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Biomedical subjects

N R MacIntyre

Publications and source records attributed to N R MacIntyre.

18 recordsLinked to original sources
PubMed1991

A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group.

OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.

Aged↗
PubMed1991

Psychological outcomes of a pulmonary rehabilitation program.

This study assessed physiologic, psychological, and cognitive functioning in outpatients with COPD. Sixty-four subjects, 53 to 82 years of age, participated in the 30-day exercise rehabilitation program. The program consisted of exercise, education and psychosocial counselling. Participants were assessed prior to beginning the program and at the end of 30 days. Assessments at both times included physiologic functioning (bicycle ergometry testing, pulmonary function tests, 12-min walk), psychological well-being (anxiety, depression, psychiatric symptoms, perceived well-being) and an abbreviated neuropsychological test battery. Results indicate significant improvement in physical endurance and pulmonary function, significant reductions in symptoms of depression and anxiety, and improvement in measures of general well-being and neuropsychological functioning. The study suggests that exercise rehabilitation of older adults with COPD contributes not only to improvements in physical functioning and endurance, but also to enhanced cognitive functioning and psychological well-being.

Aged↗
PubMed1991

Effects of initial flow rate and breath termination criteria on pressure support ventilation.

To assess whether adjustments in the initial flow rate or breath termination criteria affected patient-ventilator synchrony, we studied the ventilatory pattern response to PS in 33 patients under two sets of circumstances: during seven different levels of delivered initial PS flow and during PS termination at 50 percent and at 25 percent of peak flow. In the study on initial PS flow, we found the following: (a) an optimal initial PS flow could be defined for a given level of PS that resulted in the patient obtaining maximal pressure and volume from the ventilator; (b) initial PS flows above and below this optimal flow were associated with faster breathing frequencies, shorter inspiratory times, smaller tidal volumes and a tendency for airway pressure to not reach the selected PS level; and (c) optimal initial PS flow was fastest in patients with the lowest compliances and the most active ventilatory drives. Changing PS termination criteria from 50 to 25 percent of peak flow had minimal effects on the ventilatory pattern or synchrony. We conclude that the initial PS flow to achieve the selected PS level is important in patient-ventilator synchrony but that termination criteria set between 25 and 50 percent of peak flow is not.

Humans↗
PubMed1990

Ventilatory muscle loads and the frequency-tidal volume pattern during inspiratory pressure-assisted (pressure-supported) ventilation.

Pressure support ventilation (PSV) is a new form of mechanical ventilatory support that assists a patient's spontaneous ventilatory effort with a clinician-selected amount of inspiratory pressure. In order to assess the muscle unloading effect and the ventilatory pattern response to increasing levels of this inspiratory pressure assist, we first utilized a computer respiratory system model with variable alveolar ventilation demands and impedances. From this model, we calculated ventilatory muscle loads (expressed either as the work/min or as the pressure time index) during simulated, unassisted breathing and during simulated breathing with levels of inspiratory pressure assist up to that which resulted in a VT of 800 ml and no work being performed by the muscles (defined as PSVmax for the model conditions being studied). The optimal ventilatory pattern (i.e., frequency-tidal volume) under each ventilation and impedance condition was defined as that which resulted in minimal muscle load. Under these model conditions, we found that PSVmax ranged from 5 to 41 cm H2O and that as the level of inspiratory pressure assist was increased from zero to PSVmax, there was a biphasic response of both the ventilatory muscle loading and the ventilatory pattern. Specifically, at low levels of inspiratory pressure assist, the model predicted that the applied pressure would only partially unload the ventilatory muscles. Continued muscle energy expenditure would thus still be required, whereas the ventilatory pattern would change little. Conversely, at higher levels of inspiratory pressure assist, the model predicted that the applied pressure would be sufficient to completely unload the ventilatory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1989

Sarcoidosis: correlation of pulmonary parenchymal pattern at CT with results of pulmonary function tests.

