Biomedical subjects

H T Thaler

Publications and source records attributed to H T Thaler.

At least 73 records · Page 4Linked to original sources

PubMed1989

High-dose leucovorin reverses acute high-dose methotrexate neurotoxicity in the rat.

Intravenous high-dose methotrexate (HD-MTX) reduces cerebral glucose metabolism and produces behavioral abnormalities and electroencephalographic slowing in an animal model of acute HD-MTX neurotoxicity and in cancer patients undergoing HD-MTX chemotherapy. We used our model of HD-MTX neurotoxicity in the rat to determine if leucovorin (5-formyltetrahydrofolate) reduces this neurotoxicity, and extended our characterization of this model to identify regional as well as global HD-MTX treatment effects and to investigate HD-MTX-induced alterations in regional brain pH. Intravenous high-dose leucovorin reversed the HD-MTX-induced decrease in cerebral glucose metabolism and associated behavioral and electroencephalographic abnormalities in the rat, but low-dose leucovorin was ineffective. The major effect of HD-MTX on cerebral glucose metabolism was a global reduction; however, smaller region-specific treatment effects were identified in auditory, thalamic, and white matter structures. HD-MTX did not alter regional brain pH. These findings suggest a potential clinical role for high-dose leucovorin in severe or prolonged acute HD-MTX neurotoxicity and provide an important justification for the role of positron emission tomography in the early detection of clinical HD-MTX neurotoxicity.

Animals↗

PubMed1989

Immunophenotypic differences between normal glia, astrocytomas and malignant gliomas: correlations with karyotype, natural history and survival.

The karyotypic and antigenic phenotypes of early passage normal and malignant glial cultures were correlated in vitro. Astrocytomas (4) were distinguished from the normal glia (8) by a mixed near-diploid karyotype and anchorage-independent growth. Malignant gliomas (41) demonstrated cytogenetic abnormalities ranging from mixed normal G- and Q-banded and near-diploid cultures, through mixed near-diploid/hyperdiploid to predominantly hyperdiploid stem-lines. This correlated with the differential expression of certain antigens and established qualitative antigenic differences from normal glia. Associations were found between histopathologic grade of glial neoplasm and the expression of antigens 5.1H11 (p = 0.0002), CNT/11 (p = 0.001), CNT/10 (p = 0.004), CAT301 (p = 0.014), M111 (p = 0.024), and L101 (p = 0.044). An ominous association was demonstrated between the duration of clinical survival and the expression of antigens 5.1H11 (p = 0.0007), CNT/10 (p = 0.027) and B2.6 (p = 0.038). Correcting for diagnosis and age, multivariate analysis demonstrated that HLA-DR (p = 0.050) and 5.1H11 (p = 0.069) were unfavorably correlated with patient survival. This suggests the application of the in vitro immunophenotype for its predictive utility, as well as a novel method of selection of tumor-associated antigens for monoclonal antibody-mediated immunotherapy.

Adolescent↗

PubMed1989

Experimental meningeal carcinomatosis selectively depresses local cerebral glucose utilization in rat brain.

Using quantitative autoradiography, we investigated the effect of meningeal carcinomatosis on local cerebral glucose utilization (LCGU). A rat model of meningeal carcinomatosis using Walker 256 tumor was used. LCGU was evaluated using 14C-2-deoxy-D-glucose according to the Sokoloff method. Thirty-one neuroanatomic structures were evaluated, both separately and as part of five functional or neuroanatomic groups: olfactory, auditory, visual, limbic, and white matter. The relationship between tumor and LCGU of underlying brain was examined. Compared with controls, there was no global change of LCGU in the experimental group that applied to all structures. However, mean LCGU was significantly depressed in olfactory cortex, temporal cortex, olfactory tubercle, amygdala, caudate/putaman, inferior colliculus, medial geniculate, anterior commissure, and corpus callosum, and the functional groups that make up the olfactory and auditory systems. There was no correlation between extent of regional tumor burden and degree of depression of LCGU in underlying structures. In meningeal carcinomatosis, tumor results in selective regional depression of LCGU. This occurs both in structures underlying tumor and those anatomically remote, but in certain cases, functionally related to structures subadjacent to tumor. These data may help to explain the diversity of neurologic dysfunction seen in patients with meningeal cancer.

Analysis of Variance↗

PubMed1989

The role of postoperative radiotherapy after resection of single brain metastases.

