The eradication of poliomyelitis.
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Child↗
Biomedical subjects
M J Hogan
Publications and source records attributed to M J Hogan.
In vivo distribution of CGS-19755 within brain in a model of focal cerebral ischemia.
The blood-brain barrier permeability of the competitive N-methyl-D-aspartate receptor antagonist CGS-19755 [cis-4-(phosphonomethyl)-2-piperidine carboxylic acid] was assessed in normal and ischemic rat brain. The brain uptake index of CGS-19755 relative to iodoantipyrine was assessed using the Oldendorf technique in normal brain. The average brain uptake index in brain regions supplied by the middle cerebral artery was 0.15 +/- 0.35% (mean +/- SEM). The unidirectional clearance of CGS-19755 from plasma across the blood-brain barrier was determined from measurements of the volume of distribution of CGS-19755 in brain. These studies were performed in normal rats and in rats with focal cerebral ischemia produced by combined occlusion of the proximal middle cerebral artery and ipsilateral common carotid artery. In normal rats the regional plasma clearance across the blood-brain barrier was low, averaging 0.015 ml 100 g-1 min-1. In ischemic rats this clearance value averaged 0.019 ml 100 g-1 min-1 in the ischemic hemisphere and 0.009 ml 100 g-1 min-1 in the nonischemic hemisphere. No significant regional differences in plasma clearance of CGS-19755 were observed in either normal or ischemic rats except in cortex injured by electrocautery where a 14-fold increase in clearance across the blood-brain barrier was measured. We conclude that CGS-19755 crosses the blood-brain barrier very slowly, even in acutely ischemic tissue.
Animals↗
Reversibility of nimodipine binding to brain in transient cerebral ischemia.
Using autoradiography, we have measured the in vivo binding of [3H]nimodipine to brain in a rat model of reversible cerebral ischemia. Ischemia was induced by simultaneous occlusion of the middle cerebral artery (MCA) and ipsilateral common carotid artery by microaneurysm clips. Rats were studied after 15 min of ischemia (ischemic group) or after 45 min of reperfusion following 15 min of ischemia (reperfused group). Regional cerebral blood flow (CBF) was determined autoradiographically using [14C]iodoantipyrine in both ischemic (n = 6) and reperfused (n = 6) groups. During ischemia blood flow in the territory of the MCA was depressed and recovered to normal only in the distal territory of the MCA following reperfusion. [3H]Nimodipine binding in the ischemic group (n = 12) was elevated in ischemic brain regions and declined significantly (p < 0.01) in these regions in the reperfused group (n = 11). The ratio of the volume of cortex showing increased binding to the total volume of the forebrain was 0.113 +/- 0.025 (mean +/- SD) in the ischemic group and declined to 0.080 +/- 0.027 following reperfusion (p < 0.005). In general, infarct was only observed in regions showing persistent elevation of nimodipine binding following reperfusion as determined by histology performed in a separate group of rats (n = 8) after 24 h of reperfusion. We conclude that increased nimodipine binding to ischemic tissue is initially reversible with prompt reestablishment of CBF and is a sensitive indicator of early and reversible ischemia-induced cerebral dysfunction.
Animals↗
Time course of cerebral blood flow and histological outcome after focal cerebral ischemia in rats.
BACKGROUND AND PURPOSE: The relation between time-dependent changes in cerebral blood flow and the appearance of infarction after focal cerebral ischemia is still a matter for debate. The aim of this study was to measure perfusion after simultaneous occlusions of the left middle cerebral artery and ipsilateral common carotid artery in rats and correlate it with the timing and distribution of histological changes. METHODS: We studied histological and cerebral blood flow changes 5 minutes and 4, 24, and 48 hours after the onset of focal ischemia. Blood flow was determined autoradiographically using [14C]iodoantipyrine. A coronal template subdivided into regions of interest was applied to the autoradiographs and the histological data. RESULTS: In some regions of the nonoccluded hemisphere, cerebral blood flow 5 minutes after occlusion fell below 50% of normal. Many ischemic structures showed stable blood flow for 48 hours after occlusion, confirming that in this model reperfusion is minimal. Infarction occurred eventually in all areas in which blood flow at 5 minutes fell below 10% of that in control rats, but infarction appeared earlier in regions in which blood flow at 5 minutes was below 5% of that in control rats. When blood flow at 5 minutes rose above 12% of that in control rats, the occurrence of infarction became unpredictable. CONCLUSIONS: Despite the general dependence of infarction on perfusion levels, blood flow was not a reliable indicator of those regions committed to infarction.
Animals↗
Evaluating an intern/residency program.
When faced with the task of program evaluation, many directors of medical education may find themselves overwhelmed. This article presents suggestions for conducting an evaluation, including the six basic elements to consider before embarking on such an undertaking. With an emphasis on selecting a model framework as a guide for conducting a program evaluation, this article examines one model--Stufflebeam's CIPP model--in depth.
