Apparatus for bronchial challenge with cold air.
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Biomedical subjects
Publications and source records attributed to E A Harris.
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Maximal expiratory flow/volume curves were recorded from 155 healthy, non-smoking Europeans aged seven to 71 yr and 42 Polynesian children aged nine to 11 yr. Forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), FEV1/FVC, peak expiratory flow (PEF) and flow at 50 and 25% of FVC (V50 and V25) were compared with the predictions made from the equations of Schoenberg, Beck and Bouhuys, describing healthy people in Connecticut, USA. In general the equations described our subjects well; the small but significant discrepancies may reflect either technical factors or possibly a true difference in populations.
The increased risk of pneumonia associated with the administration of immunosuppressive drugs has prompted investigations of mechanisms for drug-induced pulmonary immunopathology. Pulmonary alveolar macrophages normally respond to chemotactic gradients, and, additionally, produce a chemotactic factor for polymorphonuclear leukocytes. A guinea pig model of immunosuppression was created, using week-long courses of cyclophosphamide, 15 mg per kg per day, or cortisone acetate, 100 mg per kg per day, to study the influences of immunosuppressive drugs on alveolar macrophage chemotactic behavior. N-formylmethionyl-leucyl-phenylalanine (f-met-leu-phe), used at 10(-8) M strength, was a potent chemotactic factor for macrophages lavaged from the lungs of normal animals. Pretreatment for 1 wk with cortisone, however, resulted in a 60% reduction in alveolar macrophage responsiveness to f-met-leu-phe (p less than 0.02, t test). In contrast, cyclophosphamide treatment did not lead to chemotactic hyporesponsiveness in pulmonary alveolar macrophages. In further studies, alveolar macrophage tissue culture supernatants from normal and drug-treated animals were compared for the presence of macrophage-derived chemotactic factor. Both cortisone and cyclophosphamide drug regimens resulted in 25% reductions (p less than 0.05) in chemotactic potency of the alveolar macrophage supernatants. Thus, both cortisone acetate and cyclophosphamide treatment appear to adversely influence certain chemotactic activities of pulmonary alveolar macrophages.
A new method of partial erythrocyte exchange for pregnancies complicated by a major hemoglobinopathy is described. The Haemonetics 30 Cell Separator allows efficient withdrawal and discard of the patient's erythrocytes. The patient's leukocytes, platelets, and plasma are conserved and returned with washed, compatible donor red cells which contain Hb AA. Three pregnant black women with significant hemoglobinopathies were treated by this modality during their pregnancies. Vaginal term deliveries were accomplished in each case. The method offers advantages in the efficiency of blood quantity displacement, patient comfort, adaptability to the patient with severe anemia, and the use of outpatient facilities. The method is suggested for use whenever a patient with an obstetrically significant hemoglobin variant needs transfusions of erythocytes.
Each of 10 patients undergoing hypothermic cardiopulmonary bypass was perfused in turn with (1) the standard flow delivered by a roller pump and (2) pulsatile flow induced by a "pulsatile assist device" (Datascope Corp., Paramus, N. J), presented in random order at the same mean flow. Whole-body oxygen consumption, blood lactate concentration, systemic vascular resistance, urinary flow, and thermal gradients were measured during each type of flow and after rewarming. No significant difference in any of these variables was seen between the two types of flow. After conventional rewarming the temperature gradient between core tissues and muscle was not influenced by the type of flow used during rewarming.
We have shown that ethylene oxide (EO), absorbed by polyvinyl chloride (PVC) and rubber components of the cardiopulmonary bypass (CPB) circuit during sterilization, is subsequently eluted by the circulating blood-prime mixture and enters the patient. The amount of EO available for elution is diminished by increasing the airing period of the tubing after sterilization, but it is still appreciable after 72 hours' airing. When tubing is used after 24 hours' airing, the amount of EO which enters the patient during 90 minutes of CPB is probably at least 70 mg. During the first few hours after CPB, the amount of EO recoverable from the patient's blood rapidly diminishes, probably because of the binding of EO in irreversible chemical combination.
The mean transit time (MTT), coefficient of variation (CoV), and index of skewness (IoS) of transit times of the forced expiratory flow/time curve have been compared with maximal mid-expiratory flow (MMEF), flow at 75, 50, and 25% of vital capacity (V75, V50, and V25), and the ratio of forced expiratory volume in 1 second (FEV1) to vital capacity (VC) in 51 asthmatic children judged on clinical grounds to be in remission. In 19 children all eight indices were normal. Of the remaining 32, MTT was normal in 5, V50 in 11, V75 in 12, and FEV1/VC and MMEF in 13 each. MTT was significantly more sensitive in detecting abnormality when other indices were normal, and abnormalities in MTT were of significantly greater magnitude when present. In 12 patients with at least one abnormal index given salbutamol aerosol, MTT was not more sensitive than MMEF, V25, FEV1/VC, or V50 in detecting change.