To assess the value of whole brain radiotherapy (WBRT) after complete resection of a single brain metastasis we reviewed the records of 98 patients who had elective craniotomy between 1978 and 1985. Seventy-nine patients received postoperative WBRT (Group A) and 19 patients no radiotherapy (RT) (Group B). Neurological relapse was designated as local (i.e., at the site of the original metastasis) or distant (i.e., elsewhere in the brain). Postoperative WBRT significantly prolonged the time to any neurological relapse (P = 0.034) with a 1-year recurrence rate of 22% in Group A and 46% in Group B patients; however, it did not specifically control either local or distant cerebral recurrence. Recurrence of metastatic brain disease was not affected by location of the original lesion; however, meningeal relapse occurred in 38% of cerebellar lesions, but only in 4.7% of supratentorial metastases (P = 0.003). The total radiation dose or fractionation scheme of RT did not affect survival nor time to neurological relapse. The median survival was 20.6 and 14.4 months for Groups A and B, respectively (not statistically different). Forty-eight percent of Group A and 47% of Group B patients survived for 1 year or longer; however, 11% of patients who had received RT and survived 1 year developed severe radiation-induced dementia. All patients with radiation-related cerebral damage received hypo-fractionated RT with high daily fractions as commonly designed for rapid palliation of macroscopic brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

A dose-response study of dexamethasone in a model of spinal cord compression caused by epidural tumor.

In order to assess the clinical and biological effects of glucocorticoids in the therapy of epidural spinal cord compression, the T8-10 epidural space of 50 rats was implanted with Walker 256 tumor. The rats were studied 10 to 20 days later when they became paraparetic. The regional blood-spinal cord transport constant (K, a function of the blood-spinal cord barrier) of 14Carbon-labeled aminoisobutyric acid was measured with quantitative autoradiography 6 hours after intravenous injection of low-dose (0.1 mg/kg), intermediate dose (1 mg/kg), and high-dose (10 mg/kg) dexamethasone. The effects of dexamethasone in these doses on the clinical signs and water content of the compressed cord were also evaluated 40 hours after treatment began. The K factor increased 730% in compressed compared with noncompressed spinal cords (p less than 0.001). Dexamethasone induced a dose-related reduction of both K (p = 0.007) and water content of the compressed cord (p less than 0.0001). Stabilization or, more rarely, improvement of weakness at 24 and 40 hours posttreatment correlated with the dose of dexamethasone (r = 0.88, p less than 0.001). This study demonstrates that dexamethasone has a dose-related beneficial clinical effect associated with an improvement of blood-spinal cord barrier breakdown and a reduction of the water content of the compressed cord. This study supports the use of highdose dexamethasone for the initial treatment of epidural spinal cord compression.

Animals↗

PubMed1988

Distribution of brain metastases.

The number and site of brain metastases were identified on the computed tomographic scans of 288 patients. There was one brain metastasis in 49%, two in 21%, three in 13%, four in 6%, and five or more in 11% of scans. In patients with one metastasis, the posterior fossa was involved in 50% of patients when the primary tumor was pelvic (prostate or uterus) or gastrointestinal, but it was involved in only 10% of patients with other primary tumors. Hemispheral metastases preferred the anatomic "watershed areas" (29% of the brain surface contained 37% of the metastases), indicating that tumoral microemboli tend to lodge in the capillaries of the distal parts of the superficial arteries. The charts of 134 patients with brain metastases from a primary tumor originating outside the lung revealed that the incidence of lung and spine metastases was the same, whether the primary tumor was pelvic or gastrointestinal or from another site. These data suggest that the high incidence of subtentorial lesions in patients with pelvic and gastrointestinal primary tumors cannot be explained by arterial embolization alone, and that this peculiar distribution is probably not explained by seeding of the brain through Batson's plexus.

Brain Neoplasms↗

PubMed1988

Central nervous system metastases from non-Hodgkin's lymphoma: treatment and prophylaxis.

