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Biomedical subjects

H Menkes

Publications and source records attributed to H Menkes.

17 recordsLinked to original sources

An unusual cause of recurrent angina two years after coronary artery bypass grafting: fistula between internal mammary artery graft to pulmonary vasculature.

A 55-year-old man developed recurrent angina pectoris 2 years after coronary artery bypass grafting. Cardiac catheterization demonstrated that the venous grafts were patent, but selective left internal mammary angiogram showed multiple fistulous connections between the internal mammary artery and the pulmonary vasculature of the left upper lobe. After surgical correction of the fistula, the angina resolved. Only three previous cases of acquired internal mammary artery graft fistulas draining to the pulmonary vasculature have been described. The etiology, clinical presentation, and management of an internal mammary artery fistula to the pulmonary vasculature are discussed.

Angina Pectoris

Ischemia and reperfusion during intermittent coronary occlusion in man. Studies of electrocardiographic changes and CPK release.

The course of 357 balloon inflations performed during 38 angioplasties for single-vessel coronary artery disease was prospectively studied using continuous ECG recording. Ischemic ECG changes appeared during 91 percent of the inflations at a mean of 20 +/- 8 seconds after inflation and resolved in 97 percent of those at a mean of 11 +/- 5 seconds after deflation. Elevation of the plasma CPK level was found in six patients who had ischemic ECG changes for at least 7.8 minutes. The duration of ischemia did not exceed 5.4 minutes in any of the patients without CPK elevation. Resolution of the ischemic changes was delayed in patients with CPK elevation and in last vs initial inflations. We conclude that in patients with noninfarcted myocardium, ECG changes follow coronary occlusion and reflow very rapidly, detecting these coronary events with a high sensitivity. Lack of rapid regression predicts lack of reperfusion, and persistence of ischemia for more than 7.8 minutes is sufficient to cause myocardial necrosis.

Adult

Protective role of epithelium in the guinea pig airway.

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466-471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

Acetylcholine

Interstitial fibrosis and collateral ventilation.

Interstitial fibrosis may increase resistance to collateral flow (Rcoll) because of decreased lung volume and destruction of collateral channels or it may decrease Rcoll because of emphysematous changes around fibrotic regions. In addition, if interstitial fibrosis involves a small region of lung periphery, interdependence from surrounding unaffected lung should produce relatively large changes in volume of the fibrotic region during lung inflation. We studied the effects of interstitial fibrosis on collateral airflow by measuring Rcoll at functional residual capacity (FRC) in nine mongrel dogs before and 28 days after the local instillation of bleomycin into selected lung segments. In six of these dogs Rcoll was also measured at a higher lung volume (transpulmonary pressure = 12 cmH2O above FRC pressure). Rcoll increased in fibrotic lung segments following local treatment with bleomycin. With lung inflation (high transpulmonary pressure) Rcoll fell a similar proportion in fibrotic and nonfibrotic lung regions. These observations suggest that collateral resistance increases in fibrotic segments because lung volume decreases or because collateral pathways are involved directly in the fibrotic process. Compensatory increases in collateral communications do not occur. In addition, pulmonary interdependence does not cause disproportionate increases in volume and decreases in Rcoll of the fibrotic region during lung inflation.

Airway Resistance

Tantalum inhalation and airway responses.

We studied the effects of tantalum inhalation bronchography on pulmonary function in 14 normal volunteers. Based on the radiographic type of deposition, the subjects were divided into three groups: (1) subjects who deposited tantalum mainly in the trachea, (2) subjects who deposited tantalum in segmental bronchi without radiographic evidence of bronchospasm, and (3) subjects who deposited tantalum in segmental bronchi with radiographic evidence of bronchospasm. Unlike the first two groups, the third group developed a significant but small decrease in the FEV. Airway reactivity as assessed by methacholine challenge did not explain the difference in response to tantalum in the third group. There were no consistent changes in total lung capacity, residual volume, or closing volume in any of the groups. Even though there were falls in FEV and specific conductance in individuals in groups 2 and 3, these changes did not pose any significant clinical risk.

