Prediction of tissue survival after stroke based on changes in the apparent diffusion of water (cytotoxic edema).

This study tested the hypothesis that the estimate of the apparent diffusion coefficient (ADC; an index of cytotoxic edema) of water is a reliable pathophysiological index of the viability of ischemic brain tissue. CBF, the partition volume of water (PVW; an index of vasogenic edema), cerebral metabolic rate of oxygen (CMRO2), and of glucose (CMR(glc)) were measured before and after permanent middle cerebral artery occlusion (MCAO) or reperfusion with positron emission tomography (PET) in pigs. Then, the ADC was measured by diffusion-weighted magnetic resonance imaging (DW-MRI) and was compared with physiological variables obtained by PET and with histological findings. Both after permanent MCAO and reperfusion, the ADC was significantly correlated to the CMRO2 and CMR(glc). The sequential decrease of ADC was also correlated to the sequential reduction of CMRO2 in relation to the residual CBF after permanent MCAO. The infarction coincided with a threshold CMRO2 of 50% of the contralateral value and a threshold ADC of 75% of the contralateral value, respectively. The PVW was decreased in relation to the magnitude of residual CBF after MCAO, whereas it was transiently increased in the severely ischemic lesions below 75% of the contralateral ADC value after reperfusion. Thus, the ADC is a reliable pathophysiological index which allows therapy to be tailored to the condition of individual patients in clinical practice.

Viability thresholds of ischemic penumbra of hyperacute stroke defined by perfusion-weighted MRI and apparent diffusion coefficient.

BACKGROUND AND PURPOSE: The penumbra of ischemic stroke consists of hypoperfused, but not irreversibly damaged, tissue surrounding the ischemic core. The purpose of this study was to determine viability thresholds in the ischemic penumbra, defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of diffusion- and perfusion-weighted MRI (DWI and PWI, respectively). METHODS: DWI and PWI were performed in 11 patients 1.63. Higher sensitivity and accuracy in predicting outcome of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT maps. The initial rCBV and apparent diffusion coefficient ratios did not differentiate between the part of the penumbra that recovered and the part that progressed to infarction. The mean rCBF ratio was optimal in distinguishing the parts of the penumbra recovering or progressing to infarction. CONCLUSIONS: The thresholds found in this study by combined DWI/PWI might aid in the selection of patients suitable for therapeutic intervention within 6 hours. However, these hypothesized thresholds need to be prospectively tested at the voxel level on a larger patient sample before they can be applied clinically.

Prediction of tissue survival after middle cerebral artery occlusion based on changes in the apparent diffusion of water.

OBJECT: In this study the authors tested the hypothesis that the estimate of the apparent diffusion coefficient (ADC) of water is a reliable pathophysiological index of the viability of ischemic brain tissue. METHODS: Cerebral blood flow (CBF) and the cerebral metabolic rates of oxygen and glucose (CMRO2 and CMRglc, respectively) were measured using positron emission tomography (PET) scanning before and after permanent middle cerebral artery occlusion (MCAO) or reperfusion in pigs. The ADC value, which was measured using diffusion-weighted magnetic resonance (DW MR) imaging was compared with physiological variables obtained by PET scanning and with histological findings. After both permanent MCAO and reperfusion, the decrease in the ADC was significantly correlated with decrease in the CMRO2 and CMRglc. The infarction coincided with a CMRO2 threshold of 50% of the value measured on the contralateral side. Thus, an ADC value of 80% or 75% of the contralateral value reflected the CMRO2 threshold after permanent MCAO or reperfusion, respectively. On DW MR images, lesions with ADC values above 80% of the contralateral value are potentially reversible until 6 hours after MCAO, whereas lesions with ADC values below 75% of the contralateral value are irreversible as early as 2 hours after MCAO. CONCLUSIONS: The ADC of water provides a reliable pathophysiological index for tailoring therapy to the condition of individual stroke patients in clinical practice.

Relationship between residual cerebral blood flow and oxygen metabolism as predictive of ischemic tissue viability: sequential multitracer positron emission tomography scanning of middle cerebral artery occlusion during the critical first 6 hours after stroke in pigs.

