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Biomedical subjects

M Grond

Publications and source records attributed to M Grond.

At least 55 records · Page 3Linked to original sources

[Polyneuropathies in monoclonal gammopathy of undetermined significance: initial manifestation of a lymphoma].

BACKGROUND: Monoclonal gammopathies-including so-called monoclonal gammopathies of undetermined significance-MGUS-may cause polyneuropathies, even if immunoglobulin concentrations are within a normal range. CASE REPORT: We report on a patient with a rapidly progressive polyneuropathy with severe motor disturbances in whom a small amount of a monoclonal IgM kappa cryoglobulin was found. Only by extensive, repeatedly performed diagnostic procedures could scattered lymphoma cells be detected. Nonspecific immunosuppression had been unsuccessful but eventually a more specific chemotherapy led to an almost complete, sustained recovery. CONCLUSION: This case shows that in patients with a polyneuropathy of uncertain etiology monoclonal immunoglobulins should be looked for and that a MGUS can precede a lymphoma. Therefore these, patients with a MGUS and clinical deterioration despite conventional immunosuppressive treatment should undergo large-scale diagnostic check-up to make sure that the chance for an adequate chemotherapy is taken.

Aged↗

Clozapine-induced agranulocytosis and thrombopenia in a patient with dopaminergic psychosis.

In patients with Parkinson' disease and dopaminergic psychosis, clozapine treatment is recommended as the drug is free from extrapyramidal side effects and does not worsen motor symptoms of the underlying disease. The use of clozapine, however, is limited due to its hematotoxic side effects. For treatment of clozapine-induced agranulocytosis, granulocyte colony-stimulating factors (G-CSF) are recommended. We report the case of a 72-years-old male patient with clozapine-induced agranulocytosis and thrombopenia. Neutropenia was successfully treated with G-CSF, but thrombopenia persisted and resolved spontaneously after 14 days. Bone marrow toxicity of clozapine is not restricted to white cell maturation, but may also impair thrombocytopoesis.

Aged↗

Repeat positron emission tomographic studies in transient middle cerebral artery occlusion in cats: residual perfusion and efficacy of postischemic reperfusion.

The wider clinical acceptance of thrombolytic therapy for ischemic stroke has focused more attention on experimental models of reversible focal ischemia. Such models enable the study of the effect of ischemia of various durations and of reperfusion on the development of infarctions. We used high-resolution positron emission tomography (PET) to assess cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) before, during, and up to 24 h after middle cerebral artery occlusion (MCAO) in cats. After determination of resting values, the MCA was occluded by a transorbital device. The MCA was reopened after 30 min in five, after 60 min in 11, and after 120 min in two cats. Whereas all cats survived 30-min MCAO, six died after 60-min and one after 120-min MCAO during 6-20 h of reperfusion. In those cats surviving the first day, infarct size was determined on serial histologic sections. The arterial occlusion immediately reduced CBF in the MCA territory to < 40% of control, while CMRO2 was less affected, causing an increase in OEF. Whereas in the cats surviving 24 h of reperfusion after 60- and 120-min MCAO, OEF remained elevated throughout the ischemic episode, the initial OEF increase had already disappeared during the later period of ischemia in those cats that died during the reperfusion period. After 30-min MCAO, the reperfusion period was characterized by a transient reactive hyperemia and fast normalization of CBF, CMRO2, and CMRglc, and no or only small infarcts in the deep nuclei were found in histology. After 60- and 120-min MCAO, the extent of hyperperfusion was related to the severity of ischemia, decreased CMRO2 and CMRglc persisted, and cortical/subcortical infarcts of varying sizes developed. A clear difference was found in the flow/metabolic pattern between surviving and dying cats: In cats dying during the observation period, extended postischemic hyperperfusion accompanied large defects in CMRO2 and CMRglc, large infarcts developed, and intracranial pressure increased fatally. In those surviving the day after MCAO, increased OEF persisted over the ischemic episode, postischemic hyperperfusion was less severe and shorter, and the perfusional and metabolic defects as well as the final infarcts were smaller. These results stress the importance of the severity of ischemia for the further course after reperfusion and help to explain the diverging outcome after thrombolysis, where a relation between the residual flow and the effectiveness of reperfusion was also observed.

Animals↗

Hypnotic catalepsy-induced changes of regional cerebral glucose metabolism.

In an attempt to elucidate the physiological basis of hypnosis, we investigated the changes of whole-brain and regional cerebral glucose metabolism, from a state of resting wakefulness to a hypnotized state with whole-body catalepsy, using positron emission tomography and the 2[18F]fluorodeoxyglucose method in 15 highly hypnotizable adults. Neither the random order of study conditions nor any of the other experimental factors had a measurable effect, and there was no statistically significant global activation or metabolic depression. However, repeated measures analysis of variance revealed a statistically significant heterogeneity of symmetric regional responses: Mainly the occipital areas, including visual and paravisual cortex, became relatively deactivated, while some metabolic recruitment was found in structures involved in sensorimotor functions. The observed pattern of changes of regional cerebral activity corresponds with the shift of attention away from normal sensory input that hypnosis is known to produce.

