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Regional tissue blood flow and pH in the brain during deep hypothermic retrograde brain perfusion.

Deep hypothermic retrograde brain perfusion is used to protect the brain during aortic arch operations. However, all experiments have failed to demonstrate retrograde blood flow in the brain tissue. We developed an experimental model of sagittal sinus and simultaneous superior vena cava perfusion. Brain tissue blood flow was mapped with colored microspheres during deep hypothermic retrograde brain perfusion in 9 dogs. Regional brain pH was mapped photometrically using neutral red as a pH-indicating dye after 90 min of retrograde brain perfusion in 28 dogs and after 60 min of circulatory arrest in 8 dogs. Cerebral surface blood flow was also measured during retrograde brain perfusion. They were analyzed as functions of driving pressure between sagittal sinus and aorta. Total brain blood flow (ml/min/100 g) was 1.4 +/- 1.3, 3.8 +/- 2.6, and 4.6 +/- 2.6 when the driving pressure was 15, 25, and 35 mmHg, respectively (P < 0.05, 15 mmHg vs 25 mmHg). Regional cerebral blood flow (ml/min/100 g) with a driving pressure of 25 mmHg was 12.1 +/- 9.4, 7.0 +/- 5.6, 4.4 +/- 2.8, and 2.2 +/- 1.4 in the frontal cortex, anterior, mid, and posterior cerebrum, respectively. Cerebral cortex pH was 6.86 +/- 0.23, 7.15 +/- 0.18, and 6.46 +/- 0.13 after 90 min of retrograde brain perfusion with driving pressure of less than 20 mmHg, after that of above 20 mmHg, and after 60 min of circulatory arrest, respectively. Brain tissue pH, blood flows measured with microspheres, and laser flowmetry were highest when driving pressure was between 25 and 35 mmHg. We conclude that retrograde brain perfusion may provide maximum brain protection with driving pressure of 25 to 35 mmHg.

Animals↗

Excitatory amino acid release from contused brain tissue into surrounding brain areas.

The EAA release from contused brain tissue and its effect on the extracellular EAA levels in brain areas surrounding the contusion were investigated with microdialysis technique in the rat. A significant increase in extracellular EAA levels was observed in the contused brain tissue. The EAA increase was significantly greater in the contused brain tissue than in the isolated but non-contused brain tissue. It was further demonstrated that EAAs were released from non-contused brain areas 1-2 mm distant from contused brain tissue. No such EAA release from surrounding brain areas was demonstrated when the cavity was filled with isolated but non-contused brain tissue. The increase in EAAs was attenuated by KYN administered through microdialysis, suggesting that the EAA release from the surrounding brain areas appears to be a consequence that is secondary to the EAA release from the contused brain tissue. Such a diffusion-reaction process is probably mediated by the neurotransmitter actions of EAAs. The results of the present study are of clinical importance, since surgical removal of contused brain tissue and administration of EAA antagonists may serve to protect the surrounding brain areas from EAA neurotoxicity.

Animals↗

Human brain natriuretic peptide-like immunoreactivity in human brain.

The presence of immunoreactive human brain natriuretic peptide in the human brain was studied with a specific radioimmunoassay for human brain natriuretic peptide-32. This assay showed no significant cross-reaction with human alpha atrial natriuretic peptide, porcine brain natriuretic peptide or rat brain natriuretic peptide. Immunoreactive human brain natriuretic peptide was found in all 5 regions of human brain examined (cerebral cortex, thalamus, cerebellum, pons and hypothalamus) (0.6-6.7 pmol/g wet weight, n = 3). These values were comparable to the concentrations of immunoreactive alpha atrial natriuretic peptide in human brain (0.5-10.1 pmol/g wet weight). However, Sephadex G-50 column chromatography showed that the immunoreactive human brain natriuretic peptide in the human brain eluted earlier than synthetic human brain natriuretic peptide-32. These findings suggest that human brain natriuretic peptide is present in the human brain mainly as larger molecular weight forms.

