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D Schiff

Publications and source records attributed to D Schiff.

At least 19 recordsLinked to original sources
PubMed2006

Farnesylthiosalicylic acid induces caspase activation and apoptosis in glioblastoma cells.

Primary glioblastomas (GBMs) commonly overexpress the oncogene epidermal growth factor receptor (EGFR), which leads to increased Ras activity. FTA, a novel Ras inhibitor, produced both time- and dose-dependent caspase-mediated apoptosis in GBM cell lines. EGFR-mediated increase in 3H-thymidine uptake was inhibited by FTA. FACS analysis was performed to determine the percent of apoptotic cells. The sub-Go population of GBM cells was increased from 4.5 to 13.8% (control) to over 45-53.6% in FTA-treated cells within 24 h. Furthermore, FTA also increased the activities of both caspase-3 and -9, and PARP cleavage. Treatment of GBMs with FTA before or after EGF addition to the cultures blocked phosphorylation of Akt and mitogen-activated protein kinases (MAPK). FTA also significantly reduced the amount of EGF-induced Ras-GTP as reflected by a decrease in the level of Ras bound to Raf-RBD-GST. This study demonstrates that inhibition of Ras methylation may provide a therapeutic target for the treatment of GBMs overexpressing EGFR.

Antineoplastic Agents↗
PubMed2001

Gliomas arising in organ transplant recipients: an unrecognized complication of transplantation?

Reported are six cases of glioma, diagnosed in the last 10 years, arising in organ transplant recipients. Five transplant recipients developed glioblastoma, and one developed oligodendroglioma. None had other risk factors for glioma. Gliomas must be considered in the differential diagnosis of space-occupying lesions in transplant recipients. Although these cases may represent coincidence, the putative HIV-glioma association suggests a pathogenetic link to immunosuppression.

Aged↗
PubMed2001

Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine.

PURPOSE: To assess thiopurine S-methyltransferase (TPMT) phenotype and genotype in patients who were intolerant to treatment with mercaptopurine (MP) or azathioprine (AZA), and to evaluate their clinical management. PATIENTS AND METHODS: TPMT phenotype and thiopurine metabolism were assessed in all patients referred between 1994 and 1999 for evaluation of excessive toxicity while receiving MP or AZA. TPMT activity was measured by radiochemical analysis, TPMT genotype was determined by mutation-specific polymerase chain reaction restriction fragment length polymorphism analyses for the TPMT*2, *3A, *3B, and *3C alleles, and thiopurine metabolites were measured by high-performance liquid chromatography. RESULTS: Of 23 patients evaluated, six had TPMT deficiency (activity < 5 U/mL of packed RBCs [pRBCs]; homozygous mutant), nine had intermediate TPMT activity (5 to 13 U/mL of pRBCs; heterozygotes), and eight had high TPMT activity (> 13.5 U/mL of pRBCs; homozygous wildtype). The 65.2% frequency of TPMT-deficient and heterozygous individuals among these toxic patients is significantly greater than the expected 10% frequency in the general population (P <.001, chi(2)). TPMT phenotype and genotype were concordant in all TPMT-deficient and all homozygous-wildtype patients, whereas five patients with heterozygous phenotypes did not have a TPMT mutation detected. Before thiopurine dosage adjustments, TPMT-deficient patients experienced more frequent hospitalization, more platelet transfusions, and more missed doses of chemotherapy. Hematologic toxicity occurred in more than 90% of patients, whereas hepatotoxicity occurred in six patients (26%). Both patients who presented with only hepatic toxicity had a homozygous-wildtype TPMT phenotype. After adjustment of thiopurine dosages, the TPMT-deficient and heterozygous patients tolerated therapy without acute toxicity. CONCLUSION: There is a significant (> six-fold) overrepresentation of TPMT deficiency or heterozygosity among patients developing dose-limiting hematopoietic toxicity from therapy containing thiopurines. However, with appropriate dosage adjustments, TPMT-deficient and heterozygous patients can be treated with thiopurines, without acute dose-limiting toxicity.

Adolescent↗
PubMed2001

Single Brain Metastasis.

