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Biomedical subjects

N Carroll

Publications and source records attributed to N Carroll.

At least 19 recordsLinked to original sources
PubMed2005

Reduced apoptosis of memory T-cells in the inner airway wall of mild and severe asthma.

Effector memory T-cells (CD45RO+) may provide pro-inflammatory signals that contribute to the persistent airway inflammation that is characteristic of asthma, and reduced apoptosis of these cells may prolong their effects. The present authors compared apoptosis of CD45RO+ T-cells in the inner airway wall in nonfatal asthma (n = 7), fatal asthma (n = 7) and control (n = 8) cases. Apoptotic cells were identified using both the terminal deoxynucleotidyl transferase dNTP nick end-labelling (TUNEL) technique and cell morphology. The percentage of CD45RO+ T-cells that were apoptotic was significantly greater in control cases compared with nonfatal and fatal cases of asthma, respectively, in small (42+/-19, 16+/-9, 7+/-6%), medium (40+/-12, 15+/-11, 12+/-8%) and large airways (42+/-15, 23+/-18, 18+/-12%). The reduction in the percentage of apoptotic CD45RO+ cells in the cases of asthma was observed in both blood vessels and the interstitium in large airways. In conclusion, these data suggest that reduced apoptosis may prolong the active life of effector memory T-cells in the airways. It is possible that survival signals may be received before cells migrate into the interstitium of the inner airway wall.

Adolescent↗
PubMed2001

A comparison of intrauterine versus intracervical insemination in fertile single women.

OBJECTIVE: To compare the efficacy of intrauterine insemination (IUI) and intracervical insemination (ICI) when used by fertile single women in a donor insemination program. DESIGN: Prospective randomized crossover study. SETTING: Donor insemination program (not an infertility clinic). PATIENT(S): Single fertile women choosing to inseminate with frozen donor semen. INTERVENTION(S): Clients received procreative counseling and screening and were then randomly assigned to begin office insemination with ICI or IUI. If additional insemination cycles were required, the clients used the method opposite their previous method of insemination until pregnancy was achieved. MAIN OUTCOME MEASURE(S): Monthly fecundity rate was compared between the two methods of insemination. RESULT(S): Sixty-two women contributed a total of 189 cycles, 94 by IUI and 95 by ICI. The monthly fecundity rate for IUI was 15%, as compared with 9% for ICI, (P=0.14). When the analysis was confined to cycles in which only one insemination was performed (64 IUI and 65 ICI cycles), the monthly fecundity rates were 14% for IUI and 5% for ICI (P=0.04). CONCLUSION(S): Intrauterine insemination with frozen donor sperm is more effective than intracervical insemination for single women without known fertility problems.

Adult↗
PubMed2001

Increased airway responsiveness and decreased alveolar attachment points following in utero smoke exposure in the guinea pig.

Maternal smoking during pregnancy has been shown to result in abnormalities in lung function in newborn infants, including reduced expiratory flow and increased airway responsiveness to inhaled agonists. The mechanisms by which this occurs remain unclear. Using a guinea pig model of in utero smoke exposure, we measured airway responsiveness and lung morphology in a group of neonatal guinea pigs 21 d after delivery. Pregnant guinea pigs were exposed to cigarette smoke from Day 28 to term (Day 68 of gestation). After delivery newborn animals did not receive any smoke exposure. Airway wall thickness, smooth muscle area, and the number of points where the alveoli attached to the airway adventitia were measured. Airway responsiveness was increased (p < 0.05) and the mean distance between alveolar attachment points was increased (mean 0.052 +/- SE 0.001 mm versus 0.046 +/- 0.001, p = 0.001) in animals exposed to cigarette smoke in utero compared with nonexposed animals. Although not statistically significant, both the inner and outer airway wall and the smooth muscle area were greater in exposed animals compared with nonexposed animals. The increased mean distance between alveolar attachments in the smoke-exposed group was the result of a reduction in the number of attachments and an increase in the outer airway wall perimeter. These findings suggest that the increased airway responsiveness observed in postnatal animals, subsequent to in utero cigarette smoke exposure, may be the result of decreased alveolar attachment points to the airways and changes in airway dimensions.