Internship and Residency↗
In vivo binding of nimodipine in the brain: I. The effect of focal cerebral ischemia.
We report the regional variation in [3H]nimodipine binding in vivo during focal cerebral ischemia. After intravenous injection, 30 min of circulation of [3H]nimodipine was sufficient to establish a secular equilibrium of distribution in the brain. Rats sustained left middle cerebral and common carotid artery occlusions for 5 min, and 4, 24, and 48 h (n greater than or equal to 6 epr group). They were decapitated 30 min after injection of 250 microCi of [3H]nimodipine and their brains were submitted to autoradiography. The concentrations of [3H]nimodipine in plasma and brain structures, corrected for metabolism of nimodipine, were used to calculate the regional volumes of distribution (V) in the ischemic left (L) and control right (R) hemispheres. Log (VL/VR) was then defined as the group mean of the logarithms of the left-to-right ratio of V of [3H]nimodipine. In the lateral caudate, binding of [3H]nimodipine on the ischemic side was highest within 5 min of occlusion. Log (VL/VR) in this region for the combined sham-operated and normal control rats and those after 5 min and 4 and 24 h of ischemia were -0.014 +/- 0.025, 0.137 +/- 0.056*, -0.201 +/- 0.367, and -0.049 +/- 0.370 (mean +/- SD, *represents p less than 0.01 compared with controls). By contrast, in the superior frontal cortex, values for log (VL/VR) in the same sequence were -0.016 +/- 0.025, 0.028 +/- 0.056, 0.284 +/- 0.228*, and 0.224 +/- 0.069*, thus showing a significant rise in [3H]nimodipine binding only at 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
In vivo binding of nimodipine in the brain: II. Binding kinetics in focal cerebral ischemia.
We report the binding characteristics of [3H]nimodipine to normal and ischemic brain in vivo. We used the 1,4-dihydropyridine, nimodipine, to label the L-type voltage-sensitive calcium channel in focal cerebral ischemia after occlusion of both the middle cerebral and ipsilateral common carotid arteries in rats. Varying concentrations of [3H]nimodipine were infused 3.5 h after the onset of ischemia and circulated for 30 min before the brain was obtained for autoradiography and determination of regional nimodipine content. In separate sets of experiments, the metabolites of nimodipine were determined and the conditions for equilibrium of nimodipine distribution were established. Increased nimodipine uptake was observed in ischemic regions. This increased binding was saturable and specific with an affinity constant, KD, of 0.45 nM and a maximal regional binding capacity, Bmax, ranging from 3.1 to 10.9 pmol/g. Only binding to ischemic tissue was specific and saturable whereas that in nonischemic tissue was nonspecific. In vivo binding of nimodipine may be used to identify cell membrane depolarization and calcium channel activation in focal cerebral ischemia.
Animals↗
Accurate attenuation correction for a 3D PET system.
An accurate attenuation correction has been developed for a small-volume three-dimensional positron emission tomography (PET) system. Transmission data were measured as twenty-four 2D slices which were reconstructed and combined to form a 3D attenuation image. Emission data were reconstructed using a backproject-then-filter technique, and each event was corrected for attenuation at backprojection time by a reprojection through the attenuation image. This correction restores the spatial invariance of the point response function, thus allowing a valid deconvolution and producing an undistorted emission image. Scattering corrections were not applied to either the transmission or the emission data but simulation studies indicated that scattering made only a small contribution to the attenuation measurement. Results are presented for two phantoms, in which transmission scans of 57,500 and 18,700 events/slice were used to correct emission images of 5.2 and 2.8 million events. Although the attenuation images had poor statistical accuracy and a resolution of 13 mm, the method resulted in accurate attenuation-corrected images with no degradation in image resolution (which was 3 mm for the first emission image), and with little effect on image noise.
Image Processing, Computer-Assisted↗
Primary aldosteronism: diagnosis and treatment.
The syndrome of primary aldosteronism produces few signs or symptoms. The diagnosis should be suspected when either spontaneous hypokalemia or easily provoked hypokalemia is found in a patient with hypertension. Hypokalemia in association with inappropriate kaliuresis, low plasma renin activity, and a high plasma aldosterone concentration/plasma renin activity ratio are the findings on initial screening tests that should suggest primary aldosteronism. The diagnosis must be confirmed by demonstrating nonsuppressible aldosterone excretion in conjunction with normal cortisol excretion. The choice of therapy is based on distinguishing unilateral from bilateral adrenal disease. With a unilateral adrenal adenoma, surgical removal reverses the hypokalemia and frequently cures the hypertension. In most patients with bilateral adrenal hyperplasia who are treated surgically, however, hypertension persists; thus, the initial treatment in these patients should be pharmacologic.
Adenoma↗
A computerized paramedical approach to the outpatient management of essential hypertension.
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Adolescent↗
Pigment epithelial ensheathment and phagocytosis of extrafoveal cones in human retina.