Adult

Reverse nitrogen gradients in the study of phase III and cardiogenic oscillations of the single-breath nitrogen test.

The slope of phase III, phase IV, the slope of phase IV, and cardiac oscillations were measured on tracings obtained by both the regular single-breath N2 test (Tech I) and by a reverse technique (Tech II) in 9 healthy volunteers. Tech II consisted of 3 consecutive vital capacities (VC) of 100% O2 followed by one VC of room air. Theoretically, this should create a reversed apicobasal N2 gradient quantitatively similar to that of Tech I. From the total lung capacity following the VC2 of air, we monitored N2 concentration continuously at the mouth during a slow expiration in a manner similar to that of the single-breath N2 test. With Tech II, it is possible to preserve phase IV and its reversed slope in the presence of an almost flat slope of phase III and markedly blunted cardiac oscillations. When compared to Tech I, the slope of phase III with Tech II decreased from 0.66+/-0.20% N2/L (mean +/-SD) to 0.19+/-0.12 (p is less than 0.001), and cardiac oscillations decreased from a mean % N2 change with each heart beat of 0.87+/-0.37 to 0.24+/-0.21 (p is less than 0.005), whereas phase IV, although reversed in direction, remained quantitatively unchanged (0.35+/-0.15 L with Tech I and 0.37+/-0.14 L with Tech II), and the slope of phase IV tended to increase (2.7+/-1.9% N2 with Tech I and 3.4+/-2.1% N2 with Tech II, p=NS). We conclude that the N2 gradients within the lungs responsible for the slope of phase III and cardiac oscillations are largely independent of the gradients that give rise to phase IV and the slope of phase IV.

Adult

Upper airways obstruction with bilateral vocal cord paralysis.

In ten patients with bilateral vocal cord paralysis, we demonstrated variable extrathoracic airway obstruction. The ratio of forced expiratory flow at 50 percent vital capacity to forced inspiratory flow at the same lung volume (VE50/VI50) was 1.65 +/- 0.77 (mean +/- 1 SD). There was marked variability of inspiratory flow obstruction with a mean VI50 of 1.63 +/- 0.75 liters/ sec and a range from 0.9 liters/sec to 3.2 liters/sec. Nine of the ten patients required tracheostomy for symptoms of dyspnea. Follow-up flow volume loops were obtained to document the effects of surgical intervention and tracheostomy.

Adult

Collateral ventilation.

Ventilation may bypass obstructed airways through collateral channels, including interalveolar pores of Kohn, bronchiole-alveolar communications of Lambert, and interbronchiolar pathways of Martin. Resistance through these channels, like resistance through small airways, increases with decreasing lung volume and with hypocapnia. But whereas the distention of collateral channels and small airways by a variety of factors is similar, the efficiency of ventilation through collateral channels is less than the efficiency through airways. Gas inspired through collateral channels is contaminated with alveolar gas from surrounding lung so that the dead space for collateral ventilation is increased. When one part of the lung ventilates out of phase with the surrounding lung, pulmonary interdependence promotes more homogeneous ventilation. In the presence of airways obstruction, interdependence may be a primary factor governing the rate of collateral ventilation. In man, collateral ventilation is unimportant in normal lungs. However, with disease, it may be critical in producing or compensating for abnormalities. For example, the long time constant for collateral ventilation in the middle lobe may be responsible for atelectasis, which results in the middle lobe syndrome. On the other hand, the short time constant for collateral ventilation in emphysema may be essential for the distribution of ventilation beyond obstructed airways.

Airway Resistance

Airflow in unilateral vocal cord paralysis before and after Teflon injection.

