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Biomedical subjects

H A Jones

Publications and source records attributed to H A Jones.

At least 37 records · Page 2Linked to original sources

Facilitating prelinguistic communication skills in young children with developmental delay.

Very little research has focused on the development and evaluation of intervention strategies designed to facilitate the acquisition of prelinguistic communication skills. We conducted two experiments to determine the effects of a milieu teaching approach on the acquisition and generalization of specific prelinguistic communication skills. In the first experiment, we utilized this intervention approach within a multiple baseline design to teach prelinguistic requesting, commenting, and vocal imitation to a single subject with Down syndrome and language delay. The results indicated that the intervention approach was effective at facilitating the child's use of these skills within the treatment setting. Therefore, in the second experiment we conducted a more comprehensive analysis of this approach with 4 subjects with mental retardation. Three of these subjects were taught to request, and 1 subject was taught both to request and to comment. The effects were experimentally evaluated with multiple baseline across subjects design. The results indicated that the intervention was effective in eliciting the intervention targets within the training setting for all 4 subjects. All 4 subjects showed evidence of generalization across stimulus materials, setting, teachers, and interaction style. There was also evidence of reciprocal effects on how classroom teachers in the generalization setting interacted with the subjects as a result of changes in the child's communication behavior.

Child, Preschool↗

Cardiopulmonary response to exercise in patients with intrapulmonary vascular shunts.

The majority of patients with intrapulmonary right-to-left shunting due to pulmonary arteriovenous malformations-exhibit good maximum exercise capacity (> 70% predicted) despite profound arterial oxygen desaturation. We studied seven such patients to assess tissue oxygen delivery during steady-state exercise. From rest to exercise [50 +/- 7 (SE) W] arterial saturation fell from 80 +/- 3 to 74 +/- 3%, and mean right-to-left shunt increased slightly from 31 +/- 4 to 34 +/- 5% (P = NS). Minute ventilation was high for oxygen uptake, and the ventilatory equivalent was raised (174 +/- 19% predicted) and was correlated with shunt size (r = 0.93). The majority of the patients maintained pulmonary alveolar blood flow within the predicted range for their power output, but total cardiac output was increased to 142 +/- 11% predicted due to flow through the shunt. Consequently, on exercise, oxygen delivery per unit oxygen consumption [2.3-3.3 (normal range 1.6-2.4)] and calculated mixed venous oxygen tension (27.0 +/- 0.8 Torr) were preserved. Arterial PCO2 rose on exercise by 2.8 +/- 1.2 Torr, in proportion to the ratio of flow through the shunt to total cardiac output (r = 0.73), but remained low (33.1 +/- 1.4 Torr) in absolute terms. The high cardiac output on exercise may be facilitated by a low pulmonary vascular resistance (0.33 +/- 0.08 mmHg.1-1.min, measured at rest), which may explain why exercise performance is better in these patients than in patients with equivalent hypoxemia from other causes.

Adolescent↗

The effect of pancreatic polypeptide on glucose disposal after surgical alterations of the pancreas.

Surgical alterations of the pancreas result in anatomic changes that can affect postoperative glucose metabolism. Pancreas transplantation results in reduction of beta-cell mass, systemic release of insulin, and denervation. The authors hypothesized that such alterations affect peripheral glucose disposal to induce an "insensitivity" to endogenously (systemically) released insulin. Additionally, they hypothesized that surgically induced deficiency of the postprandial hormone, pancreatic polypeptide, might contribute to altered glucose disposal. The authors studied two surgical models in dogs known to be devoid of pancreatic polypeptide--70% proximal pancreatectomy (PPx) and PPx plus distal pancreas autotransplantation (PAT/B). Oral glucose challenge and euglycemic hyperinsulinemic clamp studies were performed before and after a 16-day "pulsed" infusion of pancreatic polypeptide. Both surgical procedures resulted in elevations in the integrated glucose response after oral glucose, which was not affected by pancreatic polypeptide infusion. Euglycemic clamp studies showed decreased hepatic glucose output (Ra) and overall glucose disposal (Rd) in the fasted state for both surgical groups. The transplant animals demonstrated significant decreases in Rd during the hyperinsulinemic challenge (3.2 +/- 0.01 versus 5.7 +/- 0.01 mg/kg/minute at 60 to 120 minutes for PAT/B versus control). After 16 days of pancreatic polypeptide infusion, however, basal Ra, as well as basal and 60- to 120-minute Rd values, were returned to control values in the transplant group. The authors conclude that pancreas transplantation results in altered glucose disposal, possibly due to an altered effectiveness of systemically released insulin. They conclude that pancreatic polypeptide is an important modulator of peripheral insulin action. Therefore, the role of pancreatic polypeptide must be taken into account when evaluating postoperative glucose metabolism in canine models of pancreas transplantation.

