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Biomedical subjects

P Bannister

Publications and source records attributed to P Bannister.

At least 19 recordsLinked to original sources

Glucose production in the human placenta.

Glucose transfer from mother to fetus by placental facilitated diffusion is the dominant mechanism by which the fetus acquires glucose. In small for gestational age pregnancies, fetal glucose concentrations tend to be lower than normal and this persists following delivery. GLUT1 is the major glucose transporter in human placenta but there is no evidence of GLUT1 deficiency as a cause of the lower fetal glucose concentration in small for gestational age pregnancy. The physiological and pathological roles of the other glucose transporters (and there are 14 currently described) are unknown. In recent years, the possibility has been raised that the placenta is itself capable of supplying glucose for fetal needs. This hypothesis derived from glucose isotope studies in normal pregnancy, where dilution of glucose isotope was demonstrated in blood samples taken from the fetal circulation during intravenous infusion of glucose isotope in the mother. Although other gluconeogenic enzymes were known to be present, the placenta was previously considered incapable of glucose secretion because it lacked functional glucose-6-phosphatase. Recent studies, however, have suggested that specific glucose-6-phosphatase may be present in placenta but it may be the product of a different gene from conventional hepatic glucose-6-phosphatase. The presence of the specific transporters necessary for glucose-6-phosphatase activity is currently being investigated. The role of placental glucose secretion in normal and growth-restricted pregnancies is an area of current study.

Amino Acid Sequence↗

Increased leucine turnover in women during the third trimester of uncomplicated pregnancy.

Plasma amino acid concentrations decrease in pregnancy despite increased requirements for both maternal and fetal protein accretion. There are few published data on changes in amino acid turnover in pregnancy. The aim of this study is to test the hypotheses that (1) whole body nonoxidative leucine disposal (NOLD) is higher and (2) whole body oxidative leucine disposal (OLD) is lower in the third trimester of pregnancy than in the nonpregnant state. After an overnight fast 8 pregnant women between 33 and 35 weeks gestation had a primed infusion of labeled [1-(13)C] leucine and a prime dose of NaH(13)CO(3). Carbon dioxide production was measured using indirect calorimetry. Gas chromatography-mass spectrometry was used to determine (13)CO(2) enrichment of expired air and oxidative and nonoxidative leucine turnover by measuring (13)C keto-isocaproate plasma enrichment, which reflects intracellular leucine enrichment. Women acted as their own controls after the puerperium. Whole body leucine turnover expressed per unit body weight was increased in pregnancy (median [interquartile range or IQR]: pregnant = 103.1 [14.9] v nonpregnant = 90.1 [10.9] micromol/kg/h). The mean (+/-SD) of the differences was 11.4 +/- 5.6 micromol/kg/h, P =.0006. NOLD was increased in pregnancy (pregnant = 86.8 [10.1] v nonpregnant = 73.3 [9.5] micromol/kg/h). The mean (+/-SD) of the differences was 10.6 +/- 5.4 micromol/kg/h, P =.0008. OLD was not significantly altered in pregnancy (pregnant = 17.3 [4.5] v nonpregnant = 15.91 [2.4] micromol/kg/h). The mean (+/-SD) of the differences was 0.84 +/- 1.94 micromol/kg/h, P =.26. In conclusion, women have significantly higher NOLD in the third trimester of pregnancy than when not pregnant but there are no significant changes in OLD.

Adult↗

Hypopituitarsim is associated with triglyceride enrichment of very low-density lipoprotein.

