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Biomedical subjects

J G Martin

Publications and source records attributed to J G Martin.

At least 145 records · Page 8Linked to original sources

Late response of the upper airway of the rat to inhaled antigen.

We studied the magnitude and time course of changes in upper airway resistance (Ruaw) of actively sensitized Brown-Norway rats after aerosol challenge with ovalbumin (OA). Two weeks after sensitization, eight rats were challenged by inhalation of aerosolized OA through the nose. The airway responses of these rats 5-10 h after OA challenge were compared with those of seven animals challenged with saline. Seven of eight test rats had increased Ruaw, and six displayed discrete late responses (LR). Ruaw during expiration was highly alinear so analysis was confined to Ruaw during inspiration (Ruaw,I). The Ruaw,I averaged over 5 h was 1.262 +/- 0.09 (SE) cmH2O.ml-1.s, 2.6 times the value for saline-challenged animals (0.476 +/- 0.143 cmH2O.ml-1.s), and it reached a peak value of 3.454 +/- 0.45 cmH2O.ml-1.s. The time to the peak of the LR was 446 +/- 37.3 min. The duration of the LR in the upper airway was 146 +/- 34.9 min. At the time corresponding to the peak value of Ruaw,I, the lung elastance in the test rats was double the value preceding the peak. Lung elastance was unchanged in the control group. We conclude that inhalation of antigen through the upper airway of the sensitized rat results in a substantial increase in upper airway resistance and a distinct LR. The predominant site of the change in respiratory system resistance is in the upper airway.

Administration, Inhalation↗

Role of leukotriene D4 in the early and late pulmonary responses of rats to allergen challenge.

To examine the role of leukotriene D4 (LTD4) in early and late pulmonary responses to antigen, we evaluated the effects of two LTD4, antagonists, MK-571 and FPL-57231, on the changes in pulmonary resistance (RL) in the 8-h period following antigen challenge of allergic rats. A total of 69 rats, aged 6 to 8 wk, were sensitized to subcutaneous ovalbumin (OA, 1 mg) and intraperitoneal Bordetella pertussis vaccine (6 x 10(9) bacilli). At 14 days after sensitization, rats were anesthetized with intraperitoneal urethane (1.1 g/kg) and intubated endotracheally. Aerosols of OA (5% wt/vol in saline for 5 min) were administered to 24 control rats, to 11 rats that were pretreated with aerosolized FPL-57231, and to 8 rats that were pretreated with MK-571; 6 rats also received MK-571 at 2 h after OA. A control group of 13 rats was challenged with aerosols of saline. We defined an early response (ER) as an increase in RL to at least 150% of the postsaline value occurring within 1 h after OA challenge. A late response (LR) was defined as a value of RL exceeding the mean plus 2 SD of all values of RL from 75 min to 8 h after OA challenge and lasting at least 30 min. An ER was observed in 17 of 24 control rats, in 8 of 11 FPL-57231-pretreated rats, and in 3 of 8 MK-571-pretreated rats (not significant). The magnitude and duration of the ER were significantly reduced by MK-571, whereas only the duration was affected by FPL-57231.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Cardiac arrhythmias during exercise in severe chronic obstructive pulmonary disease.

We studied the effect of maximal exercise on the prevalence of arrhythmias in 122 subjects with severe COPD. At rest, ten subjects had supraventricular arrhythmias while 13 had unifocal VPB greater than or equal to 6/min or ventricular bigeminy. At peak exercise, six subjects had supraventricular arrhythmias while 24 had VAs. Univariate and multivariate analysis with logistic regression did not show relationships between exercise-related cardiac arrhythmias and the severity of pulmonary disease, oxyhemoglobin desaturation or ECG evidence of chronic lung disease. Exercise-related arrhythmias were significantly associated with the presence of arrhythmias at rest and 87 percent of subjects who had no arrhythmias at rest did not have any during exercise. In patients with COPD, the development of potentially serious arrhythmias during exercise is uncommon without clinically apparent CAD or arrhythmias at rest. However, routine cardiac monitoring during exercise testing should not be abandoned in this population since VAs can occur despite their absence at rest.

Aged↗

Sonographic imaging of the fetal azygous vein. Normal and pathologic appearance.

Sonologists should be familiar with the frequency of resolution and the ultrasonic appearance of the normal fetal azygous vein. In this study, 66 consecutive uncomplicated pregnancies were scanned to determine the frequency of imaging the fetal thoracic azygous vein. Between 21.7 and 30 gestational weeks, the azygous vein could be imaged in 50% of the cases and measured 1-2 mm in caliber. In the last 10 weeks of pregnancy, the azygous vein could be imaged in 98% of the cases and measured 2-4 mm. A case of fetal azygous continuation of the inferior vena cava is shown where the vein was abnormally dilated to a caliber of 8 mm.

