Biomedical subjects
T J Stephenson
Publications and source records attributed to T J Stephenson.
Mutant p53 oncogene expression in keratoacanthoma and squamous cell carcinoma.
The tumour suppressor gene p53, located on the short arm of chromosome 17, encodes for a nuclear protein which regulates cell proliferation by inhibiting cells entering S-phase. p53 mutations are alleged to be the commonest genetic abnormality in human cancer. We studied mutant p53 oncoprotein expression, using PAb1801 monoclonal antibody immunohistochemistry, in 25 'ideal' keratoacanthomas and 26 well-, 19 moderately and 18 poorly differentiated squamous cell carcinomas of the skin. While there was a highly significant trend in the proportion of p53 oncoprotein-positive lesions from keratoacanthomas to poorly differentiated squamous cell carcinomas (chi 2 = 17.13, df = 1, exact P = 0.00003), p53 expression was inadequate for distinguishing keratoacanthoma from well-differentiated squamous cell carcinoma (chi 2 = 2.55, df = 1, exact P = 0.18; corresponding to a sensitivity of 0.84 and a specificity of only 0.36).
Histopathology for minor surgery.
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Evaluation of techniques for delivery of steroids to lungs of neonates using a rabbit model.
Little is known about delivery of aerosolised steroids to neonatal patients undergoing assisted positive pressure ventilation and after extubation. A rabbit model has been established to investigate factors influencing drug delivery. Beclomethasone dipropionate, in a metered dose inhaler, was radiolabelled with technetium 99m. The mass median aerodynamic diameter of the aerosol was 3.3 (2.0) microns and the impactor measurements confirmed that the technetium distribution corresponded with that of the drug particles. The metered dose inhaler was actuated into a collapsible spacer that was used to ventilate and deliver aerosol to anaesthetised rabbits by a tracheostomy. From each actuation of the drug 2.9 (0.4)% of the aerosol deposited in the trachea and main bronchi and 1.2 (0.4)% in the lung. When the drug was delivered by a spacer device, with face-mask attachment, to rabbits breathing freely through a tracheostomy, aerosol deposition increased to 4.4 (2.1)% in the trachea and main bronchi and 1.9 (0.9)% in the lung lobes. The maximum change in systolic blood pressure after administration of aerosol by the collapsible spacer was a decrease of 13%. The methods described may prove useful for the delivery of inhaled steroids to neonatal patients likely to develop bronchopulmonary dysplasia.
Factors influencing plasma renin and renin substrate in premature infants.
Concentrations of plasma renin (PRC) and plasma renin substrate (PRS) were measured during the first week of life in 52 infants born at less than 37 weeks' gestation (mean (SEM) gestation 30 (0.4) weeks, mean (SEM) birth weight 1.35 (0.08) kg). Both PRC (median 35, interquartiles 16.3, 94.5 ng/ml/hour) and PRS (median 2.3, interquartiles 1.3, 5.0 micrograms/ml) were raised compared with adults. The proportional rise in PRC was much greater than that in PRS, suggesting that PRS may be rate limiting in the generation of angiotensin I. Log10 PRC was inversely proportional to gestational age and a high urinary sodium loss was associated with a significantly raised log10 PRC. In hypoxaemic infants, there was a strong correlation between log10 PRS and haemoglobin concentration; this is a new observation in human infants but consistent with data available from other species.
A dose ranging study of ibuprofen suspension as an antipyretic.
A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic.
Primary leiomyosarcoma of the liver.
A case of primary leiomyosarcoma of the liver is described and the problems in diagnosis and management are discussed together with a review of the available literature. These tumours have a favourable prognosis when diagnosed preoperatively and the value of electron microscopic findings in this situation are highlighted.
Assessment of osteopenia at autopsy.
Osteoporosis is a common problem for the pathologist in the elderly female population where pathological fractures particularly of the neck of femur are frequent. Yet how should we assess osteoporosis at autopsy? This study reports on autopsy assessment of osteopenia, comparing our subjective findings of rib fracturability and vertebral compressibility with histological and histomorphometric assessment on a bone biopsy. We have shown a poor correlation between gross autopsy and histological techniques. There is good correlation between two gross autopsy techniques and these methods have been shown to be reproducible between observers. We believe that the most useful test of whether a patient's bones are likely to break is to assess the fracturability of the ribs (and possibly the vertebral bodies) at autopsy. This should be supplemented with undecalcified histology sections from the iliac crest where possible. Further studies are clearly warranted in this area.
