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Biomedical subjects

A Wilton

Publications and source records attributed to A Wilton.

15 recordsLinked to original sources

Predictability of designing specific binding interactions for DNA minor groove ligands from NMR spectroscopy and molecular modeling: a copper(II)-activated DNA cleaver based on Hoechst 33258.

Analogs of Hoechst 33258 have been designed and synthesized to incorporate a 3,4-catecholic or a 3,4,5-trihydroxyphenyl function in place of the 4-phenolic group of the template molecule. Molecular design was based on the three-dimensional models of the solution structures of the Hoechst 33258 and its m-hydroxy isomer which had been derived from high-field NMR spectroscopic analysis. The predicted solution structure of the catecholic analog as its minor groove complex with duplex d(CGCGAATTCGCG)2 was confirmed by direct high-resolution NMR spectroscopy combined with molecular dynamics, using NMR-derived distance restraints. While the 3,4-catecholic analog was unable to cleave DNA in the presence of Cu(II) ions, the 3,4,5-trihydroxyphenyl analog of Hoechst 33258 was found to be an effective cleaver of DNA at low concentration when activated by copper(II) ions, a difference ascribed to the inaccessibility for copper chelation of the 3,4-dihydroxy site in its minor groove complex with DNA.

Base Sequence↗

Endoscopic intubation of oesophago-gastric malignancy.

OBJECTIVE: To determine what percentage of inoperable oesophageal and oesophagogastric malignancies could be successfully intubated for palliation, and to compare Atkinson and Celestin tubes. DESIGN: A consecutive series of 210 patients who had been referred for palliation underwent endoscopy and intubation with the Nottingham introducer. PATIENTS: One hundred and nineteen men and 91 women aged 31-91 (mean age 71) years with inoperable malignant obstruction of the oesophagus or gastro-oesophageal junction were studied. One hundred and five tumours were in the lower third of the oesophagus, 78 in the middle third, 25 in the upper third and seven in the gastric fundus. Four tracheo-oesophageal fistulae resulting from bronchial carcinomas were also successfully intubated. MAJOR OUTCOME MEASURE: Eighty-nine per cent of gastro-oesophageal malignancies were successfully intubated using 120 Atkinson and 67 Celestin tubes. RESULTS: Eleven patients (5.2%) suffered oesophageal perforations during intubation, of whom six died. Nine of the perforations occurred in the first 100 patients treated but only two (2.3%) in the subsequent 87. Seven patients (3.7%) developed aspiration pneumonia, of whom five died. The mean survival time after intubation was 4.5 months (range 0.5-20 months), and 74% of patients required no further procedure. During follow-up, five (4.2%) Atkinson tubes displaced upwards, compared with 12 (17.9%) Celestin tubes (P < 0.01). Eighteen (9.6%) patients had recurrent dysphagia as a result of bolus obstruction and 11 (5.9%) had tumour overgrowth of the tube. CONCLUSION: Palliative intubation of malignant dysphagia is possible in approximately 90% of patients. The mortality associated with the procedure is low (5%) and effective relief of symptoms is achieved, with 74% of patients requiring no further treatment.

Aged↗

Continuing need for mineralocorticoid therapy in salt-losing congenital adrenal hyperplasia.

Four patients with salt-losing congenital adrenal hyperplasia (CAH) who had stopped mineralocorticoid therapy for several years, showed raised plasma concentrations of 17OH-progesterone and plasma renin activity, despite adequate glucoticoid therapy. One patient was able to reduce urinary sodium excretion when the sodium intake was restricted. Another patient who was a salt-loser, developed signs of an adrenal crisis when salt deprived. In comparison, one nonsalt-loser and 2 normal subjects decreased urinary sodium excretion in response to sodium restriction. The addition of fludrocortisone (100 micrograms) to usual maintenance doses of glucocorticoid, resulted in normal levels of plasma 17OH-progesterone and plasma renin activity in all 4 salt-losers. Two female salt-losers, with raised plasma testosterone concentrations, began menstruating when their plasma testosterone concentrations returned to normal after treatment with fludrocortisone. It is recommended that salt-losing CAH patients should be given mineralocorticoid, in addition to glucocorticoid therapy, at least until adult life.

Adolescent↗

The variation in contact angle of fissure sealant on enamel surfaces.

For strong adhesion of ultraviolet initiated polymeric fissure sealants to dental enamel, a well-formed tag structure is necessary. This requires that the unpolymerized sealant must be able to flow quickly into the etched surface before polymerization is initiated. The variation in contact angle, O, with time (the spreading ability) of unpolymerized Nuva-Seal has been measured on unetched, etched and moist enamel surfaces. This spreading ability varies with the condition of the surface. It is estimated that, in the system investigated, the roughness of the enamel surface is increased by up to 13% on etching, but is reduced again if moisture is present, due to condensation into the etch pits. An etched, moisture free enamel surface is therfore necessary for strong adhesion of polymeric materials.

Acid Etching, Dental↗

Radioimmunoassay of unprocessed sheep blood extracts to follow angiotensin metabolism.

The acceptability of radioimmunoassay to determine the levels of compounds antigenic to anti-angiotensin antibodies, in unprocessed methanolic blood extracts, was established for sheep blood. This approach was used to follow the clearance of antigenic compounds after administration of angiotensins I and II and fragments of angiotensin II in anesthetized sheep. The organs supplied by the systemic circulation and also the lungs effectively removed angiotensin I, but the removal of octapeptide occurred only in the peripheral tissues. The blood concentrations of compounds reacting with the anti-angiotensin II antibody always increased with passage of angiotensin I through the pulmonary circulation but not with passage of angiotensin II. The results indicate that factors other than efficiency of removal by the tissue is important in establishing blood levels. The sites of administration and of sampling were shown to be important in relation to ratios of the concentrations of antigenic material. There was a similar uptake of both hormones in the kidney; the relative inability of angiotensin I to reduce renal blood flow, therefore, does not result from a failure of uptake.

Angiotensin I↗

The pattern reversal VEP in short-gestation infants.

Visual evoked potentials (VEPs) to pattern reversal stimulation have been obtained in 10 premature babies. The babies were born between 32 and 35 weeks gestational age and had pattern reversal VEPs recorded on at least 2 separate occasions. The responses were obtained from 33 weeks gestational age, and all babies had their initial recording at or before 37 weeks gestational age. The pattern reversal stimulation was produced on a small hand-held television monitor. The black and white checks subtended a visual angle of 2 degrees. Flash VEPs were also recorded on each occasion for comparison. The pattern reversal response consisted of a major positive (P1) component around 280 msec. The latency of the P1 component correlated negatively with gestational age. Although the flash VEP in the same babies was often dominated by the initial negative component no similar negative components were seen in the pattern reversal response.

Evoked Potentials, Visual↗