Aged↗

Study on brain interstitial fluid distribution and blood-brain barrier transport of baclofen in rats by microdialysis.

PURPOSE: This study was performed to examine the distribution in the brain interstitial fluid (ISF) and the blood-brain barrier (BBB) transport of baclofen in rats by a microdialysis technique. METHODS: Following an i.v. bolus administration and/or the constant i.v. infusion of baclofen to the microdialysis cannula-bearing anesthetized rats, the concentrations of baclofen in the hippocampal ISF, whole brain tissue, cerebrospinal fluid (CSF), and plasma were determined by high-performance liquid chromatography (HPLC). Data were kinetically analyzed to estimate the transport parameters, i.e., the influx clearance (CLin) from plasma to brain and the efflux rate constant (keff) from brain to plasma, and the steady-state volume of distribution in the brain (Vd). RESULTS: The concentrations of baclofen in ISF, whole brain tissue, and CSF at the pseudo-steady state were almost 30-fold lower than the plasma unbound concentration, suggesting the restricted distribution of baclofen in the brain. The estimated values of CLin and keff were 0.00157 +/- 0.00076 ml/min/g of brain and 0.0872 +/- 0.0252 min-1, respectively. The efflux clearance (CLout) calculated by multiplying keff by Vd (0.816 +/- 0.559 ml/g of brain) was 0.0712 +/- 0.0529 ml/min/g of brain, and it was significantly 40-fold greater than the CLin value and fully greater than the convective flow in ISF. Furthermore, no significant concentration gradient was observed between ISF and CSF. These results suggest that the CLout value mainly reflects the efflux clearance through the BBB. Additionally, the hippocampal ISF/plasma concentration ratio of baclofen was markedly increased by both systemic administration of probenecid and its direct instillation into ISF. CONCLUSIONS: The restricted distribution of baclofen in the brain ISF may be ascribed to the efficient efflux from the brain through the BBB which is regulated possibly by a probenecid-sensitive organic anion transport system.

Animals↗

Brain-behaviour relationships. Some models and related statistical procedures for the study of brain-damaged patients.

The study of brain-damaged patients provides the opportunity to examine the anatomy of brain functions, and has been renewed by the development of structural neuroimaging. Despite the development of neuroimaging and neuropsychological assessment, major uncertainties persist on the exact delimitation of the brain areas involved in specific processes, and these contribute to the enduring controversies over the effective lesions associated with neuropsychological disorders. These uncertainties are mainly due to the methods used in the study of brain-behaviour relationships, which frequently rely on a group comparison design. The aim of this study was to provide models for the study of brain-behaviour relationships and to assess the reliability of related statistical procedures. In the present work, four theoretical modes of brain-behaviour relationship consistent with neuropsychological data are put forward: unicity, equivalence, association and summation. The first experimental study was based on a simulated population of patients. Lesions associated with the occurrence of a deficit were predetermined according to modes of brain-behaviour relationship and were compared with lesions selected by statistical analysis. The study showed that (i) the group comparison design did not allow determination of the effective lesion, (ii) stepwise regression analysis was sensitive to the relative frequency of lesions, especially when the occurrence of a deficit depended on two lesions, but did not allow determination of the mode of brain-behaviour relationship, and (iii) the classification tree test described the data very satisfactorily and permitted the determination of the mode of brain-behaviour relationships. In order to assess the validity of statistical analyses, a second study was performed in which lesion locations associated with motor weakness in stroke patients were examined. Selected lesions were compared with the anatomy of the human motor system. The study mainly showed that (i) the stepwise regression analysis of selected lesions was not related to the presence of a motor deficit, and (ii) the classification tree test provided perfect agreement with motor weakness predicted by lesion locations and suggested an equivalence mode of brain-behaviour relationship consistent with current neurological knowledge. These studies provide models of brain-behaviour relationships and related statistical procedures that may allow more precise documentation of the anatomy of brain functions and its pathology, and further investigation of the modalities of brain-behaviour relationships.

