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Biomedical subjects

R D Fairshter

Publications and source records attributed to R D Fairshter.

At least 19 recordsLinked to original sources
PubMed1990

Long-term survival of a lung cancer patient treated with photodynamic therapy.

A 63-year-old male, status post-right pneumonectomy, presented with hemoptysis. Although chest X-ray and CAT scan film findings were negative, bronchoscopy with biopsy from the left mainstem bronchus demonstrated squamous cell carcinoma. Because of the inoperable location of the lesion, the patient was treated with photodynamic therapy (PDT) in February 1984. At present, the patient is cancer free more then 6 years after PDT.

Carcinoma, Squamous Cell↗
PubMed1990

Effect of age on changes in flow rates and airway conductance after a deep breath.

The effects of aging on changes in maximal expiratory flow rates and specific airway conductance after a deep breath were evaluated in 64 normal subjects. Flow rates (Vp) on partial expiratory flow-volume curves (PEFV), initiated from 60-70% of the vital capacity (VC), were compared with those (Vc) on maximal flow-volume curves (MEFV), initiated from total lung capacity (TLC), at a lung volume corresponding to 25% of VC on the MEFV curves. Specific airway conductance was measured before (sGaw) and after a deep inspiration (sGawDI). Bronchodilation after inspiration to TLC was inferred by Vp/Vc less than 1 and sGaw/sGawDI less than 1. The mean Vp was less than Vc. However, the ratio Vp/Vc increased significantly with age (r = 0.75, P less than 0.001). Specific conductance also increased after a deep inspiration (sGaw less than sGawDI). The ratio sGaw/sGawDIj increased slightly but significantly with age (r = 0.28, P less than 0.02). Measurement of lung elastic recoil pressures before and after a deep breath in a subgroup of patients (n = 14) suggested that the age-related increase in Vp/Vc was secondary to a decrement in the ability of a deep breath to decrease the upstream airway resistance. These findings suggest that even though changes in airway size after a deep breath as measured by sGaw/sGawDI have minimal age dependence, aging diminishes expiratory flow rates of MEFV curves relative to PEFV curves because of a decrease in the ability of a deep breath to increase the size of the peripheral airways.

Adolescent↗
PubMed1989

Effects of thoracic gas compression on maximal and partial flow-volume maneuvers.

Airway hysteresis can be evaluated by comparing maximal (MEFV) and partial (PEFV) expiratory flow-volume curves. The maneuvers are often obtained from pulmonary function systems that are subject to gas-compression artifacts. Because gas-compression artifacts might differentially affect PEFV vs. MEFV curves, we simultaneously obtained MEFV and PEFV curves by use of a spirometer and a volume-displacement plethysmograph (a method not subject to gas-compression artifacts) in normal and asthmatic subjects. Plethysmographic flow rates exceeded spirometric flow rates on all MEFV and PEFV maneuvers. When maximal flow exceeded partial flow (or vice versa) in the plethysmograph, the same result was virtually always observed for spirometric measurements. Alveolar pressure (PA) was higher on MEFV than on PEFV maneuvers in asthmatic subjects; comparisons between PA (on PEFV and MEFV maneuvers) in normal subjects varied at different lung volumes. Ratios of Vmax on PEFV maneuvers to Vmax on MEFV maneuvers (Vmax-p/Vmax-c) obtained from a volume-displacement plethysmograph differ quantitatively from ratios determined in systems subject to gas-compression artifacts; qualitatively, however, failure to account for thoracic gas compression ordinarily will not influence the ability to identify airway hysteresis (or lack thereof) by use of Vmax-p-to-Vmax-c ratios.

Adult↗
PubMed1989

The MVV/FEV1 ratio in normal and asthmatic subjects.

