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Biomedical subjects

W T Couldwell

Publications and source records attributed to W T Couldwell.

At least 73 records · Page 4Linked to original sources
PubMed1996

Petroclival meningiomas: surgical experience in 109 cases.

The surgical removal of petroclival meningiomas has historically been associated with a high incidence of morbidity and mortality. The 109 consecutive patients included in the present retrospective study represent a combined series of tumors operated on by the four authors during a period from 1980 to 1992. The series is composed of 40 men and 69 women ranging in age from 25 to 75 years (mean 51 years). Surgical approaches to tumors in this series included simple retromastoid (60 cases), combined supra- and infratentorial petrosal (22), transtemporal (primary transsigmoid retrolabyrinthine, translabyrinthine, or transcochlear (12), subtemporal (11), and frontotemporal transcavernous (eight). Gross-total removal was achieved in 75 patients (69%). Recurrence or progression of disease occurred in 14 patients (13%) over a 6.1-year mean follow-up period, and it was found within the cavernous sinus in 12 of these cases. Four recurrent cases demonstrated histological compatibility with malignant meningioma. Perioperative death occurred in four patients, and there were 56 significant complications in 35 other patients. Review of this series, with the attendant complications, has facilitated the authors' decision-making when considering the risk of gross-total removal in selected patients with asymptomatic cavernous sinus invasion or tumor adherent to the brainstem.

Adult↗
PubMed1996

Inhibition of cellular growth and induction of apoptosis in pituitary adenoma cell lines by the protein kinase C inhibitor hypericin: potential therapeutic application.

Protein kinase C (PKC) is an enzyme involved in the regulation of cellular growth, proliferation, and differentiation in a number of tissues including the anterior pituitary, in which it is also believed to play a role in hormone secretion. Protein kinase C activity and expression have been found to be greater in adenomatous pituitary cells than in normal human and rat pituitary cells and higher in invasive pituitary tumor cells than in noninvasive ones. Inhibition of PKC activity has been shown in a variety of tumor cells to inhibit growth in a dose-related fashion. The purpose of the current study was to determine whether hypericin, a potent inhibitor of PKC activity that may be administered clinically, alters the growth and proliferation in established pituitary adenoma lines and to determine if inhibition of PKC activity induces apoptosis, as reported in some other tumor cell types. Two established pituitary adenoma cell lines, AtT-20 and GH4C1, were treated with hypericin in tissue culture for defined periods following passage. Inhibition of growth was found to be dose dependent in all three cell lines in low micromolar concentrations of hypericin, as determined by viable cell counts, methylthiotetrazole assay, and [3H]thymidine uptake studies. Concentrations of hypericin as low as 100 nM also induced apoptosis in these established lines, whereas treatment of normal human fibroblasts with a concentration of 10 microM failed to induce apoptosis. The potential use of hypericin in the therapy of pituitary adenomas warrants additional in vitro investigations with the aim of later moving toward therapeutic trials in selected patients in whom surgical or medical therapy has failed.

Adenoma↗
PubMed1996

Experience with use of extended length peritoneal shunt catheters.

The placement of a ventriculoperitoneal (VP) shunt is the current treatment of choice for diversion of cerebrospinal fluid associated with hydrocephalus. Although there are a host of reported potential abdominal complications related to the procedure, they are notably uncommon. The authors report their experience with the primary insertion of an extended length open-ended peritoneal tubing (120 cm) undertaken expressly to avoid the need for a lengthening procedure because of growth of the patient. In a review of new insertions of VP shunts using the extended length tubing over a 14-year period at Childrens Hospital of Los Angeles, a total 998 shunts were placed in 952 patients, with a mean follow-up period of 6.7 years. The patients experienced a total of 52 distal shunt revisions for a variety of malfunction etiologies. In patients ranging in age from premature neonate to 20 years, there was no increase in the distal complication rate, and specifically no complications were experienced that were directly related to the use of the extended length tubing. The authors conclude that the use of an extended length peritoneal shunt catheter is not associated with an increase in complications and eliminates the need to lengthen the peritoneal catheter for growth of the patient.

Adolescent↗
PubMed1996

Treatment of recurrent malignant gliomas with chronic oral high-dose tamoxifen.

