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Biomedical subjects

I Rubinstein

Publications and source records attributed to I Rubinstein.

At least 145 records · Page 8Linked to original sources

Thyroid hormone modulates membrane currents in guinea-pig ventricular myocytes.

Thyroid hormones have been previously shown to alter cardiac electrophysiological and mechanical properties in humans and in experimental animals. To investigate electrophysiological mechanisms responsible for some of these alterations, we recorded action potentials and membrane currents from isolated ventricular myocytes obtained from euthyroid, hypothyroid and hyperthyroid guinea-pigs. Hyperthyroidism was induced by injecting 150 micrograms/kg triiodothyronine for 8-11 days, and hypothyroidism was induced by propylthiouracil treatment for 35-45 days. We found that the slow inward current, was increased by hyperthyroidism and decreased by hypothyroidism: in euthyroid, hyperthyroid and hypothyroid myocytes peak slow inward current was (mean +/- SEM): -1.08 +/- 0.06 nA, -1.83 +/- 0.18a nA and -0.64 +/- 0.07a nA, respectively (a, p less than 0.005). In addition, the membrane potential at which peak slow inward current occurred was modified by the thyroid state and in euthyroid, hyperthyroid and hypothyroid myocytes it was (mean +/- SEM): 4.8 +/- 0.7 mV, -1.8 +/- 1.6a mV and 11.0 +/- 1.4a mV, respectively. The outward rectifying current, was also affected by the thyroid state, and in euthyroid, hyperthyroid and hypothyroid myocytes, the amplitude at VM = +60 mV was (mean +/- SEM): 0.51 +/- 0.09 nA, 1.15 +/- 0.08a nA and 0.49 +/- 0.05 nA, respectively. a, p less than 0.001 compared to euthyroid myocytes. Intraperitoneal administration of a single dose of triiodothyronine to guinea-pigs, 2 h prior to the electrophysiological experiment, increased the slow inward current amplitude, as was seen with chronic hyperthyroidism, but had no significant effect on the outward current and on the action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Glottic dimensions in healthy men and women.

Glottic aperture is important in modulating respiratory system resistance. Male patients with obstructive sleep apnea (OSA) have a smaller glottic cross-sectional area compared to controls. Since OSA has a strong male predominance, we reasoned that glottic dimensions may differ between healthy men and women. Therefore, we utilized the acoustic reflection to measure glottic cross-sectional area in 44 non-smoking, non-obese, healthy subjects, 25 men and 19 women. Glottic area was measured during a continuous slow expiration from total lung capacity (TLC) to residual volume (RV). We compared glottic areas in men and women at three lung volumes: TLC, 50% of vital capacity (VC), and RV. We found that in all but 2 subjects, glottic areas at TLC was greater than at 50% VC or RV. At any given lung volume, there was no significant difference in glottic area between men and women. The reduction in glottic area between TLC and RV was also similar between men and women (36 +/- 24% and 33 +/- 21%, respectively). However, this reduction in glottic area occurred mainly at low lung volumes in women, and more uniformly throughout the vital capacity range in men. We conclude that changes in glottic dimensions are dependent on lung volume, that healthy men and women have similar glottic areas, and that the glottic aperture shows similar variation with lung volume among both sexes.

Adult↗

Local mediator release after antigen challenge of a bronchial segment in allergic dogs.

To investigate the local intraluminal bronchial response to an antigenic stimulus, we developed a bronchoscopic double-balloon system to challenge and lavage a segment of the left main-stem bronchus. We studied whether fluid from above or below the occlusion balloons leaked into the bronchial segment. Lavage was performed before and after placement of red and blue pigments proximal and distal to the inflated balloons, respectively, and the recovered lavage fluid was analyzed visually and spectrophotometrically in three experiments. There was no evidence for pigment leakage into the segment. In six anesthetized ragweed-allergic dogs, local ragweed antigen challenges were performed. After balloon inflation in the left main-stem bronchus, we performed two baseline lavages of the interballoon segment, introduced a ragweed antigen solution, and performed two postchallenge lavages. The recovered fluid was analyzed for the concentrations of prostaglandin D2 (PGD2; radioimmunoassay) and histamine (fluorometric technique) and for total and differential cell counts. Antigen challenge was associated with a significant increase in PGD2 concentration in the recovered fluid, rising from a median of 178 pg/ml (range, 157-647) before to 919 pg/ml (range, 149-2,452) after challenge. Median histamine concentrations were 3.1 ng/ml (range, 1-5.4 ng/ml) before and 5.6 ng/ml (range, 1-16.2) after challenge (P = not significant). In four dogs, a control challenge with the antigen vehicle alone showed no change in either mediator. Changes in cell counts after challenge were inconsistent.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Virus induces airway hyperresponsiveness to tachykinins: role of neutral endopeptidase.

