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Biomedical subjects

M Salcman

Publications and source records attributed to M Salcman.

At least 91 records · Page 5Linked to original sources
PubMed1983

Brain tumors in elderly patients.

Mental slowing, forgetfulness and personality change are frequent accompaniments of aging; such symptoms are also the first warning signals of an intracranial tumor. Cerebral metastases, malignant astrocytomas and benign meningiomas are the most common types of brain tumor in patients over 65 years of age. The symptoms and signs of a brain tumor depend primarily on its location and on intracranial pressure. In addition to producing dementia and seizures, tumors occasionally present in an apoplectic fashion and mimic the onset of stroke.

Aged↗
PubMed1982

Morphologic effect of dimethyl sulfoxide on the blood-brain barrier.

Dimethyl sulfoxide (DMSO) opens the blood-brain barrier of mice to the enzymatic tracer horseradish peroxidase. A single injection of horseradish peroxidase in 10 to 15 percent DMSO into the tail vein along with 10 to 15 percent DMSO delivered intraperitoneally allowed horseradish peroxidase to fill the extracellular clefts throughout the brain within 2 hours. In the absence of DMSO, peroxidase failed to enter brain parenchyma except through the circumventricular organs. Opening of the blood-brain barrier by DMSO is reversible. Dimethyl sulfoxide stimulated the pinocytosis of horseradish peroxidase by the cerebral endothelium; the peroxidase was then directed to lysosomal dense bodies for degradation. Vesicular transport of horseradish peroxidase from the luminal to the abluminal wall of the endothelial cell was not observed. Dimethyl sulfoxide did not alter the morphology of endothelial cells or brain parenchyma.

Animals↗
PubMed1982

Epidermoid tumor of the fourth ventricle: use of metrizamide-computed tomography.

This report describes two cases of epidermoid tumor of the fourth ventricle diagnosed with metrizamide computed tomography. They both presented as a low-density lesion in the region of the fourth ventricle on computed tomography. They did not show any enhancement after intravenous injection of contrast medium and had no hydrocephalus. Metrizamide-enhanced computed tomography demonstrated the irregular fourth-ventricular filling defect characteristic of epidermoid tumors.

Adult↗
PubMed1982

Cyclophosphamide plasma and cerebrospinal fluid kinetics with and without dimethyl sulfoxide.

Ten patients with brain tumors and indwelling ventricular reservoirs were pretreated with 5% to 10% dimethyl sulfoxide (DMSO) (intravenous, oral, or both) and were then treated with 1.0 to 1.25 gm/m2 cyclophosphamide (CYC). All patients were also on anticonvulsants and dexamethasone. CYC and alkylating activity (alk act) in plasma and concomitant ventricular cerebrospinal fluid (CSF) were measured by gas chromatography and p-nitrobenzyl pyridine assay. CYC entered the CSF without difficulty and was lost from CSF more slowly than from plasma. Alk act did not enter CSF as well as did CYC. DMSO did not alter any measured aspect of CYC or alk act disposition. Specifically, it did not alter the CYC plasma half-life (t1/2), CSF t1/2, peak CSF: peak plasma CYC concentration ratio, or the urinary excretion of CYC. DMSO did not alter the plasma t1/2 or urinary excretion of alk act or the peak CSF:peak plasma concentration ratio of alk act. Our data show reduced plasma t1/2 of CYC and increased plasma and urinary alk act. This may reflect tht effect of long-term therapy with anticonvulsants or steroids.

Adult↗
PubMed1982

Brain tumors and the geriatric patient.

