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Biomedical subjects

R L Clancy

Publications and source records attributed to R L Clancy.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cellular immunity in recurrent vulvovaginal candidiasis.

Impaired T cell function has been reported to predispose women to recurrent vulvovaginal candidiasis, but conflicting results have been noted in the literature. Most clinical episodes occur in the late luteal phase, suggesting hormonal influence on host resistance. The present study assesses the cellular immune responses of 28 women with recurrent vaginal candidiasis (patients) and 25 control women (controls), noting results in relation to whether the women were in the follicular or luteal phase of the menstrual cycle at the time of sampling. Candida-stimulated peripheral blood lymphocyte proliferation was significantly reduced in patients compared with controls. Interferon-gamma (IFN-gamma) production in response to both Candida and purified protein derivative (PPD) stimulation was significantly lower in patients compared with controls. Skin test responses were comparable in both groups. A significant reduction in Candida-stimulated IFN-gamma production was seen in patients but not controls in the follicular phase compared with those in the luteal phase. There was also a trend towards lower proliferation in response to Candida in patients but not controls in the follicular phase compared with patients in the luteal phase. These results suggest that there is a partial T cell dysregulation in recurrent vaginal candidiasis which may be exacerbated by the hormonal balance present during the follicular phase, correlating with the risk of clinical infection.

Adult↗
PubMed1998

Technique to obtain positron emission mammography images in registration with x-ray mammograms.

X-ray mammograms reveal abnormal tissue densities, while metabolic images identify regions of abnormal metabolism. Conventional nuclear medicine and radiologic breast images must be acquired at different times with different patient positions making coregistration difficult. Accurate coregistration of metabolic and x-ray images of the breast is likely to be important when acquiring information about the location and diagnosis of suspicious lesions or tumors. Our PEM-1 (positron emission mammography) system detects metabolic activity within the breast. The two planar detectors are integrated into a conventional x-ray mammography unit. This arrangement simplifies the image registration process by allowing a breast metabolic image to be acquired immediately after performing an x-ray mammogram. The patient is not moved between procedures. A coregistration tool has also been developed. A thin plastic sheet with a wire frame protrudes from the side of the upper PEM detector. With the tool positioned over the suspicious area of the breast, a magnified film density image is made using the available x-ray equipment. A radio-opaque rectangular outline of the wire frame is visible on the film image. During a positron emission metabolic scan, detectors acquire a 49 x 59 mm2 image of the same region. The PEM detectors can be positioned anywhere along the width of the breast. This provides an image of a particular region of interest. Several contiguous images may be combined to provide a complete scan.

Breast Neoplasms↗
PubMed1998

Acute neutropenia decreases inflammation associated with murine vaginal candidiasis but has no effect on the course of infection.

We have used a mouse model of vaginal candidiasis to determine the effect of neutrophil depletion on (a) the clearance of Candida albicans and (b) the degree of inflammation associated with infection. No differences in recoverable yeast number or rate of clearance were observed between normal and neutrophil-depleted mice; however, vaginal inflammation was significantly decreased in neutrophil-depleted animals.

Acute Disease↗
PubMed1998

Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude.

Maximal exercise heart rate (HRmax) is reduced after acclimatization to hypobaric hypoxia. The low HRmax contributes to reduce maximal cardiac output (Qmax) and may limit maximal O2 uptake (VO2max). The objective of these experiments was to test the hypothesis that the reduction in Qmax after acclimatization to hypoxia, due, in part, to the low HRmax, limits VO2max. If this hypothesis is correct, an increase in Qmax would result in a proportionate increase in VO2max. Rats acclimatized to hypobaric hypoxia [inspired PO2 (PIO2) = 69.8 +/- 3 Torr for 3 wk] exercised on a treadmill in hypoxic (PIO2 = 71.7 +/- 1.1 Torr) or normoxic conditions (PIO2 = 142.1 +/- 1.1 Torr). Each rat ran twice: in one bout the rat was allowed to reach its spontaneous HRmax, which was 505 +/- 7 and 501 +/- 5 beats/min in hypoxic and normoxic exercise, respectively; in the other exercise bout, HRmax was increased by 20% to the preacclimatization value of 600 beats/min by atrial pacing. This resulted in an approximately 10% increase in Qmax, since the increase in HRmax was offset by a 10% decrease in stroke volume, probably due to shortening of diastolic filling time. The increase in Qmax was accompanied by a proportionate increase in maximal rate of convective O2 delivery (Qmax x arterial O2 content), maximal work rate, and VO2max in hypoxic and normoxic exercise. The data show that increasing HRmax to preacclimatization levels increases VO2max, supporting the hypothesis that the low HRmax tends to limit VO2max after acclimatization to hypoxia.

