Publications
112 results found
Winter RJ, Zhao L, Krausz T, et al., 1991, Neutral endopeptidase 24.11 inhibition reduces pulmonary vascular remodeling in rats exposed to chronic hypoxia., Am Rev Respir Dis, Vol: 144, Pages: 1342-1346, ISSN: 0003-0805
Inhibition of the metabolism of endogenous atrial natriuretic peptide (ANP), by continuous infusion of a specific inhibitor of neutral endopeptidase (membrane metalloendopeptidase E.C. 3.4.24.11), UK 73,967 (candoxatrilat), was undertaken in rats, in which chronic hypoxia was used as a stimulus to induce pulmonary hypertension and right ventricular hypertrophy. Inhibition of neutral endopeptidase 24.11 with low-dose and high-dose UK 73,967 (NEI) increased endogenous plasma ANP by greater than 155% during the development of pulmonary hypertension. NEI treatment reduced mean pulmonary arterial pressure in hypoxia as follows: vehicle 26.6 +/- 4.0 mm Hg; low-dose NEI 22.7 +/- 1.9 mm Hg, and high-dose NEI 22.6 +/- 2.5 mm Hg (both p less than 0.01 compared with hypoxic vehicle); however, it was without effect on pulmonary arterial pressure in normoxia (17.6 +/- 2.2 mm Hg) or on systemic blood pressure. The development of right ventricular hypertrophy was also reduced in both groups treated with NEI (right ventricular weight/left ventricular weight: 0.43 +/- 0.03 vehicle; 0.40 +/- 0.02 low-dose NEI and 0.40 +/- 0.02 high-dose NEI, both p less than 0.05 compared with vehicle). Remodelling of the pulmonary vasculature, characterized by extension of the muscle within the small pulmonary arteries toward the periphery of the lung, was reduced by NEI treatment (percentage of thick-walled peripheral vessels; 19.2 +/- 3.1% vehicle; 10.4 +/- 2.3% low-dose NEI and 8.1 +/- 1.8% high-dose NEI, both p less than 0.001 compared with vehicle). In the isolated blood perfused rat lung pulsed doses of NEI had no effect on pulmonary vascular tone in the absence of ANP. Specific inhibition of the enzyme neutral endopeptidase reduces vascular remodelling, the development of pulmonary hypertension, and right ventricular hypertrophy. Endogenous ANP modulates vascular remodelling in vivo. Retarding the metabolism of endogenous ANP through inhibition of neutral endopeptidase 24.11 represents a pote
WINTER RJD, ZHAO L, KRAUSZ T, et al., 1991, NEUTRAL ENDOPEPTIDASE 24-11 INHIBITION REDUCES PULMONARY VASCULAR REMODELING IN RATS EXPOSED TO CHRONIC HYPOXIA, AMERICAN REVIEW OF RESPIRATORY DISEASE, Vol: 144, Pages: 1342-1346, ISSN: 0003-0805
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- Citations: 45
Zhao L, Winter RJ, Krausz T, et al., 1991, Effects of continuous infusion of atrial natriuretic peptide on the pulmonary hypertension induced by chronic hypoxia in rats., Clin Sci (Lond), Vol: 81, Pages: 379-385, ISSN: 0143-5221
1. The effects of the continuous infusion of atrial natriuretic peptide on the development of pulmonary hypertension were studied in rats exposed to chronic hypoxia. 2. Continuous intravenous infusion of two doses of synthetic rat atrial natriuretic peptide, 300 ng/h per rat (0.10 pmol/h per rat) and 800 ng/h per rat (0.28 pmol/h per rat), attenuated the development of pulmonary hypertension in rats exposed to chronic hypoxia (fractional concentration of oxygen in inspired air = 10%) for 7 days: (i) the pulmonary artery pressure (mean +/- SD) in the vehicle-treated hypoxic group was 45 +/- 6 mmHg compared with 28 +/- 6 mmHg in the vehicle-treated normotoxic group (n = 8, P less than 0.001); (ii) treatment with atrial natriuretic peptide in normoxia did not alter the pulmonary artery pressure, systemic blood pressure or heart rate; (iii) treatment with atrial natriuretic peptide in hypoxia resulted in a lower pulmonary artery pressure in the group treated with 800 ng of atrial natriuretic peptide/h per rat (38 +/- 8 mmHg, P less than 0.05 compared with the vehicle-treated hypoxic group) without affecting the systemic blood pressure or heart rate. 3. Chronic hypoxia resulted in an extension of vascular smooth muscle towards the periphery of the lung with the development of muscle in normally non-muscularized vessels (remodelling).(ABSTRACT TRUNCATED AT 250 WORDS)
