Reducing ventilatory response to carbon dioxide by breathing cold air

To study the effect of cooling of nasal receptors on breathing we had 10 normal male volunteers rebreathe through their noses 8% CO2 in oxygen at "warm" (23 to 30 degrees C) and at "cold" (-4 to 10 degrees C) temperatures. In order to further examine the effect of nasal receptors on the control of breathing, 11 subjects had their nasal response to CO2 measured at the warm temperature before and after topical nasal anesthesia. To exclude an increase in nasal resistance as the cause of the reduced response to CO2, 10 subjects had their nasal resistance measured before and after nasal rebreathing of cold 8% CO2 in oxygen. To also exclude increased bronchial resistance, forced expiratory volume in one second (FEV1) was measured in 12 subjects before and after nasal breathing of cold oxygen for 3 min. The mean ventilatory response to CO2 was reduced from 3.0 +/- 1.6 L/min/mmHg to 2.5 +/- 1.1 L/min/mmHg (p less than 0.05) by the cold air. Topical nasal anesthesia increased the response to CO2 at the warm temperature from 2.4 +/- 0.7 to 2.7 +/- 0.9 L/min/mmHg. The effect of nasal breathing of 8% CO2 in oxygen at the cold temperature was to reduce nasal inspiratory resistance at 1 L/s from 4.3 +/- 3.0 cm H2O L/s to 2.6 +/- 1.0 cm H2O L/s (p less than 0.05). Expiratory resistance at 1 L/s fell from 3.7 +/- 1.5 cm H2O L/s to 2.4 +/- 0.7 cm H2O L/s (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation of cardiac surface QRST distributions to ventricular fibrillation threshold in dogs

The relation between ventricular fibrillation threshold (VFT) and cardiac surface QRST area distributions was studied in eight pentobarbital-anesthetized dogs. Unipolar epicardial electrograms were recorded from 64 sites evenly distributed on the right and left ventricles. Localized areas of short repolarization properties were produced by directing five intensities of light onto the surface of the anterior right ventricle through apertures of three sizes. VFT, measured at the center of the lesion, decreased during warming and had a high negative correlation to the change (warming-control) in QRST area (delta QRST1) in the electrogram recorded from the center of the lesion. This correlation was independent of lesion size. For the six experiments, the correlation coefficients for 400-, 800-, and 1,600-mm2 lesions averaged -0.95, -0.94, and -0.96, respectively. The correlation between VFT and delta QRST1 without regard to lesion size averaged -0.88. VFT also had a negative correlation to root mean square (RMS)delta QRST because of warming. RMS delta QRST was calculated from the change in QRST areas (warming-control) in all 64 electrograms. The correlation between VFT and RMS delta QRST was dependent on lesion size. For all experiments, the correlation between VFT and RMS delta QRST averaged -0.97, -0.93, and -0.93 for 400-, 800-, and 1,600-mm2 lesions, respectively. The correlation between VFT and RMS delta QRST without regard to lesion size, however, was considerably lower, -0.59. The results of this study provide the first direct evidence that VFT is correlated with cardiac surface QRST area distributions.     

Effect of exercise on dilution estimates of extravascular lung water and on the carbon monoxide diffusing capacity in normal adults.

Previous studies in exercising animals have demonstrated that the extravascular lung water accessible to measurement by dilution methodology increases in the transition from rest to low-level exercise and thereafter does not change with progress to high-level exercise. In normal humans, similar systematic examination is essential to provide a background for the interpretation of changes in measured extravascular lung water in pathophysiological states. Moreover, such an examination might provide new insight into the mechanisms underlying the change in the pulmonary diffusing capacity with exercise. We therefore measured both the pulmonary extravascular lung water (by use of the triple indicator-dilution technique) and the diffusing capacity for carbon monoxide in 11 subjects, seated on an exercise bicycle, at rest and usually during two levels of exercise. The central blood volume increased by 50% with a tripling of the cardiac output. The accessible lung water increased from an average of 2.16 g/kg to 2.55 g/kg in the transition from rest to low-level exercise, but it did not increase further at the higher level of exercise. The simultaneously measured diffusing capacity for carbon monoxide (single breath and steady state) continued to increase over the whole range of cardiac outputs. We infer that the proportion of the pulmonary parenchyma perfused by blood flow increases slightly in the transition from rest to low-level exercise but increases no further at the higher level of exercise. The continued increase in the pulmonary diffusing capacity over the range in which the estimated lung water values do not change appears to imply that part of this increase may be blood flow dependent rather than dependent on the recruitment of additional surface for exchange.     

Tuberculosis control in a border state. Treatment of the foreign-born

As the epidemiology of TB in the United States changes, with more foreign-born and fewer native-born residents developing the disease, treatment can be expected to become more complicated and expensive.     