Central nervous system (CNS) lymphoma was identified in 96 patients treated for non-Hodgkin's lymphoma at Memorial Sloan-Kettering Cancer Center between 1975 and 1981. During the same period, 68 other patients with non-Hodgkin's lymphoma but no CNS disease received prophylactic CNS chemotherapy. In the 156 total patients, the lymphomas were diffuse in 96 percent, and 67 percent were stage IV at diagnosis. CNS involvement was present at initial diagnosis in 27 percent, at relapse in 26 percent, and during the course of progressive systemic disease in 47 percent. CNS involvement was asymptomatic in 10 percent. Cytologic study of the cerebrospinal fluid was the most sensitive and specific laboratory test, but often (22 percent) more than one lumbar puncture was required to identify malignant cells. CNS lymphoma was treated in 85 patients, 46 by intracerebroventricular cannulae; 81 percent improved. Although median survival after the diagnosis of CNS disease was four months, there were seven long-term disease-free survivors and the CNS disease contributed to death in only 14 percent. In 52 percent of treated patients, there was no CNS lymphoma at autopsy. CNS prophylaxis was with methotrexate or cytosine arabinoside, usually by lumbar puncture; an intraventricular cannula was used in seven patients. Although this group of high-risk patients with non-Hodgkin's lymphoma had a high systemic response rate and the median projected survival was greater than five years, CNS lymphoma developed in eight patients (12 percent). In five, CNS lymphoma occurred as an apparently isolated relapse site. The role of CNS chemoprophylaxis in high-risk patients with non-Hodgkin's lymphoma is still uncertain.

Adult↗

PubMed1988

A model of radiation myelopathy in the rat. Pathology, regional capillary permeability changes and treatment with dexamethasone.

In order to identify the effects of x-irradiation on spinal cord histology and capillary permeability, we irradiated the upper thoracic spinal cord of adult rats with 3500 cGy to a single lateral field. After 165 +/- 14 (SD) days the rats became paraplegic over 4 to 8 days. Quantitative autoradiography using 14C-amino-isobutyric acid demonstrated a biphasic curve of regional capillary permeability changes (K1). K1 first increased 70 to 85% in all regions of the cord at 30 days, then normalized at 60 days. From 60-151 +/- 8 days in asymptomatic animals there was an apparently exponential increase of K1 in all spinal cord regions progressing at varying rates among regions, most rapidly in the posterior columns and least rapidly in grey matter. K1 continued to rise when the animals became paraplegic. Morphologically, the asymptomatic period was characterized by myelin pallor and vacuolation evident at 30 days, maximal at 60 days, without progression until 151 +/- 8 days when microscopic foci of necrosis appeared in the posterior columns of some clinically normal ('preparetic') animals. The paretic period was characterized by extensive posterior and lateral column necrosis with preservation of grey matter. High dose dexamethasone or indomethacin had no preventative effect when administered just prior to irradiation. Dexamethasone transiently improved motor strength in symptomatic rats and reduced K1 in nonnecrotic portions of the cord. This study suggests that, after a transient peak of 'early delayed' changes in regional capillary permeability, there is progressive damage to the endothelium that may play a primary role in delayed radionecrosis.

Angiography↗

PubMed1988

The risk factors for arrhythmic death in a sample of men followed for 20 years.

In a sample of 301 men, aged 54-62 years, who were employed in the telephone industry in New Jersey, and who were followed prospectively from 1963/1964 to 1984, 65 of 148 deaths were manifested by the abrupt occurrence of fatal ventricular arrhythmias. On multivariate analysis, the factors present at the initial examination that were significantly related to the subsequent occurrence of arrhythmic deaths were: abnormal patterns of QRS conduction; the level of blood pressure; the number of cigarettes currently being smoked; chronic myocardial ischemia; chronic airway disease; and failure to engage in any exercise or heavy physical activity. Among 28 other potential risk factors representing myocardial disorders, ventricular dysrhythmias, other disorders of cardiac rate, rhythm, conduction, and repolarization, and non-cardiac risk factors (including cholesterol level, serum uric acid level, diabetes mellitus, alcohol intake, general arteriosclerosis, other non-cardiac disease, and social, behavioral, and attitudinal variables), none significantly added to risk for arrhythmic death. The risk factors related to the subsequent occurrence of other deaths, manifested by the gradual development of circulatory failure, were significantly different from the risk factors related to arrhythmic deaths.

Aged↗

PubMed1988

Neuropsychological characterization of the AIDS dementia complex: a preliminary report.

The AIDS dementia complex (ADC) is a frequent complication of advanced HIV infection. In order to better define the neuropsychological character and progression of the ADC, four groups of subjects were studied with a battery of neuropsychological tests: an HIV-seronegative comparison group (n = 20), asymptomatic HIV-seropositive patients (n = 16), newly diagnosed AIDS patients (n = 44) and AIDS patients who were referred for neurological consultation (n = 40). Results showed significant reductions in performance in the two AIDS groups, with impairment being most prominent in tests that assessed motor speed and fine control, concentration, problem solving and visuospatial performance. This pattern of neuropsychological dysfunction is consistent with the characterization of the ADC as a subcortical dementia.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Perforation of the gastrointestinal tract in patients receiving steroids for neurologic disease.