ZHAO L, WINTER RJD, KRAUSZ T, et al., 1991, EFFECTS OF CONTINUOUS INFUSION OF ATRIAL-NATRIURETIC-PEPTIDE ON THE PULMONARY-HYPERTENSION INDUCED BY CHRONIC HYPOXIA IN RATS, CLINICAL SCIENCE, Vol: 81, Pages: 379-385, ISSN: 0143-5221
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- Citations: 34
Jones HA, Lakshminarayan S, Becket JM, et al., 1991, Comparison of estimates of cardiac output by indicator dilution and freon 22 uptake during gas mixing in dogs., Cardiovasc Res, Vol: 25, Pages: 523-528, ISSN: 0008-6363
STUDY OBJECTIVE: The aim was to measure cardiac output while rebreathing tidal volumes, by correction of soluble gas uptake for gaseous mixing. DESIGN: Simultaneous measurements of cardiac output by indocyanin green and freon 22 uptake during rebreathing were made. Mixing for a hypothetical gas of identical gaseous diffusivity to freon 22 was calculated by interpolation between concentrations of two insoluble gases, helium and sulphur hexafluoride. Mixing efficiency was estimated by the number of breaths for helium to become 99% equilibrated with lung gas (n99-He). EXPERIMENTAL MATERIAL: Five anaesthetised dogs rebreathed at intervals with 300 ml of test gas. MEASUREMENTS AND MAIN RESULTS: 63 comparisons of cardiac output using indocyanin green and freon 22 uptake (over breaths 7-13 using the mean mixed volume of distribution), gave a mean (95% confidence interval) underestimation of 0.345 (0.093-0.597) litre.min-1 (14%). Exclusion of 12 points in which n99-He was greater than 15 resulted in a mean underestimation of 0.052(-0.163-0.267) litre.min-1 (2%). Without correction for gaseous mixing, freon 22 uptake for these data overestimated blood flow by a mean of 1.31 litre.min-1 (overestimation = 2.7 over breaths 5-11). Use of the equilibrium volume of distribution resulted in an overestimation of blood flow relative to green dye of 1.2 litre.min-1 (breaths 5-11) and 0.76 litre.min-1 (breaths 7-13). CONCLUSIONS: Estimates of cardiac output by soluble gas uptake are optimal when correction is made for mixing of gas of identical diffusivity. The mean mixed gas volume gives the best correlation with the reference method, implying a selective distribution of blood flow to the better ventilated areas.
Trotman-Dickenson B, Weetman AP, Hughes JM, 1991, Upper airflow obstruction and pulmonary function in acromegaly: relationship to disease activity., Q J Med, Vol: 79, Pages: 527-538, ISSN: 0033-5622
Pulmonary function and disease activity were assessed in a large series of patients with acromegaly (19 men and 16 women). Large lungs, defined as a vital capacity greater than 120 per cent of predicted normal occurred in six of 19 males and six of 16 females. Ten of the 12 patients with elevated vital capacity had active disease (growth hormone greater than 5 mU/l during a glucose tolerance test). There was no association with duration of disease. Diffusing capacity was normal overall but DLCO greater than 120 per cent occurred in six of 14 females and one of 18 males. Significant intrathoracic airflow obstruction occurred in eight of 35 patients, six of whom were nonsmokers. Upper (extrathoracic) airflow obstruction was the most common pulmonary function abnormality. A maximal expiratory/inspiratory flow ratio greater than 1.0 at 50 per cent vital capacity occurred in 13 of 18 males and four of 16 female patients, and there was an association with disease activity (17 of 25 subjects with active disease had upper airflow obstruction compared to one of nine in remission; p = 0.01). Nocturnal hypoxaemia occurred in three of 13 patients studied: six of this group had upper airways obstruction. They were all male with elevated growth hormone levels and upper airflow obstruction. In summary, in 35 acromegalics (26 with active disease), large lungs occurred in 12 patients (34 per cent) and upper airflow obstruction in 17 patients (50 per cent). The latter may develop nocturnal hypoxaemia--this was seen in three of six patients with upper airflow obstruction. Upper airways obstruction was more common in males (13 of 18 compared to four of 16 females; p = 0.04) and its presence in males should arouse suspicion of nocturnal hypoxaemia.
