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Biomedical subjects

Keith M Rich

Publications and source records attributed to Keith M Rich.

18 recordsLinked to original sources
PubMed2006

Clinical features and outcome in North American adults with moyamoya phenomenon.

BACKGROUND AND PURPOSE: To describe baseline clinical features and outcomes of adults with moyamoya phenomenon treated at a single North American institution. METHODS: We identified 34 adults with moyamoya phenomenon by review of angiographic records. Clinical presentation and baseline stroke risk factors were obtained by chart review. Follow-up was obtained prospectively. A 5-year Kaplan-Meier stroke risk was calculated. RESULTS: The median age was 42 (range 20 to 79) years. Twenty-five were women. The initial symptom was ischemia, hemorrhage, or asymptomatic in 24, 7, and 3 patients, respectively. Twenty-two had bilateral involvement and 12 had unilateral moyamoya vessels. Baseline stroke risk factors were similar between groups. The median follow-up in 31 living patients was 5.1 (range 0.2 to 19.6) years. Fourteen patients were treated with surgical revascularization (20 total hemispheres). In medically treated symptomatic hemispheres, the 5-year risk of recurrent ipsilateral stroke was 65% after the initial symptom and 27% after angiographic diagnosis. Patients with bilateral involvement presenting with ischemic symptoms were at the highest risk of subsequent stroke (n=17, 5-year risk of stroke with medical treatment after first symptom of 82%). In surgically treated hemispheres, the 5-year risk of perioperative or subsequent ipsilateral stroke or death was 17%. This was significantly different compared with medical treatment after first symptom (P=0.02) but not after angiographic diagnosis. CONCLUSIONS: Moyamoya phenomenon in North American adults is associated with a high risk of recurrent stroke, particularly those with bilateral involvement and ischemic symptoms. These data suggest a potential benefit with surgery if diagnosis could be made earlier.

Adult↗
PubMed2006

Postural tremor suppression is dependent on thalamic stimulation frequency.

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) reduces tremor in people with essential tremor (ET), yet the dependence of tremor suppression on stimulation frequency remains unclear. To address this issue, we tested tremor suppression for three 15-second measurements during a variety of stimulation frequencies in 11 ET patients treated with VIM DBS. Stimulation frequencies at or above 100 Hz produced maximal benefit; higher frequencies provided no additional benefit. If this short-term measure predicts long-term response in routine activities at home, then this stimulation frequency setting will prolong battery half-life compared to higher frequency settings. These findings suggest that ET patients treated with VIM DBS may receive adequate benefit from stimulation frequencies about 100 Hz and this setting compared to commonly used higher settings will prolong battery life of surgically implanted pulse generators.

Aged↗
PubMed2006

Percutaneous transvenous embolization of a dural arteriovenous fistula through a mastoid emissary vein. Technical note.

Definitive endovascular treatment of dural arteriovenous fistulas (DAVFs) requires obliteration of the site of the fistula: either the diseased dural sinus or the pial vein. Access to this site is often limited by occlusion of the sinus proximal and distal to the segment containing the fistula. The authors describe a technique in which the mastoid emissary vein is used to gain access to a Borden-Shucart Type II DAVF in the transverse-sigmoid sinus. Recognition of this route of access, if present, may facilitate endovascular treatment of these lesions. Access to the transverse sinus via this approach can be straightforward and may be underused.

Catheterization, Peripheral↗
PubMed2005

Gamma knife radiosurgery for trigeminal neuralgia: the Washington University initial experience.

Seventy-three patients were evaluated for the changes in pain relief, numbness and paresthesias after Gamma Knife radiosurgery to a maximum dose of 76-87 Gy for trigeminal neuralgia. Patients experienced pain relief as follows: 59% attained complete pain relief without prior surgery (33% with prior surgery); 25% achieved > or = 50% pain reduction (28% with prior surgery); 11% of surgery patients obtained minor pain relief, and 16% of patients without surgery had no relief (28% with prior surgery). Level of pain decreased rapidly within 6 weeks after radiosurgery. Numbness/paresthesias developed slowly over the first 12-15 months. Bothersome levels were experienced by 15% of the patients without prior surgery (22% with prior surgery). Comparison of the occurrence of numbness/paresthesias, with respect to prior surgery, was not statistically significant. Only 2% of all patients had persistently bothersome side effects. In conclusion, radiosurgery is an effective treatment of trigeminal neuralgia, especially for those patients not having prior surgery.