Between 1980 and 1984, of 107 patients receiving 16 mg/d of dexamethasone for spinal cord compression, three (2.8%) developed gastrointestinal (GI) perforation and two (1.9%) GI bleeding; of 226 being tapered from 100 mg/d of dexamethasone, perforation occurred in six (2.7%) and GI bleeding in eight (3.5%). Of 125 patients with GI perforations treated between 1979 and 1986, 41 (33%) were on steroids, 24 for neurologic disease. Median duration of steroid therapy was 24 days; 20 (91%) of the neurologic patients perforated within 30 days. The steroid group had more free peritoneal involvement (p less than 0.00001), but fewer signs and symptoms of peritonitis (p less than 0.000001) than the nonsteroid group. Seventeen patients were receiving steroids for cord compression; they had significantly more rectosigmoid perforations (p less than 0.014) and associated constipation (p less than 0.000001) than the 108 remaining patients. GI perforation is a less well-recognized complication of steroid therapy in neurologic patients than is GI bleeding though it occurs as frequently, is more difficult to diagnose, and far more serious. In steroid-treated patients, prevention of constipation might avert this serious complication, while early diagnosis will improve the outcome.

Adolescent↗

PubMed1988

MRI demonstrates descending transtentorial herniation.

Descending cerebral transtentorial herniation (DTH) is a serious and often fatal complication of intracranial mass lesions. The condition can be inferred from clinical neurologic signs, but has not been visualized during life. Using midsagittal magnetic resonance images (MRIs), we compared vertical brainstem position on 50 images from normals and 21 images from 15 clinically stable patients with large supratentorial tumors. The length of Twining's line (T), the perpendicular distance from T to the pontomesencephalic junction (T-PMJ), and from T to the apex of the midbrain aqueduct (T-A) were measured. We also measured lateral shifts of the diencephalon and midbrain on axial images. T-PMJ decreased from 2.04 +/- 0.06 mm in normals to 0.94 +/- 0.2 mm in patients with large cerebral tumors (p less than 0.0001). Similarly, T-A decreased from 6.35 +/- 0.13 mm in normals to 4.83 +/- 0.35 mm in patients (p = 0.001). Lateral diencephalic-midbrain shifts often accompanied DTH but to an unpredictable degree. Either lateral or downward brainstem shift could occur alone and did not necessarily produce specific neurologic signs or an altered state of consciousness. Anatomic DTH occurs in life, it can be quantified with MRI, and in slowly developing cerebral mass lesions the process can precede the appearance of neurologic signs and symptoms that indicate lower-diencephalic or midbrain dysfunction.

Brain Diseases↗

PubMed1988

High dose versus low dose dexamethasone in experimental epidural spinal cord compression.

A compound of methylcellulose-silicone expanding progressively over a 1-week period by moisture absorption was implanted in the midthoracic epidural space of 17 Sprague Dawley adult rats. When the animals became paraplegic 6.3 +/- 1.6 days later, they were randomized into three groups: untreated control (n = 5), high dose dexamethasone (HD, 1.25 mg/kg intramuscularly, twice daily, n = 5), and low dose dexamethasone (LD, 0.125 mg/kg intramuscularly, twice daily, n = 7). Motor strength was evaluated daily by an observer unaware of the treatment given to the rats. Animals treated with dexamethasone (HD or LD) improved faster than untreated control animals. No significant difference in the rate of recovery or degree of motor improvement was noted between the HD and LD groups. Mortality was higher in the HD group because of infections and gastrointestinal perforation/bleeding.

Animals↗

PubMed1986

Acute high-dose methotrexate neurotoxicity in the rat.

Intravenous high-dose methotrexate chemotherapy may produce acute, subacute, or chronic neurotoxicity in patients with cancer. Acute encephalopathies following high-dose methotrexate treatment are recognized with increasing frequency. This study describes a model of acute high-dose methotrexate neurotoxicity in the rat characterized by a profound dose-dependent depression of cerebral glucose metabolism in association with behavioral and electroencephalographic abnormalities. Alterations in the amino acid profile, similar to those described in cancer patients after high-dose methotrexate treatment, were observed in the absence of biochemical evidence of systemic organ toxicity. This model facilitates the study of the biochemical mechanisms of antifolate neurotoxicity in humans and permits the evaluation of potential therapeutic interventions.