Hughes JM, Lockwood DN, Jones HA, et al., 1991, DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis., Respir Physiol, Vol: 83, Pages: 155-166, ISSN: 0034-5687
Pulmonary diffusing capacity for carbon monoxide (DLCO) and pulmonary capillary blood flow (Qp) were measured on exercise in patients with a low DLCO with the aim of predicting, from the overall DL/Qp ratio, diffusion limitation for oxygen and relating it to the fall in arterial oxygen saturation actually observed. Five patients with cryptogenic fibrosing alveolitis (DLCO ranging from 20-54% predicted normal) exercised for 5 min at a work load equal to 60% of their maximum (45 to 90 watts). At 5 min (and previously at rest) they rebreathed rapidly for 15 sec from a 1.0 L bag containing helium (He), sulphur hexafluoride (SF6) and freon-22, 30% oxygen in argon and less than 1 ppm 11C-labelled carbon monoxide. Pulmonary capillary blood flow (Qp) and diffusing capacity (DLCO) were measured from flow-weighted breath-by-breath concentrations of freon-22 and 11CO, after correction for gas mixing delays (using He and SF6). Oxygen saturation (SaO2) (ear oximetry), MO2 and MCO2 and cardiac frequency were measured. PAO2 (ideal) was derived and mixed venous O2 saturation and content were calculated (Fick); PaO2 and PVO2 were derived from standard dissociation curves. For comparison, DLCO and Qp were measured in a similar fashion in five normal subjects exercising at 60 watts. Mean DLCO in patients with fibrosis was 9.62 (SD 2.88) ml.min-1, mm Hg-1 on exercise and mean Qp was 10.48 (SD 1.79) L.min-1 giving mean DLCO/Q ratios of 0.92 (SD 0.28). At 60 watts mean DLCO/Qp in normal subjects was 2.54 (SD 0.3), 2.76-times greater than in patients. SaO2% fell in patients by 3-15% on exercise. Predictions of alveolar-end capillary PO2 gradients from these overall DL/Q gradients showed that diffusion limitation accounted for 99% of the alveolar-arterial PO2 gradient on exercise in fibrosing alveolitis. Hughes (1991 Respir. Physiol. 83:167-178) [corrected] suggests that this simple approach overestimates the contribution of diffusion limitation by about 30%.
Marguerie C, Bunn CC, Beynon HL, et al., 1990, Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes., Q J Med, Vol: 77, Pages: 1019-1038, ISSN: 0033-5622
The clinical and laboratory features of 29 patients who had one of three anti-aminoacyl-tRNA synthetase autoantibodies, anti-Jo1 (histidyl-tRNA synthetase), anti-PL12 (alanyl-tRNA synthetase) or anti-PL7 (threonyl-tRNA synthetase) were analysed and compared with the findings of other published reports. These autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis (24 patients) and pulmonary fibrosis (23 of 29), but also including inflammatory arthritis (26/29), keratoconjunctivitis sicca (17/29), sclerodactyly (21/29), Raynaud's phenomenon (27/29), hepatitis (8/29) and subcutaneous calcinosis (7/29). The most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease. No patient fulfilled the classification criteria for systemic lupus erythematosus, although 10 had autoantibodies to extractable nuclear antigens including Ro, La, RNP, and Sm, and two patients had anti-dsDNA antibodies. Although it seems unlikely that anti-aminoacyl-tRNA synthetase antibodies are directly responsible for causing disease, they may provide an important clue to the aetiology of this unusual syndrome.
