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Biomedical subjects

S Herold

Publications and source records attributed to S Herold.

At least 19 recordsLinked to original sources

Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task.

BACKGROUND: This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow. METHOD: Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers. RESULTS: In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition. CONCLUSION: These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex.

Adult

Adjustment formulae for maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated oestriol to maternal weight and smoking.

Serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) were measured in serum samples of 4131 non-smoking and 1018 smoking women during the second trimester of pregnancy. The levels of all three analytes decreased with increasing body weight. The AFP median was significantly increased in smokers in a dose-response association; hCG decreased by 21 per cent and uE3 decreased by 3 per cent in smokers in a non-dose-related fashion. Regression functions for adjustment of serum levels for weight and smoking should be considered in risk estimation for Down syndrome in order to give a woman's individual risk more precisely.

Body Weight

Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age.

Regional cerebral blood flow (CBF), oxygen extraction ratio (OER), oxygen utilization (CMRO2) and blood volume (CBV) were measured in a group of 34 healthy volunteers (age range 22-82 yrs) using the 15O steady-state inhalation method and positron emission tomography. Between subjects CBF correlated positively with CMRO2, although the interindividual variability of the measured values was large. OER was not dependent on CMRO2, but highly negatively correlated with CBF. CBV correlated positively with CBF. When considering the values of all the regions of interest within a single subject, a strict coupling between CMRO2 and CBF, and between CBF and CBV was found, while OER was constant and independent of CBF and CMRO2. In 'pure' grey and white matter regions CMRO2, CBF and CBV decreased with age approximately 0.50% per year. In other regions the decline was less evident, most likely due to partial volume effects. OER did not change or showed a slight increase with age (maximum in the grey matter region 0.35%/yr). The results suggest diminished neuronal firing or decreased dendritic synaptic density with age.

Adult

Cerebral blood flow and metabolism of oxygen and glucose in young autistic adults.

Regional cerebral blood flow, oxygen consumption and glucose consumption were measured by positron emission tomography in six young autistic men. No significant differences were found between patients and normal controls for any of the physiological variables. The results do not substantiate the previous finding of glucose hypermetabolism in autism; the likely reasons for the variance in findings are discussed.

Adult

The cerebral metabolism of glucose and oxygen measured with positron tomography in patients with mitochondrial diseases.

Cerebral oxygen and glucose metabolism have been studied in 8 patients with biochemically defined mitochondrial myopathies and 7 normal control subjects using positron emission tomography. Four patients had myopathy alone and 4 had predominantly central nervous system (CNS) disease. Cerebral oxygen and glucose metabolism were measured concurrently in the two groups of patients with 15O, 11C and 18F labelled tracers and positron emission tomography (PET). Patients with major CNS disease showed an uncoupling of glucose and oxygen metabolism when compared with patients without cerebral disease and normal subjects. The mean ratio between oxygen and glucose utilization was 3.8 moles of oxygen per mole of glucose in patients with CNS disease, compared with 5.6 for controls and 6.4 for patients with myopathy alone. The altered stoichiometry in CNS cases indicates aerobic glycolysis to lactate and/or other intermediate metabolites. Patients with major CNS disease showed a 50% reduction in cerebral oxygen utilization compared with cerebrally unaffected patients and normal subjects. These findings indicate that in patients with a mitochondrial encephalopathy the defect identified in skeletal muscle is also expressed in the brain.

Adult

Assessment of cerebral haemodynamic reserve: correlation between PET parameters and CO2 reactivity measured by the intravenous 133 xenon injection technique.

Regional cerebral blood flow (CBF), oxygen utilisation, fractional oxygen extraction (OER) and cerebral blood volume (CBV) were measured by positron emission tomography (PET) in 21 patients with occlusive carotid artery disease. In the same patients, measurements of cerebral CO2 reactivity were performed using the intravenous xenon-133 technique. A significant correlation was found in symptomatic hemispheres between the CBF/CBV ratio and CO2 reactivity. Four patients had significant increases in OER and this was associated with a reduction in CBF/CBV ratio implying exhaustion of haemodynamic reserve. CO2 reactivity was reduced below 1.5% mm Hg in all four cases with raised OER but only in two cases with normal OER. In patients with CO2 reactivities above 1.5% mm Hg, OER was normal in all cases. It is concluded that measurements of CO2 reactivity provide a satisfactory method for assessing cerebral haemodynamic reserve.

