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J R Clarke

Publications and source records attributed to J R Clarke.

At least 19 recordsLinked to original sources
PubMed1995

Bronchial responsiveness in the neonatal period as a risk factor for wheezing in infancy.

Bronchial responsiveness is closely associated with asthma in schoolchildren. We wished to test the hypothesis that bronchial responsiveness in the neonatal period might be a risk factor for lower-respiratory illnesses (LRI), typically cough and wheezing with viral infection, in infants. A cohort of 73 full-term healthy infants of atopic parents were observed during the first year of life. Respiratory illness was recorded and ascertained retrospectively by questionnaires administered to parents at 6-mo intervals, and infants were classified as having: LRI (one or more episode of wheezing in the first year) or no LRI (no wheezing). At approximately 1 mo of age, lung function was measured under sedation, and bronchial responsiveness (BR) to histamine aerosol was determined and expressed as PC30, the provocative concentration of histamine that induced a 30% decrease in maximum flow at FRC (V'maxFRC) by the squeeze technique. For the whole group, no index of lung function predicted subsequent wheezing. Among boys, however, there was a trend toward a lower V'maxFRC in those who subsequently developed LRI than in the group without LRI (median values 62 versus 98 ml/s; 95% CI: -1 to 68; p = 0.06), while among girls the major difference was in PC30, for which those who subsequently had LRI were significantly more responsive as neonates (PC30 was lower) than the group without LRI (1.4 versus 8.3 g/L; 95% CI: 1.0 to 13.1; p < 0.05). These findings suggest that sex differences in airway structure and responsiveness present soon after birth, and representing differences in fetal lung development, are associated with differences in the risk of subsequent LRI with wheezing.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial Hyperreactivity↗
PubMed1995

Granulated metrial gland cells in the uterine wall and placenta of the pregnant woodmouse, Apodemus sylvaticus.

The differentiation of the decidua and the fetal placenta in the woodmouse, Apodemus sylvaticus, was studied with particular attention to the differentiation and migration of granulated metrial gland cells. Numerous granulated metrial gland cells, characterised by their glycoprotein-containing cytoplasmic granules, were found to differentiate in the decidua basalis and metrial gland of the uterine wall during the first half of pregnancy. Many granulated metrial gland cells appeared to pass into the lumina of blood vessels in the uterine wall and reach the maternal blood spaces of the fetal placenta. In the labyrinthine placenta some granulated metrial gland cells were found associated with degenerate cytotrophoblast lining the maternal blood spaces. This finding supports previous studies of the mouse, Mus musculus, suggesting that the labyrinthine placenta is an important site for the function of the bone marrow-derived granulated metrial gland cell.

Animals↗
PubMed1994

Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease.

BACKGROUND: The purpose of this study was to estimate the sensitivity and specificity of diagnostic tests for gallstones and acute cholecystitis. METHODS: All English-language articles published from 1966 through 1992 about tests used in the diagnosis of biliary tract disease were identified through MEDLINE. From 1614 titles, 666 abstracts were examined and 322 articles were read to identify 61 articles with information about sensitivity and specificity. Application of exclusion criteria based on clinical and methodologic criteria left 30 articles for analysis. Cluster-sampling methods were adapted to obtain combined estimates of sensitivities and specificities. Adjustments were made to estimates that were biased because the gold standard was applied preferentially to patients with positive test results. RESULTS: Ultrasound has the best unadjusted sensitivity (0.97; 95% confidence interval, 0.95 to 0.99) and specificity (0.95; 95% confidence interval, 0.88 to 1.00) for evaluating patients with suspected gallstones. Adjusted values are 0.84 (0.76 to 0.92) and 0.99 (0.97 to 1.00), respectively. Adjusted and unadjusted results for oral cholecystogram were lower. Radionuclide scanning has the best sensitivity (0.97; 95% confidence interval, 0.96 to 0.98) and specificity (0.90; 95% confidence interval, 0.86 to 0.95) for evaluating patients with suspected acute cholecystitis; test performance is unaffected by delayed imaging. Unadjusted sensitivity and specificity of ultrasound in evaluating patients with suspected acute cholecystitis are 0.94 (0.92 to 0.96) and 0.78 (0.61 to 0.96); adjusted values are 0.88 (0.74 to 1.00) and 0.80 (0.62 to 0.98). CONCLUSIONS: Ultrasound is superior to oral cholecystogram for diagnosing cholelithiasis, and radionuclide scanning is the test of choice for acute cholecystitis. However, sensitivities and specificities are somewhat lower than commonly reported. We recommend estimates that are midway between the adjusted and unadjusted values.

