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Biomedical subjects

L J Edwards

Publications and source records attributed to L J Edwards.

54 records · Page 3Linked to original sources
PubMed1996

Relief of the 'air hunger' of breathholding. A role for pulmonary stretch receptors.

Fowler (Fowler, W.S., 1954, J. Appl. Physiol. 6:539-545) showed that rebreathing, despite worsening PCO2 and O2 saturation, relieved the distress of breathholding; he suggested a role for vagal input in the relief. We studied effects on respiratory sensation of breathholding and rebreathing in normals, patients with bilateral lung transplants (LT), who have a decrease in number of pulmonary stretch receptors (PSR), and heart transplant recipients (HT). Subjects held their breath until distress became intolerable, rebreathed various combinations of CO2 and O2, then performed another maximal breathhold. Respiratory distress was rated continuously (visual analog scale) by each subject. Both LT and HT had earlier onset of and more rapidly developing distress during breathholding, resulting in shorter breathhold times, than normals. Relief with rebreathing was neither as rapid nor as great in LT as in HT and normals. Our findings suggest that mechanisms that produce respiratory distress in HT and LT are similar, but differ from normals. However, reduction in distress on rebreathing is more rapid and greater in HT and normals than in LT. This is compatible with the loss during rebreathing of the inhibitory effect of PSR input on neural mechanisms that lead to respiratory distress.

Adult↗
PubMed1996

Acute safety and effects on mucociliary clearance of aerosolized uridine 5'-triphosphate +/- amiloride in normal human adults.

Impaired mucociliary clearance contributes to the pathophysiology of several airways diseases including cystic fibrosis, asthma, and chronic bronchitis. Extracellular triphosphate nucleotides (adenosine 5'-triphosphate [ATP], uridine 5'-triphosphate [UTP]) activate several components of the mucociliary escalator, suggesting they may have potential as therapeutic agents for airways diseases. We conducted initial (Phase I) studies of acute safety and efficacy of aerosolized UTP alone and in combination with aerosolized amiloride, the sodium channel blocker, in normal human volunteers. Safety was assessed by measurement of pulmonary function. Neither UTP alone nor in combination with amiloride caused any clinically significant adverse effects on airway mechanics, (subdivisions of) lung volumes, or gas exchange. Acute efficacy of UTP and amiloride alone and in combination, was assessed by measuring changes in the clearance of inhaled radiolabeled particles. A 2.5-fold increase in mucociliary clearance was seen in response to UTP alone and in combination with amiloride. We conclude that aerosolized UTP +/- amiloride clearly enhances mucociliary clearance without acute adverse effects in normal adults, and may have therapeutic potential to enhance airways clearance in diseases characterized by retained airways secretions.

Adult↗
PubMed1995

A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis is a monogenic disease that deranges multiple systems of ion transport in the airways, culminating in chronic infection and destruction of the lung. The introduction of a normal copy of the cystic fibrosis transmembrane conductance regulator (CFTR) gene into the airway epithelium through gene transfer is an attractive approach to correcting the underlying defects in patients with cystic fibrosis. We tested the feasibility of gene therapy using adenoviral vectors in the nasal epithelium of such patients. METHODS: An adenoviral vector containing the normal CFTR complementary DNA in four logarithmically increasing doses (estimated multiplicity of infection, 1, 10, 100, and 1000), or vehicle alone, was administered in a randomized, blinded fashion to the nasal epithelium of 12 patients with cystic fibrosis. Gene transfer was quantitated by molecular techniques that detected the expression of CFTR messenger RNA and by functional measurements of transepithelial potential differences (PDs) to assess abnormalities of ion transport specific to cystic fibrosis. The safety of this treatment was monitored by nasal lavage and biopsy to assess inflammation and vector replication. RESULTS: The adenoviral vector was detected in nasal-lavage fluid by culture, the polymerase chain reaction (PCR), or both in a dose-dependent fashion for up to eight days after vector administration. There was molecular evidence of gene transfer by reverse-transcriptase PCR assays or in situ hybridization in five of six patients treated at the two highest doses. However, the percentage of epithelial cells transfected by the vector was very low (< 1 percent), and measurement of PD across the epithelium revealed no significant restoration of chloride transport or normalization of sodium transport. At the lower doses of vector, there were no toxic effects. However, at the highest dose there was mucosal inflammation in two of three patients. CONCLUSIONS: In patients with cystic fibrosis, adenoviral-vector-mediated transfer of the CFTR gene did not correct functional defects in nasal epithelium, and local inflammatory responses limited the dose of adenovirus that could be administered to overcome the inefficiency of gene transfer.

Adenoviruses, Human↗
PubMed1995

Relief of distress of breathholding: separate effects of expiration and inspiration.