Aged

Measurement of glucose utilisation with [18F]2-fluoro-2-deoxy-D-glucose: a comparison of different analytical methods.

A number of different analytical methods were applied to dynamic scans obtained with [18F]2-fluoro-2-deoxy-D-glucose and positron emission tomography. In particular, methods applying three, four, standard, or no rate constants were compared in four studies on three normal subjects. In addition, regional cerebral blood flow, oxygen utilisation, and blood volume were measured using the oxygen-15 steady-state inhalation technique. There was a large difference between values of glucose utilisation obtained with the various analytical methods, in particular between methods using three or four rate constants. This difference was not due to contamination of the tracer with [18F]2-fluoro-2-deoxy-D-mannose. For dynamic techniques, the separate measurement of regional cerebral blood volume was essential. Static techniques (single scans with standard or no rate constants) were best related to dynamic techniques utilising four rate constants. From the results, it followed, however, that these static techniques can only be applied clinically if relatively large disturbances of glucose metabolism and no changes in rate constants are anticipated. The lumped constant was assessed from the combined measurement of oxygen and glucose utilisation and was higher than previously reported.

Deoxy Sugars

[Plasma exchange in acute abdomen with multiple organ failure--a case report].

Following four weeks of conservative treatment of acute pancreatitis a 43 years old female was admitted to our ICU in severe circulatory shock (MAP less than 50 mmHg despite dopamine and dobutamine 5 mcg/kg/min, and norepinephrine 0.4 mcg/kg/min), respiratory failure, incipient renal failure and coma. Laboratory examination revealed thrombopenia (14 G/l) and leucopenia (0.5 G/l), as well as impaired prothrombine time (20%) and partial thromboplastine time (greater than 2 min). As abdominal sepsis was suspected to be the most likely cause of the patients multiple organ failure, a laparotomy was planned. To improve coagulation prior to surgery, plasmapheresis was performed exchanging 4.8 liters of plasma with fresh frozen plasma. In addition 3 units of platelets were transfused. The effects of the plasmapheresis were an improvement of circulatory as well as coagulatory parameters. Laparotomy revealed toxic megacolon, whereas the pancreas seemed to be normal; a coecostomy and a transversostomy were performed. The patient thereafter improved gradually; catecholamine doses were reduced, renal function recovered and five days postoperatively weaning from the ventilator was possible. Platelet substitution (6 more units), fresh frozen plasma administration (76 units à 200 ml) and AT III substitution (total 10,500 U) had to be continued throughout the first week. Five weeks after this operation, which would have been impossible without preoperative plasmapheresis, the patient was discharged in good health.

Abdomen, Acute

Glucose transport across the blood-brain barrier in normal human subjects and patients with cerebral tumours studied using [11C]3-O-methyl-D-glucose and positron emission tomography.

The kinetics of the regional cerebral uptake of [11C]3-O-methyl-D-glucose ([11C]MeG), a competitive inhibitor of D-glucose transport, have been studied in normal human subjects and patients with cerebral tumours using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and blood flow enabled corrections for the contribution of intravascular tracer signal in PET scans to be carried out and regional unidirectional cerebral [11C]MeG extractions to be determined. A three-compartment model containing an arterial plasma and two cerebral compartments was required to produce satisfactory fits to experimental regional cerebral [11C]MeG uptake data. Under fasting, resting conditions, normal controls had mean unidirectional whole-brain, cortical, and white matter [11C]MeG extractions of 14, 13, and 17%, respectively. Mean values of k1 and k2, first-order rate constants describing forward and back transport, respectively, of tracer into the first cerebral compartment, were similar for [11C]MeG and [18F]2-fluoro-2-deoxy-D-glucose (18FDG), a second competitive inhibitor of D-glucose transport. k3, a rate constant describing FDG phosphorylation, was 20 times higher for cortical FDG uptake than the k3 fitted for [11C]MeG cortical uptake. Glioma [11C]MeG extractions ranged from normal levels of 12% to raised levels of 30%. Transport of [11C]MeG in and out of contralateral cortical tissue was significantly depressed in patients with gliomas. It is concluded that under fasting, resting conditions, regional cerebral glucose extraction remains relatively uniform throughout normal brain tissue. Gliomas, however, may have raised levels of glucose extraction. The nature of the second cerebral compartment required to describe [11C]MeG uptake is unclear, but it could represent either a useless phosphorylation-dephosphorylation cycle or nonspecific tracer uptake by a cerebral subcompartment.

