Value of ventilation/perfusion scans versus perfusion scans alone in acute pulmonary embolism.
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Biomedical subjects
Publications and source records attributed to A Gottschalk.
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The data base of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) was used to test the accuracy of the stripe sign for the exclusion of embolic perfusion defects on lung scintigrams. Lung scan readings showed the presence and location of this sign in 50 (4.7%) of 1,064 patients. Perfusion defects showing the stripe sign were not associated with pulmonary embolism in the same lung zone (upper, middle, or lower third of each lung) in 93% (79 of 85) of instances. Thirty-eight percent (n = 32) of lung zones with the stripe sign had associated chest radiographic abnormalities, and 69% (n = 59) had ventilation scan abnormalities. Formulation of the scan diagnosis according to PIOPED criteria showed fewer indeterminate readings in patients with the stripe sign and without pulmonary embolism when the stripe sign was used. Use of the sign changed diagnosis in less than 1% of the total population, however, because of its low overall prevalence. The stripe sign is a useful adjunct to standard criteria in the interpretation of pulmonary scintigrams for evaluation of suspected acute pulmonary embolism.
A mathematical model of the three-phase respiratory network proposed by Richter et al. (News Physiol. Sci. 1: 109-112, 1986) is developed and its properties are examined. The model reproduces the experimentally determined trajectories of membrane potential for the five physiologically distinct types of neurons included. Stepwise parameter changes can produce a respiratory rhythm with only two separate electrophysiological phases, result in apnea, or produce more complex patterns of firing. The phase-resetting behavior of the model was obtained with perturbing stimuli and is comparable to experimentally determined phase-resetting data. There is reasonable agreement between model predictions and experimental results. In the model, the properties of the phase singularity make termination of the respiratory rhythm by an appropriately timed perturbation virtually impossible, which is in agreement with experimental observations. The rhythm can be stopped by alterations that simulate the effect of input from the superior laryngeal nerve; the rhythm is locked in the postinspiratory phase. We conclude that our results are consistent with the concept of a network oscillator as the source of the respiratory rhythm.
Periodicities of ventilation are common in elderly subjects during stage 1/2 sleep. The mechanism producing these periodicities is unknown. We hypothesized that the oscillations in ventilation might be related to oscillations in sleep state. To address this hypothesis, we examined, using cross correlation, the relationship between the oscillations in ventilation and parameters (alpha power, mean frequency) derived from spectral analysis of the electroencephalogram. In wakefulness, although ventilation and mean frequency, and ventilation and alpha power, were related, there were no consistent patterns to these relationships. Both positive and negative correlations were found. Clearer relationships were found in stage 1/2 sleep. Correlation between mean frequency and ventilation was the most consistent. All correlations were positive; i.e., ventilation fell as mean frequency fell. The maximum correlation occurred at zero lag between the time series. Thus these oscillations are synchronous within the time resolution of our methodology. These data are compatible with the hypothesis that the initiation of apnea in stage 1/2 sleep is related to a reduction in the state-dependent input to the ventilatory control system.
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The diagnostic features of acute pulmonary embolism among 72 patients greater than or equal to 70 years old were evaluated and compared with characteristics of pulmonary embolism among 144 patients 40 to 69 years and 44 patients less than 40 years old. Syndromes characterized by either 1) pleuritic pain or hemoptysis, 2) isolated dyspnea, or 3) circulatory collapse were observed with comparable frequency among patients greater than or equal to 70 years old and younger patients. One of these presenting syndromes occurred in 64 (89%) of the 72 patients greater than or equal to 70 years old. Those who did not show these syndromes were identified on the basis of unexpected radiographic abnormalities, which may have been accompanied by tachypnea or a history of thrombophlebitis. Among the 72 patients greater than or equal to 70 years with pulmonary embolism, dyspnea or tachypnea (respirations greater than or equal to 20/min) occurred in 66 (92%), dyspnea or tachypnea or pleuritic pain in 68 (94%) and dyspnea or tachypnea or radiographic evidence of atelectasis or a parenchymal abnormality in 72 (100%). Complications of angiography were evaluated among patients with and without pulmonary embolism. Major complications of pulmonary angiography among patients greater than or equal to 70 years old (2 [1%] of 200) were not more frequent than among younger patients (6 [1.1%] of 562) (p = NS). However, renal failure (major or minor) was more frequent in patients greater than or equal to 70 years old than in younger patients (6 [3%] of 200 versus 4 [0.7%] of 562) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The value of bedside examination and noninvasive tests in the diagnosis of acute pulmonary embolism (PE) among patients with a normal chest radiograph was investigated. Normal chest radiographs were present in 20 of 260 patients (8%) with acute PE and in 113 of 642 (18%) with suspected acute PE, in whom the diagnosis was excluded. A partial pressure of oxygen in arterial blood less than or equal to 70 mm Hg in a dyspneic patient with a normal chest radiograph was more often seen among patients with PE (9 of 17, 53%) than among patients in whom PE was excluded (18 of 93, 19%; p less than 0.01). However, no combinations of blood gases, signs and symptoms were strictly diagnostic. High probability ventilation/perfusion scans among patients with a normal chest radiograph were indicative of PE in only 6 of 9 patients (67%). Among patients with low-probability ventilation/perfusion scans, 8 of 47 (17%) had PE. This study showed that the combination of dyspnea and hypoxia in a patient with a normal chest radiograph is a useful clue to the diagnosis of PE. Although intuition suggested that ventilation/perfusion scans would yield better results in patients with a normal chest radiograph, the ability to diagnose PE by ventilation/perfusion scans in this subset of patients was not enhanced, except by a reduction of the percentage of patients with intermediate probability scans.