The dyslipidemia associated with hypopituitarism may contribute to increased vascular mortality. The atherogenic potential of lipoproteins is determined not only by concentration but also by their composition. We therefore studied very low-density lipoprotein composition and apolipoprotein B kinetics in 16 hypopituitary subjects and 16 controls. Hypopituitarism was associated with reduced high-density lipoprotein cholesterol (0.98[0.82-1.18] vs. 1.35[1.15-1.41] mmol/liter, P < 0.001) and increased triglyceride concentrations (1.64[1.09-2.77] vs. 1.12[0.66-1.67] mmol/liter, P = 0.01). Total (P = 0.76) and low-density lipoprotein cholesterol (P = 0.56) concentrations were similar. Very low-density lipoprotein- triglyceride was significantly increased (1.48[1.02-2.55] vs. 0.9[0.31-2.30] mmol/liter, P = 0.004), but very low-density lipoprotein cholesterol levels were similar (P = 0.93). The molar ratios of very low-density lipoprotein-triglyceride:apolipoprotein B (6193[4283-9566] vs. 3599[3188-6854], P = 0.005) and very low-density lipoprotein-triglyceride:cholesterol (2.8[1.98-3.78] vs. 1.6[1.44-2.80], P < 0.003) were significantly increased; very low-density lipoprotein-cholesterol:apolipoprotein B molar ratios (P = 0.93) were similar. Very low-density lipoprotein apolipoprotein B fractional synthetic rate (a measure of apolipoprotein B catabolism, P = 0.42) and pool size (P = 0.63) were similar. The very low-density lipoprotein apolipoprotein B absolute synthetic rate (a measure of apolipoprotein B synthesis) tended to be higher in hypopituitarism (17.7[2.91-19.50] vs. 26.6[19.64-28.05] mg/kg per day, P = 0.24) but failed to reach statistical significance. The absolute synthetic rate, and hence very low-density lipoprotein production, correlated with very low-density lipoprotein triglyceride:apolipoprotein B ratio (P = 0.02, Rs = 0.63), suggesting that triglyceride enrichment of very low-density lipoprotein is important in the mechanism underlying very low-density lipoprotein overproduction in hypopituitarism. Because triglyceride-enriched lipoproteins are proatherogenic, this may contribute to the vascular mortality observed in hypopituitarism. The reasons for these observations are unknown; GH deficiency or routine endocrine replacement may be important.

Adenoma↗

Glucose production by the human placenta in vivo.

The human placenta transports glucose by facilitated diffusion down a concentration gradient from mother to fetus. It has previously been considered incapable of glucose synthesis. However, recent work has demonstrated the presence in placental tissue of glucose-6-phosphatase, which is required for the final step in the synthesis of glucose. Following continuous intravenous infusion into the maternal circulation of the stable isotope, 6,6-(2)H(2)glucose, during elective caesarean section, we have observed isotope dilution in the umbilical vein, without further dilution in the umbilical artery. Using a mathematical model containing maternal, placental and fetal compartments, the data were compatible with the release of glucose by the placenta. We conclude that the human placenta at term can produce glucose.

Adult↗

Reproducibility and comparability of insulin sensitivity indices measured by stable-label intravenous glucose tolerance test.

We have investigated the reproducibility of (1) insulin sensitivity (S*I) and glucose effectiveness (S*G) as measured by the stable-label (one compartment) minimal model, and (2) insulin sensitivity (S*Ib), plasma clearance rate (PCR), basal hepatic output (HGOb), and total hepatic glucose output (HGO0-240) as measured by the novel stable-label two compartment model of glucose disappearance during labelled intravenous glucose tolerance test (IVGTT) using 6,6-(2)H-glucose. Ten normal male subjects were studied on two occasions one week apart. Both models provided estimates of all indices with acceptable precision (CV of parameter estimates < or =50%). The within subject CVs of S*I and S*Ib were comparable (17% vs 19%) as were the within subject CVs of S*G and PCR (13% vs 16%). A highly significant linear relationship was observed between S*Ib and S*I (0.303 +/- 0.046 ml kg(-1) min(-1) per mU l(-1) vs 13.04 +/- 1.89 10(-4) min(-1) per mU l(-1), y = 0.0037 x + 0.0002, r = 0.90, p < 0.001; mean +/- SE), but not between PCR and S*G (1.98 +/- 0.15 ml kg(-1) min(-1) vs 0.0089 +/- 0.0005 min(-1), rs = 0.34, NS). The two compartment model provided a plausible time-profile of hepatic glucose output during IVGTT, reproducible estimates of HGOb (1.96 +/- 0.18 mg kg(-1) min(-1), 15%; mean +/- SE, within subject CV), and a highly reproducible HGO0-240 (7%; within subject CV). We conclude that the stable-label (one compartment) minimal model and the stable-label two compartment model provide reproducible estimates of parameters of glucose kinetics in normal subjects. Insulin sensitivity indices estimated by the two models are strongly linearly related.

Adult↗

Motor and cognitive function in Lewy body dementia: comparison with Alzheimer's and Parkinson's diseases.

