Visual loss associated with bromocriptine.
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Aged↗
Biomedical subjects
W T Couldwell
Publications and source records attributed to W T Couldwell.
Osseous metastases from a benign intraventricular meningioma. Case report.
The authors report a case of a 6 month-old male presenting with increasing head circumference and a large benign intraventricular meningioma which was grossly removed at the initial surgery. Twenty-four months later, the patient returned with subcutaneous and osseous metastatic lesions at the site of the previous craniotomy, revealing the same histology as the original tumour. The presentation, pathology and management of this unique case are discussed.
Cerebral Ventricle Neoplasms↗
Production of soluble autocrine inhibitory factors by human glioma cell lines.
Gliomas in vitro exhibit density-limited growth upon the attainment of confluency, an effect usually attributed to cell-cell contact inhibition. Since gliomas have been demonstrated to secrete an array of soluble factors which can enhance tumor growth, we undertook this study to ascertain whether production of soluble factors by the tumor may also inhibit growth in an autocrine manner, and whether production of such factors is associated with the growth phase of the glioma. We observed that cell-conditioned medium (supernatants) from non-confluent glioma cultures induced growth, while confluent culture supernatants produced pronounced growth suppression. These latter supernatants enhanced proliferation of non-transformed astrocytes. Supernatants derived from all stages of confluency produced inhibition of lymphocyte proliferation. To characterize these factors, dialyzed supernatant was tested and found to continue to produce lymphocyte suppression but no glioma growth limitation. Growth of tumors in indomethacin or in acetylsalicylic acid to abolish prostanoid synthesis abrogated the inhibitory influence on glioma growth but only partially reversed the lymphocyte suppressive capacity. These studies suggest that gliomas do produce a growth phase dependent autocrine inhibitory factor(s), and that the production of these small molecular weight factors is at least partially under control of the cyclooxygenase pathway.
Adult↗
Malignant glioma-derived soluble factors regulate proliferation of normal adult human astrocytes.
Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non-transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo.
Astrocytes↗
Protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of protein kinase C.
The proliferation rates of gliomas may be modulated by the protein kinase C (PKC) signal transduction system. The present study was undertaken to further examine the role of PKC system in growth regulation of gliomas in vitro by measurement of PKC activity over various phases of tumor growth and by assessing its potential role as a signal transduction system induced by serum mitogens and the known glioma mitogens epidermal growth factor and fibroblast growth factor. All human glioma lines examined, and the rat glioma C6, displayed high PKC activity relative to nonmalignant glial cells, which correlated with their proliferation rates over their respective growth phase. Frozen surgical human malignant glioma specimens also displayed high PKC activity. The relatively selective PKC inhibitor staurosporine (SP) reduced PKC activity and corresponding growth rates in a dose-related manner. Stimulation of PKC with phorbol esters under different concentrations of serum in the growth medium indicated that the high PKC activity, which correlated with their rapid growth rates, is highly susceptible to down-regulation by these agents. Epidermal growth factor and fibroblast growth factor increased both PKC activity and the growth rate of glioma line A172; addition of SP reduced the growth rate to levels observed in SP-treated control tumors, indicating that PKC may be a common signal transduction system induced by these mitogens. These results implicate PKC as an important signal transduction system regulating glioma growth, and offers a potential target for tumor inhibition.
Animals↗
Adhesion molecules and malignant gliomas: implications for tumorigenesis.
Adhesion molecules, a family of cell-surface molecules, are likely to be of central importance in mediating cell-extracellular matrix and specific cell-cell interactions within both neoplastic and inflammatory sites. The recently discovered expression of adhesion molecules on glioma cells, tumor-infiltrating lymphocytes, and endothelial cells within the tumor offers insight into the molecular basis of the interactions both between the glioma cell and surrounding heterologous cell types within the tumor environment, and between the tumor cell and the extracellular matrix. Such interactions suggest that these molecules may play roles in the homing of immune cells to these tumors and in regulating the extent of local tumor invasion. The ability to modulate adhesion molecule expression on either immune cells or their respective ligands on gliomas provides an approach to modify cell-cell interactions that may be used to increase tumor kill by the immune system. A similar approach in the modulation of adhesion molecules involved in tumor cell adhesion to the extracellular matrix or endothelial cells may be a method to limit local invasion in these lesions.
Cell Adhesion Molecules, Neuronal↗
Neurosurgery, molecular medicine, and the Pandora-Panacea continuum: future implications for glioma therapy?
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Brain↗
Cysticercosis cerebri.