Hughes JM, 1990, Fleischner lecture. Radionuclides and the lung: past, present, and future., AJR Am J Roentgenol, Vol: 155, Pages: 455-463, ISSN: 0361-803X
CHILVERS ER, WHYTE MKB, JACKSON JE, et al., 1990, EFFECT OF PERCUTANEOUS TRANSCATHETER EMBOLIZATION ON PULMONARY-FUNCTION, RIGHT-TO-LEFT SHUNT, AND ARTERIAL OXYGENATION IN PATIENTS WITH PULMONARY ARTERIOVENOUS-MALFORMATIONS, AMERICAN REVIEW OF RESPIRATORY DISEASE, Vol: 142, Pages: 420-425, ISSN: 0003-0805
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- Citations: 66
Hughes JM, Allison DJ, 1990, Pulmonary arteriovenous malformations: the radiologist replaces the surgeon., Clin Radiol, Vol: 41, Pages: 297-298, ISSN: 0009-9260
Fidler H, Booth A, Hodgson HJ, et al., 1990, Portal vein thrombosis in myeloproliferative disease. Uses of thrombolytic and antiplatelet treatment., BMJ, Vol: 300, Pages: 590-592, ISSN: 0959-8138
WIENER CM, MCKENNA WJ, MYERS MJ, et al., 1990, LEFT LOWER LOBE VENTILATION IS REDUCED IN PATIENTS WITH CARDIOMEGALY IN THE SUPINE BUT NOT THE PRONE POSITION, AMERICAN REVIEW OF RESPIRATORY DISEASE, Vol: 141, Pages: 150-155, ISSN: 0003-0805
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- Citations: 35
Jackson JE, Whyte MK, Allison DJ, et al., 1990, Coil embolization of pulmonary arteriovenous malformations., Cor Vasa, Vol: 32, Pages: 191-196, ISSN: 0010-8650
Sixteen patients with pulmonary arteriovenous malformations (PAVM) have been treated by percutaneous transvenous coil embolization. In the ten patients who have had all their angiographically demonstrable PAVM's embolised there has been a reduction of right to left shunting from a mean of 28.1% to 13% and an improvement in mean arterial oxygen saturation from 87.4% to 92.4%. Eight of these ten patients now have oxygen saturations of more than 90%. All patients have shown symptomatic improvement. There have been three complications relating to the embolizations, none of which has been serious. Coil embolization of PAVM's is an effective, safe and well tolerated procedure. Embolization should be performed in all cases of PAVM's to prevent paradoxical embolization.
Rhodes CG, Valind SO, Brudin LH, et al., 1989, Quantification of regional V/Q ratios in humans by use of PET. I. Theory., J Appl Physiol (1985), Vol: 66, Pages: 1896-1904, ISSN: 8750-7587
With positron emission tomography, quantitative measurements of regional alveolar and mixed venous concentrations of positron-emitting radioisotopes can be made within a transaxial section through the thorax. This allows the calculation of regional ventilation-to-perfusion (V/Q) ratios by use of established tracer dilution theory and the constant intravenous infusion of 13N. This paper considers the effect of the inspiration of dead-space gas on regional V/Q and investigates the relationship between the measured V/Q, physiological V/Q, and V/Q defined conventionally in terms of bulk gas flow (VA/Q). Ventilation has been described in terms of net gas transport, and the term effective ventilation has been introduced. A simple two-compartment model has been constructed to allow for the reinspiration of regional (or personal) and common dead-space gas. By use of this model, with parameters representative of normal lung the effective V/Q ratio for 13N [(VA/Q)eff(13N)] is shown to overestimate VA/Q by 18% when VA/Q = 0.1 but underestimate VA/Q by 68% when VA/Q = 10. For physiological gases, the model predicts that the behavior of O2 should be similar to that of 13N, so that, in terms of gas transport, V/Q ratios obtained using the infusion of 13N closely follow those for O2. Values of the effective V/Q ratio for CO2 [(VA/Q)eff(CO2)] lie approximately halfway between (VA/Q)eff(13N) and VA/Q. These results indicate that dead-space ventilation is far less a confounding issue when V/Q is considered in terms of net gas transport (VAeff), rather than bulk flow (VA).(ABSTRACT TRUNCATED AT 250 WORDS)
Rhodes CG, Valind SO, Brudin LH, et al., 1989, Quantification of regional V/Q ratios in humans by use of PET. II. Procedure and normal values., J Appl Physiol (1985), Vol: 66, Pages: 1905-1913, ISSN: 8750-7587
Regional measurements of tissue isotope concentration, made using positron emission tomography (PET), allow tracer models to be used in a quantitative manner to provide topographic distributions of many structural and functional parameters, each derived for the same well-defined lung element. In this paper we describe a technique to measure regional ventilation-perfusion ratios (V/Q), in absolute units, by use of PET and the continuous intravenous infusion of an inert gas isotope, 13N, and report on measurements made in 12 normal subjects (4 smokers). Data were obtained from a single lung section (slice thickness, 1.7 cm full width at half-maximum response to a line source) at the level of the right ventricle in the supine posture during quiet breathing. For the 12 subjects, volume-weighted mean values of V/Q, averaged over individual right and left lung fields, ranged from 0.50 to 1.29. Analysis of these means showed no difference between lungs: right, 0.80 +/- 0.23 SD; left, 0.76 +/- 0.20 SD. Topographically, a systematic fall of V/Q in the ventrodorsal direction was observed in eight of the subjects (mean ventrodorsal difference 0.39, range 0.19-0.90), whereas two showed a clear increase toward dependent lung regions (range 0.16-0.26). Seven of the subjects with a falling ventrodorsal V/Q gradient also exhibited discrete regions of low V/Q at the dorsal lung border. We conclude that, in normal subjects, ventilation and perfusion are generally well matched in the supine posture, but isolated mismatching often occurs in dependent lung regions.