Adult↗
PubMed2005

Postoperative radiation therapy for grade II and III intracranial ependymoma.

PURPOSE: To retrospectively determine the long-term outcome of intracranial ependymoma patients treated with surgery and postoperative radiation therapy. METHODS AND MATERIALS: Sixty patients were treated at our institution between 1964 and 2000. Forty patients had World Health Organization Grade II ependymoma, and 20 patients had Grade III ependymoma. The median patient age was 10.7 years. The majority of patients were male (55%), had infratentorial tumors (80%), and had subtotal resections (72%). Postoperative radiation therapy was delivered to all patients to a median total dose of 50.4 Gy. Craniospinal radiation therapy was used in the earlier era in only 12 patients (20%). RESULTS: The median follow-up of surviving patients was 12.5 years. The 5-year and 10-year disease-free survival rates for all patients were 58.4% and 49.5%, respectively. The 5-year and 10-year overall survival rates for all patients were 71.2% and 55.0%, respectively. Supratentorial tumor location was independently associated with a worse disease-free survival. Subtotal resection and supratentorial location predicted a worse overall survival, but this failed to reach statistical significance. No statistically significant effect on prognosis was observed with tumor grade, patient age, or radiation dose or volume. CONCLUSION: Our long-term follow-up indicates that half of ependymoma patients will have disease recurrences, indicating the need for more effective treatments.

Adolescent↗
PubMed2005

Retinamide-induced apoptosis in glioblastomas is associated with down-regulation of Bcl-xL and Bcl-2 proteins.

Glioblastomas are among the most difficult neoplasms to treat with continued poor prognosis for long-term survival. Glioblastomas have developed effective mechanisms to resist chemotherapy including levels anti-apoptotic proteins, Bcl-xL and Bcl-2. Chemotherapy agents that promote down-regulation of Bcl-xL and Bcl-2 may enhance sensitivity to chemotherapy in glioblastomas. The ability of the synthetic retinoid N-(4-hydroxyphenyl) retinamide to modulate these anti-apoptotic proteins and to enhance apoptosis and chemotherapy was examined in glioblastoma cells. Expression of Bcl-2 family member proteins Bcl-xL and Bcl-2 were assessed in glioblastomas from three cell lines including U87, U251, and U138. Cells were treated with either retinamide alone or in combination with the chemotherapy agent, BCNU. The incidence of apoptosis was determined with flow cytometry analysis (FACS). Based on Western blots the levels of Bcl-2 and Bcl-xL were decreased in glioblastoma cells after treatment with retinamide. Retinamide treatment resulted in increased ratios of deamidated verses transamidated levels of Bcl-xL in U87 cells. BCNU chemotherapy combined with retinamide markedly down-regulated levels of both Bcl-xL and Bcl-2 proteins in glioblastoma and enhanced the incidence of apoptosis in U87 cells. These studies demonstrate that modulation of levels of the anti-apoptotic proteins, Bcl-xL and Bcl-2, may enhance the sensitivity of glioblastoma toward chemotherapy.

Antineoplastic Agents↗
PubMed2005

Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase 2.