OBJECTIVE: Motor and cognitive function were compared in patients with Lewy body dementia, Parkinson's disease, or Alzheimer's disease, to identify features that may be clinically useful in differentiating Lewy body dementia from Alzheimer's disease and Parkinson's disease. METHODS: A range of neuropsychological function and extrapyrimidal signs (EPS) was assessed in 16 patients with Lewy body dementia, 15 with Parkinson's disease, 25 with Alzheimer's disease, and 22 control subjects. RESULTS: The severity of total motor disability scores increased in the following order: controls approximately = Alzheimer's disease << Parkinson's disease < Lewy body dementia. Compared with patients with Parkinson's disease, patients with Lewy body dementia had greater scores for rigidity and deficits in the finger tapping test, but rest tremor and left/right asymmetry in EPS were more evident in Parkinson's disease. Patients with Lewy body dementia were also less likely to present with left/right asymmetry in EPS at the onset of their parkinsonism. "Sensitivity" to neuroleptic drugs was noted in 33% of patients with Lewy body dementia. Alzheimer's disease and Lewy body dementia groups had greater severity of dementia compared with the Parkinson's disease group and controls. Neuropsychological evaluation disclosed severe but similar degrees of impaired performances in tests of attention (digit span), frontal lobe function (verbal fluency, category, and Nelson card sort test) and motor sequencing in both Lewy body dementia and Alzheimer's disease groups, than Parkinson's disease and controls. In the clock face test, improved performance was noted in the "copy" compared to "draw" part of the test in controls, patients with Alzheimer's disease, and those with Parkinson's disease, but not in the patients with Lewy body dementia, who achieved equally poor scores in both parts of the test. CONCLUSIONS: EPS in Lewy body dementia resemble those seen in idiopathic Parkinson's disease, although less rest tremor and left/right asymmetry but more severe rigidity favours a diagnosis of Lewy body dementia. The unique profile of patients with Lewy body dementia seen in the clock face test suggests that this simple and easy to administer test may be useful in the clinical setting to differentiate Lewy body dementia and Alzheimer's disease.

Aged↗

Constant infusion and bolus injection of stable-label tracer give reproducible and comparable fasting HGO.

We have investigated the reproducibility of fasting hepatic glucose output (HGO) estimates by use of isotope dilution methodology of stable-label tracers. Six normal subjects were studied on two occasions 1 wk apart. After an overnight fast, the subjects received a bolus injection of 7 mg/kg of [U-13C]glucose and, simultaneously, a primed constant infusion of 0.05 mg.kg-1.min-1 of [6,6(-2)H]glucose. The bolus injection provided one estimate of HGO (HGOBOL), and the constant infusion provided two estimates of HGO, namely, HGO at 2 h (HGOINF2) and HGO at 4 h (HGOINF4), both with the assumption of steady-state conditions. All estimates were similar in value; HGOBOL was highest, followed by HGOINF2 and HGOINF4 [2.30 +/- 0.11 (SE), 2.17 +/- 0.12, and 2.01 +/- 0.13 mg.kg-1.min-1]. The constant infusion gave highly reproducible results. In the case of HGOINF2, the within-subject coefficient of variation (CV) was only 3% compared with 5% of HGOINF4. The reproducibility of HGOBOL was comparable with the within-subject CV of 7%. We conclude that a constant infusion and a bolus injection of stable-label tracer give reproducible and comparable estimates of HGO.

Adult↗

Frost resistance and susceptibility to ice formation during natural hardening in relation to leaf anatomy in three evergreen tree species from New Zealand.

Foliar frost resistance of three endemic New Zealand land trees, Nothofagus menziesii (Hook. f.) Oerst. (Fagaceae), Pittosporum eugenioides A. Cunn. (Pittosporaceae) and Griselinia littoralis Forst. f. (Cornaceae), was examined as the trees hardened from late summer to midwinter in a lowland forest site. The lowest temperatures causing 50% damage (LT(50)) occurred in late winter and were similar to those recorded for other forest trees native to New Zealand (-11.7 degrees C in N. menziesii, -10.7 degrees C in P. eugenioides, and -10.6 degrees C in G. littoralis). All three species hardened by 4-7 degrees C, with G. littoralis showing the least frost resistance in summer and hence the greatest degree of hardening. Thermal analysis during freezing indicated that all three species became more tolerant of extracellular ice formation in winter. Measurements of chlorophyll a fluorescence correlated well with visible injury. The differing patterns of frost damage development in the three species were related to leaf anatomy: visible injury was localized within the small compartments formed by the highly septate leaves of the most resistant species, N. menziesii, and was somewhat localized in the partially septate leaves of P. eugenioides, whereas damage could be initiated anywhere in the aseptate leaves of G. littoralis,which was the least frost resistant species, particularly in summer.

