PubMed Health⌕ Search

Biomedical subjects

P Enblad

Publications and source records attributed to P Enblad.

At least 37 records · Page 2Linked to original sources
PubMed2001

Changes in intervention and outcome in elderly patients with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The elderly constitute a significant and increasing proportion of the population. The aim of this investigation was to study time trends in clinical management and outcome in elderly patients with subarachnoid hemorrhage. METHODS: Two hundred eighty-one patients >/=65 years of age with aneurysmal subarachnoid hemorrhage who were accepted for treatment at the Uppsala University Hospital neurosurgery clinic during 1981 to 1998 were included. Hunt and Hess grades on admission, specific management components, and clinical outcomes were recorded. Three periods were compared: A, 1981 to 1986 (before neurointensive care); B, 1987 to 1992; and C, 1993 to 1998. RESULTS: The volume of elderly patients (>/=65 years of age) increased with time, especially patients >/=70 years of age. Furthermore the proportion of patients with more severe clinical conditions increased. A greater proportion of patients had a favorable outcome (A, 45%; B, 61%; C, 58%) despite older ages and more severe neurological and clinical conditions. In period C, Hunt and Hess I to II patients had a favorable outcome in 85% of cases compared with 64% in period A. This was achieved without any increase in the number of severely disabled patients. CONCLUSIONS: Elderly patients with subarachnoid hemorrhage can be treated successfully, and results are still improving. The introduction of neurointensive care may have contributed to the improved outcome without increasing the proportion of severely disabled patients. A defeatist attitude toward elderly patients with this otherwise devastating disease is not justified.

Age Distribution↗
PubMed2001

Increase of interstitial glycerol reflects the degree of ischaemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion-reperfusion primate model.

OBJECTIVE: To evaluate interstitial glycerol as a marker of ischaemia by studying the changes in glycerol in direct relation to changes in regional cerebral metabolic rate of oxygen (CMRO(2)), the lactate/pyruvate ratio (LP ratio), and glutamate. METHODS: Transorbital 2 hour middle cerebral artery occlusion (MCAO) was performed in eight monkeys, which were studied with continuous microdialysis for 24 hours. Interstitial fluids were collected by microdialysis and analysed for glycerol, lactate, pyruvate, and glutamate with an enzymatic assay and high performance liquid chromatography. Sequential PET studies of cerebral blood flow (CBF), CMRO(2), oxygen extraction ratio (OER), and cerebral blood volume (CBV) were performed. The microdialysis probe regions were classified as severe ischaemia or penumbra, depending on whether the mean CMRO(2) side to side ratio was below or above 60%, respectively. RESULTS: A nine-fold, sustained increase in glycerol was registered after MCAO in severe ischaemia regions. In penumbra regions, the increase in glycerol was five-fold, but the glycerol concentration returned to baseline within 8 hours of clip removal. The difference between severe ischaemia and penumbra glycerol values was statistically significant. As expected from previous studies, the interstitial LP ratio and glutamate increased markedly in severe ischaemia, with a less pronounced change in penumbra regions. There was a time lag between the biochemical changes in severe ischaemia regions, with the LP ratio preceding glutamate, followed by glycerol. CONCLUSIONS: A marked, sustained increase in interstitial glycerol is indicative of severe ischaemia in this stroke model. A transient, diminutive increase in interstitial glycerol may reflect a penumbra situation. Interstitial glycerol in combination with other biochemical markers such as the LP ratio and glutamate may be useful for clinical monitoring of the ischaemic brain, reflecting a sequence of secondary pathophysiological events.

Animals↗
PubMed2001

Middle cerebral artery occlusion and reperfusion in primates monitored by microdialysis and sequential positron emission tomography.