Animals↗
PubMed2000

Airway smooth muscle in health and disease; methods of measurement and relation to function.

Smooth muscle is present and probably functional in the airways in utero and increases in absolute area during growth with little further change during adulthood. It encircles the entire airway below the level of the main bronchus, in a roughly circular orientation, except at high lung volumes. It occupies relatively more of the airway wall in the peripheral airways, reaching a maximum in the membranous bronchioles. Measurement of smooth muscle area in the airway wall is confounded by clinical classification of cases, methods of tissue retrieval and preparation, staining and orientation of sections, magnification, image analysis and statistical methods of comparison between groups. Airway smooth muscle area is pathologically increased in inflammatory conditions of the airways such as chronic obstructive pulmonary disease, in relation to airways obstruction, and asthma, in relation to severity and airway size (between 25 and 250% compared with control cases). It is increased in sudden infant death syndrome, but there are few studies in other conditions such as bronchiectasis. In asthma, smooth muscle must shorten (not necessarily to an abnormal degree) for the structural abnormalities of the airway to manifest as excessive airway narrowing. Not surprisingly there is renewed interest in the relationships between the mechanical and contractile properties of smooth muscle, parenchymal properties and lung volume and how these interact to determine smooth muscle length. The relative importance of smooth muscle area and mechanical properties, altered airway structure and airway inflammation in disease are yet to be determined.

Adult↗
PubMed2000

Pulmonary vascular congestion selectively potentiates airway responsiveness in piglets.

The influence of pulmonary vascular congestion on the response of the airways and lung tissue to low doses of inhaled methacholine (MCh) was studied by inflating a balloon catheter in the left atrium of the heart in six piglets, with an additional five piglets serving as control animals. Congestion alone resulted in small increased in baseline airway (Raw) (14.6 +/- 3.7%) and tissue (Rti) resistance (8. 1 +/- 6.5%). Low-dose inhaled MCh (0.3 mg/ml) increased Raw and Rti in the control group by 10.8 +/- 10.3% and 42.2 +/- 29.5%, respectively. The increase in Raw with MCh in the presence of vascular engorgement was significantly greater (67.8 +/- 18.9%) but the increase in Rti (38.1 +/- 13.2%) was similar to that seen in the control group. Morphometric measurements were performed on transverse sections of large and small airways from nine additional piglets (three congested only, three MCh only, and three congestion plus MCh). The thickness of the inner airway wall was similar in all groups. Compared with MCh only piglets, the thickness of the outer airway wall (between the outer border of the smooth muscle and the surrounding lung parenchyma) was increased (p < 0.05) in engorged only and engorged plus MCh piglets. Compared with MCh only and engorgement only, the amount of airway smooth muscle shortening was greater (p < 0.05) in all airway size groups in piglets that underwent engorgement plus MCh challenge. The results of this study demonstrate that pulmonary vascular engorgement, induced by increased left atrial pressure, selectively enhances the airway, but not the parenchymal, response to inhaled MCh. These changes are associated with increased thickness of the outer airway wall in response to vascular congestion, suggesting that uncoupling of the mechanical interdependence between the airway smooth muscle and the lung parenchyma may have occurred. Mechanical uncoupling may reduce the load opposing smooth muscle shortening resulting in increased airway narrowing in response to low doses of inhaled methacholine.

Animals↗
PubMed2000

PCR-based evidence of bacterial involvement in eyes with suspected intraocular infection.