Journal Article↗

Neuroleptic malignant syndrome among acute psychiatric admissions in Barbados.

The main features of the Neuroleptic Malignant Syndrome (NMS), a complication of neuroleptic therapy, are fever, muscle rigidity, autonomic dysfunction, and an alteration in consciousness level. We describe five cases of NMS comprising 0.6% of acute neuroleptically-treated admissions to a psychiatric hospital over a one-year period. All patients, four females aged 26 to 63 years, and one male, aged 65 years, were of African origin and received multiple neuroleptic drugs, at least one of which was a depot preparation. Four were being treated for functional psychiatric disorders while one had dementia. All patients had fever and depressed consciousness level while four had rigidity and autonomic dysfunction. Serum creatine phosphokinase was elevated in 4 cases, and there was indirect evidence of myoglobinuria in 3 cases suggested by a positive urine dipstick test for blood despite the absence of red cells on microscopy. Rhabdomyolysis was associated with renal failure in one case. Both bromocriptine mesylate and dantrolene sodium were given in two cases. Three patients died in hospital, one with persistent rigidity and progressive decubitus ulceration, one from peritonitis following peritoneal dialysis, and another suddenly. Early recognition of NMS is important; it should be considered in any patient on neuroleptic therapy who develops fever, rigidity or alteration in consciousness level.

Adult↗

Protein metabolism after abdominal surgery: effect of 24-h extradural block with local anaesthetic.

We have studied the effect of intraoperative and postoperative (24 h) extradural block with local anaesthetic on whole body protein turnover (stable isotope methodology) and urinary excretion of urea nitrogen, adrenaline, noradrenaline and cortisol in a group of well nourished elderly patients undergoing colorectal surgery who received a constant nutritional intake before (7 days) and after (4 days) surgery. One group (control, n = 8) received routine anaesthetic and surgical care. Patients in the test group (extradural, n = 9) received extradural bupivacaine, and sensory block (T4-S5) was maintained during and after surgery for a period of 24 h. Whole body protein breakdown and amino acid oxidation increased significantly after surgery in both groups (P less than 0.05), but the increase in protein breakdown in the extradural group was significantly less than that in the control group. Urinary excretion of urea nitrogen, adrenaline and noradrenaline increased in the control group after surgery, whilst the increase in the extradural group was very small. In contrast, urinary excretion of cortisol increased significantly in both groups after surgery. We conclude that extradural block maintained for 24 h after surgery significantly minimized postoperative protein breakdown without compromising whole body protein synthesis.

Abdomen↗

Dysphagia in the elderly: what does it mean to the endoscopist?

The role of fibreoptic endoscopy in the investigation of dysphagia in an elderly population was investigated. Three hundred and sixty-five subjects were studied. Two hundred and sixty subjects had abnormalities with extra oesophageal disease accounting for symptoms in a substantial minority. Endoscopy was safe, offered the advantage of immediate therapy and was well tolerated. Sub-group analysis showed it to be preferable to radiological investigation in diagnosing both benign and malignant mucosal lesions.

Adenocarcinoma↗

Use of sensitive thyrotrophin measurements in an elderly population.

The investigation of thyroid disease in the elderly is difficult. Conventional tests are influenced by ill health and abnormal concentrations of thyroid binding proteins. To screen for thyroid disease thyroxine (T4), then tri-iodothyronine (T3) or TSH and an index for binding proteins are normally measured, methods which are expensive and time-consuming. TSH immunoradiometric assays (IRMA) offer the potential of a single test assessment of thyroid function in the elderly. This was assessed by comparing the measurement of IRMA-TSH with T4, T3 and the free thyroxine indices in 290 elderly subjects. Concordant results were obtained in 236 subjects. Non-concordant results were seen in 54 subjects. The commonest cause was sick euthyroid syndrome but 4 cases of high T4 and normal TSH were seen with amiodarone therapy.

Aged↗

Severe herpes zoster infection in the United Kingdom: experience in a regional infectious disease unit.

Seventy-three cases of severe herpes zoster infection admitted to a regional infectious disease unit over a 3-year period were reviewed. Complications were common. Elderly patients were in the majority (55%), were hospitalized for longer and accounted for 78% of all complications. Acyclovir therapy was used in 44 cases with a reduction in both the duration of hospital stay and complication rate.

Acyclovir↗