Graft-versus-host disease after orthotopic liver transplantation in a child.
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Biomedical subjects
Publications and source records attributed to S Humphreys.
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In investigating the interrelations of plasma acetate with glucose metabolism, we established that fasting plasma acetate levels (mmol/l) were greater in the diabetic than non-diabetic individuals (p less than 0.001). Plasma acetate and glucose levels correlated in all subjects (non-diabetic and diabetic) as a whole (rs 0.28, p less than 0.0001) and in the diabetics alone (rs 0.35, p less than 0.001). After i.v. glucose (20 g/m2 body surface area), plasma acetate levels increased further in the diabetic and non-diabetic individuals. Plasma acetate also increased when non-diabetic individuals consumed 75 g oral glucose. Moreover, while plasma acetate levels had returned to fasting values by 90 min in the non-diabetic subjects after oral and i.v. glucose, levels remained elevated in the diabetics after i.v. glucose. The K rate constant of glucose elimination after i.v. glucose in the diabetics correlated negatively with acetate values at many time points. In the non-diabetics, changing acetate and glucose levels after oral glucose also correlated at multiple time points. These results suggest that the plasma acetate level is influenced by variations in glycaemia and provide further evidence for an impaired rate of acetate metabolism in diabetes.
The occurrence of osteonecrosis following renal transplantation is well recognised but its pathogenesis remains unknown. We have quantified the number of empty osteocytic lacunae in the subchondral bone of femoral heads from a control group of patients, and compared these with femoral heads from a group of renal transplant recipients without evidence of overt osteonecrosis. There is a significant increase in empty osteocytic lacunae in renal transplant patients. We conclude that loss of osteocytes precedes other manifestations of osteonecrosis.
When 10 diabetic (five insulin-dependent) subjects with reasonable glycemic control were randomized from their usual (U) diet (about 30 g fiber/day) between two different but isocaloric high fiber diets, each sequentially over 6 wk [HF (55 g fiber/day) and HFS (55 g fiber/day with sucrose taken as 15 g three times daily, with meals)], plasma acetate (mmol/L) increased by 35% on both high fiber diets from 0.21 +/- 0.06 (SD) to 0.28 +/- 0.10 (HF) and 0.30 +/- 0.10 (HFS) (both p less than 0.01). This was higher than the random weekly variation in plasma acetate levels of 11% in six other glycemically stable diabetic patients. When the acetate value was expressed as acetate/glucose, i.e., relative to the fasting glucose level (since fasting levels of acetate and glucose consistently positively correlate), the increase was about 80%. Fasting plasma non-esterified fatty acid (NEFA) levels fell during the high fiber diets and correlated negatively with the fasting acetate level (rs -0.51, p less than 0.005). The fall in NEFA and rise in acetate levels appeared greatest with the sucrose-supplemented meals. These results suggest increased exogenous contribution to the plasma acetate level from increased colonic fermentation of dietary fiber and raise the possibility of using such measurements in the assessment of compliance to high fiber diets. The fall in NEFA levels associated with raised plasma acetate levels may contribute to the beneficial effects on glycemic control observed with the high fiber diets.
We measured plasma levels of acetate, glucose, insulin, fatty acids and 'ketone bodies' (KB), during fat infusion and continuous simultaneous infusion of insulin and glucose according to a computerized algorithm to maintain fasting euglycaemia and derive indices of tissue insulin sensitivity (hyperinsulinaemic euglycaemic clamping HEC). (i) Plasma acetate levels (mmol/l) approximately doubled (0.14 +/- (SEM) 0.02 to 0.25 +/- 0.02, p less than 0.01) during INTRALIPID infusion in 7 non-diabetic individuals while total 'ketone bodies' and non-esterified fatty acids (NEFAs) increased 10-fold. (ii) Early in the HEC, plasma acetate levels decreased as did NEFAs in 13 non-diabetic (0.17 +/- 0.01 to 0.12 +/- 0.01, p less than 0.001) and 9 diabetic (0.22 +/- 0.02 to 0.15 +/- 0.01, p less than 0.005) individuals. However while acetate levels later rose to fasting values in the non-diabetics, they remained low in the diabetics. NEFA levels were low throughout the clamp but glucose flux was increased as judged from the glucose infusion even with maintained euglycaemia. The change in acetate values during the second hour of the clamp correlated with neither BMI nor two indices of insulin sensitivity (glucose metabolic clearance rate and steady state glucose infusion rate). These results accord with acetate production from glucose and fat oxidation, via acetyl CoA. The differing metabolism of acetate in the second hour of clamping between diabetics and non-diabetics may reflect altered post-receptor glucose metabolism with the onset of diabetes.