Acclimatization↗
PubMed1998

Epidemiological association of airway inflammation with asthma symptoms and airway hyperresponsiveness in childhood.

The role of airway inflammation in childhood asthma is not well defined, despite modern treatment approaches recommending potent anti-inflammatory therapy for an increasing number of children. In this study, induced sputum analysis was used to investigate the relationships among sputum inflammatory cells (eosinophils and mast cells), asthma symptoms, and airway hyperresponsiveness to hypertonic saline in a cohort of 170 children aged 8-14 years. Children who reported asthma symptoms in the past 2 wk had a 2. 25-fold (95% to CI, 1.20-4.24) increased odds of having significant sputum eosinophilia. Hyperresponsiveness to hypertonic saline was strongly associated with higher levels of sputum eosinophils ([OR] 4. 36, 1.70-11.20), sputum mast cells (OR 7.46, 2.48-22.75), and nasal eosinophils (OR 4.73, 1.89-11.86). Interestingly, boys were more likely than girls to have features of airway inflammation (sputum mast cells, OR 3.33, 1.15-9.65; nasal eosinophils, OR 3.25, 1.72-5. 97), which is consistent with the known increase in asthma prevalence in boys in this age group. Airway inflammation with eosinophils and mast cells is likely to be important in the pathogenesis of asthma in childhood. Induced sputum analysis can be used to evaluate this problem and has the potential to be a useful tool for monitoring therapy.

Adolescent↗
PubMed1998

Effects of volume control, pressure control, and pressure-regulated volume control on cardiopulmonary parameters in a normal rat lung.

The purpose of this study was to investigate the differences in diaphragm shortening and cardiopulmonary parameters at varying tidal volumes during volume control (VC), pressure control (PC), and pressure-regulated volume control (PRVC). A miniaturized ultrasonic sensor attached to the inferior surface of the upper costal surface of the right hemidiaphragm of 16 Sprague-Dawley rats provided a direct assessment of diaphragm shortening. Within each control mode of mechanical ventilation, the tidal volume was increased from 3 to 12 ml in increments of 3 ml. There were no differences in cardiac output, mean arterial pressure, central venous pressure, peak inspiratory pressure, or end-tidal CO2 among the three modes of mechanical ventilation. At equivalent tidal volumes, diaphragm shortening was less during PRVC than during VC or PC. This finding suggests that differences in diaphragm shortening may be caused by shorter resting (end-expiratory) diaphragm muscle length. The cardiopulmonary data obtained in this study provide new information for clinicians to consider when using various modes of ventilation, particularly PRVC.

Animals↗
PubMed1997

Role of beta-adrenergic and cholinergic systems in acclimatization to hypoxia in the rat.

To role of beta-adrenergic and muscarinic cholinergic systems on maximal treadmill exercise performance and systemic O2 transport during hypoxic exercise (PIO2 approximately 70 Torr) was studied in rats acclimatized to hypobaric hypoxia (PIO2 approximately 70 Torr for 3 weeks, A rats) and in non-acclimatized littermates (NA rats). Untreated A rats had lower resting (fH) and maximal heart rate (fHmax) and cardiac output (Q), and higher maximal O2 uptake (VO2max) than NA. The only effect of cholinergic receptor blockade with atropine (Atp) was an increase in pre-exercise fH to comparable levels in A and in NA. beta 1-adrenergic receptor blockade with atenolol (Aten) lowered pre-exercise fH and (fHmax) to comparable values in A and in NA rats. However, since both pre-exercise fH and fHmax were lower in untreated A, the effect of Aten was relatively smaller in A. Aten reduced maximal exercise cardiac output (Qmax) in NA; however, tissue O2 extraction increased such that VO2max was not affected. Aten did not influence Qmax or any other parameter of systemic O2 transport in A. In conclusion the increased cholinergic tone may be responsible for the lower resting fH but not the lower fHmax of A; the integrity of the beta-adrenergic system is not necessary to attain VO2max in hypoxia either in A or in NA; the decreased response to beta-adrenergic stimulation in A limits the efficacy of this system on the mechanisms of systemic O2 transport and reduces the effect of its blockade on these mechanisms.