The present clinical trial was undertaken to assess the clinical safety and possible efficacy of administering tamoxifen to patients with recurrent malignant glial tumors at dosages calculated to achieve levels sufficient to inhibit protein kinase C within the tumor cells. Chronic p.o. tamoxifen was administered in very high dosages to 32 patients (20 males and 12 females; age range, 26-75 years; mean, 49 years) with histologically verified malignant glioma [anaplastic astrocytoma (12 patients) or glioblastoma multiforme (20 patients)] who had demonstrated clinical and radiographical progression or recurrence following external beam radiation therapy (and additional chemotherapy in 11; immunotherapy in 2). The dosage of tamoxifen administered was 200 mg/day to males and 160 mg/day to females given in a twice daily schedule. Clinical and radiographical (defined as a greater than 50% decrease in volume of the enhancing lesion volume on magnetic resonance imaging and a decrease in metabolic activity on serial positron emission tomographic scans) response was noted in 8 patients (25%; 4/12 with anaplastic astrocytoma and 4/20 glioblastoma multiforme), with an additional 6 patients (19%) exhibiting stabilization of disease with minimal side effects. Median survival from the time of diagnosis for the entire cohort was 24 months (104 weeks), for the anaplastic astrocytoma group 42.5 months (185 weeks), and for the glioblastoma group 17.4 months (75.5 weeks). From the initiation of tamoxifen, median survival for the entire cohort was 10.1 months (44 weeks), for the anaplastic astrocytoma group 16 months (69 weeks), and for the glioblastoma group 7.2 months (31 weeks). The mean length of follow-up of all patients after initiating tamoxifen was 16 months (69 weeks), while the mean length of follow-up of alive patients is 22.6 months (98 weeks) (range up to 51 months). These data suggest that a subgroup of patients with malignant gliomas respond or stabilize with chronic high-dose tamoxifen therapy. This therapy may represent an alternative or adjuvant to existing chemotherapies for these tumors; further clinical trials are warranted.

Administration, Oral↗
PubMed1996

Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro.

Hypericin, an antidepressant and antiviral agent being evaluated in phase I and II trials for patients with HIV infection, is known to be a potent protein kinase C inhibitor. We have investigated its effects on cellular response to radiation via a tetrazolium-formazan cell growth rate assay using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and clonogenic assay in three human glioblastoma cell lines, U87-MG, A-172, and T98G, and a low-passage malignant glioma culture, 93-492. At a concentration of 5 microM, hypericin inhibited these cells slightly but caused significant radiosensitization (e.g., the cell survival rate after the radiation treatment was 50.2 and 26.0% in cells treated with 6 Gy and 6 Gy plus 5 microM hypericin in U87-MG cells, respectively; P = 0.0285). Hypericin also enhanced the radiosensitivity significantly in the low-passage glioma 93-492 cells. These findings suggest that hypericin represents a potential new agent in combination with radiation therapy of malignant gliomas.

Anthracenes↗
PubMed1995

Growth inhibition and apoptosis in human neuroblastoma SK-N-SH cells induced by hypericin, a potent inhibitor of protein kinase C.

The effect of hypericin, an antiviral agent and inhibitor of protein kinase C (PKC), on cell proliferation and programmed death was investigated in the human neuroblastoma cell line SK-N-SH. Hypericin induced significant growth inhibition in a dose-dependent manner demonstrated by a microculture tetrazolium (MTT) assay. DNA isolated from cells treated with hypericin at concentrations over 1 microM exhibited a 'ladder' pattern of oligonucleosome-sized fragments characteristic of apoptosis. Similarly, treatment of the cells with the PKC inhibitors staurosporine, tamoxifen or phorbol ester PMA for 72 h also resulted in apoptosis, suggesting that hypericin may be triggering an apoptotic signal in neuroblastoma cells, which at least in part may be mediated by the inhibition of PKC.

Alkaloids↗
PubMed1995

Limited efficacy of experimental anti-epileptic drugs in refractory temporal lobe epilepsy: implications for patient management and study recruitment.

Patients with refractory temporal lobe epilepsy (TLE) are commonly recruited for investigational anti-epileptic drug (XAED) studies. However, the long-term outcome of TLE after exposure to XAEDs is poorly documented. In this pilot study, we report the USC Epilepsy Center's experience of 19 patients with TLE enrolled in three XAED trials. The data reinforce that TLE is a drug-resistant epilepsy, and referral of good surgical candidates for surgery rather than XAED trials is more likely to result in remission.

