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Biomedical subjects

R A Zappulla

Publications and source records attributed to R A Zappulla.

At least 37 records · Page 2Linked to original sources

Physiological and electrophysiological consequences of etoposide-induced blood-brain barrier disruption.

The present study investigates the effects of etoposide-induced blood-brain barrier (BBB) disruption on systemic blood pressure (SBP), intracranial pressure (ICP), and electroencephalographic (EEG) activity. A total of 29 rats were divided into two groups. In Group 1, 8 control animals received intracarotid normal saline; in Group 2, 21 animals received intracarotid etoposide. SBP, ICP, and EEG were monitored continuously under general anesthesia and controlled ventilation after tracheostomy. Intravenous Evans blue dye was used for determination of BBB disruption. Although none of the Group 1 animals showed BBB disruption, 57% of the animals in Group 2 showed marked BBB disruption (3+). A slight but statistically significant increase in ICP was noted in the Group 2 animals with 3+ BBB disruption, although lesser degrees of barrier disruption (1+ or 2+) resulted in no significant alteration in ICP. The amplitude and frequency of the EEG decreased significantly ipsilateral to the side of intracarotid infusion in all animals with 3+ barrier disruption with a tendency to return toward normal within 2 hours. The degree of transient EEG change observed correlates well with the degree of barrier disruption, potentially allowing clinical determination of BBB disruption by this method.

Animals↗

Isolated central nervous system metastasis from transitional cell carcinoma of the bladder: report of a case and review of the literature.

Although systemic metastases from transitional cell carcinoma of the bladder occur frequently, involvement of the central nervous system is uncommon. We describe a patient with an isolated cerebral metastasis who had previously undergone resection of a Grade III, Stage B2 carcinoma of the bladder. We have been able to find only one previous case report of a solitary intracerebral metastasis from transitional cell carcinoma of the bladder without evidence of primary recurrence or additional sites of spread. Central nervous system metastasis from bladder carcinoma must be considered in the differential diagnosis of solitary intracerebral lesions.

Antineoplastic Combined Chemotherapy Protocols↗

Neurological deterioration after lumbar puncture below complete spinal subarachnoid block.

The risk of neurological deterioration after removal of cerebrospinal fluid below the level of a complete spinal subarachnoid block is generally accepted. The actual incidence of deterioration after lumbar puncture in the presence of a complete block remains unknown. The present retrospective case analysis includes a review of 100 patients found to have complete block on myelography: 50 cases with a lumbar puncture and 50 cases with a C1-2 puncture. Each group consisted of a similar age range, neurological status prior to myelography, level of block, and nature of disease. Seven patients (14%) had significant neurological deterioration after lumbar puncture, while no deterioration was seen after a C1-2 puncture. A summary of those cases in which deterioration followed lumbar puncture is presented and the possible pathophysiology is discussed. From this analysis, the estimated risk of downward spinal coning after lumbar puncture below a complete spinal subarachnoid block caused by a mass lesion is at least 14%.

Abscess↗

Etoposide induced blood-brain barrier disruption in rats: duration of opening and histological sequelae.

The intracarotid infusion of the antineoplastic compound etoposide enhances blood-brain barrier (BBB) permeability. In a rat model system, the functional reversibility and anatomic sequelae of etoposide induced BBB disruption were investigated. Etoposide, in a dose range from 3.0 to 22.5 mg/kg, was infused into the left internal carotid artery of Sprague-Dawley rats. BBB disruption was evaluated by the appearance in the infused hemisphere of systemically administered Evans blue dye and quantitatively by the ratio of counts of the technetium labeled chelate of diethylenetriaminepentaacetic acid in the infused to the noninfused hemisphere. Functional reversibility of altered BBB permeability was investigated at three dose levels of etoposide (3.0, 15.0, and 22.5 mg/kg) by the administration of Evans blue dye at the time of etoposide infusion and the administration of the technetium labeled chelate of diethylenetriamine-pentaacetic acid at varying time intervals after etoposide infusion. Fourteen groups of 12 rats each were studied to define the time course of altered BBB permeability at these three doses. The anatomic sequelae of etoposide induced BBB disruption were investigated at varying time intervals (up to 3 weeks) after intracarotid etoposide infusion. Nineteen rats were examined after sacrifice by intracardiac fixation perfusion with 10% formalin. Each brain was sectioned coronally and examined under light microscopy after hematoxylin and eosin staining. Evidence of BBB disruption was seen at all dose levels of etoposide. The degree of BBB disruption increased with increasing doses of etoposide. The duration of altered BBB permeability increased from less than 1 day at 3.0 mg/kg to between 3 and 4 days at 22.5 mg/kg. Histological studies revealed no evidence of parenchymal damage, although at 4 days postdisruption, a mild perivascular lymphocytic infiltration was noted in the infused hemisphere. Etoposide infusion and subsequent BBB disruption were well tolerated by all test animals. In a rat model system the intracarotid infusion of etoposide is capable of producing prolonged reversible BBB disruption.