Acclimatization↗
PubMed1997

In vitro susceptibility patterns of nonserotypable Haemophilus influenzae from patients with chronic bronchitis.

The antimicrobial susceptibility patterns of 76 nonserotypable Haemophilus influenzae (biotypes I-IV) from patients with chronic bronchitis were compared against ten orally administered antimicrobial agents. In addition the sputum ampicillin concentrations one hour after standard therapy were determined in five patients with chronic bronchitis. Ampicillin resistance was demonstrated in one strain (biotype IV) which produced beta-lactamase and two strains (biotype II) with innate resistance (MIC = 4 mg/l). Resistance to trimethoprim, chloramphenicol, ciprofloxacin and cefaclor was not detected. The incidence of resistance to tetracycline was 0.5% and cephalexin 13.2%. A high incidence of resistance to erythromycin (95%) was noted. There was no association between resistance and biotype of nonserotypable H. influenzae. The sputum ampicillin concentrations from four out of five patients given standard antibiotic doses were shown to be sufficient to inhibit the growth of the majority of nonserotypable H. influenzae strains one hour after treatment. This study shows that the incidence of nonserotypable H. influenzae resistant to ampicillin is low in this community but that resistance levels to erythromycin, commonly prescribed for the management of acute bronchitis, are high. Regular sensitivity screens are important in monitoring the value of various antibiotic regimens in the management of acute bronchitis.

Administration, Oral↗
PubMed1997

Vaccine strategies against Pseudomonas aeruginosa infection in the lung.

Pseudomonas aeruginosa is an environmentally ubiquitous, extracellular opportunistic gram-negative bacteria that causes significant morbidity and mortality to a disproportionately high degree for infections with this bacteria compared with other gram-negative bacteria. Patients at particular risk of infection are those with compromised respiratory function, in intensive-care support and taking immunocompromising pharmaceutical agents. Once acquired, infection is difficult to eradicate with chemotherapy and attempts to vaccinate against infection have been of little success. Over the past five years, we have pursued the concept of mucosal immunisation against respiratory infection with P. aeruginosa. Initial studies in an acute animal model clearly demonstrated that mucosal immunisation with a killed whole bacterial cell preparation could induce protective immune responses in the lung. Subsequent studies have shown that the protective immune mechanisms were dependent on antigen specific CD4+ T cells, the activation of alveolar macrophages, the recruitment and activation of polymorphs, predominantly neutrophils, the controlled secretion of TNF-alpha, IL-1 and IFN gamma and the presence of antibody. We have hypothesised that the protective response is under the control of T cells. A pre-clinical human trial of an oral whole killed cell preparation has been completed with no adverse side effects. A limited open trial in patients with bronchiectasis has also been completed. Preliminary analysis of the results has demonstrated that after oral vaccination, specific lymphocyte responses were observed to P. aeruginosa.

Animals↗
PubMed1996

Pneumococcal antibody responses in elite swimmers.