It is well known that rebreathing relieves the respiratory distress of maximal breathholding despite worsening blood gases, and it has been suggested that vagal input has a role in ameliorating this sensation via activation of pulmonary stretch receptors (PSR). However, it is believed by divers that expiration can lead to partial relief of distress of breathholding at total lung capacity (TLC) allowing a prolongation of breathholding. We studied the independent effects of an expiration and an inspiration on relief of respiratory distress of breathholding. Subjects held their breath at TLC until distress became intolerable, then exhaled to FRC and performed a second breathhold. When distress again became intolerable, subjects inspired to TLC a gas that resembled their exhaled gas and performed a third breathhold. Subjects noted partial relief with both an expiration and an inspiration. However, relief of distress was greater and the subsequent breathhold longer after an inspiration than after an expiration. We suggest that relief of distress after an inspiration is compatible with the inhibitory effect of PSR input; the mechanism of relief that occurs after an expiration is as yet uncertain.

Functional Residual Capacity↗
PubMed1995

Racial differences in the patterns of preterm delivery in central North Carolina, USA.

In order to assess racial differences in rates of idiopathic preterm labour, preterm premature rupture of membranes, and medically indicated preterm delivery, the authors analysed data on 388 preterm (< 37 completed weeks of gestation) births (7.9% of all births) occurring between 1 September 1988 and 31 August 1989, in three central North Carolina counties. The crude relative risk (RR) of preterm birth among black women compared with white women was 2.6 [95% confidence interval (CI) 2.1, 3.1]. With adjustment for age, gravidity, marital status, education, and county of residence, the estimated relative risk for black women compared with white women was 2.1 (95% CI 1.1, 4.1) for medically indicated preterm delivery, 1.6 (95% CI 1.1, 2.3) for preterm birth as a result of preterm labour, and 1.9 (95% CI 1.2, 3.1) for preterm premature rupture of membranes. Compared with white women, black women were at the highest risk of a preterm birth before 34 weeks of gestation (RR = 2.9; 95% CI 1.8, 4.7). The risk of medically indicated preterm delivery at 36 weeks was considerably higher for black women than for white women (RR = 3.4; 95% CI 1.1, 10.2). For a better understanding and ultimately a reduction of the risk for preterm delivery among black women, investigation of specific aetiological pathways and gestational age groups may be required.

Adolescent↗
PubMed1994

The Fowler breathholding study revisited: continuous rating of respiratory sensation.

The respiratory distress of breathholding has been shown to be relieved by breathing, even without correction of worsening blood gases (Fowler, 1954). We repeated the study by having untrained normal subjects perform maximal breathholds which were followed by the rebreathing of a gas mixture containing 7.5% CO2 and 8.2% O2, and then by second breathholds. In addition, we had the subjects continuously rate their respiratory distress using a visual analog scale (VAS). The ratings were easy to perform and were highly reproducible on repeated trials in a given subject. Subjects experienced increasing distress during the breathhold, rapid and substantial relief upon rebreathing, and then were capable of performing second breathholds, all consistent with Fowler's results. The findings are consistent with animal studies in which a neural mechanism associated with stimulation of pulmonary stretch receptors inhibits the firing of midbrain neurons which may be involved in transmission to the cortex of sensory information about breathing.

Adult↗
PubMed1993

Glucose transport and metabolism in rabbit oviduct epithelial cells.

The respiration of intact slices and of isolated epithelial cells from rabbit oviducts was compared. The oxygen consumption of the slices was approximately double that of the cells, but glucose was found to be a preferred substrate in each case. Isolated cells exhibited a Crabtree effect in that glucose concentrations greater than 5.55 mmol l-1 inhibited the respiratory rate. The oviduct epithelial cells grown in primary culture on collagen-impregnated filters formed a polarized monolayer, enabling the transepithelial movement of glucose to be studied under defined conditions. The cells, grown in this manner exhibited an asymmetry characteristic of an epithelium, transporting glucose preferentially in a basal to apical as opposed to apical to basal direction, and corresponding to net glucose transport into the oviduct lumen in vivo. Eighty-one per cent of glucose metabolized under these conditions could be accounted for by the formation of lactate, which appeared predominantly in the basal medium. Glucose was transported across the epithelial cells by facilitated diffusion in association with a smaller, passive component. The rate of glucose transport fell and the transepithelial resistance rose in cells removed and cultured 3 days after mating. The data indicate that rabbit oviduct epithelial cells may be grown as a polarized monolayer in primary culture and that endocrine changes induced in vivo persist under these conditions.

Animals↗
PubMed1992

Nontuberculous mycobacteria in adult patients with cystic fibrosis.

