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Biomedical subjects

D Rushing

Publications and source records attributed to D Rushing.

12 recordsLinked to original sources
PubMed1999

A pilot study of melphalan, tumor necrosis factor-alpha and 41.8 degrees C whole-body hyperthermia.

PURPOSE: To evaluate the feasibilitv of sequencing (based on preclinical modeling) tumor necrosis factor-a (TNF) at two dose levels with melphalan (L-PAM) and 41.8 C whole-body hyperthermia (WBH) for 60 min. PATIENTS AND METHODS: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 microg/m2) and six patients were treated at TNF dose level II (100 microg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/ m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. RESULTS: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with <25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). CONCLUSION: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

Adult↗
PubMed1997

Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in cancer patients.

PURPOSE: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes. PATIENTS AND METHODS: Sixteen patients with refractory cancer were treated (May 1992 to May 1995) with WBH alone during week 1) thereafter patients were randomized to receive either L-PAM alone on week 2 and L-PAM plus WBH on week 5, or the reverse sequence. Patients who demonstrated clinical improvement received WBH plus L-PAM monthly. Dose levels of L-PAM were 10 mg/m2 (n = 3), 15 mg/m2 (n = 3), 17.5 mg/m2 (n = 6), and 20 mg/m2 (n = 4). L-PAM was administered at target temperature; WBH was administered with an Aquatherm radiant-heat device (patent pending; Cancer Research Institute, New York, NY). RESULTS: Comparisons of mean WBC count and platelet nadirs for L-PAM alone and L-PAM plus WBH demonstrated that the addition of WBH resulted in nadir counts that were, on average, 25% lower. There were no instances of febrile neutropenia or bleeding. Toxicities allowed for escalation of L-PAM to 20 mg/m2; all four patients at this level experienced grade 4 myelosuppression. No significant myelosuppression was observed at 10 and 15 mg/m2. Grade 3 myelosuppression was observed in two of six patients at 17.5 mg/m2. Responses included complete remission (CR) of pancreatic cancer (10 mg/m2), partial remission (PR) of malignant melanoma in two patients (20 mg/m2), and transient clinical and/or serologic improvement in five patients. The pharmacokinetics of L-PAM were not altered by WBH. Observed cytokine induction by WBH is also discussed in detail. CONCLUSION: We conclude that L-PAM with 41.8 degrees C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

Adult↗
PubMed1996

A 56-year-old woman with recurrent episodes of weakness and hypoglycemia.

The differential diagnosis for a 56-year-old woman with recurrent episodes of weakness and hypoglycemia is discussed in the setting of a clinicopathological conference at the Louisiana State University Medical Center in Shreveport, Louisiana. The diagnostic approach to the workup of a patient presenting with hypoglycemia is outlined.

Female↗
PubMed1989

Myelodysplastic syndrome and acute nonlymphocytic leukemia secondary to mitolactol treatment in patients with breast cancer.

One thousand four hundred sixty patients with 2,590 patient-years of follow-up were treated on 15 protocols for metastatic breast cancer with dibromodulcitol (mitolactol; DBD)-containing regimens since 1976. Twenty-three patients developed myelodysplastic syndrome (MDS) and/or acute nonlymphocytic leukemia (ANLL). The overall risk of developing MDS or ANLL per person is 1.6%. In patients who had received more than 16,000 mg of DBD the risk per person is 6%, and in the high-dose subsets of patients who received no prior radiation or alkylator therapy, it is 7.9%. The risk per person increases to a maximum by 30 to 36 months (5.3%). The high risk was seen despite a study population of metastatic breast cancer patients with a median survival of 16 months. This analysis strongly suggests that DBD is one of the most potent of the reported leukemogenic-inducing agents. Further use of this drug in both the adjuvant and metastatic situation should be reconsidered.

Adult↗
PubMed1982

Hydroxyurea versus busulfan in the treatment of chronic myelogenous leukemia.

A retrospective analysis of 67 patients with chronic myelogenous leukemia treated with hydroxyurea (41 patients) and busulfan (26 patients) compared the effectiveness of treatment and resulting survival. After 4 days of treatment, the white blood count in the hydroxyurea group fell at a rate of 31% +/- 10% per day compared to 10% +/- 8% for the busulfan group. At 6 months, the hemoglobin was similar, but in the busulfan group, the white blood count was significantly lower (12,500 vs. 29,900) (p = greater than 0.03). The platelet count was lower (311,000 vs. 481,000) in the busulfan group; however, the difference was not significant. When treatment was discontinued because of progression of the disease, the hemoglobin and white blood counts for both groups were similar. The platelet count was higher in the hydroxyurea group (762,000 vs. 269,000) (p greater than 0.02). The duration of therapy for both groups was similar. The median survival was also similar (hydroxyurea = 51 months; busulfan = 45 months). Hydroxyurea was associated with less life-threatening toxicity. Hydroxyurea is as effective as busulfan in treating chronic myelogenous leukemia.

Actuarial Analysis↗
PubMed1982

Hemoglobin solutions as red cell substitutes.

Hemoglobin solutions have potential as temporary red cell substitutes. Their efficacy has been demonstrated by their ability to maintain life-supporting levels of O2 consumption and CO2 production in animals virtually free of red cells. They do not exhibit major toxic effects, but transient alterations in renal function remain a concern. Cardiac output does not increase in the face of acute anemia associated with isovolemic exchange transfusion with hemoglobin solution. However, cardiac reserve does not diminish significantly after infusion of hemoglobin solution. Alterations in production techniques may lead to a polymerized hemoglobin solution that has a hemoglobin concentration and P50 close to fresh whole blood. Though this development is encouraging, it is clear that no perfect red cell substitute currently is available.

Animals↗
PubMedDate not supplied

Evaluation and comparison of four reticulocyte enrichment procedures.

Four reticulocyte enrichment techniques were compared: differential centrifugation, and density gradient centrifugation with phthalate esters, Percoll-Renografin (PR), and silicone oil. The reticulocyte yields were 2.6, 7.4, 13.5, and 13.1 percent, respectively. The differential centrifugation procedure did not separate a statistically significant higher number of reticulocytes than were counted in an unseparated sample. The PR density gradient procedure was the best for our needs because it yielded the highest number of reticulocytes and was the easiest and quickest of the four procedures to perform; however, the method requires a high-speed centrifuge.

Blood Component Removal↗