We compared the ratio of maximal voluntary ventilation/forced expiratory volume in one second (MVV/FEV1) in normal individuals and asthmatic subjects. Our hypothesis was that MVV/FEV1 would be lower in asthmatic subjects. We also compared MVV/FEV1 results with the effects of deep inspiration (DI) on bronchomotor tone and with methacholine responsiveness. In normal subjects, MVV/FEV1 was higher than that in asthmatic subjects. Specific conductance (SGaw) increased after a single DI or an MVV maneuver in normal individuals. An MVV maneuver caused SGaw to decrease in asthmatic subjects. In asthmatic subjects, there was a significant correlation between MVV/FEV1 ratio and magnitude of decrease in SGaw after an MVV maneuver. Results of methacholine testing indicated that asthmatic subjects with low MVV/FEV1 ratios were more responsive to methacholine than those whose MVV/FEV1 ratios were within normal range. We conclude that MVV/FEV1 ratios are abnormally low in many asthmatic subjects and that low MVV/FEV1 ratios may indicate increased bronchial responsiveness to methacholine.

Adult↗
PubMed1988

How much theophylline is enough?

Theophylline not only is a bronchodilator but also has other effects (inhibition of mediator release, enhancement of mucociliary clearance, enhancement of diaphragmatic contractility) that are potentially beneficial to asthmatic patients. Recent studies suggest that theophylline pharmacodynamics vary among asthmatic patients. However, on average, most of the total bronchodilatory response occurs at serum theophylline concentrations of 0 to 10 mg/liter. Additional (but less) bronchodilatation occurs at serum theophylline levels between 10 and 20 mg/liter. Pharmacodynamic relationships are not well established for other therapeutic effects of theophylline, such as attenuation of pharmacologically induced bronchoconstriction. An important feature of oral controlled-release theophylline therapy is timing of drug administration. Because airway reactivity increases and airway caliber decreases at night, it has been suggested that the greatest benefit is derived from theophylline when peak serum concentration is reached during the night or the early morning.

Asthma↗
PubMed1988

Adverse effects of (15S)-15-methyl-prostaglandin E1 in normal and paraquat-exposed rats.

Single, daily injections of approximately 1 mg/kg of (15S)-15-methyl-PGE1 (mPGE1), a PGE1 analog, have been reported to inhibit inflammation and to prolong survival in several animal models of local and systemic inflammation. We examined the effect of this dose of mPGE1 on paraquat toxicity in rats. A significant increase in early mortality was identified in mPGE1-treated rats as early as 3 hr following injection of paraquat and appeared associated with increased respiratory effort. Rats given mPGE1 without paraquat also appeared to increase respiratory effort but did not die. Rats killed at 3 hr following injections demonstrated increased lung weights in both paraquat-injected and control animals receiving mPGE1. Although a neutrophilia was identified in these animals, no significant increase in lung lavage neutrophils or albumin was identified. These data suggest that large intermittent doses of a PGE1 analog may adversely affect the respiratory system of normal and injured animals, and will accelerate mortality following exposure to potentially lethal doses of paraquat.

Alprostadil↗
PubMed1988

Effect of dimethylthiourea on plasma paraquat concentration.

In a previous study, administration of the hydroxyl radical scavenger, dimethylthiourea (DMTU), and paraquat was associated with higher mortality in rats than was paraquat alone. In the present study, the possibility was evaluated that administration of DMTU increased plasma paraquat levels. Plasma paraquat concentrations were measured in Sprague-Dawley rats 1, 2, 4, 8 and 24 h after intraperitoneal (i.p.) injection of 29 mg paraquat cation/kg body wt. Another group of rats was treated identically except that they received i.p. injections of DMTU before injections of paraquat. Administration of DMTU was associated with increased plasma paraquat concentration (P less than 0.01). Pharmacokinetic analyses indicated that, compared to rats receiving paraquat alone, rats given paraquat and DMTU showed: (1) greater area under the paraquat concentration time-curve; (2) lower total body paraquat clearance; and (3) smaller apparent volume of distribution. Plasma biochemical studies indicated that paraquat caused hyperglycemia as well as an early reduction (compared to controls) in hepatic enzymes. We conclude that: (1) DMTU administration is associated with increased plasma paraquat concentrations; and (2) impaired synthesis or inhibition of release of hepatic proteins may be an early effect of paraquat.