We examined the effects of viral respiratory infection by Sendai virus on airway responsiveness to tachykinins in guinea pigs. We measured the change in total pulmonary resistance induced by substance P or capsaicin in the presence or absence of the neutral endopeptidase inhibitor, phosphoramidon, in infected and in noninfected animals. In the absence of phosphoramidon, the bronchoconstrictor responses to substance P and to capsaicin were greater in infected than in noninfected animals. Phosphoramidon did not further potentiate the responses to substance P and to capsaicin in the infected animals, whereas it did so in noninfected animals. Studies performed in vitro showed that nonadrenergic noncholinergic bronchial smooth muscle responses to electrical field stimulation were also increased in tissues from infected animals and that phosphoramidon increased the response of tissues from noninfected animals greatly but increased the responses of tissues from infected animals only slightly. Responses to acetylcholine were unaffected by viral infection. Neutral endopeptidase activity was decreased by 40% in the tracheal epithelial layer of the infected animals. We suggest that respiratory infection by Sendai virus causes enhanced airway responsiveness to tachykinins by decreasing neutral endopeptidase-like activity in the airway epithelium.

Animals↗

Glottic and cervical tracheal narrowing in patients with obstructive sleep apnea.

There are several studies showing that patients with idiopathic obstructive sleep apnea (OSA) have a narrow and collapsible pharynx that may predispose them to repeated upper airway occlusions during sleep. We hypothesized that this structural abnormality may also extend to the glottic and tracheal region. Consequently, we measured pharyngeal (Aph), glottic (Agl), cervical tracheal (Atr1), midtracheal (Atr2), and distal (Atr3) tracheal areas during tidal breathing in 66 patients with OSA (16 nonobese and 50 obese) and 8 nonapneic controls. We found that Aph, Agl, and Atr1, but not Atr2 or Atr3, were significantly smaller in the OSA group than in the control group. Obese patients with OSA had the smallest upper airway area, although the nonapneic controls had the largest areas. Multiple linear regression analysis revealed that the pharyngeal area, cervical tracheal area, and body mass index were all independent determinants of the apnea-hypopnea index, accounting for 31% of the variability in apnea-hypopnea index. Aph, Agl, and Atr showed significant correlation with the body mass index. We conclude that sleep-disordered breathing is associated with diffuse upper airway narrowing and that obesity contributes to this narrowing. Furthermore, we speculate that a common pathophysiological mechanism may be responsible for this reduction in upper airway area extending from the pharynx to the proximal trachea.

Adult↗

Effect of exercise, hyperpnea, and bronchoconstriction on plasma atrial natriuretic peptide.

To examine whether endogenous secretion of atrial natriuretic peptide (ANP) modifies the bronchomotor response to moderately strenuous exercise and, conversely, whether hyperpnea of exercise or bronchoconstriction alone modulates the release of ANP, we compared the rise in specific airway resistance and the rise in circulating immunoreactive ANP (IR-ANP) induced by a 5-min submaximal exercise and by eucapnic hyperpnea with cold dry air and exercise-matched minute ventilation in six healthy individuals and in five subjects with clinically stable asthma. As expected, the increase in specific airway resistance from base line provoked by exercise was greater in the asthmatic subjects (from 11.8 +/- 7.1 to 34.0 +/- 18.6 l.cmH2O.l-1.s-1) than in the healthy subjects (from 3.7 +/- 1.2 to 4.5 +/- 1.9 l.cmH2O.l-1.s-1). In both groups, exercise was associated with a similar and significant rise in plasma IR-ANP levels, ranging from 222 to 550% from base-line value in the healthy group and from 176 to 1,120% from base-line value in the asthmatic group. Peak plasma IR-ANP levels occurred from 3 to 15 min after completion of exercise with a return to base-line values within 60 min. Although eucapnic hyperpnea was associated with a similar increase in specific airway resistance as was exercise, it provoked an increase in circulating IR-ANP in only one subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Expiratory glottic widening in asthmatic subjects during exercise-induced bronchoconstriction.