The ability of elite swimmers to mount an antibody response to the pneumococcal vaccine, Pneumovax 23, was assessed at the end of an intensive 12-week training programme. Antibody titres to six pneumococcal polysaccharide types were measured in 20 elite swimmers (10 male, 10 female) aged 17-23 years and 19 sedentary age- and sex-matched students (eight male, 11 female) aged 18-23 years. Blood samples were tested 14 days apart to assess the magnitude of the antibody response and changes in serum immunoglobulin isotypes and IgG subclasses. There were no significant differences in any of the pneumococcal antibody responses to the Pneumovax between swimmers and controls, and no gender effect, either before or after vaccination. The clinically adequate response to the vaccine was greatest for the pneumococcal serotype 4, which was 97% for the total study population. There were no significant correlations between the magnitude of any of the pneumococcal antibody responses and (i) changes in the scores for the swimmers' international performance; (ii) infection rates in either swimmers or controls; (iii) any psychological variables, assessed by the Profile of Mood States (POMS) questionnaire for either swimmers or controls. Swimmers had significantly lower concentrations of serum IgG2 (P = 0.04) and IgG3 (P = 0.002) before pneumococcal vaccination. The swimmers had an increase in all immunoglobulin isotypes and IgG subclasses post-vaccination, suggesting a polyclonal response to the vaccine that was not observed in control subjects. The magnitude of the subclass responses after vaccination was significantly greater in swimmers compared with controls for IgG1 (P = 0.04), IgG3 (P = 0.04) and IgG4 (P = 0.01). The data indicated that elite swimmers undertaking an intensive training programme were capable of mounting an antibody response to pneumococcal antigens equivalent to that of age- and sex-matched sedentary control subjects, despite the swimmers having lower prevaccination levels of serum immunoglobulins.

Adolescent↗
PubMed1996

Development of bronchial hyperreactivity following transient absence of salivary IgA.

In a birth cohort of 114 normal children, this study examined the hypothesis that a transient absence of salivary IgA in the first year of life was associated with an increased risk of developing atopy, asthma, or bronchial hyperreactivity (BHR) later in life. Episodes of transient absence of IgA in saliva, of less than 1 mo, occurred in 18% of the study population in the first year of life. The children were assessed at age 7.5 to 12 yr for the presence of atopy (skin prick test to inhaled allergens), asthma (wheeze in the previous 12 mo), and BHR (histamine provocation). The transient absence of salivary IgA in the first year of life was associated with an increased risk of BHR (adjusted odds ratio [Adj OR]: 11.6; 95% confidence interval [CI]: 2.2 to 60.9) and a trend toward a lowered risk of atopy to inhaled allergens (raw OR: 0.35; CI: 0.11 to 1.11). There was no relationship between the transient absence of salivary IgA and a clinical diagnosis of asthma (Adj OR: 0.9; CI: 0.2 to 3.6). The inconsistency in the relationships between the transient absence of salivary IgA and atopy, asthma, and BHR supports the concept that atopy, wheeze, and bronchial hyperreactivity are independent clinical outcomes. One possible explanation for the relationships observed in this study is that the transient absence of IgA in saliva in the first year of life identifies a cohort with mucosal hypoimmunity. These subjects are thus less likely to develop atopy and less able to effectively respond to a mucosal infection. Presentation of a mucosal antigen in these subjects may subsequently be associated with an inappropriate inflammatory response, which conditions bronchial hyperreactivity, and which is independent of atopy.

Air Pollutants↗
PubMed1996

A clinical evaluation in children of the Pharmacia ImmunoCAP system for inhalant allergens.

BACKGROUND: The Pharmacia ImmunoCAP system (CAP) for assaying serum IgE specific antibodies was evaluated in a clinical setting against skin-prick test (SPT) performed using Dome/Hollister-Steir allergen extracts. The five common inhalant allergens D. pteronyssinus, D. farinae, mould mix, grass mix and cat epithelium were tested concurrently by both methods in 167 children aged 7.5-12 years. The specific SPT for D. pteronyssinus and D. farinae were also tested against the CAP house dust mite (HDM) mix. OBJECTIVE: The purpose of the study was to determine the sensitivity and specificity of the Pharmacia ImmunoCAP system for detecting serum IgE specific antibodies to inhalant allergens in a clinical setting, using SPT result as the "gold standard'. METHODS: The SPTs were performed using Dome/Hollister-Steir allergen extracts. The serum IgE specific antibodies were quantitated using the radioimmunoassay version of the Pharmacia ImmunoCAP system. A history of allergic disease was assessed using a validated questionnaire. RESULTS: SPT gave more positive reactions than CAP with the exception of cat epithelium. The concordance between SPT and CAP results was 91% over all the tests. The concordance with SPT was slightly higher for the specific CAP for D. pteronyssinus and D. farinae (93% and 95% respectively) than for the CAP HDM mix (86% and 90% respectively). There was a higher proportion of positive results for both SPT and CAP in the 115 children defined as having a history of allergic disease. Using SPT defined allergy as the gold standard, the sensitivity of the CAP system was 87% for the two specific house dust mites but was lower for cat epithelium (67%), mould mix (59%) and grass mix (46%). The sensitivity of the CAP system improved for D. pteronyssinus (96%) and the HDM mix (91%) when tested in subjects defined as having a history of allergy associated disease. The specificity of the CAP system showed less variation between allergens and ranged from 90-99%. CONCLUSION: The results of this study of children aged 7.5-12 years demonstrate that, for the inhalant allergens tested, the Pharmacia ImmunoCAP system performs well in the setting of known allergic disease.

