Serrated W/M osteotomy.
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Biomedical subjects
Publications and source records attributed to J Livesey.
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Stability of an alkamide and a phenolic phytochemical marker in a hydro-alcoholic extract of Echinacea purpurea root and a dried powder prepared by evaporation of the extract was assessed in storage for 7 months at three temperature regimes: -20, 25 and 40 degrees Celsius. In the extract, the major alkamide, dodeca-2E, 4E, 8Z, 10E/Z-tetraenoic acid isobutyl amide, was not significantly affected by storage at any of the temperatures, but cichoric acid content declined as significantly (P = 0.05) at both 25 degrees C and 40 degrees C as compared to low-temperature storage. In the powder, the major alkamide showed a significantly reduced level at 25 degrees C and 40 degrees C while cichoric acid did not decline significantly. These results suggest that more attention should be given to the effect of formulation and temperature on storage of Echinacea products.
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This report describes neurogenesis in the adult human olfactory epithelium in vitro. Olfactory epithelium was collected at autopsy and by biopsy, and grown in serum-free medium. Basic fibroblast growth factor induced the differentiation of bipolar cells which were immunopositive for several neuronal proteins but not glial proteins. [3H]thymidine autoradiography confirmed that these neurones were born in vitro. The results demonstrate that the adult human olfactory epithelium retains the capacity for neurogenesis and neuronal differentiation, at least until the age of 72 years. It is now possible to examine neurones and neurogenesis in biopsies from patients with disorders that may involve a neurodevelopmental or neurodegenerative aetiology such as schizophrenia, bipolar disorder and Alzheimer's disease.
L-Homocysteine thiolactone (L-HCTL) was evaluated for its potential as an intravenously-administered central nervous system (CNS) radioprotector in C3H mice and F344 rats. Toxicity assessments in the mouse yielded a LD50 of 297 mg/kg and in the rat 389 mg/kg. Biodistribution studies in tumor-bearing mice showed that brain specimens contained more label at 10 min than the tumors but less at 30 or 60 min. Brain uptake relative to the tumors, the brain/tumor ratio, ranged between 0.5 and 3.3. The cervical spinal cord of non-tumor-bearing rats was irradiated with 32 Gy 137Cs with or without prior treatment with L-HCTL following which the time to forelimb or hindlimb paralysis was measured to determine the relative protective factors (RPFs) for this radiation dose. For forelimb paralysis the RPF was 1.9 (+/- 1.0, SD) and for hindlimb it was 2.0 (+/- 1.1, SD). 36B-10 glioma cells irradiated in vitro with or without L-HCTL and assayed for colony forming capacity demonstrated a dose modifying factor (DMF) of only 1.15 (+/- 0.16, SE). Rats bearing intracerebral 36B-10 glioma received 137Cs irradiation with or without L-HCTL after which the tumors were similarly assayed in vitro. From this the glioma DMF was 1.2 (+/- 0.30, SE). Compared to prior results with phosphorothioates our data show that the toxicity of L-HCTL is roughly the same as WR2721, WR77913 and WR3689 and that it distributes at higher levels in the CNS after systemic administration. L-HCTL may well equal these phosphorothioates at protecting normal CNS tissue without requiring administration directly into the cerebrospinal fluid-containing spaces and it does not protect the 36B-10 glioma.
We measured levels of immunoreactive insulin (IRI) and proinsulin using a sensitive and specific immunoradiometric assay (IRMA), in non-obese recently diagnosed type 2 diabetic subjects. The proinsulin IRMA showed full cross reaction with intact proinsulin, des 31-32 proinsulin and des 64-65 proinsulin, but no reaction with insulin or C-peptide. In a group of 41 recently diagnosed non-obese Caucasian type 2 diabetic subjects (study group), mean fasting proinsulin levels were greater than that of 40 age and body mass index (BMI) matched controls (study group 17.4 +/- 2.0, controls 10.1 +/- 0.9 pmol-1, P < 0.001). Following a standard test meal, 30 and 60 min levels were not significantly different between groups but 90- and 120-min proinsulin levels were elevated in the study group. The maximum proinsulin to IRI ratio was 20% in the fasting state and did not differ between study and control groups. Proinsulin profiles were similar in subjects receiving oral hypoglycaemic agents and those on dietary treatment alone. Proinsulin did not correlate with indices of glycaemic control, total cholesterol, triglycerides or HDL cholesterol, but a relationship was observed with IRI before and after the meal. These results suggest that increased secretion of insulin precursors of low biological activity occurs in non obese recently diagnosed type 2 diabetic subjects under reasonably good glycaemic control; in such individuals the elevated levels of these precursors are approximately in proportion to the increase in IRI and are less than those reported in some previous studies.
