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Biomedical subjects

J Butler

Publications and source records attributed to J Butler.

At least 145 records · Page 8Linked to original sources
PubMed1985

O6-Methylguanine methyltransferase activity is increased in rat tissues by ionising radiation.

The effect of whole body ionising radiation from a linear accelerator on rat tissue O6-methylguanine (O6-meG) methyltransferase (MT) activity has been assessed using an assay which measures the transfer of 3H-radioactivity from 3H-methylated substrate DNA to protein. The maximal effect occurred 2 days after a 1 krad dose, at which time activity in liver extracts was increased approximately 5-fold in two different rat strains. Activity in lung and kidney was increased approximately 4- and 2-fold, respectively. Similar degrees of enhancement were found in these three tissues using an h.p.l.c. method for measuring MT activity. The increase in activity was reflected in an increased capacity to repair O6-meG produced in liver DNA by administration of [14C]dimethylnitrosamine (DMN): this effect was dose dependent, being detectable after 30 rads and maximal after 600 rads. Incorporation of labelled breakdown products of the DMN into adenine in DNA increased as the dose radiation increased suggesting an inhibition of DNA synthesis. The implications of these results for the mechanism of enhancing O6-meG repair are discussed.

Animals↗
PubMed1985

Predicting tumor response in patients with colorectal hepatic metastases.

Until now, there has been no reliable means of predicting tumor response to chemotherapy in patients with metastatic colorectal cancer. Using arterial nuclide flow scans as a determinant of tumor response, the degree of tumor perfusion was evaluated in a blinded prospective study. Seventy-three patients with colorectal hepatic metastases received continuous hepatic arterial (N = 52) or systemic intravenous (N = 21) chemotherapy using an implantable pump. All patients had pretreatment hepatic arteriography and arterial flow scans using 99mTc macroaggregated albumin (99mTc-MAA). An arteriogram was characterized as positive if it showed tumor hypervascularity; the 99mTc-MAA flow scan was considered positive if it showed increased tumor uptake relative to the liver. Of 47 patients with an evaluable 99mTc-MAA flow scan who were treated with arterial infusion, 31 had a positive scan; in this group 16 responded to chemotherapy. The 99mTc-MAA scan was negative in 16 patients, of whom one responded to chemotherapy (p less than 0.006). The 99mTc-MAA scan had the greatest predictive value in previously untreated patients (sensitivity = 91%; specificity = 77%). The arteriogram was positive in 25 of 46 evaluable patients, but this finding had little predictive value for tumor response (sensitivity = 56%; specificity = 46%). Of 21 patients receiving systemic intravenous infusion, the scan was positive in nine patients, of whom seven responded to chemotherapy. The 99mTc-MAA scan was negative in 12 patients, of whom one responded to chemotherapy (sensitivity = 88%; specificity = 85%). When 99mTc-MAA-positive and -negative groups were compared, there were no differences in mean patient age, per cent liver involvement, tumor size, or plasma liver function tests. Hepatic tumor perfusion as determined by MAA arterial flow scan is a reliable predictor of tumor response in patients with metastases from large bowel cancer. The test provides a valuable criterion for selecting individuals for treatment of metastases from large bowel cancer by infusion chemotherapy.

Adult↗
PubMed1985

Regulation of increase in anastomotic blood flow following pulmonary arterial occlusion.

We have previously shown that there is an acute increase in anastomotic bronchial blood flow (Qbr) after pulmonary arterial obstruction in dogs. We examined the role of arachidonic acid metabolites in mediating this increase. The left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in open-chested anesthetized dogs (n = 19). Qbr was measured from the amount of blood that overflowed from the closed vascular circuit of the suspended LLL and changes in its weight. In the control animals, there was a prompt and significant increase in Qbr following pulmonary arterial obstruction. Pretreatment with indomethacin (n = 6) or sodium salicylate (n = 4) almost completely blocked this rise in Qbr. Following pulmonary arterial occlusion, there was a rise in both thromboxane and a prostacyclin metabolite (6-keto-PGF1 alpha) in the blood of the pulmonary circulation of the LLL, although the 6-keto-PGF1 alpha rose relatively more. Pretreatment with indomethacin caused a fall in both thromboxane and prostacyclin levels (n = 3), which no longer rose after pulmonary arterial occlusion. These findings suggested that the balance of the vasodilator (prostacyclin) and vasoconstrictor (thromboxane) prostaglandins may play an important role in mediating the rise in Qbr that follows pulmonary arterial obstruction.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Transmission of airway pressure to pleural space during lung edema and chest wall restriction.