3-halo-4,5-dihydroisoxazoles are attractive warheads for the selective inhibition of nucleophilic active sites in biological systems. A series of 3-bromo-4,5-dihydroisoxazole compounds were prepared and tested for their ability to irreversibly inhibit human transglutaminase 2 (TG2), an enzyme that plays an important role in the pathogenesis of diverse disorders including Celiac Sprue and certain types of cancers. Several compounds showed high specificity for human TG2 (k(inh)/K(I) > 2000 min(-1)M(-1)) but essentially no reactivity (k < 1 min(-1)M(-1)) toward physiological thiols such as glutathione. The pharmacokinetic and pharmacodynamic properties of a prototype dihydroisoxazole inhibitor, 1b, were evaluated; in mice the compound showed good oral bioavailability, short serum half-life and efficient TG2 inhibition in small intestinal tissue, and low toxicity. It also showed excellent synergism with N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU, carmustine) against refractory glioblastoma tumors in mice. A fluorescent dihydroisoxazole inhibitor 5 facilitated microscopic visualization of TG2 endocytosis from the extracellular surface of HCT-116 cells. Together, these findings demonstrate the promise of dihydroisoxazole compounds as probes for the biology of TG2 and its role in human disease.

Animals↗
PubMed2005

Tissue transglutaminase 2 inhibition promotes cell death and chemosensitivity in glioblastomas.

Tissue transglutaminase 2 belongs to a family of transglutaminase proteins that confers mechanical resistance from proteolysis and stabilizes proteins. Transglutaminase 2 promotes transamidation between glutamine and lysine residues with the formation of covalent linkages between proteins. Transglutaminase 2 also interacts and forms complexes with proteins important in extracellular matrix organization and cellular adhesion. We have identified the novel finding that treatment of glioblastoma cells with transglutaminase 2 inhibitors promotes cell death and enhances sensitivity to chemotherapy. Treatment with either the competitive transglutaminase 2 inhibitor, monodansylcadaverine, or with highly specific small-molecule transglutaminase 2 inhibitors, KCA075 or KCC009, results in induction of apoptosis in glioblastoma cells. Treatment with these transglutaminase 2 inhibitors resulted in markedly decreased levels of the prosurvival protein, phosphorylated Akt, and its downstream targets. These changes promote a proapoptotic profile with altered levels of multiple intracellular proteins that determine cell survival. These changes include decreased levels of the antiapoptotic proteins, survivin, phosphorylated Bad, and phosphorylated glycogen synthetase kinase 3beta (GSK-3beta), and increased levels of the proapoptotic BH3-only protein, Bim. In vivo studies with s.c. murine DBT glioblastoma tumors treated with transglutaminase 2 inhibitors combined with the chemotherapeutic agent, N-N'-bis (2-chloroethyl)-N-nitrosourea (BCNU), decreased tumor size based on weight by 50% compared with those treated with BCNU alone. Groups treated with transglutaminase 2 inhibitors showed an increased incidence of apoptosis determined with deoxynucleotidyl transferase-mediated biotin nick-end labeling staining. These studies identify inhibition of transglutaminase 2 as a potential target to enhance cell death and chemosensitivity in glioblastomas.

Animals↗
PubMed2004

Effect of stimulation frequency on tremor suppression in essential tremor.

We sought to determine the effect of deep brain stimulation (DBS) frequency on tremor suppression in essential tremor (ET) patients with deep brain stimulators implanted in the ventral intermediate nucleus (VIM) of the thalamus. A uniaxial accelerometer was used to measure tremor in the right upper extremity of subjects with a diagnosis of ET who had DBS electrodes implanted in the left VIM. The root-mean-square acceleration was used as the index of tremor magnitude and normalized to the OFF DBS condition. There was a highly significant inverse sigmoidal relationship between stimulation frequency and normalized tremor acceleration (X(2)/DoF = 0.42, r(2) = 0.997). Tremor acceleration had a nearly linear response to stimulation frequencies between 45 and 100 Hz with little additional benefit above 100 Hz. These findings have two important implications. Clinically, frequency of thalamic stimulation is an important variable for optimal tremor control with maximal benefit achieved with 100 to 130 Hz in most patients. Second, thalamic DBS provides tremor benefit in a graded manner and is not an all-or-nothing phenomenon.

Adult↗
PubMed2004

The efficacy of stereotactic radiosurgery in the management of intracranial ependymoma.