Adult↗

Cognitive impairment in Alzheimer's disease correlates with ventricular width and atrophy-corrected cortical glucose metabolism.

We compared the correlation of PET and MRI with neuropsychological tests in 26 patients with probable Alzheimer's disease (AD). The width of the temporal horns and the third ventricle, regional metabolic rates of glucose (rCMRGlu) and the proportion of cerebrospinal fluid space in mesial temporal and temporoparietal cortical regions were measured with three-dimensionally coregistered PET and MRI in two planes perpendicular to the Sylvian fissure. Highly significant correlations between rCMRGlu and neuropsychological tests were found mainly in the temporoparietal cortex, with and without correction for atrophy. Correlations of similar magnitude were seen also between most tests and the width of the temporal horns and third ventricle. Changes in the third ventricle and mesial temporal lobe were best seen with MRI, whereas PET most clearly depicted alterations in neocortical association areas. These two aspects of the disease correlated with the severity of dementia to a similar degree.

Aged↗

P300 in Alzheimer's disease: relationships to dementia severity and glucose metabolism.

In 45 patients (aged 48-85 years) with probable Alzheimer's disease (AD) according to current research criteria (NINCDS-ADRDA) with different stages of dementia severity (Mini Mental Status Examination (MMSE) 7-27) the auditory evoked P300 waves were mapped and regional cerebral metabolic rates of glucose were measured by positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose. Age adjusted P300 latency was significantly correlated to dementia severity (r = -0.33, p = 0.028), but no significant relationships were found for P300 amplitudes. Dependencies existed among cortical glucose metabolic rates and MMSE with the highest correlation coefficient for the metabolic ratio of regions typically affected and non-affected in AD (r = 0.75, p = 0.0001). A significant correlation was also calculated between P300 latency and metabolic ratio (r = -0.44, p = 0.002), but no relationships were observed among P300 amplitudes and glucose metabolic rates of individual brain regions. These results indicate that P300 latency and metabolic rates but not P300 amplitudes qualify as measures of severity in AD. The lack of regional correlations among P300 amplitudes and glucose metabolism is not consistent with a cortical contribution to P300 generation.

Aged↗

Severity of vascular dementia is related to volume of metabolically impaired tissue.

The relation between dementia severity and regional cerebral metabolic rate of glucose was studied in 28 patients with vascular dementia (VD) in comparison with 20 age-matched patients who were suffering from Alzheimer's disease (AD) and 24 normal subjects by using positron emission tomography with fludeoxyglucose F 18. Similar metabolic impairment was found in the temporoparietal and frontal association cortex in patients with VD and in those with AD. Metabolism of the basal ganglia, thalamus, and cerebellum was reduced significantly in patients with VD only. The total volume of regions with metabolism below the 95% confidence interval of control values was significantly related to the severity of dementia but did not differ between patients with VD and those with AD. A metabolic ratio of regional cerebral glucose metabolism of association areas divided by regional cerebral glucose metabolism of structures that were typically not affected by AD was significantly lower in patients with AD than in those with VD. This ratio was also related to dementia severity in both types of dementia.

Aged↗

Subcortical damage and cortical dysfunction in progressive supranuclear palsy demonstrated by positron emission tomography.

Regional cerebral glucose metabolism was studied in nine patients with progressive supranuclear palsy (PSP). (18F)-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) revealed general cerebral hypometabolism in all PSP patients in comparison with an age-matched reference group. When comparing the degree of regional metabolic deterioration, a consistent pattern of the most affected brain regions became obvious: the strongest significant alteration of cerebral glucose metabolism was observed in subcortical regions, e.g. in caudate nucleus, lentiform nucleus and upper mid-brain, which showed nerve cell loss in previous pathological studies. Less severe, but still significant hypometabolism was observed in frontal cortex. This pattern of hypometabolism was distinctly different from that typically seen in dementias of Alzheimer's type. The present data show that PET findings agree with histopathological studies: PSP is a primarily subcortical disease with secondary inactivation of cortical, especially of frontal brain regions.

Aged↗

Quantitative EEG mapping and PET in Alzheimer's disease.

Quantitative analysis of topographical EEG was studied in comparison with measurement of regional glucose metabolism by PET in 42 patients with clinical diagnosis of probable dementia of Alzheimer type (AD) and in 15 age-matched normal controls. Measures analyzed included global and regional data from areas typically affected and not affected by AD pathology. While disturbance of metabolism followed a typical regional pattern, relative alpha, theta and delta power were more globally altered without selectivity for specific regions. Separation between AD and age matched controls by relative theta power was correct in 86% and was close to that by temporo-parietal glucose metabolism (correct classification 87%). Relative theta power as well as temporo-parietal glucose metabolism were significantly correlated (tau B = 0.54 and -0.53, respectively) to severity of AD assessed by the global deterioration scale. These results indicate that EEG measures may be used with an accuracy close to metabolic values from PET for the assessment of severity of AD.

Aged↗

Positron emission tomography in the differential diagnosis of organic dementias.