Because patients with cystic fibrosis (CF) may be predisposed to airway infections with unusual microorganisms, we screened the sputum of adult CF patients for mycobacterial organisms. Acid-fast bacilli (AFB) smears and mycobacterial culture were performed on 297 sputum specimens from 87 patients. Cultures for mycobacteria were frequently overgrown with other bacteria; 22.6 percent of cultures were contaminated. Despite this limitation of mycobacterial culture, 17 patients had at least one positive culture for a Mycobacterium other than tuberculosis (MOTT). Eleven patients were positive for Mycobacterium avium-intracellulare (MAI), two for MAI and M chelonei, three for M chelonei, and one for M fortuitum. None was positive for M tuberculosis. Patients with CF with MOTT were similar to patients with CF without MOTT; only a slightly different (older) age distribution was recognized. The clinical significance of MOTT was difficult to determine in any individual patient, but patients with positive AFB smears appeared more likely to suffer pathogenic effects. We conclude that MOTT is frequently recovered from adult CF patients in the southeastern United States. A specific risk factor for colonization and/or pathogenic infection in this patient group was not evident. The general prevalence and clinical pathogenesis in CF patients in the United States remains to be determined.

Adolescent↗
PubMed1990

A pilot study of aerosolized amiloride for the treatment of lung disease in cystic fibrosis.

Excessive active absorption of sodium is a unique abnormality of the airway epithelium in patients with cystic fibrosis. This defect is associated with thickened mucus and poor clearance of airway secretions and may contribute to the pulmonary disease in these patients. To study whether the inhibition of excessive absorption of sodium might affect the course of lung disease in cystic fibrosis, we performed a double-blind, crossover trial comparing aerosolized amiloride (5 mmol per liter; 3.5 ml four times daily), a sodium-channel blocker, with vehicle alone. Fourteen of the 18 adult patients initially enrolled in the study completed the one-year trial (25 weeks for each treatment). The mean (+/- SEM) loss of forced vital capacity (FVC) was reduced from 3.39 +/- 1.13 ml per day during treatment with vehicle alone to 1.44 +/- 0.67 ml per day during treatment with amiloride (P less than 0.04). A measured index of sputum viscosity and elasticity was abnormal during treatment with vehicle alone and improved during treatment with amiloride. Calculated indexes of mucociliary and cough clearance also improved during amiloride treatment. No systemic, respiratory, or subjective toxic effects of amiloride were noted. We conclude from this preliminary study that aerosolized amiloride can be safely administered to adults with cystic fibrosis. The slowing of the loss of FVC and the improvement in sputum viscosity and elasticity suggest a beneficial clinical effect. Aerosolized amiloride deserves further evaluation in the treatment of lung disease in patients with cystic fibrosis.

Absorption↗
PubMed1983

In vitro activity of Bay 09867, a new quinoline derivative, compared with those of other antimicrobial agents.

The in vitro activity of Bay 09867, a new quinoline derivative, was compared with those of norfloxacin, nalidixic acid, ceftazidime, cefaclor, cefuroxime, gentamicin, and other antimicrobial agents, when appropriate, against 410 recent clinical isolates. The minimal inhibitory concentrations of Bay 09867 for 90% of Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, streptococci, Staphylococcus aureus, and Bacteroides fragilis strains were between 0.008 and 2 micrograms/ml. Bay 09867 was considerably more active against the gram-negative bacteria tested than were other agents tested. Gentamicin-resistant Enterobacteriaceae, P. aeruginosa, and methicillin-resistant S. aureus were highly susceptible to Bay 09867. Strains less susceptible to nalidixic acid and norfloxacin tended to be less susceptible to Bay 09867. The protein binding of Bay 09867 was about 20%.

Anti-Bacterial Agents↗
PubMed1967

Calcareous septa formed in snail shells by larvae of snail-killing flies.

Larvae of 13 species of Pherbellia and Colobaea that feed in exposed aquatic snails uitilize a product of the Malpighian tubules before they pupate to form a plate-like structure within the shell or to reinforce the anterior end of the puparium. The substance is partly calcium carbonate, and carbonic anhydrase may be involved in its production.

Animals↗
PubMedDate not supplied

Pathologic apnea and brief respiratory pauses in preterm infants: relation to sleep state.

The development of pathologic apnea, respiratory pauses, and periodic respiration was examined in 71 high-risk preterm infants, observed weekly. Respiration was recorded every 10 seconds; apnea length and periodic respiration were scored from a tape. All subjects had respiratory pauses, and 36 had pathologic apnea. The mean length of respiratory pauses was longer in quiet sleep, and the frequency of respiratory pauses was greater in active sleep. The mean length of respiratory pauses and probability of pathologic apnea in both sleep states and frequency of pauses in quiet sleep decreased with age. Sex, theophylline treatment, race, and length of mechanical ventilation affected the developmental trajectories of some apnea variables. Apnea in preterm infants cannot be considered a unitary phenomenon.

Age Factors↗