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Biomedical subjects
Publications and source records attributed to M Gleeson.
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We examined body mass index (BMI) as a proxy for percent body fat among 26 men and women successfully undergoing orthotopic heart transplantation. Percent body fat was determined by use of bioelectrical impedance techniques. We found that, although BMI was well correlated with percent body fat (r = 0.58, p < 0.01), use of a BMI of greater than 27 kg/m2 to define obesity potentially misclassified patients when compared with defining obesity as a percentage of body fat as both greater than 30% (BMI = 9 of 26 patients vs percent body fat = 6 of 26 patients) and greater than 40% (BMI = 9 of 26 versus percent body fat = 1 of 9). We conclude that percent body fat measurements are more methodologically appropriate means for J Heart Lung Transplant 1997;16:563-5.
Since mucosal surfaces represent the interface between the host and the environment and are the most common portal of pathogen entry, early development of functional mucosal immune defense is essential for survival. The development of mucosal immune function is profoundly influenced by maternal, environmental, and behavioral factors and although the impact of these is greatest during the prenatal and immediately postnatal periods, their influence extends beyond this period and patterns of development in postnatal life determine many of the immune outcomes in later life. This review will correlate information regarding age-related changes occurring in mucosal-associated lymphoid tissue from a variety of animal models and in humans and will explore how the interactions which exist between the immune and neuroendocrine systems orchestrate these effects. In particular the role of prenatal and postnatal stressors, feeding patterns, nutritional factors, infections, and exposure to allergens and toxins are addressed. A clear understanding of the way in which these factors interact to influence development and control of mucosal immune function will assist in the design of neonatal vaccination and disease management strategies.
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.
Sequence analyses 5' ends of the 60-kDa cysteine-rich outer membrane protein genes (Omp2) of Chlamydia psittaci and Chlamydia pecorum strains indicate that these species have approximately 70% nucleotide identity. On the basis of this sequence information, PCR primers were designed to allow the specific amplification of DNA extracted from C. psittaci S26/3 (abortion strain), P94/1 (pigeon strain), and C. pecorum W73 (fecal strain) in one reaction tube. By using nested reactions (with primers PCR-D1 and PCR-D2 followed by the specific primers and PCR-D2), 0.6, 0.2, and 8 inclusion-forming units of S26/3, P94/1 (both diluted in tissue culture-negative placental material), and W73 (diluted in culture-negative fecal material) per ml, respectively, were detected. The differentiation of C. psittaci and C. pecorum strains of ovine and bovine origins was carried out, and the results were in agreement with those obtained from AluI restriction enzyme analysis of DNA amplified from corresponding strains by PCR. This approach allows the simultaneous detection and typing of C. psittaci and C. pecorum strains and the identification of samples containing both species.
OBJECTIVE: To investigate the effects of long term (> 10 years) endurance training and submaximal exercise on the phagocytic activity of circulating neutrophil granulocytes. METHODS: The ability of stimulated blood neutrophils isolated from well trained cyclists [n = 8; VO2max 61.0(SD 8.8) ml.kg-1.min-1; age 38(4) years] and age matched sedentary controls [n = 8; VO2max 37.4 (6.6) ml.kg-1.min-1] to ingest nitroblue tetrazolium was assessed at rest and following a standardised submaximal bout of exercise on a cycle ergometer. RESULTS: Trained subjects had a lower resting blood neutrophil count (P < 0.01). Acute exercise caused a rise (P < 0.01) in the blood neutrophil count irrespective of training status, but the magnitude of the rise was smaller in the trained subjects (P < 0.05). The circulating neutrophil phagocytic capacity was approximately 70% lower in trained individuals at rest compared with the control subjects (P < 0.01). Acute submaximal exercise increased this variable in both groups, but phagocytic capacity remained substantially lower in the trained subjects compared with the controls (P < 0.05) despite the observation that a higher proportion of the circulating neutrophils were stimulated to undergo phagocytosis in the trained subjects [57(14)% v 32(7)%; P < 0.01). CONCLUSIONS: Although neutrophil phagocytic activity is only one variable that contributes to immunological status, prolonged periods of endurance training may lead to increased susceptibility to opportunistic infections by diminishing this activity at rest.
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.
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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.
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The operating microscope is an integral part of many neurosurgery and otolaryngology procedures; the surgeon often uses the microscopic view for a large portion of the operation. Information from preoperative radiological images is often viewed only on X-ray films. The surgeon then has the difficult task of relating this information to the appearance of the surgical view. Image guidance techniques attempt to relate these two sets of information by registering the patient in the operating room to preoperative images using locating devices. Conventionally, image data are presented on a computer monitor, which requires the surgeon to look away from the operative scene. We describe a guidance system, for procedures in which the operating microscope is used, which super-imposes image-derived data upon the operative scene. We create a model of relevant structures (e.g., tumor volume, blood vessels, and nerves) from multimodality preoperative images. By calibrating microscope optics, registering the patient to image coordinates, and tracking the microscope and patient intraoperatively, we can generate stereo projections of the three-dimensional model and project them into the microscope eyepieces, allowing critical structures to be overlaid on the operative scene in the correct position. Measurements with a head phantom gave a root mean square (RMS) error of 1.08 mm, and the estimated error for a human volunteer is between 2 and 3 mm. Initial evaluation in the operating room was very promising.