At present, PET is the only technology affording the quantitative, three-dimensional imaging of various aspects of brain function. Since function and metabolism are coupled, and since glucose is the dominant substrate of the brain's energy metabolism, studies of glucose metabolism by PET of 2(18F)-fluoro-2-deoxy-D-glucose (FDG) are widely applied for investigating the participation of various brain systems in simple or complex stimulations and tasks. In focal or diffuse disorders of the brain, functional impairment of affected or inactivated brain regions is a reproducible finding. While glucose metabolism is decreased slightly with age in a regionally different degree, in most types of dementia severe changes of glucose metabolism are observed. Degenerative dementia of the Alzheimer type is characterized by a metabolic disturbance most prominent in the parieto-occipito-temporal association cortex and later in the frontal lobe, while primary cortical areas, basal ganglia, thalamus, and cerebellum are not affected. By this typical pattern Alzheimer disease can be differentiated from other dementia syndromes, as e.g., Pick's disease (with the metabolic depression most prominent in the frontal and temporal lobe), multi infarct dementia (with multiple focal metabolic defects), and Huntington's chorea (with metabolic disturbance in the neostriatum). In demented patients PET studies can also be applied to the quantification of treatment effects on disturbed metabolism.

Alzheimer Disease↗

Impaired metabolic activation in Alzheimer's disease: a PET study during continuous visual recognition.

Regional cerebral metabolic rate of glucose (rCMRGl) was studied in 21 patients with probable Alzheimer's disease (AD) and nine age-matched normal controls by positron emission tomography (PET) of 2(18F)-fluoro-deoxy-D-glucose (FDG) at rest and during stimulation with a continuous visual recognition task. While global metabolism at rest was comparable in both groups, rCMRGl in the temporo-parietal junction area, the mid-temporal and the frontal cortex was typically decreased in the AD patients. The continuous visual recognition task adapted to the individual performance capacity increased the global metabolic rate in the controls by 21 +/- 18%, while in the AD patients the metabolic change (5.7 +/- 11.1%) during activation was significantly weaker (P = 0.023). Due to the tasks chosen the activation of rCMRGl in both groups was most prominent in the visual cortex and the temporo-parietal association areas, although the recognition task additionally involved widespread brain structures with varying rCMRGl. A significant correlation was found between rCMRGl in areas usually severely affected by AD pathology, e.g. the temporo-parietal cortex, and GDS scores, and became stronger during metabolic activation. Neither at rest nor during stimulation was there a relationship between the rCMRGl of structures usually less involved in AD, e.g. the sensorimotor cortex, and the severity of dementia as assessed by the global deterioration scale (GDS). From these results it can be concluded that metabolic rate at rest reflects the extent of morphologic damage, while PET studies during activation indicate the brain's reserve capacity to respond to functional tasks. Since metabolism in AD patients during activation is more severely impaired than at rest, PET studies during functional tests could help in the selection of patients with a potential to benefit from therapeutic intervention.

Alzheimer Disease↗

[Polyneuropathies following administration of tetanus toxoid].

Two cases are reported: one with an asymmetric polyneuropathy involving the left lower extremity, the other with a generalised chronic relapsing-remitting demyelinating polyneuropathy, hitherto not described in this context. The findings are discussed with regard to the relevant literature.

Adult↗

Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type.

The effect of age on regional cerebral metabolic rate of glucose (rCMRGl) was studied in 14 patients with presenile dementia of Alzheimer type (DAT) and 24 patients suffering from senile DAT in comparison to 20 age-matched normal subjects by positron emission tomography (PET) of 2-(18F)-fluoro-2-deoxy-D-glucose (FDG). The metabolic pattern was condensed to a single metabolic ratio. It was calculated as the quotient of rCMRGl in regions typically affected by AD (frontal and temporoparietal cortex) divided by that in regions typically not affected. In normals this ratio was 1.05 +/- 0.04 and did not depend on age. In patients, the metabolic ratio was generally smaller and there was a significant difference between presenile (0.82 +/- 0.1) and senile DAT (0.90 +/- 0.1). This was due to a different metabolic pattern in the two age groups: metabolic impairment was focused on frontal and temporo-parietal cortex in presenile DAT, whereas more global rCMRGl reductions were present in senile DAT. The results suggest a more generalized disorder in senile dementia impairing metabolism globally in addition to the more localized changes that are typical for DAT.

Aged↗

Estimation of regional cerebral blood flow levels in ischemia using [(15)O]water of [(11)C]flumazenil PET without arterial input function .

Determination of residual flow within the ischemic brain may be important in patients eligible for thrombolytic therapy. Conventional cerebral blood flow (CBF) quantification often cannot be achieved in these cases because arterial blood sampling required for the input function is prohibited. Quantitative CBF was measured in 20 patients with ischemic stroke using [(15)O]water and [(11)C]flumazenil PET with arterial blood sampling and compared with normalized nonquantified data of the same patients. For both comparisons, percentiles were derived, allowing the determination of a normalized blood flow level corresponding to an absolute CBF value below which 95% of all pixels are located. These normograms can be used to derive absolute CBF levels in milliliters per 100 g per minute from normalized data without the need for measuring an arterial input function.

Aged↗