BACKGROUND AND PURPOSE: In a previous investigation concerning the hemodynamic and metabolic changes over time displayed by sequential positron emission tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate model, a metabolic threshold for irreversible ischemia could be identified (reduction of metabolic rate of oxygen [CMRO(2)] to approximately 60% of the contralateral hemisphere). To evaluate the potential of microdialysis (MD) as an instrument for chemical brain monitoring, the aim of this subsequent study was to relate the chemical changes in MD levels directly to the regional metabolic status (CMRO(2) above or below the metabolic threshold) and the occurrence of reperfusion, as assessed by PET. METHODS: Continuous MD (2 probes in each brain) and sequential PET measurements were performed during MCA occlusion (2 hours) and 18 hours (mean) of reperfusion in 8 monkeys (Macaca mulatta). Energy-related metabolites (lactate, pyruvate, and hypoxanthine) and glutamate were analyzed. The MD probe regions were divided into 3 categories on the basis of whether CMRO(2) was below or above 60% of the contralateral region (metabolic threshold level) during MCA occlusion and whether reperfusion was obtained: severe ischemia with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra with reperfusion (n=5). RESULTS: The lactate/pyruvate ratio, hypoxanthine, and glutamate showed similar patterns. MD probe regions with severe ischemia and reperfusion and probe regions with severe ischemia and no reperfusion displayed high and broad peaks, respectively, during MCA occlusion, and the levels almost never decreased to baseline. Penumbra MD probe regions displayed only slight transient increases during MCA occlusion and returned to baseline. CONCLUSIONS: This experimental study of focal ischemia showed that the extracellular changes of energy-related metabolites and glutamate differed depending on the ischemic state of the brain during MCA occlusion and depending on whether reperfusion occurred. If MD proves to be beneficial in clinical practice, it appears important to observe relative changes over time.

Animals↗
PubMed2001

Intracerebral microdialysis in neurointensive care: the use of urea as an endogenous reference compound.

OBJECT: When evaluating the results of intracerebral microdialysis, the in vivo performance of the microdialysis probe must be considered, because this determines the fraction of the interstitial concentration obtained in the microdialysis samples. The in vivo performance is dependent on several factors, for example, the interstitial compartment's diffusion characteristics, which may vary during the course of the acute brain injury process. In the present study the authors investigated the method of controlling the in vivo performance by using urea, which is evenly distributed in all body fluid compartments, as an endogenous reference compound and by comparing the urea levels in three compartments: the brain (CNS), abdominal subcutaneous tissue (SC), and blood serum (BS). METHODS: Sixty-nine patients with traumatic brain injury or cerebrovascular disease were included in the study. In 63 of these patients a CNS probe was used, an SC probe was used in 40, and both were used in 34. Urea was measured by enzymatic methods, at bedside for the microdialysis samples and in routine clinical laboratory studies for the BS samples, with the probe calibrated to give identical results. The correlation coefficient for CNS/SC urea was 0.88 (2414 samples), for CNS/BS urea it was 0.89 (180 samples), and for SC/BS urea it was 0.98 (112 samples). CONCLUSIONS: Urea levels in the CNS, SC, and BS were highly correlated, which supports the assumption that urea is evenly distributed. The CNS/SC urea ratio can therefore be used for monitoring the CNS probe's in vivo performance. Fluctuations in other substances measured with microdialysis are probably caused by biological changes in the brain, as long as the CNS/SC urea ratio remains constant.

Adipose Tissue↗
PubMed2000

Modulation of phenotype and induction of irregular vessels accompany high tumorigenic potential of clonal human glioma cells xenografted to nude-rat brain.

Three phenotypically different clonal human glioma cell lines were injected stereotactically into nude-rat brains, to determine their individual growth potential and to establish an in vivo system in which different therapeutic modalities could be tested. As assessed by serial sectioning, microscopic evaluation, and computer analysis, the mean approximate tumour volume after 3-7 weeks in vivo was 0.42 mm(3) for U-343 MG, 2.6 mm(3) for U-343 MGa Cl2:6, and 50.3 mm(3) for U-343 MGa 31L. When compared with the initial injected cell volume, only U-343 MGa 31L had increased in size, U-343 MGa Cl2:6 remained approximately the same but showed a certain proliferative potential, and U-343 MG regressed. Thus, only U-343 MGa 31L cells had high tumorigenic potential, invaded and replaced brain tissue in every direction, while U-343 MGa Cl2:6 cells grew in sheet-like tumour extensions along white-matter nerve-fibre tracts, in this respect mimicking foetal astrocytes. The tumorigenic potential of the U-343 MGa 31L cell clone was associated with a variable phenotype, as observed when the in vivo and in vitro characteristics were compared. The in vivo phenotype was characterized by the loss of GFAP immunoreactivity, the gain of heterogeneously distributed cellular tenascin, fibronectin, and laminin, but absence of extracellularly deposited material, and by the formation of irregular vessels. It appears that the intrinsic capacity of glioma cells to adapt to in vivo conditions is decisive for their tumorigenicity in the brain, rather than any single phenotypic property in itself. Moreover, the 2 glioma cell clones best suited for in vitro growth were no longer tumorigenic.

Animals↗
PubMed2000

Multi-centre assessment of the Spiegelberg compliance monitor: preliminary results.