With increasing immigration from endemic regions, the incidence of cysticercosis in North America is rising. This fascinating disease with its varied presentations may pose complex management dilemmas whose resolutions often require a combined approach to treatment involving medical and, in some cases, selected surgical intervention. The treatment course must be individualized depending on the symptomatology, anatomic location of the cysts, and host inflammatory response.
Brain↗
Malignant glioma modulation of immune function: relative contribution of different soluble factors.
We analyzed a series of human glioma cell lines with regard to establishing what variables may contribute to their overall functional immunomodulating capability. We observed that supernatants derived from the gliomas, but not those from non-malignant human astrocyte cultures, suppressed lymphocyte proliferation. The extent of suppression elicited differed between tumors and for the same tumor depending upon its growth phase. For individual gliomas, supernatants from cultures approaching or at confluency elicited maximal lymphocyte suppression. For the series of tumors, levels of production of the immunosuppressive molecules transforming growth factor beta 2 and prostanoids (prostaglandin E2) did not correlate with the levels of functional suppression observed at any of the different growth phases. In some cases, glioma cultures grown in the presence of indomethacin to abolish prostanoid synthesis resulted in supernatants with net stimulatory activity. Our results indicate that malignant transformation of astrocytes is associated with acquisition of immunosuppressive capability which is determined by the combined effect of multiple immunomodulatory soluble factors, inhibitory or enhancing, and is dependent on the growth phase of the tumor.
Dinoprostone↗
Definition of the role of contemporary surgical management in cisternal and parenchymatous cysticercosis cerebri.
With increasing immigration from endemic regions, the incidence of neurocysticercosis in North America is rising. This retrospective study was undertaken to examine the role of surgery in those cases presenting with large cystic parenchymal and cisternal lesions in the current era of anthelminthic agents administered orally. A total of 237 patients presented with newly diagnosed neurocysticercosis to our institution over a recent 5-year period (mean age, 31.2 years). Among those who presented with cystic mass lesions predominantly affecting the brain parenchyma and cisternal spaces, 20 (8.4%; mean age, 40.2 years) with large cystic lesions subsequently underwent surgical intervention, either because of an emergent presentation or because they were refractory to medical management. Clinical presentation included increased intracranial pressure, focal neurological deficit, and seizure. Radiographic imaging (computed tomography and/or magnetic resonance imaging) demonstrated 12 cases with cisternal lesions, 7 with parenchymal lesions, and 1 involving both compartments. Based on imaging guidelines, 30 operative procedures (excluding shunt revisions) were performed (14 craniotomies, 8 cerebrospinal fluid diversions, 7 stereotactic procedures, and 1 burr hole drainage). Fifteen (75%) showed neurological or symptomatic improvement over a median follow-up period of 36.4 months. There were three surgery-related complications and no deaths.
Adult↗
Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro.
Direct measurement of protein kinase C (PKC) activity in vitro revealed a significant increase in the activity of the enzyme in all human malignant glioma lines examined and the rat C6 tumor in comparison with control nonneoplastic astrocyte and mixed glial cultures. The total and particulate PKC activity in these cell types correlated strongly [r = 0.98 (P less than 0.001) and 0.94 (P = 0.002), respectively] with the maximal growth rates as measured by 3H-thymidine incorporation in each of the samples. An alteration in the growth rate of an individual glioma line (A172) by varying the serum concentration in the growth medium produced comparative changes in the measured PKC activity. The addition of the phorbol ester phorbol-12-myristate-13-acetate to this tumor line under high serum conditions produced down-regulation of the enzyme, which was accompanied by a corresponding reduction in thymidine incorporation. The administration of the PKC inhibitor staurosporine produced a dose-related decrease in the basal proliferation rate of glioma lines A172 and C6, as measured by 3H-thymidine uptake and confirmed by flow cytometry, indicating that the high intrinsic PKC activity is amenable to pharmacological manipulation. Cytofluorometric deoxyribonucleic acid cell cycle analysis of the tumors treated with PKC modulators demonstrated that reduced proliferation rates were caused by an inhibition of entrance into the deoxyribonucleic acid synthesis (S) phase (decrease in proliferative index), supporting the evidence that these modulators are not slowing the tumor growth in a nonspecific cytotoxic manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Alkaloids↗
Utilization of unilateral and bilateral stereotactically placed adrenomedullary-striatal autografts in parkinsonian humans: rationale, techniques, and observations.
