Biomedical subjects
J H Ellis
Publications and source records attributed to J H Ellis.
Detection of mammalian cell mutagens in urine from carcinogen-dosed mice.
Urine from drug-treated rodents was tested directly in the L5178Y TK+/-leads to TK-/- gene mutation assay for the induction of trifluorothymidine-resistant (TFTR) mutants. 18-h urine samples collected from male CD-1 mice which had been treated with either 2-aminofluorene, cyclophosphamide, or lucanthone were incubated with beta-glucuronidase, then added directly to cultures of L5178Y TK+/- mouse lymphoma cells for 3 h. All 3 urine sources produced significant, dose-dependent increases in the frequency of TFTR mutants compared to normal urine or saline controls. When these same chemicals were tested directly as mutagens in L5178Y TK+/- cells, lucanthone and, to a lesser extent, cyclophosphamide were positive both with or without metabolic activation; and aminofluorene was only positive with activation. These results indicate that the urinary metabolites of aminofluorene, cyclophosphamide, and either the parental molecule or urinary metabolites of lucanthone can readily be detected as mutagens in a mammalian cell assay.
Unusual cause of posterior splenic defect.
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Efficient computer subroutines for interconversion of oxygen tension and saturation.
Two digital computer subroutines are described. NORSAT computes human hemoglobin saturation from oxygen tension data; NORINV performs the inverse computation. Each subroutine is based on an algorithm that is a direct mathematical inverse of the other. The effects of nonstandard conditions of temperature, pH, and CO2 tension on the saturation curve can be computed. The relative efficiency of these subroutines is compared to that of published subroutines having similar function. The new subroutines use computer time more efficiently with no loss of accuracy. The subroutines are provided in FORTRAN in a form suitable for direct inclusion in a number of user-specified programs.
Systemic lupus erythematosus: an unusual cause of bilateral hilar lymphadenopathy.
Systemic lupus erythematosus is usually not associated with bilateral hilar adenopathy. We report a young woman with arthralgias, fever, pleuritic pain, peripheral and hilar lymphadenopathy, high titer ANA, and a low serum complement. Transbronchial lung biopsy revealed interstitial pneumonitis. SLE should be considered an unusual cause of hilar adenopathy.
Improvement of platelet survival time with oxygen in patients with chronic obstructive airway disease.
Platelet survival time has been found to be shortened in hypoxemic patients, and these patients may have an increased risk of thromboembolism. Supplemental O2 was administered to 10 men with sever chronic obstructive airway disease and hypoxemia. Oxygen increased platelet survival time from a mean +/- SE of 1.9 +/- 0.16 to 2.5 +/- 0.21 days (P less than 0.005; normal half-time, 3.7 +/- 0.03 days); the survival half-time was increased by 0.03 days or more in 9 of these 10 men. Arterial Po2 was increased (46.0 +/- 1.1 to 60.0 +/- 1.5 mm Hg; P less than 0.001) in all men. Results suggest that hypoxemia is associated with shortened platelet survival time and that an increase in arterial Po2 is associated with an increase in platelet survival time. Although not established by this study, the increase in platelet survival time associated with supplemental O2 may decrease the risk of thromboembolism.
Methoxamine-induced increase in afterload. Effect on left ventricular performance in chronic obstructive pulmonary disease.
With a radionuclide technique, left ventricular ejection fraction and stroke volume index were measured in the basal state and after the stress of a methoxamine-induced increase in afterload in 10 men with severe chronic obstructive pulmonary disease. The resting mean left ventricular ejection fraction was normal in all 10 patients. After an acute increase in resistance to left ventricular ejection with methoxamine, the left ventricular ejection fraction and the stroke volume index did not decrease significantly, even in the presence of cor pulmonale in 5 patients. Mean pulmonary capillary wedge pressure was normal before, and did not change significantly after, methoxamine infusion. The data suggest that latent left ventricular dysfunction is not present in this group of patients with severe chronic obstructive pulmonary disease.
Diagnosis of opportunistic infections using the flexible fiberoptic bronchoscope.
