Measurement of true glomerular filtration rate in renal transplant patients receiving cyclosporine.
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Biomedical subjects
Publications and source records attributed to A Wilkinson.
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The distance between the inferior surface of the occiput and the superior surface of the vault of the skull was measured weekly during the first nine weeks of life in 56 preterm but appropriately grown babies with birthweights less than 1850g. For seven babies with dilatation of the cerebral ventricles (shown by ultrasonography) the suboccipito-vault height increased above the 97th centile within the first five weeks of life, although over the same period the occipitofrontal head circumference did not exceed the 75th centile. In the only other baby with ventricular dilatation the suboccipito-vault height did not increase while therapy with frequent removal of lumbar cerebrospinal fluid was performed. Suboccipito-vault height is a sensitive early indicator of progressive dilatation of the cerebral ventricles, and may be of value in centres without ultrasound facilities.
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A new delta-selective opiate antagonist has been synthesised in which the two glycine residues of diallyl leucine enkephalin have been replaced by 4-aminobenzoic acid. The compound has a different conformation to that of ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu).
Dry powdered surfactant was used in two randomised, controlled trials to study its immediate effects, influence on mortality, and safety in babies born after less than 32 weeks' gestation. The lecithin/sphingomyelin (L/S) ratio was measured in pharyngeal aspirate taken before surfactant therapy to establish surfactant deficiency. 32 babies intubated during resuscitation (trial I) and a group of 24 other babies, all with immature L/S ratios, in whom severe hyaline membrane disease developed (trial II), were stratified for sex. In half 25 mg surfactant was insufflated through the endotracheal tube; it could be detected in tracheal secretions for at least the next 24 h. There was no significant difference in ventilator pressures or oxygen therapy used nor in neonatal mortality and morbidity in the first 2 years of life between the surfactant-treated and control groups in either trial.
We reviewed infectious complications during 7,671 days of central venous (Hickman) catheter use in 47 patients receiving intensive cytotoxic and supportive therapy for malignant disease. Colonization of the catheter was identified in eight cases of septicemia, two associated with endocarditis. Septicemia was successfully treated in four of five patients after removal of the catheter and in two of three in whom the catheter remained in situ. Infection of the exit site occurred in five patients but in only one was there associated septicemia. Poor patient compliance with the recommended regimen for catheter care was suspected. Thus, the overall rate of catheter-related infection was 1.6 per 1,000 days. Guidelines are discussed for removal of the catheter for suspected catheter-related infection.
Cysts in the periventricular region of the brain were demonstrated by ultrasound in eight of 102 preterm infants (birthweight less than 1501g or less than 34 weeks gestation) during a 14-month period. All eight babies survived, but developed serious neurological problems: five had spastic quadriplegia and three had spastic diplegia. Six had impaired vision and six had delayed speech development, but there was no evidence of impaired hearing. The cysts probably represent the infarcted lesions of periventricular leukomalacia.
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To investigate the role of intravenously administered, radioiodinated peanut lectin (131I-PNA) in the non-invasive detection of cancer, the pharmacokinetics and scintigraphic distribution of this novel tumor-seeking compound were studied in 8 patients with metastatic cancer of the colon, breast or lung. Scintigraphic localization of 131I-PNA was apparent at certain anatomical sites of known metastases in 2 patients and in a further 2 patients an adjacent malignant pleural effusion was visualized. The rapid clearance of radioactivity from the whole body and plasma with marked renal concentration and rapid urinary excretion of significant amounts of intact 131I-PNA (mol. wt. 107,000, pI 5.95) implied that this molecule was excreted selectively by the renal tubules. PNA or other lectins may find a role in the scintigraphic detection of selected types of cancer.
Thirty preterm infants (gestational age 26 to 30 weeks) were investigated by cross sectional echocardiography using a 5 or 7.5 MHz transducer positioned in the suprasternal notch or the left subclavicular position to enable visualisation of the aortic arch, main pulmonary artery, left pulmonary artery, and ductus arteriosus. Each infant was investigated on at least one occasion during both the first and second weeks of life and when possible between the ages of 26 and 31 days. There was prolonged patency of the ductus arteriosus during the first two weeks of life in all infants, and complete closure of the ductus arteriosus occurred only in four patients, all of whom had reached a postconceptional age of 32 to 34 weeks. Eighteen infants received intravenous indomethacin between the age of 5 and 10 days. In these patients ductal narrowing did not occur until a maximum postconceptional age of 29 weeks.