The effect of unilateral vocal cord paralysis and intracordal Teflon injection on maximum expiratory and inspiratory flows was studied in 15 consecutive patients. Ten patients had a ratio of forced expiratory flow to forced inspiratory flow at 50% vital capacity (Ve50/Vi50) more than one. Of the remaining five, four had low Ve50 consistent with underlying bronchial disease. Repeat studies were obtained in 10 patients two or more weeks after Teflon injection into a vocal cord for voice therapy. Maximum expiratory flow rates did not change (means 6.64 +/- 0.881/sec before and 6.47 +/- 1.101/s after injection). Inspiratory flow at 50% vital capacity improved in all six patients with a forced expiratory volume in one second (FEV1) greater than 75% of the forced vital capacity (FVC). In patients with an FEV1 less than 75% FVC, no consistent changes could be seen. We conclude that a high Ve50/Vi50 suggestive of variable extrathoracic airways obstruction is a frequent finding in the presence of unilateral vocal cord paralysis. Teflon injection does not cause a significant reduction in forced expiratory flows and improves inspiratory flows in subjects without evidence of underlying bronchial disease.

Airway Obstruction

Pulmonary function in young smokers: male-female differences.

To delineate the pattern of pulmonary function abnormalities and associated pathophysiologic mechanisms in young smokers, 205 volunteers between the ages of 18 and 25 were studied with a variety of pulmonary function tests. Differences between male and female smokers were observed. Pulmonary function abnormalities consistent with small airway dysfunction were noted in male smokers, but not in female smokers. Decreased forced expiratory flows at high lung volumes suggesting large airway dysfunction were noted in both male and female smokers. Decreases in diffusing capacity for CO consistent with abnormalities of the pulmonary vascular system were seen in smokers of both sexes, but were more prominent in females. Because men develop chronic obstruction pulmonary disease more frequently than do women even when adjustments for smoking are made, and because women develop primary pulmonary hypertension more frequently than do men, these chronic diseases may reflect distinct pathophysiologic response of the 2 sexes to agents such as cigarettes.

Adolescent

The effect of atropine on acute antigen-mediated airway constriction in subjects with allergic asthma.

Exposure to antigen by inhalation challenge may produce airway constriction in patients with allergic asthma. To examine the role of reflex bronchoconstriction mediated by the vagus nerve in the antigen-induced airway response, we compared the responses of 6 asthmatic volunteers to inhaled ragweed antigen alone and to antigen given after pretreatment with atropine sulfate, a parasympathetic blocking agent. We found significant increases in airway resistance, limitation of parasympathetic blocking agent. We found significant increases in airway resistance, limitation of forced expiratory flow, increases in lung volumes, and alterations in the distribution of inspired gas after antigen was given. When subjects were pretreated with atropine, we found a mean increase in the 1-sec forced expired volume of 0.380 liter (P less than 0.025) and a mean increase in specific airway conductance of 0.067 sec-1-cm H2O-1 (P less than 0.005). Atropine pretreatment did not prevent the responses to antigen in our subjects. After atropine pretreatment subjects began the antigen challenge with better pulmonary function and at a given antigen dose maintained a better level of function compared to when antigen was given alone. Differences in the absolute level of pulmonary function between the two challenges became smaller with the administration of larger antigen doses. We conclude that reflex bronchospasm involving postganglionic efferent parasympathetic nerve pathways is not a major component of the response to inhaled antigen in human allergic asthma.

Adult

Airway responses to methacholine in allergic and nonallergic subjects.

After inhalation challenge with methacholine, bronchoconstrictor responses were produced in allergic subjects with asthma and hay fever as well as nonallergic subjects. Our results indicate that allergic persons possess a greater pulmonary responsiveness to inhalation of this parasympathomimetic agent than nonallergic subjects; however, patterns of response were different in the 2 types of allergic subjects, those with asthma and those with hay fever. Whereas both types of allergic subjects responded with changes in specific airway conductance when nonallergic subjects did not, only asthmatic subjects differed from nonallergic subjects when comparisons of spirometry were made. These data suggest that there is hypersensitivity of both central and peripheral airways in asthmatics and in the larger central airways of nonasthmatic allergic subjects.

Adult

A comparison of pulmonary function in male smokers and nonsmokers.