Acute Disease↗
PubMed1994

Evaluation of a tidal expiratory flow index in healthy and diseased infants.

Patterns of tidal respiratory flow have been shown to relate well to airway function in adults, and one epidemiological study in infants has demonstrated the value of the ratio of time to reach peak tidal expiratory flow to the total expiratory time (tpef/te) in predicting subsequent wheezing. The aim of this study was to evaluate tpef/te as a measure of lung function, by sequential observations over the first year, on a group of 22 healthy infants and on 32 infants with a history of mild recurrent lower respiratory illness (LRI), and by single observations on 20 infants with asthma and 20 with severe chronic lung disease of prematurity. We compared tpef/te measured in quiet, supine sleep (under sedation) through a face mask and pneumotachograph, with a measure of airway function, maximal flow at functional residual capacity (VmaxFRC), obtained from partial forced expiratory flow volume loops using the "squeeze" technique. In healty infants tpet/te was significantly longer at 1 month than at 6 months (median values, 0.38 (95% CI, 0.36-0.43) and 0.28 (95% CI, 0.26-0.33), respectively). Between 6 and 12 months tpef/te did not alter significantly and it was independent of VmaxFRC. Both tpef and te as well as their ratio varied with frequency of breathing over the first year of life, but not within each individual age band, due to the narrow spread of frequencies at each age. In assessing airway obstruction, tpef/te was less sensitive than VmaxFRC. There was no difference between healthy infants, those with LRI, and infants with asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

HIV-1 proviral DNA copy number in peripheral blood leucocytes and bronchoalveolar lavage cells of AIDS patients.

In this study we have determined by polymerase chain reaction (PCR) the quantity of HIV-1 proviral DNA in cells obtained by bronchoalveolar lavage (BAL) from the lung of HIV-1+ individuals. This has been compared quantitatively with the proviral DNA in peripheral blood leucocytes (PBL) obtained simultaneously from the same patients. The mean HIV DNA copy number per 10(6) cells was 391 for PBL, with a range of 1-9000, and 2971 for BAL cells, with a range of < 1-70,000. The quantity of HIV DNA detected in BAL cells was higher than that detected in the corresponding PBL samples in 44 out of 78 (56%) individuals, whilst more HIV DNA was detected in the PBL compared with BAL cells in 14 out of 78 (18%) patients. In both BAL and PBL higher levels of HIV DNA were detected in the adherent (monocyte/macrophage) enriched cell populations compared with other non-adherent cells (leucocytes). A direct relationship between HIV DNA copy number and ability to recover infectious HIV progeny in vitro by co-cultivation with cord blood leucocytes was found for both PBL and BAL cells. Individuals known to be receiving azidothymidine treatment had a lower mean HIV DNA load in all cell fractions compared with those patients on no antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Characterization and measurement of elastance with application to underwater breathing apparatus.

The elastic loads inherent in underwater breathing apparatus (UBA) can affect diver performance. This work quantitatively examines elastance, its measurement by static tests, and its relationship to UBA. A rigid, fixed-volume container and a vertical water column with straight and parallel sides produce elastic loads that have application to closed-circuit UBA. We derived equations to describe the pressure-volume relationships of these elements from first principles and tested the equations experimentally for system pressure produced by a swept volume in a breathing machine. Our work demonstrates that simplified equations to describe elastance may not be sufficiently accurate for all situations. In addition, static measurements of elastance of a UBA or other element will not be reproducible unless all the volumes within the testing apparatus are accounted for; we provide experimental and mathematical techniques for doing so.

Diving↗
PubMed1993

Comparative study of the isolation of human immunodeficiency virus from the lung and peripheral blood of AIDS patients.

