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Biomedical subjects

F S Vogel

Publications and source records attributed to F S Vogel.

At least 19 recordsLinked to original sources
PubMed1994

Superiority of PCNU over AZQ in the treatment of primary brain tumors: results of a prospective randomized trial (81-20) by the Brain Tumor Study Group.

PURPOSE: A two-arm randomized clinical trial was performed to determine the efficacy of PCNU and AZQ in the treatment of de novo or recurrent primary brain tumors. An additional objective was to gather information on the administration and toxicity of these compounds, supplementing that obtained previously in phase I/II studies. METHODS: During 1982 and 1983 the Brain Tumor Study Group randomized 152 adult patients with primary brain tumors to receive PCNU 75-100 mg/m2 intravenously (IV) every 8 weeks or AZQ 15 mg/m2 IV once a week for 4 weeks, every 6-8 weeks. All patients who had not received 'full dose' radiotherapy before randomization received it concurrently with the first course of protocol chemotherapy. The data were analyzed for the total randomized population (RP), and for 130 patients in the valid study group (VSG) formed by excluding 22 patients for whom the histologic diagnosis was not documented by central review. RESULTS: Median survival times were 11.0 months for the PCNU group and 8.4 months for the AZQ group. The difference in survival curves was statistically significant for the RP (p = 0.01) and the VSG (p = 0.02). Life-table analysis of the VSG showed estimated 2-year survivals of 34% for PCNU and 11% for AZQ. The advantage of PCNU remained significant (p = 0.006) after adjustment for histopathologic category, age, initial performance status, and interval from initial reported surgery. Myelosuppression was the principal toxicity in both groups.

Antineoplastic Agents↗
PubMed1993

Phase II evaluation of echinomycin (NSC-526417) in patients with central nervous system malignancies. A Southwest Oncology Group study.

The objective of this trial was to determine the efficacy of echinomycin (1.2 mg/m2) administered on a weekly times four schedule in the treatment of patients with recurrent or progressive central nervous malignancies despite adequate radiotherapy. Thirty-five patients were registered on study. The majority of patients (20) had glioblastoma multiforme. Ten had anaplastic astrocytoma. Eight patients had received prior nitrosoureas. SWOG performance status was 1 in 11 patients and 2 in 22. The median age was 51 years (25-75 years). One patient had a partial remission (3%:95% confidence interval: 1%-16%). Twenty two patients had progressive disease. The median survival was 5.9 months. Toxicity was primarily gastrointestinal with nausea and vomiting in 13 patients and nausea only in 11 patients. Hepatotoxicity occurred in 10 patients. Echinomycin given at this dose and schedule is not effective in treating patients with recurrent or progressive glioblastoma multiforme or anaplastic astrocytomas.

Adult↗
PubMed1991

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease.

The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects. The protocol provides neuropathologic definitions of such terms as "definite Alzheimer's disease" (AD), "probable AD," "possible AD," and "normal brain" to indicate levels of diagnostic certainty, reduce subjective interpretation, and assure common language. To pretest the protocol, neuropathologists from 15 participating centers entered information on autopsy brains from 142 demented patients clinically diagnosed as probable AD and on eight nondemented patients. Eighty-four percent of the dementia cases fulfilled CERAD neuropathologic criteria for definite AD. As increasingly large numbers of prospectively studied dementia and control subjects are autopsied, the CERAD neuropathology protocol will help to refine diagnostic criteria, assess overlapping pathology, and lead to a better understanding of early subclinical changes of AD and normal aging.

Aged↗
PubMed1989

Ataxia, chorea, seizures, and dementia. Pathologic features of a newly defined familial disorder.

Five generations of a family exhibit a unique autosomal dominant neurologic disorder characterized by the development (usually between 15 and 30 years of age) of ataxia, seizures, choreiform movements, progressive dementia, and death after 15 to 25 years of illness. Neuropathologic findings in two deceased family members revealed remarkably similar findings, including marked neuronal loss of the dentate nucleus, microcalcification of the globus pallidus, neuroaxonal dystrophy of the nucleus gracilis, and demyelination of the centrum semiovale. The clinical and pathologic findings are closely correlated. Ataxia and chorea are related to severe neuronal loss in the dentate nucleus with calcification in the globus pallidus. Dementia occurs with progressive demyelination of the centrum semiovale, and loss of posterior column function occurs with neuroaxonal dystrophy of the nucleus gracilis and nucleus cuneatus.

Adolescent↗
PubMed1988

Increasing incidence of primary brain lymphoma in the US.