Relation of quantitative coronary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography

To assess the relation of quantitative measures of coronary stenoses to the development of exercise-induced regional wall motion abnormalities, 34 patients with isolated, single vessel coronary artery lesions and normal wall motion at rest underwent exercise echocardiography and quantitative angiography on the same day. Although all 11 patients with a visually estimated stenosis greater than or equal to 75% had an ischemic response and 10 (91%) of 11 patients with a less than or equal to 25% visually estimated stenosis had a normal response by exercise echocardiography, among 12 patients with a visually estimated stenosis of 50%, 6 (50%) had an ischemic response and 6 (50%) had a normal exercise echocardiogram. Quantitative measurements of stenosis severity distinguished patients with ischemic (group 1) from normal (group 2) exercise echocardiographic responses as follows: minimal luminal diameter (mm), group 1 1.0 +/- 0.4 versus group 2 1.7 +/- 0.4, p less than 0.0001; minimal cross-sectional area (mm2), group 1 0.9 +/- 0.6 versus group 2 2.5 +/- 1.1, p less than 0.0001; percent diameter stenosis, group 1 68.3 +/- 14.2 versus group 2 42.2 +/- 12.1, p less than 0.0001; and percent area stenosis, group 1 87.5 +/- 7.8 versus group 2 64.8 +/- 15.9, p less than 0.0001. These data validate the utility of exercise echocardiography by demonstrating that 1) coronary stenosis severity measured by quantitative angiography is closely related to wall motion abnormalities detected by exercise echocardiography, and 2) exercise echocardiography can be used as a noninvasive means to assess the physiologic significance of coronary artery lesions.     

Determination of transmural location of onset of activation from cardiac surface electrograms

Methods of estimating depth of origin of ventricular activation from cardiac surface electrograms were evaluated in experiments on eight dogs. The ventricles were paced via multielectrode needle arrays placed transmurally in from four to six locations in the wall of the left ventricle. A multiplexed data-recording system was used to simultaneously record from 64 unipolar cardiac surface electrodes during pacing at each multielectrode needle site. The four indexes evaluated were the maximum and average gradients of activation isochrones around the site of earliest epicardial activation, the QRS area at the site of earliest epicardial activation, the interval between the QRS onset computed from all 64 epicardial surface electrograms, and the time of the minimum dV/dt in the electrogram displaying the earliest epicardial activation time (t(ee)-t(rmso) interval). Correlation coefficients between depth of stimulation and average and maximum gradients of isochrones, QRS area at the site of earliest epicardial activation, and t(ee)-t(rmso) interval were 0.985 or higher. These methods, particularly those involving gradients of isochrones, should be useful for evaluating electromaps of patients undergoing surgery for ablation of tachyarrhythmias.     

Distinct error-correcting and incidental learning of location relative to landmarks and boundaries

Associative reinforcement provides a powerful explanation of learned behavior. However, an unproven but long-held conjecture holds that spatial learning can occur incidentally rather than by reinforcement. Using a carefully controlled virtual-reality object-location memory task, we formally demonstrate that locations are concurrently learned relative to both local landmarks and local boundaries but that landmark-learning obeys associative reinforcement (showing "overshadowing" and "blocking" or "learned irrelevance"), whereas boundary-learning is incidental, showing neither overshadowing nor blocking nor learned irrelevance. Crucially, both types of learning occur at similar rates and do not reflect differences in levels of performance, cue salience, or instructions. These distinct types of learning likely reflect the distinct neural systems implicated in processing of landmarks and boundaries: the striatum and hippocampus, respectively [Doeller CF, King JA, Burgess N (2008) Proc Natl Acad Sci USA 105:5915-5920]. In turn, our results suggest the use of fundamentally different learning rules by these two systems, potentially explaining their differential roles in procedural and declarative memory more generally. Our results suggest a privileged role for surface geometry in determining spatial context and support the idea of a "geometric module," albeit for location rather than orientation. Finally, the demonstration that reinforcement learning applies selectively to formally equivalent aspects of task-performance supports broader consideration of two-system models in analyses of learning and decision making.     

Sequential chemotherapy and late intensification for malignant lymphomas of aggressive histologic type

Fifty-six patients with malignant lymphoma of aggressive histologic type (51 large cell, three diffuse undifferentiated, and two nodular mixed) were treated with three non-cross-resistant combination chemotherapy regimens that were introduced sequentially according to the response to therapy. The objective was to increase the complete remission rate by changing the chemotherapy regimen early if the patient did not attain a complete remission after three courses of treatment. Late intensification was also used with the aim of prolonging the duration of complete remission. The overall complete remission rate obtained with this approach was 82 percent (100 percent in stages I to III and 66 percent in stage IV). The projected survival at four years is 71 percent (93 percent for stages I to III and 55 percent for stage IV). Eighty percent of patients with complete remission are projected to have continued remission at four years. Compared with previous experience with Adriamycin-based combination regimens, these results represent an improvement in remission and survival parameters. The most significant gains occurred in the prolongation of survival of patients with stages I to III disease and in the improved duration of complete remission of patients with stage IV disease. Toxicity included 15 documented infections among 320 courses of therapy, four cases of congestive heart failure, one case of bleomycin lung toxicity, and two cases of liver dysfunction. This multiple combination regimen represents an improvement over previous results utilizing Adriamycin-based combination chemotherapy.