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Biomedical subjects

R Sawaya

Publications and source records attributed to R Sawaya.

At least 19 recordsLinked to original sources

Postoperative venous thromboembolism and brain tumors: Part III. Biochemical profile.

The plasminogen activator activity of 31 human brain tumor samples was assessed and the results correlated with clinical parameters and the postoperative occurrence of venous thrombosis. A significant negative correlation was found between plasminogen activator activity and venous thrombosis (P = 0.02), while positive correlations were observed between plasminogen activator activity and peritumoral brain edema (P = 0.03) and alpha 2 antiplasmin measured in the systemic circulation (P = 0.01). Tissue plasminogen activator was found in higher concentrations in meningioma tissue but did not correlate significantly with the occurrence of venous thrombosis. The results of this study suggest a local enzymatic degradation effect of plasminogen activator on thrombogenic substances present in the brain tumor and/or its environment.

Blood Coagulation Tests

Postoperative venous thromboembolism and brain tumors: Part I. Clinical profile.

Forty-six patients who underwent surgery for brain tumors were studied prospectively with 125I labeled Fibrinogen leg scans to detect postoperative venous thrombosis. The incidence of thrombosis was 72% for meningioma patients, 60% for glioblastoma patients, and 20% for brain metastasis patients. Correlation between the occurrence of venous thrombosis and the various clinical factors thought to be responsible for the high incidence of thrombosis generally failed to show statistical significance. This finding, along with the marked variation in the incidence of venous thrombosis between the different brain tumor groups, strongly suggests that biological factors play a more important role than clinical factors in determining which brain tumor patient will suffer a postoperative thrombotic event.

Brain Neoplasms

Postoperative venous thromboembolism and brain tumors: Part II. Hemostatic profile.

Preoperative hemostatic data were obtained on 42 brain tumor patients and correlated with the subsequent occurrence of venous thrombosis detected with 125I-labeled fibrinogen leg scans. The occurrence of thrombosis correlated significantly with an increased prothrombin time, plasminogen, and total fibrinolytic activity and a decreased fibrinogen level. This overall trend in the group of patients with postoperative thrombosis indicates that the hemostatic disorder noted in brain tumor patients is most closely related to a subclinical form of chronic disseminated intravascular coagulation syndrome. Differences in hemostatic parameters seen with the various types of brain tumors suggest that biological factors specific to each tumor are likely responsible for the described hemostatic disorder and support the need for further research directed at the tumor tissue level.

Blood Coagulation Tests

Intracranial osteolytic malignant meningiomas appearing as extracranial soft-tissue masses.

Malignancy is rare in intracranial meningiomas. Although the topic is widely discussed, there is little agreement in the literature as to the histological and radiological features that warrant the diagnosis of malignant meningioma. Three patients are described who had soft-tissue masses and underlying osteolytic lesions on computed tomography. All three patients also had a large intracranial component that proved to be a malignant meningioma. Rarely do meningiomas have all three of these features. We propose that a meningioma causing osteolysis and soft-tissue extension should be considered malignant until proven otherwise.

Aged

Plasma fibrinolytic profile in patients with brain tumors.

Changes in the fibrinolytic and coagulation values measured preoperatively in brain tumor patients have not been done systematically using individual rather than global assays. Such measurements can provide meaningful information on the status of tumor-host interactions and could potentially help in predicting thromboembolic and hemorrhagic tendencies. A complete fibrinolytic profile including total fibrinolytic activity (TFA), tissue plasminogen activator (t-PA), plasmin inhibitor (PI), plasminogen activator inhibitor (PAI), protein C (PC) and plasminogen (PLG) was obtained preoperatively in 114 brain tumor patients. PLG and PI did not show much variation among the groups. TFA was slightly reduced (15%) in patients with malignant brain tumors. t-PA, however, was abnormally low in several patients and in almost 40% of patients with brain metastasis. PAI was above the upper limit of normal in approximately 50% of the patients but particularly in glioma, glioblastoma and metastasis patients. Finally, mean PC was abnormally increased in the glioblastoma and metastasis groups (p less than 0.001). This is the first study that has measured protein C in brain tumor patients. In conclusion, plasma fibrinolytic levels show marked changes in a substantial number of brain tumor patients prior to surgery--suggesting an ongoing tumor-host interaction.

Brain Neoplasms

Neurosurgery issues in oncology.