Animals↗
PubMed1988

Effect of chestwall removal on expiratory flow in dogs.

We studied the effect of chestwall removal on Flow-Volume (F-V) curves in anesthetized dogs, by applying suction at the airway opening. Pressure and volume ranges utilized were comparable to those by others in the past for studies of expiratory flow in canine models. It was found: 1) Expiratory flow became nil at residual volume (RV) in the intact animal. On the contrary, flow after chestwall removal continued below RV, until the lung reached its minimal volume (Vmin) which averaged 11 +/- 6% TLC or 50% RV. 2) At high lung volumes, flow, particularly peak flow of F-V curves, was greater before than after chestwall removal. Thus the chestwall has a bimodal effect on flow. At low lung volumes, particularly below RV, the chestwall inhibits expiratory flow, and chestwall removal always results in flow increase, such that the lung can empty until all airways are collapsed, down to a volume of about 50% RV. On the contrary, the chestwall facilitates expiratory flow at high lung volumes, particularly at peak flow. The bimodality of chestwall effect on expiratory flow is consistent with the well known directional reversal of chestwall elastic recoil as volume changes, being nil at chestwall resting volume (Vcwr), and directing inwards (thus helping expiration) above Vcwr, or outwards (thus inhibiting expiration) below this volume (12). In a hypothetical situation of no chestwall resistance, chestwall effect on flow would be nil at Vcwr. In our experimentation, we found that the volume where the chestwall had no effect on expiratory flow averaged 71% TLC, clearly higher than Vcwr (49% TLC). We attribute the difference to the chestwall resistance.

Animals↗
PubMed1987

Relationships between minute ventilation, oxygen uptake, and time during incremental exercise.

It has recently been reported that blood and muscle lactate increased exponentially during incremental exercise, casting some doubt upon the concept of 'anaerobic threshold'. To gain further insight into this controversy, we examined the relationships between minute ventilation (VE), time and oxygen uptake (VO2) in normal subjects during incremental exercise. During exercise, the relationship of VE to either time of exercise or to VO2 appeared curvilinear; VE was reliably described as an exponential function (y = axb + c) of both time of exercise (r2 = 0.96) and VO2 (r2 = 0.92). We also compared variables from 30-second incremental tests with variables obtained from quasi-steady-state incremental tests using cycle and treadmill ergometry. With the exception of heart rate, variables measured at maximum exercise were similar during short-duration and quasi-steady-state incremental tests. These data support the ideas that: there is no abrupt change in metabolism and oxygen availability during progressive exercise, and results of rapid incremental and quasi-steady-state exercise tests are generally comparable in normal individuals.

Adult↗
PubMed1987

Evaluation of a metered-dose aerosol delivery system using partial flow-volume curves.

In 12 normal subjects, FEV1, FVC, peak expiratory flow rate, and flow at 25% of FVC on maximal (MEFV) and partial (PEFV) expiratory flow volume maneuvers were measured before and after inhalation of 2.6 mg of metaproterenol from a metered-dose inhaler (MDI) or from an MDI-holding chamber (MDI-HC) delivery system. The 2 delivery systems were studied on separate days using a randomized crossover design. Premetaproterenol pulmonary function results were very similar on both days. However, on the MDI-HC day, significantly greater bronchodilatation was observed; this was only detectable on PEFV maneuvers. Compared with those on the MDI day, postmetaproterenol PEFV rates on the MDI-HC day were approximately 11% higher (p less than 0.02); premetaproterenol to postmetaproterenol increments in PEFV rates were also larger on the MDI-HC day (p less than 0.05). These results can be explained by the phenomenon of airway hysteresis. The deep breath taken prior to performance of the FVC maneuver reduced bronchomotor tone in almost all subjects, thereby limiting the magnitude of possible change from inhaled bronchodilator. Partial flow-volume curves were not preceded by deep inspiration and were more sensitive in detecting bronchodilatation.

Adult↗
PubMed1987

Pulmonary physiology in the postoperative period.