There have been a number of clinical reports suggesting an increasing incidence of primary brain lymphoma unrelated to acquired immune deficiency syndrome (AIDS) and organ transplantation. To investigate this issue, the US incidence of this rare lymphoma was assessed using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program (1973 through 1984). Never-married men, a relatively high risk group for AIDS, were excluded from the analyses. Brain lymphoma incidence increased from 2.7 in 1973 through 1975 to 7.5 cases per ten million population in 1982 through 1984 (chi-square trend, 15.25; P less than 0.001), and it increased among both men (chi-square trend, 6.74; P = 0.009) and women (chi-square trend, 10.48; P = 0.001). Increases in incidence also were observed among persons younger than 60 years of age (chi-square trend, 4.10; P = 0.04) and persons 60 years of age and older (chi-square trend, 9.16; P = 0.002). This increased incidence of brain lymphoma appears to be real: It antedates the AIDS epidemic and does not appear to be related to organ transplantation, another cause of increased risk of brain lymphoma. Although part of the increase may be an artifact of improvements in diagnostic technology and practice, most of the observed increase antedates the widespread use of such technologies. Finally, the increase in incidence of brain lymphoma does not appear to be related to overall trends in the incidence of brain tumors and non-Hodgkin's lymphoma, and it is not related to time trends in nosology.

Age Factors↗
PubMed1988

"Chordoid" meningeal tumors in young individuals with peritumoral lymphoplasmacellular infiltrates causing systemic manifestations of the Castleman syndrome. A report of seven cases.

Seven young patients ranging in age from 8 to 19 years had surgically removed meningeal neoplasms with a peculiar myxoid-chordoid pattern. The tumors were surrounded by massive polyclonal lymphoplasmacellular infiltrates with follicles and germinal centers. The patients preoperatively manifested iron-resistant hypochromic microcytic anemia, and one of them had dysgammaglobulinemia and stunted growth. After the masses were removed, the blood picture of the patients normalized, and the adolescent with retarded somatic development resumed normal growth, but two patients developed local recurrence with identical histology and again became anemic. It appears that the peritumoral lymphoplasmacellular infiltrates, which in these instances may be regarded as reactive rather than primary cell proliferations, nevertheless brought about the type of systemic manifestations known as the Castleman syndrome, characteristically seen in patients with angiofollicular lymphoid hyperplasia (hamartoma) of soft tissues, or Castleman's tumor. In one of our patients the inflammatory infiltrate extended far into the surroundings of the meningioma, resulting in the erroneous initial diagnosis of "encephalitis" from a needle biopsy of the brain near the tumor.

Adolescent↗
PubMed1986

Randomized comparisons of radiotherapy and carmustine versus procarbazine versus dacarbazine for the treatment of malignant gliomas following surgery: a Southwest Oncology Group Study.

Between 1977 and 1981, the Southwest Oncology Group entered 278 patients on a randomized study (SWOG 7703) to compare the effect of three different chemotherapeutic agents given in combination with radiotherapy (6000 rads over 7 weeks) following surgery for malignant gliomas. The chemotherapy regimens were: carmustine (BCNU)--80 mg/m2 iv daily X 3 every 6 weeks; procarbazine (PCB)--100 mg/m2 orally; or dacarbazine (DTIC)--175 mg/m2 iv daily X 5 every 4 weeks. Patients were stratified according to age, and degree of resection, with no differences identified between groups. The response rates (complete plus partial) for BCNU and DTIC were significantly better than for PCB [BCNU, 39%; PCB, 13%; and DTIC, 38% (P less than 0.01)]. The response duration and survival were somewhat better in patients treated with BCNU and DTIC, but compared to patients treated with PCB, the difference was not statistically significant. Median survival times were: BCNU, 45 weeks; PCB, 31 weeks; and DTIC, 49 weeks (P greater than 0.3). There were six toxic deaths with BCNU and four with PCB, most of which were due to infection associated with leukopenia. The high toxicity and minimal benefit of chemotherapy added to radiotherapy compared to historical results with radiotherapy alone suggest that combined treatment may not be indicated for some patients.

Brain Neoplasms↗
PubMed1985

Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications.

A total of 1440 malignant astrocytic gliomas from three Phase III trials of the National Brain Tumor Study Group were studied to document the clinical usefulness of subclassifying these lesions as either an anaplastic astrocytoma or a glioblastoma multiforme. As defined by a previous "blind" pathology review, the two groups of patients were compared as to mean age, mean duration of preoperative symptoms, and postrandomization survival. In addition, 10 histologic variables were studied in 150 patients with the anaplastic astrocytoma to establish internal correlations, and to relate specific histologic variables to patient age and postrandomization survival. There were highly significant differences in the age, duration of preoperative symptoms, and post randomization survival between the two groups. Internal correlations between histologic variables in the anaplastic astrocytoma disclosed statistically significant associations between the presence of lymphocytes and gemistocytic astrocytes. It is concluded that the subclassification of malignant gliomas into the anaplastic astrocytoma and the glioblastoma multiforme defines groups of patients that are significantly different in regard to age, duration of symptoms, and length of survival. The problems of tissue sampling are recognized, however, the assignment, by a blind pathology review, to two such different groups indicates that the classification has utility for large randomized clinical trials. The analysis of histologic variables in the anaplastic astrocytomas confirms previous suggestions that lymphocytes and gemistocytes frequently coexist in malignant gliomas, but in this study these inflammatory cells did not appear to influence survival. The study reemphasizes the association between advancing age and shorter survivals in patients with malignant gliomas.