To elucidate the mechanisms that lead to sleep-disordered breathing, we have developed a mathematical model that allows for dynamic interactions among the chemical control of respiration, changes in sleep-waking state, and changes in upper airway patency. The increase in steady-state arterial PCO2 accompanying sleep is shown to be inversely related to the ventilatory response to CO2. Chemical control of respiration becomes less stable during the light stage of sleep, despite a reduction in chemoresponsiveness, due to a concomitant increase in "plant gain" (i.e., responsiveness of blood gases to ventilatory changes). The withdrawal of the "wakefulness drive" during sleep onset represents a strong perturbation to respiratory control: higher magnitudes and rates of withdrawal of this drive favor instability. These results may account for the higher incidence of periodic breathing observed during light sleep and sleep onset. Periodic ventilation can also result from repetitive alternations between sleep onset and arousal. The potential for instability is further compounded if the possibility of upper airway occlusion is also included. In systems with high controller gains, instability is mediated primarily through chemoreflex overcompensation. However, in systems with depressed chemoresponsiveness, rapid sleep onset and large blood gas fluctuations trigger repetitive episodes of arousal and hyperpnea alternating with apneas that may or may not be obstructive. Between these extremes, more complex patterns can arise from the interaction between chemoreflex-mediated oscillations of shorter-cycle-duration (approximately 36 s) and longer-wavelength (approximately 60-80 s) state-driven oscillations.
The purpose of this study was to assess the impact of prior cardiac or pulmonary disease upon the utility of ventilation/perfusion (V/Q) scans in the diagnosis of acute pulmonary embolism (PE). Ventilation/perfusion scans were evaluated among 365 patients with no prior cardiac or pulmonary disease and compared to V/Q scans in 526 patients with prior cardiac or pulmonary disease. Among patients with no prior cardiac or pulmonary disease, PE was present in 117 and PE was excluded in 248. Among patients with prior cardiac or pulmonary disease, PE was present in 140 and excluded in 386. The positive predictive value for PE of high probability V/Q scans among patients with prior cardiac or pulmonary disease, 55 of 66 (83 percent), was not significantly lower than among patients without prior cardiac or pulmonary disease, 50 of 54 (93 percent) (NS). The positive predictive value of low probability V/Q scans was similar with prior cardiac or pulmonary disease, 25 of 182 (14 percent), and without prior cardiac or pulmonary disease, 17 of 113 (15 percent) (NS), as was the predictive value of near normal/normal V/Q scans, 2 of 51 (4 percent), vs 3 of 79 (4 percent) (NS). The sensitivity of high probability V/Q scans, with pre-existing cardiac or pulmonary disease and without, 55 of 140 (39 percent) vs 50 of 117 (43 percent), did not differ significantly. The specificity of high probability V/Q scans with prior cardiac or pulmonary disease and without, 375 of 386 (97 percent) vs 244 of 248 (98 percent) was also similar (NS). In conclusion, the diagnostic utility of V/Q scans for acute PE was not impaired by the presence of pre-existing cardiac or pulmonary disease. Fewer patients, however, with no prior cardiac or pulmonary disease, had intermediate (indeterminate) V/Q scans.