After upper abdominal or thoracic surgery, loss of lung volume, manifested most importantly by reduced FRC, and abnormal gas exchange, manifested by postoperative reduction in PaO2, are the rule rather than the exception. These physiologic alterations in lung function occur in the absence of superimposed complications such as pneumonia and/or lobar atelectasis; the usual physiologic alterations do, in fact, predispose to pulmonary complications (approximate 20 per cent incidence) which, when present, further compromise lung function. The mechanisms of postoperative impairment in lung function are multiple, interactive, and at the present, incompletely understood. An attempt to summarize the more important causes of impaired postoperative lung function is shown in Figure 6.

Humans↗
PubMed1986

Time dependence of airways and lung parenchymal recoil hysteresis.

Hysteresis of airways and lung parenchymal recoil was examined in normal subjects by measuring specific conductance (sGaw) and lung elastic recoil (Pst,L) before and 5, 10, 15, and 30 s after deep inspiration (DI). Routine lung function tests were normal before and after inhaled metaproterenol. sGaw increased significantly for 10 s after DI. Also, sGaw(DI) was greater than sGaw in 11 of 12, 8 of 12, 7 of 12, and 6 of 12 subjects at 5, 10, 15, and 30 s, respectively, after DI. The response of sGaw to DI and metaproterenol correlated significantly with each other (r = 0.82, P less than 0.001). However, after metaproterenol, sGaw(DI) did not exceed sGaw. Pst,L decreased significantly for 15 s after DI, with the lowest measured Pst,L(DI) values occurring 5 s after DI (P less than 0.01-0.001). Both sGaw(DI) and Pst,L(DI) values returned to base line (preinspiration) in a time-dependent exponential manner, with time constants of 9.2 +/- 4.9 and 11.3 +/- 6.1 s, respectively; these time constants were not significantly different from each other. We conclude that airways hysteresis is the predominant finding in normal subjects (even without prior pharmacological bronchoconstriction) before but not after metaproterenol; Pst,L decreases after DI and, in normal individuals, returns to base line in a time-dependent manner; and the time-dependent behavior of airways and lung parenchymal hysteresis have opposite (and unequal) effects on airway caliber.

Adult↗
PubMed1986

Comparison of once-a-day and twice-a-day theophylline in asthma.

Sustained-release theophylline compounds given once (Uniphyl) or twice (Theodur) daily were compared in adult asthmatics. Following a single dose of oral medication, large and peripheral airways bronchodilation occurred; response to theophylline correlated significantly with the log plasma theophylline concentration. Cardiac output and stroke volume, measured noninvasively using the acetylene technique, also increased significantly. During maintenance therapy, both preparations caused similar improvements in pulmonary function and symptoms; however, side effects were less with once-daily therapy.

Asthma↗
PubMed1986

Supine change in arterial oxygenation in patients with chronic obstructive pulmonary disease.

In normal subjects, recumbent PaO2 differs from upright PaO2 as a function of the relationship between FRC and closing volume. However, in patients with lung disease, the factors controlling PaO2 change. Furthermore, the distribution of airway closure does not strictly reflect gravitational gradients in pleural pressure. Hence, we evaluated the effects of recumbency on PaO2 in patients with advanced COPD. We conducted pulmonary function tests and measured PaO2, AaPO2, change from upright to supine FRC, VE, cardiac output (QT), and mixed venous oxygen saturation (SvO2). Eight patients with COPD in whom PaO2 decreased in the supine position (Group I) were compared with 8 patients with COPD in whom PaO2 improved in the recumbent position (Group II); the only anthropometric difference between the groups was greater body weight in Group II (p less than 0.05). Pulmonary function was comparable in the 2 groups. In both groups, FRC decreased with recumbency, but supine FRC and delta FRC did not differ between groups nor correlate significantly with PaO2, AaPO2, or venous admixture (QVA/QT). Supine SVO2 increased in both groups, but supine QT increased significantly only in Group I. In Group II, recumbent QVA/QT did not change significantly, whereas recumbent QVA/QT increased (p less than 0.02) in Group I. The cause for increased QVA/QT in Group I was reduced VE plus increased QT while supine; in contrast, by maintaining a higher supine VE and by not increasing QT significantly, an increase in QVA/QT was prevented in Group II subjects, an increase that would otherwise have overwhelmed the benefits of increased recumbent SVO2 on PaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1985

Comparison of clinical effects and pharmacokinetics of once-daily Uniphyl and twice-daily Theo-Dur in asthmatic patients.