Abnormalities, Multiple↗

Transvaginal sonographic detection of the pseudogestational sac associated with ectopic pregnancy.

Fifty-seven of 261 patients (21.8%) referred with a presumptive diagnosis of an ectopic gestation had an extrauterine pregnancy. Five of the 57 ectopic pregnancies (8.8%) had a pseudogestational sac on transvaginal sonography. In four of these five cases, a single beta-hCG level had been obtained and did not help in differentiating an ectopic gestation from an early intrauterine pregnancy. A thorough assessment of the adnexa and cul-de-sac should be performed if a patient suspected of having an ectopic pregnancy has an apparent intrauterine gestational sac without a normal yolk sac or without detectable fetal cardiac activity.

Extraembryonic Membranes↗

Regional variability in the response of collateral resistance to histamine in the dog: effects of cyclooxygenase inhibition.

The aim of the study was to examine the role of cyclooxygenase metabolites in determining the variability in histamine responsiveness of the collateral channels of different lung segments of the dog. Using the wedged bronchoscope technique we measured the change in collateral resistance (Rcoll) to aerosolized histamine in two different lung segments of 5 anaesthetized, paralyzed, intubated, mongrel dogs. The same lung segments were examined twice under baseline conditions, and twice after indomethacin (INDO) pretreatment. Rcoll measurements were obtained under control conditions, after saline aerosol, and then after increasing concentrations of histamine (range 0.1 microgram/ml-10.0 mg/ml) were ultrasonically nebulized into the wedged segment. The concentration of histamine that elicited a 50% increase in Rcoll was calculated by log linear interpolation. In addition we performed bronchoalveolar lavage (BAL) in the wedged segment at the completion of the concentration-response curves, and assayed the BAL fluid for TXB2, PGE2, and 6-oxo-PGF1 alpha. The geometric mean ratio of histamine responsiveness between lung segments of each animal was 42.5-fold under control conditions and fell to 9.1-fold after INDO (P less than 0.05). While the concentration of TXB2 fell in the BAL after INDO, concentrations of PGE2 and 6-oxo-PGF1 alpha did not. Moreover, there was no correlation between levels of prostanoids and either responsiveness or variability in responsiveness of the collateral channels. Hence while cyclooxygenase blockade altered the regional variability in histamine responsiveness in the collateral channels, this change was not reflected in the levels of prostanoids in the BAL fluid.

Animals↗

Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats.

We examined the effects of elastase-induced emphysema on lung volumes, pulmonary mechanics, and airway responses to inhaled methacholine (MCh) of nine male Brown Norway rats. Measurements were made before and weekly for 4 wk after elastase in five rats. In four rats measurements were made before and at 3 wk after elastase; in these same animals the effects of changes in end-expiratory lung volume on the airway responses to MCh were evaluated before and after elastase. Airway responses were determined from peak pulmonary resistance (RL) calculated after 30-s aerosolizations of saline and doubling concentrations of MCh from 1 to 64 mg/ml. Porcine pancreatic elastase (1 IU/g) was administered intratracheally. Before elastase RL rose from 0.20 +/- 0.02 cmH2O.ml-1.s (mean +/- SE; n = 9) to 0.57 +/- 0.06 after MCh (64 mg/ml). A plateau was observed in the concentration-response curve. Static compliance and the maximum increase in RL (delta RL64) were significantly correlated (r = 0.799, P less than 0.01). Three weeks after elastase the maximal airway response to MCh was enhanced and no plateau was observed; delta RL64 was 0.78 +/- 0.07 cmH2O.ml-1.s, significantly higher than control delta RL64 (0.36 +/- 0.7, P less than 0.05). Before elastase, increase of end-expiratory lung volume to functional residual capacity + 1.56 ml (+/- 0.08 ml) significantly reduced RL at 64 mg MCh/ml from 0.62 +/- 0.05 cmH2O.ml-1.s to 0.50 +/- 0.03, P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Transepithelial prostacyclin gradient in isolated canine trachea.