Animals↗

Electroencephalographic consequences of sodium dehydrocholate-induced blood-brain barrier disruption: Part 1. Acute and chronic effects of intracarotid sodium dehydrocholate.

Prior work has shown that the intracarotid infusion of sodium dehydrocholate can produce prolonged reversible blood-brain barrier (BBB) disruption. Associated with barrier disruption is the occasional presence of behavioral seizure activity. Electroencephalographic changes were monitored in 32 rats after BBB disruption by the left internal carotid artery infusion of sodium dehydrocholate. The electroencephalogram (EEG) was monitored for 3 hours after disruption in 20 animals, and the remaining 12 animals were followed for 24 hours. The EEG was also monitored in 8 additional control animals: 4 had undergone carotid artery infusion with normal saline, and 4 had received sodium dehydrocholate intravenously. The 20 rats monitored for up to 3 hours postinfusion were found to have varying grades of BBB disruption as measured by the presence of Evans blue staining of the brain. EEG alterations in this group included decreased amplitude and slowing as well as the presence of spike activity over the disrupted and the nondisrupted hemispheres. The more extensive the disruption, the more severe the EEG changes. In animals with minimal to moderate disruption, the EEG usually returned to base line levels within 3 hours after infusion. Animals with marked disruption usually had bilaterally flat EEGs before the end of the observation period. The remaining 12 animals were followed for 24 hours postinfusion. Of 9 animals surviving 24 hours, 1 animal had a decrease in amplitude over the disrupted hemisphere; in the remaining 8 animals, the spontaneous EEG was unchanged from predisruption levels except for occasional spikes in 2 animals. Animals infused with intracarotid saline or intravenous sodium dehydrocholate demonstrated no EEG changes or Evans blue staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Electroencephalographic consequences of sodium dehydrocholate-induced blood-brain barrier disruption: Part 2. Generation and propagation of spike activity after the topical application of sodium dehydrocholate.

Sodium dehydrocholate was applied topically to the right hemispheric cortex of eight rats and the electrocorticogram was monitored from both the treated cortex and the homotopic cortex of the contralateral hemisphere. All animals developed blood-brain barrier (BBB) disruption in the treated cortex as evidenced by cortical staining with systemically administered Evans blue dye. Spike activity developed in three of eight animals after the topical application of dehydrocholate. The subsequent intravenous injection of sodium dehydrocholate provoked spike activity in both hemispheres in all eight animals. Dependent and independent spike activity was recorded in the nondisrupted hemisphere. The intravenous administration of gamma-aminobutyric acid (GABA) resulted in alterations in spike activity in four of five animals because of penetration of the GABA through the altered BBB. These findings demonstrate that sodium dehydrocholate can result in increased BBB permeability when applied directly to the cortical surface. Spike activity subsequent to the topical application of dehydrocholate can be enhanced by systemic loading with dehydrocholate. Spike activity occurring over the nontreated cortex (secondary focus) represents interhemispheric propagation of spike activity from the disrupted hemisphere (primary focus). The lack of Evans blue staining in the actively discharging secondary focus suggests that spike activity does not account for the increases in BBB permeability observed with dehydrocholate treatment.

Administration, Topical↗

Response threshold determination of the brain stem auditory evoked response: a comparison of the phase versus magnitude derived from the fast Fourier transform.

An ensemble of 10 groups of brain stem evoked responses (BAERs), each consisting of 200 sweeps, was collected for different intensity levels and for a no-stimulus condition. A fast Fourier transform was calculated for the separate groups, which permitted a phase variance to be derived. The phase variance was compared to the magnitude value for selected frequency components making up the BAER. It was found that the phase variance was a better predictor of signal than magnitude. The superiority of prediction by phase results from intersubject variation being smaller for phase compared to magnitude.

Acoustic Stimulation↗

Changes in contralateral brain-stem auditory evoked responses to cerebellopontine angle compression in rats.

Eleven rats were subjected to graded compression of the brain stem at the cerebellopontine angle (CPA) following craniectomy and cerebellectomy. Clicks were delivered to the ear contralateral to the compression site, and brain-stem auditory evoked responses (BAER's) were collected before and during compression. With increasing compression, there was an increase in the latency and a decrease in the amplitude of the peaks of the BAER. The later peaks of the BAER (V and VI) demonstrated changes with minimal compression that progressed as compression increased, while changes in the amplitude and latency of the earlier peaks (II, III, and IV) occurred at the higher grades of compression. Following decompression of the brain stem, there was a decrease in the latencies of most of the BAER peaks. Peak amplitude remained depressed following brain-stem decompression. These experimental findings corroborate clinical reports of abnormal BAER's elicited from stimulation of the ear contralateral to a CPA tumor. The relative sensitivity of the later peaks of the BAER to even minimal brain-stem compression explains the prolonged III to V interpeak latency reported in the literature in patients with brain-stem compression from a CPA lesion. The possible mechanisms for the BAER changes that were observed contralateral to compression are discussed.

Animals↗

Effect of intracarotid etoposide on opening the blood-brain barrier.