The prognosis, site of occurrence, and histologic type of primary brain tumors are age-dependent phenomena. In general, the incidence of meningiomas, acoustic Schwannomas, and glioblastomas increases with advancing age until the end of the eighth decade. Of 99 patients consecutively admitted to an aggressive multimodality treatment program for glioblastoma multiforme, 18 per cent were in the 61-70 age group and 4 per cent in the 71-80 group; the oldest was 85. The operative mortality was only 4 per cent. In 16 patients over 65, the 6- and 12-month calculated survival probabilities were 0.65 and 0.31, respectively. The Kaplan-Meier survival curve for these patients was significantly different from that for 26 patients under the age of 40. Grade 4 astrocytomas were present in 62 per cent of patients under 40 but in 83 per cent of patients over 61. In all glioblastoma populations, age is the most significant prognostic variable. The incidence of metastic brain tumors also increases with age, and all of the usual primary sites are represented. The prognosis for elderly patients with metastatic brain tumor is uniformly worse than that for younger patients, even though modern diagnostic and operative techniques carry virtually the same morbidity and mortality rates in older patients as in younger ones. It is vitally important, therefore, that the clinical effects of treatable intracranial tumors in the elderly are not ascribed to dementia, the aging process, the systemic effects of cancer, or the side effects of cancer therapy, without suitable diagnostic investigation.

Aged↗
PubMed1982

Effect of age and reoperation on survival in the combined modality treatment of malignant astrocytoma.

Before the advent of the operating microscope and the carbon dioxide laser, reoperations were performed in less than 5% of patients with malignant astrocytoma. Between 1978 and 1981, a consecutive series of 74 adult patients were prospectively treated therapy, all patients eligible for further treatment were offered reoperation with the microscope and/or laser before treatment with Phase I agents (microwave hyperthermia, dimethyl sulfoxide (DMSO)-Adriamycin, DMSO-Cytoxan, or azaridinylbenzoquinone (AZQ)). Forty-six per cent of the patients were referred from outside institutions for intensive treatment. In 36 months, 40 patients received second operations directed at their tumor and had a median calculated survival from the time of reoperation of 37 weeks. The length of survival after the second operation was independent of patient age, performance status, tumor grade, and interoperative interval. Sixty-five per cent of patients under 40 and 48% of patients over 40 underwent reoperation with minimal morbidity and no deaths. The single most important prognostic factor for survival in both reoperated and single-operated patients was age. Tumor grade had no influence on survival in the series as a whole, in patients under 40 years of age, or in reoperated patients. The calculated median survival for the entire series was 15 months, with a predicted 2-year survival rate of 0.25. These figures include all patients treated without exclusion for incomplete radiotherapy or chemotherapy. It is concluded that reoperation for malignant astrocytoma is safe, feasible, and of potential benefit in combination with other therapies. The routine use of reoperation to "set up" other treatment modalities deserves further study.

Adolescent↗
PubMed1982

Transplantable canine glioma model for use in experimental neuro-oncology.

The need for a large animal tumor model in experimental neuro-oncology led us to re-evaluate and to modify the transplantable canine glioma of Wodinsky and Walker. Successive passages of the original tumor brei were made in purebred beagles, from beagle to mongrel, and between various mongrel strains until an intracerebral injection of 0.1 cc on Days 1 to 3 of life produced a 93% incidence of tumor take in all breeds. The mean survival was 13.5 +/- 1.9 days after injection (range, 10 to 19 days) in 10 litters. The tumor was invariably fatal and possessed many of the histological characteristics of human glioblastoma (i.e., capillary proliferation, pseudopallisading, frequent mitotic figures, and multinucleated giant cells). The animals were large enough to be scanned on the Pfizer 450 scanner, and the tumors were visualized in vivo as typical "ring" lesions after the injection of contrast agent. Intravital staining with Evans blue outlined the areas of contrast enhancement observed in the same tumors by computed tomography. The apparent defect in the blood-brain barrier could be explained in part by the absence of endothelial tight junctions on electron microscopy. Stability in the histology and activity of the tumor could be demonstrated after more than 14 months of storage at -70 degrees C. The transplantable canine glioma model has many advantages including low cost, reproducible morphology, a short survival time, and relative safety for the investigator. The large size of the animal preparation allows the use of complex surgical instrumentation and radiographic study, as well as repeated sampling of cerebrospinal and other fluids.