The management of single brain metastases has evolved substantially over the last decade. The advent of triple-dose contrast-enhanced MRI scans has improved the radiologists' capacity to resolve small tumors, and, thereby, has resulted in a declining percentage of brain metastases classified as single. Only 25% to 30% of brain metastases are single; single brain metastases in the absence of systemic metastases are termed solitary. Randomized trials suggest that patients not in imminent danger of herniation are best managed initially with dexamethasone 2 to 4 mg administered orally twice daily. The routine use of prophylactic anticonvulsants is discouraged. Patients with refractory progressive systemic tumor likely to prove fatal within 3 to 6 months should receive fractionated whole brain radiotherapy. Patients with highly radiosensitive primary tumors such as small cell lung cancer, lymphoma, and germinoma should also receive whole brain radiotherapy. Patients with inactive or controllable systemic cancer and good performance status benefit from the addition of local strategies like surgery or radiosurgery to whole brain radiotherapy. Although surgery and radiosurgery have not been compared in a randomized controlled trial, data suggest that results are similar. Consequently, for most metastases that fall within the size constraints of radiosurgery (3.5 cm or smaller in diameter), radiosurgery is preferred for its relatively noninvasive nature. Patients with larger or cystic tumors, with obstructive hydrocephalus, or neurologic instability despite corticosteroids are best treated with craniotomy. Fractionated whole brain radiation following surgical or radiosurgical management of single brain metastasis appears to decrease the risk of recurrent brain metastasis, although it has not been shown to improve survival. We recommend its use in most patients, although patients with tumors likely to be highly resistant to fractionated radiotherapy or at high risk of radiation neurotoxicity may reasonably defer its use.

Journal Article↗
PubMed2001

Intramedullary spinal cord metastasis (ISCM) in renal cell carcinoma: a series of six cases.

Intramedullary spinal cord metastasis (ISCM) has been infrequently diagnosed during the clinical course of renal cell carcinoma (RCC). With the advent of more sensitive diagnostic procedures including magnetic resonance imaging (MRI), more cases of ISCM have been documented. The management of these cases is particularly challenging as lack of prompt intervention often results in irreversible progressive neurological deficits. We describe the management and clinical course in six patients with RCC who developed ISCM. Two of these patients were treated surgically while four were treated with radiation therapy (RT). Although no major improvements in neurological function were noted, stabilizations were common. This prolonged their ability to live independently, a matter of utmost importance in these terminally ill patients.

Adult↗
PubMed1999

Metastatic spinal cord compression in patients with colorectal cancer.

BACKGROUND: A retrospective study was performed to examine the outcome of patients with colorectal cancer who had metastatic spinal cord compression (MSCC) and received radiation therapy (RT). METHODS: Forty episodes of MSCC were treated with external beam RT in 34 patients with metastatic colorectal cancer. The median total dose was 3000 cGy (1800-4750 cGy), and the daily fraction size was 300 cGy (151-400 cGy). All patients were followed until death. RESULTS: Median overall survival for the entire cohort was 4.1 months. Of 21 patients ambulatory before RT, 20 remained ambulatory after treatment, whereas only 2 of 9 patients who were nonambulatory regained full ambulatory status. Patients with rectal primary tumors had improved survival (median 7.9 months) compared with those who had colon primary tumors (2.7 months) (P = 0.002). Patients who received a total dose of more than 3000 cGy had a better survival (7 months) than those who received 3000 cGy or less (3.1 months) (P = 0.024). There was a trend for improved survival in patients fully ambulatory at diagnosis (P = 0.056) and after RT (P = 0.07). Unlike other primary sites in which approximately 70% of lesions are located in the thoracic spine, the location of epidural metastasis in colorectal primary tumors was most frequently in the lumbar spine (55% of lesions). CONCLUSIONS: Prognostic features and outcomes for MSCC with primary colorectal cancer are similar to those for other primary sites. There is a suggestion that rectal primary tumors may be associated with an improved outcome compared with colon primary tumors. Patients who received more than 3000 cGy total dose had a longer survival than those who received lower total doses.

Adult↗
PubMed1999

Morbidity and survival after 1,3-bis(2-chloroethyl)-1-nitrosourea wafer implantation for recurrent glioblastoma: a retrospective case-matched cohort series.

