Hemodynamic and metabolic changes following cerebral revascularization in patients with cerebral occlusive diseases

Changes in cerebral hemodynamics and metabolism following cerebral revascularization were evaluated using positron emission tomography (PET). Ten patients who had received nonsurgical treatment for 3-6 months for minor completed stroke underwent superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery. All patients showed no extensive infarction on MR, and responsible vascular lesions were detected in the anterior circulation. A PET study of cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral metabolic rate for glucose (CMRGlu) measurements was performed before and 1.5 months after surgery using a steady state technique. Angiographically, anastomotic sites were patent in all patients. Seven patients showed neurological improvement after surgery and the others showed no improvement. The decreases in CBF, CMRO2 and CMRGlu recovered to some extent not only on the lesion side but also on the contralateral side after surgery. The increase in OEF values on the lesion side subsequently decreased after surgery. CMRO2 and CMRGlu showed parallel changes. It is concluded that the metabolic improvement afforded by the cerebral revascularization resulted in the neurological improvement, and that PET study is a powerful method for evaluating patients with cerebral occlusive diseases.     

E1 protein of bovine papillomavirus 1 is not required for the maintenance of viral plasmid DNA replication

Derivatives of bovine papillomavirus 1 (BPV1) with temperature-sensitive and dominant-negative mutation the E1 gene were used to determine the requirement for E1 in the maintenance of viral plasmid DNA replication. The abilities of these mutant BPV1 genomes to replicate as nuclear plasmids were monitored at permissive (32 degrees C) and nonpermissive (37 degrees C) temperatures in mouse C127 cells. We found that the temperature-sensitive E1 mutant BPV1 genomes replicate as nuclear plasmids as efficiently as does wild-type BPV1 in C127 cells after shifting to the nonpermissive temperature. These findings indicate that BPV1 does not require E1 for the maintenance of viral plasmids.     

Repeat cytoreduction and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal carcinomatosis of appendiceal origin

Background

The purpose of this study was to clarify the role of repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in the management of recurrent peritoneal carcinomatosis of appendiceal origin.

Methods

Data were retrieved on 42 patients who underwent CRS + HIPEC; 29 repeat surgical procedures were performed in 13 patients.

Results

Complete cytoreduction was achieved in 12 of 13 patients by the second CRS. Repeat recurrence was detected in 11 patients, eight of whom underwent a third CRS. The peritoneal cancer index decreased from initial CRS to repeat CRS but was still higher than 18 in nine patients at the second CRS. Preoperative chemotherapy was given to three patients with early recurrence. Grade 3–5 morbidity and 90-day mortality were not significantly different between initial and repeat CRS. Five-year survival rates after first and second CRS were 75.5 and 67.7%, respectively. Complete cytoreduction at second CRS was a significant prognostic factor. Among patients with recurrence after the second CRS, patients who underwent a third CRS showed a better prognosis than those who did not.

Conclusions

Repeat CRS is oncologically beneficial, and the morbidity rate was as high as that of initial CRS. Complete cytoreduction was the key to successful long-term results. Although further recurrence was common, aggressive resection was useful, even in cases of diffuse recurrence.

     

Outcomes of early surgery for infective endocarditis with moderate cerebral complications

Objectives

We sought to clarify the effect of stroke severity on clinical outcomes in patients with infective endocarditis (IE) with cerebral complications and evaluate the impact of early surgery in the active phase on long-term prognosis in patients with nonsevere neurologic deficits.

Electrophysiological analysis of the hippocampal-septal projections: II. Functional characteristics

Summary 1. The septum and dorsal hippocampus were exposed in rats by the ablation of the overlying cortex and corpus callosum. The hippocampal efferent system, fornix and fimbria, were stimulated with either single or paired shocks and field potentials, extra- and intra-cellular unitary potentials were recorded in the lateral septal nucleus. 2. The double-shock pairing within the same hippocampal system resulted in facilitation of the monosynaptic test field response. 3. Pairing across systems resulted in long-term suppressions of the mono-synaptic test field response. 4. IPSPs and lack of convergence of excitatory input are responsible for the long-term suppression. 5. It is suggested that the IPSPs are mediated via interneurons, and that some of which at least are activated recurrently. 6. Hippocampal stimulation suppresses the amygdaloid evoked field response for very long periods, often beyond 1000 msec.This study was supported by U.S. Public Health Service Grants RR 5384 and NB 00405.     

