidogenesis in at least four ways depending on concentration and adrenocortical cell type. Firstly, at micromolar concentrations, they inhibit steroidogenic enzymes. Competition for microsomal 17- and 21-hydroxylase activity explains the inhibition of ACTH-stimulated aldosterone and cortisol synthesis by diazepam and midazolam. At slightly higher concentrations, we have evidence that 11 beta-hydroxylase activity is also inhibited. Secondly, at sub-micromolar concentrations, calcium influx is inhibited. T-type and L-type calcium channels appear to be blocked, this impairs signal response coupling and, in particular, decreases angiotensin- and K(+)-stimulated aldosterone synthesis in zona glomerulosa cells. Thirdly, the mitochondrion of steroidogenic tissues is a sensitive site for the stimulatory effects of benzodiazepines. Aldosterone synthesis from added HDL-cholesterol by cultured bovine zona glomerulosa cells is stimulated by diazepam, RO5-4864 and PK11195. The fourth site of benzodiazepine's effect on steroidogenesis is particular to zona glomerulosa cells. In addition to cholesterol side chain cleavage, the final part of the aldosterone biosynthetic pathway, the conversion from deoxycorticosterone is controlled. Although high micromolar concentrations of diazepam appear to be inhibitory, lower nanomolar concentrations stimulate the synthesis of aldosterone from added deoxycorticosterone. In vivo, a fifth site of benzodiazepine activity may influence plasma steroid concentrations. Competition between steroids and benzodiazepines for hepatic clearance enzymes may affect half lives of both drugs and hormones.
Adrenal Glands↗
Checking quality of health care records.
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Feedback↗
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↗
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↗