OBJECTIVE: A retrospective analysis was performed to determine the outcome of patients with intracranial ependymoma treated with stereotactic radiosurgery (SRS). METHODS: Nine ependymoma patients have been treated with SRS (four with linear accelerator and five with Gamma Knife) since 1990. Two patients had WHO grade III tumors, and the remaining seven had WHO grade II tumors. Eight of nine patients received external beam radiation therapy at some point prior to radiosurgery to a total median dose of 54 Gy. The radiosurgery dose ranged from 14 to 20 Gy. RESULTS: The median follow-up was 28 months. The median age of patients at diagnosis was 35 years. Four patients developed progressive disease following radiosurgery, and two patients have died of progressive disease. The 3-year relapse-free survival was 55.6%. The 3-year overall survival was 71.1%. Patients treated with radiosurgery as a component of initial treatment (generally as a boost following external beam) had an improved relapse-free survival (100%) compared to those treated with radiosurgery to salvage an external beam local failure (20%). CONCLUSION: SRS is an effective treatment for intracranial ependymoma. Further clinical trials are warranted incorporating radiosurgery as a component of initial management in selected ependymoma patients.

Adolescent↗
PubMed2004

BCNU down-regulates anti-apoptotic proteins bcl-xL and Bcl-2 in association with cell death in oligodendroglioma-derived cells.

Oligodendroglial differentiation in gliomas is associated with enhanced sensitivity to chemotherapy. Antiapoptotic proteins, Bcl-xL and Bcl-2, are over-expressed in early passage cell lines derived from glioblastomas. Down-regulation of Bcl-xL and Bcl-2 with DNA antisense oligonucleotides promotes cell death in glioblastoma cells. Changes of expression of Bcl-xL and Bcl-2 after chemotherapy treatment have not been studied in glioma subtypes. The current experiments correlate decreased expression of both Bcl-xL and Bcl-2 after BCNU chemotherapy and cell death in two oligodendroglioma-derived cell lines. Expression of Bcl-2 family member proteins Bcl-xL, Bcl-2, and Bax were assessed in glioma cells both before and after chemotherapy treatment. Cell survival was assessed with a crystal violet bioassay. Levels of expression of Bcl-2 and Bcl-xL were elevated in two early passage oligodendroglioma-derived cell lines compared with a non-neoplastic glial cell line. BCNU chemotherapy markedly down-regulated expression of Bcl-xL and Bcl-2 proteins in both oligodendroglioma-derived cell lines. Changes in expression of Bcl-xL and Bcl-2 were associated with the increased sensitivity to chemotherapy. There were no changes noted in expression of Bax after BCNU treatment. Modulation of expression of the anti-apoptotic proteins, Bcl-xL and Bcl-2, in the two oligodendroglioma-derived cell lines was associated with increased sensitivity to BCNU chemotherapy. Down-regulation of Bcl-xL and Bcl-2 resulted in reversal of the ratio of Bax/Bcl-xL and Bax/Bcl-2 and enhanced cell death after treatment with BCNU. Mechanisms that control expression of the anti-apoptotic proteins Bcl-xL and/or Bcl-2 may be effective targets in treatment strategies in patients with malignant gliomas.

Antineoplastic Agents, Alkylating↗
PubMed2004

Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells.

The mechanism of lovastatin-induced cell death was examined in three established human glioblastoma cell lines; U87, U251, and U138. Changes in potential modifiers of apoptosis, including Bcl-2 family proteins and MAP kinase targets after such lovastatin treatment, were evaluated. Lovastatin (5 microm) treatment causes extensive cell death in two of the cell lines, U87 and U251; but only minimal in a third, U138. Lovastatin-induced death occurs in correlation with significantly increased levels of the BH3-only protein, Bim. The up-regulation of Bim levels was directly associated with an increased incidence of apoptosis. Lovastatin treatment in U87 cells results in activation of targets of three major mitogen-activating protein kinase cascades including Erk1/2, JNK and p38. Changes in levels of Bim, as well as increase phosphorylation of Erk1/2, c-jun, and p38 are all prevented by co-incubation of lovastatin and the isoprenylation metabolite, geranylgeranyl pyrophosphate. Inhibition of the MAP kinase pathways failed to block the increased expression of Bim expression or cell death. Further elucidation of the mechanisms of lovastatin-induced up-regulation of Bim and apoptosis in glioblastoma cells are important in determining a potential role for lovastatin as a chemotherapy agent.