A limited clinical pilot study involving an amalgam of specialized disciplines including neurology, neuropharmacology, neuropsychology, neurosurgery, neuroanesthesia, neuroradiology, surgical pathology, neuropathology, and urological surgery was organized to clarify issues related to patient selection, optimization of grafting materials, design of a safe, effective, standardized, and reproducible surgical technique, and possible modification of clinical patterns. After initial assessment of 82 Parkinsonian patients for periods of 6 to 20 months, 10 (age, 39-68 years) were selected for unilateral or bilateral adrenomedullary autografts to the caudate nucleus with ependymal and cerebrospinal fluid contact, employing image-directed stereotactic methods. Selection was made only after clear definition of clinical pattern and optimization of medication responses. Adrenal glands were harvested by a retroperitoneal approach (mean estimated blood loss less than 75 ml). Care was taken to maximize the graft content of medullary tissue. Stereotactic methods afforded standardized, reproducible, precise targeting and transit trajectory with unilateral or bilateral placement of materials within the striatum (tissue volume, 80 mm3) with access to the ventricular fluid of the frontal horn. Considerable variability in satisfactory donor medullary tissue was encountered. One patient did not undergo grafting because of unsatisfactory medullary tissue. No significant surgical complications were noted and all patients were ready for discharge 7 days after surgery. One patient who manifested no apparent clinical change died 6 weeks after bilateral grafting of unrelated causes during a lithotripsy procedure. Postmortem examination disclosed precise graft placement with a paucity of structurally preserved medullary cells. Postoperative observations, including parameters of clinical observation, medication schedules and records, patient and family commentaries, and imaging studies (computed tomograms and single photon emission computed tomograms), have been made for periods from 16 to 20 months. Sustained improvement in preexisting clinical patterns and reduction in drug requirements were observed in 4 of 8 patients. No increased benefit could be ascribed to bilateral graft placement. These observations would indicate a safe, and reproducible surgical method. In addition, the clinical observations indicate favorable alterations in the established pattern of the disorder, which would justify further cautious exploration of alternate donor sources or refinements of biological graft site manipulations.
Adrenal Medulla↗
Initial experience related to the use of the Cosman-Roberts-Wells stereotactic instrument. Technical note.
Initial experience with a new arc-radius design of stereotactic frame that interfaced with the existing components of the Brown-Roberts-Wells instrument is reported. Over a 6-month period, 32 procedures were performed on 23 males and nine female patients (mean age 32 years); these included 27 stereotactic biopsy procedures, two stereotactic implantations of cyst catheter reservoirs, two ventriculoscopic aspirations of third ventricular colloid cysts, and one stereotactic aspiration of a craniopharyngioma. In all cases successful targeting was achieved and verified by postoperative computerized tomography. There were no operation-related complications. This new frame offers rapid and accurate targeting and is a useful adjunct to the stereotactic armamentarium.
Adult↗
Inhibition of growth of established human glioma cell lines by modulators of the protein kinase-C system.
The protein kinase-C (PKC) second messenger system contributes to regulation of cell growth and differentiation. This study was undertaken to examine the effects of modulators of the PKC enzyme system on the state of differentiation and proliferation rates of human gliomas in vitro. The administration of the PKC-activating phorbol esters 4-beta-phorbol-12,13-dibutyrate (PDB) and phorbol-12-myristate-13-acetate (PMA) resulted in a dose-related inhibition of growth of human glioma cell lines in vitro as measured by 3H-thymidine uptake. The synthetic nonphorbol PKC activator (SC-9) produced an even more pronounced decrease of 3H-thymidine uptake. Diacylglycerol, an endogenous activator of the system, applied externally, transiently decreased the proliferation, in concordance with its short-lived existence in vivo. Conversely, the administration of 4-alpha-phorbol-12,13-didecanoate (alpha-PDD), a phorbol ester that binds but does not activate the enzyme, had no effect on the proliferation rate. At the dosages that maximally decreased proliferation, there was no evidence of direct glioma cell lysis induced by these agents as measured by a chromium-release assay. Immunocytochemical analysis and cytofluorometric measurement of glial fibrillary acidic protein (GFAP) staining in the treated cultures revealed an increase in GFAP staining over control cultures. In contrast to the response of glioma cells, nonmalignant human adult astrocytes treated with the PKC activators responded by increasing their proliferation rate. The authors postulate that the diametrically opposed effects of PKC activators on nonmalignant astrocytes versus glioma growth may be due to a high intrinsic PKC activity in glioma cells, with resultant down-regulation of enzyme activity following the administration of the pharmacological activators.
Astrocytes↗
Pituitary gland metastasis from adenocarcinoma of the prostate. Case report.
A case of prostatic carcinoma metastasis to the pituitary gland is reported. The presentation and rarity of such a lesion is addressed. The literature review yielded only isolated case reports of symptomatic brain metastases unassociated with bone disease from adenocarcinoma of the prostate. The management options of such a lesion are discussed.
Adenocarcinoma↗