Reciprocity and licensure by credentials--European style.
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Biomedical subjects
Publications and source records attributed to N Davies.
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The histone-DNA contacts in the 167 bp 2-turn core particle have been compared with those in the 146 bp 1.75-turn core particle by the methodology developed by Mirzabekov and his colleagues. The contacts in the 167 bp 2-turn core particle retain the essential features of those in the 146 bp 1.75-turn core particle but contacts for histones H3 and H2A were found in the 10 bp extension that discriminates the two particles. In addition the contact for histone H2A near the dyad axis was far more pronounced in the case of the 146 bp core particle.
The preparation of hybrid histone octamers with wheat histone H2A variants replacing chicken H2A in the chicken octamer is described. The fidelity of the reconstituted hybrid octamers was confirmed by dimethyl suberimidate cross-linking. Polyglutamic-acid-mediated assembly of these octamers on long DNA and subsequent micrococcal nuclease (MNase) digestion demonstrated that, whereas chicken octamers protected 167 base-pairs (representing 2 full turns of DNA), hybrid histone octamers containing wheat histone H2A(1) with its 19 amino acid residue C-terminal extension protected an additional 16 base pairs of DNA against nuclease digestion. The protection observed by hybrid histone octamers containing wheat histone H2A(3) with both a 15 residue N-terminal and a 19 residue C-terminal extension was identical with that observed with H2A(1)-containing hybrid histone octamers with only the 19 residue C-terminal extension. These results suggest that the role of the C-terminal extension is to bind to DNA of the "linker" region. The thermal denaturation of chicken and hybrid core particles was identical in 10 mM-Tris.HCl.20 mM-NaCl, 0.1 mM-EDTA, confirming that there was no interaction between the basic C-terminal extension and DNA of the core particle. Denaturation in EDTA, however, showed that hybrid core particles had enhanced stability, suggesting that the known conformational change of core particles at very low ionic strength allows the C-terminal extension to bind to core particle DNA under these conditions. A model accounting for the observed MNase protection is presented.
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A series of 34 children with 40 primary refluxing ureters were treated endoscopically with a subureteric injection of polytetrafluoroethylene paste (Polytef). The amount injected ranged between 0.1 and 0.8 ml (mean 0.3). A single injection cured the reflux in 26 ureters (65%) and the grade of reflux improved in a further 9 ureters. Seven ureters required a second injection and reflux was cured in 6 of these. The overall cure rate was therefore 80% after the second injection. There was one complication due to self-limiting ureteric obstruction following injection. The procedure is quick, easy to perform and effective. We have some reservations about the long-term efficiency and safety of subureteric Polytef injection in children.
In 104 severely growth-retarded fetuses, the mean white blood cell count (WBC), as well as neutrophil, lymphocyte and monocyte counts were reduced. Furthermore, the severity of the leucopenia was significantly related to the degree of fetal 'smallness' and anaemia. These findings suggest that leucopenia observed in growth-retarded neonates may be a consequence of intra-uterine starvation due to deficiency of haematinics.
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Oestrogen receptor status has been determined by an immunocytochemical assay using fine-needle aspiration samples of primary breast cancers in elderly patients. In a prospective study 56 patients were treated with tamoxifen only. Satisfactory assays were achieved in 49 patients. Disease was controlled by tamoxifen in 32 of 35 (91%) patients with oestrogen receptor positive tumours, compared with only 1 (7%) of 14 who were receptor negative. Immunocytochemical assay on fine-needle aspiration samples is relatively non-invasive and simple to perform, it accurately predicts response to tamoxifen in elderly patients and can be used to select patients for tamoxifen only therapy.
Eighty-five cases of irreducible inguinal hernia in children below 2 years of age were reviewed. Non-operative treatment was successful in 71 (84 per cent); 14 children required emergency surgery. The younger the child and the longer the duration of symptoms at presentation, the worse was the outcome of non-operative treatment. In 35 (41 per cent) children the diagnosis of inguinal hernia had been made before irreducibility. There is an increased incidence of postoperative complication associated with irreducibility, especially in preterm infants. Early diagnosis of inguinal hernia in young children and prompt referral for surgery is recommended.