The association between extrafoveal cone outer segments and pigment epithelial cells was studied by transmission electron microscopy in three human retinas; ages 5,45 and 60. The pigment epithelial apical surface from a fourth human retina, age 38,was viewed in the scanning electron microscope. Multiple villous-like apical processes protrude from the pigment epithelium into the space above each cone. Sometimes one or more of these processes is sheet-like in form and contains a wealth of intracellular organelles, including mitochondria. One or more of the villous-like procesess reaches the cone and expands to ensheath the upper one-third of the outer segment. Llike vertebrate rods, extrafoveal human cones shed their terminal disks in packets and these packets are phagocytosed by the ensheathing apical processes. The phagosomes then ascend in the processes toward the pigment epithelia soma. Digestion of phagosomes appears to begin in the apical processes.
Adult↗
Concurrent hypercortisolism and hypermineralocorticoidism.
Hypertension and hypokalemia occur in patients with Cushing's syndrome whereas aldosterone production is normal and plasma renin activity is usually normal or increased. A normal aldosterone level in the face of suppressed plasma renin activity is unusual and suggests excess mineralocorticoid hormone activity. Our patient, who had Cushing's syndrome due to adrenocortical adenoma, can be classified as having low renin hypertension (suppressed renin and normal aldosterone levels). The mineralocorticoid hormone in excess was deoxycorticosterone which suppressed renin. The aldosterone production was normal and was produced solely by the adenoma. Contralateral adrenal gland suppression of both the zona glomerulosa by deoxycorticosterone via renin, and of the fasciculata by cortisol via ACTH was demonstrated after removal of the adenoma. Normal adrenal function was gradually restored.
Adenoma↗
Management of small elevated pigmented choroidal lesions.
The diagnosis of small choroidal melanomas may be difficult, and the natural history of these small tumours is poorly understood. We followed up 20 patients with the diagnosis of small choroidal melanomas for from 2 to 20 years. In 11 of these patients the melanoma was observed to grow. Nine of these patients have undergone enucleation. Eight of the eyes contained spindle B melanomas and one contained a melanoma of mixed cell type. None of the 20 patients has developed detectable metastatic disease. From this series and others reported it appears that close serial examinations without therapeutic intervention is safe in patients with small melanomas until growth is observed, and that there is little evidence to suggest that photocoagulation or radiotherapy is of greater benefit in those patients than close serial examination.
Adult↗
Interpersonal problem solving: a theoretical perspective and methodology for the evaluation of residency education and its' relationship to health care processes and outcomes.
The study conceptualizes and implements an interaction model of interpersonal problem solving in the clinical milieu. This method of representing the interpersonal problem solving process and its relation to patient adherence is shown as an important tool for the evaluation of residency programs.
Evaluation Studies as Topic↗
Clinical problem solving: the relationship of cognitive abilities to PMP performance.
The relationship between patterns of individual differences on PMP performance and selected Gulford's Structure of Intellect test of cognitive abilities is shown. The groups were interpretable using the Guilford tests and confirm the use of the individual differences model.
Clinical Competence↗
Location of aldosterone-producing adenomas with 131I-19-iodocholesterol.
We used 131I-19-iodocholesterol as an adrenal-imaging agent in 27 hypertensive patients who had biochemical evidence of abnormalities in the renin-angiotensin-aldosterone system. In 10 of 12 patients in whom the biochemical findings suggested the presence of an aldosterone-producing adenoma the adrenal uptake was asymmetric. The adenoma was subsequently confirmed in all eight patients in this group who underwent operation. In contrast, the adrenal uptake was asymmetric in only one of 13 patients with biochemical evidence of iodopathic hyperaldosteronism or low-renin essential hypertension. Two patients with adrenal carcinoma causing primary aldosteronism did not concentrate the isotope in their tumors. When metabolic studies suggest an aldosterone-producing adenoma, adrenal imaging with 131I-19-iodocholesterol may locate the tumor before operation.
Adenoma↗
Correlation between degree of malignancy and the radioactive phosphorus uptake test in ocular melanomas.
Twenty-nine patients who had undergone enucleation for ocular malignant melanoma were studied. The results of the radioactive phosphorus uptake (32P) tests were correlated with histopathologic observations. There was a positive correlation between the 32P test results and the histologic degree of malignancy. Mixed cell melanomas were more frequent in the patients ranked with higher 32P test results. Spindle cell melanomas occurred more frequently in patients with lower 32P test results. Mitoses per field and degree of malignancy correlated positively with 32P test results when ranked in a masked manner by two ocular pathologists. Tumor volume and clinical factors did not correlate with the 32P test results. While patients with mixed cell melanomas had higher mean 32P test results than those with spindle cell melanomas, a large variance was noted. Because of this the 32P test is unreliable in predicting the histopathology of a tumor in individual cases.
Aged↗
Jules Stein, MD.
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History, 19th Century↗