Biomedical subjects
Publications and source records attributed to J D Harrison.
We report a case of massive rectal haemorrhage arising from a single ectatic arterial vessel above the haemorrhoidal cushion in normal rectal mucosa. Use of an anal retractor enable identification of the bleeding vessel and avoided a major laparatomy.
Sympathetic innervation of cardiac myocytes in vitro induces growth independent of anatomic contact between the neurons and myocytes and is not mediated by alpha- or beta-adrenergic receptor stimulation. To establish a model system that will allow purification and identification of the neuronal factor(s) responsible for mediating this regulation, we have initiated studies utilizing conditioned medium from the PC12 cell line. PC12 cells acquire a cholinergic sympathetic neuronal phenotype when exposed to nerve growth factor. Culture medium conditioned by neuronal PC12 cells, but not nonneuronal PC12 cells, induces growth in newborn rat cardiac myocytes as measured by surface area and [35S]methionine incorporation into protein and increases expression of atrionatriuretic peptide, a marker for myocyte hypertrophy. The magnitude of the growth response is dose-dependent and mimics the response to sympathetic innervation. The myocyte response to conditioned medium is not detectable after 24 h of exposure; maximal rate of protein synthesis is obtained within 48 h. Neuronally differentiated PC12 cell-conditioned medium stimulation of growth could not be mimicked by alpha- or beta-adrenergic agonists or muscarinic agonists, nor inhibited by alpha- or beta-adrenergic antagonists, nor by muscarinic antagonists. Neuropeptide Y and somatostatin, peptides known to be present in PC12 cells and sympathetic neurons, were also ineffective at reproducing the effect of neuronally differentiated PC12 cell-conditioned medium. These data indicate that neuronal cells release a soluble factor, different from neurotransmitter, which stimulates myocyte growth. They further identify the PC12 cell line as providing a convenient and abundant supply of this molecule, thus facilitating its further characterization.
OBJECTIVES: Many studies have suggested that glycogen in donor livers is an important fuel during cold ischemic time and at reperfusion. However, it remains unclear as to whether the depression of glycogen content in the graft results in a critical derangement of energy metabolism after reperfusion. The purpose of this study was to assess the possible implications of the glycogen concentration of donor livers for the hepatic energy metabolism after reperfusion. METHODS: The glycogen content of 28 donor livers and the plasma concentrations of metabolic substrates were measured during liver transplantation. RESULTS: Gluconeogenesis was maintained even in the glycogen-depleted graft at reperfusion. However, glycogen-depleted grafts produced more ketone bodies until 24 h after reperfusion. Free carnitine concentrations in these patients were significantly higher than those in the patients with glycogen-nondepleated grafts until 48 h after reperfusion. CONCLUSIONS: A glycogen-depleted liver graft may restore essential metabolic function by producing energy substrates through enhanced ketogenesis in the postreperfusion period. The enhanced production of carnitine by the graft provides a substrate for the production of ketone bodies and thus may be relevant to the enhanced ketogenesis.
This paper looks at the design of housing for an ageing population in the coming years, particularly the frail elderly, and at criteria which an architect would need to apply to provide for their social needs and various physical disabilities which may accompany old age. Recent local and overseas initiatives in providing special housing for elderly people are discussed and some proposals are made for more universal solutions, in the form of "lifetime homes".
BACKGROUND: Hepatocyte growth factor (HGF) plays a key role in the regulation of liver regeneration after hepatocyte damage. Changes in HGF production reflect the status of the regeneration process. METHODS: Serum concentrations of HGF and energy substrates were measured during and after liver transplantation in 30 recipients. RESULTS: In the patients with compromised grafts (group A) HGF concentrations were persistently high after reperfusion, whereas in the patients with well-functioning grafts (group B), HGF concentrations decreased rapidly and remained low 4 hours after reperfusion. The patients in group A who died had persistently high concentrations of HGF. The surviving patients with reversible primary graft dysfunction in group A exhibited low concentrations 48 hours after reperfusion. The decrease in HGF concentration preceded the decrease in aspartate aminotransferase concentration. The metabolic parameters that reflect carbohydrate metabolism by the graft paralleled the changes in HGF. CONCLUSIONS: HGF may be more sensitive and specific in predicting early graft function than prothrombin time, ratio, aspartate aminotransferase, or arterial ketone body ratio. The determination of HGF levels after liver transplantation may yield valuable information for evaluating early graft function and making an early decision to repeat a graft procedure in an acutely ill patient.