OBJECT: The authors tested the hypothesis that oxygen metabolism is the key factor linking the long-term viability of ischemic brain tissue to the magnitude of residual blood flow during the first 6 hours following a stroke. METHODS: Eleven anesthetized pigs underwent a series of positron emission tomography studies to measure cerebral blood flow (CBF) and metabolism before and for 7 hours after the animals were subjected to permanent middle cerebral artery (MCA) occlusion. The extent of collateral blood supply was assessed using angiography. Abnormal metabolism of the ischemic tissue progressed as a function of time in inverse proportion to the magnitude of residual CBF, and the volume of the infarct grew in inverse proportion to the residual blood supply. Ten hours after occlusion of the MCA, the infarct topographically matched the tissue with a cerebral metabolic rate of oxygen consumption below 50% of values measured on the contralateral side. This was also the threshold for the decline of the oxygen extraction fraction below normal, which was critical for the prediction of nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not reach the cerebral metabolic rate of oxygen threshold of viability during the first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12-30 m1/100 g/ min) reached the threshold of viability in 3 hours; and severely ischemic tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour. CONCLUSIONS: The relationship between the residual CBF and both oxygen metabolism and extraction is critical to the evolution of metabolic deficiency and lesion size after stroke.

Cerebral blood flow and blood volume measured by magnetic resonance imaging bolus tracking after acute stroke in pigs: comparison with [(15)O]H(2)O positron emission tomography.

BACKGROUND AND PURPOSE: Early and accurate assessments of cerebral ischemia allow therapy to be tailored to individual stroke patients. We examined the feasibility of using a novel method for measuring cerebral blood flow (CBF) of ischemic tissue based on MRI after middle cerebral artery occlusion (MCAO). Moreover, the regional correlations between CBF and cerebral blood volume (CBV) were investigated in the regions with acute ischemic stroke. METHODS: CBF and CBV were measured before and after MCAO or reperfusion by positron emission tomography (PET) in 13 pigs. Just after the PET scans, CBF and CBV were measured by MR bolus tracking and were compared with results obtained by PET at 6 hours after permanent MCAO or reperfusion. The infarction was verified histologically. RESULTS: The MR method yielded parametric CBF and CBV maps with tissue contrast in good agreement with parametric PET images, which demonstrated hypoperfused and hyperperfused areas after MCAO or reperfusion. Both MRI and PET technology showed that CBF values below 60% of the contralateral value induced a reduction of CBV, which committed the tissue to infarction. CONCLUSIONS: The novel MR method provides accurate measurement of CBF and CBV in acute stroke and hence gives useful information for planning the appropriate therapeutic intervention.

The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted to a minipig model of Parkinson's disease: preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers.

A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, which had been manipulated to secrete glia cell line-derived neurotrophic factor (GDNF) (approximately 2 ng GDNF/h/10(5) cells). MPTP was administered (1 mg/kg/day, SC) for 7-10 days until the pigs had developed mild parkinsonian symptoms of muscle rigidity, hypokinesia, and impaired coordination, especially of the hind limbs. Approximately 2 weeks after the last MPTP dose, animals received a T1-weighted magnetic resonance imaging (MRI) scan, and a series of dynamic PET recordings. After the first series of PET scans, four grafts of porcine embryonic mesencephalic tissue (E28 days) were placed in each striatum of some MPTP-intoxicated pigs, using MRI-based stereotactic techniques. Immunosuppression of some animals with cyclosporin and prednisolone began just prior to surgery. Two more series of PET scans were performed at 4-month intervals after surgery. After the last scans, pigs were killed and the brains were perfused for unbiased stereological examination of cytological and histochemical markers in striatum and substantial nigra. The behavioral impairment of the animals (the "Parkinson's score") had been evaluated throughout the 8-month period. Kinetic analysis of the first set of PET scans has indicated that the rate constant for the decarboxylation of FDOPA in catecholamine fibers was reduced by 33% in striatum of the mildly parkinsonian pigs. The rate of association of [11C]NS-2214 to catecholamine uptake sites was reduced by 62% in the same groups of pigs. No significant difference was found in the binding potential of [11C]raclopride to the dopamine D2-like receptors in striatum of the MPTP-intoxicated versus control pigs. These preliminary results are suggestive that the activity of DOPA decarboxylase may be upregulated in the partially denervated pig striatum.