Anticonvulsants↗
PubMed1995

High-dose tamoxifen in treatment of brain tumors: interaction with antiepileptic drugs.

The incidence of seizures related to primary brain tumors is 20-80%. High-dose tamoxifen was recently reported as a novel treatment for patients with malignant gliomas who have failed standard therapies. Tamoxifen inhibits protein kinase C (PKC) in vitro and thus may regulate glioma cell growth by modulating intracellular signal transduction. We report a patient with a recurrent supratentorial pilocytic astrocytoma who had an untoward interaction between high-dose tamoxifen therapy and phenytoin (PHT), drugs that share a common enzyme for metabolism, therefore emphasizing the need to monitor concomitant antiepileptic drug (AED) levels when high-dose tamoxifen therapy is instituted.

Adult↗
PubMed1995

Cerebral neurocytoma: an unusual cause of refractory epilepsy. Case report and review of the literature.

We report a patient with medically refractory complex partial seizures (CPS) caused by a cerebral neurocytoma located near the amygdala. Neurocytoma represents an important addition to the differential diagnosis and, in particular, must be differentiated from oligodendroglioma and dysembryoplastic neuroepithelial tumor. Accurate pathological differential has therapeutic and prognostic implications.

Adult↗
PubMed1995

Frontal foramina in pediatric skull in cases of congenital hydrocephalus.

PURPOSE: To describe a new observation, frontal calvarial foramina, in pediatric patients with congenital hydrocephalus secondary to central nervous system malformation. MATERIALS AND METHODS: Frontal foramina were initially identified in three female patients with Chiari II malformation. Subsequently, head computed tomographic (CT) scans in 99 patients with congenital hydrocephalus were retrospectively reviewed. CT scans in a control group of 116 patients without hydrocephalus were also retrospectively reviewed. RESULTS: Frontal foramina were found in eight of 61 (13%) patients with Chiari II malformation, in one child with Dandy-Walker malformation, and in one child with occipital horn dilatation (colpocephaly), but not in control patients. Sequential CT examinations in three patients with frontal foramina depicted gradual closure after ventriculoperitoneal shunt placement. CONCLUSION: Frontal foramina may represent an abnormality variably expressed in certain central nervous system malformations that cause congenital hydrocephalus. The presence of frontal foramina palpated or visualized on plain radiographs may help in the diagnosis of congenital hydrocephalus and central nervous system malformation.

Adolescent↗
PubMed1995

Third ventricular cysticercal cyst mimicking a colloid cyst: case report.

We describe a case of a 28-year-old Latino man who presented with signs and symptoms of raised intracranial pressure and radiographic evidence of a third ventricular cystic lesion. The cyst was removed via a transcallosal approach; the histology was noted to be a cysticercal lesion. The radiographic and histological features of this interesting case are discussed.

Adult↗
PubMed1995

Paradoxical elevation of Ki-67 labeling with protein kinase inhibition in malignant gliomas.

The monoclonal antibody Ki-67 recognizes a nuclear antigen expressed in the G1, S, G2, and M phase of the cell cycle and has been used extensively as an indicator of cellular proliferation in malignant gliomas, both in the laboratory and clinically. Recently, protein kinase C (PKC) inhibitors have been demonstrated to inhibit malignant glioma growth both in in vitro and in vivo. This study was undertaken to determine whether Ki-67 could function as an indicator of cellular proliferation rate after PKC inhibition in gliomas and to explore cell cycle specificity of such inhibition. Both established and low-passage malignant glioma cell lines have previously been shown to be sensitive to growth inhibition by the PKC inhibitors staurosporine and tamoxifen in vitro (IC50 in the nanomolar and micromolar ranges, respectively), as measured by cell numbers, [3H]thymidine uptake, and flow-cytometric DNA analysis. However, in the same cells that are inhibited by staurosporine and tamoxifen on these assays, and on the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay in the present study, the Ki-67 labeling index paradoxically increased in a dose-related manner with the same treatments, as measured by immunohistochemistry and confirmed by flow cytometry. For example, in established line U-87, a 20.5% decrease in thymidine uptake and a 28.5% decrease in absorbance on the MTT assay produced by tamoxifen at 1 microM was associated with an increase in Ki-67 labeling from 42% to 62%; staurosporine, which produces a 78.8% decrease in thymidine uptake in cell line A-172 at 10 nM, produced an increase in Ki-67 labeling from 19% to 32%. In this regard, Ki-67 labeling of glioblastoma tissue from a patient treated with high-dose tamoxifen yielded results within the range of 10% to 15% (consistent with values seen in untreated glioblastoma), despite tumor regression with treatment. The authors' interpretation of these results is that these PKC inhibitors are halting the cell cycle in the G1 phase or the G1-S transition (beyond G0 but before S-phase), resulting in a paradoxical increase in labeling while arresting growth. Two important implications from these observations are that Ki-67 is not a reliable indicator of cellular proliferation after treatment with PKC inhibitors and that these inhibitors used at the doses given above halt cell growth in a phase-specific manner.

