Robert B. Epstein

Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder

To assess the potential use of bone marrow stromal cell (BMSC)‐seeded biodegradable scaffold for bladder regeneration in a canine model, by characterizing BMSCs and comparing them to bladder smooth muscle cells (SMCs) by immunohistochemistry, growth capability, and contractility.

Allogeneic Marrow Engraftment Following Whole Body Irradiation in a Patient with Leukemia

A 46-year-old man with blastic crisis of chronic myelogenous leukemia was given 950 rads whole-body irradiation followed immediately by 17.6 x 109 marrow cells. The marrow donor was the patients sister who matched the patient in 11 of 12 HL-A groups and whose leukocytes reacted to the patients leukemic cells in mixed leukocyte culture. The patients white blood cell count began to go up on the 13th day and marrow engraftment was confirmed by repeated cytogenetic analyses. Secondary disease with skin rash and diarrhea was evident by the end of the second week but appeared to be controlled by methotrexate. The patient then developed fever, recurrent diarrhea and pneumonitis and died 56 days after irradiation. Autopsy showed inclusion bodies typical of cytomegalovirus. There was no histological evidence of acute secondary disease nor of leukemia.

Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer. A Southwest Oncology Group Study

Small cell lung cancer patients who failed primary systemic therapy or who failed after response were randomly assigned to salvage treatment with etoposide (VP‐16) and cisplatin (CDDP) or bis‐chloroethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC). Good risk patients were those who had tolerated prior chemotherapy well, those who had not had prior radiation therapy, and those who were 65 years of age or younger. Patients with a history of poor tolerance, prior radiation therapy, or those who were older than 65 years of age were classified as poor risk. Forty‐five patients were randomized to the BTOC regimen and 58 to the VP‐16/CDDP regimen. The overall remission rate was 13% (13 of 103 patients). Good risk patients treated with the BTOC regimen had a remission rate of 27% (three of 11 patients), which was the same rate as patients treated with the VP‐16/CDDP regimen (three of 11 patients). Poor risk patients had remission rates of 9% (three of 34 patients) with the BTOC regimen and 9% (four of 47 patients) with the VP‐16/CDDP regimen. The median survival time from the start of therapy was 16 weeks for all patients. BTOC good risk patients had a median survival time of 10 weeks, as compared with 14 weeks for poor risk patients. VP‐16/CDDP good risk patients had a median survival time of 35 weeks, as compared with 12 weeks for poor risk patients. Although based on small numbers, the advantage in survival time for good risk patients treated with VP‐16/CDDP over those treated with BTOC is statistically significant. Prior exposure to VP‐16 did not influence the outcome of patients treated with VP‐16/CDDP. Both regimens produced moderate toxicity, but were generally well tolerated. It was concluded that VP‐16/CDDP may be a useful salvage treatment for good risk patients, despite its limited remission rate. Also, it was found that BTOC has no value for patients in this setting and that neither regimen helps patients who are poor risk.

Management of cyclosporine overdose in a hematopoietic stem cell transplant patient with sequential plasma exchange and red blood cell exchange

Cyclosporine is commonly used as an immunosuppressive agent in both solid organ and bone marrow transplant. While used for graft rejection in organ transplantation, cyclosporine has been used to enable tolerance and for prevention of acute graft‐versus‐host disease in bone marrow transplant [ Ratanatharathorn et al., Blood 1998;92:2303–2314 ]. Cyclosporine has a narrow therapeutic window, and many patients develop some level of toxicity even within the therapeutic range. Common toxicities include hypertension, nephrotoxicity, electrolyte abnormalities, hyperglycemia, and neurotoxicity [ Woo et al., Bone Marrow Transplant 1997;20:1095–1098 ]. Management of cyclosporine toxicity is not clearly defined and is primarily supportive in nature. In cases of significant elevations of cyclosporine levels, limited data are available but suggest that whole blood exchange may be effective [ Kwon et al., J Heart Lung Transplant 2006;25:483–485; Leitner et al., Transplantation 2003;75:1764–1765 ]. We present a case of successful rapid clearance of cyclosporine utilizing a combined approach of red cell exchange and plasma exchange. J. Clin. Apheresis, 2011.

Systemic molecular and cellular changes induced in rats upon inhalation of JP-8 petroleum fuel vapor

Limited information is available regarding systemic changes in mammals associated with exposures to petroleum/hydrocarbon fuels. In this study, systemic toxicity of JP-8 jet fuel was observed in a rat inhalation model at different JP-8 fuel vapor concentrations (250, 500, or 1000 mg/m3, for 91 days). Gel electrophoresis and mass spectrometry sequencing identified the α-2 microglobulin protein to be elevated in rat kidney in a JP-8 dose-dependent manner. Western blot analysis of kidney and lung tissue extracts revealed JP-8 dependent elevation of inducible heat shock protein 70 (HSP70). Tissue changes were observed histologically (hematoxylin and eosin staining) in liver, kidney, lung, bone marrow, and heart, and more prevalently at medium or high JP-8 vapor phase exposures (500–1000 mg/m3) than at low vapor phase exposure (250 mg/m3) or non-JP-8 controls. JP-8 fuel-induced liver alterations included dilated sinusoids, cytoplasmic clumping, and fat cell deposition. Changes to the kidneys included reduced numbers of nuclei, and cytoplasmic dumping in the lumen of proximal convoluted tubules. JP-8 dependent lung alterations were edema and dilated alveolar capillaries, which allowed clumping of red blood cells (RBCs). Changes in the bone marrow in response to JP-8 included reduction of fat cells and fat globules, and cellular proliferation (RBCs, white blood cells-WBCs, and megakaryocytes). Heart tissue from JP-8 exposed animals contained increased numbers of inflammatory and fibroblast cells, as well as myofibril scarring. cDNA array analysis of heart tissue revealed a JP-8 dependent increase in atrial natriuretic peptide precursor mRNA and a decrease in voltage-gated potassium (K+) ion channel mRNA.

Phase II evaluation of bisantrene hydrochloride in refractory malignant melanoma - A southwest oncology group study

Patients with a pathologically proven diagnosis of malignant melanoma were entered into a phase II trial of bisantrene. Eligibility criteria included: measurable, metastatic disease; performance status 0–2 SWOG; and adriamycin total cumulative dose of < 400 mg/m2. The initial bisantrene dosing schedule was 260 mg/m2 every three weeks for good risk patients. Due to the absence of an objective response and the lack of severe toxicity in the first 25 bisantrene treated patients, the starting dose was increased to 300 mg/m2 for good risk patients. Fifty-one patients received a median of two bisantrene courses (range 1–11 courses). Leukopenia was the major toxicity. Fifteen (68%) of the 22 good risk, intermediate dose patients (260 mg/m2), and 8 (80%) of the 10 good risk, high dose patients (300 mg/m2) evaluable for toxicity experienced mild-severe leukopenia. None of the 51 patients experienced a complete or partial response to bisantrene. Median survival was 3.3 months. We conclude that bisantrene is ineffective in the treatment of metastatic melanoma.