Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS: Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS: The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION: The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma.

BACKGROUND: Diagnosis of primary central nervous system lymphoma (PCNSL) is usually made by identifying malignant lymphocytes in the brain, cerebrospinal fluid (CSF), or vitreous. However, these cells are few and friable, and misdiagnosis can occur, even in properly prepared specimens. Recent data suggest that levels of interleukin 10 (IL-10) are elevated in the serum and vitreous of patients with non-Hodgkin lymphoma; levels of interleukin 6 (IL-6) are elevated in the vitreous of patients with intraocular inflammation unrelated to a malignant neoplasm. We investigated whether PCNSL involving the vitreous or CSF is associated with elevated ratios of IL-10 to IL-6. PATIENTS: Vitreous specimens were obtained from 5 patients with PCNSL involving the eye and from 13 control patients with intraocular inflammation not related to a malignant neoplasm; CSF specimens were obtained from 11 patients with PCNSL. RESULTS: Levels of IL-10 exceeded those of IL-6 in all 5 patients with intraocular lymphoma but in none of the 13 patients with uveitis (P < .001). In patients with PCNSL, levels of IL-10 exceeded those of IL-6 in 6 of 11 CSF samples with malignant cells compared with 7 of 53 samples without malignant cells (P = .01). The calculated odds ratio (OR) suggests that the risk for malignant involvement of the CSF is about 8 times higher when IL-10 levels exceed IL-6 levels. METHODS: Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay in both vitreous and CSF specimens. CONCLUSIONS: The occurrence of PCNSL in the eye was strongly associated with elevated vitreous levels of IL-10 relative to levels of IL-6. Moreover, among patients with diagnosed PCNSL, malignant cells were significantly more likely to be present in CSF when levels of IL-10 exceeded those of IL-6.

Intraocular levels of methotrexate after intravenous administration.

PURPOSE: To determine if adequate intraocular levels of methotrexate are achieved after intravenous administration. METHODS: After intravenous administration, methotrexate levels were determined in the serum, the anterior chamber, and the cerebrospinal fluids of a patient with recurrent ocular lymphoma. A fluorescence polarization immunoassay was used to make the determinations. RESULTS: At seven hours into a 24-hour intravenous infusion, methotrexate was at cytotoxic level in all samples. At 74 hours, cytotoxic levels were present only in the aqueous humor. CONCLUSION: Sustained cytotoxic ocular methotrexate levels are achievable after systemic administration.

Some factors affecting the preservation of the cytoskeleton of cells in culture for scanning electron microscopy.

This paper reports some preliminary findings on the effects of the composition of the detergent extraction medium on the morphological and molecular preservation of the cytoskeleton of Balb/c 3T3 cells as visualized by scanning electron microscopy and SDS-PAGE. Specific variables tested are the concentrations of sodium, potassium, calcium and magnesium ions, and the osmolarity of the medium. The results suggest that the ionic composition of the medium is more important than osmolarity in determining the composition of the cytoskeleton obtained with Triton X-100 detergent. Calcium is particularly deleterious to morphological preservation, and better preservation is obtained when potassium is the principal cation than when sodium is. The best preservation of cytoskeletal structures and the greatest molecular complexity was obtained by extracting in a buffer composed of 1mM EGTA, 4% polyethylene glycol 6000, 1 mM GTP and 100 mM PIPES, pH 6.9.

Scanning electron microscopic study of the microarchitecture of the lung of the giant salamander Amphiuma tridactylum.

This paper reports observations made using scanning electron microscopy (SEM) on the internal structure of the lung of Amphiuma tridactylum. This lung is highly septate at the cranial end, but the septa become gradually reduced in size and number with increasing distance caudally until the septa are reduced to ridges in the wall of the lung. However, there is no respiratory dead space as respiratory epithelium is found throughout the lung. Treatment of isolated lung segments with acetylcholine causes the septa to shorten and thicken which in turn causes the lung diameter to decrease and the alveoli to collapse. These observations are consistent with the hypothesis that the collapse of the Amphiuma lung in vivo, which is responsible for the highly efficient ventilation of the lungs, is brought about by the contraction of pulmonary smooth muscle in the septa and wall of the lung.