PURPOSE: To assess the usefulness of polymerase chain reaction (PCR) in detection of bacteria in ocular samples. METHODS: Thirty-seven samples (aqueous and vitreous) were collected from 25 eyes showing typical symptoms and clinical signs of bacterial endophthalmitis. Ocular samples were also collected from 38 eyes that underwent routine surgery and from 15 eyes with intraocular inflammation due to nonbacterial causes. Panbacterial PCR was performed with a nested pair of 16S rRNA gene primers. Subsequent bacterial identification was completed for 18 paired samples (nine eyes) using restriction fragment length polymorphism (RFLP) and DNA sequencing. RESULTS: A 100% concordance was obtained between PCR and culture-positive samples. A PCR product was amplified from all 37 intraocular samples from eyes with suspected infection, whereas only 15 of 22 vitreous samples and 5 of 15 aqueous samples were culture positive. Culture-negative PCR-positive samples contained a preponderance of gram-negative bacterial sequences. Cloning and DNA analysis revealed 30 DNA sequences and included eight bacterial 16S rDNA, which currently remain unidentifiable. The presence of bacterial DNA was associated with an inflammatory response suggestive of infection and not colonization. All 15 samples from inflamed eyes with diverse uveitis diagnoses were PCR negative. The false-positive rate, due to contamination during sampling, was 5%. CONCLUSIONS: Bacterial DNA was detected in all patients with typical clinical signs of endophthalmitis. Gram-negative organisms seem to play a much more important role in the pathogenesis of this disease than previously thought. PCR-based techniques have great value in the confirmation of the diagnosis of bacterial endophthalmitis especially in culture-negative eyes.

Adult↗
PubMed1999

Nitrotyrosine formation in the airways and lung parenchyma of patients with asthma.

BACKGROUND: Recent evidence has shown that nitric oxide (NO) levels are increased in asthmatic airways. Although the role of NO in asthma is unknown, reactive metabolites of NO may lead to nitrotyrosine formation and promote airway dysfunction. OBJECTIVE: The aim of this study was to determine whether nitrotyrosine, as a marker of nitrating species, could be found in the airways and lung parenchyma of subjects with asthma who died of status asthmaticus or other nonrespiratory causes. METHODS: Lung tissue specimens were obtained from 5 patients who died of status asthmaticus, 2 asthmatic patients who died of nonrespiratory causes, and 6 nonasthmatic control subjects who died of nonrespiratory causes. Lung sections were stained for immunofluorescence with use of an antinitrotyrosine antibody, followed by a indiocarbocyanine (Cy5, Jackson Immunochemicals, Westgrove, Pa)-conjugated secondary antibody. RESULTS: Nonasthmatic lungs showed little or no nitrotyrosine staining, whereas asthmatic lungs demonstrated significantly more staining of nitrotyrosine residues distributed in both the airways and lung parenchyma. CONCLUSION: This study demonstrates the presence of nitrotyrosine, and hence evidence of formation of nitrating species, in the airways and lung parenchyma of patients with asthma who died of status asthmaticus or other nonrespiratory causes. This finding supports the concept that widespread airway and parenchymal inflammation occurs in asthma, and, more specifically, that NO and its reactive metabolites may play a pathophysiologic role in asthma.

Adolescent↗
PubMed1999

Increased airway smooth muscle in sudden infant death syndrome.

The underlying pathophysiological mechanism behind death in the sudden infant death syndrome (SIDS) is uncertain. Although infants dying of SIDS frequently have a postmortem examination performed, no specific diagnostic pathology in any organ system has been identified. Previous theories relating to the cause of death in SIDS have included increased lower airway closure. We examined the airway morphometry of 57 infants who died of SIDS and compared these findings with those obtained from 21 age-matched infants who had died of non-SIDS causes. Airway wall dimensions, epithelial thickness, and the area of smooth muscle within the airway wall were measured. Airways from infants who died of SIDS showed a significantly higher proportion of airway smooth muscle than control airways when corrected for age and sex (p < 0.01). There was no significant difference between the groups for wall thickness or epithelial thickness. Increased airway smooth muscle in infants who have died of SIDS may contribute to excessive airway narrowing, raising the possibility that the cause of death in this condition is related to abnormalities in lower airway function.

Airway Resistance↗
PubMed1999

Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy.

