Biomedical subjects

A T Scardella

Publications and source records attributed to A T Scardella.

13 recordsLinked to original sources

PubMed2000

Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.

Adolescent↗

PubMed1999

Variable extrathoracic airflow obstruction and chronic laryngotracheitis in Gulf War veterans.

STUDY OBJECTIVES: To study the flow-volume loop for evidence of variable extrathoracic airflow obstruction in Persian Gulf War veterans. DESIGN: Retrospective case-control, single-center study. SETTING: The pulmonary division of an academic health-care center. SUBJECTS: A convenience sample of the Persian Gulf Registry. MEASUREMENTS AND INTERVENTIONS: (1) Midvital capacity ratio (ratio of maximum forced midexpiratory to maximum forced midinspiratory flow). This ratio is the criterion standard for the diagnosis of variable extrathoracic airflow obstruction. (2) Evaluation of the anatomy and function of the extrathoracic airway by fiberoptic bronchoscopy. (3) Further investigation into the airway abnormality by histologic evaluation of tracheal biopsy samples in Gulf War veterans only. RESULTS: Midvital capacity was > 1.0 in 32 of 37 Gulf War veterans compared with only 11 of 38 control subjects. The mean (+/-SD) value was 1.37+/-0.4 among Gulf War veterans and 0.88+/-0.3 among control subjects (p=0.0000005). FVC and its ratio to FEV1 were normal in all these subjects. Bronchoscopy showed inflamed larynx and trachea in all (n=17) Gulf War veterans. Histologic study showed chronic inflammation of the trachea in everyone (n=12) who had an adequate biopsy sample. CONCLUSION: Physicians should be made aware of the presence of chronic inflammation of the upper airways and inspiratory airflow limitation in a number of Gulf War veterans.

Adolescent↗

PubMed1993

Respiratory muscle acidosis stimulates endogenous opioids during inspiratory loading.

Activation of endogenous opioid pathways during intense inspiratory flow-resistive loading (IRL) results in greater inhibition of EMG activity in the external oblique (EMGeo) relative to the diaphragm (EMGdi). Dichloroacetate (DCA) abolishes opioid-mediated inhibitory influences upon these muscles, suggesting a causal relationship between respiratory muscle lactic acidosis and activation of endogenous opioid pathways, during IRL. We tested the hypothesis that a more intense acidosis of the external oblique relative to the diaphragm may be the signal that determines the differential inhibitory opioid-mediated effect upon the respiratory muscles during IRL. Unanesthetized goats were exposed to IRL (50 cm H2O/1/s) for 120 min, before and after intravenous pretreatment with DCA (50 mg/kg) or saline. We measured peak phasic EMGdi and EMGeo, and respective muscle interstitial pH (pHdi, pHeo) using flexible pH probes. After 120 min IRL with saline, pHdi, and pHeo declined by -0.12 +/- 0.03 (mean +/- SEM) and -0.20 +/- 0.04 units, respectively (p < 0.05, pHdi versus pHeo). Naloxone (NLX), 0.3 mg/kg given intravenously at this time, increased EMGdi by 26.5 +/- 6.1%, but EMGeo by 81.9 +/- 13.3% (p < 0.05, EMGdi versus EMGeo). DCA blunted both the change in pHdi and pHeo during IRL (to -0.01 +/- 0.01 and -0.08 +/- 0.03 units, respectively) (p < 0.05, DCA versus saline) and the increase in EMGdi and EMGeo with NLX (to -1.0 +/- 2.6% and 5.7 +/- 5.8%, respectively) (p < 0.05, DCA versus saline).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗

PubMed1993

Strength and endurance characteristics of the normal human genioglossus.

Since activity of the genioglossus muscle plays a primary role in maintaining upper airway patency during sleep, its strength and endurance characteristics are of potential importance. The purpose of this study was 2-fold. First, to define the strength and endurance characteristics of the normal human genioglossus. Second, we hypothesized that because the genioglossus has a high proportion of fast glycolytic muscle fibers, brief periods of increased activity would make it more susceptible to fatigue. In five normal male subjects strength of the tongue was evaluated by measuring maximal anterior force using a transducer (Fmax). In each subject tongue endurance was then tested at 100%, 80%, and 50% Fmax. To test the effect of a short-term increase in genioglossal activity on its endurance, an inspiratory flow-resistive load with mild hypercapnia was presented to the upper airway for 10 min, after which genioglossal endurance at 80% Fmax was repeated. On a separate day the effect of inspiratory loading plus hypercapnia on thoracic inspiratory muscle endurance was also tested. Our results showed that mean Fmax was 1,267 +/- 125 (SEM) g. Endurance time (Tlim) decreased progressively during 50%, 80% and 100% Fmax trials. Short-term activation of the genioglossus caused a reduction in Tlim at 80% Fmax to 51.4 +/- 4.8% of its value before loading (p < 0.05). Tlim for the inspiratory muscles, however, was unaffected. We conclude that, like other skeletal muscles, genioglossal endurance is reduced as the force of contraction increases. In addition, genioglossal endurance is significantly reduced by short-term activation insufficient to fatigue the thoracic inspiratory muscles.

