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Biomedical subjects

N A Vick

Publications and source records attributed to N A Vick.

At least 37 records · Page 2Linked to original sources

Efficacy of vincristine and cyclophosphamide in the therapy of recurrent medulloblastoma.

We conducted a Phase II study of combination therapy with vincristine and cyclophosphamide in the treatment of patients with recurrent or metastatic medulloblastoma. Fourteen patients were treated with vincristine 2 mg/m2 (2.0-mg maximal dose) by intravenous bolus on Day 1 and cyclophosphamide 1 g/m2 by intravenous infusion on Days 1 and 2, with cycles repeated every 4 weeks. All 4 patients with extraneural disease (biopsy-proven bony metastases) responded (duration of responses 2+, 6+, 8, and 16+ months) and 4 of 8 evaluable patients with neuraxis disease responded (duration of response 2, 2+, 2+, and 21+ months). Toxicity was limited to neutropenia without any episodes of infection. These therapeutic results compare favorably with other reports of therapy for recurrent medulloblastoma and support the inclusion of vincristine and cyclophosphamide in randomized adjuvant therapy trials of patients with medulloblastoma.

Adolescent↗

Vascular malformations of the thalamus with normal angiograms.

We describe two patients with fatal vascular malformations of the thalamus whom we thought had gliomas. They had progressive neurological impairment with subacute onset as adults. Computed tomography showed lesions of increased density with slight post-contrast enhancement; cerebral angiography was normal. Without biopsy, they received radiation therapy without benefit. Two other patients with similar radiological studies have done well with conservative treatment. We believe that these lesions have a distinctive appearance on CT, that vascular malformations can be diagnosed, even with normal cerebral angiograms, and distinguished with reasonable certainty from gliomas.

Adult↗

Murine sarcoma virus-induced brain tumors. Concurrent measurements of blood flow and transcapillary transport.

Intracerebral inoculation of Murine Sarcoma Virus (MSV) into rats induces highly vascular brain tumors. Blood flow, F, and a unidirectional blood-to-tissue transfer constant, K, were measured concurrently in 16 separate brain tumors in 13 rats. Regional measurements of F and K were obtained using double-label quantitative autoradiography with 131I-iodoantipyrine, 14C-alpha aminoisobutyric acid, and computerized microdensitometry with image analysis. Regional tissue extraction fractions (E) were calculated for different brain and tumor regions. The following observations were made: intracerebral inoculation of MSV in rats of different ages produced a single histologic tumor type (angiosarcoma), although tumor yield decreased and latency increased when older rats were inoculated; whole tumor blood flow values averaged 63.9 +/- 20.9 (SD) ml hg-1 min-1, less than F of tumor-free gray matter; the mean value of the transfer constant was 1.19 +/- 0.84 ml hg-1 min-1, 5 times the value in contralateral tumor-free brain; moderate regional variation of F and K values were observed within each tumor, with increased K values extending into the regions of brain around tumor; mean extraction fractions (E) of AIB for whole tumor were low (range = 0.0021 to 0.08), with a distinct and decreasing gradient from tumor center to BAT; there was poor correlation between F, K and E values, and tumor histology, including regions that microscopically appeared highly vascular; in most regions of the MSV-induced brain tumors, capillary permeability and/or surface area seem to be determinant in blood-to-tissue transport processes.

Aminoisobutyric Acids↗

Pleomorphic xanthoastrocytoma. Ultrastructural and immunohistochemical study of a case with a rapidly fatal outcome following surgery.

In 1979, researchers described a series of young patients with clinically and histologically distinctive supratentorial gliomas which were designated pleomorphic (meningocerebral) xanthoastrocytomas (PXA). Significantly, patients with these neoplasms were reported to have a relatively favorable prognosis. The authors present a new case of PXA in a 32-year-old man. This case is unique for two reasons: (1) a relatively rapid fatal outcome with death 21 months after diagnosis; and (2) the presence, at autopsy, of extensive recurrent tumor with features of a malignant astrocytoma. Detailed electron microscopic and immunohistochemical studies, supporting the proposed subpial astrocytic origin of PXA, are presented. Literature pertaining to PXA is reviewed. This report illustrates the unique features of PXA and demonstrates its potential for aggressive behavior.

Astrocytoma↗

Spatial distribution of proliferating cells in avian sarcoma virus-induced gliomas.