HIV-1 proviral DNA was detected by the polymerase chain reaction (PCR) in leucocytes from the peripheral blood (PBL) and bronchoalveolar lavage (BAL) of 100% and 72%, respectively, of HIV-1 seropositive patients. Infective virus isolated by cocultivation was recovered from the PBL and BAL of 50% and 59% of individuals, respectively. Isolation of HIV-1 was more readily made from the lung of individuals undergoing Pneumocystis carinii pneumonia (PCP) than from patients with non-PCP lung infections. The concomitant infection of lung cells with cytomegalovirus did not affect the isolation rate of HIV-1 from the lung. HIV-1 was isolated from BAL of 23 out of 36 (64%) individuals receiving no antiviral chemotherapy and from 13 out of 24 (54%) patients who were receiving AZT.

AIDS-Related Opportunistic Infections↗
PubMed1993

Comparison of the squeeze technique and transcutaneous oxygen tension for measuring the response to bronchial challenge in normal and wheezy infants.

The aim of this study was to compare the fall in transcutaneous oxygen tension (PtcO2) as an outcome measure during bronchial provocation with histamine, with changes in airway function measured by the squeeze technique in healthy infants and those with wheezing disorders. PtcO2 was measured during histamine challenge in 20 infants, aged 6-16 months, of whom 14 had recurrent cough or wheeze (lower respiratory illness, LRI), and 6 were healthy. All were symptom free at the time of testing. The minimum value of PtcO2 after each nebulization was compared with the minimum baseline value. The response to increasing concentrations of histamine was also assessed by measuring maximal flow at functional residual capacity (VmaxFRC) by the squeeze technique. The inhaled concentration of histamine causing a 30% fall in VmaxFRC was calculated to give the provoking concentration (PC30). Baseline VmaxFRC was lower in symptomatic infants (117 mL/s) than the normal infants (322 mL/s; P < 0.005), but the PC30 was not significantly different (7.7 and 5.7 g/L, respectively). There was no difference in baseline PtcO2 between the two groups. The infants with LRI had significant reductions in PtcO2 at both the final and preceding concentrations of histamine, whereas the normal infants had a significant and smaller reduction in PtcO2 only at the provoking concentration. Reduction in PtcO2 during bronchial challenge was a less sensitive index of bronchial response in healthy infants than in infants with a history of recurrent LRI.

Asthma↗
PubMed1993

The epidemiology of HIV-1 infection of the lung in AIDS patients.

OBJECTIVE: To examine the relationship between HIV-1 infection of cells obtained by bronchoalveolar lavage (BAL) from the lung and the pathogenesis of AIDS. DESIGN: Prospective study of 121 consecutive HIV-1-seropositive patients undergoing investigation for respiratory symptoms or abnormal chest radiograph. METHODS: Polymerase chain reaction (PCR) for the detection of HIV-1-specific proviral DNA. Cocultivation of leukocytes obtained from BAL with donor cord blood leukocytes (CBL) to isolate HIV-1. RESULTS: HIV-1 was detected by PCR in the lung cells of 78 out of 121 (65%) patients. It was detected in 55% of patients who had been seropositive for less than 1 year, but in over 80% of patients who had been seropositive for more than 3 years. HIV-1 was isolated from 61 out of 106 (58%) individuals. The ability to detect or isolate HIV-1 from the lung correlated directly to CD4 cell count in peripheral blood. HIV-1 was detected significantly more frequently in the BAL cells of smokers compared with non-smokers (P = 0.01). CONCLUSIONS: HIV-1 was frequently detected and isolated from the lung of AIDS patients undergoing a respiratory episode. HIV-1 infection of the lung became more frequent with time from serodiagnosis. Patients who smoked were more likely to succumb to HIV-1 infiltration into the lung and HIV-1 infection of the lung was associated with progression to death.

Adult↗
PubMed1993

Pulmonary function hysteresis during compression to, and decompression from 31.3 ATA.