Animals↗
PubMed1982

Aggressive multimodality therapy based on a multicompartmental model of glioblastoma.

Glioblastoma multiforme is composed of multiple cellular compartments with different morphologic, kinetic, metabolic, vascular, and genetic properties. Optimal therapy may consist of a variety of therapeutic strategies designed for individual compartments, administered in close temporal relation. These concepts may turn out to be valid for other solid tumors as well. Microwave-induced hyperthermia can be used to treat metabolically quiescent, relatively hypoxic, nondividing cells (Go) otherwise resistant to radiation and chemotherapy. Similarly, polychemotherapy can treat a broad spectrum of cell types if the blood-brain barrier can be circumvented. Radical surgery, repetitively applied, can be safely used to "set up" experimental agents if the operation microscope and laser are employed. A consecutive series of 74 adult patients with malignant astrocytoma were treated with primary resection, radiation therapy, and 1,3,-bis(2 chloroethyl) 1 nitrosourea chemotherapy. At recurrence, all patients were offered reoperation with the microscope and the laser prior to administration of phase-I agents--hyperthermia via an implantable miniature microwave antenna (6 cases); aziridinylbenzoquinone chemotherapy (13 cases); and blood-brain barrier reversal with dimethyl sulfoxide (DMSO) and polychemotherapy (9 cases). It was concluded that temperatures of 45 degrees C could be safely achieved and human tumors could not efficiently dissipate heat; that DMSO plus drug therapy could be tolerated but blood-brain barrier reversal demonstrated by us in animals could not be shown in humans; and that aggressive multimodality therapy and reoperation could produce a 40% 2-year survival rate for patients younger than 40 years.

Brain Neoplasms↗
PubMed1981

Neurosarcoidosis: a review of the rarer manifestations.

Neurosarcoidosis characteristically presents with the onset of cranial nerve palsies or endocrine and electrolyte disturbances in a patient with known systemic sarcoid. However, the disease may occasionally manifest itself in patients with no evidence of somatic involvement and with a variety of neurological signs and symptoms. We present two cases that demonstrate several of the rare manifestations of the illness and review the literature on the diagnosis and treatment.

Adult↗
PubMed1981

Expanding the definition of the blood-brain barrier to protein.

Tight junctions between cerebral endothelial cells and the near absence of pinocytosis and vesicular transport of blood-borne protein into and across these cells are believed to constitute the mammalian blood-brain barrier. In the present investigation evidence is provided to indicate that the capillary endothelium of the mouse brain pinocytosis the enzymatic tracer horseradish peroxidase (EC 1.11.1.17) from cerebral blood under normal conditions. This protein and the internalized endothelial surface membrane associated with it are directed, for the most part, to acid hydrolase-positive lysosomes for degradation. Although peroxidase was never seen in the perivascular clefts, the lysosomes of pericytes were peroxidase-positive. Pericytes are macrophage-like cells located on the abluminal surfaces of cerebral microvasculature; these cells may serve as the first line of defense once the blood-brain barrier is breached. The definition of the blood-brain barrier should be expanded to include consideration of the lysosomal system of organelles in endothelial cells and pericytes.

Acid Phosphatase↗
PubMed1981

Clinical hyperthermia trials: design principles and practice.

The initial development of a significant risk device is predicated upon demonstrable medical need and an adequate biophysical rationale. Although microwave and radiofrequency thermotherapy systems strongly meet these requirements, their clinical evaluation has often suffered from inadequate or inappropriate preclinical laboratory experimentation. It is suggested that devices be tested in animals rather than phantoms and that thermal profiles, cooling curves, power vs. temperature studies et al be carried out in the organ or organs of interest. Clinical trials can then be designed in which an attempt is made to replicate laboratory measurements in humans in order to develop physical dose-response relationships and toxicity data (i.e. a phase-I or feasibility study). The experimental paradigm for clinical drug testing can also be applied, with some modifications, to the further evaluation of devices for the determination of therapeutic response rates (phase-II) and for controlled evaluation against available treatments in a homogeneous patient population (phase-III). It is extremely important that early clinical trials not be contaminated by the possible effects of other concurrent therapies and that sophisticated statistical design be employed to protect human subjects from unnecessary exposure to experimental treatments. The ethical issues involved are best dealt with by good scientific design.