REM-related oxygen desaturation occurs in advanced Duchenne muscular dystrophy (DMD) and might be an independent predictor of disease progression. We have followed 18 patients for 10 yr after an initial respiratory sleep study or until death or onset of nasal ventilation. We measured baseline spirometry, blood gas tensions, maximal respiratory pressures, and body mass index. In 11 cases, VC was recorded serially. Median survival was 50 (range, 13 to 89) mo from initial study and unrelated to age at time of study, BMI, or mouth pressures but correlated with PaCO2 (r = -0.72, p < 0.005, n = 17), minimal nocturnal SaO2 (r = 0.62, p < 0.007, n = 18) and VC (r = 0. 65, p < 0.005, n = 17). Cox regression analysis showed a VC of less than 1 L at the time of study to be the best single predictor of subsequent survival. The only measure associated with age of death was the age at which the VC fell below 1 L (r = 0.79, p < 0.004). These data suggest measurement of PaCO2 or serial assessment of VC should be studied further as valid methods of assessing prognosis in DMD.

Adolescent↗
PubMed1998

Increased perception of airway narrowing in patients with mild asthma.

To compare the perception of airway narrowing of nonasthmatic subjects with those having wheeze or mild asthma (doctor-diagnosed), the relationship between FEV1 and breathlessness was examined in 123 subjects from a general population sample. Scores for breathlessness, using the Borg scale, were recorded before and after inhaling incremental doses of methacholine to a maximal dose of 196 mcmol or a maximum change in FEV1 of 50%. A history of asthma symptoms, including wheeze in the previous 12 months, and doctor-diagnosed asthma was obtained by questionnaire. At any given level of FEV1 there was wide variation in Borg scores between subjects, however median Borg scores and the mean slope of Borg score on FEVI was greater in the asthmatic subjects or those with wheeze compared with nonasthmatic subjects or those without wheeze. In both nonasthmatic and asthmatic subjects, those with airway hyperresponsiveness had increased maximum symptom scores and maximum changes in FEVI, but similar Borg scores relative to change in FEVI, compared with those without hyperresponsiveness. We conclude that the perception of mild and moderate degrees of airway narrowing varies widely between individuals but is increased in subjects with a history of mild asthma or wheeze in the last 12 months, independently of airway responsiveness.

Adult↗
PubMed1997

Diencephalic tumours presenting as behavioural problems in the workplace.

Two patients presented with histories of significant behavioural disturbance and deteriorated work performance. Subsequent investigations confirmed the presence of a craniopharyngioma and a prolactinoma. Occupational physicians should consider excluding organic pathology in employees with histories of an unexplained marked change in work performance and behaviour.

Adult↗
PubMed1997

Development and validation of a computerized screening test for personality disorders in DSM-III-R.

The available self-report instruments designed to measure personality disorder (PD) are time-consuming to administer and/or score and can be impractical for routine clinical use. There is a need for a computerized method of personality assessment based on contemporary systems of classification. A computerized DSM-III-R-based questionnaire was developed and validated against the structured clinical interview for DSM-III-R Axis-II disorders on a sample of 60 subjects. The computerized test showed moderate validity as a diagnostic instrument (mean kappa coefficient = 0.47). With adjusted cut-off scores it was valid as a screening instrument (mean sensitivity = 0.87). Antisocial, borderline and avoidant PD scores were strongly correlated across measures and not subject to significant observer bias.

Adult↗
PubMed1997

The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics.

Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma. In cases of fatal asthma (n = 10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n = 10), and control cases (sudden death with no history of respiratory illness, n = 10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin. Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p < 0.001). Eosinophils were increased (p < 0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r = 0.60; p < 0.0001), and to a lesser extent in the nonfatal (r = 0.34; p = 0.001) and control groups (r = 0.32; p = 0.001). These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.

Adolescent↗
PubMed1996

Spinal cord diameters in cadaveric specimens and magnetic resonance scans, to assess embalming artefacts.