To investigate the influence of positive end-expiratory pressure (PEEP) on hemodynamic measurements we examined the transmission of airway pressure to the pleural space during varying conditions of lung and chest wall compliance. Eight ventilated anesthetized dogs were studied in the supine position with the chest closed. Increases in pleural pressure were similar for both small and large PEEP increments (5-20 cmH2O), whether measured in the esophagus (Pes) or in the juxtacardiac space by a wafer sensor (Pj). Increments in Pj exceeded the increments in Pes at all levels of PEEP and under each condition of altered lung and chest wall compliance. When chest wall compliance was reduced by thoracic and abdominal binding, the fraction of PEEP sensed in the pleural space increased as theoretically predicted. Acute edematous lung injury produced by oleic acid (OA) did not alter the deflation limb pressure-volume characteristics of the lung, provided that end-inspiratory volume was adequate. With the chest and abdomen restricted OA was associated with less than normal transmission of airway pressure to the pleural space, most likely because the end-inspiratory volume required to restore normal deflation characteristics was not attained. Together these results indicate that the influence of acute edematous lung injury on the transmission of airway pressure to the pleural space depends importantly on the peak volume achieved during inspiration.

Airway Resistance↗
PubMed1985

Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes.

We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments.

Animals↗
PubMed1985

Increases in intrathoracic pressure do not explain the rise in left ventricular end-diastolic pressure that occurs during exercise in patients with chronic obstructive pulmonary disease.

During exercise, patients with chronic obstructive pulmonary disease (COPD) increase their pulmonary arterial wedge (Ppaw) and left ventricular (LV) end-diastolic pressures more than normal control subjects. The increase in pressure is commonly attributed to an increase in intrathoracic pressure (Pit). However, mean esophageal pressure (Pes) does not increase with supine exercise in patients with COPD. Because changes in Pes may not represent changes in Pit when recorded in the supine position, we measured Ppaw and Pes during upright exercise in 8 patients with severe air-flow limitation (mean +/- SD) FEV1, 0.88 +/- 0.27 L secondary to COPD and no history or electrocardiographic abnormalities suggesting a previous myocardial infarct, history of angina, evidence of systemic hypertension, or use of cardiac medications. In addition, all patients completed a progressive exercise test to exhaustion without angina or ST segment changes, and all had normal LV function at rest assessed by equilibrium radionuclide ventriculography. The Ppaw increased a mean of 7.2 +/- 4.3 mmHg, whereas Pes increased a mean of only 1.3 +/- 1.6 mmHg. By multiple linear regression analysis, Ppaw was significantly associated with the work level performed (p less than 0.01), but had no significant association with Pes (p greater than 0.1). The change in Ppaw could not be attributed to changes in Pes. If changes in Pes during upright exercise are representative of changes in Pit or juxtacardiac pressure, a rise in Pit does not explain the exercise-induced increase in Ppaw and LV end-diastolic pressure that occurs in patients with COPD.

Blood Gas Analysis↗
PubMed1985

Nifedipine dilates the pulmonary vasculature without producing symptomatic systemic hypotension in upright resting and exercising patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Vasodilator therapy may lower pulmonary vascular resistance in patients with chronic air-flow limitation. However, the effects of these agents on left ventricular afterload, cardiac output, and bronchial smooth muscle could lower the calculated pulmonary vascular resistance without specifically affecting pulmonary vascular tone. In addition, systemic hypotension in the upright position and worsening ventilation/perfusion heterogeneity could limit their use. We determined the pulmonary driving pressure (pulmonary arterial-pulmonary arterial wedge pressure) to flow relationship, as well as the transmural pulmonary arterial pressure in 9 patients with severe chronic air-flow limitation with pulmonary hypertension while in a clinically stable condition. Measurements were made at rest and during 3 stages of progressively increasing upright exercise on a bicycle before and after a single 20-mg dose of nifedipine. Nifedipine displaced both the driving pressure to flow and the pulmonary arterial transmural pressure to flow relationships towards higher flows in every subject, suggesting an active vasodilation. In the upright position, PaO2 did not change, and the systemic arterial pressure was only mildly reduced. In patients with pulmonary hypertension from chronic air-flow limitation, acute administration of nifedipine to upright patients causes pulmonary, as well as systemic vasodilation without causing symptomatic hypotension or reducing arterial oxygenation.

