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Biomedical subjects

P Butler

Publications and source records attributed to P Butler.

At least 19 recordsLinked to original sources

Use of chromosomal gene fusions to investigate the role of repetitive DNA in regulation of genes involved in lipopolysaccharide biosynthesis in Haemophilus influenzae.

The lic3 locus of Haemophilus influenzae consists of four open reading frames. The derived amino acid sequences of orf2 and orf4 exhibit homology to Escherichia coli GalE and AdK, respectively. The functions of orf1 and orf3 remain unknown. orf1 contains multiple tandem repeats of the tetrameric DNA sequence CAAT near the 5' end. Two possible translational starts (ATG1 and ATG2) lie upstream. We have used lacZ fusions to investigate whether changes in the number of CAAT repeats in conjunction with differential usage of the upstream frames control the expression of lic3-orf1. Phase-variable expression of lacZ was observed for individual colonies and could be related to variable numbers of CAAT repeats. Of the three possible upstream frames, only one, containing the more downstream of the two possible ATG start codons (ATG2), is used for strong expression of lacZ. Utilization of the more upstream ATG (ATG1) or ATG2 was observed with medium-level expression, while utilization of any of the three possible frames was observed when lacZ was expressed at low to undetectable levels, indicating that other mechanisms may affect expression. To investigate this, lacZ was fused in frame with ATG2 of lic3-orf1, with concomitant deletion of the repeats. Phase-variable expression was still observed, supporting the view that an alternative level of control operates in conjunction with the repeat mechanism.

Amino Acid Sequence

Use of [3-3H]glucose and [6-14C]glucose to measure glucose turnover and glucose metabolism in humans.

[3-3H]glucose is frequently used to measure glucose turnover in humans. If fructose 6-phosphate-fructose 1,6-diphosphate cycling (Fpc) is negligible in both liver and muscle, then [3-3H]- and [6-14C]glucose (corrected for Cori cycle activity) should provide equivalent measures of glucose turnover. In addition, if glycogenolysis is fully suppressed, then [14C]lactate specific activity should equal that of [6-14C]glucose from which it was derived, and oxidation of [6-14C]glucose, as measured by rate of generation of 14CO2, should equal total glucose oxidation (i.e., that derived from intra- and extracellular pools) as measured by indirect calorimetry. To address these questions, glucose turnover was measured simultaneously with [3-3H]- and [6-14C]glucose in the basal state and in presence of low (approximately 200 pM) and high (approximately 750 pM) insulin concentrations. Glucose turnover rates measured with [3-3H]- and [6-14C]glucose were equivalent at all insulin concentrations, indicating that Fpc had no detectable effect on measurement of glucose appearance. [14C]lactate specific activity was lower (P less than 0.01) than that of [6-14C]glucose in the basal state but not during either low- or high-dose insulin infusion, implying that all lactate was derived from extracellular glucose. On the other hand, glucose oxidation as measured by rate of generation of 14CO2 was lower (P less than 0.05) than glucose oxidation as measured by indirect calorimetry during both insulin infusions, implying either that suppression of glycogenolysis was not complete in all tissues or that one or both of these techniques do not accurately measure glucose oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The influence of needle size on post-myelography headache: a controlled trial.

This study aimed to test the hypothesis that the use of fine rather than larger calibre needles for myelography reduces the incidence of post-procedural headache. 160 patients were randomized in a prospective controlled trial of 22 gauge versus 26 gauge needles. The incidence and overall severity of headache as measured at 1, 4 and 21 days after myelography was not significantly different in the two groups.

Female

Effects of chronic systemic insulin delivery on insulin action in dogs.