Allergens↗
PubMed1995

Protection against non-typable Haemophilus influenzae following sensitization of gut associated lymphoid tissue: role of specific antibody and phagocytes.

Rats intestinally immunized with whole killed non-typable Haemophilus influenzae clear this organism from the lungs faster than non-immunized rats. This study investigated the role of antibody and phagocytes in the clearance mechanism. First, dose-response experiments demonstrated that while lowering the dose of non-typable H. influenzae reduced the level of detectable specific antibody in bronchial washings, the ability to accelerate bacterial clearance persisted to much lower doses. Second, specificity experiments showed that intestinal immunization with non-typable H. influenzae cross-protected against Pseudomonas aeruginosa, even though antibodies were not absorbed out of serum by incubation with P. aeruginosa. Third, serum antibody was shown to be bactericidal for non-typable H. influenzae in the presence of complement (P < 0.05), while bronchial washings antibody was not. The bactericidal effect of the serum was abrogated by the addition of bronchial washings. Fourth, an ELISA quenching assay demonstrated that neutrophils from intestinally immunized rats were able to phagocytose more bacteria in a given time period (P < 0.05) than unimmunized rats and rats immunized by other routes. In the fifth experiment, the chemotactic response of neutrophils to casein was shown to be significantly depressed by the addition of bronchial washings obtained from immunized rats (P < 0.01). It is proposed that specific antibody in bronchial washings does not have a direct role in opsonizing bacteria for killing or phagocytosis, but instead has an anti-inflammatory effect. Non-specific effectors such as neutrophils driven by specific immune cells are a likely means of clearance of bacteria following intestinal immunization and acute challenge.

Animals↗
PubMed1995

Modifiers of the human mucosal immune system.

This review focuses on saliva as a measure of mucosal immunity in man. The review will cover studies of parameters that modify the early ontogeny patterns of mucosal immunity and the impact of infections and physiological variables on the human mucosal immune system. The most significant modifiers of human mucosal immunity are events that occur in the neonatal maturation period and, later in life, the interplay between the immune system and the neuroendocrine systems. IgA antibodies are the predominant isotype involved in the human mucosal immune response and are important for protection at mucosal surfaces. The level of IgA in mucosal secretions is modified by antigenic stimulation as well as by many physiological variables. Studies have also revealed that IgM plays a significant immunoregulatory role at mucosal surfaces, particularly during episodes of infection or stress. The detection patterns of IgD in saliva of neonates suggests a role for IgD in the initial maturation process of mucosal immunity. The role of IgG at mucosal surfaces is unclear and although IgG may play a compensatory role in IgA deficiency, the detection of high levels of IgG in saliva appears to be associated with periods of increased membrane permeability.

Adolescent↗
PubMed1995

Pulmonary immunity to Pseudomonas aeruginosa.

Pseudomonas aeruginosa, an opportunistic bacterial pathogen, is a major course of morbidity and mortality in subjects with compromised respiratory function despite the significant advances in therapeutic practices. The bacteria produces an armoury of products which modify its infective niche to ensure bacterial survival. The role of antibody in protection against pulmonary infection remains poorly defined. Protection appears to be associated with opsonizing antibody whilst some other antibody responses may be deleterious and promote further lung damage. Cell mediated responses are clearly important in protection against infection. This review proposes a vaccine strategy aimed at enhancing specific T cell responses in the lung which, though T cell-derived cytokines, drive the recruitment of neutrophils to the lung and the subsequent activation of these cells results in the clearance of bacteria from the lung.

Antibody Formation↗