Animals↗

Rapid analysis for metabolites of 11C-labelled drugs: fate of [11C]-S-4-(tert.-butylamino-2-hydroxypropoxy)-benzimidazol-2-one in the dog.

Positron emission tomography (PET) requires the use of compounds labelled with short-lived, positron-emitting isotopes (e.g., t1/2 of 11C approximately 120 min). As the concentration of unbound, non-metabolised drug is required as the input function for modeling, this presents particular problems for the study of the kinetics and metabolism of such compounds. We have now developed a rapid extraction procedure, followed by high-performance liquid chromatography using a short analytical column coupled to an on-line gamma-detector to determine the metabolism and kinetics of a non-selective beta-adrenergic antagonist of high affinity, S-4-(tert.-butylamino-2-hydroxypropoxy)benzimidazol-2-one. This antagonist is potentially well suited to the non-invasive localisation of beta-receptors in vivo. The ligand was rapidly taken up into the beta-receptor pool or excreted in urine, with less than 5% of the drug converted to metabolites. Plasma protein binding was only 16%. No significant metabolism of the ligand was observed in the anaesthetised dog, and, therefore, no correction for blood metabolite concentration is required for kinetic analysis of the 11C-labelled ligand during PET studies in this species. The analytical method reported here should be widely applicable: quantification of metabolites enables accurate estimation of the input function and is critical to the interpretation of PET data.

Adrenergic beta-Antagonists↗

DLCO/Q and diffusion limitation at rest and on exercise in patients with interstitial fibrosis.

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%.

Adult↗

Comparison of estimates of cardiac output by indicator dilution and freon 22 uptake during gas mixing in dogs.

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.

Animals↗

A rapid rebreathing method for measurement of pulmonary gas volume in humans.

We have developed a rapid gas-dilution technique, with which pulmonary gas volume can be measured in only 20 s, even in the presence of maldistribution of ventilation. The subject rebreathes from a 0.75-liter anesthetic bag filled with 10% He and 30% O2 in argon. Breath-by-breath flow-weighted inspired concentrations of all gases present are calculated from continuous measurement by mass spectrometry. Insoluble gas concentrations are corrected continuously for shrinkage of the system volume. By use of these corrected values a mathematical extrapolation predicts the equilibrium concentration for He in the absence of complete mixing. Validation of the technique was carried out by comparing volumes calculated from the predicted equilibrium value with those obtained by whole-body plethysmography in 7 normal subjects and 12 patients with lung disease. In normal subjects equilibrium was usually attained within the 20 breaths and no extrapolation was required. In most of the patients, however, equilibrium was not reached and the use of the extrapolation technique increased the proportion of the lung volume measured by gas dilution from 0.82 +/- 0.16 (SD) to 0.95 +/- 0.12 of that measured by plethysmography.

Adult↗

Modification of pulmonary gas mixing by postural changes.

Mixing for two gases of markedly different gaseous diffusivity, helium (He) (mol wt = 4) and sulfur hexafluoride (SF6) (mol wt = 146) has been studied by a rebreathing method in different postures. In nine normal subjects duplicate measurements were made in the erect (seated), supine, and lateral decubitus posture, at a constant tidal volume (700 ml) and frequency (1 Hz) starting from functional residual capacity (FRC). Additional measurements were made on four of the subjects, rebreathing seated erect at a volume similar to the relaxed FRC supine and supine at a volume similar to the relaxed FRC seated. In the supine posture the mean breath number to reach 99% equilibrium (n99), was not significantly different for the two gases, 8.9 for He and 9.8 for SF6. There was a difference (P less than 0.01) when erect; n99 (He) = 8.2 and n99 (SF6) = 10.9. The greatest He-SF6 difference (P less than 0.001) was in the lateral decubitus position n99 (He) = 10.1 and n99 (SF6) = 15.9. The mean relaxed FRC as percent of seated was 71% supine and 75% in lateral decubitus posture. Rebreathing seated at a lower volume did not abolish the He-SF6 mixing difference nor did rebreathing at a higher volume when supine induce a He-SF6 mixing difference. Thus the effect of posture on gas mixing cannot be due solely to lung volume and must represent a convective and diffusive dependent change in the distribution of ventilation per unit lung volume.