Behavior↗

Tightness of the blood-brain barrier and evidence for brain interstitial fluid flow in the cuttlefish, Sepia officinalis.

Cephalopod molluscs have complex brains and behaviour, yet little is known about the permeability of their blood-brain interface. The accompanying paper characterized the fluid compartments of the brain and presented evidence for restricted permeability of the blood-brain interface to albumin. The present paper investigates the permeability of the interface to small non-electrolytes. [14C]Polyethylene glycol (PEG, mol. wt. 4000), and [51Cr]EDTA (mol. wt. 342) were injected intravenously or intramuscularly, and their penetration into brain and muscle studied up to 48 h. Tracers equilibrated with muscle interstitial fluid (ISF) at relatively short times, but in brain ISF reached only 0.5-0.65 X their plasma concentration. This is qualitative evidence for the presence in brain of a barrier to these molecules and an efficient drainage mechanism for ISF. Quantitative treatment of the uptake data allows calculation of the permeability X surface area product (PS) and the permeability coefficient (P). For the brain PS and P are in the range 1-3 X 10(-4) ml g-1 min-1 and 1-3 X 10(-8) cm s-1 respectively, (PEG), and 3 X 10(-4) ml g-1 min-1 and 3-4 X 10(-8) cm s-1 respectively (Cr-EDTA). The P values are close to those reported for mammalian brain. Assuming that the lack of equilibration in brain is due to ISF flow, the rate of flow can be calculated. Values for vertical and optic lobe are approximately 0.2 microliter g-1 min-1, again close to those reported for mammalian brain. It is concluded that the tightness of the Sepia blood-brain barrier approaches that of mammals, and a flowing ISF system is present. An association between a tight barrier and higher central nervous system integrative function is suggested. The significance of these findings for the evolution of control of the brain microenvironment is discussed.

Animals↗

The human leukemic T-cell line, TALL-104, is cytotoxic to human malignant brain tumors and traffics through brain tissue: implications for local adoptive immunotherapy.

Preclinical studies with the human MHC nonrestricted cytotoxic T-cell leukemic line, TALL-104, were performed in anticipation of its use in cellular immunotherapy trials for primary malignant brain tumors. In this study, we have: (a) quantitated the in vitro brain tumor cell lysis; (b) measured the cytokine secretion upon coincubation of TALL-104 cells with brain tumor cells; (c) investigated the effect of dexamethasone on brain tumor cell cytolysis by TALL-104 cells; (d) explored the effects of lethal irradiation and cryopreservation on TALL-104 cell viability and lytic efficacy; and (e) estimated the damage TALL-104 cells induce to murine normal and tumor brain cells and their trafficking patterns in both normal and tumor-bearing rat brain upon intracranial infusion. In vitro coincubation of TALL-104 cells with human brain tumor cells, explants, and cell lines resulted in significant lysis of them, but normal brain cells were spared. Lysis of tumor at 4 h was unaffected by dexamethasone or lethal irradiation. Secretion of tumor necrosis factor-alpha, tumor necrosis factor-beta, IFN-gamma, or granulocyte/macrophage-colony stimulating factor upon TALL-104 cell coincubation with brain tumor cells variably occurred without always correlating with lysis. In vivo experiments using irradiated TALL-104 cells, placed at multiple times into normal cannulated rat brain, produced focal sterile abscesses at the instillation site but no widespread allergic encephalitic reaction. Cells morphologically consistent with TALL-104 cells specifically trafficked from the site of instillation through the neuropil, occasionally into the contralateral brain, and egressed at perivascular and leptomeningeal spaces. In vivo experiments with cannulated rats bearing 9L gliosarcoma showed a preferential localization of the TALL-104 cells in tumor compared with normal brain. Taken together, these data support the concept that TALL-104 cells can be used as a novel nontoxic and efficacious paradigm for cellular immunotherapy trials in human primary malignant brain tumors.