Antineoplastic Agents↗
PubMed2003

Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death.

The functions of the antiapoptotic proteins Bcl-2 and Bcl-xL were examined in glioblastoma cells. Expression of both Bcl-2 and Bcl-xL were found to be elevated in protein lysates from seven early passage cell lines derived from human glioblastoma tumors compared with non-neoplastic glial cells. Down-regulation of both bcl-2 and bcl-xL expression in glioblastoma cell lines U87 and NS008 with bcl-2/bcl-xL bispecific antisense oligonucleotide resulted in spontaneous cell death. The mechanism of cell death was partially caspase-dependent. Executioner caspase 6 and caspase 7, but not caspase 3, were involved in apoptosis induced by bcl-2/bcl-xL antisense treatment. Interestingly, western blots failed to demonstrate expression of caspase 3 in two of the seven glioblastoma cell lines examined. The data support the hypothesis that Bcl-2 and Bcl-xL are important in preventing cell death in glioblastoma cells. It also suggests that there are functional pathways capable of successful completion of caspase-dependent cell death in gliomas. These findings support a potential role of bcl-2/bcl-xL bispecifc antisense oligonucleotide therapy as a treatment strategy to enhance caspase-dependent cell death in patients with glioblastoma.

Caspases↗
PubMed2002

Diffusion-weighted MR imaging in the preoperative assessment of brain abscesses.

BACKGROUND: Diffusion-weighted MR imaging (DWI) has recently shown promise in differentiating ring-enhancing lesions such as brain abscess and malignant neoplasm. The ability of DWI to strongly suggest brain abscess enables a neurosurgeon to alter stereotactic planning to optimize diagnosis. We report our experience with DWI in 5 patients with lesions on MR imaging and review the literature to assess the usefulness of this technique in the preoperative evaluation of cerebral abscess. METHODS: The MR images of 5 patients presenting with ring-enhancing lesions that ultimately proved to be brain abscesses were retrospectively reviewed. In addition to standard MR sequences, trace DWI and apparent diffusion coefficient (ADC) calculations were performed on all patients. Additionally, 15 recently published articles or references in press concerning DWI in cerebral abscesses were reviewed. RESULTS: All lesions were markedly hyperintense on DWI and had diminished ADC. Thirty-eight of 39 previously reported abscesses were hyperintense on DWI with reduced ADC. Of 165 nonpyogenic lesions with DWI findings, 87 were hypointense or isointense, 78 lesions had variable hyperintensities, and few manifested the degree of hyperintensity observed with abscesses. Most of these included chordomas and epidermoids, which are not likely to be confused with abscesses. CONCLUSIONS: Restricted water diffusion, as indicated by hyperintensity on DWI and low ADC, in ring-enhancing lesions assists in differentiating brain abscess from necrotic tumor. This information facilitates stereotactic surgical planning: abscesses should be preferentially centrally aspirated, whereas necrotic brain tumors should have diagnostic tissue biopsied from cavity walls. Although not definitive for brain abscess, restricted water diffusion is an important MR imaging sign and is useful in neurosurgical treatment strategies for ring-enhancing lesions.

Adult↗
PubMed2002

Frameless stereotaxy without rigid pin fixation during awake craniotomies.