OBJECTIVE: To determine the risks and survival benefit associated with implantation of an absorbable, 1,3-bis(2chloroethyl)-1-nitrosourea-impregnated polymer wafer, we prospectively studied patients with recurrent glioblastoma multiforme and compared them with a demographically matched cohort group. METHODS: Over a 29-month period, 62 patients underwent operations. All had tumor growth despite standard treatment, a Karnofsky performance score of > or =70, and histopathological confirmation of glioblastoma. Seventeen patients underwent gross total resection with placement of 1,3-bis(2-chloroethyl)-1-nitrosourea wafers (wafer group) at a median 44 weeks from diagnosis (6 women, 11 men; median age, 56 years). A cohort group of 45 patients undergoing surgery for recurrent glioblastoma during the same time period, but not receiving wafers, was identified. Surgery was performed at a median 47 weeks from diagnosis (14 women, 31 men; median age, 54 years). RESULTS: Within 6 weeks of surgery, 13 complications were identified in 8 patients in the wafer group. In the cohort group, 6 patients sustained 8 complications. We were unable to identify any survival advantage using Kaplan-Meier analysis. In the wafer group, median survival was 58 weeks from diagnosis and 14 weeks from wafer implantation. In the cohort group, median survival was 97 weeks from diagnosis and 50 weeks from operation. CONCLUSION: 1,3-bis(2-chloroethyl)-1-Nitrosourea wafer implantation for recurrent glioblastoma was associated with a higher risk of postoperative complications, particularly those related to infection and wound healing. No clear survival benefit associated with wafer implantation was identified.

Antineoplastic Agents, Alkylating↗
PubMed1999

Phase II study of phenylacetate in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report.

PURPOSE: To determine the response rate, time to treatment failure, and toxicity of phenylacetate in patients with recurrent malignant glioma and to identify plasma concentrations achieved during repeated continuous infusion of this agent. PATIENTS AND METHODS: Adult patients with recurrent malignant glioma were treated with phenylacetate. The schedule consisted of a 2-week continuous, intravenous infusion followed by a 2-week rest period (14 days on, 14 days off). A starting dose of 400 mg/kg total body weight per day of phenylacetate was initially used and subsequently changed to 400 mg/kg/d based on ideal body weight. Intrapatient dose escalations were allowed to a maximum of 450 mg/kg ideal body weight/d. Tumor response was assessed every 8 weeks. The National Cancer Institute common toxicity criteria were used to assess toxicity. Plasma concentrations achieved during the patients' first two 14-day infusions were assessed. RESULTS: Forty-three patients were enrolled between December 1994 and December 1996. Of these, 40 patients were assessable for toxicity and response to therapy. Reversible symptoms of fatigue and somnolence were the primary toxicities, with only mild hematologic toxicity. Thirty (75%) of the 40 patients failed treatment within 2 months, seven (17.5%) had stable disease, and three (7.5%) had a response defined as more than 50% reduction in the tumor. Median time to treatment failure was 2 months. Thirty-five patients have died, with a median survival of 8 months. Pharmacokinetic data for this dose schedule showed no difference in the mean plasma concentrations of phenylacetate between weeks 1 and 2 or between weeks 5 and 6. CONCLUSION: Phenylacetate has little activity at this dose schedule in patients with recurrent malignant glioma. Further studies with this drug would necessitate an evaluation of a different dose schedule.

Adult↗
PubMed1999

Risk of injury to cranial nerves after gamma knife radiosurgery for skull base meningiomas: experience in 88 patients.

OBJECT: In this study the authors sought to determine the neurological risks and potential clinical benefits of gamma knife radiosurgery for skull base meningiomas. METHODS: A consecutive series of 88 patients harboring skull base meningiomas were treated between 1990 and 1996 by using the Leksell gamma knife in a prospective clinical study that included a strict dose-volume protocol. Forty-nine patients had previously undergone surgery, and six had received external-beam radiotherapy. The median treatment volume was 10 cm3, and the median dose to the tumor margin was 16 Gy. The radiosurgical dosage to the optic nerve, the cavernous sinus, and Meckel's cave was calculated and correlated with clinical outcome. The median patient follow-up time was 35 months (range 12-83 months). Two tumors (2.3%) progressed after radiosurgery; the progression-free 5-year survival rate was 95%. At last follow-up review, 60 (68%) tumors were smaller and 26 (29.5%) remained unchanged. Clinical improvement (in vision, trigeminal pain, or other cranial nerve symptoms) occurred in 15 patients. Functioning optic nerves received a median dose of 10 Gy (range 1-16 Gy), and no treatment-induced visual loss occurred. Among nine patients with new trigeminal neuropathy, six received doses of more than 19 Gy to Meckel's cave. CONCLUSIONS: Gamma knife radiosurgery appeared to be an effective method to control the growth of most skull base meningiomas in this intermediate-term study. The risk of trigeminal neuropathy seemed to be associated with doses of more than 19 Gy, and the optic apparatus appeared to tolerate doses greater than 10 Gy. Considering the risks to cranial nerves associated with open surgery for comparable tumors, the authors believe that gamma knife radiosurgery is a useful method for the management of properly selected recurrent, residual, or newly diagnosed skull base meningiomas.