Clinical Trials as Topic↗
PubMed1981

Value of sequential computed tomography in the multimodality treatment of glioblastoma multiforme.

Previous assessments of the value of sequential computed tomographic (CT) scanning in brain tumor patients have suffered from the heterogeneous nature of the study populations in regard to (a) pathology, (b) treatment plan, and (c) time of scanning. This report is based on the first 21 of 30 consecutive cases of glioblastoma multiforme entered into a cumulative high dose chemotherapy study. Each patient received a maximal surgical resection, 5800 to 6300 rads of radiation therapy, and BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) chemotherapy (beginning at 100 mg/m2/day X 3 days) every 8 to 10 weeks for the life of the patient. CT scans were obtained pre- and postoperatively at each admission for chemotherapy; the scan at the time of the first BCNU course served as the postradiotherapy scan. Edema was present on 94% of the initial scans, and 94% of the tumors demonstrated contrast enhancement. In 70 instances it was possible to compare clinical status and an enhanced scan at the time of adjuvant treatment. When the scan was improved or unchanged so was the patient (46 of 46), but worsening of the scan was accompanied by worsening of the patient only 62% of the time (15 of 24). Sequential CT scanning proved useful in (a) detecting the positive effect of a treatment plan in clinically stable patients; (b) detecting non-tumor related causes of clinical deterioration; (c) detecting early treatment failure as a prelude to reoperation and/or a change in drug protocol before clinical deterioration; and (d) detecting asymptomatic complications of the treatment plan (i.e., a 20% incidence of ventricular enlargement).

Adolescent↗
PubMed1981

Calculated recovery rates in severe head trauma.

In a series of 120 head-injured patients, recovery rates (rr) were calculated separately on the basis of either Glasgow come scale (GCS) scores or Maryland coma scale (MCS) scores; the latter contains the three variables of the GCS, excludes unevaluable responses, and provides more information concerning the status of brain stem reflexes and motor lateralization. The early (Day 3/4 vs. Day 1) and late (Day 8/14 vs. Day 1) recovery rates from the two scales generally agree (r = 0.76; r = 0.79), but in 39 of 94 patients the MCSrr and GCSrr disagreed by more than 10%. When the MCSrr was greater than the GCSrr, it more accurately reflected a favorable outcome. Graphic representations of clinical courses through serial plots of raw scores were more reliable when unaffected by intubation, sedation, swollen eyelids, casts, etc.; this was more often achieved with serial plots of MCS scores, which are graded as percentages of testable function. Final outcomes (good/disabled vs. vegetative/dead) were well predicted by Day 1 MCS scores above or below 35% (chi 2 = 27.63; p less than 0.001) and Day 1 GCS scores above or below 7 (chi 2 = 23.21; P less than 0.001). However, in 57 very sick patients (Day 1 GCS less than or equal to 7), the GCS did no better than chance (26 good, 31 bad outcomes), whereas 20 of 26 patients with a Day 1 MCS score of less than or equal to 35% had bad outcomes. In patients with severe multiple injuries, the Maryland coma scale may provide a more sensitive index of clinical course; a Day 1 MCS raw score of less than or equal to 35% is of grave prognostic significance.

Adolescent↗
PubMed1981

Steroids in severe head injury: A prospective randomized clinical trial.