Fifty patients with suspected renal artery stenosis (RAS) were studied with renal scintigraphy before and after administration of captopril. Twenty-three patients had RAS (greater than or equal to 75% RAS or greater than or equal to 50% RAS with poststenotic dilatation) and 27 had normal renal arteries at angiography. Angiotensin-converting enzyme inhibitors were discontinued 24 hours prior to renal scintigraphy; all other medications were continued. Each patient was evaluated with a simplified captopril renal scintigraphic protocol: renal imaging after administration of 12 mCi (444 MBq) of technetium-99m diethylenetriaminepentaacetic acid (DTPA), a 3-hour wait, oral administration of 50 mg of captopril, a 1-hour wait, and another scintigram obtained after administration of 12 mCi (444 MBq) of Tc-99m DTPA. Times of peak renal activity (Tmax) were determined from renal time-activity curves, and glomerular filtration rates (GFRs) were calculated with the Gates technique. A Tmax greater than or equal to 11 minutes after injection or a GFR ratio (larger GFR/smaller GFR) greater than 1.5 enabled detection of RAS with 91% sensitivity, 93% specificity, and 92% accuracy. Renal scintigraphy without captopril had only 43%-68% sensitivity in detecting RAS, depending on the criteria used.
The uptake ratios of radiolabeled antibodies (Ab) commonly are two to three times the uptake ratios of the normal surrounding tissue. In an experimental crush injury model, we also defined a two to three times greater range of uptake of type I anticollagen antibody (Ac-Ab-I) from 1.5 hours to 48 hours after tail injury in the rat. Specific target uptake, however, often is further categorized by comparing the uptake ratio of Ab to that of a nonspecific protein. We present data to indicate that this nonspecific uptake may represent a significant variable. We found that sheep IgG gave consistently less nonspecific uptake in our model than did rabbit IgG. In the acute model (protein injected 1.5 hours after injury), damaged: normal tail ratios were Ac-Ab-I = 2.34, sheep = 0.8, and rabbit = 1.6. The extent of specific Ab uptake seems dependent upon the choice of "irrelevant" IgG controls.
Plasma fibronectin, a glycoprotein that is a component of blood thrombi, was evaluated for the in vivo scintigraphic detection of pulmonary emboli in dogs. Fibronectin (canine or human) was labeled with either 131I or with 111In and diethylenetriaminepenta-acetic acid (DTPA) as the bifunctional chelating agent using a modification of the mixed anhydride method. The radiolabeled proteins were administered intravenously 20 to 30 minutes after the embolization of a 99mTc-labeled thrombus. The uptake of radioactivity by the embolus was monitored scintigraphically up to 24 hours. At the end of each experiment, the animal was killed and in vitro tissue counting of radioactivity was performed. Comparative study of the 131I- and 111In-labeled agent is presented with particular reference to their pharmacokinetics. The in vivo uptake of radioactivity by the emboli was limited, indicating that radiolabeled fibronectin is not a good scintigraphic agent for the detection of pulmonary emboli.
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Since the fibrinolytic system of the swine is close to that of human, the use of a swine model may assume increasing prominence in future studies of thrombosis. Swine platelets were labeled with 111In in a modified Tyrode's solution, suspended in plasma, then injected intravenously into swine. The average radioactivity incorporated into the platelets was 44 +/- 27%. The recovery of labeled platelets at 5 minutes post-injection was 81.7 +/- 5.3%. The platelets retained their label throughout their life span. The survival of 111In-platelets was described by a one component exponential equation, with a life span of 157.9 +/- 25.3 hrs.
The conjugation of antibodies (Ab) with DTPA in the presence of contaminating low molecular weight proteins is inefficient. The selective precipitation of Ab with 18% Na2SO4 as a preparative purification method for small aliquots of low Ab concentrations is successful in eliminating all contaminants as monitored by high performance liquid chromatography at 214 nm and in allowing IgG recoveries greater than 94%. Subsequently, this allows efficient conjugation and radiolabelling of Ab.
By conventional criteria, perfusion defects that correspond to radiographic parenchymal opacities of similar size have less diagnostic significance for pulmonary embolism (PE) than perfusion defects in areas that are radiographically clear, regardless of the findings on ventilation scan. It was proposed that the demonstration of normal ventilation in areas with matched radiographic opacity and perfusion defects does support the diagnosis of PE. To test this hypothesis, a retrospective review was done of selected cases from a consecutive series of 85 pulmonary angiography studies. Cases were reviewed if the following criteria were met: chest radiography, ventilation-perfusion scintigraphy, and angiography of the relevant regions had all been performed within 24 hours of one another, and there was a radiographic opacity corresponding to the perfusion defect. Sixteen cases fulfilled these criteria. Six patients had normal ventilation in the regions of the radiographic infiltrate and perfusion defect, and all had PE. No patient had an area of opacity and perfusion defect and normal ventilation without PE.
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