Animals↗

Brain edema: a classification based on blood-brain barrier integrity.

Brain edema is a frequent complication of a variety of brain injuries and disorders. Two primary types of brain edema can be distinguished depending upon the integrity of the blood-brain barrier. With intact-barrier edema, the permeability of the blood-brain barrier is normal and brain edema results from a disturbance in ionic homeostasis. This type of edema is typically associated with swelling of the brain cells and a contraction of the extracellular space. In open-barrier edema, the permeability of the blood-brain barrier is increased and brain edema results from the oncotic forces generated by an influx of serum proteins into brain. In this case, the edema fluid accumulates primarily in the extracellular space. To a greater or lesser extent, both types of edema occur simultaneously in the majority of clinical conditions; however, one form usually predominates and demands the attention of both the scientist and clinician. Furthermore, classification of brain edema based upon blood-brain barrier integrity is useful to focus research on common mechanisms for brain edema formation and to direct therapy. This review considers intact-barrier and open-barrier edema with regard to their (a) histological features, (b) biophysical forces, (c) possible biochemical mediators, (d) mechanisms of resolution, and (e) implications for therapy.

Blood-Brain Barrier↗

Use of diffusion-weighted magnetic resonance imaging in differentiating purulent brain processes from cystic brain tumors.

OBJECT: Brain abscesses and other purulent brain processes represent potentially life-threatening conditions for which immediate correct diagnosis is necessary to administer treatment. Distinguishing between cystic brain tumors and abscesses is often difficult using conventional imaging methods. The authors' goal was to study the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to differentiate between these two pathologies in patients within the clinical setting. METHODS: Diffusion-weighted MR imaging studies and calculation of the apparent diffusion coefficient (ADC) values were completed in a consecutive series of 16 patients harboring surgically verified purulent brain processes. This study group included 11 patients with brain abscess (one patient had an additional subdural hematoma and another also had ventriculitis), two with subdural empyema, two with septic embolic disease, and one patient with ventriculitis. Data from these patients were compared with similar data obtained in 16 patients matched for age and sex, who harbored surgically verified neoplastic cystic brain tumors. In patients with brain abscess, subdural empyema, septic emboli, and ventriculitis, these lesions appeared hyperintense on DW MR images, whereas in patients with tumor, the lesion was visualized as a hypointense area. The ADC values calculated in patients with brain infections (mean 0.68 x 10(3) mm2/sec) were significantly lower than those measured in patients with neoplastic lesions (mean 1.63 x 10(3) mm2/sec; p < 0.05). CONCLUSIONS: Diffusion-weighted MR imaging can be used to identify infectious brain lesions and can help to differentiate between brain abscess and cystic brain tumor, thus making it a strong additional imaging modality in the early diagnosis of central nervous system purulent brain processes.

Adult↗

Whole brain radiotherapy for the treatment of multiple brain metastases.