Alkaloids↗
PubMed1995

The transfacet pedicle-sparing approach for thoracic disc removal: cadaveric morphometric analysis and preliminary clinical experience.

A number of operative techniques have been described for the treatment of herniated thoracic discs. The transfacet pedicle-sparing approach allows for complete disc removal with limited spinal column disruption and soft-tissue dissection. Fifteen cadaveric spinal columns were used for evaluation of exposure, development of thoracic microdiscectomy instrumentation, and establishment of morphometric measurements. This approach was used to remove eight thoracic discs in six patients. Levels of herniation ranged from T-7 through T-11. Preoperatively, all patients had moderate to severe axial pain, and three (50%) of the six had radicular pain. Myelopathy was present in four (67%) of the six patients. Through a 4-cm opening, the ipsilateral paraspinal muscles were reflected, and a partial facetectomy was performed. The disc was then removed using specially designed microscopic instrumentation. Postoperatively, the radiculopathy resolved in all patients. Axial pain and myelopathy were completely resolved or significantly improved in all patients. The minimal amount of bone resection and muscle dissection involved in the operation allows for: 1) decreased operative time and blood loss; 2) diminished perioperative pain; 3) shorter hospitalization time and faster return to premorbid activity; 4) avoidance of closed chest tube drainage; and 5) preservation of the integrity of the facet-pedicle complex, with potential for improvement in outcome related to axial pain. This technique appears best suited for the removal of all centrolateral discs, although it has been used successfully for treating a disc occupying nearly the entire ventral canal. The initial experience suggests that this approach may be used to safely remove appropriately selected thoracic disc herniations with good results.

Adult↗
PubMed1994

Lovastatin induces growth inhibition and apoptosis in human malignant glioma cells.

The competitive HMG-CoA reductase inhibitor lovastatin has been shown to suppress growth and induce morphological changes in a variety of non-glioma tumor cell lines. This study assesses the effects of this agent on the growth and survival of the human malignant glioma cell lines A172 and U87-MG. The response to the drug was investigated using a cell proliferation assay which revealed significant dose-dependent growth inhibition. Treatment with as little as 100 nM lovastatin over a period of 72 hours led to DNA degradation into nucleosome-sized fragments characteristic of apoptosis. Our data suggest that HMG-CoA reductase inhibitors such as lovastatin merit further investigation as potential therapeutic agents for the treatment of malignant gliomas.

Apoptosis↗
PubMed1994

Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines.

Previous work has demonstrated the importance of the protein kinase C (PKC) system in regulating glioma growth, and has led to clinical trials utilizing PKC inhibitors as adjuncts in the therapy of patients harboring malignant gliomas. This study was performed to explore the possibility that inhibition of PKC in gliomas was triggering an apoptosis signal. Glioma cell lines were treated with PKC inhibitors staurosporine (10 nM), and tamoxifen (10 microM). DNA from cells treated with each of these drugs exhibited a 'ladder' pattern of oligonucleosome-sized fragments characteristic of apoptosis, thus suggesting that in glioma cells, these drugs may be cytocidal in action.

Alkaloids↗
PubMed1994

CSF neuron-specific enolase after methohexital activation during electrocorticography.

We report changes in CSF and serum neuron-specific enolase (NSE) before and after methohexital infusion during electrocorticography in three patients undergoing epilepsy surgery. NSE is a critical enzyme for energy metabolism that accounts for 1.5% of all soluble brain protein and is an accepted marker of neuronal injury. CSF NSE rose three- to fourfold from baseline within 60 minutes after methohexital activation. Serum NSE was unchanged. This report supports evidence that CSF NSE rises acutely after induction of epileptiform activity and suggests that CSF NSE is a marker of seizure activity.

Biomarkers↗