In ten healthy subjects, bilateral contacts between opposing cuspid and first molar teeth were recorded during one sequence of unilateral chewing of apple, peanuts, and banana. Unknown magnitudes of mechanophysical (masticatory) forces were inferred to act directly on the chewing-side cuspid teeth in 71% of all masticatory cycles and on the nonchewing-side cuspid teeth in 68% of all masticatory cycles. In addition, unknown magnitudes of mechanophysical forces were inferred to act directly on the chewing-side first molar teeth in 74% of all masticatory cycles and on the nonchewing-side first molar teeth in 86% of all masticatory cycles. During the chewing of peanuts, the total number of chewing-side cuspid contacts exceeded significantly the total number of nonchewing-side cuspid contacts, suggesting more repetitive direct mechanophysical loading of the chewing-side cuspid teeth. During the chewing of apple, the total number of nonchewing-side first molar contacts exceeded significantly the total number of chewing-side first molar contacts, suggesting more repetitive direct mechanophysical loading of the nonchewing-side first molar teeth. The variable contact patterns were, to a large extent, explained by rotational movements of the entire mandible resulting in translational movements of the hemimandible.
Using isolated rat seminiferous tubules as an in vitro model, we have found that 238Pu can cross the blood-tubule barrier and accumulate within tubules in a time dependent manner. Furthermore, similar to 59Fe, tubule 238Pu uptake was inhibited by the addition of excess transferrin, suggesting that plutonium may utilize the physiological iron-transferrin pathway to cross the blood-tubule barrier. However unlike 59Fe, 238Pu was only transiently associated with the tubules, suggesting differences in the intracellular processing of these radionuclides. The assumptions made in the estimation of doses to the human testis from incorporated plutonium are considered.
Stromal tumours of the rectum and anal canal are rare, representing 0.02-0.03% of malignant neoplasms in the region. Current advice in their management is treatment by abdomino-perineal resection. We report a case of malignant spindle cell stromal tumour in which adequate clearance was obtained whilst preserving the anal sphincter, using a posterior parasacral approach.
The behaviour of radionuclides after entry into the body and the radiation doses received by individual tissues depend on the chemical nature of the element, the physicochemical form of the intake, the radioactive half-life of the isotope and the type and energy of the emissions. Ingestion of radionuclides in insoluble particles will result in radiation doses being delivered to tissues of the gastrointestinal (GI) tract; other tissues will also be irradiated by nuclides with penetrating photons emissions (gamma) but doses may be largely confined to the GI tract for charged particle emissions (alpha, beta). Ingestion of more soluble forms will lead to greater absorption to blood and deposition in other tissues and therefore may result in greater doses to other tissues. Similar considerations apply to inhaled material and to the entry of radionuclides through cuts or wounds. For ingested materials, including particles, more information is needed on uptake and retention in intestinal tissues and consequent doses to sensitive cells, particularly for alpha emitters. There has been concern that the pattern of distribution of activity throughout irradiated tissues may influence the extent of damage, particularly for alpha emitters because of the localised deposition of energy and their greater relative biological effectiveness compared with beta/gamma emitters. Aggregation of activity has the potential to result in greater acute tissue damage and has been shown, for example, to result in focalised pneumonitis and fibrosis in the lung and ulceration of the skin. The main long-term effect of irradiation of tissues is the induction of malignant change, although hereditary disease may also be of concern following irradiation of the gonads. There are only limited data available to compare the effect on cancer induction of heterogeneous and homogeneous irradiation of tissues. However, the available information, for irradiation of the lung, skin or liver, indicates that in general nonuniform alpha irradiation from radioactive particles is no more hazardous, and may be less hazardous, than if the same activity is uniformly distributed.
Fifty-five patients undergoing orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) were reviewed retrospectively. After OLT there were significantly more episodes of acute rejection in 31 patients with a previous history of inflammatory bowel disease (IBD) than in 24 without such a history. Patients who had severe acute rejection were significantly younger at diagnosis of IBD. Five patients with histological features suggestive of recurrent PSC after OLT were significantly younger at the time of transplantation than those who did not develop recurrence. Patients with poor control of IBD after OLT had a significantly lower age at diagnosis of bowel inflammation. The presence of IBD did not affect the outcome after OLT, but was associated with a higher rate of acute rejection. Younger patients had a greater risk of developing severe rejection, recurrent PSC and poor control of IBD after liver transplantation.