Effects of altering umbilical flow and umbilical free fatty acid concentration on transfer of free fatty acids across the rabbit placenta.
The transfer of free fatty acids across the placenta perfused in situ was studied in anaesthetized rabbits in late gestation. In the first series of experiments, umbilical flow rate was varied between 0.6 and 4.0 ml/min in nine rabbits. Although increasing umbilical flow rate significantly decreased the free fatty acid concentration in the umbilical venous effluent (P = 0.0001), placental clearance of free fatty acids from the maternal circulation was not significantly changed by alterations in umbilical flow rate. In the second series of experiments, the materno-fetal free fatty acid concentration gradient was varied between + 1.58 mmol/l and -2.81 mmol/l in eight rabbits. There was a significant relationship between increasing materno-fetal gradient and increasing transfer of free fatty acids across the placenta (P less than 0.001). Moreover, net transfer of free fatty acids into the umbilical circulation was observed even with zero concentration gradient. Net transfer of free fatty acids from fetus to mother occurred when umbilical arterial free fatty acid concentration exceeded maternal arterial concentration by 1.3 mmol/l.
Factor XIIIa positive cells in granulomatous lymph node lesions.
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Atrial natriuretic factor: the heart as an endocrine organ.
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D(+)-glyceric aciduria: etiology and clinical consequences.
A family comprising mother, father, and five children is described. Four of the children were found to excrete massive amounts of D(+)-glyceric acid in their urine. This was verified by gas chromatography-mass spectrometry and the configuration determined by capillary gas chromatography of O-acetylated menthyl esters. The excretion ranged from 10.8 to 19.9 mmol/24 h. The remaining child and the parents showed no evidence of this unusual metabolite. The virtual absence of clinical manifestations in this family was particularly interesting. Only two of the children showed any clinical abnormality and this was limited to mild microcephaly and speech delay; the other two children found to excrete large amounts of D(+)-glycerate were healthy and developmentally normal at 7 y and 9 y of age. There was a marked increase in the excretion rate of D(+)-glycerate in response to both oral fructose and serine loading. These results are consistent with a deficiency of D(+)-glycerate kinase and indicate the potentially benign nature of this disorder.
A double-blind dose-ranging trial with paediatric ibuprofen.
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Maternal to fetal transfer of free fatty acids in the in situ perfused rabbit placenta.
The transfer of free fatty acids (FFA) across the placenta perfused in situ was studied in anaesthetised rabbits in late gestation. [14C]Palmitic acid and antipyrine were infused into 11 pregnant rabbits and samples collected for up to 90 min from the mother and the umbilical vessels. Levels of total FFA, radioactivity and antipyrine, a marker of placental integrity, were measured. Net FFA flux across the placenta increased with maternal FFA concentrations, confirming observations made using different methods. The specific activity of [14C]palmitic acid in perfusate also related to maternal levels and indicated that almost half of the FFA crossing the rabbit placenta must be derived from sources other than circulating maternal FFA. The composition of the perfusate FFA had a profile similar to that of circulating maternal FFA, except for an increase in a number of long chain, polyunsaturated fatty acids. These findings are consistent with maternal triacylglycerol as the other fatty acid source, with the placenta adding the longer chain, polyunsaturated fatty acids.
Short-term effects of extracorporeal shock wave lithotripsy on the human gallbladder.
Extracorporeal shock wave lithotripsy (ESWL), whereby shock wave energy is focused upon gallstones causing their disintegration into fragments sufficiently small to be passed via the biliary system, offers a promising non-invasive alternative to surgery for gallstone disease. The tissue effects in humans of ESWL are poorly characterized and no systematic study of the tissue effects of ESWL by piezoelectrically generated shock waves has been published. Sixteen patients for elective cholecystectomy were therefore subjected to ESWL before surgery and detailed histology of the gall-bladders (including scanning electron microscopy of the mucosa) was compared with that from 20 age/sex-matched control cases. The gall-bladders treated by ESWL, in addition to showing the histological changes associated with chronic cholecystitis, showed serosal vasodilatation, mural oedema, and serosal and mucosal petechial haemorrhages focally over the entire surface. Between 10 and 90 per cent epithelial denudation was observed, but all cases showed surviving columnar epithelial cells in the crypts. No case showed vascular thrombosis, tissue necrosis, or acute inflammation. These tissue effects are likely to be reversible and unlikely to present a risk of perforation, although the long-term clinicopathological effects await investigation.
Piezoelectric shockwave fragmentation of biliary calculi.
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