BACKGROUND: Brain radiotherapy is used to treat cancer patients who have brain metastases resulting from various primary malignancies. OBJECTIVES: To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) in adult patients with multiple metastases to the brain. SEARCH STRATEGY: CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CANCERLIT, and CINAHL were searched. SELECTION CRITERIA: Randomized controlled trials (RCTs) in which adult patients with multiple metastases to the brain from any primary cancer and treated with WBRT were included. Trials of prophylactic WBRT were excluded as well as trials that dealt with surgery or WBRT, or both, for the treatment of a single brain metastasis. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted information for each predetermined outcome: overall survival at six months, intracranial progression-free duration, local brain response, local brain control, quality of life, symptom control, neurological function, and the proportion of patients able to reduce the daily dexamethasone dose. Adverse effects were also collected. MAIN RESULTS: Eight published reports (nine trials) showed no benefit of altered dose-fractionation schedules as compared to control fractionation (3000 cGy in 10 fractions) of WBRT on the probability of survival at six months. These studies also showed no difference in symptom control nor neurologic improvement among the different dose-fractionation schemes. The addition of radiosensitizers, in five RCTs, did not confer additional benefit to WBRT in either overall median survival times or brain tumor response rates. The addition of the radiosensitizer motexafin gadolinium did not improve quality of life nor time to neurologic progression overall. For the radiosensitizer misonidazole, there was no improvement in Karnofsky performance score outcomes. Three RCTs found no benefit in overall survival with the use of WBRT and a radiosurgery boost as compared to WBRT alone for selected patients with multiple brain metastases (up to four brain metastases). Overall, however, there was a statistically significant improvement in local brain control favoring the whole brain radiotherapy and radiosurgery boost arm. Only one trial of radiosurgery boost with WBRT reported an improved Karnofsky performance score outcome and improved ability to reduce dexamethasone dose. One RCT examined the use of WBRT and prednisone versus prednisone alone and produced inconclusive results. AUTHORS' CONCLUSIONS: None of the RCTs with altered dose-fractionation schemes as compared to standard delivery (3000 cGy in ten fractions) found a benefit in terms of overall survival, neurologic function, or symptom control. The use of radiosensitizers or chemotherapy in conjunction with WBRT remains experimental. A radiosurgery boost with WBRT may improve local disease control in selected patients, although survival remains unchanged. The benefit of WBRT as compared to supportive care alone has not been studied in RCTs. It may be that supportive care alone, without WBRT, may be appropriate for some patients, particularly those with advanced disease and poor performance status.

Adult↗

Effects of brain hypothermia on brain edema formation after intracerebral hemorrhage in rats.

Patients with intracerebral hemorrhage (ICH) may deteriorate progressively after the initial ictus because of the brain edema around the hematoma. Recently, thrombin has become known to play an important role in the brain edema formation after ICH. In this study, we examined the effect of brain hypothermia on brain edema formation after hematoma and thrombin injection into the brain in rats and clarified the mechanism of hypothermia on brain damage. Anesthetized Sprague-Dawley rats received an injection of 100 microL of autologous blood or 10 units of bovine thrombin into the basal ganglia. Animals were divided into the normothermic and hypothermic groups, which were housed in a room at 25 degrees C and in a cold room at 5 degrees C respectively, for 24 hours. Brain water content was significantly reduced with hypothermia in the cortex (80.8 vs. 79.7% p < 0.05) after hematoma induction. After thrombin injection, brain water content was also significantly reduced with hypothermia in the basal ganglia (84.5 vs. 82.2%; p < 0.01), accompanied by a significant reduction in blood-brain barrier (BBB) permeability to Evan's blue (29.4 vs. 11.6 ng/g tissue; p < 0.05) and in accumulation of polymorphonuclear leukocytes (3.03 vs. 0.27 U of myeloperoxidase/g tissue; p < 0.01). This study indicates that brain hypothermia significantly reduces brain edema formation after hematoma and thrombin injection into the brain in rats. Inhibition of thrombin-induced BBB breakdown and inflammatory response with hypothermia appear to contribute to brain protection in this model.

Animals↗

A qualitative comparison of the glucocorticoid receptor in cytosol from human brain and rat brain.

The glucocorticoid receptor in cytosol from human brain was studied using isoelectric focussing in slabs of polyacrylamide gel. [3H]Dexamethasone was used as tracer for receptor analysis. The glucocorticoid receptor from human brain was compared to the glucocorticoid receptor in rat brain. A similar peak of radioactivity with a pI of about 6.1 was obtained by isoelectric focussing of cytosol from both human brain and rat brain. The trypsin-induced fragmentation patterns of the glucocorticoid receptor from human brain and rat brain were very similar when analyzed by isoelectric focussing. The hormone specificity of the glucocorticoid receptor in human brain and in rat brain cytosol was compared by competition experiments using unlabelled dexamethasone, betamethasone, cortisol and corticosterone as competitors. No difference between human brain and rat brain cytosol was detected. It is concluded that the hormone specificity and the protein structure of the glucocorticoid receptors in human brain and in rat brain are similar.