We have developed a computer model of chest-mounted counterlungs, which accounts for counterlung shape, effective volume, and pressure centroid. The model has been validated and the principles are applicable to other counterlung systems. The highly non-linear and discontinuous behavior of a counterlung is predicted by use of a sophisticated numerical integration method that computes variables such as pressure and volume in the time domain. Three separate stiffness (reciprocal of compliance) terms have been used which contribute to the diver's work of breathing: material elastic stiffness, "gas" stiffness, and "hydrostatic" stiffness. The model provides a significant advance in the understanding of counterlung behavior, allowing the performance of practical equipment to be predicted.
The possibility that the ACE inhibitors, enalapril and captopril, may decrease plasma EPO concentrations was studied in a single-blind, cross-over study in 10 healthy volunteers. Plasma EPO concentrations, haemoglobin concentration, red blood cell count, plasma creatinine concentration and mean arterial pressure were measured at baseline and after 28 days treatment with both ACE inhibitors. A significant fall in mean plasma EPO concentration occurred with both ACE inhibitors and returned to baseline after stopping the drugs. It is likely that ACE inhibitors decrease EPO formation, by inhibition of angiotensin-II production. This effect could be important in patients with renal failure, renal transplantation or other chronic conditions with an associated anaemia. Haematological parameters should be monitored in such patients when they are treated with an ACE inhibitor.
We developed a fluorometric assay for endopeptidase-24.11 (EC 3.4.24.11) in human plasma. Substrate [glutaryl-Ala-Ala-Phe-amidomethylcoumarin(AMC)] was incubated with plasma (20 microL, 30 min, pH 7.6) with (control) or without the endopeptidase-24.11 inhibitor phosphoramidon. Further incubation with aminopeptidase M released free AMC. Within-assay CVs were 4.5% and 8.6%, respectively, at 3.31 and 0.27 nmol of AMC released per milliliter per minute. The between-assay CV was 10.4% at 0.31 nmol/mL per minute and the detection limit was 0.05 nmol/mL per minute. A highly skewed distribution of endopeptidase-24.11 in 41 normal samples was found, ranging from 0.12 to 6.84 nmol/mL per minute (median = 0.44). Mean endopeptidase-24.11 concentrations were significantly higher in hypertensive subjects (0.68 nmol/mL per minute) than in normotensive subjects (0.34 nmol/mL per minute; P less than 0.05). Compared with placebo administration, the oral endopeptidase-24.11 inhibitor UK 79300 significantly inhibited the plasma enzyme at doses of 100 mg (twice daily). Although in normotensive subjects the enzyme was unaffected with doses of 25 mg, the same dose (25 mg) inhibited the plasma enzyme in hypertensive subjects. No activity was detected in sheep plasma, but addition of exogenous endopeptidase-24.11 to sheep plasma in vitro allowed in vivo assessment of the effect of infused endopeptidase-24.11 inhibitor SCH 39370.
A short-term training program involving 2 h of daily exercise at 59% of peak O2 uptake (VO2max) repeated for 10-12 consecutive days was employed to determine the significance of adaptations in energy metabolic potential on alterations in energy metabolism and substrate utilization in working muscle. The initial VO2max determined before training on the eight male subjects was 53.0 +/- 2.0 (SE) ml.kg-1.min-1. Analysis of samples obtained by needle biopsy from the vastus lateralis muscle before exercise (0 min) and at 15, 60, and 99 min of exercise indicated that on the average training resulted (P less than 0.05) in a 6.5% higher concentration of creatine phosphate, a 9.9% lower concentration of creatine, and a 39% lower concentration of lactate. Training had no effect on ATP concentration. These adaptations were also accompanied by a reduction in the utilization in glycogen such that by the end of exercise glycogen concentration was 47.1% higher in the trained muscle. Analysis of the maximal activities of representative enzymes of different metabolic pathways and segments indicated no change in potential in the citric acid cycle (succinate dehydrogenase, citrate synthase), beta-oxidation (3-hydroxyacyl CoA dehydrogenase), glucose phosphorylation (hexokinase), or potential for glycogenolysis (phosphorylase) and glycolysis (pyruvate kinase, phosphofructokinase, alpha-glycerophosphate dehydrogenase, lactate dehydrogenase). With the exception of increases in the capillary-to-fiber area ratio in type IIa fibers, no change was found in any fiber type (types I, IIa, and IIb) for area, number of capillaries, capillary-to-fiber area ratio, or oxidative potential with training.(ABSTRACT TRUNCATED AT 250 WORDS)
The haemodynamic and hormonal responses of patients with autonomic neuropathy and others with adrenomedullary deficiency were compared with mild hypertensives (range of blood pressure 90-100 mmHg diastolic and 140-160 mmHg systolic) and uncomplicated diabetics during standard exercise and postural manoeuvres using continuous arterial blood pressure monitoring. There was no difference in these parameters between the groups when at rest or on standing. During exercise there was no significant difference in blood pressure and heart rate between the groups and all showed significant increases in plasma noradrenaline (mean rise for all groups 2730-22 105 pm 1(-1), P less than 0.03) and (in all but the adrenalectomized subjects) adrenaline (mean rise for remaining three groups 946-3384 pm 1(-1), P less than 0.03; adrenalectomized group showed no rise). The group with autonomic neuropathy showed a significant rise in plasma cortisol from basal 450 +/- 40 to 845 +/- 72 nm 1(-1), P less than 0.005 after exercise, but the other groups showed no significant change. The maximum level attained for plasma cortisol in the adrenalectomized subjects after exercise was significantly less (260 +/- 41 nm 1(-1) than in the diabetic groups (696 +/- 68 nm 1(-1) (non-neuropaths), 845 +/- 72 nm 1(-1) (neuropaths), P less than 0.01). We have demonstrated normal blood pressure and pulse responses to posture and sustained exercise in diabetics with autonomic neutropathy. The findings of similarly normal responses in patients with adrenomedullary deficiency suggest that circulating adrenaline is not obligatory to a normal haemodynamic response to exercise.