We studied the regional distribution of proliferating tumor cells in five avian sarcoma virus-induced gliomas. The labeling index and spatial distribution of [3H]thymidine (dThd)-labeled tumor cells were determined in serial sections of each tumor with a computer-assisted digitizing system. The density of [3H]dThd-labeled cells showed marked regional variation in each tumor, and the ratio of the density of [3H]dThd-labeled cells in tumor periphery to tumor center varied from 0.86 to 1.38. The labeling index generally, but not always, reflected [3H]dThd-labeled cell density. This study indicates that proliferating pools of glioma tumor cells exhibit regional variability in concentration and that the highest numbers of proliferating cells may be predominantly located in central regions of tumor and not in tumor periphery as assumed previously. In all tumors, large numbers of proliferating cells were present in all parts of the tumor.

Animals↗

Regional measurements of blood flow in experimental RG-2 rat gliomas.

Regional measurements of blood flow (F) were performed in transplanted intracerebral RG-2 rat gliomas using [14C]iodoantipyrine, Kety-Schmidt blood flow equations, and quantitative autoradiography. Twenty-nine intracranial tumors in ten rats were analyzed by location; 18 intraparenchymal, seven meningeal, two third-ventricular, and two fourth-ventricular tumors were studied. For all tumors, averaged mean F was 91 +/- 33 (S.D.) ml/hg/min. In all but one tumor, mean F was intermediate between normal cortex and corpus callosum values. There was moderate regional variation: averaged mean F was lower in tumor center (78 +/- 47 ml/hg/min) than in tumor periphery (93 +/- 30 ml/hg/min). Within individual tumors, F showed moderate variation which correlated to some extent with histological features; a regional F of less than 10 ml/hg/min was observed in only one tumor within an area of necrosis. F in regions of brain immediately surrounding the tumor was higher than in tumor periphery. Blood flow to RG-2 tumors seems unlikely to limit drug delivery any more than to normal brain, and the consistent levels from tumor to tumor and within individual tumors make the RG-2 model an excellent one with which to study drug delivery in experimental brain tumors.

Animals↗

Regional measurements of blood-to-tissue transport in experimental RG-2 rat gliomas.

Regional measurements of blood-to-tissue transport were performed in transplanted RG-2 rat gliomas using [alpha- 14C]aminoisobutyric acid (AIB), quantitative autoradiography, and equations to express a unidirectional transfer constant. Thirty-eight intracranial tumors in ten rats were analyzed according to location; 23 intraparenchymal tumors, eight meningeal tumors, six fourth-ventricular tumors, and one third-ventricular tumor were studied. Except for the small third-ventricular tumor, the transfer constant (K) for AIB was similar in all groups and ranged from 0.031 to 0.038 ml/g/min. Within individual tumors, regional variation of K was also small, although some local variation could be correlated with histological features. The K for AIB decreased in brain around tumor and, at a distance of 300 microns from tumor edge, had returned to values similar to those of normal cortex (0.002 ml/g/min). An average extraction fraction (E) of 0.09 was calculated for AIB in the RG-2 tumors. The low E suggests that delivery of water-soluble chemotherapeutic drugs to RG-2 tumors should be limited more by capillary permeability or surface area than by blood flow. RG-2 is an ideal experimental tumor with which to test drug delivery and the methods that attempt to increase drug delivery in brain tumors.

Aminoisobutyric Acids↗

Permeability of different experimental brain tumor models to horseradish peroxidase.

The permeability of different brain tumor models to horseradish peroxidase (HRP) was examined by determining the fraction of tumor that contained HRP after intravenous administration. The intracerebral tumor models studied were Avian Sarcoma Virus (ASV)-induced tumors and tumors from transplanted RG-2, S69-C1-5, and 9L cell lines. The average fraction of RG-2 tumors permeable to HRP was .95; of S69-C1-5 tumors, .699; of ASV-induced tumors. .63; and of 9L tumors, .52. Except for the RG-2 tumors, there was considerable regional variation in HRP permeability, which was most marked in the ASV-induced tumors. In ASV-induced tumors, HRP permeability did not correlate with tumor histological classification, size, or anatomic location within the brain. The subcutaneous tumor models studied were RG-2-, S69-C1-5, and 9L-transplanted tumors in rats, and human glioblastoma cell lines transplanted into nude mice. All were completely permeable to HRP. These results indicate that significant differences in permeability to HRP exist among brain tumor models when the tumors are intracerebral, and that all subcutaneous tumors from transplanted glial cell lines are completely permeable to HRP. These variables must be considered in future studies of permeability in experimental brain tumors. Care must be exercised in extrapolating results about permeability from one brain tumor model to another.

