PubMed Health⌕ Search

Biomedical subjects

H I Robins

Publications and source records attributed to H I Robins.

116 records · Page 7Linked to original sources

Dynamic changes in serum erythropoietin levels in solid tumour patients undergoing 41.8 degrees C whole body hyperthermia and/or chemotherapy.

Whole Body Hyperthermia (WBH) has been shown to have physiological effects on myeloid and megakaryocytic haematopoietic tissue via both cytokine induction, as well as hormonal changes. In order to extend this knowledge base to the erythroid cells, endogenous erythropoietin (EPO) levels were studied in 17 cancer patients receiving 41.8 degrees C WBH and/or chemotherapy, as well as in 53 anaemic and non-anaemic control patients. Pre-treatment EPO levels showed a 'blunted' EPO response in cancer patients compared to the control patients. Post-treatment data demonstrated a significant chemotherapy induced increase in EPO levels with a peak at 36 to 48 hours (independent of changes in haemoglobin) and 10 to 13 days post chemotherapy (simultaneously with a drop in haemoglobin levels). The early change in EPO levels was not influenced by the addition of 41.8 degrees C (x 60 min) WBH to the same chemotherapy regimen, i.e., ifosfamide, carboplatin, and etoposide. Taken collectively, our data show that endogenous EPO levels in cancer patients can be effected by chemotherapy (independent of changes in haemoglobin). This EPO response to chemotherapy is not impacted on by 41.8 degrees C WBH. A relevant secondary conclusion can also be derived from this investigation, i.e., caution should be exercised as to the use of EPO levels during chemotherapy as predictors of exogenous EPO efficacy.

Adult↗

Influence of circadian rhythm on 41.8 degrees C whole body hyperthermia induction of haematopoietic growth factors.

It has previously been reported by the authors that the induction of a series of cytokines by 41.8 degrees C Whole Body Hyperthermia (WBH), i.e., interleukin (IL)-1 beta, IL-6, IL-8, IL-10, tumour necrosis factor alpha, and granulocyte colony stimulating factor (G-CSF). As cytokine levels are known to fluctuate as a function of time, i.e. circadian rhythm, the influence of circadian time structure on specific haemotopoetic growth factors is studied, i.e. granulocyte macrophage colony stimulating factor (GM-CSF), G-CSF and IL-3. Samples derived from four cancer patients undergoing extracorporeal WBH resulted in the following observations: G-CSF is induced by WBH, but unaffected by circadian rhythm, IL-3 fluctuates with circadian rhythm, but is unaffected by WBH. Specifically, a biphasic temporal pattern of IL-3 (i.e. with a peak at 2:00 and 5:00 a.m. and a nadir concentration at 5:00 p.m.) was found by analysis of variance. GM-CSF was below the lower detection limit pre and post WBH. The data show the importance of measuring cytokines as a function of time to circumvent conflicting results in the inter-relationship of 'true' cytokine induction and circadian rhythm. The implications of the differential induction of G-CSF, GM-CSF, and IL-3 for myeloprotection after WBH are discussed.

Circadian Rhythm↗

Non-Hodgkin's tumor and Pancoast's syndrome.

A 60-year old man presented with Horner's syndrome, and acute right hand and lower extremity weakness. Chest X-ray and MRI revealed a right apical lung tumor (presumed to be a primary lung cancer), with brachial plexus infiltration and spinal cord compression. Emergent radiotherapy was initiated for spinal cord compression and a biopsy was obtained 24 h later. A careful review of pathology demonstrated a non-Hodgkin's lymphoma. The patient subsequently received chemotherapy, and is now in remission. This case illustrates the importance of a tissue diagnosis before initiating therapy for a Pancoast's tumor.

Carcinoma↗

Glioblastoma multiforme: MR imaging at 1.5 and 9.4 T after injection of polylysine-DTPA-Gd in rats.