3-O-Methylglucose

Regional cerebral glucose transport in insulin-dependent diabetic patients studied using [11C]3-O-methyl-D-glucose and positron emission tomography.

Regional cerebral [11C]3-O-methyl-D-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 mM), and four were studied at hyperglycaemic plasma glucose levels (mean 13 mM). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 mM had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and D-glucose for the passive facilitated transport carrier system for hexoses across the blood-brain barrier (BBB). It is concluded that the number and affinity of D-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of D-glucose across the BBB.

3-O-Methylglucose

Hydrogen clearance method for determining local cerebral blood flow. I. Spatial resolution.

To define the effective spatial resolution of the hydrogen clearance method, serial local CBF (LCBF) measurements were performed at different distances from the cortico-white matter junction of the cat brain. Twenty-five platinum-wire microelectrodes with a sensitive surface of 0.07 mm2 were inserted into the cerebral cortex of three cats through burr holes in the skull and advanced toward the ear-to-ear level in 1- or 0.1-mm steps. Most electrodes passed from high-perfusion regions into low-perfusion areas, indicating that the cortico-white matter junction had been traversed. Whereas within the gray and white matter the LCBF values were fairly constant, a striking decrease of CBF was registered at the cortico-white matter junction. Here the mean LCBF from 12 electrodes showed significant differences in flow between two locations 1 mm apart. On two occasions, a significant difference in CBF was found for locations only 0.1 mm apart. Despite this high spatial resolution, monoexponential clearance curves were detected only in the vicinity of the cortico-white matter junction. It is therefore assumed that factors other than flow might influence H2 clearance.

Animals

Hydrogen clearance method for determining local cerebral blood flow. II. Effect of heterogeneity in cerebral blood flow.

The time course of hydrogen uptake and washout was followed simultaneously in extracranial arterial blood, cortex, subcortical white matter, and caudate nucleus of the cat brain to study intercompartmental hydrogen concentration differences. A clear delay of 1-2 min was seen between the onsets of concentration increase in arterial blood and low-flow brain tissues. Equilibration time was dependent on local CBF and varied between 3 and 34 min. Hydrogen was not cleared simultaneously from the regions under detection. This led to considerable concentration differences within the cerebral tissue during washin and washout phases. Analysis of the clearance curves revealed that secondary equilibration occurs during washout. Hydrogen concentration in the external carotid artery was not a reliable reflection of tracer input in the brain tissues. The consequences of these observations for other techniques of CBF measurement using less diffusive gases and external detection are discussed.

Animals

A comparison between regional cerebral blood flow measurements obtained in human subjects using 11C-methylalbumin microspheres, the C15O2 steady-state method, and positron emission tomography.

Regional cerebral blood flow (rCBF) values were measured in nine normotensive subjects with known previous myocardial infarctions using 15 mu 11C-methylalbumin microspheres and positron emission tomography (PET). Microspheres were injected directly into the left ventricle of each subject during routine cardiac angiography and blood flow calibrated using the reference sample technique. rCBF values were compared with those obtained for a group of fifteen age-matched normal controls using the C15O2 steady-state inhalation technique. Using 1 cm radius circular regions of interest, the 11C-microspheres approach yielded mean blood flow values of 51 ml/100 ml/min and 48 ml/100 ml/min for regions of interest dominated by temporal and frontal cortical grey matter respectively. An rCBF value of 32 ml/100 ml/min was obtained for regions of interest dominated by frontal white matter. Mean rCBF values obtained for these regions using the C15O2 method were not significantly different (52 ml/100 ml/min, 44 ml/100 ml/min, and 28 ml/100 ml/min respectively), but the C15O2 approach gave a significantly lower rCBF value than the 11C-microspheresfor regions of interest dominated by occipital grey matter. Although the two groups of subjects studied were not strictly equivalent, the good agreement between blood flow values obtained using the 11C-microspheres and the C15O2 techniques is of interest, and suggests that the assumptions of the C15O2 steady-state approach do not lead to large errors in practice.

Aged