The appearances of the lungs on radiographs and computed tomographic (CT) scans were correlated with degree of uptake on gallium scans and results of pulmonary function tests (PFTs) in 27 patients with sarcoidosis. CT scans were evaluated both qualitatively and quantitatively. Patients were divided into five categories on the basis of the pattern of abnormality at CT: 1 = normal (n = 4); 2 = segmental air-space disease (n = 4); 3 = spherical (alveolar) masslike opacities (n = 4); 4 = multiple, discrete, small nodules (n = 6); and 5 = distortion of parenchymal structures (fibrotic end-stage sarcoidosis) (n = 9). The percentage of the volume judged to be abnormal (CT grade) was correlated with PFT results for each CT and radiographic category. CT grades were also correlated with gallium scanning results and percentage of lymphocytes recovered from bronchoalveolar lavage (BAL). Patients in CT categories 1 and 2 had normal lung function, those in category 3 had mild functional impairment, and those in categories 4 and 5 showed moderate to severe dysfunction. The overall CT grade correlated well with PFT results expressed as a percentage of the predicted value. In five patients, CT scans showed extensive parenchymal disease not seen on radiographs. CT grades did not correlate with the results of gallium scanning or BAL lymphocytes. The authors conclude that patterns of parenchymal sarcoidosis seen at CT correlate with the PFT results and can be used to indicate respiratory impairment.

Airway Obstruction↗
PubMed1989

Mechanical loads on the ventilatory muscles. A theoretical analysis.

Two indices of the total mechanical load on the ventilatory muscles, i.e., the work per minute (W.min-1) and the inflation pressure time index (PTI), have been developed to better assess muscle energy demands and fatigue potential. However, the relationship of these two indices to the various individual determinants of load and to muscle energy demands and fatigue potential are not well understood. To investigate these relationships in a theoretical fashion, we first constructed a computer model to quantitate the magnitude and relative effects of changes in the ventilation component of load, i.e., alveolar ventilation demands (VA) and dead space volume (VD), and changes in the respiratory system impedance component of load, i.e., compliance (Crs) and resistance (Raw), on W.min-1 and PTI over a wide, clinically relevant, range of ventilatory conditions. From this analysis, we demonstrated that: (1) high mechanical loads could be developed over a wide range of circumstances (i.e., W.min-1 ranged from 0.29 kg.m.min-1 to 30.55 kg.m.min-1 and PTI ranged from 1.22 to 28.8 cm H2O as ventilation increased from 7 to 39 L.min-1 and impedances worsened from normal to a combined restricted and obstructed pattern); (2) each load determinant (i.e., VA, VD, Crs, and Raw) contributed substantially to these two indices of total mechanical load; (3) although impedance changes had comparable effects on W.min-1 and PTI, ventilation changes, as would be expected, had a greater effect on W.min-1 than on PTI.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗
PubMed1988

New forms of mechanical ventilation in the adult.

Although mechanical ventilatory support in the 1980s clearly provides adequate gas exchange with minimal side effects, there remains a need for ventilation and oxygenation in those with severe gas exchange abnormalities, for reduced airway pressure effects in those at risk for barotrauma, for a better muscle reconditioning approach in those with muscle dysfunction, and for better ventilator-patient interactions (synchrony) in many patients receiving mechanical ventilatory support. The new approaches outlined previously address these issues. However, research and development for new and better techniques are needed. Specific areas that require better understanding include the effects of intrathoracic pressure on the lungs and the circulation, the matching of ventilation and perfusion under different support modes, the function of the respiratory muscles during fatigue and recovery, and the ventilatory reflexes operational during mechanical ventilation. Only with this information can we design the optimal ventilatory support system.

Adult↗
PubMed1987

Jet ventilation in support of fiberoptic bronchoscopy.

Mechanical ventilatory support of bronchoscopic procedures by conventional volume-cycled ventilation (VCV) is technically difficult and can result in unreliable gas delivery or excessive alveolar pressure. An alternate support mode is jet ventilation through an open, uncuffed endotracheal tube. To quantitate gas delivery and airway pressures (Paw) during bronchoscopy using this technique, we used a mechanical-lung model and 15 human subjects. Jet ventilation pulsed gases at 60 to 100 cycle/min through a catheter in an uncuffed, jet endotracheal tube with a 5.9-mm (OD) bronchoscope in place. Inspiratory time was constant at 33% of cycle time, and jet-drive pressures ranged from 5 to 30 psi. In the mechanical-lung model, the jet technique provided up to 30 L/min of ventilation with mean airway pressures (Paw) always less than 10 cm H2O. In contrast, VCV with an inflated cuff, while providing similar levels of ventilation, resulted in substantial air trapping and over twice the Paw. VCV with a deflated cuff provided much lower levels of ventilation, although Paw levels were also low. These delivered minute ventilations, and Paw levels were similar in six normal volunteers jet ventilated through a 9-mm jet endotracheal tube with a bronchoscope in place. Finally, in nine patients requiring mechanical ventilatory support during bronchoscopic procedures, this jet technique provided alveolar ventilation (i.e., PaCO2) and Paw levels comparable to those obtained on baseline VCV before bronchoscopy.

