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Biomedical subjects

A Hakim

Publications and source records attributed to A Hakim.

At least 73 records · Page 4Linked to original sources

Anatomical-functional correlation using an adjustable MRI-based region of interest atlas with positron emission tomography.

A procedure is described for combining anatomical information from magnetic resonance imaging (MRI) or computerized tomography (CT) and functional information from positron emission tomography (PET) in a rapid fashion. MRI data are combined with a procedure for the definition, storage, and recall of anatomically based regions of interest. An atlas of standard regions of interest, defined for a set of 18 parallel planes spaced at 6-mm intervals, provides an initial region of interest template for each patient slice. Global adjustments to scale, orientation, and position are applied to obtain an initial match. Individual regions of interest may then be moved, deleted, or redrawn as needed. The ability to store region of interest templates ensures reproducibility of analysis over long periods and introduces a standardization of analysis technique. In 25 brain structures, the mean coefficient of variation in cerebral glucose utilization rate (CMRGlc) measurements among five neuroanatomically trained observers was reduced from 8.1% for manual region of interest definition to 4.0% using the template approach with MRI. Template analysis for space-occupying lesions such as tumors or infarcts is illustrated with PET data from a stroke study, emphasizing the facility for rapid, reproducible analysis of multifunctional studies. MRI-PET matching for a structurally intact caudate nucleus having reduced CMRGlc in Huntington's disease emphasizes the accuracy of anatomical localization required to quantify small structures.

Adult↗

Workshop on schizophrenia, PET, and dopamine D2 receptors in the human neostriatum.

Recently, two research groups published numbers for D2 receptor sites in the neostriatum of drug-naive schizophrenic patients, obtained in vivo by positron emission tomography (PET). One study appeared to confirm the increase of D2 receptor numbers, while the other study did not. A workshop was convened in Montreal to examine the reasons for the discrepancy between the results obtained by the two groups. The workshop considered patient populations, PET instrumentation and scanning methods, pharmacology, and modeling. The workshop identified differences between the approaches of the two groups that could contribute to the divergent results, including age and chronicity of the patient samples, brain region selected for study, metabolism of the different radioligands in blood and brain, reversibility of binding, PET instrumentation, and complexity of data analysis. The workshop concluded that these initial efforts had made considerable progress in establishing the role of PET in the understanding of the biochemical processes underlying mental illness. In particular, the unique ability to quantify regional neuroreceptor density at different stages in the evolution of the disease has been implemented. At the same time, the work so far and this conference served to identify the main sources contributing to the different findings from the two centers. This information will be important in designing the next phase of the research which will build upon and reconcile these apparent discrepancies.

Adult↗

Suppression of lymphocyte function with breast carcinoma I-active glycopeptides.

Patients with metastatic breast carcinoma (BCa) have defective peripheral blood lymphocyte (PBL) responsiveness to mitogenic and antigenic stimulation. In the following experiments, glycopeptides were isolated from the pronase digests of breast carcinoma tissue. After elution from Sephadex G-50, glycopeptides from BCa inhibited PBL responsiveness to mitogenic (PHA) stimulation. The glycopeptides contained blood group I-antigenic determinants. These experiments demonstrate the presence of blood group I-active peptides in breast carcinoma that suppress peripheral blood lymphocyte functions. Further studies are in progress.

Blood Group Antigens↗

Borderzone ischemia.

Positron emission tomography was used to measure cerebral perfusion and metabolism in 7 patients with severe carotid stenosis. None of the patients had sustained a major stroke, and all had a normal neurological examination except 1 patient with a mild neurological deficit from a capsular lacuna. Cerebral blood flow (CBF), cerebral blood volume, the cerebral blood flow/cerebral blood volume ratio, oxygen metabolism, and the fractional extraction of oxygen by the brain were measured in the cerebral cortex of both hemispheres in the anterior and middle cerebral artery distributions, in the borderzone regions between the anterior and middle cerebral arteries (anterior borderzone), and between the middle cerebral and posterior cerebral arteries (posterior borderzone). Results obtained in patients were compared, using Student's t test, to those obtained in 6 neurologically normal, elderly volunteers. Cerebral blood flow and the cerebral blood flow/cerebral blood volume ratio were both significantly decreased (p less than 0.025 and p less than 0.05, respectively) in the anterior borderzone ipsilateral to the carotid stenosis. In the same region there was a tendency toward a rising fractional extraction of oxygen with the oxygen metabolism maintained in the low-normal range. Cerebral blood flow was also significantly decreased (p less than 0.05) in the contralateral anterior borderzone. Hemodynamic and metabolic variables in other vascular territories were not significantly different from values obtained in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

An immunosorbent assay for blood group I antigens in breast carcinoma.