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1H NMR spectra were obtained in fully deuterated dimethyl sulphoxide of sodium chondroitin 4-sulphate and of the tetrasaccharide, hexasaccharide and octasaccharide prepared from it. Two types of NH resonance were observed, at 7.6 ppm and 8.8 ppm. The latter was the only one in the polymer spectrum, whereas both were present in the oligomer spectra: N-acetylchondrosinate produced only the 7.6-ppm signal. The upfield resonance (7.6 ppm) is characteristic of "normal", monomeric acetamido sugars and disaccharides, while the downfield resonance (8.8 ppm) suggests a hydrogen-bonded NH. The elongation of disaccharide to tetrasaccharide produces a new environment, involving a hydrogen bond at the non-reducing disaccharide NH. A structure, with three hydrogen bonds per tetrasaccharide unit, is proposed which accounts for the quantitative and qualitative aspects of the NMR spectra of polymers and oligomers. A laser light-scattering study showed that sodium chondroitin 4-sulphate has the same molecular weight in water as in dimethyl sulphoxide. The observed hydrogen bonds are therefore intramolecular, as required by the proposed structure, and probably exist in water as well as in dimethyl sulphoxide.
Diallylation of the amino group of [Leu]enkephalin methyl ester yields a moderately potent, delta-selective opiate receptor antagonist. The diallyl congeners of a larger range of potent mu-and delta-selective enkephalin agonists have been prepared and were found to be weak, non-selective antagonists as assessed by their ability to antagonise the effects of normorphine and [Leu]enkephalin on the field-stimulated mouse vas deferens. Conversely, whereas [Gly3 psi (CH2S)Phe4,Leu5]enkephalin and [Gly3 psi(CH2S)-D-Phe4,Leu5]enkephalin are virtually inactive as opiate agonists the corresponding diallyl analogues are moderately potent, highly selective delta-antagonists. Analogues of diallyl[Leu]enkephalin in which the Gly2 and Gly3 residues have been replaced by D- and L- Ala have also been prepared and tested as delta-receptor antagonists. In addition, the empiric energy program ECEPP has been used to derive eighteen low energy conformations of diallyl[Leu]enkephalin and to estimate the effect of the D- and L-Ala substitutions on the conformer energies. Two conformers were identified for which there was a partial correlation between the variations in conformational energy and delta-antagonist potency.
Sialor, a sialogogue, was studied in a double-blind crossover trial in patients with autoimmune exocrinopathy (Sjögren's syndrome). Sialor appears to frequently alleviate the symptoms of xerostomia and increase salivary flow rate, and it is rarely associated with side effects. Sialor is useful in management of xerostomia in patients with Sjögren's syndrome and may also be of value in the treatment of xerophthalmia.
The effects of 300 micrograms of oral clonidine were studied in nine patients with unilateral renal artery stenosis proved by selective renal arteriography. Blood pressure, heart rate, plasma renin activity (PRA) levels, plasma noradrenaline levels, and sedation were measured before and for eight hours after dosage. After clonidine administration, both systolic and diastolic blood pressure fell within the first hour, was maximum in the fourth hour, and remained lower than predosage levels even in the eighth hour. There was a fall in heart rate, maximum in the fourth hour. There were minimal changes in PRA levels after giving the clonidine. Plasma noradrenaline levels fell, with the maximum fall in the sixth hour. Sedation occurred within one hour of dosage and was maximum in the second hour. We conclude that in patients with unilateral renal artery stenosis clonidine causes a substantial and prolonged fall in blood pressure not accompanied by suppression of PRA levels but by a reduction in plasma noradrenaline levels. This suggests a role for central pressor mechanisms, probably linked to angiotensin II and central sympathetic activation, in the maintenance of hypertension in patients with renal artery stenosis.