Adult↗
PubMed1985

Progression of cardiovascular disease in acromegalic patients treated by external pituitary irradiation.

Cardiovascular complications are a major cause of morbidity and mortality in acromegaly and seem to be related to the long duration of the disorder. Conventional external pituitary irradiation for acromegaly produces a consistent, but slow, fall in elevated serum growth hormone (GH) levels. It has not been established whether such treatment is effective in preventing the development of cardiovascular complications. The evolution of cardiovascular disease has therefore been studied in 11 acromegalic patients followed up for a mean 10 years (range 3-17) after external pituitary irradiation. At the final follow-up fasting serum GH were significantly (P less than 0.01) lower than pre-irradiation levels, but cardiovascular events (myocardial infarction, dysrhythmias, hypertension, major arterial disease, heart failure) increased significantly in prevalence (P less than 0.01) during this period. Electrocardiographic abnormalities also increased in prevalence. At the final follow-up 6 patients had cardiomegaly on chest X-ray and echocardiographs (10 patients) were abnormal in every case. All 11 patients had evidence of complete or partial anterior hypopituitarism. We confirm that external pituitary irradiation is effective in reducing elevated serum GH levels in acromegaly, but suggest that such a slow reduction in serum GH levels does not retard the development of cardiovascular complications.

Acromegaly↗
PubMed1985

Guillain-Barré syndrome with cytomegalovirus infection of peripheral nerves.

Cytomegalovirus (CMV) infection involving multiple organ systems is a common finding in the acquired immunodeficiency syndrome. Acute CMV neuritis was a complication in two patients with acquired immunodeficiency syndrome. The diagnosis was made in both patients at autopsy, where typical CMV inclusions in the lumbar dorsal roots were noted in one patient and the same inclusions were found in the retroperitoneal peripheral nerves in a second patient. Electron microscopy confirmed the presence of viral particles in affected nerve segments. Patient 1 was hospitalized for ascending motor paralysis that remained unexplained at the time of death. In patient 2 the finding of CMV neuritis was incidental. Although CMV infection has been cited as an event antecedent to acute inflammatory polyradiculopathy (Guillain-Barré syndrome), to our knowledge morphologic evidence of the presence of virus has not been documented in this disease previously.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Direct electrical stimulation promotes growth and enhances survival of aneurogenic muscles of the chick embryo.

Analyses of embryonic aneurogenic muscles indicate that several processes associated with early myogenesis in vivo proceed in the absence of peripheral nerves. However, aneurogenic muscles demonstrate impaired growth and limited survival. To investigate whether neurally mediated activity is responsible for these phenomena, aneurogenic muscles of the chick embryo were directly stimulated in vivo via implanted electrodes. Volumetric analyses of stimulated aneurogenic brachial (latissimus dorsi) muscles from Stage (St) 33 (7.5 to 8 days) through St 37 (11 days) demonstrated that growth was enhanced significantly beyond the level characteristic of unstimulated aneurogenic muscles. Moreover, for the majority of embryos, the stimulation regimen actually rescued the posterior latissimus dorsi muscle which characteristically does not survive beyond St 32 (7.5 days) in the aneurogenic state. Thus, our results implicate activity per se as an important factor necessary for the proper growth and survival of brachial muscles during early embryogenesis. The stimulation regimen, however, did not alter myosin ATPase profiles.

Animals↗
PubMed1985

The radiation chemistry of some platinum-containing radiosensitizers and related compounds.

Oxidation and reduction of cis- and trans-dichlorodiammine platinum II (cis- and trans-PDD), cis-dichlorobis(1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole-N3)-p latinum II (cis-Flap), and cis-dichlorobis(isopropylamine)-trans-dihydroxyplatinum IV (Chip) have been studied using pulse radiolysis. Spectra corresponding to platinum in various oxidation states have been observed and several rate constants have been obtained. Reduction of all the compounds, except cis-Flap, produces species of a lower oxidation state of platinum which subsequently have both chloride ligands replaced. Ultimately, these products disproportionate. In the case of cis-Flap, reduction occurred on the nitroimidazole ligand. This was verified by the absence of platinum metal after disproportionation. Oxidation of all four compounds consists of production of a higher oxidation state of platinum followed by replacement of chloride ligands and finally disproportionation of the products. Only cis-Flap and Chip could be reduced by oxidized DNA bases. The one-electron reduction potential of cis-Flap was found to be -370 +/- 10 mV. trans-Flap had almost the same value. It was not possible to measure the potentials of the other compounds since their ligands were replaced rapidly but it is estimated that the one-electron reduction potentials decrease in the order cis- or trans-Flap greater than Chip greater than cis-PDD greater than trans-PDD.