Polylysine-DTPA-Gd, a new MR contrast agent, was injected into the aorta of rats 7 days after C6 glioblastoma was implanted in their brains; MR imaging was performed 3 days later. The imaging was done at two field strengths: (1) 1.5 T with a 3-mm slice thickness and in-plane resolutions of 600 microns and (2) 9.4 T with a 125- or 500-microns slice thickness and in-plane resolutions of 95 microns. In animals injected with polylysine-DTPA-Gd (1 microgram or more per rat), the T1-weighted images and mixed T1, T2 images of the C6 glioblastoma revealed a higher signal intensity at the marginal region between tumor and normal brain than that seen in surrounding normal brain. The central tumor region had a low signal intensity. The concentration of Gd in the C6 glioblastoma, after injection of 1 microgram polylysine-DTPA-Gd per rat, was calculated to be 0.14 mumol/l. The central tumor region also had a low signal intensity in animals that were not injected with the contrast agent, but the margin between tumor and normal brain was resolved poorly, if at all. The polylysine-DTPA-Gd revealed the microvasculature of the C6 glioblastoma in the 125-micron-thick slices obtained at 9.4 T. This is the first study to reveal the utility of the 9.4-T MR imager for examination of glioblastomas in situ and to demonstrate the utility of polylysine-DTPA-Gd as a contrast agent for the definition of the margin between glioblastoma and normal brain tissue.

Animals↗

Rationale and clinical status of 41.8 degrees C systemic hyperthermia tumor necrosis factor, and melphalan for neoplastic disease.

Dramatic clinical results have been obtained in malignant melanoma and sarcoma using hyperthermic limb perfusion in combination with tumor necrosis factor (TNF) and melphalan (L-PAM). In order to extrapolate these results to systemic treatment, a preclinical research program was initiated to study the interactions of hyperthermia, TNF, and L-PAM. Based on these results, a Phase I clinical trial of whole body hyperthermia (WBH) and L-PAM was initiated and completed. Clinical results obtained were consistent with initiating two second generation studies: a) a Phase II study of WBH and L-PAM for malignant melanoma; b) a Phase I study of WBH, TNF and L-PAM. Both of these studies are currently active at the University of Wisconsin Comprehensive Cancer Center. The following review summarizes the laboratory and clinical data obtained to date regarding this systemic multi-modality treatment approach.

Antineoplastic Agents, Alkylating↗

Rationale and clinical status of local hyperthermia, radiation, and chemotherapy in locally advanced malignancies.

The combination of ionizing irradiation and local hyperthermia therapy has been demonstrated to be efficacious in a variety of localized neoplasms. One of the most consistent conclusions from this experience, however, is the finding that large tumor size is a significant negative prognosticator for attaining complete tumor regression. During the past decade investigators have begun to look at the possibility of adding chemotherapy to thermo-radiotherapy in order to improve the efficacy of treatment in patients with large tumors. This review article summarizes the recent clinical experience with such triple modality therapy.

Antineoplastic Agents↗

Systemic hyperthermia and ICE chemotherapy for sarcoma patients: rationale and clinical status.

Preclinical studies are consistent with the concept that 41.8 degrees C whole body hyperthermia (WBH) can enhance the therapeutic index of specific chemotherapeutic agents. These laboratory investigations resulted in 2 phase I clinical studies, which also support this hypothesis. These trials were extended to 2 sequential phase II investigations of WBH plus ifosfamide, carboplatin and etoposide (ICE) for refractory sarcoma patients. The first study (involving 12 patients) using extra-corporeal WBH was prematurely closed to adopt a less toxic WBH technology, i.e., the radiant heat Aquatherm. To date, 12 patients have been accrued to the Aquatherm trial. Projections regarding reduced morbidity were correct. The response rate for ICE/WBH is currently 63%. The review to follow will summarize the results of these trials, as well as the laboratory and clinical data which serve to explicate the dramatic clinical results observed to date.

Antineoplastic Combined Chemotherapy Protocols↗