Adult↗

Performance of the large-reservoir oxygen mask (Ventimask).

The performance of large-reservoir Venturi masks ('Ventimask') giving nominal inspired oxygen (O2) concentrations ranging from 24% to 60% was assessed in a face model, in six normal subjects, and in ten patients with severe chronic airflow obstruction at the O2 flow rates recommended. Instantaneous oxygen concentrations were measured with a mass spectrometer ('Centronics MGA200') and volume-weighted to give mean inspired concentrations (FiO2). In human studies volume-weighting was achieved by simultaneous measurement of tidal volume from chest and abdominal motion by the use of a respiratory inductance plethysmograph ('Respitrace'). Reinspiration of dead space from the mask was assessed by measuring FiCO2, which varied from 0.2 to 0.4% (normals) and was 0.6 +/- 0.4% in patients. In normal subjects and patients breathing at rest the FiO2% in 24, 28, 35, and 40% ventimasks was within 1.9% absolute of nominal (range-1.2 to +1.9%) but the 60% mask read low (50.3%). Various factors can make FiO2 less than nominal but the human and model studies indicated that reinspiration of dead space from the mask was more important than hyperventilation. In tachypnoeic patients (frequency greater than 30/min), the O2 flow should be increased to 50% above recommended.

Aged↗

Effect of posture on inter-regional distribution of pulmonary ventilation in man.

Regional ventilation per unit alveolar volume (V/VA) and regional lung expansion (FRCR/TLCR) were measured in twelve normal male human subjects in seated, supine, lateral decubitus and prone postures using a gamma camera and inhalation of the radioactive gases 81Krm (half-life 13 sec) and 85Krm (half-life 4.4 h). FRCR/TLCR decreased from superior to inferior in all postures except prone where it was uniform; V/VA increased from superior to inferior except in the prone position where it was uniform. In the horizontal axis FRCR/TLCR and V/VA were uniformly distributed except for cranial to caudal gradients (with lower values caudally) in supine and lateral decubitus postures. In the prone posture V/VA tended to be higher in caudal lung zones.

Adult↗

Effect of posture on inter-regional distribution of pulmonary perfusion and VA/Q ratios in man.

Using a gamma camera regional pulmonary perfusion per unit alveolar volume (Q/VA) and ventilation-perfusion ratios (VA/Q) were measured in fourteen normal male volunteers in upright, supine, lateral decubitus, prone and prone suspended postures with inhalation and intravenous infusion of radioactive 81Krm (half-life 13 sec) and inhalation of radioactive 85Krm (half-life 4.4 h). In the vertical axis, Q/VA increased from upper to lower lung regions in upright, lateral decubitus, prone and prone suspended postures but was uniform in supine and within the dependent lung in decubitus postures. Horizontally, Q/VA decreased from cranial to caudal in lateral decubitus, prone suspended, and near the diaphragm in supine. Vertically, VA/Q decreased from upper to lower in all postures except in supine and within the dependent decubitus lung where it increased. VA/Q tended to increase from cranial to caudal in horizontal postures. The effects of gravity on Q/VA and VA/Q vertical distributions are modified when FRC is low (supine, lower decubitus lung) because perfusion is more uniformly distributed. Horizontal gradients of Q/VA and VA/Q are more pronounced under conditions of high local lung volume but also occur in postures where FRC is low.

Adult↗

Quantitative measurement of intrapulmonary and extrapulmonary right-to-left shunt.