Cyclooxygenase products of arachidonic acid, potential modulators of airway smooth muscle, have recently been described in bronchoalveolar lavage from canine lungs. To evaluate the possibility that airway epithelium represents a barrier to movement of prostacyclin (PGI2), an important bronchodilator synthesized by isolated airway, we measured the concentrations of 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha), the stable degradation product of PGI2, on the mucosal and serosal sides of isolated canine tracheal segments (CTS) mounted in Ussing chambers. 6-oxo-PGF1 alpha was measured by radioimmunoassay after purification by high-performance liquid chromatography. The concentration of 6-oxo-PGF1 alpha was significantly higher on the serosal than the mucosal side of CTS (1,262 +/- 252 vs. 390 +/- 168 pg.min-1.g-1, n = 8, P less than 0.05). A significant correlation was present between 6-oxo-PGF1 alpha measured on both sides of each CTS (r = 0.778, n = 26, P less than 0.01). 6-oxo-PGF1 alpha production from CTS stripped of mucosa was significantly greater than from isolated mucosa. Radiochromatograms obtained after incubation with [3H]arachidonic acid and calcium ionophore A23187 confirmed PGI2 as the predominant cyclooxygenase product of the submucosa, whereas the mucosa produced only small amounts of PGI2 in proportion to other cyclooxygenase products. PGI2 (10(-8) to 10(-6) M) applied to the mucosal surface of closed tracheal segments precontracted with histamine resulted in no significant relaxation, whereas serosal application showed a concentration-dependent effect. Radiolabeled 6-oxo-PGF1 alpha did not cross the isolated epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Effect of nutritional status on exercise performance in patients with chronic obstructive pulmonary disease.

The purpose of our study was to examine the nutritional status of patients with severe chronic obstructive pulmonary disease (COPD) (mean predicted FEV1, 30 +/- 11%) and to explore its relationship to functional capacity. Functional capacity was evaluated by measuring peak oxygen consumption (VO2max) using an incremental cycle ergometry test, a 6-min walk test, self-perceived level of dyspnea, and quality of life. The percentage ideal body weight (%IBW) was less than 90% in 33 of 135 subjects. Triceps skinfold thickness was less than 60% of normal in 19 of 33 of these subjects. Total lymphocyte count was not different between groups, whereas hemoglobin (14.9 versus 15.9 g/dl) and albumin (4.0 versus 4.1 g/dl) were marginally reduced in underweight subjects. Dyspnea and overall quality of life were unaffected by nutritional status. Maximal inspiratory (Pimax) and expiratory mouth pressures (PEmax) were weakly associated with %IBW (R2 = 0.04; p = 01 and R2 = 0.15; p less than 0.01, respectively). The %IBW was a predictor of VO2max (percent predicted) after controlling for FEV1 in regression analysis (partial R2 = 0.08; p less than 0.001). Despite the association of weight status with VO2max, the 6-min walk was not influenced by %IBW. The perceived intensity of exercise as judged by the Borg score was far greater with the bicycle exercise that with the 6-min walk (mean score, 10.6 +/- 1.2 versus 4.6 +/- 1.9). This was supported by the difference in heart rate after these two tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗

Inhalation toxicity of high flash aromatic naphtha.

A petroleum distillate--a high aromatic naphtha--consisting of a 50/50 blended mixture of equivalent products. SHELLSOL A* and SOLVESSO 100**, containing C9 isomers (75 percent) particularly trimethyl benzenes, was examined for systemic toxicity in rats by inhalation exposure. A preliminary 13-week inhalation study with SHELLSOL A had resulted in liver and kidney weight increases in female rats at the high (7400 mg/m3) and medium (3700 mg/m3) exposure levels, and a low grade anaemia in females at all exposure levels (7400, 3700 and 1800 mg/m3). The follow-up 12-month inhalation study in rats described here used atmosphere generated from the SHELLSOL A/SOLVESSO 100 blend of 1800, 900 and 450 mg/m3. Initial reduction in body weight gain occurred in both male and female rats at the higher exposures. Various statistically significant haematological changes were transiently seen in males up to six months, but were not considered biologically significant. High exposure male liver and kidney weights were increased at 6 and 12 months but, in the absence of histopathological changes, were considered to be physiological adaptive responses. No treatment-related histopathological abnormalities were found. It is concluded that chronic exposure to this high aromatic naphtha is without systemic toxicity in rats under the conditions of these studies.

Administration, Intranasal↗

Negative pressure ventilation. Effects on ventilation during sleep in normal subjects.

Negative pressure ventilation (NPV) is used for ventilatory support of patients with respiratory failure due to neuromuscular disorders and thoracic deformities, and to provide ventilatory muscle rest for patients with severe chronic airflow limitation. To determine whether NPV would result in episodes of upper airway obstruction during sleep, we studied five normal subjects on two consecutive nights with the first night serving as a control and NPV being administered on the second night. Ventilators were adjusted so as to reduce the peak phasic diaphragm electromyogram signal by at least 50 percent. All subjects demonstrated an increase in the total number of apneas + hypopneas per hour on NPV control nights. Although differences were not significant, there was a tendency to develop decreased sleep efficiency, sleep fragmentation and altered sleep architecture with NPV. We conclude that nocturnal NPV can induce sleep apneas and impair sleep quality in normal subjects.