Tracheal gas density breathing heliox at 31.3 atmospheres absolute (O2 at 0.42 ATA) is 6.287 g l-1, or approximately 5.5 times greater than air at 1 ATA. This constitutes a significant respiratory load, previously shown to induce respiratory adaptation. During a saturation dive to 31.3 ATA, five divers were exposed to this load for 16 days. This project aimed at investigating possible hysteresis in pulmonary function during dive compression, adaptation and decompression phases. Pulmonary function tests were performed at the surface in air, and at four pressure stops during compression and decompression, with divers breathing the helium-oxygen gas mixture. Significant hysteresis patterns were observed for pooled maximal voluntary ventilation, forced expired volume at 1 s, peak expiratory flow, and maximum expiratory flows (P < 0.05), with post-adaptation flows consistently exceeding those observed during compression. Two mechanisms may explain these observations. Differences may be attributable to positive effort-dependence in the forced expiratory flow; or it is possible the subjects adapted to the respiratory load by modifying neural input to airway smooth muscle, thereby modifying airway resistance.

Adult↗
PubMed1993

Delivery of salbutamol by metered dose inhaler and valved spacer to wheezy infants: effect on bronchial responsiveness.

The efficacy of a new valved spacer device, the Babyhaler inhaler (Glaxo) for administering metered dose inhaler treatment via a facemask to infants was assessed. In a double blind, single dose study, salbutamol (800 micrograms) or placebo were given on separate days to 12 sedated, sleeping, wheezy infants during a symptom free interval. Lung function was measured before and after administration and the bronchial response to aerosol challenge with methacholine was then assessed using the squeeze technique. A small increase in heart rate and a drop in arterial oxygen tension followed salbutamol administration. No other change in lung volume or air flow obstruction was detected. Bronchial responsiveness decreased significantly after the administration of salbutamol by Babyhaler, the PC30 (provoking concentration of methacholine causing a 30% fall in maximal flow at functional residual capacity by the squeeze technique) increasing from a median of 3.8 g/l after placebo to 12.5 g/l after salbutamol. The Babyhaler is an effective device for administering bronchodilator to wheezy infants. The small scale of the response may be attributable to the uncertain effect of beta agonists in this population. Furthermore, pulmonary deposition of inhaled aerosols may be reduced in nose breathing, sleeping infants.

Albuterol↗
PubMed1993

Relation of HIV-I in bronchoalveolar lavage cells to abnormalities of lung function and to the presence of Pneumocystis pneumonia in HIV-I seropositive patients.

BACKGROUND: HIV is present in bronchoalveolar lavage cells of some but not all HIV seropositive patients. Abnormalities of lung function have been described in such patients in the absence of clinically overt pneumonia or other respiratory infections. It is possible that the presence of HIV in alveolar macrophages could account for these abnormalities. It is also possible that the presence of HIV in alveolar macrophages contributes to immunosuppression and an increased incidence of opportunistic infections. METHODS: This was a prospective study of 157 HIV seropositive patients requiring diagnostic bronchoscopy for investigation of new respiratory symptoms, chest radiograph abnormality, or pneumonic illness. Presence of HIV in bronchoalveolar lavage cells obtained at diagnostic bronchoscopy was determined by polymerase chain reaction to detect proviral DNA and in vitro cocultivation to detect productive virus infection. With these two techniques the presence or absence of HIV in bronchoalveolar lavage was compared with the presence of abnormalities of lung function or presence of Pneumocystis pneumonia. RESULTS: HIV was detected in bronchoalveolar lavage cells in 65% of patients by means of the polymerase chain reaction and 59% with cocultivation. With both methods of detection there was no association between the presence or absence of HIV and the presence of Pneumocystis pneumonia; nor was there a relation between the presence of HIV and abnormalities of lung function. CONCLUSION: The presence of HIV in bronchoalveolar lavage cells does not predispose to an increased incidence of Pneumocystis pneumonia; nor does it contribute to abnormalities of lung function.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Evidence for human immunodeficiency virus infection of the lung.

Pulmonary disease is a frequent manifestation in the terminal stages of acquired immune deficiency syndrome (AIDS), and is caused mainly by a number of opportunistic microorganisms, most commonly Pneumocystis carinii. Despite the extensive involvement of the lung in the pathogenesis of AIDS, until recently little was known about the role of human immunodeficiency (HIV). In this review we will discuss the cellular tropism and phenotypic characterisation of HIV strains isolated from the lung. The available literature on HIV infection of the lung is reviewed, and the mechanisms of HIV-induced pathogenesis in the lung is discussed.

AIDS-Related Opportunistic Infections↗