The metabolic consequences of the prolonged systemic insulin delivery associated with human pancreas transplantation have not been precisely defined. To determine if systemic insulin delivery in the absence of immunosuppressive agents results in alterations in hepatic or extrahepatic insulin action, three groups of dogs were studied 2 months after either a sham operation or after their pancreatic venous drainage was severed and anastomosed to the inferior vena cava or portal vein (sham, peripheral and portal groups, respectively). The pattern of venous drainage was documented by measuring vena cava and portal insulin concentrations before and after glucose injection. Systemic insulin concentrations were higher (p less than 0.05) in the peripheral group than in the portal group both following a 14-h fast and after intravenous glucose. During a hyperinsulinaemic euglycaemic clamp (1 mU.kg-1.min-1), glucose utilization (measured using [6(3)H]glucose) was slightly lower (p = 0.07) in the peripheral than in the portal group. Hepatic glucose release was equal in all groups. Carbon dioxide incorporation into glucose (an estimate of gluconeogenesis) was higher in the portal than peripheral group in the fasted state but not during insulin infusion. Plasma concentrations and flux rates of fatty acids and amino acids did not differ between groups. We conclude that chronic systemic insulin delivery results in a) systemic but not portal hyperinsulinaemia, b) a minimal impairment in insulin-stimulated glucose uptake, without altering insulin-induced suppression of hepatic glucose release, and c) no effect on fatty acid or amino acid turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Digital subtraction angiography (DSA) of the extracranial cerebral vessels: a direct comparison between intravenous and intra-arterial DSA.

Fifty patients being investigated for ischaemic cerebrovascular disease underwent both intravenous digital subtraction angiography (IV-DSA) and intra-arterial arch digital subtraction angiography (arch-DSA) to enable a direct comparison to be made between the two techniques. The overall quality of the images obtained by arch-DSA was better than that obtained by IV-DSA, but there was no significant difference between the number and gradation of stenoses detected by the two techniques. No significant stenosis was missed by IV-DSA and the technique was found to be sufficiently accurate for it to be used as a screening procedure for carotid bifurcation stenoses suitable for carotid endarterectomy. The advantages and limitations of both techniques are discussed.

Adult

The value of CT scanning in chronic suppurative otitis media.

High definition CT has been advocated for the evaluation of chronic suppurative otitis media (CSOM) either generally or in selected cases. It is said to be capable of producing the fine detail needed to detect lateral canal fistulae, exposed dura and facial canal dehiscences, and to demonstrate the ossicular chain. At present there is no agreement on either the indications for CT scanning in CSOM or the most appropriate scanning plane. To determine the value of high definition CT in CSOM and to decide a unit policy for its application, 36 cases of CSOM underwent pre-operative CT scanning and their scans were compared with the operative findings. Our results show CT to be highly sensitive to the presence of soft tissue disease and bone erosion, moderately sensitive to the presence of lateral canal fistulae but less sensitive to the presence of small areas of exposed dura, ossicular continuity and facial canal dehiscence. Axial scans were better able to demonstrate the lateral canal but otherwise coronal scans were superior; ideally patients should be scanned in both planes. The principle value of CT in CSOM is its ability to demonstrate disease which is not clinically apparent.

Cholesteatoma

Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans.

Growth hormone excess can cause postprandial carbohydrate intolerance. To determine the contribution of splanchnic and extrasplanchnic tissues to this process, subjects were fed an isotopically labeled mixed meal after either a 12-h infusion of saline or growth hormone (4 micrograms.kg-1.h-1 [corrected]). Growth hormone infusion resulted in higher glucose and insulin concentrations both before and after meal ingestion. Despite growth hormone-induced hyperglycemia and hyperinsulinemia, postprandial hepatic glucose release and carbon dioxide incorporation into glucose (a qualitative estimate of gluconeogenesis) were similar to those present during saline, suggesting altered hepatic regulation. This was confirmed when glucose was infused in the absence of growth hormone to achieve glucose (and insulin) concentrations comparable to those present during growth hormone infusion. Although growth hormone excess did not alter splanchnic uptake of ingested glucose, it resulted in a fivefold increase in postprandial hepatic glucose release (578 +/- 31 vs. 117 +/- 10 mg.kg-16 h-1, P less than 0.01), less suppression of carbon dioxide incorporation into glucose (-13 +/- 9 vs. -53 +/- 12 mg.kg-1. 6-h-1, P less than 0.01), and lower glucose uptake (1,130 +/- 59 vs. 1,850 +/- 150 mg.kg-1.6 h-1, P less than 0.01). The decrease in postprandial glucose uptake did not appear to be mediated by a change in substrate uptake since postprandial plasma concentrations and forearm balance of lactate, free fatty acids, and ketone bodies did not differ in the presence and absence of growth hormone excess.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid

Small deep cerebral infarcts associated with occlusive internal carotid artery disease. A hemodynamic phenomenon?

