Clinical science and molecular medicine最新文献

1. The spectrum of transit times of sodium o-iodohippurate (Hippuran) through the kidney can be derived from an 131I- (or 123I-) labelled Hippuran renogram by deconvolution. In the rabbit and pig, as has previously been shown in man, the frequency distribution curve for the transit times was bimodal. Since the transit time is likely to be proportional to the nephron length, the area of the first mode is likely to represent plasma flow to the shorter outer cortical nephrons whereas the delayed mode represents flow to the long juxtamedullary nephrons. 2. This interpretation was tested by simultaneously comparing renography with the microsphere method of measuring intrarenal plasma flow distribution in 12 rabbits and two pigs with a variety of anaesthetics. A close agreement was found between both methods for the percentage of plasma flow distributed to the outer cortical nephrons, thus supporting the use of "transit renography" to determine the intrarenal distribution of plasma flow.

1. Spiral strips of human digital arteries have been studied in vitro to investigate whether DL-propranolol, D-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. DL-and D-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific alpha-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effect on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.

1. Structural changes in the thymus during the evolution experimental renal hypertension were investigated to determine their possible role in the genesis of hypertensive vascular disease. 2. The thymus, adrenal glands and the progression of hypertensive vascular lesions were investigated in rats during the first 30 days after occlusion of the aorta between the two renal arteries. 3. Hypertension was initially accompanied by marked atrophy of the thymus, most pronounced 9 days after operation. During this time, the adrenal glands doubled in size and the heart became enlarged. 4. After 21 days the thymus regenerated and became hypertrophic. Histological features of hyperactivity accompanied by infiltration of plasma cells were evident, while the adrenal glands remained enlarged. 5. The observed structural changes of the regenerated thymus in the presence of sustained adrenal hypertrophy indicate that the thymus may contribute to the production of hypertensive vascular disease.

1. Hepatic carbohydrate metabolism was studied by an intravenous galactose test in control patients, malnourished non-septic patients, patients with prolonged severe sepsis and patients after recovery from sepsis. 2. Blood galactose half-life was not significantly increased in the septic group despite abnormal liver-function tests, whereas it was approximately doubled in the malnourished patients. 3. The rise in blood glucose after galactose injection was less in both the septic and malnourished groups, as compared with that in the control subjects. 4. Fasting blood glucose, lactate and pyruvate concentrations were similar in all groups, whereas blood ketone bodies were increased in the malnourished and septic groups, and blood alanine was decreased only in the septic group. 5. The changes in hepatic metabolism and function were reversible on recovery from sepsis. 6. It is suggested that alterations in hepatic blood flow and the metabolic fate of galactose within the liver may explain the changes in the metabolic response to galactose observed in malnourished or septic patients.

1. The change in arterial pressure and heart rate resulting from alteration of carotid sinus transmural pressure by a median--34 mmHg and +33 mmHg by means of a variable-pressure neck chamber was tested in seven male volunteer subjects, at rest and during exertion of 35, 45 and 65% of maximum voluntary handgrip. 2. During 60 s of 35 and 45%, and during 30 s of 65%, of maximal voluntary handgrip there was virtually no alteration of the response of blood pressure to alteration carotid sinus transmural pressure. 3. The bradycardic response to increase in carotid sinus transmural pressure was reduced at various times after the commencement of handgrip at 45 and 65% of maximum voluntary contraction. 4. It is concluded that a reduction in arterial baroreceptor reflex sensitivy does not play an important role in the initiation of the increase in arterial blood pressure and heart rate caused by isometric exercise. 5. The hypothesis is advanced that some of the cardiovascular changes in exercise may result from elevation of the central 'set point' for blood pressure.

1. The continued uptake of 18F, 85Sr and 47Ca by bone after death has been studied in rats and rabbits after aortic injection followed by quick killing, a period of recirculation of tracer before death, and perfusion of the carcase. In each case an approximately linear increase of bone radioactivity was observed during a period of 1 h at about the same rate. The proportionate increase depended on the initial concentration of bone-seeking nuclide, ranging from a factor of 1.5 to 4.5. Boiling the carcase did not increase the migration rate. 2. Delay between death and dissection may therefore lead to spuriously high bone concentrations of these radionuclides, leading to over-estimates of bone uptake, extraction ratio or bone blood flow.

1. Plasma and urine free dopamine (3,4-dihydroxyphenethylamine) were measured in six normal male volunteer subjects and the urinary clearance of dopamine was calculated for each subject. 2. The excretion rates for free dopamine in man were greater than could be explained by simple renal clearance. It was concluded that free dopamine must, therefore, be formed in the kidney. 3. Changes in urinary dopamine excretion were studied in four groups of rats initially maintained on low sodium diet and then given equimolar dietary supplements of NaCl, NaHCO3, KCl or NH4Cl, to study the specificity of the previously observed increase in dopamine excretion after increased dietary NaCl. 4. The mean dopamine excretion increased significantly in rats given NaCl, KCl and NH4Cl, whereas dopamine excretion decreased in those given NaHCO3. 5. The failure of dopamine excretion to rise in response to loading with NaHCO3 was unexpected, and argues against a simple effect of volume expansion by the sodium ion. The increase in dopamine excretion with KCl and NH4Cl showed that this response was not specific to the sodium ion.

1. The effects of varying PCO2 on glucose output and the intracellular concentrations of lactate, pyruvate, phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate were studied in the isolated rat liver perfused with differing concentrations of lactate. 2. When the perfusate lactate concentration is above 1.5 mmol/l respiratory acidosis (simulated by high perfusate PCO2) inhibits gluconeogenesis from lactate, whereas respiratory alkalosis stimulates gluconeogenesis. 3. In general there were significant positive correlations between intracellular pH (pHi) and hepatocyte phosphoenolpyruvate, 2-phosphoglycerate and 3-phosphoglycerate concentrations, and negative correlations between pHi and lactate and pyruvate concentrations; there were usually significant correlations in the opposite sense between these metabolites and log PCO2. 4. The results suggest that CO2 exerts an inhibitory effect on gluconeogenesis at a step between pyruvate and phosphoenolypruvate; however, this is not the only effect of CO2 on the gluconeogenic sequence. CO2 probably acts by changing pHi, but direct effects of CO2 and HCO-3 cannot be excluded. 5. Except at low lactate concentrations, nonionic diffusion probably does not play a major role in the entry of lactate into the hepatocyte.