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Biomedical subjects

C A Hamilton

Publications and source records attributed to C A Hamilton.

At least 163 records · Page 9Linked to original sources
PubMed1975

Effect of phenformin on gluconeogenesis from lactate and intracellular pH in the isolated perfused guinea pig liver.

Gluconeogenesis from lactate and hepatic cell pH (pHi) were measured in the isolated perfused livers of starved guinea pigs in the presence and absence of phenformin (phenethylbiguanide). The observed decrease in lactate consumption and glucose output in the presence of phenformin was associated with a fall in pHi. The fall in glucose output observed was considerably greater than accountable for by the decrease in lactate consumption. A possible mechanism for the pathogenesis of clinical lactic acidosis due to phenformin therapy is suggested.

Acidosis↗
PubMedDate not supplied

Effects of intravoxel velocity distributions on the accuracy of the phase-mapping method in phase-contrast MR angiography.

The phase-mapping method of phase-contrast magnetic resonance angiography is shown to be based on an implicit assumption that the intravoxel velocity distribution is symmetric about its mean velocity. The effect of asymmetric distributions on the accuracy of quantitative average velocity measurements is determined analytically and verified experimentally. An explicit formulation is developed for the estimated average velocity in a voxel as a function of the true average velocity and the asymmetry of the distribution about the true average velocity. Worst-case distributions are determined for unidirectional and bidirectional flow, and the special case of laminar flow is also investigated. Computer simulations and phantom imaging experiments demonstrate the accuracy of the analysis. For voxels with unidirectional flow, the phase-mapping method produces accurate estimates of average velocity, while results for bidirectional flow indicate possible large errors unless the aliasing velocity is increased, which decreases the signal-to-noise ratio in the resultant velocity map image.

Algorithms↗
PubMedDate not supplied

Effects of intravoxel velocity distributions on the complex difference method of phase-contrast MR angiography.

The complex difference method of phase-contrast MR angiography is affected not only by the degree of velocity encoding applied during the scan but also by the variance of the intravoxel velocity distribution. The reconstructed intensities of voxels with the same average flow rate but different variances of the velocity distribution can differ significantly. Mathematical analysis and scanner phantom experiments confirm this conclusion.

Humans↗
PubMedDate not supplied

Depiction of intracranial vessels with MRA: utility of magnetization transfer saturation and gadolinium.

PURPOSE: The purpose of this work was to quantitate the individual and combined effects of magnetization transfer (MT) saturation and gadolinium (Gd) on the visualization of intracranial vessels with MR angiography (MRA). METHOD: Thirty-five subjects underwent two three-dimensional time-of-flight MRA sequences without and with MT and/or Gd. There were 14 MR angiograms without Gd or MT, 18 with MT only, 17 with Gd only, and 21 with both Gd and MT. On a projection image, a region of interest was drawn to delineate the arteries in the middle cerebral artery territory. The total area of blood vessels in the region of interest was calculated for each MR angiogram. Mean vessel areas for the four types of MRA were compared with analysis of variance. RESULTS: MRA with either MT or Gd alone showed significantly more vessel area than MRA without either (p < 0.05). MRA with MT alone and MRA with Gd alone were not different from each other (p = 0.29). The improvement in vessel area measured by using MT and Gd together was significantly more than expected from the cumulative improvement of adding each alone (p < 0.05). CONCLUSION: Combining MT and Gd synergistically improved the visualization of intracranial vessels on MRA.

Adult↗
PubMedDate not supplied

Magnetization transfer imaging of skeletal muscle in autosomal recessive limb girdle muscular dystrophy.

PURPOSE: The purpose of this work was to characterize magnetization transfer (MT) contrast of skeletal muscles in limb girdle muscular dystrophy (LGMD). METHOD: The calf muscles of five LGMD patients and 10 normal volunteers were imaged with an off-resonance MT suppression pulse applied to T1-weighted images. MT suppression ratios were calculated for anterior tibialis, posterior tibialis, soleus, and gastrocnemius muscles in the LGMD and control groups. The relationship between MT of individual muscles and the duration of LGMD symptoms was determined. RESULTS: Strong MT contrast was observed in normal calf muscles, with mean (+/-SD) suppression ratios ranging from 37.9% (+/-3.0) to 41.1% (+/-2.1). In diseased muscle, MT signal suppression ranged from 11 to 38%, demonstrating an inverse relationship between symptom duration and suppression ratios. MT contrast in the LGMD patients, as a reflection of muscle tissue integrity, was preserved in posterior or anterior tibialis, soleus, and gastrocnemius muscles, respectively. Suppression ratios were dramatically reduced in muscles with gross fatty infiltration but also were reduced in muscle tissues without visual evidence of fatty infiltration. CONCLUSION: MT imaging provides a quantitative measure of pathologic changes occurring within the skeletal muscles of patients with LGMD relative to normal and may be useful in evaluating disease extent, progression, and response to new therapies as they become available.

Adolescent↗
PubMedDate not supplied

Effects of chronic beta-adrenoceptor antagonism on plasma catecholamines and blood pressure in hypertension.

Plasma catecholamines were measured before and after treatment with beta-adrenoceptor antagonists in 17 hypertensive patients. Chronic treatment with beta-adrenoceptor antagonists caused substantial reductions in heart rate and intra-arterial blood pressure recorded continuously during ambulation. Before treatment, a quantitative relationship was observed between plasma norepinephrine and blood pressure and heart rate during a variety of activities; a similar relationship was also observed after chronic treatment five of six patients, suggesting that plasma norepinephrine remains an index of sympathetic activity despite the influence of beta-adrenoceptor antagonism. After treatment, plasma norepinephrine tended to be higher at any level of blood pressure, although not significantly so. Chronic treatment caused no significant change in mean resting plasma levels of norepinephrine and epinephrine. During exercise, plasma norepinephrine and epinephrine levels were significantly elevated above control after acute but not after chronic treatment. These observations do not support the hypothesis that beta-adrenoceptor antagonist drugs lower blood pressure in hypertensive man through a sympatholytic mechanism in he central nervous system or at peripheral presynaptic receptors.