Acute brain injury states (e.g. head injury, subarachnoid haemorrhage) show clear inverse relationships of ICP vs compliance, with ICP instability at times of lower compliance states. Variance in compliance values is large in hydrocephalus where ICP is relatively lower and compliance higher. Nonetheless, early experience shows that compliance data influence decisions on CSF diversion treatments. Future work will focus on the ability of intracranial compliance to predict ensuing ICP instability and methodological refinement for monitoring patients who have higher compliance states.

Brain↗
PubMed2000

A metabolic threshold of irreversible ischemia demonstrated by PET in a middle cerebral artery occlusion-reperfusion primate model.

OBJECTIVE: to evaluate the predictive value of measurements of regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction ratio (OER) for assessment of the fate of ischemic brain tissue. MATERIALS AND METHODS: Sequential PET measurements were performed during middle cerebral artery occlusion (MCAO; 2 h) and 12-24 h (mean 18 h) of reperfusion in a primate model (Macaca mulatta, n = 8). A penumbra region was delineated on the MCAO PET image (OER > 125% and CMRO2> or = 45% of the values observed in the contralateral hemisphere, respectively) and an infarction region was delineated on the last PET image (CMRO2 <45% of the values observed in the contralateral hemisphere). The penumbra regions delineated during MCAO and the infarction regions delineated at the final PET, were copied on to the images from all other PET sessions for measurements of CBF, CMRO2 and OER. Ratios were calculated by dividing the mean values obtained by the values of the corresponding contralateral region. RESULTS: Histopathology verified the adequacy of the criteria applied in the last PET for delineation of the infarction region. The penumbra region and infarction region were separated in all cases, except in two cases where a minimal overlap was seen. CBF and OER showed considerable variation over time and there was no consistent difference between the penumbra and infarction regions. CMRO2 showed a more stable pattern and the difference between penumbra and infarction regions was maintained from the time of MCAO throughout the entire reperfusion phase. With CMRO2 as predictor, all 50 observations could be correctly predicted as penumbra or infarction when using an optimal threshold ratio value estimated to be in the interval of 61% to 69% of the corresponding contralateral region. CBF and OER proved to have low power as predictors. CONCLUSIONS: The results indicate that CMRO2 is the best predictor of reversible or irreversible brain damage and the critical metabolic threshold level appears to be a reduction of oxygen metabolism to between 61% and 69% of the corresponding contralateral region.

Animals↗
PubMed1999

Neurointensive care of aneurysmal SAH.

This paper briefly reviews some basic principles of neurosurgical intensive care of patients with aneurysmal subarachnoid hemorrhage. The importance of early identification of secondary insults are underlined. Special attention is paid to the newly introduced method for neurochemical monitoring by means of intracerebral microdialysis. It is concluded that a well functioning neurointensive care unit constitutes an important organisational frame for the detection, prevention and treatment of secondary insults, after aneurysmal subarachnoidal hemorrhage and that improved results can be expected by applying a modern neurointensive care strategy also for patients with aneurysmal subarachnoid hemorrhage.

Critical Care↗
PubMed1998

Interstitial glycerol as a marker for membrane phospholipid degradation in the acutely injured human brain.

OBJECTIVE: Brain interstitial glycerol was studied as a potential marker for membrane phospholipid degradation in acute human brain injury. METHODS: Glycerol was measured in microdialysis samples from the frontal lobe cortex in four patients in the neurointensive care unit, during the acute phase after severe aneurysmal subarachnoid haemorrhage. Microdialysis probes were inserted in conjunction with a ventriculostomy used for routine intracranial pressure monitoring. Clinical events involving hypoxia/ischaemia were diagnosed by neurological signs, neuroimaging (CT and PET), and neurochemical changes of the dialysate-for example, lactate/pyruvate ratios and hypoxanthine concentrations. RESULTS: Altogether 1554 chemical analyses on 518 microdialysis samples were performed. Clinical events involving secondary hypoxia/ischaemia were generally associated with pronounced increases (up to 15-fold) of the dialysate glycerol concentration. In a patient with a stable condition and no signs of secondary hypoxia/ischaemia the glycerol concentration remained low. Simultaneous determination of glycerol in arterial plasma samples showed that the changes in brain interstitial glycerol could not be attributed to systemic changes and an injured blood brain barrier. CONCLUSIONS: This study suggests that membrane phospholipid degradation occurs in human cerebral ischaemia. Interstitial glycerol harvested by microdialysis seems to be a promising tool for monitoring of membrane lipolysis in acute brain injury. The marker may be useful for studies on cell membrane injury mechanisms mediated by for example, Ca2+ disturbances, excitatory amino acids, and reactive oxygen species; and in the evaluation of new neuroprotective therapeutic strategies.