Laryngeal carcinoma in childhood is rare and most commonly classified as squamous cell carcinoma. Although mucoepidermoid carcinoma of the larynx has been noted in adults, it has not previously been reported in a child. A 13-year-old boy presented to our department with an epiglottic mass which was determined histologically to be mucoepidermoid carcinoma. A total epiglottectomy was performed and one year postoperatively the child is without disease.
Fifteen cases of soft tissue chondroma have been reviewed. This lesion shows an equal sex incidence and occurs predominantly in middle-aged individuals. The majority arise in the hands and feet. Histologically these tumours are largely composed of adult-type hyaline cartilage, but in all cases foci show nuclear atypia and pleomorphism. In cartilaginous lesions of the axial skeleton or large limb bones this would probably have led to a diagnosis of well differentiated chondrosarcoma. Despite these worrying features none of the seven cases for which follow-up information is available recurred. The importance of recognizing the benign nature of these little-known tumours is stressed. The differential diagnosis of soft tissue cartilaginous tumours is briefly discussed.
Urinary albumin excretion during pregnancy has been studied using a sensitive radioimmunoassay. One hundred pregnant women attending a high-risk antenatal clinic and 14 normal pregnant women were investigated serially, during pregnancy and post-partum. The normal subjects showed a small but significant rise in albumin excretion in the third trimester, which was sustained pre-delivery and in the first postnatal week. Twenty-six women were classified as having mild pre-eclampsia and 44 as having chronic hypertension without evidence of superimposed pre-eclampsia. In neither group was there evidence of proteinuria by conventional testing, nor was the median albumin excretion different from normal antenatally; in the first week after delivery a significant increase was observed, but this regressed to normal 6 weeks later. Eight patients developed severe pre-eclampsia, of whom one had evidence of underlying renal disease. Three presented with proteinuria already established. In the remaining five patients, the shift from normal to high albumin excretion occurred rapidly, usually preceded by a rise in uric acid and a decrease in the platelet count. These data suggest that proteinuric pre-eclampsia, as defined by relatively insensitive routine laboratory measurement, is not preceded by a phase of increasing albumin loss which can be detected by more sensitive assays.
Thirteen cases of fibroma of tendon sheath have been reviewed. This lesion presents predominantly in middle-aged adults, particularly men, and usually arises in the dermis and subcutis of the extremities, most especially the hands. Histologically these tumours are always well circumscribed and may be lobulated. They are largely composed of interlacing bundles of hyalinised, hypocellular fibrous tissue with occasional more cellular areas. A constant feature is the presence of slit-like vascular channels. They are benign lesions with little tendency to recur and, although becoming more generally recognised are not yet familiar to dermatologists.
A method is described for the measurement of acetate in plasma by an enzymatic technique using acetate kinase, either manually or with the Multistat centrifugal analyser. The technique was used to compare concentrations in diabetic and non-diabetic subjects and to determine correlates with other intermediary metabolites.
The clinical and pathological findings in a case of early avascular necrosis of the femoral head following renal transplantation are described. Regions of subchondral bone distant from the principal lesions showed increased numbers of empty osteocytic lacunae. This has been quantified and it is suggested that a loss of osteocytes is perhaps one of the earliest lesions leading to established avascular necrosis.
Five years after entry into a study prospective from diagnosis of non-insulin-dependent (Type 2) diabetes, 17 patients were known to be dead and 197 alive. On analysis of 136 patients (12 deaths) in whom there was complete information from clinical, metabolic and hormonal examination both before and 1 yr after start of treatment, an index of liability to death within this first 5 yr was calculated, to separate best the dead from the living. One index value correctly ascribed 83% of the dead and 90% of the living (89% of all predictions correct; Youden's "J" value = 0.73). Estimates from the less complete data on the other 78 patients (5 deaths) did not alter the predictive factors. Prediction is more successful with non-cardiac than with cardiac deaths. Five factors contributed to the predictive index for death. One was a long duration of symptoms as recalled at diagnosis. The other 4 factors all came from the 1-yr review (no death then). These were (a) greater glucose intolerance, as expressed by the KG rate constant for disappearance of i.v. injected glucose from the blood (more useful than fasting glucose concentration); (b) higher systolic blood pressure (more useful than diastolic); (c) less obesity, as expressed by the Body Mass Index, and (d) higher fasting blood glycerol concentration. As expected, hyper-glycaemia (as reflected in the KG value) is important, but adrenergic factors may contribute to (a), (b) and (d). From these results earlier diagnosis of this type of diabetes could well be associated with an improved outlook, and in addition this alone might ameliorate the other factors, but measures to normalise them post-diagnosis also require testing.