Animals↗

Acute transverse myelitis due to Mycoplasma pneumoniae infection.

We examined a woman who had acute transverse myelopathy (ATM) associated with respiratory illness due to Mycoplasma pneumoniae. To our knowledge, only one previously described case documented this relationship with serologic studies of spinal fluid. Since 16% to 35% of ATM patients experience antecedent respiratory illness, evidence of M pneumoniae infection should be sought in all cases.

Acute Disease↗

Computed tomography of virally induced canine brain tumors: a preliminary report.

Seven neonatal dogs were inoculated intracerebrally with Avian Sarcoma Virus (ASV) and studied by computed tomography (CT) for intracranial tumors. The tumor yield was five anaplastic astrocytomas and two sarcomas, with an average latency of 57 days. Computed tomography accurately detected all tumors over 5 mm in diameter and predicted the size of the tumors within 3 mm. The intensity of contrast enhancement was directly related to the dose of Conray-60. The area of enhancement on the CT scan correlated precisely with tumor permeability as determined histologically with horseradish peroxidase (HRP). Edema seen in CT scans correlated well with edema present in histological sections. Peritumoral edema was impermeable to both Conray-60 and HRP. The ASV-induced canine brain tumor model appears well suited for future CT studies.

Animals↗

Neuroradiological evaluation of lateral recess syndrome.

Fifty asymptomatic patients and 35 with surgically proved lateral recess syndrome (LRS) were studied retrospectively to determine the depth of the normal and abnormal lateral recess. Plain radiography, polytomography, CT, and myelography of the lumbosacral area were performed. The normal and abnormal ranges are presented and the role of the various radiographic procedures in the diagnosis of LRS is discussed.

Humans↗

Comparative permeability of different glioma models to horseradish peroxidase.

Seven different experimental glioma models were studied to determine their capillary permeability to horseradish peroxidase. The models were the autochthonous ASV-viral model, intracerebral (ic) and (sc) injections of rat 9L and RG-2 tumor cell lines, the sc rat S-69C15 tumor cell line, and human glioblastoma cell lines in nude mice. The ASV-viral model showed an average HRP permeability of 63% of tumor volume, the ic RG-2 tumors were 100% permeable, and the ic 9L tumors were 41% permeable. The permeability of the marginal zone (brain-tumor interface) showed similar variation from group to group. In contrast, all of the sc tumors were 100% permeable regardless of the cell line used to create the tumors. Our results show the variability between these glioma models, and suggest that RG-2 ic gliomas and all sc gliomas should be optimal to assess the tumoricidal effect of drugs, because access to the tumor compartment from the vascular compartment is complete.

Animals↗

Dominantly inherited pseudohypertrophic muscular dystrophy with internalized capillaries.

We describe two families with a father and son with the phenotypic appearance of benign (Becker's) muscular dystrophy. Other family members were normal, though in one kindred the paternal grandfather probably had the same disorder of muscle. Muscle histology resembled that seen in Becker's muscular dystrophy with, in addition, central cores and internalized capillaries in type I fibers. These capillaries seemed to be due to an unexplained ingrowth from vessels normally located outside muscle fibers and could not be ascribed to the phenomenon of fiber splitting. The internalized capillaries were histologically normal. They may be a histologic marker for dominantly inherited pseudohypertrophic muscular dystrophy, since they have not been described in other dystrophies. We suggest that fathers and paternal relatives be evaluated, in addition to the customary screening of female family members, in all instances of apparently benign (Becker's) pseudohypertrophic muscular dystrophy.

Adult↗

Demyelinating radiculopathy in the Kearns-Sayre syndrome: a clinicopathological study.

In the few previously autopsied patients with the Kearns-Sayre form of progressive ophthalmoplegia, the most prominent abnormalities have been in muscle, with less conspicuous changes in the central nervous system, primarily in the brainstem. Similar findings were present in the case reported here, but in addition there was severe demyelination in the initial few millimeters of the cranial and spinal motor roots distal to the glial-Schwann cell junction. Milder demyelination was observed in the dorsal spinal and afferent cranial nerve roots, including the eighth nerve, but deafness was due to virtually total destruction of the organ of Corti. Our observations suggest that a radiculopathy may be a feature in some cases of Kearns-Sayre syndrome.

Adult↗