Transfer of 210Po to the foetus measured 3 days after administration in rat and 7 days later in guinea pig increased with increasing gestational age to about 0.1% injected activity per rat foetus at birth and 0.6% per guinea pig foetus on day 57, corresponding to whole-body foetus:mother concentration ratios of about 0.1:1 in both species. The greatest concentrations of 210Po were measured in the rat yolk sac during its haemopoietic stage, an order of magnitude greater than concentrations in the placenta and two orders of magnitude greater than foetal concentrations. The results obtained have been used to estimate in utero doses to haemopoietic tissues, taking account of transfer to the blastocyst/egg cylinder, yolk sac, liver and bone marrow. The concentration ratios relative to maternal liver for these tissues were taken to be 1, 3, 0.1 and 0.05 respectively and were applied to periods of human gestation of 0-2.5, 2.5-6, 6-12 and 12-38 weeks respectively. For chronic maternal intake by ingestion of 210Po during the year of pregnancy giving a committed effective dose (CED) to the mother of 1 mSv, the total in utero dose to haemopoietic tissue was about 340 microSv compared with a maternal red bone marrow dose of 2.2 mSv. The yolk sac and bone marrow accounted for 66 and 27% of the in utero dose respectively. In addition, the total CED to the offspring was calculated assuming a whole-body foetus:mother concentration ratio of 0.1:1 and that the distribution of 210Po between tissues was the same in the foetus as in adults and children. For chronic intake of 210Po during the year of pregnancy as assumed above, the CED to the offspring was estimated to be 8% of that to the mother.
This paper provides a review and reanalysis of data relating to gastrointestinal (GI) uptake of uranium in humans. Estimates of GI uptake of uranium in adult humans have been derived from results of three controlled experimental studies involving short-term oral intake of an elevated quantity of uranium in fluids, from a controlled balance study conducted in a metabolic research ward of a hospital, and from a variety of environmental studies in which urinary uranium could be related to total intake or total excretion of this element in the same population. For controlled studies, uptake values range from less than 0.1% to about 6% for individual subjects, with central values for different studies falling in the range 1-2.4%. Environmental studies yield central estimates in the range 0.3-3.2%. Expressed as a percentage of total intake of uranium in food and fluids, average GI uptake of uranium in adult humans appears to be about 1-1.5%. Limited intake and excretion data for environmentally exposed human subjects > or = 5 y of age do not reveal important differences with age in uranium uptake, but more definitive information is needed for children. More information is also needed to determine whether fractional uptake of uranium increases with decreasing levels of intake and whether uptake from drinking water is substantially higher than uptake from food. Data for laboratory animals indicate that fractional uptake of uranium depends strongly on the chemical form ingested and the length of time since the last intake of food.
Groups of male and female CBA/H mice were given intraperitoneal injections of 40 kBq kg-1 of 239Pu, 241Am and 233U citrate solutions and the retention and distribution of the three radionuclides compared at times up to 448 days. Similar results were obtained for males and females and showed that: 1. Whole body retention at 448 days was very similar for 239Pu and 241Am, accounting for about 20% of injected activity for each nuclide; retention of 233U was much lower at about 3%. 2. The skeleton accounted for 85% or more of retained 239Pu, 241Am and 233U activity from 6 weeks after injection. 3. The greatest concentrations of each radionuclide were measured in the main body of the spine, limb girdles and ribs, with lowest concentrations in the paw bones, head bones and caudal vertebrae. The inhomogeneity of distribution was in the order Pu > U > Am; with a trend to more uniform activity with time. 4. Average bone doses to 448 days were calculated as about 1.6 and 1.7 Gy for 239Pu and 241Am, respectively, and 0.3 Gy for 233U, with ranges for individual bones of 0.7-3.0 Gy, 1.1-2.5 Gy and 0.1-0.6 Gy, respectively. Average liver doses to 448 days were calculated as about 0.9 Gy, 0.6 Gy and 0.007 Gy for 239Pu, 241Am and 233U respectively, whilst the dose to the kidney for 233U was about 0.1 Gy. 5. Autoradiographic studies of the distribution of the nuclides in the femur showed differences in their initial distribution and subsequent movement. Initially, concentrations of 239Pu were greater on endosteal than periosteal surfaces while 241Am distributed more evenly on bone surfaces. The initial deposition of 233U on all surfaces was uneven with concentrations probably on active surfaces. Burial of all three nuclides in areas of bone growth was observed. Transfer of activity to the marrow was greatest for 239Pu and least for 233U.
