Biomedical subjects
D Hamilton
Publications and source records attributed to D Hamilton.
114Inm oxine-labelled lymphocytes--therapeutic applications.
It has shown that, after intravenous administration of autologous lymphocytes labelled with the beta-emitting radionuclide 114Inm, the cells initially migrate normally before succumbing to the toxic effects of the radiation. The radioactive material is then released from the cell and taken up by neighbouring radioresistant macrophages, thereby localizing a field of radiation to the site of lymphocyte death. Using this technique, lymphocytopoenia has been produced in rats. We have measured the whole-body distribution and excretion of radioactivity in patients who received escalating activities of 114Inm-labelled lymphocytes. All patients had active non-Hodgkin's lymphoma involving the spleen and liver which proved resistant to combination chemotherapy and conventional radiotherapy. Following intravenous administration, the labelled cells cleared rapidly from the vasculature with only 15% remaining in the peripheral blood at 30 min. The radioactivity continued to fall over the next 5 days to approximately 3% and was maintained at approximately 2% for up to 90 days. There was an almost immediate uptake of radioactivity by the spleen and liver which reached approximately 85% of the injected dose by 48 h. The localization of radioactivity stabilized by 48 h and thereafter the whole-body content fell by approximately 0.8% per day. Up to 5% of the administered radioactivity accumulated in the bone marrow. The activities administered were too low to produce a therapeutic response and no toxicity was experienced by the patients. A therapeutic study at higher activities is now underway.
For A.I.D.S. patients, little things can mean a lot. Living with A.I.D.S.: a nurses's story.
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School results as predictors of medical school achievement.
In Queensland, scores in the final 2 years of secondary school scaled by an independent aptitude test are used to determine admission to tertiary education. The validity of this procedure for medical school enrollment has been investigated. Data were from four cohorts which entered the medical school to commence the course in each of the years 1975-1978, a total of 943 students. In addition to the school subject scores, overall order of merit scores and results of an independent aptitude test used to scale these scores were included with the predictors. Criteria were derived from the grades obtained in the 33 medical school subjects over the 6-year course, or from a broad pass/fail classification. We demonstrate that the school science subjects were of moderate value for prediction of preclinical achievement, but that school English was the most important predictor of performance in the clinical years, which is perhaps an indication of the value of communication skills.
Clinical excellence, but too high a cost: the Metropolitan Life Insurance Company Visiting Nurse Service (1909-1953).
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Faith and finance.
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Studies on the mechanism of hemorrhage production by five proteolytic hemorrhagic toxins from Crotalus atrox venom.
The sites and relative rates of peptide bond hydrolysis of the oxidized B chain of bovine insulin by two hemorrhagic proteinases, Ht-a and Ht-b, isolated from the venom of the Western Diamondback Rattlesnake, Crotalus atrox, were investigated. The results were compared with previous results on the digestion of the same substrate by the C. atrox hemorrhagic proteinases Ht-c, d, and e. Both toxins, Ht-a and Ht-b, were found to cleave the His5-Leu6, His10-Leu11, Ala14-Leu15, and Tyr16-Leu17 bonds of the oxidized insulin B chain. In addition, Ht-a cleaves the Asn3-Gln4 bond, whereas Ht-b cleaves the Gly23-Phe24 bond. The cleavage specificity of Ht-b on the insulin B chain is identical to that of the weakly hemorrhagic isoenzymes Ht-c and Ht-d. Hemorrhagic proteinase Ht-a cleaves the Ala14-Leu15 bond most rapidly, having a turnover number of 12.6 min-1 which was approximately twice as fast as the Tyr16-Leu17 bond turnover of cleavage. Hemorrhagic proteinase Ht-b, on the other hand, cleaves the Tyr16-Leu17 bond fastest, having a turnover number of 61.3 min-1. The Ala14-Leu15 bond is the peptide bond cleaved the second fastest by Ht-b, with a turnover number of 48.2 min-1. The five hemorrhagic toxins from Crotalus atrox venom were also examined for their capability to hydrolyse basement membrane preparations, and the identities of the digested proteins comprising the basement membrane were determined. From the results it is concluded that all five hemorrhagic toxins cleave laminin and the component of the basement membrane referred to as band a.(ABSTRACT TRUNCATED AT 250 WORDS)
The behavior of autologous indium-114m-labeled lymphocytes in patients with lymphoid cell malignancy.
It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that 114mIn deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples, and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.
The effect of glucocorticoids on corticosteroid binding globulin.
To evaluate the effect of glucocorticoids on corticosteroid binding globulin (CBG), we measured the binding capacity and binding affinity of cortisol for CBG in normal subjects, patients receiving glucocorticoids and patients with Cushing's syndrome. Normal subjects had a mean binding capacity of 3.8 (+/- SD 0.7) X 10(-7) mol/l and mean binding affinity of 1.96 +/- 0.48 X 10(-8) M. Patients with Cushing's syndrome had a 40% decrease in binding capacity (2.3 +/- 0.4 X 10(-7) mol/l) compared to control subjects and significantly lower mean binding capacity than patients receiving pharmacological (2.9 +/- 0.6 X 10(-7) mol/l) and physiological doses of glucocorticoids (3.4 +/- 0.6 X 10(-7) mol/l) (P = 0.05 one-way analysis of variance). Patients with endogenous cortisol excess also had significantly lower mean binding affinity (1.54 +/- 0.37 X 10(-8) M) than normal subjects and glucocorticoid treated subjects. These changes suggest that both endogenous and exogenous glucocorticoids can modulate circulating levels of CBG and may have important implications for patients receiving steroid therapy.