Adult↗

PubMed1992

Dichloroacetate blocks endogenous opioid effects during inspiratory flow-resistive loading.

Inspiratory flow-resistive loading (IRL) in unanesthetized goats causes central elaboration of endogenous opioids, which is accompanied by inhibition of several respiratory muscles. The peripheral stimulus responsible for mediating this phenomenon is unknown. We hypothesized that lactic acid mediates release of endogenous opioids during IRL. Unanesthetized goats were pretreated with either saline or dichloroacetate (DCA; 50 mg/kg iv), a blocker of lactic acid formation, and subjected to IRL (50 cmH2O.l-1.s) for 120 min followed by naloxone (NLX; 0.3 mg/kg iv). Electromyographic activities of the diaphragm (EMGdi), external oblique (EMGeo), and external intercostal (EMGei) were measured and expressed as a percentage of activity at an end-tidal CO2 of 8%. DCA blocked the NLX-induced augmentation of all EMGs observed after 120 min of IRL as follows (means +/- SE): delta EMGdi from 20.8 +/- 5.6% (saline) to 1.2 +/- 2.7% (DCA), delta EMGeo from 116.6 +/- 30.9% (saline) to 5.3 +/- 11.4% (DCA), and delta EMGei from 43.8 +/- 11.3% (saline) to -4.5 +/- 5.6% (DCA) (all P less than 0.05, DCA vs. saline). We conclude that lactic acid produced by the contracting respiratory muscles is the stimulus responsible for endogenous opioid pathway activation during IRL.

Afferent Pathways↗

PubMed1990

Effect of naloxone on spectral shifts of the diaphragm EMG during inspiratory loading.

Shifts in the power spectrum of the diaphragm EMG to lower frequencies may occur in the presence of fatiguing inspiratory flow-resistive loads (IRL). However, such a shift of the centroid frequency (fc) could follow a reduction in central output through a differential reduction in end-inspiratory high-frequency power (HFP). In unanesthetized goats, we tested the hypothesis that activation of the endogenous opioid system by IRL would differentially reduce central respiratory output, causing a reduction in fc. IRL was imposed for 180 min after which naloxone (0.1 mg/kg, NLX) was given. fc was computed from the power spectral density estimated by the Welch method. IRL reduced fc from 148.0 +/- 9.8 (SE) Hz at base line to 141.1 +/- 8.9 Hz or to 95.5 +/- 1.3% of base line by 180 min (both P less than 0.05). NLX increased fc to 148.9 +/- 9.9 Hz or to 100.6 +/- 1.1% of base line (both P less than 0.05). The decline in fc during IRL was found to be the result of a reduction in HFP, predominantly toward the end of inspiration. The reversibility of this fc shift with NLX suggests a central mechanism consequent to elaboration of endogenous opioids and not a peripheral (muscular) event consequent to muscle fatigue.

Animals↗

PubMed1990

Endogenous opioid effects on abdominal muscle activity during inspiratory loading.

In a previous study in unanesthetized goats, we demonstrated that continuous naloxone (NLX) administration during inspiratory flow-resistive loading (IRL) significantly increased tidal volume (VT) but not diaphragm electromyogram (EMGdi). End-expiratory gastric pressure did increase with NLX, implying that increased abdominal muscle activity may have accounted for the NLX effect. In the current study we directly tested the hypothesis that endogenous opioid elaboration depresses the abdominal muscle response to a continuous inspiratory flow-resistive load. In seven unanesthetized goats, VT, arterial blood gases, EMGdi, and EMG activity of external oblique (EMGeo), transversus abdominis (EMGta), and external intercostal (EMGei) muscles were monitored. IRL (50 cmH2O.l-1.s) was continued for 3 h, after which NLX (0.1 mg/kg) or saline was given. Our results showed that VT decreased from 323 +/- 32 (SE) ml at baseline to 260 +/- 16 ml 5 min after the load was imposed (P less than 0.05) and further decreased to 229 +/- 18 and 217 +/- 15 ml by 120 and 180 min, respectively (180 vs. 5 min, P less than 0.05). EMGdi increased from 62 +/- 5 to 83 +/- 4% max at 5 min (P less than 0.05) but was unchanged thereafter. In contrast, for this same time period EMGeo increased from 35 +/- 5 to 58 +/- 11% max but decreased from 67 +/- 11% max at 120 min to 37 +/- 5% max at 180 min (P less than 0.05). NLX administration resulted in significant increases in EMGeo (91% above 180-min value). In contrast, EMGdi increased minimally after NLX (15% above 180-min value).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1989

Naloxone alters the early response to an inspiratory flow-resistive load.