Adult↗
PubMed1998

Neuroimaging and treatment implications of patients with multiple epidural spinal metastases.

BACKGROUND: Although multiple spinal epidural metastases (MEMs) commonly occur in cancer patients, their clinical significance remains uncertain. The authors attempted to ascertain the incidence of MEMs and their association with the completeness of spinal imaging by magnetic resonance (MR) scanning versus myelography to determine how often they are missed because of incomplete spinal imaging and to assess their prognostic and treatment implications. METHODS: A review of 337 epidural spinal cord compression (ESCC) cases seen at the Mayo Clinic between 1985 and 1993 was conducted. RESULTS: ESCC patients undergoing myelography only were significantly more likely to undergo complete spinal imaging (CSI)than patients undergoing either MR scan only or both imaging modalities (P < 0.0001). MEMs were detected in 32% of patients undergoing CSI and 18% of patients with incomplete spinal imaging (P=0.02). Failure to image the cervical spine in patients with symptomatic thoracic or lumbar epidural lesions would have missed secondary epidural lesions in only 1% of patients; however, this figure increased to 21% for failure to image either the thoracic or lumbosacral spine when symptomatic disease was located elsewhere. Radiation oncologists included secondary epidural deposits in treatment ports in 93% of MEM cases. In a multivariate model, the presence of MEMs was an independent prognostic factor for poorer survival. CONCLUSION: The incidence of MEMs in patients with ESCC is approximately 30%, and their presence frequently alters treatment plans. It appears safe to forgo cervical spine MR scanning in patients with radiographically verified thoracic or lumbar ESCC; however, careful imaging of the thoracic and lumbar spine should be considered in all ESCC patients to detect MEMs.

Adolescent↗
PubMed1998

Risk factors for primary central nervous system lymphoma: a case-control study.

BACKGROUND: The incidence of primary central nervous system lymphoma (PCNSL) has increased over time in both immunocompetent and immunodeficient individuals. The reasons for the increase among immunocompetent patients are unclear. METHODS: The authors conducted a case-control study of PCNSL at the Mayo Clinic based on cases from local community and referral practices. Cases were all PCNSL patients without immunodeficiency diagnosed between 1975 and 1994 (n = 109). Two groups of controls were selected from the same referral practice, namely, patients with other cancer (cancer controls; n = 101), and patients with a different neurologic disease (neurologic controls; n = 109) seen at our institution during the same time period. RESULTS: PCNSL was significantly associated with lower education when cases were compared with cancer controls but only suggestively when cases were compared with neurologic controls. PCNSL cases were less likely to have had a history of tonsillectomy or oral contraceptive use compared with both control groups. The findings regarding autoimmune disorders and cardiovascular diseases were inconsistent for the two control groups. Neither farming nor prior personal or family history of cancer appeared to be risk factors for PCNSL. CONCLUSIONS: The findings of this study warrant further investigation of tonsillectomy and oral contraceptives as possible factors for PCNSL.

Adolescent↗
PubMed1998

CD8(+), radiosensitive T cells of parental origin, oppose cells capable of down-regulating cytotoxicity in murine acute lethal graft-versus-host disease.