Adult↗

A sonographic and karyotypic study of second-trimester fetal choroid plexus cysts.

A prospective study was undertaken of 513 women between 15.6-24.1 weeks' gestation who had a level II ultrasound examination followed immediately by a genetic amniocentesis. The presence or absence of fetal choroid plexus cysts was noted and the results correlated with the fetal karyotype. Thirteen cases of choroid plexus cysts were observed sonographically, a prevalence of 2.5%. The size of the cysts ranged from 3-10 mm, with a median of 6 mm. There were no other sonographically detectable congenital abnormalities in these 13 cases, and the fetal karyotype was normal in all. An association between fetal choroid plexus cysts and autosomal trisomies was not found in this series.

Amniocentesis↗

The site of airway responses to methacholine or antigen inhalation challenge.

We evaluated changes in upper airway and lower pulmonary resistance after methacholine or ovalbumin challenge in inbred rats. Methacholine or antigen were inhaled through the intact upper airway and through a tracheostomy, in two groups of normal sensitized animals. Methacholine challenge resulted in both upper airway and lower pulmonary resistance increase regardless of the inhalation route. Lower airway ovalbumin challenge caused an increase in lower pulmonary resistance with no change in upper airway resistance. By contrast ovalbumin inhalation through the nose provoked a striking increase in upper airway resistance. Atropine pretreatment of lower airways reduced lower pulmonary response to antigen. We conclude that: 1) the increase in upper airway resistance following methacholine challenge occurs through a reflex mechanism; 2) upper airway constriction following antigen challenge through the nose results from a local mechanism; 3) the site of airway constriction depends on local mechanisms and vagal reflexes.

Airway Resistance↗

Structure-activity analysis of a class of orally active hydroxamic acid inhibitors of leukotriene biosynthesis.

The nature of the carbonyl and nitrogen substituents of hydroxamic acids has a major influence on the biological profile of these compounds. Hydroxamates with small groups such as methyl appended to the carbonyl and relatively large nitrogen substituents generally have longer duration in vivo, produce greater plasma concentrations, and often are more potent inhibitors of in vivo leukotriene biosynthesis than hydroxamic acids with the opposite arrangement. The structure-activity relationships that describe in vitro 5-lipoxygenase inhibitory activity and in vivo leukotriene biosynthesis inhibitory potency for a group of these hydroxamic acids were investigated. While most of the compounds examined were potent in vitro inhibitors of 5-lipoxygenase, their in vivo potencies varied widely. This discrepancy was usually attributable to differences in bioavailability. Substitution patterns are described that produce potent, orally active inhibitors of leukotriene biosynthesis.

Acylation↗

Effect of lung volume on interrupter resistance in cats challenged with methacholine.

To examine the effects of changes in lung volume on the magnitude of maximal bronchoconstriction, seven anesthetized, paralyzed, tracheostomized cats were challenged with aerosolized methacholine (MCh) and respiratory system resistance (Rss) was measured at different lung volumes using the interrupter technique. Analysis of the pressure changes following end-inspiratory interruptions allowed us to partition Rss into two quantities with the units of resistance, one (Rinit) corresponding to the resistance of the airways and the other (Rdif) reflecting the viscoelastic properties of the tissues of the respiratory system as well as gas redistribution following interruption of flow. Rinit and Rdif were used to construct concentration-response curves to MCh. Lung volume was increased by the application of 5, 10, and 15 cmH2O of positive end-expiratory pressure. The curve for Rinit reached a plateau in all cats, demonstrating a limit to the degree of MCh-induced bronchoconstriction. The mean value of Rinit (cmH2O.ml-1.s) for the group under control conditions was 0.011 and rose to 0.058 after maximal bronchoconstriction; the volume at which the flow was interrupted was 11.5 +/- 0.5 (SE) ml/kg above functional residual capacity (FRC). It then fell progressively to 0.029 at 21.2 +/- 0.8 ml/kg above FRC, 0.007 at 35.9 +/- 1.3 ml/kg above FRC, and 0.005 at 52.0 +/- 1.8 ml/kg above FRC. Cutting either the sympathetic or parasympathetic branches of the vagi had no significant effect on the lung volume-induced changes in MCh-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