The effect of an intracarotid artery infusion of etoposide on blood-brain barrier (BBB) integrity was investigated in a rat model system. The external carotid arteries of Sprague-Dawley rats were catheterized in a retrograde manner. Etoposide in a dose range from 3.0 mg/kg to 22.5 mg/kg was infused into the internal carotid artery by this technique. BBB disruption was evaluated qualitatively by the appearance in the infused hemisphere of the systemically administered dye Evans blue and quantitatively by the ratio of counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the infused to the noninfused hemisphere. Evidence of increased BBB permeability was seen at all doses of etoposide. Degree of BBB disruption increased with increasing doses of etoposide. The intracarotid infusion and subsequent BBB disruption were well tolerated. Further clinical trials employing the intracarotid administration of etoposide should be cognizant of the potential for BBB disruption.

Animals↗

Etoposide-induced blood-brain barrier disruption. Effect of drug compared with that of solvents.

The intracarotid infusion of the anti-neoplastic compound, etoposide, has been shown to exert a dose-dependent effect on blood-brain barrier (BBB) permeability. Etoposide, however, is formulated in a complex solvent solution containing alcohol, Tween 80, polyethylene glycol 300, and citric acid. To investigate the contribution of the solvent solution to BBB disruption, the authors studied Sprague-Dawley rats after the internal carotid artery infusion of the solvent solution with and without the addition of etoposide. Experiments were performed at four doses of drug and/or solvent. Disruption of the BBB was evaluated qualitatively by the appearance of the systemically administered dye, Evans blue, in the cerebral hemispheres and quantitatively by the ratio of gamma counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the ipsilateral:contralateral hemisphere. Significant barrier opening was obtained in all four groups of animals infused with solvent plus etoposide. In the corresponding groups of rats infused with the solvent solution alone, BBB disruption was markedly lower. Only in the group infused with the largest dose of solvent was the hemispheric ratio of 99mTc-DTPA significantly different from saline-infused animals. Each of the groups with solvent plus etoposide had 99mTc-DTPA ratios significantly different from the control group. Intracarotid infusion and subsequent BBB disruption were well tolerated by the animals receiving either solvent alone or solvent and etoposide. Disruption of the BBB secondary to the intracarotid infusion of etoposide is primarily caused by the drug itself and not by the solvent solution.

Animals↗

Learning disability assessed through audiologic and physiologic measures: a case study.

This report describes a child with central auditory dysfunction. Audiologic tests (Willeford Battery and Staggered Spondaic Word Test) indicate a brain-stem dysfunction but normal cortical functioning. Electrophysiologic tests corroborated these results. Brain-stem auditory-evoked responses (BAERs) indicated an absent contralateral peak III bilaterally when stimulating each ear separately. This is the first reported case where brain-stem dysfunction on audiologic tests were associated with specific electrophysiologic changes in the BAER.

Audiometry↗

Intracarotid dehydrocholate infusion: a new method for prolonged reversible blood-brain barrier disruption.

An animal model for prolonged reversible blood-brain barrier (BBB) disruption has been developed. The external carotid arteries of Osborn-Mendel rats were catheterized in a retrograde manner. Varying concentrations of sodium dehydrocholate were infused into the internal carotid artery by this technique. BBB disruption was evaluated qualitatively by the appearance in the infused hemisphere of the systemically administered dyes Evans blue and sodium fluorescein and quantitatively by the ratio of counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the infused to the noninfused hemisphere. The ability of sodium dehydrocholate to disrupt the BBB was documented with all three markers. As the concentration of the infused dehydrocholate was increased, both the incidence and the degree of BBB disruption increased. Reversibility of BBB disruption was evaluated by the administration of sodium fluorescein and 99mTc-DTPA at varying times after BBB disruption. Depending on the concentration of the infused sodium dehydrocholate, altered BBB permeability can be maintained for over 3 days. This new model of prolonged reversible BBB disruption deserves further investigation both for basic studies of the BBB and for therapeutic studies of drug delivery into the central nervous system.

Acute Disease↗

Prediction of cerebellopontine angle tumors based on discriminant analysis of brain stem auditory evoked responses.

Multivariate discriminant analysis of brain stem auditory evoked response component latency intervals in patients with cerebellopontine angle tumors allowed accurate detection of 90% (35 of 39) of the tumor population with response data recordable from at least one ear. Eight-five per cent (23 of 27) of these could be detected by using information from the unaffected ear. One of 21 normal subjects was misclassified. Tumors significantly increased the I-III and III-V intervals on the side of the tumor. Increases in III-V interval latency were also observed on the unaffected side. The size of the tumor was significantly correlated with both discriminant scores derived from the analysis of the unaffected ear and delays in the III-V intervals from either the affected or the unaffected ear. These results were attributed to physiological factors and mechanical distortions of the brain stem. Regression equations derived from linear discriminant analysis for cerebellopontine angle tumors are presented and discussed in terms of their predictive validity.

Brain Neoplasms↗