Mean transit time (MTT), coefficient of variation (COV), and index of skewness (IOS) of transit times were measured, with the more conventional derivatives of the forced expiratory spirogram, in 178 healthy people aged 6-71 yr breathing air, and in 18 healthy adults breathing 20% oxygen in helium (O2He) in addition. Breathing O2He very significantly altered MTT and all derivatives with dimensions of flow or time, but altered COV and IOS very little. Between 6 and 30 yr mean MTT, after adjustment for expired volume, remained constant and then increased to 71 yr. Mean COV and IOS increased from 6 to 71 yr, though with an apparent change in rate during the early teens. The results suggest that whereas the resistance of large airways falls in proportion to growth of the lungs, small-airway resistance becomes less uniform during both childhood and adult life.
Myocardial oxygen consumption (Vo2) and lactate flux were measured in 12 patients with aortic valve disease and left ventricular hypertrophy during cardiac surgery with hypothermic cardiopulmonary bypass and artificial coronary perfusion. Coronary flow was varied from "standard" flow-defined as giving a "line pressure" of 110 mm. Hg-to 25 or 50 percent higher than standard flow. Lactate flux was not significant at any flow. Vo2 was higher at +25 percent flow that at standard flow, but no significant further increase in Vo2 occurred at +50 percent. Myocardial Q10 and coronary vascular resistance also approached optimal values at a flow of +25 percent, corresponding with a mean coronary flow of 203 ml. times min -1. The difficulties are discussed of standardizing coronary perfusion in useful practical terms.
Small insulinomas may be undetectable by arteriography or palpation of the pancreas. They can be identified, however, by the point at which high insulin levels are detected in the venous effluent sampled at several sites by catheterisation of the splenic and portal veins at laparotomy or via the percutaneous transhepatic route. Diagnosis by catheterisation techniques made it possible to resect only that part of the pancreas containing the tumour (in one patient the head and in another the body of the pancreas). Improved localisation is essential in planning an operation, and often removes the need for lengthy trials of medical therapy before laparotomy.
1. Data have been combined from three previous series to provide revised standards for the prediction of physiological dead-space volume (VD), arterial oxygen tension (Pa,O2), alveolar-to-arterial oxygen-tension difference (PAO2--Pa,O2) and venous admixture fraction (QVa/Qt) in the sitting position. 2. These standards, based on measurements in 96 healthy men and women aged from 20 to 74 years, largely confirm conclusions drawn from the first series of 48 subjects. 3. VD is best predicted on age, height, tidal volume and the reciprocal of respiratory frequency. Pa,O2,(PA,O2--Pa,O2) and Qva/Qt are adequately predicted on age alone.
The linearity and repeatability of measurements of total haemoglobin concentration ([Hb]) and oxygen saturation (So2) by the OSM2 oximeter have been studied. Standard deviations (SD) of measurements from linearity were as follows: [Hb], 4.2 g . litre-1; So2, 1.14 to 1.08% between zero and 100% saturation. Reproducibility by a single operator was within SD 1.1 g . litre-1 for [Hb] and 0.32% for So2, and between operators the means of 5 measurements had SD 0.42 g . litre-1 for [Hb] and 0.19% for So2, suggesting little if any extra variation from one operator to another. Foetal haemoglobin behaved as adult haemoglobin, but carboxyhaemoglobin caused a systematic and reproducible error in So2 measurement, from which HbCO concentration can be derived.
Cardiac output, venous admixture, physiological dead space, blood gas tensions, inspired gas distribution, and other respiratory variables were measured in 10 patients breathing both air and oxygen before and on five occasions up to 10 days after coronary artery vein-graft operations under cardiopulmonary bypass with moderate hypothermia. Cardiac output was unchanged at 8 hours but fell 8 percent by 22 hours. Thereafter it progressively increased and at 10 days was higher than before the operation. Venous admixture rose to a maximum at 28 to 48 hours, postoperatively, but the increase was inversely related to the magnitude of preoperative admixture. The part played by airway and alveolar closure in determining venous admixture is discussed. While admixture increased, the nitrogen-clearance curve improved, presumably due to progressive "dropout" of the worst-ventilated regions. Physiological dead space fell to a minimum at 28 hours after operation; this was attributed to a fall in the end-inspiratory position consequent upon a reduction in both functional residual capacity and tidal volume. There was an increase in ventilation after operation, and this persisted at 10 days; it appeared to be due to reflex stimulation from the lungs and chest wall.