In a previous study in unanesthetized goats, we demonstrated that cerebrospinal fluid levels of beta-endorphin were significantly elevated after 2.5 h of inspiratory flow-resistive loading. Naloxone (NLX) (0.1 mg/kg) administration partially and transiently reversed the tidal volume depression seen during loading. In the current study, we tested the hypothesis that endogenous opioid elaboration results in depression of respiratory output to the diaphragm. In six studies of five unanesthetized goats, tidal volume (VT), transdiaphragmatic pressure (Pdi), diaphragmatic electromyogram (EMGdi), and arterial blood gases were monitored. A continuous NLX (0.1 mg/kg) or saline (SAL) infusion was begun 5 min before an inspiratory flow-resistive load of 120 cmH2O.l-1.s was imposed. Our data show that the depression of VT induced by the load was prevented by NLX as early as 15 min and persisted for 2 h. At 2 h, Pdi was still 294 +/- 45% of the base-line value compared with 217 +/- 35% during SAL. There was no difference in EMGdi between the groups at any time. However, the augmentation of Pdi was associated with a greater increase in end-expiratory gastric pressure in the NLX group. We conclude that the reduction in VT and Pdi associated with endogenous opioid elaboration is not mediated by a decrease in neural output to the diaphragm, but it appears to be the result of a decrease in respiratory output to the abdominal muscles.

Airway Resistance↗

PubMed1988

Hypoxia does not increase CSF or plasma beta-endorphin activity.

The ability of moderate (30-50 Torr arterial PO2) and severe (less than 30 Torr arterial PO2) hypoxia to generate endogenous opioids that modulate ventilation was studied in unanesthetized goats. Ventilation and its components, arterial blood gas tensions and pH, and plasma and cerebrospinal fluid (CSF) beta-endorphin activity were measured before and after 4 h of sustained moderate or severe hypoxia. Ventilation, as expected, increased with hypoxia. There were no significant changes in either plasma or CSF beta-endorphin activity after sustained hypoxia. To rule out elaboration of endogenous opioids other than beta-endorphin after hypoxia, naloxone or saline was administered to five of the seven goats exposed to 4 h of severe hypoxia, and their ventilatory responses were compared for 30 additional min of hypoxic breathing. No significant differences in ventilation occurred in the two treatment groups during this time period. We conclude that, unlike increases in airway resistance, moderate and severe hypoxia do not cause the elaboration of endogenous opioids that modify respiratory output in unanesthetized adult goats. The apparent ability of hypoxia to cause elaboration of endogenous opioids in the neonate may represent a maturational phenomenon.

Analysis of Variance↗

PubMed1988

Modulation by endogenous opioids of pulmonary vasoconstrictor response to acute lung injury.

The effects of endogenously generated opioids on distribution of pulmonary perfusion (as assessed by radiolabeled microspheres) and overall gas exchange in acute acid-induced lung injury were studied. In 14 anesthesized dogs, sufficient acid was given to one lung to double shunt fraction (Qs/Qt) from 14.2 +/- 0.8 to 32.4 +/- 2.6% (SE). This resulted in a significant decrease in Po2 from 495 +/- 9 to 136 +/- 21 Torr, cardiac output from 2.47 +/- 0.27 to 1.46 +/- 0.15 1/min, and blood pressure from 139 +/- 3 to 116 +/- 5 mmHg and a significant rise in pulmonary arterial pressure from 9.6 +/- 0.8 to 14.9 +/- 0.8 mmHg. After acid instillation, microsphere distribution to the injured lung segments decreased to 50% of the base-line value. At the same time, microsphere distribution in the normal segments increased to 160% of base line. In 7 of the 14 dogs the effects of naloxone (1 mg/kg) given after lung injury were compared with the other 7 animals that were given saline. Naloxone administration caused a significant redistribution of regional pulmonary perfusion such that microsphere distribution in the injured lung segments increased by a factor of 2 at 35 min compared with the animals given saline. Consistent with this finding, Qs/Qt in the naloxone group increased to 34.7 +/- 5.0% at 35 min, whereas that of the saline group decreased to 28.2 +/- 2.5%. The difference between the two groups was significant at 35 min. These changes occurred without further alterations in cardiac output, pulmonary arterial pressure, or systemic blood pressure in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Chemical respiratory drive as a determinant of postoperative ventilation in the non-Pickwickian obese patient.