Acute Disease↗
PubMed1998

[PET scan in neuro-intensive care and research].

The main objective of neurointensive care is to counteract the development of secondary brain ischemia. The management is focused on preventing, detecting and correcting secondary insults that are likely to produce ischemic brain damage. This requires intensive multimodality monitoring of the brain. There is no reliable technique available for continuous monitoring of cerebral blood flow and therefore intermittent methods have to be used in some cases for objective measurement of cerebral perfusion. PET allows measurements of both cerebral blood flow and metabolism, which is essential for the assessment of the energy metabolic state of the brain tissue. PET may be used to guide therapeutic intervention, to evaluate the effect of treatment, to validate new techniques for monitoring of the brain and to determine the efficacy of potential neuroprotective drugs. The possibilities that PET offers in neurointensive care and research are illustrated. The experiences from the application of PET in the evaluation of pharmacological treatment of increased intracranial pressure in head injured patients and the use of PET in combination with intracerebral microdialys, in an MCA-occlusion-reperfusion primate model and in patients with subarachnoid hemorrhage, to validate intracerebral microdialysis as an instrument for chemical monitoring of the brain during neurointensive care, are reported.

Critical Care↗
PubMed1997

Impact on clinical outcome of secondary brain insults during the neurointensive care of patients with subarachnoid haemorrhage: a pilot study.

OBJECTIVE: To analyse the occurrence and influence on outcome of secondary brain insults during neurointensive care of patients with subarachnoid haemorrhage. METHODS: Sixty one seriously ill patients with subarachnoid haemorrhage with a poor neurological grade, acute hydrocephalus, or intraventricular and/or intracerebral haemorrhages, who were referred as emergency cases to the neurosurgical intensive care unit during 1990 and 1991, comprised the study patients. RESULTS: The follow up performed according to the Glasgow outcome scale 14 months (median) later showed 23 patients with good recovery (38%), 11 with moderate disability (18%), seven with severe disability (11%), and two in a vegetative state (3%); 18 patients had died (30%). Clinical outcome was significantly related to the CT modified Hunt and Hess grade (P = 0.006). In total, 164 secondary brain insults (potentially avoidable factors) of various types were seen at the unit during the first seven days after the haemorrhage. Patients with a favourable outcome had significantly fewer secondary insults than patients with an unfavourable outcome (P = 0.0008). The occurrence of insults in each patient was related to the neurological grade (CT modified Hunt and Hess grade, P = 0.05). Multivariate analysis with the CT modified Hunt and Hess grade and the number of secondary brain insults during the first week as explanatory variables and favourable outcome as the dependent variable, showed that the number of complications was a significant independent predictor of favourable outcome (beta = -0.38, SE(beta) = 0.17, P = 0.03), whereas the CT modified Hunt and Hess grade did not reach significance (beta = -1.2, SE(beta) = 0.81, P = 0.14). CONCLUSIONS: The clinical outcome after subarachnoid haemorrhage is at least partly determined by the number of secondary insults. Therefore, vigorous attempts should be made to avoid all events that may potentially increase the risk of secondary cerebral ischaemia. Prospective studies must be initiated to define the role of "priming" of the brain and the impact of specific individual secondary insults in patients with subarachnoid haemorrhage.

Adult↗
PubMed1997

PET-methionine of skull base neuromas and meningiomas.

Eighteen patients with intracranial skull base tumours diagnosed at CT or MR as neuromas or meningiomas were studied with positron emission tomography (PET) using L-(methyl-11C) methionine. Compared with normal cerebellar tissue, the uptake of methionine in the tumours increased more rapidly and reached a higher level, and showed a slow decline after a peak occurring about 5 min after the injection. All the meningiomas exhibited considerably higher accumulation of the tracer compared with the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding cerebellar tissue, which made the tumour easy to identify and to demarcate from the surrounding structures (tumour to cerebellum ratios 2.62-5.37, mean 3.63). The uptake was homogeneous in all meningiomas, which were all of the syncytial type. The neuromas showed lower contrast against the cerebellum (tumour to cerebellum ratios 1.1-1.87, mean 1.48). Some neuromas displayed an irregular pattern with regions of decreased tracer uptake corresponding to small cystic areas within the neuroma. There was no overlap in methionine uptake between the two tumour groups. The results indicate that PET-methionine may contribute to the evaluation, treatment planning and follow-up of patients with skull base meningiomas and neuromas.