Adrenalectomy↗

Cocaine concentrations in fetal C57BL/6 mouse brain relative to maternal brain and plasma.

Cocaine concentrations in maternal plasma and brain and fetal brain of mice were evaluated as a model for fetal brain exposure during maternal cocaine use. On days 12-18 of gestation, mice (C57BL/6; N = 5-7/group) received SC cocaine-HCI: 20 or 40 mg/kg. Maternal plasma and brain (accumbens and caudate nuclei removed), and fetal brain were collected at 0.5, 1, and 2 h following the last injection. Analysis was by GC-MS. Brain cocaine levels in the dams declined from 9.6 to 3.4 and 20.9 to 12.5 micrograms/g [corrected] during the 0.5-1-h period after the low and high doses, respectively, and were 7.5-14.3 times greater than plasma levels. The corresponding fetal brain concentrations changed from 1.6 to 1.3 and 2.9 to 3.4 micrograms/g [corrected]. By 2 h, brain cocaine concentrations in dams declined to approximately 10% of their 0.5-h values, with a slower drug decay occurring in fetal brain. Maternal plasma cocaine concentrations correlated with those of maternal brain (r = 0.94, p < 0.01) and fetal brain (r = 0.69, p < 0.01). The present results indicate that cocaine accumulates to a lesser extent in fetal brain than in maternal brain of C57BL/6 mice; however, the duration of exposure appears to be more sustained in the fetus, a phenomenon that may have toxicological implications for human in utero cocaine exposure.

Animals↗

Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro.

The brain is the most cholesterol-rich organ in the body. Brain cholesterol is characterized by a very low turnover with very little exchange with lipoproteins in the circulation. Very recently we showed that there is a continuous age-dependent flux of 24(S)-hydroxycholesterol from the human brain into the circulation (Lütjohann, D., Breuer, O., Ahlborg, G., Nennesmo, I., Sidén, A., Diczfalusy, U., and Björkhem, I. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 9799-9804). Here we measured the rate of synthesis of cholesterol as well as the conversion of cholesterol into 24(S)-hydroxycholesterol in rat brain in vivo with use of an 18O2 inhalation technique and mass isotopomer distribution analysis. Cholesterol synthesis was found to correspond to 0.03 +/- 0.01% of the pool per h. Conversion of cholesterol into 24(S)-hydroxycholesterol was of a similar magnitude, about 0.02% of the pool per h. Brain microsomes converted endogenous cholesterol into 24(S)-hydroxycholesterol at a similar rate when incubated in the presence of NADPH. When incubated with whole homogenate and subcellular fractions of rat brain, there was no significant conversion of tritium-labeled 24-hydroxycholesterol into more polar products. Plasma from 18O2-exposed rats contained 24(S)-hydroxycholesterol with an enrichment of 18O similar to that in 24(S)-hydroxycholesterol in the brain. The results suggest that the present 24(S)-hydroxylase mediated mechanism is most important for elimination of cholesterol from the brain of rats. There is a slow conversion of brain cholesterol into 24(S)-hydroxycholesterol with a rapid turnover of the small pool of the latter oxysterol due to leakage to the circulation (half-life of brain 24(S)-hydroxycholesterol is about 0.5 days as compared with 2-4 months for brain cholesterol). It is evident that the 24(S)-hydroxylation greatly facilitates transfer of cholesterol over the blood-brain barrier and that this hydroxylation may be critical for cholesterol homeostasis in the brain.

Animals↗

Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures.