Morphological and electrophysiological characteristics of pyramidal tract neurons in the rat

Summary Responses evoked in neurons of rat sensorimotor cortex upon stimulation of the pyramidal tract and ipsilateral cerebral peduncle were analysed using intracellular recording. Neurons responding antidromically to pyramidal tract stimulation (PT cells) and neurons failing to respond anti-dromically but exhibiting orthodromic responses were both stained by intracellular injection of horse-radish peroxidase (HRP). Layer V pyramidal neurons, including those responding antidromically, exhibited prominent long lasting membrane hyperpolarizations and inhibitions of action potentials following pyramidal tract or cerebral peduncle stimulation. Upon passage of polarizing intracellular current two components were identified within the hyperpolarizing potential. A short duration initial component readily reversed with hyperpolarizing current. Frequently this earlier component over-lapped a period of early excitation consisting of action potentials arising from recurrent EPSPs or large slow depolarizing potentials (SDPs). The second, much longer duration hyperpolarizing component did not reverse with passage of hyperpolarizing current and was often followed by a rebound period of depolarization and action potential generation. Both the excitatory and the inhibitory portions of these responses could be demonstrated in animals with acute thalamic transections severing the ascending lemniscal pathway to cortex. Following intracellular staining with HRP, two types of PT cells were identified by their different intracortical axonal arborizations. Most of the injected neurons had local axonal fields extending widely in layers V and VI, but with few or no collaterals extending radially toward the more superficial layers. A second type of PT cell had axon collaterals limited to a narrow zone around the dendritic field but extending radially as far as layer I. Cells of both types were observed to send axon collaterals into neostriatum. Both types of neurons exhibited morphological and physiological characteristics of slow PT cells, and we could find no cells comparable to the fast conducting PT cells observed in other species.Supported by NIH grants NS 20743 (to CJW), NS 20702 (to STK) and a FRSQ fellowship (to PL)     

Morphological and physiological properties of neostriatal neurons: An intracellular horseradish peroxidase study in the rat

The physiological and morphological (light and electron microscopic) properties of four categories of neostriatal neurons (two types of medium spiny cells and two types of aspiny cells) were analyzed using the technique of intracellular recording and intracellular labeling with horseradish peroxidase. All of the neurons in this study had excitatory responses following stimulation of the cortex and substantia nigra except for the large aspiny neuron for which only substantia nigra inputs were tested. Morphologically, these neurons differed with respect to the size and shape of their somata, density and distribution of dendritic spines and distribution of their axons and axon collaterals. Ultrastructurally, observed somatic differences included the quantity and distribution of organelles and conformation of the nuclear envelope.The axons of one type of medium spiny neuron and the large aspiny neuron were myelinated. Unmyelinated axon collaterals arose from the axons of both types of medium spiny neurons and formed synapses on the dendritic shafts and possibly with the necks of spines of other neostriatal neurons. The parent axons of the most common type of medium spiny neurons were followed to the globus pallidus and, in some cases, to the internal capsule.     