We have developed a new technique that enables the shunting of blood from the right to the left side of the circulation to be partitioned into a cardiac and a lung component. The effects of recirculation are minimal, and the method does not require on-line data analysis. Quantitative estimates of these components have been made in two normal dogs and in five patients with raised pulmonary arterial pressures, some of whom were known to have a patent foramen ovale. The results were compared with oxygen shunt measured during air breathing. A poorly soluble gas, nitrogen, radiolabelled with 13N in solution is injected first into a central vein while matched samples of blood are drawn from the pulmonary artery and the aorta. A second solution containing 13N is injected into the right ventricle and sampled from the aorta only. Standardized gamma-counting techniques were used to analyze both the injected radioactivity and the radioactivity in the samples. These two measurements enable us to calculate the total right-to-left shunt, the pulmonary shunt, and by subtraction the extrapulmonary cardiac shunt.

Animals↗

The contribution of heart beat to gas mixing in the lungs of dogs.

The mixing efficiency for two gases of different gaseous diffusivity, helium (He) and sulphur hexafluoride (SF6) have been studied in anaesthetised dogs, closed and open chested, with and without the heart beating. Equilibration of He and SF6 was studied during rebreathing at frequency of 0.5 Hz and a tidal volume of either 0.3 or 0.5 L. Circulation and gas exchange were taken over by a complete heart and lung bypass circuit during the periods when the heart was stopped. The number of breaths required to reach 99% equilibration (n99) ranged from 4 to 14 for He and from 6 to 17 for SF6. There was no significant change in mixing efficiency in any situation. Stopping the heart increased the n99 for He by only 0.4 +/- 11% (1 SD) (n = 21). Opening the chest increased n99 by 1.4 +/- 13% with the heart beating and 2.5 +/- 19% with the heart stopped. The n99 for SF6 was 30 +/- 22% higher than that for He with the chest closed with or without the heart beating. This increased to 37% with the chest opened but was not altered by stopping the heart. The findings for the final phase equilibration rate constant were similar. We conclude that the beating action of the heart does not affect gas mixing in the lungs in the tidal breathing range.

Animals↗

Lung tissue volume estimated by simultaneous radiographic and helium dilution methods.

The pulmonary total tissue volume (blood, extravascular water, and dry tissue volume) was measured by finding the difference between the radiographic displacement volume of the thorax (RDVT) and the lung gas volume. Simultaneous determinations of RDVT and gas volume were made in 10 healthy subjects sitting upright. RDVT was determined from posteroanterior and lateral chest radiographs, a computerised modification of the Barnhard method being used; and gas volume was measured by helium dilution with each radiographic exposure. At functional residual capacity pulmonary total tissue volume was 843 +/- 110 ml (1 SD). The density of the lung (ml tissue per ml tissue and gas) was 0.19 +/- 0.03 (1 SD). This method, different in principle from indicator-dilution and acetylene rebreathing studies, provides measurements of total tissue volume.

Adult↗

Rate of uptake of carbon monoxide at different inspired concentrations in humans.

The rate of uptake of carbon monoxide (CO) in the lungs of normal subjects were measured at inspired concentrations of less than 1, 300, and 3,000 ppm (less than 0.0001-0.3%) using radioactive CO (11CO). In nine subjects the rate of uptake was monitored at the mouth during rebreathing. At inspired CO concentrations of approximately 1, 300, and 3,000 ppm and a mean alveolar O2 fraction of 0.15, the mean lung diffusing capacity was 25.8, 26.4, and 25.3 ml . min-1. Torr-1, respectively. In seven subjects the measurements were repeated after a period of O2 breathing, giving a mean alveolar O2 fraction of 0.78. The calculated membrane diffusing capacity was 31.9, 33.7, and 32.0 ml . min-1. Torr-1 at less than 1, 300, and 3,000 ppm inspired CO. We conclude that there is no difference in the rate of uptake of CO over the range of concentrations studied in these experiments. No evidence for the presence of a facilitated transport system for CO in the normal human lung was found.

Adult↗

A conscious dog model for study of regional lung function.

Using a specially designed mask and steady-state administration of the short-lived radioactive gas 81mKr, we measured the distribution of the ventilation-perfusion ratio (VA/Q) in the lungs of normal conscious standing greyhound dogs during tidal breathing. This model allows measurement of regional lung function unaffected by anesthesia and mechanical ventilation. An assessment of the distribution of VA/Q in the lungs of normal greyhound dogs revealed that topographically, ventilation and blood flow are well matched in the conscious dog.

Animals↗