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Biomedical subjects

G G DeBlois

Publications and source records attributed to G G DeBlois.

5 recordsLinked to original sources

Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep.

Recombinant interleukin 2 (rIL-2) administration, a new form of therapy for patients with far-advanced cancer, is associated with a "third space" syndrome, i.e., pulmonary edema, respiratory distress, and hypoxemia, which limits the dose and duration of treatment. To extend our knowledge regarding this toxicity, we established a sheep chronic lung lymph fistula model and measured hemodynamics, arterial blood gases, caudal mediastinal (lung) lymph flow (QL), and blood and lung lymph cellular changes before, during, and after (recovery) a 3-day continuous rIL-2 infusion (9 x 10(5) U/kg). Moderate systemic hypotension, mild pulmonary hypertension, and an increase in alveolar-arterial PO2 gradient was present on day 3 of rIL-2 infusion. QL increased from a base line of 1.9 +/- 0.2 to a maximum of 4.3 +/- 1.1 ml/15 min on day 3 of rIL-2 infusion. At no time was there a change in lymph-to-plasma protein ratio. The leukocyte count increased significantly to 16.1 +/- 4.5 x 10(3) cells/mm3 at recovery day 1. The percentage of blood lymphocytes decreased significantly by day 1 of rIL-2 infusion, returned to base-line levels on day 3, and significantly increased on day 2 of recovery. Lung lymph lymphocytes decreased significantly on days 1 and 2 of rIL-2 infusion. There was a shift in their size; i.e., their area increased from 32 +/- 7 to 57 +/- 19 micron 2 (P less than 0.05) by day 2 of rIL-2 infusion. By day 1 of recovery, lung lymph lymphocyte counts increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of the cardiopulmonary effects of continuous versus bolus infusion of recombinant interleukin-2 in sheep.

The systemic administration of recombinant interleukin-2 (rIL-2) is used for the treatment of patients with far advanced cancer. However, treatment may be limited by a so-called "third space" syndrome. Whether these side effects are due to the total dose used or the method of administration is unclear. To define whether the continuous (Group 2) or bolus (Group 3) i.v. infusion of 9 x 10(5) units/kg rIL-2 over 72 h is associated with similar toxicities, we established a chronic sheep model and monitored changes in systemic and pulmonary vascular pressures, cardiac function, and gas exchange. At 72 h lung lymph flow, lymph/plasma protein ratios, lung histology, and extravascular lung water/dry lung weight were obtained. In both groups the infusion of rIL-2 resulted in an increase in high protein lung lymph flow, an increase in cardiac output, and a decrease in systemic vascular resistance. Large lymphoid cells were found by histology to be infiltrating the lung interstitium. In Group 2, in addition, there were mild pulmonary hypertension [pulmonary artery pressures increased from 14 +/- 5 to 22 +/- 6 mmHg (P less than 0.05)], systemic hypotension [81 +/- 7 compared to a baseline of 95 +/- 9 mmHg (P less than 0.01)], and worsening gas exchange. We conclude that a 72-h continuous or bolus infusion of equivalent doses of rIL-2 are associated with cardiopulmonary toxicity; however, pulmonary hypertension, systemic hypotension, and gas exchange are worse in animals receiving the continuous infusion.

Animals↗

Cardiopulmonary effects of recombinant interleukin-2 infusion in sheep.

The systemic administration of recombinant interleukin-2 (rIL-2) with or without lymphokine-activated killer (LAK) cells, a new treatment for patients with advanced cancer, is associated with a presumed "third-space" syndrome. To further define the extent and time course of this toxicity, we established a chronic sheep model and monitored changes in systemic and central vascular pressures, cardiac function, and gas exchange during a 72-h continuous intravenous infusion of rIL-2 at a total dose of 5 (group 3) or 9 x 10(5) U/kg (group 4). At 72 h, caudal mediastinal lymph flow, histology, and extravascular lung water-to-dry lung weight ratio (EVLW/DLW) were obtained. During the rIL-2 infusion there was a dose-dependent significant decrease in systemic blood pressure and arterial Po2 and an increase in core temperature. In group 4, pulmonary arterial pressure increased from a base line of 13 +/- 5 to 21 +/- 6 mmHg (P less than 0.05). Lung lymph flow was significantly increased in groups 3 and 4 compared with animals receiving 0.9% NaCl or excipient infusions (groups 1 and 2). EVLW/DLW values were elevated in groups 3 and 4 (P less than 0.01). In animals receiving rIL-2, histological evaluation revealed a dose-dependent infiltration of lung tissue by lymphoblastoid cells that stained esterase negative. We conclude that rIL-2 infusion in doses comparable to those given to humans results in alterations in systemic and central hemodynamics, gas exchange, high-protein lung lymph flow, and infiltration of lymphoblastoid cells into the lung parenchyma.

Animals↗

Fatal pulmonary fibrosis from low-dose bleomycin therapy.

Six weeks after receiving a total dose of 20 units of bleomycin sulfate as part of BACOP therapy for non-Hodgkin's lymphoma, our patient had dyspnea and cough with marked hypoxemia. Open lung biopsy established the diagnosis of "bleomycin lung," confirmed by postmortem examination. Fatal bleomycin pulmonary toxicity can develop with any dosage, and routine tests are incapable of detecting early, reversible toxicity.

Aged↗

Hemispherical spondylosclerosis: MR appearance.

We present a case of hemispherical spondylosclerosis (HSS) in a middle-aged woman with low back pain. The plain radiographic findings, CT and MR appearance, and pathological examination are described, and the difficulties encountered in differentiating HSS from malignancy and infection are discussed.

Adult↗