Quantitative PET analysis of regional cerebral blood flow and glucose and oxygen metabolism in response to fenfluramine in living porcine brain.

The serotonin agonist fenfluramine has been used widely in humans for studying neuronal activation. We carried out the present study in order to determine whether anesthetized pigs could be used for studying effects of fenfluramine on cerebral functions using positron emission tomography (PET). We obtained quantitative measures of regional cerebral blood flow (rCBF) and of glucose and oxygen utilization (rCMRglc and rCMR(O2)) during intravenous administration of fenfluramine, using [15O]water, [18F]FDG and [15O]oxygen, respectively. Fenfluramine (25 mg/h i.v.) caused a significant rise in rCBF and, to a lesser extent, in rCMR2(O2), but it failed to affect rCMRglc. The findings indicate that quantitative estimation of rCBF by repeated injection of [15O]water was more sensitive than either rCMRO2 or rCMRglc for detecting effects of fenfluramine on serotonin neurotransmission in living porcine brain.

[Spontaneous regression of cerebral arterio-venous malformation following major artery thrombosis proximal to dominant feeders: a case report].

A rare case of spontaneous regression of cerebral arterio-venous malformation (AVM) is reported. A 76-year-old male was admitted to Juzen General Hospital due to generalized convulsion on August 24, 1987. On admission, results of physical and neurological examinations were normal. Plain CT scans showed an iso-density lesion with a slightly high density spot in the left frontal lobe, and enhanced CT scans showed multiple, irregularly tubular enhancements in the lesion. Left carotid angiogram (CAG) demonstrated an arteriovenous malformation (AVM) in the left frontal lobe, which was fed by the left ACA and MCA and drained by the ascending cerebral vein and superficial Sylvian vein. There was also an anterior communicating artery aneurysm. At the patient's request, he was treated conservatively and was discharged without neurological deficit. Though he continued to take anticonvulsants thereafter, he felt weakness or numbness of the right extremities once a year. Five years after the first admission, he developed sudden onset of right hemiparesis, aphasia and consciousness disturbance. On admission, his platelet aggregation function was elevated. At this time, enhanced CT scans did not show any enhanced area in the left frontal lobe where AVM had been found previously. T2-weighted magnetic resonance image showed a mixed intensity area without any flow void phenomenon suggesting thrombosis of the nidus. Left CAG demonstrated occlusion of the A1-A2 junction of the anterior cerebral artery and disappearance of the AVM. He was treated conservatively again, and was discharged without neurological deficit.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancing effects of pertussis toxin B oligomer on the immunogenicity of influenza vaccine administered intranasally.

Influenza vaccines together with pertussis toxin B oligomer (PTB) purified from a culture supernatant of Bordetella pertussis were administered intranasally into mice to test for an adjuvant effect of the PTB. An inactivated virus vaccine and an ether-treated HA vaccine prepared from influenza virus A/Yamagata/120/86 (H1N1) and formulated with PTB, stimulated production of serum haemagglutinin inhibition (HI) antibody and pulmonary and endotracheal secretory IgA antibody to high titres. In addition, mice immunized with the influenza vaccines formulated with PTB were protected against exposure with a challenge virus. These results demonstrate that PTB can enhance the immunogenicity of influenza vaccines administered intranasally.

Cranial fasciitis of childhood: a case report.

Cranial fasciitis of childhood is very rare, only 17 cases having been reported in the literature. We report an additional case of this rare disease. The patient was a 5-year-old boy who complained of left exophthalmos and double vision. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large epidural mass in the left frontal region that had invaded into the underlying anterior skull base. The tumor showed homogeneous, low density with nonhomogeneous contrast enhancement on the CT scans, and low intensity on the T1-weighted and high intensity on the T2-weighted MRI images. A whitish-pink, elastic, hard tumor was revealed in the epidural space in the left anterior cranial fossa, which was totally excised with curettage of the affected anterior skull base. The origin of the tumor was suspected to be the fibrous connective tissue of the sphenofrontal suture. The histological diagnosis was that of cranial fasciitis. There was no evidence of recurrence 1 year postoperatively.