A pharmacokinetic study using theophylline syrup in adult asthmatic patients demonstrated a mean apparent volume of distribution of 0.38 liters/kg, mean elimination rate constant of 0.10 hours-1, and variable rates of clearance of theophylline (total body clearance of 0.38 to 0.96 ml/kg per minute). Subsequently, the asthmatic patients were compared using a cross-over design after maintenance Uniphyl (once daily at 8 a.m. or at 8 p.m.) and Theo-Dur (twice daily at 8 a.m. and 8 p.m.). Total daily maintenance theophylline dosage, calculated from the pharmacokinetic data, was identical in all three cross-over phases. At the end of each phase, plasma theophylline levels were measured every two hours and spirometric determinations were made every four hours (excluding 4 a.m.) for 24 hours. The following results were observed: highest peak and mean plasma theophylline concentration and area under the concentration-time curves with evening Uniphyl (p less than 0.05); prolonged time-to-peak theophylline concentration after nocturnal compared with daytime dosing; diurnal variation in pulmonary function and plasma theophylline concentrations; no significant differences between the three maintenance treatments in asthmatic symptoms or spirometric results.

Adult↗
PubMed1985

Magnesium and potassium therapy in multifocal atrial tachycardia.

Eight patients with multifocal atrial tachycardia received 7 to 12 gm of magnesium sulfate intravenously over a 5-hour period. Potassium supplements were given initially or added later. Initial arterial blood gases showed mean pH 7.48 +/- 0.03, PcO2 39.7 torr, PO2 72 torr, HCO-3 29.8 +/- 4.5 mEq/L, and base excess 6.84 +/- 3.78 mEq/L. Initial serum magnesium correlated well with initial serum potassium. Three patients had subnormal levels of magnesium and potassium. The level of serum magnesium rose with an intravenous injection magnesium and serum potassium levels tended to fall unless they were supplanted with potassium. There were seven patients who retained more than 20 mEq of the infused magnesium. Multifocal atrial tachycardia was successfully converted to sinus rhythm or sinus tachycardia in seven patients. Multifocal atrial rhythm (at slow rate) persisted in one patient. Two patients with falling serum potassium levels required potassium supplements. Results of this study confirm that patients with multifocal atrial tachycardia respond favorably to parenteral magnesium and potassium. We believe that serum magnesium administered together with serum potassium stabilizes the ionic balance of atrial cells and thus prevents spontaneous ectopy.

Aged↗
PubMed1985

Role of Alternaria and Penicillium spores in the pathogenesis of asthma.

The ability to harvest spore-rich isolates of molds permitted quantitative studies of their role in the pathogenesis of asthma. Alternaria and Penicillium were selected as examples of ubiquitous molds that readily induce IgE antibodies and are of contrasting sizes. Extracts from those spores were prepared for skin tests and aerosol bronchial challenges. Intact spores were used in the same subjects in bronchial challenges delivered by a Spinhaler. Seven patients with a history of mild asthma received a total of 16 bronchial challenges with the mold to which they had been sensitized. Provocative doses in spore equivalents for a 35% drop in SGaw, 20% drop in FEV1, or 25% drop in PEFR were sought for each challenge. Density dependence-flow rates were also determined. Environmental spore survey data were obtained and compared with the challenge doses for these spores. It was found that immediate-type asthma was readily provoked by both whole spores and by their extracts, in some subjects fewer intact than extracted spores were required, delayed-type asthma occurred only after whole spore challenges, SGaw was the most sensitive and equally specific of the pulmonary function tests, and provocative doses of spore equivalents were within natural exposure ranges. The study confirmed that Alternaria and Penicillium spores in relatively natural states and numbers were potent immunopathogens for asthma.

Adolescent↗