Glottic caliber is modulated in a way that optimizes the airway resistance and the work of breathing. The midexpiratory glottic narrowing that normally occurs during tidal breathing is enhanced during histamine- or methacholine-induced airway narrowing. Exercise is associated with increased ventilatory demand and midexpiratory glottic widening in healthy subjects. However, the relative contribution of glottic aperture to airflow limitation during exercise-induced asthma is unknown. Consequently, we used the acoustic reflection technique to test whether a decrease in midexpiratory glottic size occurred also during exercise-induced bronchoconstriction in seven asthmatic subjects. Exercise resulted in a 38 +/- 16% (SD) fall in FEV1 from the baseline value (p less than 0.001) and a significant increase in midexpiratory glottic cross-sectional area from 1.89 +/- 0.45 cm2 before to 2.36 +/- 0.71 cm2 during bronchoconstriction (p less than 0.05). This midexpiratory glottic widening was also associated with increased tidal flow rates. We conclude that in marked contrast to airway obstruction induced by histamine or methacholine, exercise-induced asthma is associated with midexpiratory glottic widening, which occurs concomitantly with a decrease in lower airway caliber. We suggest that modulation of glottic aperture during acute asthma is heterogeneous and depends partly on the initiating stimulus.

Adult↗

Lung volume-related changes in the pharyngeal area of obese females with and without obstructive sleep apnoea.

The majority of male patients with obstructive sleep apnoea (OSA) have an abnormal pharyngeal structure and function, with episodic complete airway occlusion during sleep. Since OSA is less common in females than in males, it is possible that other abnormalities are active in female patients with OSA. Consequently, we measured pharyngeal area and its lung volume-related changes (LVRC) from functional residual capacity (FRC) to residual volume (RV) in overweight females, 14 with OSA and 14 without OSA. Pharyngeal areas were measured using the acoustic reflection technique. While there were no significant differences in pharyngeal area between the OSA and control groups at either FRC (mean +/- SD, 3.49 +/- 0.46 cm2 vs 3.08 +/- 0.63 cm2) or RV (2.86 +/- 0.47 cm2 vs 2.67 +/- 0.49 cm2), the reduction in pharyngeal area between FRC and RV was significantly greater in the OSA group (0.63 +/- 0.23 cm2 vs 0.33 +/- 0.32 cm2, p less than 0.05). Furthermore, although the expiratory reserve volume (ERV) was not significantly different between the two groups (0.4 +/- 0.2 l vs 0.4 +/- 0.3 l), LVRC, defined as the reduction in pharyngeal area normalized by ERV, was significantly higher in the females with OSA than in the non-apnoeic controls (2.68 +/- 2.24 cm2.l-1 vs 1.17 +/- 1.23 cm2.l-1, p less than 0.02). We conclude that females with OSA have abnormal pharyngeal mechanics similar to males with OSA.

Adult↗

Determinants of blood pressure in snorers.

To examine the hypothesis that the tendency to raised blood pressure in snorers is associated with nocturnal hypoxaemia and snoring, blood pressure was measured and snoring, oxyhaemoglobin saturation (SaO2), and thoraco-abdominal movements were monitored overnight in 372 snorers. Snoring was quantified as number of snores per hour of sleep (snoring index). The data were analysed by multiple linear regression of diastolic blood pressure against age, body mass index (BMI), apnoea-hypopnoea index (AHI, number of episodes per hour), snoring index, and SaO2. Diastolic blood pressure correlated significantly with BMI, AHI, and mean nocturnal oxygen saturation, but not with the snoring index. However, snoring index correlated with BMI, AHI, and mean nocturnal oxygen saturation. Snoring is thus not a direct risk factor for hypertension, but may influence blood pressure via its association with obesity, obstructive sleep apnoea, and nocturnal hypoxaemia.