Tumor cells elaborate and release into the circulation a variety of glycoproteins. An enzyme-linked immunosorbent assay (ELISA) was developed to monitor carbohydrate structures secreted into the circulation. Among these antigens are the structures specific for the blood group I antigens, which are incompletely converted to ABH antigens on the membranes of tumor cells. The I antigens in the sera of 67 women with breast carcinoma (BCa), 58 with benign breast disease (BBD), and 47 controls were measured by the ELISA. In this assay, I antigen from ovarian cyst mucin was bound to the wells of polystyrene microtiter plates. The monoclonal human anti-I antibody (Hy) was added to the wells along with perchloric acid extracts of patient and control sera at five different dilutions. The anti-I binding to the solid-phase I antigen was determined after incubation steps with peroxidase-labeled anti-human IgM and substrate. The amount of sera extracts giving 50% inhibition of anti-I (Hy) binding was determined from the inhibition curves which were corrected by integrating the slope values into that of the standard curve obtained with extracts of normal sera. The I antigens were significantly higher in pathologic stage (PS) IV sera (P less than 0.001), and comparable in PS I, PS II, and PS III and BBD sera to those in control sera. The anti-I (Hy) binds strongly Gal 1,4 GlcNAc 1,6 Gal (alpha GalNAc); Gal 1,4 GlcNAc 1,6 (Gal 1,4 GlcNAc 1,3) Gal; and to a lesser extent Gal 1,4 GlcNAc 1,3 Gal 1,4 GlcNAc (0.06, 0.09, and 0.35 mM, giving 50% inhibition, respectively). It was concluded that similar or related structures may be expressed on the membrane of metastatic BCa cells.

Antibodies, Neoplasm↗

Hemodynamic and metabolic effects of cerebral revascularization.

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.

Aged↗

Effect of vascular activity in the determination of rate constants for the uptake of 18F-labeled 2-fluoro-2-deoxy-D-glucose: error analysis and normal values in older subjects.

Regional cerebral blood volume (CBV) can be calculated using data obtained during the kinetic analysis of 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) uptake measured by positron emission tomography (PET). As a result the influence of vascular activity upon the determination of FDG rate constants can be minimized. The method is investigated by simulation experiments and by analysis of PET studies on seven older, healthy human volunteers aged 52-70 years. The accuracy of measured FDG rate constants k1, k2, and k3, obtained either by omitting the early portion of the uptake curve or by explicit inclusion of CBV as a fit parameter, is compared. The root mean square error in measured rate constant for the latter method is equivalent to that obtained by omitting the first 2.5-3 min of tissue data and neglecting the CBV term. Hence, added information about the physiological state of the tissue is obtained without compromising the accuracy of the (FDG) rate constant measurement. In hyperemic tissue the explicit determination of the vascular fraction results in more accurate estimates of the FDG rate constants. The ratio of CBV determined by this method to CBV obtained using C15O in six subjects with CBV in the normal range was 0.92 +/- 0.32. A comparison of the CBV image obtained by this method with that obtained using C15O in an arteriovenous malformation case demonstrates the accuracy of the approach over a wide range of CBV values. The mean value for CBV fraction in gray matter obtained by this method in the older control group was 0.040 +/- 0.014. Average gray matter rate constants obtained were k1 = 0.084 +/- 0.012, k2 = 0.150 +/- 0.071, and k3 = 0.099 +/- 0.045 min-1.

Aging↗

Acute respiratory failure in motor neuron disease.

Five patients with sudden deterioration in respiratory function were studied. In three a history of motor neuron disease was known but in two the first evidence of the disease was severe hypoventilation. No other cause for the respiratory difficulty could be detected in any, and all eventually achieved important partial or even complete independence from mechanical support. Severe hypoventilation can be the initial symptom of motor neuron disease, and not all patients with this complication of the disease have the poor prognosis usually expected.

Acute Disease↗

[Investigations of the activity of disaccharidases in growing sheep. 1. Suckling lambs from birth to an age of 4 weeks].

Investigations of the course disaccharidases take in duodenum and pancreas were made with 20 suckling lambs (straw litter, supplementary feed from 3rd week onwards) at an age between 1 and 30 days. In the first week of the Lambs' lives the activity of lactase in the duodenal mucosa was highest. In the following weeks there was a slightly falling tendency. During the first four weeks of the lambs' lives there were no statistically significant differences concerning the maltase activities in the duodenal mucosa. At the beginning of the first and at the end of the fourth week of the lambs' lives the activity of lactase in the content of the duodenum was significantly lower than at the end of the first and up to the third week. The maltase in the contents of the duodenum showed a significantly higher activity at the end of the fourth week of life. Enzyme activities in the contents of the duodenum were significantly lower then those in the mucosa. After maltase activity in the pancreas had shown high values in the first two days of life, it decreased distinctly toward the end of the first week and than increased again up to the fourth week of life. In the period investigated, saccharase activity in the duodenal mucosa and in the contents of the duodenum could not be detected in any lamb.

Animals↗