In vitro photoradiation therapy of the rat 9L gliosarcoma.
The authors have investigated various factors involved in the photoradiation treatment of 9L glioma cells. The cells were grown in tissue culture and exposed to light from a laser source that allowed accurate quantitation of the light energy. Cell death was determined following treatment using the trypan blue exclusion test. It was shown that the treatment is very wavelength-dependent following the absorption spectrum of hematoporphyrin derivative (HPD). The absorption peaks in the lower part of the spectrum are more efficient than those of higher wavelengths. Photoradiation therapy is more effective the higher the concentration of HPD. Intensity of light is a very important factor in calculating the total dose of light necessary for this treatment.
An illustration of skin graft rejection and sympathetic medicine from 1661.
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Naloxone enhances motion sickness: endorphins implicated.
This study evaluated the time course to Malaise III in human subjects given naloxone and placebo with a double-blind cross-over protocol in the prevention of motion sickness induced by exposure to coriolis stimulation in a rotating chair. During naloxone tests, subjects reached the designated level of sickness sooner than during the placebo testing (significance greater than 0.05) and their discomfort lingered for up to 3 d--a feature not seen with the placebo. This implicates endogenous opiates with an endogenous protective or adaptive role in the control of motion sickness. It is suggested that when subjects experience endogenous opioid withdrawal, such as post exercise, they could be in a state of neuron hypersensitivity, and thus more prone to any form of exogenous emetic stimuli. Greater tolerance to motion stresses could be experienced in subjects whose endorphins were repeatedly elevated, thus avoiding a hypersensitivity state from endogenous opiate withdrawal. Subjects whose endorphins have not been elevated in the first instance cannot secondarily suffer opioid abstinence.
Epilepsy and army physicians.
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Oesophageal lesions at autopsy in black children.
Oesophagi of black children dying from a variety of diseases examined at autopsy showed features of chronic oesophagitis and atypical basal cell hyperplasia in a significant percentage of cases. The possible significance of this finding in relation to carcinoma of the oesophagus is discussed.
Regional specific mean expiratory gas flow from 81mKr equilibrium inhalation data.
A new method of analysing the data available from routine 81m Kr equilibrium inhalation investigations has been developed. The data for analysis are acquired from a gamma camera in the form of a sequential series of images from which multiple breath activity-time curves are generated for eight regions in the lung. The method is based on a description of the behaviour of the radioactive gas in the lung using a mathematical model. Values of specific mean expiratory gas flow, that is mean expiratory gas flow per unit lung volume, are calculated from the application of the model to the expiratory phase only of a single breath activity-time curve which is generated from the multiple breath activity-time curve using post-acquisition gating. This method overcomes the problem of non-uniform inspiratory concentration of tracer gas experienced in previously reported techniques of analysing inhalation data obtained using poorly soluble radioactive gases. The model is shown, in simulation studies, to be an adequate description of the behaviour of radioactive gas in the lung and the analysis technique is shown, in clinical studies, to be both reproducible and sensitive to disease state.
Does medical training affect personality?
We have compared results obtained for psychometric tests (Cattell's 16 PF and Eysenck's personality inventory) on a cohort of medical students who sat the tests in their second medical school year and repeated them in their sixth and final year. Most of the changes were in the direction expected of students maturing through the 19-24 year age period, but there were some significant differences from those obtained by other workers using the same tests on general student populations. Thus, in our study male students became 'brighter', more 'emotionally stable', less 'timid', more 'tough-minded', and more 'self-controlled', all of these to a significantly greater extent than expected with the general student population. Similar changes were observed from females, although except for an increase in emotional stability, these were not significantly different from the values expected in the general population.
Depressive disorders in relatives of anorexia nervosa patients with and without a current episode of nonbipolar major depression.
The first-degree relatives of anorexia nervosa patients with current nonbipolar major depression had a higher rate of depression than the relatives of anorexic patients without current depression, whose rate was similar to that for relatives of normal control subjects.
Metabolic dependence of glycolytic enzyme binding in rat and sheep heart.
Perfused rat hearts show a markedly increased binding of phosphofructokinase and fructose-bisphosphate aldolase as a consequence of ischaemia, but little change in binding of pyruvate kinase, lactate dehydrogenase or glyceraldehyde-3-phosphate dehydrogenase. After 10 min ischaemia over one quarter of the phosphofructokinase and three quarters of the aldolase are bound. The effect of anoxia is less well marked in its influence on binding with only aldolase showing a significant increase in binding. These results suggest that one factor involved in the increased binding during ischaemia is the fall in pH of the heart. Binding studies with isolated myofibrils confirm that the affinity and stoichiometry of aldolase binding are considerably increased as the pH is lowered over a range comparable to that which occurs in ischaemic heart. The low level of binding of glyceraldehyde-3-phosphate dehydrogenase in perfused rat hearts correlates with the relatively low affinity of this enzyme for binding to rat or rabbit cardiac myofibrils. There are species differences in the enzyme binding response to ischaemia. Sheep hearts show rapid and large increases in the binding of glyceraldehyde-3-phosphate dehydrogenase in addition to changes in aldolase and phosphofructokinase binding. The greater binding of glyceraldehyde-3-phosphate dehydrogenase reflects the greater affinity of sheep cardiac myofibrils. It is suggested that the altered metabolic demands of ischaemia are satisfied by changes in glycolytic enzyme organisation as the enzymes shift from the soluble to the particulate phase of cardiac muscle.