Age Factors↗

Comparison of glottic areas measured by acoustic reflections vs. computerized tomography.

We compared measurements of glottic area obtained by acoustic reflection technique with anatomically equivalent area measured from computerized tomographic (CT) scans of the neck in 11 subjects with glottic pathology. Both measurements were performed in the supine position during tidal breathing at functional residual capacity. We found excellent agreement in glottic areas obtained by both methods: the mean (+/- SD) values were 1.8 +/- 0.8 cm2 for the acoustic method and 1.7 +/- 0.9 cm2 for the CT method. Linear regression analysis revealed the following relationship between the area measured by acoustic technique (AAC) and that measured by CT (ACT): AAC = 0.81.ACT + 0.36. There was a significant correlation between the two measurements of glottic area (r = 0.95, P less than 0.0001). We conclude that the acoustic reflection technique may be used reliably in clinical and physiological studies concerned with glottic geometry.

Acoustics↗

Assessment of maximal expiratory pressure in healthy adults.

Maximal static expiratory pressure developed at the mouth (PEmax) provides a useful clinical index of expiratory muscle function; however, the range of normal values among laboratories shows considerable variation. We examined the hypothesis that the wide variability could be attributable to the differences in technique among laboratories. We measured PEmax at functional residual capacity (PEmax FRC) in 28 healthy subjects using the following five techniques: 1) using a scuba-type mouthpiece with the cheeks supported by the hands ("hands on"), 2) without supporting the cheeks ("no hands"), 3) using a rigid, circular mouthpiece (2.8 cm ID, "tube"), 4) using the scuba-type mouthpiece but with the cheeks supported by an observer ("other hands"), and 5) using a large-bore circular mouthpiece (4.1 cm ID, "new tube"). Mean PEmax FRC obtained with hands on was significantly higher than no-hands and tube methods. PEmax FRC values obtained by the other-hands and new-tube maneuvers were similar to the hands-on maneuver. We conclude that the technique used to measure PEmax FRC can significantly affect the results and suggest that it should be measured using a large-bore circular mouthpiece or a scuba-diving mouthpiece with the cheeks supported.

Adult↗

Dichotomous airway response to exercise in asthmatic patients.

The extent and location of airway narrowing in asthmatic subjects are usually inferred from measurements of maximal expiratory flow rates and airway resistance. In the present study, we used the acoustic reflection technique to measure the airway cross-sectional area in 14 asthmatic subjects and 8 normal controls before and following treadmill exercise tests. In normal subjects, exercise caused no significant change in FEV1 and bronchial area, but did cause a significant increase in the intrathoracic tracheal area from 2.0 +/- 0.7 cm2 to 3.1 +/- 0.7 cm2 (p less than 0.002). In the asthmatics, exercise was followed by a 37 +/- 15% reduction in forced expiratory volume in 1 s(FEV1), and a 36% decrease in bronchial area from 8.5 +/- 2.8 cm2 to 5.4 +/- 1.1 cm2 (p less than 0.001); however, extra- and intrathoracic tracheal areas increased significantly. These findings provide direct and quantitative evidence that the bronchi are the main site of airway narrowing in exercise-induced asthma, and draw attention to the phenomenon of tracheal dilatation that occurs concomitant with bronchoconstriction in asthmatic patients.

Adult↗

Improvement in upper airway function after weight loss in patients with obstructive sleep apnea.

