Interrelationship of erythropoietic recovery, marrow recovery, colony-forming units, and erythropoiesis-stimulating factors after sublethal x-irradiation.
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Animals↗
Biomedical subjects
D Fulton
Publications and source records attributed to D Fulton.
Radioprotective effect of Rauscher leukemia virus in the SJL-J mouse.
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Animals↗
Comparison of erythropoietin response in mice following polycythemia induced by transfusion of hypoxia.
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Animals↗
High dose misonidazole with dexamethasone rescue: a possible approach to circumvent neurotoxicity.
With a view to modifying misonidazole (MISO) neurotoxicity, we initiated a randomized clinical study to assess a possible drug interaction and toxicity protection when dexamethasone (DXM) is administered concomittantly with MISO. The ongoing study consists of: 1. Pharmacokinetic evaluation; 2. Assessment of toxicity. Fourteen patients undergoing radiation therapy for different types of malignant neoplasia (excluding brain tumors) have been randomized to receive either MISO alone, or DXM one week prior and during treatment with MISO. Five of seven patients receiving MISO alone developed peripheral neuropathies while only one out of 7 patients that received MISO with DXM coverage developed a transient and mild neuropathy. Pharmacokinetic evaluation of MISO in plasma and urine of those patients receiving DXM has shown no evidence of drug interaction. It is postulated that the mechanism of action of DXM is at the nerve cell membrane level, restoring and stabilizing cell surface properties. In future studies we will investigate the use of DXM with increasing doses of MISO above the recommended maximum dose of 12 gm/m2, hoping to achieve a higher tumor tissue level of MISO while avoiding unacceptable toxicity. The effect of Allopurinol on the plasma kinetics of MISO was studied in four additional patients, observing also no evidence of drug interaction.
Allopurinol↗
Pharmacokinetic interaction of BCNU and misonidazole in humans.
Although considerable laboratory in vitro and in vivo evidence is now available suggesting that misonidazole (MISO) enhances chemotherapy tumor responses, experience with human tumors is limited. Further, the mechanism of this enhancement is not definitely known. One possible mechanism is that MISO alters the pharmacokinetics of the chemotherapeutic agent, vice versa or both. We studied a group of patients with recurrent malignant gliomas, following radiotherapy. After proven recurrence, they were treated with i.v. BCNU in combination with oral MISO in an 8 week cycle. Our aims were: 1. To obtain a second remission; 2. To assess the toxicity of this combination; 3. To assess the plasma pharmacokinetics of each drug alone and in combination. Six patients entered the protocol. Four of six patients obtained either a partial or subpartial response. Prolonged moderate myelosuppression was observed in 2/6 patients after 3 cycles; 2/6 patients experienced seizures after the first cycle of chemotherapy for the first time in the course of their disease. The plasma pharmacokinetic data indicates no evidence of a MISO-BCNU drug interaction.
Bone Marrow Diseases↗
Acute otitis media caused by Branhamella catarrhalis: biology and therapy.
Since 1980, we have observed an epidemic of otitis media caused by Branhamella catarrhalis. This event was characterized by studying the nasopharyngeal colonization of infants and children with B. catarrhalis and the clinical presentation and therapeutic outcome of acute otitis media caused by this organism. Pharyngeal colonization with B. catarrhalis was commoner in winter than summer. B. catarrhalis was present in middle-ear fluid (MEF) of 17% of children with otitis media, and was commoner in fall and winter (20%) than in spring and summer (11%, P less than .05). Seventy-five percent of isolates produced beta-lactamase (Ravasio type). In five of 20 patients, treatment with beta-lactamase-susceptible agents failed to sterilize B. catarrhalis-infected MEF. All of these five patients were infected with beta-lactamase-producing strains. The increasing prominence of antibiotic-resistant B. catarrhalis in acute otitis media may lead to a reevaluation of initial antibiotic therapy for acute otitis media, particularly in winter or in areas where colonization with such strains is prevalent.
Acute Disease↗
The position of NO among endogenous vasodilators.
Bradykinin stimulates phospholipases to release arachidonic acid (AA) which can be metabolized by cyclooxygenase, lipoxygenase and cytochrome P450 (P450) to yield vasoactive products that may contribute to the effect of the peptide. In the rat kidney, pharmacological evidence suggests that a substantial component of the vasodilator response is dependent on P450-AA metabolism. In the heart, the vasodilator response to bradykinin is independent of NO and prostaglandins but reduced by inhibitors of P450, including 17-ODYA, an inhibitor of fatty acid metabolism, also suggesting a role of P450-AA. Moreover, the renal and coronary vasodilator responses to bradykinin are associated with release of P450-AA products measured by gas chromatography-mass spectrometry (GC-MS). The coronary vasodilator response to bradykinin is also dependent on activation of K+ channels linking P450-AA and hyperpolarization. Formation of vasodilator eicosanoids derived via the P450 pathway may make important contributions to the control of vascular tone, local blood flow and, thereby, blood pressure.
Acetylcholine↗