Small deep cerebral infarcts, often referred to as lacunes, have been traditionally associated with small-vessel disease affecting the deep penetrating arterial system. We describe 10 cases where these infarcts were associated with severe, ipsilateral internal carotid artery occlusive disease. Seven of these patients also had severe occlusive disease of the contralateral internal carotid artery. The clinical and radiologic features, in combination with studies of cerebral blood flow, were consistent with hemodynamically mediated cerebral ischemia. Occlusive internal carotid artery disease may be more commonly associated with hemodynamic cerebral ischemia than previously believed, and small cerebral infarcts in the deep arterial border zone areas are likely to be an important manifestation of this process.

Adult

Feasibility of percutaneous transluminal angioplasty for carotid artery stenosis.

Percutaneous transluminal balloon angioplasty was attempted in seven patients with internal carotid artery stenosis, including one patient who had two procedures. All had recurrent, carotid territory, neurological symptoms considered haemodynamic in origin. Six had occlusion of the contralateral internal carotid artery. Cerebral blood flow studies confirmed diminished cerebrovascular reserve in six patients studied. In five patients (six procedures) angioplasty of the stenosed internal carotid artery was carried out successfully. With two patients technical difficulty in crossing the stenosis prevented angioplasty and in one patient with bilateral stenosis the procedure was not attempted on the second side because of the severity of the stenosis. In two patients transient aphasia developed during cannulation of the carotid artery and in another a transient monoparesis developed during the procedure. Both these haemodynamic complications recovered within ten minutes. No other complications occurred. Our experience suggests that balloon angioplasty is technically feasible in the management of stenotic carotid disease associated with haemodynamic stroke. It is a technically simple procedure requiring only a brief admission to hospital. However, its general application to patients with thromboembolic carotid-territory stroke will depend on the risk/benefit ratio compared to carotid endarterectomy or to conventional medical treatment.

Angiography, Digital Subtraction

Cerebellar syndrome with hydrocephalus due to Mycoplasma pneumoniae infection.

A 27 year old woman developed a cerebellar syndrome with serological evidence of recent Mycoplasma pneumoniae infection. The cranial computed tomographic scan showed effacement of the fourth ventricle, enhancement of the basal meninges and hydrocephalus affecting the lateral and third ventricles. Clinical and radiological recovery occurred over 5 weeks. We propose that this was a manifestation of immune-mediated encephalomyelitis induced by the infection rather than direct invasion of the central nervous system.

Adult

Insulin resistance in type II diabetes mellitus.

In vivo studies indicate that patients with NIDDM have defects in both insulin secretion and insulin action. The decrease in insulin action is due to both hepatic and extrahepatic insulin resistance. The impairment in glucose uptake is associated with alterations in both oxidative and nonoxidative disposal. Defective glucose transport may limit both of these processes. NIDDM also is associated with increased concentrations and rates of oxidation of plasma free fatty acids. Insulin resistance appears to be familial and in at least some individuals antedates glucose intolerance. In vitro studies indicate that insulin resistance can involve a variety of insulin sensitive tissues including adipocytes, muscle and liver. While most studies note that insulin binding and insulin receptor kinase activity are decreased in insulin sensitive tissues in obese patients with NIDDM, further delineation of the contribution of obesity and diabetes is required. Alterations in glucose transporter number and function likely account at least in part for impaired glucose transport. The cause of the alterations in other insulin responsive pathways and the role of an abnormal metabolic milieu versus intrinsic cellular defects remain to be established.

Adipose Tissue