Results of certain tests of pulmonary function, including a questionnaire, single-breath N2 test of closing capacity, forced expiration, and diffusing capacity were significantly different in groups of male smokers and nonsmokers. The influence of age on these smoking-related changes of pulmonary function was evaluated. The analyses indicated that (1) some tests including number of symptoms; closing capacity, i.e., closing volume plus residual volume as a percentage of total lung capacity; residual volume as a percentage of total lung capacity; Phase III of the single-breath N2 test, and steady-state diffusing capacity (ml of CO/mm Hg - min) revealed significant differences between adjusted mean smoker and nonsmoker values but did not reveal differences associated with age. (2) Tests of forced expiration (1-sec forced expiratory volume/vital capapity, reciprocal of the maximal mid-expiratory flow, maximal flow at 50 per cent of vital capacity; and moments) however, revealed differences between smoker and nonsmoker means )adjusted and unadjusted), as well as increasing smoker-nonsmoker differences with increasing age. It is suggested that the first group of tests probably measured an all-or-none response that occurred with the onset of smoking and was not affected by duration of smoking. The second group of tests probably measured the effects of continued smoking and indicated increasing abnormality associated with longer exposure (years of smoking). Test showing age-related differences between smokers and nonsmokers may reflect cummulative, irreversible changes in pulmonary function to a greater extent than test that do not.

Adolescent

Clinical, epidemiologic, and pulmonary function studies in alpha,-antitrypsin-deficient subjects of Pi Z type.

The results of pulmonary function testing and systematic medical history and epidemiologic data collection are reported for 20 persons with alpha 1-antitrypsin deficiency of Pi Z phenotype. The most common symptom, reported in 19 subjects (95 per cent), was dyspnea on exertion; 16 subjects (80 per cent) gave a history of wheezing, and 8 (40 percent) reported chronic cough and sputum production. The 8 women who had been pregnant reported a miscarriage rate of 29 per cent for all pregnancies. Respiratory symptoms and disease were commonly reported in the children of study subjects. Pulmonary function testing revealed abnormalities for 18 of 20 subjects, all of those 26 or more years of age. The test that was most frequently abnormal was the 1-sec forced expiratory volume expressed as a per cent of the forced vital capacity. All pulmonary function studies demonstrated a trend toward increased impairment with increased age, which was evident by the fourth decade. Within this group of persons having severe alpha1-antitrypsin deficiency, there was no correlation between serum concentrations of antitrypsin and subjective or objective indices of pulmonary disease. A group of 7 subjects who were incidentally found to have Pi Z alpha1-antitrypsin deficiency exhibited symptoms and pulmonary function abnormalities comparable to those of 13 subjects who were originally referred for known or suspected pulmonary disease. These data suggest that if interventions such as smoking cessation and occupational counseling are to be effective, they should be initiated before the fourth decade of life.

Adult

Effect of intrathoracic pressure on pressure-volume characteristics of the lung in man.

Quasi-static pressure-volume (P-V) curves in normal seated human subjects were determined with pressure at the airway opening (Pa0) set below (negative pressure), above (positive pressure), or equal to ambient pressure. Dynamic compliance (Cdyn) during controlled continuous negative pressure breathing (CNPB) was also studied. Quasi-static P-V curves at negative pressure were decreased in slope, reflected a decrease in total lung capacity, and intersected the P-V curve obtained at ambient Pa0. At positive pressure the P-V curves showed an increase in slope and an increase in total lung capacity. During CNPB a fall in Cdyn was found. The fall in Cdyn was rapid and persisted for the duration of CNPB. Cdyn promptly returned to control levels when Pa0 was adjusted to ambient pressure.

Adult

Vascular interdependence in postmortem human lungs.

Interdependence of arteries and the surrounding lung was estimated in excised, postmortem human lungs. At low vascular pressures, vessel diameter increased as the lung was inflated. At high vascular pressures, vessel diameter decreased as the lung was inflated. Compared to the effects of interdependence in excised dog lobes, those in human lungs at low transpulmonary pressures were small. The following conclusions were reached: (1) the diameter of intrapulmonary arteries is stabilized (more constant with changes in intravascular pressure) when the lung has a high transpulmonary pressure; (2) increases in pulmonary vascular resistance at high lung volumes may be related to extra-alveolar, as well as intra-alveolar, vessel compression; (3) interdependence in human lungs differs markedly from interdependence in dog lungs.

Adolescent