In six patients undergoing coronary vein graft operations under cardiopulmonary bypass and hypothermia, the temperatures of arterial and mixed-venous blood, nosopharynx, oesophagus, liver, rectum, deltoid and vastus lateralis muscles and 10 skin sites were recorded. Whole-body oxygen consumption was measured before cooling and twice during hypothermia. On average, a patient lost 1000 kJ of heat by the end of hypothermia, of which 84% was lost to the heat-exchanger and pump circuit. Evaporative and convective loss amounted to 380 kJ, while the patient's metabolism supplied 220 kJ. During rewarming, the pump returned 670 kJ to the patient. Nasopharyngeal temperature reflected accurately venous, oesophageal and hepatic temperatures in the steady state; however, it was slow to reflect changes. Compared with other sites, muscle remains warmer during hypothermia and cooler after rewarming.
Eight patients undergoing cardiopulmonary bypass with hypothermia received, during part of the hypothermic phase, an infusion of sodium nitroprusside (SNP). Oxygen consumption was measured during the infusion and during control periods. Despite causing a marked reduction of arterial pressure, SNP was not shown to have any significant effect upon whole-body oxygen consumption or lactate concentration in the blood.
A systematic investigation was undertaken to determine which factors affect the calibration of a Gilford monochromatic densitometer used for recording indicator-dilution curves with indocyanine green. Calibration was not influenced by variation of withdrawal speeds from 6.4 to 20.6 cm3/min but varied with differing sampling systems. Variation in haemoglobin from 10 to 17.5 g-dl-1 or in haematocrit from 30 to 60% did not affect calibration. Calibration lines showed both curvature and hysteresis. The opitcal properties of indocyanine green were not affected by storage of diluted dye in the dark for 24 hours but were altered by the presence of contrast media used in angiography. No systematic error resulted from the substitution of stored ACD blood for patient's blood in calibration although random error was increased. Recommendations based on these findings are made for a simple calibration technique which avoids systematic error.
Alveolar-arterial PO2 difference ([A-a]PO2), venous admixture, and physiologic dead space were measured in 24 healthy men and women 23 to 72 years of age in the sitting and supine positions, breathing air, breathing O2, and breathing O2 in deep breaths. In the supine (but not the sitting) position, (A-a)PO2 and venous admixture, breathing both air and O2, were more highly correlated with the difference between closing volume and expiratory reserve volume than with age. The change in (A-a)PO2 and venous admixture from sitting to lying was related to the change in closing volume minus expiratory reserve volume, during both air and O2 breathing. These results confirm previous work on the contribution of gravity-dependent airway closure to the air-breathing venous admixture. They further indicate that the same mechanism is important when O2 is breathed, and it may account for most of the alveoli that close during O2 breathing because of critically low ventilation perfusion ratios. Physiologic dead space in the supine position may be predicted by subtracting 12.5% from the normal sitting value for the same tidal volume and respiratory frequency.
The effects of single oral doses of the cardioselective beta adrenoceptor blocking drugs, metoprolol and tolamolol, on specific airways resistance (SRaw) were compared with those of propranolol and practolol in 6 healthy volunteers and in 12 patients with bronchial asthma. Whole-body plethysmography was used to measure SRaw and the blocking potency of different antagonists assessed by the degree of inhibition of tachycardia due to exercise on a treadmill. The changes correlated with plasma drug levels. Propranolol and practolol were measured fluorometrically and metoprolol by electron-capture gas-liquid chromatography. In normal subjects, about 30% reduction in exercise-induced tachycardia resulted from single doses of 80 mg propranolol (plasma levels, 50.3, SD, 29.5 to 60.8, SD, 26 ng/ml), 250 mg practolol (plasma levels, 1.05, SD, 0.32 to 1.10, SD, 0.55 mug/ml), 100 mg metoprolol (plasma levels, 137, SD, 111 to 152, SD, 100 ng/ml), and 100 mg tolamolol. In patients, these doses of the drugs produced significant increases in SRaw. These increases were greater than those after placebo but significantly so only during the peak effect 1 hr after propranolol. Compared with changes after placebo, significant effects on SRaw were also found in 3 patients given 200 mg of tolamolol. None of the drugs had a significant effect on SRaw in normal subjects. It is concluded that metoprolol, practolol, and tolamolol may impair ventilatory function in asthmatics less than propranolol and that at high doses this difference may not be demonstrable.