Actuarial Analysis↗
PubMed1981

The correlation of histologic changes in the human breast with the menstrual cycle.

Histologic changes in the normal human mammary gland associated with the menstrual cycle were sought in tissues derived from a defined population of patients undergoing subcutaneous mastectomy or reduction mammoplasty for reasons other than neoplasia. Ninety patients were selected for their regular menstrual cycling, abstinence from hormone use, and absence of disease which might influence pituitary-ovarian cycling. Morphologic changes in the mammary stromal and epithelial components were identified as they related to specific pituitary-ovarian events, and histologic criteria were identified that allowed reproducible morphologic categorization of the mammary gland into five specific phases: proliferative (Days 3-7); follicular phase of differentiation (Days 8-14); luteal phase of differentiation (Days 15-20); secretory (Days 21-27); and menstrual (Days 28-2). Double-blind reviews of tissues confirmed the validity and the reproducibility of these histologic criteria in identifying the menstrual phase. The findings further characterize the morphologic correlates of hormone responsiveness of the normal human mammary gland. The recognition of menstrual-cycle-dependent histologic changes may be expected to provide a basis for extending the interpretation of the morphologic characteristics of the breast in surgically acquired specimens that may be associated with hormonal aberrations.

Adolescent↗
PubMed1981

The melanocytotoxicity of gamma-L-glutaminyl-4-hydroxybenzene: a study of the pigmented cells in the mouse eye.

The administration of gamma-L-glutaminyl-4-hydroxybenzene (GHB) to neonatal black mice resulted in selective necrosis of the melanocytes in the choroid but had no apparent effect on the retinal pigment epithelium and pigmented cells of the iris and ciliary body. No changes were noted in any of the ocular melanocytes when GHB was administered to adult black mice or neonatal albino mice. The administration of p-aminophenol, which may be a metabolite of GHB in mammalian cells, produced identical cytologic changes in the eyes of neonatal black mice. The findings indicate that in the presence of an active melanogenic environment, the metabolism of GHB generates products that are promptly cytolytic. In the immature retina of both black and albino mice, the administration of GHB also resulted in scattered necrosis in the inner layer of the developing neuroblastic cells in the form of cellular condensation. This effect, which is independent of the process of melanogenesis, could not be elicited beyond the fifth postnatal day and may represent a quantitative exaggeration of a normal cellular phenomenon.

Age Factors↗
PubMed1980

Subacute diencephalic angioencephalopathy--report of an additional case.

The following report presents an additional example of subactue diencephalic angioencephalopathy. The patient, a 68-year-old man, unexplicably withdrawn and asocial throughout his life, presented with an altered mental status of relatively recent onset. His illness was marked by progressive dementia and ended in death within 7 weeks. The neuropathologic findings were essentially identical to those described in the previous case in both their histology and topographic localization within the thalamus. The etiology, pathogenesis, and reason for the localization of this entity are unknown. Nevertheless, the lesion underscores the major role of the thalamus in cognitive function, emotional behavior, and awareness.

Aged↗
PubMed1980

The role of gamma-glutamyl transpeptidase in the nephrotoxicity of an Agaricus bisporus metabolite.

The mushroom metabolite gamma-L-glutaminyl-3,4-dihydroxybenzene (GDHB) was found to have an LD50 of 100 to 200 mg/kg in neonatal C57Bl/6J mice. Adult mice given 200 mg/kg GDHB showed histopathologic evidence of proximal convoluted tubular injury as early as 2 hours after injection, which progressed by 24 hours to profound acute tubular necrosis. Focal acinar epithelial cell necrosis in the pancreas was also observed. The time course and location of the injury suggested that appearance of the ultimate toxic metabolite could be due to cleavage of GDHB by gamma-glutamyl transpeptidase (GGTP). The reaction in vitro of GDHB with crude porcine GGTP resulted in the release of 4-amino-catechol which air oxidized to 2-hydroxy--4-iminoquinone (HIQ), a known sulfhydryl reagent and cytotoxic compound. Synthesis of N2-methyl-gamma-glutaminyl-3,4-dihydroxybenzene (MeGDHB) provided a compound whose oxidized derivatives, when compared with those of GDHB, had similar half-wave potentials and visible absorption maxima. MeGDHB was resistant to cleavage by GGTP and was without apparent toxicitiy at 2-3 times the LD50 of GDHB. Therefore, cleavage by GGTP, an enzymatic transformation accessible to GDHB but unavailable to MeGDHB, is proposed as the mechanism of activation of the mushroom metabolite. The following pathogenic sequence is indicated: 1) release of 4-aminocatechol from GDHB by the action of GGTP and 2) irreversible injury resulting both from the generation of free radicals by the autoxidation of 4-aminocatechol and from the reaction of HIQ with cellular nucleophils, particularly sulfhydryl groups.

Agaricales↗