Phase 1 clinical tests of influenza MDP-virosome vaccine (KD-5382).

MDP-virosome vaccine, which contains haemagglutinin (HA) and neuraminidase (NA) antigens isolated from influenza virus combined with 6-O-(2-tetradecylhexadecanoyl)-N-acetylmuramoyl-L-alanyl-D-isoglutamine) (B30-MDP) and cholesterol was tested, in comparison with a currently used HA vaccine, for immunogenicity and adverse reactions on 77 adult male volunteers. The volunteers were divided into eight groups, and each individual was injected subcutaneously once, or twice at a 4 week interval, in their upper arm with one of seven different MDP-virosome vaccine preparations or with HA vaccine as control. Of the three virus strains used as vaccine antigens, MDP-virosome vaccines induced higher haemagglutination inhibiting (HI) antibody to A/Yamagata/120/86 (H1N1) and A/Fukuoka/C29/86 (H3N2) than did HA vaccine, whereas it induced lower HI antibody to B/Nagasaki/1/87, comparable with that induced by HA vaccine. Regarding local adverse reactions, MDP-virosome vaccinees frequently developed mild local pain, reddening and swelling, which disappeared within 5 days; as regards systemic no adverse reactions, leucocytosis developed among the MDP-virosome vaccines, but no other reactions were observed. The leucocytosis may have been caused by the pharmacoimmunological activity of B30-MDP derivatives.

Foramen magnum decompression for syringomyelia associated with basilar impression and Chiari I malformation--report of three cases.

Anterior or posterior decompression of the foramen magnum was performed in three patients with syringomyelia associated with basilar impression and Chiari I malformation. The operative results were evaluated using the pre- and postoperative magnetic resonance (MR) images. Two patients with combined anterior and posterior cervicomedullary compression due to basilar impression and tonsillar descent received suboccipital craniectomy, upper cervical laminectomy, and dural plasty without any intradural manipulations via the posterior approach. One patient with prominent anterior cervicomedullary compression due to basilar impression and a sharp clivoaxial angle was operated on by the transoral anterior approach. Postoperatively, all patients showed a sustained shrinkage of the syrinx and rounding of the flattened cerebellar tonsils. Two patients showed upward movement of the herniated tonsils. All patients had improved symptoms during 2-4 years follow-up. Treatment of syringomyelia associated with basilar impression and Chiari I malformation requires more efficient decompressive procedures at the foramen magnum based on neurological and MR findings.

Further evaluation of the pertussis component vaccine produced by apoceruloplasmin affinity chromatography.

The heat-treated apoceruloplasmin (Apocp) is a useful protein as an affinity ligand for the purification of pertussis toxin (PT). The amounts of Apocp in the purified antigens or the pertussis component vaccine were determined. Anti-Apocp antibodies were not detected by the passive cutaneous anaphylaxis (PCA) test in rats. No anti-Apocp antibody was detected after hyperimmunization of rabbits with the vaccine. Apocp was not detected in PT and filamentous hemagglutinin (FHA) by ELISA using rabbit anti-Apocp IgG. In the experiments using 125I-labelled Apocp, 125I-Apocp was not detected in either PT or FHA which were purified by 125I-labeled Apocp-Sepharose, DEAE Sepharose, and cellulose sulfate chromatography. The contents of human DNA were also determined to be less than 10 pg per 1 mg of Apocp, by the dot-blot hybridization method using the 32P-labeled DNA probe of Alu sequence. In the tests for the presence of inapparent viruses, HBs antigen and HTLV-III antibody, no contamination was found in either the Apocp or in the vaccine. Large amounts of various viruses, which were intentionally added to the Apocp (spiking test), were completely inactivated by heating at 65 degrees C for 18 hr. Both the Apocp and the vaccine passed the general pharmacology and acute toxicity tests. From these results, the heat-treated Apocp was considered to be a suitable affinity ligand for the purification of the antigens for the pertussis component vaccine.