Adult↗
PubMed1987

Rest and exercise cardiac output and diffusing capacity assessed by a single slow exhalation of methane, acetylene, and carbon monoxide.

To study rest and exercise pulmonary capillary blood flow (Qc) and diffusing capacity (DLexh) assessed by the rapid analysis of methane, acetylene, and carbon monoxide during a single, slow exhalation, we evaluated 36 subjects during first-pass radionuclide angiography (RNA). At rest (N = 36) and at exercise (N = 21) there was no difference in the respective measurements of cardiac output (Qc = 6.0 +/- 1.7 and CORNA = 6.9 +/- 2.5 at rest; Qc = 13.7 +/- 3.2 and CORNA = 14.5 +/- 4.1 at exercise, L/min, mean +/- SD, r = .80). Mild maldistribution of ventilation, as manifested by an increased phase 3 alveolar slope for methane (CH4 slope), did not significantly influence the results. CH4 slope and DLexh did increase significantly with exercise, while total lung capacity remained unchanged (CH4 slope: 6.2 +/- 5.0 vs 12.5 +/- 6.8% delta CH4/L, mean +/- SD, p less than 0.001; Dsb: 27.7 +/- 9.2 vs 42.0 +/- 17.9 ml/min/mm Hg, mean +/- SD, p less than 0.001; TLC: 5.47 +/- .20 vs 5.96 +/- 1.20 L, mean +/- SD). DLexh was related to CORNA (r = .68) and RNA stroke volume (r = .50). Qc was significantly less than CORNA in the subset of studies with valvular regurgitation (VHD) (N = 7). On the other hand, Qc was significantly greater than CORNA in the setting of coronary artery disease (CAD) and severe wall motion abnormalities (N = 7). These differences may be attributed to regurgitant fractions in VHD, and the influence of wall motion abnormalities on the estimation of left ventricular volume by the area-length method in CAD. These two noninvasive methods compare well at rest and exercise in clinical subjects and may provide complementary information in certain cardiopulmonary diseases.

Acetylene↗
PubMed1986

Distribution and uptake of helium, carbon monoxide, and acetylene in the lungs during high frequency oscillatory ventilation.

In order to obtain a better understanding of intrapulmonary gas mixing and alveolar-capillary gas transport during high frequency oscillatory ventilation (HFO), we measured insoluble gas (He) equilibration, and soluble gas (CO, C2H2) uptake in the lungs of ten anesthetized dogs during closed system HFO (i.e. no fresh gas bias flow). These gases were introduced as a bolus into the lumen of an endotracheal tube and their concentrations were subsequently measured for 20-25 sec from a catheter in the distal end of this tube. Analysis of He concentrations over time was performed using a two compartment series model to calculate a value for effective ventilation (Veff). This Veff was found to range from 0.83 to 23.8 L/min and was directly related to oscillator output (f X VT product, r = 0.77). Analysis of CO and C2H2 concentrations during HFO using a similar two-compartment model having alveolar capillary gas transport in series with Veff allowed for the calculation of pulmonary capillary blood flow (QHFO) and lung diffusing capacity (DHFO). These values for QHFO were found to be not significantly different from simultaneous thermodilution determinations of cardiac output and these values for DHFO were found to be not significantly different from single breath or rebreathing determinations of CO diffusing capacity. Moreover, QHFO and DHFO did not vary with Veff. We conclude that this two compartment in series model is a reasonable way to characterize insoluble and soluble gas behavior during HFO, that Veff is related to oscillator output, and that QHFO and DHFO are not affected by HFO over the range of Veff studied.

Acetylene↗
PubMed1986

Jet ventilation at 100 breaths per minute in adult respiratory failure.