Amino Acids↗

PubMed1986

Evaluation of malignant lymphomas using three classifications and the working formulation. 482 cases with median follow-up of 11.9 years.

Three classifications and the Working Formulation for non-Hodgkin's lymphomas have been studied in 482 patients with a median follow-up of 11.9 years. Each classification was evaluated independently, and their similar and discrepant aspects were analyzed by comparing subgroups in the different schemes. Clinical staging was essential in the evaluation of some categories. There are several differences between the classifications that are not readily reconcilable. The Rappaport classification's principal groups are heterogeneous. Separation of follicular lymphomas into small and large cleaved cell types (Lukes-Collins) is significant. The addition of a follicular mixed cell type (Rappaport, Working Formulation) detracts from this significance. Centrocytic and lymphoplasmacytic tumors (Kiel) are well-defined categories and important in understanding some deficiencies in the other classifications. The small cleaved cell type, diffuse (Lukes-Collins, Working Formulation) is heterogeneous. Diffuse lymphomas of mixed cell types are poorly defined subgroups. Excluding lymphoblastic types, the presence of plasmacytic differentiation is important in identifying the high-grade lymphomas with the poorest prognosis. These results suggest that adjustments should be made in the classifications and in the Working Formulation.

Adolescent↗

PubMed1986

Comparative analysis of surface membrane immunoglobulin determination by flow cytometry and fluorescence microscopy.

The analysis of membrane surface immunoglobulin (SmIg) on B lymphocytes was carried out in 59 normal individuals and nine patients with B-cell non-Hodgkin's lymphomas by conventional immunofluorescence microscopy and flow cytometry. Five channel settings of a cytofluorograph were evaluated (100, 150, 200, 250, 300) and the mean and standard deviation of the percent positive cells were calculated and compared to the mean and standard deviation of the microscope reading. On the basis of the relative fluorescence reactivity, we were able to determine a fluorescence intensity at which the results of flow cytometry and fluorescence microscopy were comparable. In normal individuals, for cells expressing surface Ia, the channel giving similar results to that of fluorescence microscopy was 150; for kappa and lambda chains, channel 200; for Fab'PV, channel 200; and for IgM, channel 250. In patients with B-cell non-Hodgkin's lymphomas, for cells expressing surface Ia the channel giving similar results to that of fluorescence microscopy was 100; for kappa, channel 100; for lambda, channel 200; for Fab'FV, channel 150; and for IgM, channel 150. Flow cytometric analysis of SmIg appears to be superior to fluorescence microscopy in efficiency, and has the added advantages of being a rapid, sensitive, and objectively quantitative methodology.

B-Lymphocytes↗

PubMed1986

Single brain metastases: surgery plus radiation or radiation alone.

We reviewed the records of patients treated for single brain metastases from non-small-cell lung cancer for 1978 through 1982. Forty-three patients received surgical treatment, including 37 who had surgery plus postoperative whole-brain radiation therapy and 6 patients who had surgery after failing to respond to radiation therapy. The surgically treated patients were matched with 43 patients treated with radiation therapy alone. The combined therapy group had significantly longer survivals than those treated with radiation therapy alone (19 months versus 9 months). The rates of local recurrence and neurologically related deaths were significantly higher in the radiation therapy-alone group. Patients treated with combined therapy survived longer, and the increased survival was due to lower recurrence of brain metastases after surgery and fewer neurologically related deaths.

Adenocarcinoma↗

PubMed1985

Effects of xenon and krypton on regional cerebral blood flow in the rat.

The effects of high inspired concentrations of xenon and krypton on regional CBF (rCBF) were assessed in the rat using [14C]iodoantipyrine and quantitative autoradiography. Inhalation of 80% xenon for 1 or 2 min and inhalation of 40% xenon for 2 min were found to have significant effects on rCBF, including average increases of 75-96% in cerebral neocortical regions. Inhalation of 40% xenon for 1 min and of 80% krypton for 2 min had no significant effect on rCBF in most brain regions studied. If xenon inhalation produces effects on rCBF in humans similar to those observed in the rat, such effects could be an important source of error in xenon computed tomography rCBF studies.

Animals↗