CHILVERS ER, PETERS AM, GEORGE P, et al., 1988, QUANTIFICATION OF RIGHT TO LEFT SHUNT THROUGH PULMONARY ARTERIOVENOUS-MALFORMATIONS USING TC-99M) ALBUMIN MICROSPHERES, CLINICAL RADIOLOGY, Vol: 39, Pages: 611-614, ISSN: 0009-9260
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- Citations: 38
Nolop KB, Rhodes CG, Brudin LH, et al., 1987, Glucose utilization in vivo by human pulmonary neoplasms., Cancer, Vol: 60, Pages: 2682-2689, ISSN: 0008-543X
Neoplastic tissue in general shows a high rate of glucose consumption under both anaerobic and aerobic conditions. Using positron emission tomography (PET) we measured the rate of uptake of the glucose analogue 18fluoro-2-deoxy-D-glucose (18FDG) in 12 patients with carcinoma of the lung. The tumor types were six squamous cell, two large cell, two oat cell, one adenocarcinoma, and one undifferentiated carcinoma. In each patient a transaxial plane was selected that contained the bulk of the tumor tissue. Regional density and blood volume were measured. Following the intravenous injection of 18FDG, the rates of uptake in the tumor and normal lung tissue were assessed from sequential scans over 1 hour. In each patient the rate of uptake of 18FDG in the tumor tissue was significantly increased relative to normal lung tissue. For the group the rate of uptake by the tumor was 211.4 +/- 69.4 ml/100 g/hr (mean +/- SD) compared to 31.9 +/- 13.2 in the contralateral lung (P less than 0.05). The tumor-to-normal tissue ratio of 6.6 (range, 2.7 to 14.6) was higher than previously reported ratios for brain and liver tumors. In contrast to brain tumors there was little correlation between tumor type and rate of 18FDG uptake. Measurements of glucose metabolism taken in vivo in human pulmonary tumors may lead to advances in screening, staging, and therapy.
MAXWELL DL, FULLER RW, CONRADSON TB, et al., 1987, CONTRASTING EFFECTS OF 2 XANTHINES, THEOPHYLLINE AND ENPROFYLLINE, ON THE CARDIORESPIRATORY STIMULATION OF INFUSED ADENOSINE IN MAN, ACTA PHYSIOLOGICA SCANDINAVICA, Vol: 131, Pages: 459-465, ISSN: 0001-6772
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Brudin LH, Rhodes CG, Valind SO, et al., 1987, Regional lung density and blood volume in nonsmoking and smoking subjects measured by PET., J Appl Physiol (1985), Vol: 63, Pages: 1324-1334, ISSN: 8750-7587
Regional lung density (DL) and regional fractional pulmonary blood volume (VB) were measured quantitatively during tidal breathing in 30 healthy supine subjects (15 smokers and 15 nonsmokers) in a 1.7-cm-thick midthoracic cross section using positron emission tomography (PET) and 11CO (inhaled)-labeled erythrocytes. Regional alveolar volume (VA), extravascular lung density (DEV), and relative alveolar size (Valv = VA/DEV) were calculated. For the nonsmokers, mean values (+/- SD between subjects) for the right lung were as follows: DL, 0.28 +/- 0.03 g/cm3; DEV, 0.10 +/- 0.02 g/cm3; and Valv, 7.1 +/- 1.9 ml/g lung tissue. In the smoking subjects DEV (right plus left lung) was 16% higher. No significant difference in VB between smokers and nonsmokers was found. The differences in DEV and VB between right and left lung were not significant. Mean values (+/- SD) of the dorsal-to-ventral ratios calculated for the right lung in the nonsmokers were as follows: DL, 1.34 +/- 0.16; VA, 0.90 +/- 0.05; VB, 1.52 +/- 0.26; DEV, 1.10 +/- 0.17; and Valv, 0.85 +/- 0.19. Almost identical ratios were found in the smokers. The influence of overall thoracic expansion was investigated in one subject restudied during voluntary hyperinflation and during positive end-expiratory pressure.
OPENSHAW PJM, JONES HA, HUGHES JMB, 1986, THE EFFECT OF SALBUTAMOL IN CHRONIC AIR-FLOW OBSTRUCTION, CLINICAL SCIENCE, Vol: 70, Pages: P69-P69, ISSN: 0143-5221
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