The gastrointestinal absorption of Fe and Co by rats and guinea pigs of different ages was measured by comparing the whole-body retention of 59Fe and 57Co after oral and intraperitoneal administrations. The age-groups studied included newborn, weanlings and adults. The absorption of both Fe and Co decreased markedly with age in both rats and guinea pigs. In the rat, absorption remained elevated during the suckling period, while in the guinea pig absorption decreased markedly during suckling. In both species, Fe and Co absorption were similar, and remained elevated above adult values for some time after weaning. The generally greater absorption of Fe and Co by rats than by guinea pigs and the longer duration of maximal absorption in the rats may have involved differences in Fe status in the two species and differences in the timing of gut maturation.
Mixtures of Np, Pu and Am were administered to primates (C. jacchus) by gastric intubation to measure their fractional gastrointestinal absorption (f1 values). The values obtained were about 2 x 10(-3) and 1 x 10(-3), respectively, for Np and Pu administered as the citrate, and 2 x 10(-3) and 6 x 10(-4), respectively, for Pu and Am in potato. The significance of these values in terms of absorption in humans is discussed.
The gastrointestinal absorption of plutonium and americium present in dusts from the Maralinga test sites in South Australia has been measured as an input to dose assessments. The materials studied were from three different areas, designated Taranaki (Q380II), TM100 (10/2) and N. Plume (26). The three dusts were fed to groups of rats, mixed with their normal food. The Taranaki and TM100 dusts were also fed to guinea pigs, as a suspension in water. Expressed as fractional absorption from the gastrointestinal tract (f1), the values obtained for plutonium were 2 x 10(-6) and 8 x 10(-6) for Taranaki dust in rats and guinea pigs, respectively, 3 x 10(-6) and 10(-5) for TM100 dust in rats and guinea pigs, respectively, and 2 x 10(-6) for N. Plume dust in rats. The f1 values obtained for americium were 3 x 10(-6) and 2 x 10(-5) for Taranaki dust in rats and guinea pigs, respectively, 10(-5) and 5 x 10(-5) for Taranaki dust in rats and guinea pigs, respectively, and 10(-5) for N. Plume dust in rats. On the basis of these results, rounded f1 values used in the dose assessments were 10(-5) for plutonium and 10(-4) for americium, applying to all intakes of dust. These values compare with the International Commission on Radiological Protection recommendations of 10(-3) for unspecified chemical forms of both elements, 10(-4) for plutonium nitrate and 10(-5) for plutonium oxides. The effect of changes in f1 values on doses from 239Pu and 241Am is considered.
Brainstem death is associated with endocrine and metabolic alterations that can result in donor hemodynamic instability. It has been suggested that these changes can be reversed through hormonal manipulation of the donor. We measured thyroid hormone levels (free triiodothyronine [fT3], free tetraiodothyronine [fT4], reverse triiodothyronine) and thyroid-stimulating hormone (TSH) in 50 consecutive adult brain dead multiorgan donors. Recipient graft function was assessed using peak and day 5 aspartate aminotransferase, peak serum bilirubin, and minimum prothrombin time during the first week after OLT. Free T3 was low in 32/50 donors and was associated with a low fT4 in 24 cases. TSH was normal in 35 donors and we found no correlation between TSH levels and fT3 or fT4. Reverse triiodothyronine was normal or high in 96% of donors. Patient and graft survival were 96% for both the low and high fT3 groups. These data suggest that euthyroid sick syndrome is the most likely cause for the endocrine and metabolic alterations seen in brainstem-dead donors. This does not appear to influence liver recipient or graft survival.
Ruthenium-106 in citrate solution was administered intravenously to rat at different stages of pregnancy and to guinea-pig either before conception or in late pregnancy. The results for rat showed that retention in the embryo/foetus measured at 3-5 days after administration increased from about 0.0002% of injected activity per embryo/foetus on day 12 of gestation to about 0.05% at birth. The relative concentrations of 106Ru in embryo/foetus and mother (Cf/Cm ratio) were about 0.1 in each case. Concentrations in the yolk sac on day 12 were about 1% g-1 compared with 0.01% g-1 in the foetus. Retention in the guinea-pig foetus in late gestation at 7 days after administration (days 50-57) was about 0.2% injected activity per foetus, corresponding to a Cf/Cm = 0.2. Retention in each foetoplacental unit was 2% of injected 106Ru with 50% in the yolk sac, 35% in the placenta and 10% in the foetus. For administration 4 weeks prior to conception, the level of 106Ru retained in the foetus on day 57 of gestation was two orders of magnitude lower than after short-term administration, with a Cf/Cm about 0.004.