OBJECTIVE: The accuracy and precision of resection with awake brain mapping is augmented when combined with frameless stereotaxy. Frameless stereotactic assisted surgery, however, typically involves immobilization in Mayfield pins. Rigid fixation, however, may be problematic for individuals undergoing awake craniotomy. We describe an alternate method of frameless stereotaxy without the use of pin fixation. METHODS: The MRI fiducials are placed in proximity to the proposed incision and prepared and draped in the operative field. After craniotomy, the epidural skull clamp (standardly used to support the electrode holder during corticography) is attached. Using the Stealth Navigational System, a spinal reference arc is then clamped onto the skull clamp base. After the fiducials and arc are registered, the probe is used for frameless guidance. RESULTS: In 14 of 15 cases (93%), this technique was successful. One case failed because of close proximity of the fiducials to the incision. The accuracy of the 14 successful cases was less than 4 mm. The error within the lesion itself was always less than 2 mm. Overall, these results are comparable to those achieved using a Mayfield head holder. In all tumor cases, postoperative imaging concurred with intraoperative assessment of a total versus subtotal resection. CONCLUSIONS: By affixing the spinal arc to the skull, the complications and discomfort associated with pin fixation are avoided completely. The patient is free to move without affecting the accuracy. The spine arc, in combination with the skull clamp, provides an efficient, well-tolerated, and accurate method of frameless navigation for the awake patient undergoing craniotomy.

Awareness↗
PubMed2002

Long-term outcome after angioplasty for symptomatic extracranial carotid stenosis in poor surgical candidates.

BACKGROUND AND PURPOSE: The optimal treatment of patients with symptomatic carotid stenosis who are poor surgical candidates is uncertain. The purposes of this study were to report the long-term outcome after angioplasty in a series of these patients and to compare these data with historical control data from the North American Symptomatic Carotid Endarterectomy Trial (NASCET). METHODS: We identified 42 consecutive patients with >70% carotid stenosis and ipsilateral ischemic symptoms within 120 days of treatment with angioplasty. All were considered poor surgical candidates by experienced surgeons. Baseline epidemiological stroke risk factors were obtained from review of medical records. Follow-up was from clinic records and by telephone. RESULTS: Baseline epidemiological stroke risk factors were similar to those of medically treated NASCET patients. Angioplasty patients tended to have higher degrees of stenosis (45% with >90% stenosis versus 24% in NASCET) and more frequent contralateral stenosis or occlusion (30% versus 9%) than NASCET patients. Three patients suffered procedural strokes; 2 of the 3 made nearly complete recoveries. One additional patient suffered a central retinal occlusion 48 hours after angioplasty. No ipsilateral strokes occurred during the mean follow-up period of 1.7 years. Three patients were lost to follow-up. The cumulative risk of stroke was 9.5% (4 of 42) compared with 26% at 2 years for medically treated patients in NASCET. CONCLUSIONS: These pilot data suggest a beneficial effect of angioplasty for patients with high-grade symptomatic carotid stenosis who are not good surgical candidates.

Adult↗
PubMed2002

Postprocedure ischemic events after treatment of intracranial aneurysms with Guglielmi detachable coils.

OBJECT: Ischemic stroke or transient ischemic attack (TIA) may occur after the treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs). The purpose of the present study is to investigate possible risk factors for thromboembolic events and to determine their frequency and time course. METHODS: The records of 178 consecutive patients with 193 treated intracranial saccular aneurysms were reviewed. A total of 159 GDC procedures were performed to treat 143 aneurysms in 133 of those patients who were in good neurological condition, allowing clinical detection of postprocedure ischemic events (TIA or stroke). The association of clinical, anatomical, and pharmacological factors with intraprocedure intraarterial thrombus and with postprocedure ischemic events was investigated by using uni- and multivariate analyses. Thrombus protruding into the parent artery was noted during six of 159 GDC procedures, resulting in a clinical deficit in one patient. No factor was associated with intraprocedure intraarterial thrombus. Ten postprocedure ischemic events occurred in nine patients. Seven events occurred within 24 hours, and three events occurred between 24 hours and 58 days. Aneurysm diameter and protruding coils were significant independent predictors of postprocedure ischemic events in multivariate analysis (both p = 0.02). The actuarial risk of stroke was 3.8%. CONCLUSIONS: Larger aneurysm diameter and protruding loops of coils are associated with postprocedure ischemic events after GDC placement. It is unlikely that GDC-treated aneurysms retain thromboembolic potential beyond 2 months.

Adult↗