Hypercapnia in patients with pulmonary disease is believed to result from an interaction between mechanical lung impairment and intrinsic chemical respiratory drive. We tested this hypothesis in this study by examining the ventilatory (delta VE/delta PCO2) and occlusion pressure (delta P100/delta PCO2) responses to CO2 in 12 obese patients with no history of alveolar hypoventilation and correlating these with their ventilatory responses to abdominal surgery. Preoperatively the mean vital capacity (VC) was 78% +/- 6% standard error of the mean predicted, the delta VE/delta PCO2 was 1.56 +/- 0.26 L/min/torr, delta P100/delta PCO2 was 0.25 +/- 0.08 cm H2O/torr, the mean PaCO2 37.9 +/- 1.1 mm Hg, and mean PO2 77.6 +/- 3.7 mm Hg. Postoperatively the VC decreased to 56% +/- 6% of the preoperative value. PCO2 values at 24 hours increased in six patients, were unchanged in three, and decreased in three patients. However, over the entire spectrum of PCO2 change, both indexes of CO2 chemosensitivity correlated strongly with the postoperative change in PCO2 (r = -0.86 for delta VE/delta PCO2 and r = -0.66 for delta P100/delta PCO2). All six patients with a delta VE/delta PCO2 of 1.5 L/min/torr or less manifested postoperative increases in PCO2, while those with greater values did not (p = 0.005). In contrast, neither preoperative nor postoperative VC showed high correlations with postoperative PCO2 (r = -0.56 and -0.43, respectively). Thus ventilatory responses to CO2 predicted postoperative PCO2 at both ends of the spectrum; low responders hypoventilated while high responders hyperventilated. We conclude that in obese subjects, CO2 chemosensitivity plays a permissive role in determining the net ventilatory responses to situations that either mechanically load the respiratory system or modulate ventilation such as postoperative pain or analgesia.

Adult↗

PubMed1986

The role of endogenous opioids in the ventilatory response to acute flow-resistive loads.

The ability of acute, short-term, inspiratory flow-resistive loading to generate endogenous opioids was studied in 6 unanesthetized goats. Endogenous opioid generation was assessed by measurement of immunoreactive beta-endorphin levels in the cisternal cerebrospinal fluid (CSF) after high (80 cm H2O/L/s) and moderate (50 cm H2O/L/s) resistive loading. The results show that CSF levels of beta-endorphin were significantly increased by both the high and moderate resistive loads (40 +/- 4 SEM pg/ml and 33.7 +/- 3.4 pg/ml, respectively) when compared with the same animals during unloaded control conditions (19.5 +/- 3.8 pg/ml). Both levels of loading also caused a significant progressive decline in tidal volume (to 82 +/- 8 and 89 +/- 8% of baseline tidal volume with the high and moderate loads, respectively). Naloxone administration (0.1 mg/kg) resulted in a transient but significant increase in tidal volume from the sixth through the twentieth minute (to 37 +/- 5 and 34 +/- 5% peak tidal volume increase with high and moderate loads, respectively). In addition, there was a significant correlation between the percent decline in tidal volume and mean inspiratory flow rate after loading and the level of beta-endorphin in the cisternal CSF. We conclude that relatively short-term, high-level, inspiratory flow-resistive loading results in elaboration of endogenous opioids within the central nervous system and that these opioids play a role in the progressive decline in tidal volume and mean inspiratory flow rate exhibited during these conditions.

Animals↗

PubMed1984

Determinants of the ventilatory responses to hypoxia during sleep.

Disagreement exists on the effect of sleep on hypoxic ventilatory responses. We hypothesized that these differences were due to variabilities in methodology of inducing hypoxia, specifically, as they pertained to the PCO2 level during the studies. We therefore measured ventilatory responses to hypoxia with (eucapnic) and without (hypocapnic) added CO2 during wakefulness and sleep in 7 goats. Eucapnic responses to hypoxia were significantly decreased during both slow wave (SWS) and REM sleep. This decrease was not apparent when hypocapnia was allowed to occur. In 4 goats also provided with electromagnetic flow probes for brain blood flow (BBF) measurements, hypocapnia significantly attenuated the increase in BBF induced by hypoxia during both the awake and SWS stages. Concomitantly measured cerebral venous blood also showed lower oxygen tension during hypocapnia. We postulate that under hypocapnic conditions, the depressant effects of brain hypoxia may contribute to the obscuring of differences in hypoxic responses during wakefulness and sleep.

Animals↗