Treatment of small cell carcinoma of lung with late dosage intensification programmes containing cyclophosphamide and mesna.
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Biomedical subjects
Publications and source records attributed to D Cunningham.
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The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug was administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls, All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p less than 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p less than 0.05) and pericardial effusion (p less than 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p less than 0.05) or IB (p less than 0.01) and in the untreated, unirradiated rabbits (p less than 0.01). Early administration of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusion, and improved survival in this experimental model of radiation-induced heart disease.
Cis-Platinum(II)diamminodichloride (cis-PDD)-induced mutations to prototrophy were studied in Escherichia coli. Mutagenesis was not detected in a recA nor in a lexA mutant, but was greater in a uvrA strain than in a repair-proficient strain, at a given treatment of cis-PDD. Increasing the plating density above 10(5) cells per plate did not give an equivalent increase in revertants per plate [crowding depression of mutagenesis (Bockrath et al., 1980)]. Growth rates were similar at different plating densities and crowding depression of mutagenesis was observed in both excision-proficient and excision-deficient strains. A filtrate of a plate wash from crowded plates, of either treated or untreated cultures, further reduced the mutation frequencies over that due to crowding depression of mutagenesis.
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Serous otitis media (SOM) is a common and troublesome disease in childhood. Although antihistamines are commonly prescribed to prevent or treat SOM, there have been no controlled clinical trials to determine the efficacy of such interventions. This study was designed to determine if antihistamines are of value in the prevention or treatment of SOM. Using a randomized double-blind method, 206 children with acute otitis media were treated with antibiotics and either brompheniramine maleate or placebo. The children were evaluated two weeks later by tympanometry and, independently, by combined pneumatoscopy and otoscopy. There were no significant differences overall between the treatment and control groups in terms of preventing SOM: 44% of those on antihistamine and 41% of those on placebo had SOM after two weeks of therapy. However, children with a history of serous otitis media did significantly better on placebo than did those on antihistamine, and children without a history of serous otitis media did significantly better on antihistamine than did those on placebo. One hundred children continued to use antihistamine or placebo for four more weeks. There were no significant differences between the treatment and control groups in terms of resolution of SOM (64% versus 68%).
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Cytochalasin A at 5 to 25 microgram/ml (1.0 x 10(-5) to 5.2 x 10(-5) M) inhibited the growth of three gram-positive bacteria, Arthrobacter sialophilus, Staphyloccus aureus, and Bacillus amyloliquifaciens, but had little or no effect on the growth of three gram-negative bacteria, Excherichia coli, Pseudomonas maltophilia, and Aeromonas proteolytica. A. sialophilus and S. aureus recovered spontaneously from cytochalasin A-mediated growth inhibition after a considerable lag period, which was dependent on the drug dose. It was demonstrated that this long-term recovery did not involve selection of resistant variants. Cytochalasin A had no detrimental effect on cell viability in A. sialophilus or S. aureus, but caused lysis of B. amyloliquifaciens. The drug prevented enzyme inductions and inhibited transport of valine, uridine, and glucose in the gram-positive organisms. It had little or no effect on these processes in the gram-negative organisms. In studies with A. sialophilus, the drug inhbitied respiration of exogenous substrates, but did not depress endogenous respiration. These results constitute the first unequivocal evidence for the bacteriostatic properties of this class of compounds and indicate that cytochalasin A halts various physiological processes in gram-positive bacteria primarily by inhibiting solute transport.
Three to twelve (7.1 +/- 3.2) months after myocardial infarction, subjects under 54 (45.0 +/- 4.7) yr were assigned randomly to high-intensity (HIE, n = 37) or low-intensity (LIE, n = 42) exercise programs. Cardiac outputs (Q) during graded bicycle ergometer exercise were measured by a CO2-rebreathing method on entry and after 6 and 12 mo of training. The initial exercise Q was low in relation to work load, due to a low stroke volume (SV). Over the year of training, the predicted maximal O2 intake of the HIE group increased significantly (from 26.0 to 30.3 ml.kg-1.min-1), while that of the LIE group showed no significant alteration. During the first 6 mo, the heart rate of the HIE group was significantly reduced at each work level. There was an associated widening of arteriovenous oxygen difference, but SV was unchanged. These findings were attributed to extracardiac factors, including a redistribution of blood flow, biochemical changes in the trained muscle, and a secondary reduction of sympathetic drive. Over the second 6 mo, the SV of the HIE group increased 10%; this may reflect an increase of intrinsic myocardial contractility that develops if high-intensity training is sustained. The LIE group showed no major changes of cardiovascular function over the year of observation.
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We studied the efficacy of (1) preventing the development of serous otitis media (SOM) by using an oral decongestant in children with acute otitis media and (2) treating SOM with an oral decongestant. In a randomized double-blind study, 190 children were treated for acute otitis media with antibiotics and either pseudoephedrine hydrochloride (Sudafed) or placebo. They were evaluated two weeks later by tympanometry and (independently) by clinical evaluation and pneumotoscopy. There were no significant differences between the two groups, except that males developed SOM significantly more often than did females. Use of decongestant and placebo was continued in 78 patients with SOM for up to four more weeks. Again, there were no siginificant differences between the treatment groups except that patients with an allergic history did significantly worse using a decongestant. Overall there was no benefit from pseudoephedrine in either the prevention or treatment of SOM.
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Human islet cell tumor tissue and isolated islets of Langerhans from rats incorporated radioactive amino acids in vitro into insulin and a larger acid-alcohol soluble protein which could be separated from insulin by gel filtration. The amino acids were incorporated into the larger protein earlier than into insulin; only after incubation of islets for approximately 30 minutes did radioactivity begin to appear in insulin. The transfer of about 70 percent of the radioactivity of the larger protein to insulin was demonstrated in the absence of new peptide bond synthesis (cycloheximide), or during incubation with unlabeled amino acid (chase). The results indicate that the larger protein is a precursor in the biosynthesis of insulin. The name "proinsulin" is suggested for this protein.
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