It would be valuable to use cadaveric models of cervical vertebrae and spinal cord to assess how varying degrees of traumatic subluxation would relate to neurological damage. However, before such a study may be undertaken, it would be important to assess the degree of shrinkage of expansion of the spinal cord that occurs during the embalming process. This is achieved in this study by comparing diameters of cadaveric spinal cord to that of sagittal magnetic resonance scans of living subjects. The geometric measurements of radiographs in living subjects has been assessed but no direct model for spinal cord injury has been described [1]. If embalmed spinal cord diameters were a good estimator of living spinal cord diameters then cadaveric cervical spines could be used as a model. By reproducing various degrees of fracture and dislocation the extent of corresponding cord compression could be assessed. Our study shows that spinal cord dimensions increase after embalming using the Cambridge procedure [4].

Aged↗
PubMed1996

Variability of airway structure and inflammation in normal subjects and in cases of nonfatal and fatal asthma.

The quantitative assessment of airway inflammation in patients with apparently similar clinical severity of asthma has yielded variable results. The aim of this study was to assess the variability of inflammatory cell counts and airway structure in large and small airways from subjects with and without asthma, and to calculate the number of cases required to detect significant differences between disease groups. Three serial transverse sections, 20 microns apart, were examined from cartilaginous and membranous bronchioles. Airway dimensions measured were the areas and perimeters defined by the luminal surface of the airway epithelium, basement membrane, outer border of airway smooth muscle, and surrounding border of the airway adventitia. Airway wall components measured were the areas of airway smooth muscle, mucous glands and cartilage. The numbers (per mm of basement membrane) of lymphocytes, eosinophils, neutrophils and plasma cells were counted using haematoxylin and eosin staining and mast cells were counted in sections stained with Toluidine blue. Measurements were repeated by two or three observers. The coefficient of variation (CV) was used to assess intraairway, intraobserver and interobserver variability. For airway dimensions the mean (+/- SD) CV within airways was 3.8% +/- 2.1%, within observers was 3.7% +/- 1.8% and between observers, 3.4% +/- 1.8%. For airway wall components, the CV within airways was 10.7% +/- 4.6%, and between observers was 8.8% +/- 2.2%. For cell counts, the CV within airways was 20.8% +/- 12.5%, within observers was 8.3% +/- 3.7% and between observers, 9.6% +/- 4.6%. There were no significant differences in variability between cases with and without asthma. Intra-airway variability was higher (p < 0.05) in membranous airways (5.6% +/- 1.7%) than in large cartilaginous airways (2.3% +/- 1.1%). We estimate that between 5 and 15 cases in each group would be required to detect differences of 50-100% between groups, depending on the parameter being compared. These findings suggest that airway structure and inflammatory cell numbers are uniform throughout the bronchial tree in normal and asthmatic cases, and that small samples of large or small airways are likely to be representative when comparing cases.

Adult↗
PubMed1996

Airway structure and inflammatory cells in fatal attacks of asthma.

Fatal attacks of asthma usually occur against a background of chronic persistent symptoms, presumably due to chronic airway inflammation and changes in airway wall structure. Death from asthma is usually attributed to excessive airway narrowing due to a combination of muscle spasm and mucous plugging. To test the hypothesis that airway wall structure and/or the inflammatory cell profile are related to the duration of a fatal attack of asthma, inflammatory cell profiles and airway structure were examined in cases of fatal asthma and related to the duration of the fatal attack. In transverse sections of large and small airways from subjects dying from asthma, the numbers of eosinophils, neutrophils and lymphomononuclear cells were counted. The amount of smooth muscle shortening, the areas of airway wall, smooth muscle, mucous gland and cartilage were measured. Cell counts, airway dimensions and muscle shortening were compared in cases dying within 2 h of the fatal attack (short duration) and those dying more than 5 h after the onset of the fatal attack (long duration). In cases with fatal attacks of short duration, the numbers of neutrophils and the mucous gland area were increased and the numbers of eosinophils were reduced compared to cases with fatal attacks of long duration. Lymphocyte numbers, airway wall thickness, the areas of smooth muscle and cartilage and the amount of smooth muscle shortening were similar in the two groups. These findings suggest fatal attacks of asthma may be triggered by an inflammatory stimulus and suggest that increased production of mucous may contribute to sudden death in such cases.

Adolescent↗