Advances in the surgical management of central nervous system neoplasms have been reported in several areas including the skull base, the spine and the stereotaxic applications in neurosurgery. A national survey of patterns of care for brain tumor patients contributed data on 11,185 patients, 97% of whom underwent surgery. Stereotaxic-guided craniotomies are providing added accuracy and shortened operative time and length of hospitalization, while the stereotaxic implantation of I125 seeds for recurrent high grade glioma has resulted in prolongation of survival between 54 and 81 weeks. Radiosurgery is being applied with increasing frequency and remarkable success in the management of skull base tumors, acoustic neuroma, and brain metastasis. The two prototypes used are the Gamma-knife and the linear accelerator-based multiple converging arcs technique. In the area of the skull base, significant anatomical details have been provided. Historical facts and clinical series related to the management of meningiomas and acoustic neuromas are reviewed. Spinal cord ependymoma is a surgically curable tumor as reported in a series of twenty-three patients followed for a mean of 62 months, and a randomized study has established the superiority of surgical resection for single brain metastasis as compared to the results obtained with radiation therapy alone.

Brachytherapy

Observations regarding DNA replication sites in human cells in vivo following infusions of iododeoxyuridine and bromodeoxyuridine.

In studies using bromodeoxyuridine (BrdUrd) and/or iododeoxyuridine (IdUrd) to label S phase cells in cancer patients, several unique observations were made regarding DNA replication sites and the organization of newly synthesized DNA in post-mitotic cells. While the majority of tumour specimens removed at the end of infusions demonstrated concentration of replication sites around the nuclear membrane, biopsies obtained in leukaemic patients 1 week later demonstrated several distinct patterns of labelling. For example, one, two or all lobes of granulocytes were labelled. Scavenger macrophages bearing labelled leukaemic cells in their cytoplasm were also seen. Sequential IdUrd/BrdUrd labelling of solid tumours showed various patterns of nuclear/nucleolar/membrane labelling, allowing more precise localization of early versus late replication sites.

Antibodies, Monoclonal

Biological significance of tissue plasminogen activator content in brain tumors.

Fresh brain-tumor samples were obtained at operation and analyzed for their content of tissue type plasminogen activator (tPA) using an activity assay (gel chromatography zymogram) and an enzyme-linked immunospecific assay. The specimens were taken from 23 glioblastomas, 35 metastatic tumors, 42 meningiomas, 16 low-grade gliomas, and seven acoustic neurinomas; seven specimens were from normal brain. A strong correlation was found between the results of the two assays (r = 0.77, p less than 0.0001). There was a threefold difference in the tPA content of the benign tumors as compared to malignant tumors (p = 0.0006), the latter having less tPA. Histologically benign meningiomas contained higher tPA than malignant meningiomas (p = 0.01); however, the difference between low-grade gliomas and high-grade gliomas was less evident. Overall regression analysis data have shown an inverse relationship between the tissue content in tPA and the presence and degree of tumor necrosis and peritumoral brain edema (p = 0.004 and p = 0.0004, respectively). This finding was most consistent in the glioblastoma group where the correlation coefficient values were r = 0.53 and r = -0.55, respectively. There was no significant correlation between the tissue tPA content and the age and sex, steroid use, or plasma tPA of the patients or the duration of symptoms. In summary, this is the first demonstration of tPA in a large series of human brain tumors and in normal brain. The differences observed have clear biological significance and, although the source of tPA in tumor tissue is still unknown, a relative reduction in tPA in tumor tissue may play an integral role in the development of tissue necrosis and tissue edema. The lack of tPA in tumor necrosis was not due to tissue destruction and cell death since urokinase was readily detectable in that tissue.

Brain Neoplasms

Fibronectin.

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Amino Acid Sequence

Primary cerebral neuroblastoma (neurocytoma) in adults.

We report a case of a third ventricular neuroblastoma (neurocytoma) in a 66 year old man. A stereotactic needly biopsy was performed to obtain a tissue diagnosis and was followed by total resection. We elected not to give radiation or chemotherapy and to follow the patient closely with serial CT scans. Presently, 48 months postoperatively, the patient is free of tumor by head CT scan and able to live independently. We reviewed the literature of primary cerebral neuroblastomas/neurocytomas occurring in adults (greater than or equal to 15 years of age) and found 32 cases. Our patient is the oldest of this group with a mean age of 32 +/- 14 years (S.D.). The location of the 33 neoplasms was intraventricular in 17 cases (52%) and intraparenchymal in 16 cases. The male to female ratio was 2:1. Of the 17 patients having a minimal follow-up period of 5 months (mean 51 months), five developed recurrences after 5 to 144 months (mean 50 months) compared to 12 patients without recurrence after a 6- to 72-month follow-up period (mean 52 months). Recurrences occurred statistically significantly more often in parenchymal neuroblastomas/neurocytomas than in intraventricular tumor locations.