Cytomegalovirus (CMV) is the most significant infectious cause of brain disorders in humans involving the developing brain. It is hypothesized that the brain disorders occur after recurrent reactivation of the latent infection in some kinds of cells in the brains. In order to test this hypothesis, we examined the reactivation of latent murine CMV (MCMV) infection in the mouse brain by transfer to brain slice culture. We infected neonatal and young adult mice intracerebrally with recombinant MCMV in which the lacZ gene was inserted into a late gene. The brains were removed 6 months after infection and used to prepare brain slices that were then cultured for up to 4 weeks. Reactivation of latent infection in the brains was detected by beta-galactosidase (beta-Gal) staining to assess beta-galactosidase expression. Viral replication was also confirmed by the plaque assay. Reactivation was observed in about 75% of the mice infected during the neonatal period 6 months after infection. Unexpectedly, reactivation was also observed in 75% of mice infected as young adults, although the infection ratio in the brain slices was significantly lower than that in neonatally infected mice. Beta-Gal-positive cells were observed in marginal regions of the brains or immature neural cells in the ventricular walls. Immunohistochemical staining showed that the beta-Gal-positive reactivated cells were neural stem or progenitor cells. These results suggest that brain disorders may occur long after infection by reactivation of latent infection in the immature neural cells in the brain.

Animals↗

Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy: prognostic factors and survival.

AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract. METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively. RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach: n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients. WBRT was applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs 8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors, respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms. Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) >=70 was 5.5 mo vs 2.1 mo for patients with KPS <70 (P<0.01, log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival. CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the number of brain metastases have a profound influence on treatment outcome.

Adult↗

Plastination of whole brain specimen and brain slices.

BACKGROUND: The human dead body specimens are plastinated for teaching purposes in medical institutions, using silicone. The silicone impregnated whole brain specimens and brain slices do not give satisfactory results. METHODS: In the present study the brain specimens were plastinated with another polymer known as Polyester-Copolymer. The brain specimens were first preserved and then fixed with 5% formalin. The specimens were then dehydrated and degreased in a volatile solvent acetone. The specimens were placed in Polyester-Copolymer solution which penetrated the brain tissue both intracellulary and intercelluraly. The specimens were then cured by gas method. RESULTS: The whole brain specimens and brain slices plastinated with Polyester-Copolymer were dry, odorless, handy and durable. It also gives a clear visual contrast between grey and white matter in brain slices whereas the brain specimens plastinated with silicone are flexible and sticky. There was no color contrast between grey and white matter. CONCLUSION: The polyester impregnated brain specimens and slices are non-toxic and ideal for teaching purposes and examinations. They require minimal aftercare. The whole organ serial sections of plastinated brain specimens will help 3-dimensional study of the normal brain and will improve the assessment of brain pathology.

Brain↗

Early monitoring of P(ti)O(2), P(ti)CO(2), pH and brain temperature in patients with brain injuries and the clinical significance.

OBJECTIVE: To explore the regulation of early brain tissue metabolic changing after brain injuries and the clinical significance. METHODS: There were 17 patients with brain injuries. Early dire ct monitoring of P(ti)O(2), P(ti)CO(2), pH and brain temperature, dynamic observation of the relation between various parameters and clinics after brain injuries were performed. RESULTS: Early changes of P(ti)O(2), P(ti)CO(2) and pH were closely correlated with outcome. The death rate obviously increased when P(ti)O(2) was continuously lower than 9 mmHg within 24 hours after injuries. Secondary brain injury prolonged and aggravated brain tissue metabolic disturbance. When intracerebral pressure was over 30 mmHg P(ti)O(2) began to decrease. The brain temperature in brain death patients was evidently lower than axillary temperature. CONCLUSIONS: The direct monitoring of P(ti)O(2), P(ti)CO(2), pH and brain temperature is safe and accurate and can find early anoxia da mage to brain tissue and provide reliable basis for clinical therapy. It ha s an instructive significance in selecting and studying a new treatment method in brain injuries. And it can be taken as a criterion in clinical judging brain deaths.

Adult↗