The inhibitory and stimulatory effects of somatostatin analogues on growth hormone secretion have been studied in the sheep. Plasma immunoreactive growth hormone (GH) was stimulated by the iv administration of the antilipolytic compound 3,5-dimethylpyrazole and was followed by infusion of somatostatin (SRIF) and analogues into the carotid artery. The analogues D-trp8-D-cys14-SRIF, des-AA1,2,4,5,12D-trp8-D-cys-14SRIF, and SRIF-Wy 40793 were shown to cause a dose-dependent suppression of plasma GH, followed by a significant rise ("rebound") on terminating the infusion. In general, the greater the suppression, the greater the rebound. A significant correlation between the rebound increase in plasma GH and dose of both SRIF and des-AA1,2,4,5,12D-trp8-cys14-SRIF was demonstrated (p less than 0.01 and p less than 0.001, respectively). This analogue and Wy-40793 showed a significantly greater rebound than did SRIF following 50% suppression of the GH response (p less than 0.01 and p less than 0.05, respectively). Although two analogues were shown to be significantly more potent than SRIF (p less than 0.01), in this sheep bioassay the duration of action did not appear to be longer than that of the native hormone for any of the three analogues.
Plasma insulin was measured fasting and after iv glucose in fifteen newly diagnosed non-grossly obese non-insulin dependent diabetics. Two-thirds had normal fasting insulin (less than 13 mU/L) and all had sub-normal responses to iv glucose. There was no significant correlation between fasting or stimulated insulin concentrations and body weight. Six subjects with totally "flat" response to iv glucose were tested after a standard 4MJ meal and after 75 g oral glucose. They now showed normal profiles of later phase insulin release to the meal test or oral glucose and a significant increase in early phase insulin concentration, but this response was still blunted when compared with control subjects. We conclude that for non-grossly obese NIDDs (1) insulin deficiency is a common and important disorder and (2) there may be a loss of beta cell sensitivity to blood glucose with retention of sensitivity to gut mediated factors.
The 41-residue ovine corticotropin releasing factor (CRF) was administered iv and intracerebroventricularly (icv) to merino sheep. A significant rise in plasma ACTH, beta-lipotropin (beta LPH) and cortisol was demonstrated after the administration of 200 micrograms, iv. A highly significant correlation between the increments in plasma ACTH and beta LPH was observed. The plasma ACTH rise was evident within 5 min and was abolished by the prior administration of 0.4-4.0 mg dexamethasone. No significant rise in plasma GH, LH, PRL, insulin, glucagon, pancreatic polypeptide, met-enkephalin, angiotensin II, aldosterone, or vasopressin could be demonstrated. Although smaller doses of CRF (50 ng to 5 micrograms) were effective when given icv, the ACTH response was more delayed. It is concluded that CRF stimulates a rapid increase in the secretion of ACTH and beta LPH in sheep. Suppression of this response by dexamethasone indicates that glucocorticoids are capable of acting on the pituitary to inhibit the ACTH response to CRF. The delayed response when CRF is given icv may be due to diffusion. The action of CRF appears to be relatively specific, in that the plasma concentrations of the other pancreatic, pituitary, and adrenal hormones measured were not affected.
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Acetylcholinesterase (AChE) was measured in the cerebrospinal fluid (CSF) of patients with a diagnosis of Huntington's disease, depression, schizophrenia, or mania and also in the CSF of normal subjects. No significant differences in CSF AChE were found between any diagnostic group and normal subjects. Furthermore, the administration of choline chloride, physostigmine, or probenecid did not significantly alter CSF AChE. No diurnal variation in CSF AChE activity was apparent. These findings, combined with the unclear relationship of brain AChE to CSF AChE, suggest that this measurement does not reflect the relative cholinergic underactivity presumed to exist in some neuropsychiatric conditions.