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Gas and high pressure liquid chromatographic properties of some 4-nitrobenzamides of amphetamines and related arylalkylamines.
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Platelet survival time in patients with hypoxemia and pulmonary hypertension.
Platelet survival time (autologous labeling with 51chromium) was measured in 63 patients in order to evaluate the role of platelets in the thromboembolic complications of patients with hypoxemia and pulmonary hypertension. Thirty-eight of these patients had chronic obstructive airways disease; 13, primary pulmonary hypertension; seven, recurrent pulmonary embolism; four, the Eisenmenger syndrome; and one, multiple pulmonary arteriovenous fistula. Forty-three patients were hypeakly associated with arterial oxygen tension ( r = 0.50), but not with the arterial carbon dioxide tension or the level of pulmonary artery pressure. Sulfinpyrazone lengthened platelet survival in 12 of 24 (50%) treated patients but this drug did not alter either arterial oxygen tension arterial carbon dioxide tension, or pulmonary artery pressure. Our results suggest that hypoxemia is associated with shortened platelet survival time and that platelets may, therefore, be involved in the thromboembolic complications that develop in patients with hypoxemia.
Right ventricular ejection fraction in severe chronic airway obstruction.
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Disseminated histoplasmosis involving an aortofemoral prosthetic graft.
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Effect of dextran loading on left ventricular performance in chronic obstructive pulmonary disease.
The status of left ventricular function in patients with chronic obstructive pulmonary disease remains controversial. With a radionuclide technique left ventricular ejection fraction, left ventricular end-diastolic volume, cardiac output, and stroke volume were measured at rest and following infusion of dextran in 23 men with severe COPD. Resting, mean LVEF was normal in 19 subjects with COPD alone; four with COPD and coronary artery disease had a depressed mean LVEF. Left ventricular end-diastolic volume index and pulmonary capillary wedge pressure were both normal at rest indicating that the left ventricle was not volume underloaded. There was a normal response to dextran infusion (750 ml.) with no deterioration in LVEF and a significant increase in cardiac index, stroke volume index, LVEDVI, and PCW. These data suggest that at rest and following volume loading with dextran left ventricular function is normal in patients with COPD.
Quantitative radiocardiography in major pulmonary thromboembolism.
Cardiac index (CI) and pulmonary blood volume index (PVBI) were measured by quantitative radiocardiographic studies using radioactive 113mindium and a scintillation probe in 37 patients with confirmed major pulmonary thromboembolism. The mean PBVI was 185 +/- 11 ml/sq m (SE) and was significantly less than normal (310 +/- 5 ml/sq m [SE]; P less than 0.001). Six patients with major pulmonary thromboembilism had a PBVI within the normal range (262 to 358 ml/sq m; mean +/- 2 SD), and the mean pulmonary vascular occlusion was 21 percent in these patients. Eighteen patients (49 percent) died, and the most significant correlate of mortality was CI, which was depressed (less than 2.7 L/min/sq m) in all but two. Twenty-three serial determinations of pulmonary blood volume (PBV) ranging from 1 to 18 days after the initial study showed a mean increase in PBV of 27 ml/day in ten survivors. Quantitative radiocardiographic studies provide a means of diagnosing major pulmonary thromboembolism by measuring decreases in PBVI; it can assess the magnitude of major pulmonary thromboembolism and can assess CI and, thereby, predict risk of mortality; and it provides a means of following the resolution rate of major pulmonary thromboembolism.
Left ventricular ejection fraction in severe chronic obstructive airways disease.