Adult↗
PubMed1996

Simultaneous intracerebral microdialysis and positron emission tomography in the detection of ischemia in patients with subarachnoid hemorrhage.

Intracerebral microdialysis (MD) was applied in patients with subarachnoid hemorrhage. The regional CBF, the CMRO2, and oxygen extraction ratio (OER) were measured with simultaneous positron emission tomography (PET). The aim was to directly correlate alterations in dialysate levels of energy-related metabolites (lactate, lactate/pyruvate ratio, hypoxanthine) and excitatory amino acids (EAAs) (glutamate and aspartate) to the energy state in the MD probe region as determined by PET. Regional ischemia was defined according to Heiss et al. and Lassen (Heiss et al., 1992; Lassen, 1966). Whole-brain ischemia was considered present when the OER for the whole brain exceeded the mean whole-brain OER + 2 SD of six reference patients. In general, the presence of whole-brain ischemia and/or regional ischemia within the region of the MD probe was associated with increased levels of energy-related metabolites and EAAs retrieved by MD. Increased levels of energy-related metabolites and EAAs were only occasionally seen when PET did not show any signs of ischemia or when signs of regional ischemia were found remote from the MD probe region. Thus, the energy-related metabolites and EAAs may be used as extracellular "markers" of ischemia. PET may be of use in defining critical ischemic regions (tissue at risk) where the MD probe can be inserted for chemical monitoring.

Aged↗
PubMed1996

Neurochemical monitoring using intracerebral microdialysis in patients with subarachnoid hemorrhage.

The authors have developed a method for routine monitoring of disturbances in brain energy metabolism and extracellular levels of excitatory amino acids using intracerebral microdialysis in 10 patients with subarachnoid hemorrhage. Microdialysis was conducted for periods ranging from 6 to 11 days after ictus. Altogether, 16,054 chemical analyses from 1647 dialysate samples were performed. Concentrations of the energy-related substances lactate, pyruvate, glucose, and hypoxanthine were measured, and the lactate/pyruvate ratio was calculated. The excitatory amino acids glutamate and aspartate were measured. The microdialysis data were matched with computerized tomography findings, clinical course, and outcome. The results support the concepts that microdialysis is a promising tool for chemical monitoring of the human brain and that extracellular fluid levels of lactate, lactate/pyruvate ratio, glucose, hypoxanthine, and glutamate are useful markers of disturbances in brain energy metabolism in neurointensive care patients. These results have generated a working hypothesis that the pattern of these extracellular markers may help differentiate between various causes of energy perturbations, such as hypoxia and different degrees of ischemia. The correlation between the dialysate levels of excitatory amino acids and outcome supports the concept of glutamate receptor overactivation in acute human brain injury.

Aged↗
PubMed1994

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid.

The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentration of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and beta-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier.

Astrocytoma↗
PubMed1993

Detailed genetic mapping of the von Hippel-Lindau disease tumour suppressor gene.

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited familial cancer syndrome characterised by a predisposition to the development of retinal, cerebellar, and spinal haemangioblastomas, renal cell carcinoma, and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p25-p26 and flanking markers identified. We report the detailed genetic mapping of the VHL disease locus in 38 families. Significant linkage was detected between VHL disease and D3S601 (Zmax = 18.86 at theta = 0.0, CI 0.0-0.025), D3S18 (Zmax = 11.42 at theta = 0.03, CI 0.005-0.08), RAF1 (Zmax = 11.02 at theta = 0.04, CI 0.007-0.01), and D3S1250 (Zmax = 4.73 at theta = 0.05, CI 0.005-0.15). Multipoint linkage analysis mapped the VHL disease locus between D3S1250 and D3S18 close to D3S601. There was no evidence of locus heterogeneity. This study has (1) confirmed the tight linkage between VHL disease and D3S601, (2) identified D3S1250 as the first marker telomeric to RAF1 which maps centromeric to the VHL disease gene, and (3) narrowed the target region for isolation of the VHL disease gene by positional cloning techniques to a 4 cM interval between D3S1250 and D3S18. These findings will improve the clinical management of families with VHL disease by improving the accuracy of presymptomatic diagnosis using linked DNA markers, and will enhance progress towards isolating the VHL disease gene.

Chromosome Mapping↗