Aged

Cerebral blood flow and metabolism in sleep.

A review is presented of the electrical activity of the brain and its global and regional blood flow and metabolism in the different stages of sleep and in wakefulness in animals and humans. During slow-wave sleep (SWS), the blood flow and metabolism of the brain decrease slightly below the level of wakefulness. During rapid eye movement the activity of the brain increases above that of SWS and sometimes above that of wakefulness. Some studies suggest that both at sleep onset and at arousal the brain stem-cerebellar complex (BSC) may be activated before the cortex and the right hemisphere before the left. Variation of hemispheric dominance seems to be a phenomenon of both wakefulness and sleep.

Brain

Hyalinizing plasmacytic granulomatosis of the falx.

Computed tomography scan in a 43-year-old woman revealed a fusiform mass involving the falx. Pathological tissue removed at craniotomy revealed a hyalinizing plasmacytic granulomatosis composed of masses of lymphocytes, plasmacytes, and various sized islands of hyalinized fibers arranged in parallel and surrounded by multinucleated giant cells. Ultrastructurally, the hyalinized fibers consisted of electron-dense, amorphous deposits. After partial removal, irradiation, and steroid therapy, the lesion decreased considerably in size.

Adult

Plasminogen activator activity and molecular weight patterns in human brain tumors.

Fresh human brain-tumor samples were assayed for their plasminogen activator (PA) content. Specific molecular weight patterns were identified for each of five common brain tumors and for normal brain, suggesting a cell-specific origin of the various PA forms. Malignant tumors contained higher PA activity and a larger number of molecular weight patterns than benign tumors, with the exception of acoustic neurinomas. Irradiated tumors contained lower PA activity than nonirradiated tumors. Finally, a slight but definite correlation between brain edema and PA activity was detected. The future role of brain-tumor PA's for diagnostic and therapeutic purposes is discussed.

Astrocytoma

Immunohistochemical demonstration of alpha-1-proteinase inhibitor in brain tumors.

Using light microscopy and immunoperoxidase methods (PAP), the presence of alpha-1-proteinase inhibitor (API) was studied in seventeen brain tumors and four normal brain samples. The brain tumors included four glioblastomas, five low-grade gliomas, two metastatic lung carcinomas, two acoustic schwannomas, and four meningiomas. Normal brain displayed a finely granular intracytoplasmic staining confined to neuronal cells. Glial cells were negative for API. Fifteen of the 17 brain tumors were positive for API. Only two of five low-grade gliomas were negative for API. Glioblastoma and metastatic tumors exhibited the strongest positivity followed by acoustic neuroma, meningioma, and low-grade glioma. All positive samples exhibited finely granular intracytoplasmic API, and 50% exhibited extracellular API positivity. Metastatic and glioblastoma tumors demonstrated prominent extracellular API staining. Our results support the concept of a local production of API by brain tumors.

Blood Proteins

Alpha-1-antitrypsin in human brain tumors.

This study was undertaken to confirm the presence of alpha-1-antitrypsin (alpha 1-AT) in human brain tumors and to attempt to elucidate its significance. Seventy-seven consecutive unselected patients with various brain tumors were entered in this study. The alpha 1-AT and alpha 2-macroglobulin contents of the tumor extracts were qualitatively assessed by Ouchterlony immunodiffusion techniques. Plasminogen activator (PA) activity was assayed electrophoretically on sodium dodecyl sulfate gels. The patients were were divided into two groups according to the positivity of their tumors to alpha 1-AT. Sixty-eight percent of the tumors were positive for alpha 1-AT, and all specimens were negative for alpha 2-macroglobulin. Clinical and biological parameters obtained in all study patients failed to show statistically significant differences between the two groups with the exception of PA activity (p = 0.001), the peritumoral edema as seen on computerized tomography, and the preoperative serum fibrinogen level. These three parameters were higher in the group with specimens positive to alpha 1-AT. This study supports the hypothesis that alpha 1-AT is produced primarily by tumor cells in proportion to the regional proteolytic and inflammatory activity, and may protect the tumor cells.

Brain Neoplasms