This is a prospective randomized study of the efficacy of steroid therapy in patients with severe head injury. One hundred patients were randomized into two equal groups: the steroid group received 5 mg/kg/day of methylprednisolone, and the nonsteroid group received no drug. The groups were similar in their clinical features. All patients received a standardized therapeutic regimen. The patients were also classified as early responders or nonresponders to the overall treatment protocol without regard to steroid administration, on the basis of change in Glasgow Coma Scale score during the first 3 days of admission. There was no statistically significant difference in the outcome of the steroid and nonsteroid group at 6 months. Of the responders who were on steroids, 74% had good outcomes or were disabled, compared with 56% of the responders who did not receive steroids. In the nonresponder group, the patients on steroids were actually associated with a worse outcome than those who did not receive steroids: 75% of the nonresponders who received steroids were dead or vegetative, compared to 56% of those who were not receiving steroids. The data suggest that: 1) the effect of steroids may be different for different patient groups; 2) in order to identify these patients, a sensitive coma scale is needed; and 3) a rational approach to steroid therapy in head-injured patients may be to start all patients on steroids, but to discontinue their use in patients identified as not benefiting from steroid therapy.

Adolescent↗
PubMed1981

Hyperthermia for brain tumors: biophysical rationale.

Hyperthermia has great potential as an antineoplastic agent because: (a) it is effective against relatively radioresistant hypoxic cells and cells in S phase; (b) unlike most chemotherapeutic agents, it is effective against poorly vascularized and metabolically quiescent tissues; (c) as a physical agent, its biological effect is related to the duration and intensity of its application; (d) it seems to have no cumulative toxicity; and (e) it potentiates the effects of both chemotherapy and ionizing radiation at the cellular level. The use of hyperthermia for malignant brain tumors is constrained by a relatively narrow therapeutic index and the considerable thermal sensitivity of normal neural tissue. Glioblastoma multiforme, by virtue of its low growth fraction and heterogeneous cell populations, seems to be an ideal candidate for hyperthermia administered as part of a combined modality treatment program. Focal hyperthermia can be produced by a number of energy sources, including those utilizing ultrasound, microwave, and radiofrequency generators. The clinical safety and feasibility of a miniature microwave radiator/sensor system for direct implantation have been demonstrated. In comparison to normal feline brain, malignant brain tumors in humans are unable to dissipate heat efficiently.

Brain↗
PubMed1980

CSF rhinorrhea associated with the empty-sella syndrome.

The empty-sella syndrome consists of the abnormal extension into the sella turcica of an arachnoid diverticulum filled with CSF, which displaces and compresses the pituitary gland. Such a diverticulum can erode through the sellar floor and lead to CSF rhinorrhea through the sphenoidal sinus. Empty-sella syndrome should be considered a diagnostic possibility in patients with nontraumatic CSF rhinorrhea. Diagnosis and treatment are best accomplished with a team approach involving the otolaryngologist, neurosurgeon, neuroradiologist, and neuroendocrinologist. Definitive diagnosis requires pneumoencephalography and thin-section polytomography. Attention should be directed to the possibility of a coexisting pituitary adenoma. Treatment can be accomplished by a transseptal, transsphenoidal approach with localization and repair of the leak.

Adult↗
PubMed1980

Survival in glioblastoma: historical perspective.

The accumulated retrospective experience with glioblastoma multiforme was reviewed. Data were extracted from 17 reports in the literature, comprising 2532 patients. Survival curves were constructed for 1561 selected cases that did not include limited surgery and/or astrocytoma Grade III. The median survival after operation for the 1561 patients was 6 months, and only 7.5% lived 2 years. The survival curve is exponential in shape; calculation of its rate constant as well as extrapolation on a least squares regression line for the semilogarithmic plot of the data both predict 3- and 5-year survival rates of 1.7 and 0%, respectively. Curves were also plotted for patients who were treated by operation alone (6 study groups, 349 cases), operation plus radiation (11 groups, 568 cases), and operation plus radiation plus chemotherapy (5 groups, 146 cases); the median survival times for the three groups were 4, 9.25, and 10 months, respectively. It was concluded that (a) all curves converge at 18 to 24 months, irrespective of treatment; (b) radiotherapy is the decisive treatment during the first 18 months; (c) survival can be predicted by adopting an exponential model; and (d) prospective studies are required to detect the marginal benefits of current therapies.

Brain Neoplasms↗