Adolescent↗
PubMedDate not supplied

Changes in alpha-adrenoceptors during long-term treatment of rabbits with prazosin.

Acute intravenous prazosin (0.05 mg/kg) caused marked falls in mean arterial pressure and postsynaptic alpha 1-adrenoceptor blockade in rabbits. During chronic oral dosing (3--21 days), tolerance developed and blood pressure returned to base-line pretreatment levels. This did not appear to be related to changes in plasma renin activity, body weight, prazosin kinetics, or alpha 2-adrenoceptor responsiveness. However, pressor responses to the alpha 1-adrenoceptor agonist phenylephrine and the mixed alpha 1/alpha 2-agonist noradrenaline increased during chronic prazosin therapy. Despite the development of apparent "tolerance," the response to bolus injections of prazosin was unchanged. No changes in the maximum number of prazosin binding sites or their dissociation constant were observed in the heart, spleen, forebrain, or hindbrain after 21 days treatment. It appears that although compensatory mechanisms develop during chronic prazosin treatment, they are not mediated by alterations in alpha 1-receptor binding but are related to changes in alpha 1-adrenoceptor responsiveness beyond the drug-receptor binding site.

Animals↗
PubMedDate not supplied

Central and peripheral alpha-adrenoceptor number and responsiveness after sinoaortic denervation in the rabbit.

The effects of bilateral sinoaortic denervation were examined in rabbits in vivo and in vitro. In the in vivo studies the effects of intravenous administration of the alpha-adrenoceptor agonists phenylephrine and guanabenz and the antagonists prazosin and phentolamine on mean arterial pressure, heart rate, and plasma catecholamine levels were investigated in intact sham-operated rabbits and after bilateral baroreceptor deafferentation. In in vitro studies the maximum number of prazosin and clonidine binding sites and their dissociation constants were investigated using radioligand binding techniques. Mean arterial pressure was labile and significantly elevated in the sinoaortic denervated rabbits. Heart rate and basal plasma noradrenaline were also raised, but plasma adrenaline and tissue noradrenaline levels were similar in intact and debuffered animals. alpha-Adrenoceptor antagonists were more effective at lowering mean arterial pressure in the sinoaortic-denervated animals. This was at least in part the result of a lack of compensatory changes in sympathetic activity and heart rate in these animals. Pressor responses to the alpha 1-adrenoceptor agonist and more markedly to the alpha 2-adrenoceptor selective agonist were increased after sinoaortic denervation. These changes could not be related to alteration in alpha 1- or alpha 2-receptor binding in either heart, spleen, or brain tissue as there was no change in number of binding sites or affinity.

Animals↗
PubMedDate not supplied

Acute effects of phenoxybenzamine on alpha-adrenoceptor responses in vivo and in vitro: relation of in vivo pressor responses to the number of specific adrenoceptor binding sites.

Pressor responses to intravenous phenylephrine, an adrenoceptor agonist, and to the alpha 2-adrenoceptor-selective agonist guanabenz were examined in conscious rabbits 30 min after treatment with a range of doses of phenoxybenzamine (10(-5) to 5 mg/kg). The maximum number of specific prazosin- and clonidine-binding sites in the spleen of rabbits sacrificed 30 min after receiving phenoxybenzamine were measured using radioligand binding techniques. Treatment with phenoxybenzamine resulted in a dose-dependent reduction in the maximum pressor response to both phenylephrine and guanabenz, although phenoxybenzamine was a more potent antagonist at postsynaptic alpha 1- than at postsynaptic alpha 2-adrenoceptors. Phenoxybenzamine treatment also caused a dose-dependent reduction in specific [3H]prazosin and [3H]clonidine binding. The maximum in vivo pressor response to guanabenz was observed only when all specific clonidine-binding sites were present. There was a close correlation between in vitro receptor number and in vivo pressor responses for alpha 2-adrenoceptor stimulation but not for alpha 1-adrenoceptor-mediated responses. The maximum pressor response to phenylephrine could be obtained in rabbits in which the number of specific prazosin-binding sites was reduced by 60%. These experiments provide an approach to relating in vitro receptor number to in vivo responses.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Cardiac and lymphocyte beta-adrenoceptors in perinephritis hypertension in the rabbit.

The effects of perinephritis hypertension on lymphocyte and cardiac beta-adrenoceptors in the rabbit were examined. Hypertensive animals 8-12 weeks after surgery had an increase in cardiac weight consistent with hypertrophy compared with sham-operated age-matched controls. Specific binding of [I125] iodocyanopindolol (ICYP) to cardiac ventricular membranes was reduced in the hypertensive animals (Bmax44 +/- 14 in hypertensives and 30 +/- 15 fmoles/mg protein in controls; p less than 0.01). However, weight-matched ventricles from a group of older sham-operated normotensive rabbits showed a similar cardiac beta-receptor number to that found in the hypertensive animals. There were no changes in affinity of the ligand for the binding site. The reduction in cardiac beta-receptor density was not accompanied by changes in the chronotropic or blood pressure responses to isoprenaline in the conscious animal. Specific ICYP binding to lymphocyte beta-receptors did not differ significantly between the hypertensive and age-matched normotensive animals. Lymphocyte beta-adrenoceptors thus may not always reflect changes in heart beta-adrenoceptors, and changes in receptor density may not be directly related to blood pressure or have identifiable functional significance.

Adrenergic beta-Antagonists↗