Murine graft-versus-host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third party alloantigen is seen in acute lethal GVH disease. In contrast to this, in chronic GVH disease there is polyclonal B cell activation, auto-antibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host veto cell which protects the F1 mouse from parental anti-F1 cytotoxicity in mice undergoing CGVH disease. This cell could be induced in vitro or in vivo in CGVH disease. Using an in vitro system, we now demonstrate that a CD4(+), radiation-sensitive, T cell does emerge in acute lethal GVH disease which is capable of down-regulating cytotoxicity. The cell does not appear to be a veto cell in that it attenuates cytotoxicity directed against nonself alloantigen. The function of this cell does not appear to be influenced by minor lymphocyte stimulatory gene products. We further report that, in ALGVH disease, regulation by this cell is not readily apparent due to the emergence of a CD8(+) T cell of parental (B6) origin, which opposes its action.

Acute Disease↗
PubMed1998

Herpes simplex encephalitis (HSE) and the immunocompromised: a clinical and autopsy study of HSE in the settings of cancer and human immunodeficiency virus-type 1 infection.

Although herpes simplex encephalitis (HSE) is not regarded as an opportunistic infection, the occurrence of HSE in immunocompromised patients has been documented and the suggestion made that unusual clinical and neuropathologic features characterize the disorder in this population. To further characterize HSE as it affects the immunodeficient, the authors reviewed the clinical and pathological findings in three immunocompromised patients with autopsy-proven HSE. Two patients had cancer (one with lymphoma and another with glioblastoma multiforme), one was known to be human immunodeficiency virus-type 1 (HIV-1)-seropositive and a second was suspected of harboring underlying HIV-1 infection. Two were receiving dexamethasone at onset of HSE. All had fever, mental status changes and new, focal neurological deficits or worsening of established deficits. Cerebrospinal fluid (CSF) pleocytosis was absent or minimal and head computerized tomographic (CT) scans, performed in all cases, were unrevealing. No patient was clinically suspected of having HSE, only one received acyclovir (for concurrent mucocutaneous herpes) and HSE played a major role in all deaths. Autopsy revealed an unusual form of HSE characterized by a noninflammatory, pseudoischemic histological presentation and the unexpected persistence of viral antigens in abundance despite survival beyond the clinical stage during which inflammatory responses usually peak and productive brain infection wanes. The incidence of HSE in the immunocompromised may be underestimated. Preexistent neurological disease, a noninflammatory CSF profile and negative CT scan may confound the diagnosis in this population, a typical clinical presentation notwithstanding. Increased clinical suspicion, the use of magnetic resonance imaging and polymerase chain reaction analysis of CSF for herpes simplex virus nucleic acid sequences may permit more rapid diagnosis and treatment. The absence of inflammatory infiltrates in some fatal cases of HSE suggests that an intact immune response is not requisite to the devastating neurological injury characteristic of this disorder.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Neurologic emergencies in cancer patients.

Neurologic emergencies are common among cancer patients and their incidence is increasing as patients live longer as a result of improved antineoplastic therapy. This article reviews acute neurologic complications in cancer patients. Among those complications reviewed are brain metastases, epidural spinal cord compression, leptomeningeal metastases, cerebrovascular disorders, complications of antineoplastic therapy, and paraneoplastic syndromes.

Antineoplastic Agents↗
PubMed1998

Neurologic perspectives of Crigler-Najjar syndrome type I.

Limited information exists on the neurologic sequelae of Crigler-Najjar syndrome type I despite this being the major morbidity of this rare autosomal recessive disorder of bilirubin conjugation that results in chronic unconjugated hyperbilirubinemia. Two patients with identical underlying genetic mutations resulting in Crigler-Najjar syndrome type I were assessed from a neurodevelopmental perspective in late childhood using age appropriate standardized measures. In addition, the English language literature of case reports and series describing the outcomes of patients with this disorder was reviewed (descriptive meta-analysis) and summarized with particular reference to neurologic symptomatology, pattern of neurologic disability, age of onset of symptoms, and therapeutic interventions. Despite radically different therapeutic interventions, our two patients did not differ in outcome measures. Review of the literature reveals distinct, often age-related, patterns of neurologic sequelae reflecting injury to basal ganglia, cerebellar, and likely hippocampal structures. Definitive prevention of the neurologic sequelae that often occur within the context of Crigler-Najjar syndrome type I requires that curative treatment (hepatic transplantation, presently, and gene therapy in the future) be applied prior to the possible onset of neurologic symptoms in adolescence.

Child↗