Developmental expression of KG-CAM in the rat neostriatum

The present study examines the developmentally regulated expression pattern of an Ig superfamily member, KG-CAM, in the neostriatum of the rat. KG-CAM is a 90-kDa glycoprotein that is related to the DM-GRASP/Neurolin family of adhesion molecules. In the embryonic and early postnatal neostriatum, the distribution of KG-CAM correlates with the distribution of dopaminergic terminals. Early in neostriatal development, KG-CAM is found in the tyrosine hydroxylase-positive patches. In the maturing neostriatum, the levels of KG-CAM remain high within the patches, and KG-CAM upregulates in the matrix compartment. As the neostriatum is reaching its adult morphology, 5 weeks postnatal, the expression of KG-CAM in the matrix is approximately equal to that of the patches. When the distribution of KG-CAM is examined at the ultrastructural level, the immunoreactivity is localized to the external surface of neuronal and glial profiles in the neuropil. KG-CAM does not appear to be associated with the guidance of dopaminergic axons from the substantia nigra to the striatum, for this pathway is not immunopositive for this member of the Ig superfamily. The present study identifies an Ig superfamily member, KG-CAM, that appears to play a major role in the development of the neostriatum. Furthermore, the high levels of KG-CAM in the adult neostriatum suggest that this Ig superfamily member may be involved in maintaining the integrity of this structure in the adult rat.     

Active membrane properties of rat neostriatal neurons in an in vitro slice preparation

Summary The active membrane properties of rat neostriatal neurons have been studied in an in vitro slice preparation. All the neurons examined had resting membrane potentials of more than 50 mV and generated action potentials with amplitudes exceeding 70 mV. The morphological characteristics of the neurons identified by intracellular labeling with HRP indicated that they were medium spiny neurons. 1. Depolarizing current injection through the recording microelectrode generated slow depolarizing potentials and repetitive action potentials with frequencies ranging from less than 10 Hz to over 300 Hz. Adaptation of action potentials was observed when long duration depolarizing current was injected. 2. Depolarizing current injections revealed that the membrane of the striatal neuron had an anomalous rectification when the membrane potential was depolarized to the resting potential. A possible bases for the anomalous rectification might involve inactivation of K-conductance and slow inward Ca- and/or Na-currents. 3. Local electrical stimulation evoked depolarizing postsynaptic potentials (DPSPs) followed by long-lasting small depolarizations. In a double stimulation test, a potentiation of the test DPSP was observed at interstimulus time interval of up to 80 ms. Post-tetanic potentiation of DPSPs was also seen in these neurons. 4. Tests utilizing depolarizing current injection, intracellular Cl^– injection, and Cl-conductance blocking drugs indicated that the DPSPs were composed of EPSPs and overlapping IPSPs. 5. The nature of the longlasting small depolarization succeeding the DPSPs could not be conclusively determined. However, available data suggest that the slow inward Cacurrent may be responsible for this response. 6. In some neurons, antidromic responses were observed following local stimulation. Spike invasion into the somatic region was blocked by an injection of hyperpolarizing current to the neuron or by synaptic inputs evoked by conditioning local stimulation. These findings may explain the difficulties encountered by previous investigators in obtaining antidromic responses from neostriatal neurons in in vivo preparation.     

Epitope-blocking enzyme-linked immunosorbent assay to differentiate west nile virus from Japanese encephalitis virus infections in equine sera

West Nile virus (WNV) is now widely distributed worldwide, except in most areas of Asia where Japanese encephalitis virus (JEV) is distributed. Considering the movement and migration of reservoir birds, there is concern that WNV may be introduced in Asian countries. Although manuals and guidelines for serological tests have been created in Japan in preparedness for the introduction of WNV, differential diagnosis between WNV and JEV may be complicated by antigenic cross-reactivities between these flaviviruses. Here, we generated a monoclonal antibody specific for the nonstructural protein 1 (NS1) of WNV and established an epitope-blocking enzyme-linked immunosorbent assay that can differentiate WNV from JEV infections in horse sera. Under conditions well suited for our assay system, samples collected from 95 horses in Japan (regarded as negative for WNV antibodies), including those collected from horses naturally infected with JEV, showed a mean inhibition value of 8.2% and a standard deviation (SD) of 6.5%. However, inhibition values obtained with serum used as a positive control (obtained after 28 days from a horse experimentally infected with WNV) in nine separate experiments showed a mean of 54.4% and an SD of 7.1%. We tentatively determined 27.6% (mean + 3 x SD obtained with 95 negative samples) as the cutoff value to differentiate positive from negative samples. Under this criterion, two horses experimentally infected with WNV were diagnosed as positive at 12 and 14 days, respectively, after infection.