To compare the ventilation and oxygenation capabilities of jet ventilation at 100 breaths per minute with those of conventional mechanical ventilation (CMV) in adults with respiratory failure, we performed a 2- to 3-h cross-over trial of jet ventilation in 65 stable patients requiring mechanical ventilation. Jet ventilation was delivered with an inspiratory time of 0.2 s through a 1.62-mm injector cannula attached to the proximal endotracheal tube. Drive pressure was adjusted to approximate the arterial PaCO2 on CMV. Measurements of arterial blood gases, peak and mean airway pressures (Paw), blood pressure (BP), and heart rate (HR) were recorded during baseline CMV, after every 30-min period during jet ventilation, and again 30 min after returning the patient to CMV. For analysis, patients were divided into 4 clinical and radiographic patterns: diffuse parenchymal disease (n = 22), focal parenchymal disease (n = 18), obstructive airway disease (n = 6), and nonpulmonary disease (n = 19). Jet ventilation "failures" were characterized by significantly higher minute ventilation requirements, higher levels of PaCO2, higher airway pressures, and smaller PaO2/FIO2 ratios on CMV as compared to the 58 ventilatory "successes." In the ventilatory "successes," peak Paw was significantly lower, but mean Paw, PaCO2, PaO2, FIO2, BP, and HR were not significantly different with jet ventilation as compared to CMV. Moreover, in this ventilatory success group, patients with an increase in the PaO2/FIO2 during jet ventilation were not significantly different from patients with a decrease in PO2/FIO2 in terms of clinical characteristics, ventilation requirements, or gas exchange capabilities on CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Respiratory function during pressure support ventilation.

Pressure support ventilation (PSV) is a pressure assist form of mechanical ventilatory support that augments the patient's spontaneous inspiratory efforts with a clinician selected level of positive airway pressure. To understand the effects of PSV on respiratory function, experiments were performed on 15 stable patients requiring synchronized intermittent mandatory ventilation (SIMV), as well as on a mechanical model simulating these patients' ventilatory systems. In the clinical study, gas exchange, airway pressures, blood pressure and heart rate were measured while SIMV was replaced by enough PSV to approximate the baseline SIMV tidal volume (VT). Measurements were repeated while this PSV level was then reduced in three 5 cm H2O steps every 10 to 15 minutes. It was found that PSV was a reasonable form of mechanical ventilatory support in patients with spontaneous ventilatory drives. It improves patient comfort, reduces the patient's ventilatory work, and provides a more balanced pressure and volume change form of muscle work to the patient. The clinical significance of these properties during the weaning process remain to be determined.

Adult↗
PubMed1985

Aerosol delivery in intubated, mechanically ventilated patients.

To study the effects of respiratory failure and mechanical ventilation on aerosol delivery to the lungs, we performed nuclear scans after aerosolization of 5 to 9 mCi of Tc-99m diethylenetriamine pentaacetic acid in seven stable, intubated, and mechanically ventilated patients. The radioactivity reaching the lungs was 2.9 +/- .7% (mean +/- SD) of the administered dose, an amount significantly less than that in three healthy nonintubated subjects and also less than what would be expected in nonintubated subjects from other published reports. We then performed a subsequent study in 15 additional mechanically ventilated patients who were receiving aerosolized bronchodilators through their endotracheal tube. In these patients, heart rate and lung mechanical function values before and after treatment were not significantly different. We conclude from these studies that aerosol delivery in mechanically ventilated patients is significantly reduced and that this is probably due to a combination of suboptimal breathing pattern, intrinsic airway disease, and the endotracheal tube functioning as both a site for aerosol deposition through impaction as well as a barrier to gastrointestinal absorption.

Aerosols↗
PubMed1978

Longevity in military pilots: 37-year followup of the Navy's "1000 aviators".

The 37-year nonmilitary mortality rate for initially healthy aviators was determined in a followup program on the U.S. Navy's "1000 Aviator" cohort. Of the 800 survivors of World War II and the Korean conflict, 95 were found to have died from nonmilitary causes over this followup period. This is markedly less than the 208 that would be expected from a random sample of white American men over a similar period (p less than 0.005). It is also significantly less than the 143 that would have been expected from a group of men who had passed an initial insurance physical (p less than 0.005). Lower-than-expected death rates occurred in all three major categories of cause of death in this age group: cardiovascular, neoplastic, and accidental. The generally good socioeconomic background, the positive genetic influence of long-lived parents, the above average intelligence, and the health and fitness orientation of the military aviator are all thought to be factors contributing to this increased longevity.

Accidents↗