In vivo nuclear magnetic resonance (NMR) spectroscopy was used to define several intracellular high energy phosphate variables of the gastrocnemius muscle of normal subjects during rest, graded plantar flexion exercise to exhaustion, and recovery. There were nine males and eight females with an average age of 34 +/- 8 years. At rest, pH averaged 7.09 +/- 0.03 and the energy cost index (ECI)--the ratio of inorganic phosphate to phosphocreatine--averaged 0.13 +/- 0.03. At peak exercise, the ECI increased markedly to 2.71 +/- 2.0 (P less than 0.001) and pH fell precipitately to 6.76 +/- 0.17 (P less than 0.001), indicating the high intensity of the exercise. Exercise endurance averaged 12 +/- 5 mins; it was not highly correlated with sex, age (r = 0.35), rest pH (r = 0.26), rest ECI (r = 0.38), peak exercise pH (r = 0.23) or peak exercise ECI (r = 0.38), nor exercise changes in pH (r = 0.17) and ECI (r = 0.28). At 23 mins post exercise all variables were similar to rest. Rest pH was the only variable different between males (7.10 +/- 0.03) and females (7.07 +/- 0.03) (P less than 0.05). Thus, dynamic exercise of large skeletal muscles in normal subjects was characterized by marked temporal changes in high energy phosphate profiles and very low pH at exhaustion. No single metabolic variable correlated highly with exercise endurance, suggesting that the intracellular pathophysiology of exhaustive muscle exercise and clinical fatigue may be multifactorial.
Although the EEG suffers from limited diagnostic significance it is a useful adjuvant to diagnosis and demands for the examination are increasing. Three hundred consecutive referrals to one unit are analysed.
In total, 103 cases were randomly selected from the Groningen, Nottingham and South Verona registers. Six raters (two in each of the register areas) were involved in coding these cases according to the ICD-9. In general, interrater agreement was satisfactory when codes were grouped into a limited number of categories. Nevertheless, considerable variation in agreement rates was found. We distinguished three steps in the diagnostic process. The selected logistic model showed that reliability is significantly affected in each step, but only substantial in the first where clinicians formulate a diagnosis.
1. Single doses of 1,2,4-trimethylbenzene (124TMB) or 14C-124TMB were administered orally to rats for metabolism and distribution studies. 2. 14C-124TMB was rapidly and widely distributed throughout the body with the highest levels in adipose tissue. No other preferential uptake of 14C-124TMB by any of the organs or tissues examined was evident. 3. Tissue levels declined rapidly within 24 h after dosage, with more than 99% of the administered radioactivity recovered in the urine during this period. 4. A complex mixture of isomeric trimethylphenols, dimethylbenzyl alcohols, dimethylbenzoic acids and dimethylhippuric acids excreted in the urine accounted for more than 81% of the administered dose. The major metabolites were 3,4-dimethylhippuric acid (30.2% dose), 2,4-dimethylbenzyl alcohol (12.7% dose, primarily as sulphate and glucuronide conjugates) and 2,5-dimethylbenzyl alcohol (11.7% dose, primarily as sulphate and glucuronide conjugates).
In a randomized, single-blind trial, 78 women having vaginal termination of pregnancy were treated with either a 1-mg gemeprost (Cervagem) pessary or a Lamicel tent inserted 3-4 h before operation. Both agents produced satisfactory cervical softening but dilatation was significantly easier after gemeprost. Pre-operative side-effects were more frequent after gemeprost but did not increase the need for analgesia. There were no differences between the two groups with regard to either postoperative symptoms and analgesic requirements or pre-operative and postoperative temperature, pulse rate and blood pressure. Gemeprost pessaries are easier, faster and less uncomfortable to administer.
The effect of nifedipine on uteroplacental blood flow was investigated in nine hypertensive women in the trimester of pregnancy and compared with the effects of a placebo in nine similar hypertensive women. An index of uteroplacental blood flow was obtained, twice before treatment and once after treatment, by measuring the increase in radioactivity in the region of the placenta with a gamma camera following an intravenous injection of indium-113m. There was no significant change in the blood flow index in either the nifedipine- or the placebo-treated groups despite a significant fall in blood pressure with nifedipine. Nifedipine lowers the blood pressure without any apparent reduction in uteroplacental blood flow.
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Neurological and cognitive deficits occur in many chronic alcoholic patients. Quantitative studies reveal a significant reduction in the number of neurons in the superior frontal gyrus of chronic alcoholics, with no change in the motor cortex. Our studies are aimed at delineating which neurotransmitter systems are altered in alcoholics and to correlate these alterations with morphometry and, where possible, clinical signs. Much evidence suggests both short- and long-term effects of ethanol on GABA-mediated neurotransmission. GABA and benzodiazepines bind to distinct, but allosterically linked, sites on the GABA/benzodiazepine receptor complex. In the absence of any detected difference in the number of benzodiazepine receptors in both the frontal and motor cortex from alcoholic and control patients, a significant increase in the amount of GABA enhancement of [3H]diazepam binding was measured in frontal cortex membranes from patients with Wernicke's encephalopathy relative to non-alcoholic controls. This finding suggests an increased coupling of the GABA and benzodiazepine recognition sites in this area, which may be due to ethanol-induced conformational changes in the receptor complex.