To determine whether age-associated alterations in the cardiac muscle twitch could be related to altered myofibrillar ATPase activity or to an altered force-pCa relationship, these variables were measured in rat cardiac preparations across a broad age range. Between 2 and 6 months, maximum ATPase activity in detergent treated myofibrils decreased approximately two fold (0.166 +/- 0.01 v. 0.078 +/- 0.02 microM Pi/min X mg protein, P less than 0.001), but did not change with further aging (12 or 24 months). The Ca2+-dependent force in thin 'Triton skinned' papillary muscles was not age-related. ATPase activity and force exhibited identical Ca2+ sensitivity from the submicromolar to micromolar range: for ATPase activity pCa for 50% activity averaged 6.1 and Hill coefficients averaged 4.5; pCa for 50% force development was 6.1 and Hill coefficients of the force-pCa relation averaged 4.5; no age differences in these parameters were observed. In the intact muscles prior to skinning, neither twitch force nor the maximum rate of force production were age-related; however, indices of the time course of contraction, time to peak force, half relaxation time, and their sum, increased progressively, changing by approximately 30% from 2 to 24 months (P less than 0.001). Since the decline in ATPase activity occurred over the maturational period only, and did not change with further ageing, while the twitch duration changed progressively with age, it is concluded that the twitch prolongation of the senescent myocardium cannot be directly related to the age-related decline in myofibrillar ATPase activity.
Protein production and processing were evaluated in vitro in dispersed submandibular gland cells from young adult (4-6 months) and aged (24 month) rats. A modest decrease (approx. 25%) in protein production (incorporation of radiolabeled amino acids into 10% CCl3COOH-insoluble material) was found with old cells in both continuous-pulse and pulse-chase studies. Also new protein processing, followed by gel electrophoresis and autofluorography of radiolabeled samples, showed specific, marked alterations in old cells. In particular a significant difference in the processing of a 225 000 molecular weight glycoprotein (likely the major rat submandibular mucin) was detected.
The purpose of the study was to determine whether the presence of dentofacial anomaly in a child would unfavourably bias a schoolteacher's expectations of the child's scholastic potential, social relationships or personality. Black and white portrait photographs of an attractive boy and girl and an unattractive boy and girl were obtained and modified so that for each face, five different photographic versions were available. In each version, the child's face was standardized except that a different dentofacial arrangement was demonstrated. These were normal incisors, prominent incisors, missing lateral incisor, severely crowded incisors and unilateral cleft lip. Each photograph was attached to a school record card which presented a standardized educational history of an average pupil. The record cards were evaluated by 320 schoolteachers, uninformed as to the true nature of the investigation, and their assessments recorded on a questionnaire. The experimental procedure was such that the effect and interaction of different levels of facial attractiveness, different dentofacial arrangements, sex of photographed child, and sex of teacher could be analysed. The hypothesis, that children's faces with a normal dental appearance or high background facial attractiveness would gain preferential bias in teacher expectations, was not supported.
The water-soluble methyl ester of amphotericin B inactivates vesicular stomatitis virus in association with morphological alterations of the envelope.
Aggregation factor, the macromolecular complex which mediates species-specific aggregation of dissociated sponge cells, was isolated from several species, partially characterized, and visualized by electron microscopy. All factors were large fibrous complexes with a backbone and side chains or arms. In some factors, the backbone is linear. In others it is circular and the complex appears as a sunburst with arms extending like rays from the circle. The size and location of the polysaccharide chains have been studied using purified preparations of Microciona prolifera. "Sunbursts" treated with ethylenediaminetraacetate (EDTA) for 4 weeks at 0 degrees C dissociate into 3 protein- and polysaccharide-containing components. Sodium dodecyl sulfate does not cause the sunburst to dissociate nor does it inhibit dissociation in the presence of EDTA suggesting that dissociation is not due to hydrolytic enzymes. The dissociation products were fractionated on a 977-A pore size micropore glass column. Fifteen percent of the material is excluded and appears in the electron microscope as the central circle of the sunburst. Digestion of the circles with 10(-3) M dithiothreitol (DTT) and 0.5 mg/ml proteinase K for 72 h at 37 degrees C produces 2 polysaccharide chains of 65,000 and 6,000 daltons as fractionated and sized on a 233-A pore size micropore glass column using Pharmacia dextrans as standards. The included fractions of the EDTA-treated material are subunits of the arms which contain 70% of the polysaccharide. A single polysaccharide of 6,000 daltons as measured on 233-A size glass beads and Sephadex G-75 is released from these subunits by proteinase digestion. Pharmacia dextrans are used as standard on both columns. We calculate that there would be four 65,000-dalton chains and one hundred 6,000-dalton chains per circle and fifty 6,000-dalton chains per arm. The third component of the EDTA-treated preparation is partially included on the column. It appears as linear fibrils in the electron microscope and contains polydisperse polysaccharides of several-hundred-thousand daltons. It may be an impurity since there is apparently less than 1 of the large polysaccharide chains per sunburst.
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