The subject of left ventricular involvement in chronic obstructive airways disease is controversial. We measured left ventricular ejection fraction (LVEF) in 120 patients with severe chronic obstructive airways disease, 92 of them acutely decompensated and 28 stable. A bedside radionuclide technic using a scintillation probe was used to measure LVEF. Of the 28 patients with acute respiratory failure, LVEF was normal (larger than or equal to 55 per cent) in 60 and subnormal in 32. Of the 28 patients with stable chronic obstructive airways disease, LVEF was normal in 12 and low in 16. Coronary artery disease could be demonstrated clinically or at autopsy in 13 of the patients with acute and in 7 of the patients with stable chronic obstructive airways disease. LVEF was 28 plus or minus 10.4 per cent (average plus or minus SEM) in the patients with acute chronic obstructive airways disease and coronary artery disease which was significantly different (P smaller than 0.001) from LVEF in patients without coronary artery disease (61 plus or minus 1.9 per cent). In the patients stable with chronic obstructive airways disease and coronary artery disease, LVEF was (42 plus or minus 3.5 per cent), significantly different (P smaller than 0.001) from LVEF in those without coronary artery disease (55 plus or minus 2.1 per cent). There was no relationship between LVEF and arterial oxygen, or carbon dioxide tension, or pH. Results suggest that LVEF is normal in patients with severe lung disease alone and that reduced LVEF in patients with chronic obstructive airways disease can reasonably be ascribed to coronary artery disease.
A comparative study on the genetic effects of hycanthone and oxamniquine.
Oxamniquine (UK-4271; 6-hydroxymethyl-2-isopropylaminomethyl-7-nitro-1,2,3,4-tetrahydroquinoline) is a new schistosomicidal agent currently undergoing clinical investigation in South America. Essentially a complete cure rate against Brazilian Schistosoma mansoni has been seen in adults with a single im dose of 7.5 mg/kg or a single oral dose of 15 mg/kg. These regimens were tolerated without significant toxicity. To assess its mutagenic potential, oxamniquine was examined in a battery of genetic tests designed to detect mutations at the gene and chromosome levels. For comparative purposes, hycanthone, a schistosomicide with extensively studied mutagenic properties, was evaluated in a similar series of tests. Point mutations were measured in a series of histidineless auxotrophs of Salmonella typhimurium in direct plate and host-mediated assays. Gross chromosomal aberrations were assessed in human leucocyte cultures and in bone marrow preparations from drug-treated mice. Effects on germ cells were tested in the dominant-lethal assay. Hycanthone showed significant mutagenic activity in the direct bacterial tests and the in vivo and in vitro cytogenetic assays. No response was detected in the host-mediated or dominant-lethal assays. On the other hand, oxamniquine produced no drug-related mutagenic effects in the cytogenetic, host-mediated, or dominant-lethal tests at doses up to 150 mg/kg administered parenterally. Oxamniquine produced a weak response in the frameshift mutant, TA1538, of Salmonella typhimurium in direct plate tests with and without liver microsomal enzymes. However, this response was achieved only by using a concentration of compound which was several orders of magnitude higher than that required to produce a similar response to hycanthone.
Effect of norepinephrine and fluid administration on pulmonary extravascular water volume in dogs.
The effects of norepinephrine-induced vasoconstriction on pulmonary extravascular water volume (PEWV) and central volume were studied before and after intravenous volume expansion with 5% dextrose and water (20 ml/kg body weight). PEWV was measured by double isotope dilution and gravimetric analysis and assessed by electron photomicrography. Comparisons were made with saline-treated control dogs. Thirty-six dogs were studied after they had been anesthetized with sodium pentobarbital. PEWV determined by indicator dilution increased during norepinephrine infusion, especially after volume expansion; in contrast, PEWV in control dogs was constant despite similar increases in pulmonary arterial and left atrial pressures. However, measurements of PEWV by gravimetric analysis and inspection of electron photomicrographs failed to reveal extravascular accumulation of water in vasoconstricted dogs. Thus, it was concluded that the increased PEWV measured by indicator dilution in norepinephrine-treated dogs compared with that in saline-treated dogs reflects more complete perfusion of pulmonary capillaries and access of the diffusible indicator to additional lung tissues and spaces. Improved capillary filling presumably is attributable to peripheral vasoconstriction and redistribution of blood into the thorax. PEWV determined by gravimetric analysis in dogs that had had open-chest procedures for lung biopsy and electron photomicrography was significantly less than that in dogs with their chests closed throughout the experiments. Although the mechanism for the water loss in unknown, the difference must be recognized when the results from various types of experiments are compared.
Platelet survival time in severe chronic airway obstruction.
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