Antineoplastic Agents↗
PubMed1984

The repair of oxidized amino acids by antioxidants.

Natural and synthetic antioxidants have been shown to repair tryptophan radicals produced from the one-electron oxidation of the free tryptophan amino acid. It has also been observed that both tryptophan and tyrosine radicals in lysozyme can be repaired by these antioxidants to varying degrees of efficiency. Although SDS-solubilized alpha-tocopherol efficiently repairs free tryptophan radicals, it is very inefficient in repairing the amino acids in lysozyme. The rigidity and immobility of solubilized alpha-tocopherol can explain this lack of efficiency.

Antioxidants↗
PubMed1984

Influence of DNA binding on the formation and reactions of tryptophan and tyrosine radicals in peptides and proteins.

The rate constant of the one-electron oxidation of the tryptophan (Trp) or tyrosine (Tyr) residues by Br- X 2 radical anions is strongly decreased when the peptides are bound to DNA. Oxidation by N X 3 is much less affected by binding. These results can be explained by electrostatic repulsion between the charged polyphosphate backbone and the Br- X 2 radicals. Once oxidized, the interacting aromatic residues react with the DNA in a first order process with a rate constant of the order 10(3) s-1. These results have been extended to the single strand binding protein: the product of gene 32 of phage T4 (gp 32). The pulse radiolysis study suggests that one Trp residue of the protein oxidized by the Br- X 2 radicals reacts with the DNA in the complex while one Tyr residue is buried upon association. It is also shown that the exposure of Trp and Tyr residues to radical attack depends on whether the T4 SSB protein is bound to native or heat-denatured DNA.

DNA↗
PubMed1984

Coughs cause systemic blood flow.

Although it is known that rhythmic coughing can preserve consciousness during ventricular fibrillation, the arterial pressure transients which result have not yet been shown to reflect forward blood flow in man. The effectiveness of cough in causing forward flow in eight normal volunteers with bradycardia was studied. They coughed between cardiac cycles, using an audio and visual display of the electrocardiogram. The force of the cough was varied and measured with an oesophageal balloon. Blood flow was recorded with a Döppler velocity probe over the radial artery and a finger or ear photoplethysmograph. Motion artefact on the Döppler record due to coughing was excluded by transiently obstructing the brachial artery. We compared the areas under 5-10 consecutive Döppler and photoplethysmograph pulse flow tracings due to the cough and heart beat with those due to the immediately preceding heart beat alone. They were significantly increased. This augmentation was greater in those flow pulses accompanied by a more vigorous cough. It is concluded that coughing is associated with an effort dependent forward flow pulse in the arterial circulation.

Adult↗
PubMed1984

Acute increase in anastomotic bronchial blood flow after pulmonary arterial obstruction.

We examined the acute changes in anastomotic bronchial blood flow (Qbr) serially for the 1st h after pulmonary arterial obstruction and subsequent reperfusion. We isolated and perfused the pulmonary circulation of the otherwise intact left lower lobe (LLL) with autologous blood in the widely opened chest of anesthetized dogs. Qbr was measured from the amount of blood overflowing from the closed pulmonary vascular circuit and the changes in the lobe weight. The right lung and the test lobe (LLL) were ventilated independently. The LLL, which was in zone 2 (mean pulmonary arterial pressure = 14.8 cm H2O, pulmonary venous pressure = 0, alveolar pressure = 5-15 cmH2O), was weighed continuously. The systemic blood pressure, gases, and acid-base status were kept constant. In control dogs without pulmonary arterial obstruction, the Qbr did not change for 2 h. Five minutes after pulmonary arterial obstruction, there was already a marked increase in Qbr, which then continued to increase for 1 h. After reperfusion, Qbr decreased. The increase in Qbr was greater after complete lobar than sublobar pulmonary arterial obstruction. It was unaltered when the downstream pulmonary venous pressure was increased to match the preobstruction pulmonary microvascular pressure. Thus, in zone 2, reduction in downstream pressure was not responsible for the increase in Qbr; neither was the decrease in alveolar PCO2, since ventilating the lobe with 10% CO2 instead of air did not change the Qbr. These findings suggest that there is an acute increase in Qbr after pulmonary arterial obstruction and that is not due to downstream pressure or local PCO2 changes.

Animals↗