Overweight patients with obstructive sleep apnea (OSA) are improved by weight reduction, although the underlying mechanisms are not clear. We tested the hypothesis that improvement in OSA after weight loss is associated with improvement in pharyngeal function. Consequently, we measured pharyngeal area at functional residual capacity (AFRC) and at residual volume (ARV), the percent change in pharyngeal area between FRC and RV (delta Aph%) defined as (AFRC - ARV)/AFRC x 100, and lung volume dependence of pharyngeal area (LVD) defined as the difference between AFRC and ARV normalized for the expiratory reserve volume (ERV)--in 12 overweight apneic patients before and after weight loss. We found that after a 26 +/- 18 kg weight loss, there was a significant reduction in the apnea/hypopnea index from 57 +/- 29 to 14 +/- 10 (p less than 0.0005) and increase in the lowest nocturnal oxygen saturation from 54 +/- 20% to 80 +/- 8% (p less than 0.001). This improvement was associated with a significant reduction in delta Aph% from 25 +/- 15% to 9 +/- 18% (p less than 0.05) and a significant decrease in LVD from 1.98 +/- 1.52 cm2/L to 0.16 +/- 0.88 cm2/L (p less than 0.005). There were four patients in whom baseline LVD was low and relatively unchanged after weight loss. Three of these patients exhibited paradoxical inspiratory narrowing of the glottis, which reversed after weight loss; these glottic abnormalities were not present in the rest of the patients with OSA. We conclude that improvement in obstructive sleep apnea after weight loss may be related to improvement in pharyngeal and glottic function.

Adult↗

Paradoxical glottic narrowing in patients with severe obstructive sleep apnea.

Most patients with obstructive sleep apnea have increased pharyngeal collapsibility (defined in the present study as an increased lung volume dependence of pharyngeal area), which predisposes them to upper airway occlusion during sleep. However, there are patients with severe obstructive sleep apnea who have low-normal pharyngeal collapsibility. The factors leading to nocturnal upper airway obstruction in such patients have not been ascertained. We studied 10 overweight male patients with severe obstructive sleep apnea and low-normal pharyngeal collapsibility to determine the site of upper airway pathology in these patients. We found that all 10 patients exhibited paradoxical inspiratory narrowing of the glottis during quiet tidal breathing. This phenomenon was not observed in a matched group of 10 snoring, nonapneic male controls. We conclude that paradoxical glottic narrowing may be a contributing factor in the pathogenesis of upper airway obstruction in patients with severe obstructive sleep apnea who have low-normal pharyngeal collapsibility.

Adult↗

Neurosarcoidosis associated with hypersomnolence treated with corticosteroids and brain irradiation.

Narcoleptic features developed in a young man with CNS sarcoidosis. This was associated with a structural lesion in the hypothalamus as demonstrated on CT scans of the head. The diagnosis of narcolepsy was established by compatible clinical history and the Multiple Sleep Latency Test. Treatment with high-dose corticosteroids was ineffective, but when the low-dose, whole-brain irradiation was added, complete resolution of the narcoleptic features ensued.

Adult↗

Snoring and upper airway properties.

Habitual snoring in adults may be related to upper airway dysfunction, although the precise relationship has never been studied. We quantitatively measured snoring and correlated it with upper airway properties in 50 apneic and 59 nonapneic adult male patients. Both groups were similar in terms of nasal airflow resistance and pulmonary function tests. We found a significant correlation between the severity of snoring and nasal airflow resistance in both groups, and between the severity of snoring and pharyngeal and glottic areas in the apneic group. We conclude that snoring may be associated with abnormalities in upper airway properties.

Adult↗

Clinical features of sarcoidosis in elderly patients.

We reviewed 17 cases of biopsy-proven sarcoidosis occurring in patients who were 65 years of age or older at the time of diagnosis in order to determine the clinical features of sarcoidosis in this group of elderly patients. A female preponderance (76%) was noted, as well as significant respiratory and cutaneous symptoms. There were no characteristic diagnostic features of sarcoidosis in this group; therefore, we suggest that tissue biopsy is needed to exclude pulmonary diseases such as neoplasm or tuberculosis. Most elderly patients having sarcoidosis remained clinically stable during the period of follow-up and did not require therapy for sarcoidosis. We propose that sarcoidosis should be considered in the differential diagnosis of elderly patients presenting with pulmonary or multisystem disease.

Aged↗