Comparison of the protective effects of the pertussis acellular vaccine with the component vaccine, which have different amounts of fimbriae, against the experimental aerosol infection of mice with Bordetella pertussis.

We obtained highly purified fimbrae from Bordetella pertussis cells which gave a single band in SDS-polyacrylamide gel electrophoresis. Using the purified fimbriae, we prepared anti-fimbriae rabbit or goat IgGs by fimbriae-Sepharose affinity chromatography, and developed ELISA for its determination. The concentration of fimbriae in our former type of acellular vaccine (80 micrograms per ml) was determined to be 20 ng per ml, and that in our component vaccine was at an almost negligible level. To estimate the protective effects of the small levels of fimbriae, we evaluated the protective activities of three types of vaccines; the former type acellular vaccine (pertussis toxin (PT): filamentous hemagglutinin (FHA): fimbriae = 15:61:0.02 (microgram per ml)), the two-component vaccine (16:64:0.0001), and the three-component vaccine (16:63:0.8). The three types of vaccines showed no significant differences in protectivity against the experimental aerosol infection suggesting that these levels of fimbriae are not effective against the experimental aerosol infection of mice with Bordetella pertussis.

Impact resistance of highly crosslinked plastic denture teeth.

The impact resistance of highly cross-linked plastic denture teeth materials such as SR-Orthosit (R), Crystal-ND (R), and Mitel-OM (R) was investigated and compared to that of conventional denture teeth materials. Dentures with upper second molars were placed on a metal model. The thicknesses of the denture teeth were 1.4, 1.0, and 0.4 mm. An impact force was repeatedly applied to the central fossae of the denture teeth with an impact test machine. Impact resistance was defined as the number of impacts sustained by the tooth material prior to fracture. The results showed that the impact resistance of highly crosslinked plastic teeth decreased with decreasing thickness, but was comparable to that of conventional plastic teeth when the teeth were 1.4 mm thick and supported by denture base resin. It is hypothesized that the layer of PMMA denture base resin beneath the denture teeth functions as a shock absorber during impact.

Influenza vaccine: enhancement of immune response by application of carboxy-vinylpolymer.

We evaluated the possibility of application of carboxy vinylpolymer (CVP) to influenza vaccine for the improvement of immune response. Our result shows that CVP induces good immune responses after inoculation of vaccines to mice both subcutaneously, intraperitoneally, and intranasally. Considering the efficacy and safety, intranasal administration of the CVP-coupled vaccine may be the best route of immunization.

Adhesive bonding of denture base resins to plastic denture teeth.

The adhesive bonding of denture teeth to denture base resins in dentures with conventional acrylic teeth and crosslinked plastic teeth was investigated. The dentures with highly crosslinked plastic teeth such as SR-Orthosit, Crystal ND, and Mitel-OM showed poor bonding at the tooth/base resin interface using the conventional bonding method. Elimination of the alginate mold lining material in the conventional bonding method effectively improved bonding at the tooth/base resin interface. The application of 4-META adhesive bonding agents to the denture teeth improved the interface bonding of highly crosslinked plastic teeth and the denture base. Dentures with Orthosit and Mitel showed differences in bonding ability when two different adhesives were used.

[The evaluation of wear resistance of hybrid denture teeth].

Wear characteristics of hybrid denture teeth, plastic denture teeth which were partially reinforced with metal, was evaluated. The plane specimens were made up with resin and metal. Light curing veneering resin, new metacolor, heat curing veneering resin, Mitel-OM and PMMA (Poly methyl methacrylate) were used for resin parts, while gallium containing filling alloy, silver alloy, palladium alloy and titanium containing chromium cobalt alloy were used for metal parts. The specimens were abraded by the rod specimens of palladium alloy with abrasion test machine. The wear depth and width were measured at 1, 5, 10 and 20 x 10(4) times of abrasion which stroke was 10 mm each. The specimens of heat cured veneering resin reinforced with chromium cobalt alloy showed the least wear loss while the specimens of PMMA reinforced with silver alloy did the most. The difference of wear ratio between light cured and heat cured veneering resin was not statistically significant.