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Delayed-onset muscle soreness following unaccustomed or eccentric exercise is associated with inflammation, tissue necrosis and the release of muscle enzymes (Newham et al. 1983). We have investigated the time course of changes in circulating leucocytes and serum levels of some acute phase reactants, serum creatine kinase activity (CK) and muscle pain after a 40-min bout of bench-stepping exercise in eight healthy untrained subjects. Leg muscle soreness was greatest 2 days after the exercise bout. Peak serum CK values [mean (SD) 540 (502) IU.1-1] occurred 1-7 days post-exercise. Serum C-reactive protein (CRP) was unchanged from pre-exercise levels [7.8 (3.4) mg.1-1] immediately post-exercise [7.9 (2.3) mg.1-1] but rose to a peak of 17.0 (3.9) mg.1-1 1 day post-exercise, thereafter declining to basal levels. Serum levels of iron and zinc fell below pre-exercise levels for 1-3 days post-exercise. Serum albumin, IgG and IgM fell below pre-exercise levels from 1 day post-exercise, reaching minimal values (about 80% of basal levels) at 7 days post-exercise. The exercise did not appear to significantly affect serum levels of alpha-1-antitrypsin and alpha-1-acid glycoprotein. Two and three days after the exercise bout the circulating numbers of total leucocytes, neutrophils, monocytes and basophils fell 15-20% below pre-exercise levels, whereas lymphocytes, eosinophils and platelets were unchanged. The results indicate that a rapid acute phase inflammatory response is initiated within 1 day of a bout of exercise that induces delayed-onset muscle soreness, and that any later tissue necrosis that may occur is not accompanied by further marked changes in acute-phase reactants such as CRP.
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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.
Short-term changes in the blood leucocyte count after exercise are known to be dependent on the intensity of exercise performed. The aim of the present study was to investigate the effects of the duration of high-intensity exercise on changes in the leucocyte and platelet count during the early recovery period. On separate occasions following a standard warm-up, eight healthy subjects (six males, two females) ran at a constant speed of 5.6 m s-1 (20 km h-1) on a level treadmill for 30, 60, 90, 120 or 150 s or to fatigue. Heart rates were increased to near maximal levels within 30 s of exercise. Significant increases in the blood leucocyte count occurred after all exercise durations compared with baseline (pre-exercise) levels. Running for 30 s increased the blood leucocyte count by 35 +/- 10% (x +/- S.D.). Running for 60 s increased the blood leucocyte count by 57 +/- 16%, but running for longer durations did not produce any further significant increase in the immediately post-exercise blood leucocyte count. After exercise to exhaustion, the leucocyte count had increased by 63 +/- 17%. This was mainly due to an increase of lymphocytes (114 +/- 20%) rather than neutrophils (34 +/- 7%). At exhaustion, plasma volume had decreased by 15.9 +/- 2.6% compared with pre-exercise. During 5 min of recovery from exercise, the leucocyte count fell significantly (after 30 and 60 s of running), remained unchanged (90 and 120 s) or increased significantly (150 s and fatigue) compared with immediately post-exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Eccentric muscle actions are known to induce delayed-onset muscle soreness (DOMS) and muscle weakness (reduced static strength and dynamic peak power output) that may persist for several days. The aim of the present study was to determine whether DOMS-inducing exercise affects physiological responses to subsequent submaximal dynamic exercise. Physiological and metabolic responses to a standardized exercise task were measured 2 days after the performance of an eccentric or concentric exercise bout. Six healthy, untrained male subjects aged 30 +/- 7 years (mean +/- S.D.) performed repeated eccentric contractions during 30 min of bench stepping (47-cm step, 15 steps min-1). On another occasion, they performed concentric contractions by walking uphill (8% incline) for 30 min at 5 km h-1, which elicited a similar heart rate response to bench stepping. Two days after the eccentric or concentric exercise, the subjects cycled for 15 min on an electrically braked cycle ergometer at a work rate (172 +/- 37 W) equivalent to 80% VO2 max. The order of the preceding treatments was randomized and the treatments were carried out 2 weeks apart. Two days after the eccentric exercise, all subjects reported leg muscle soreness and exhibited elevated levels of serum creatine kinase activity (P < 0.01) and plasma cortisol concentration (P < 0.05). After uphill walking, the subjects were not sore and serum creatine kinase activity was unchanged. Minute volume, breathing frequency, respiratory exchange ratio, heart rate, rating of perceived exertion, venous blood lactate concentration and plasma cortisol concentration were all higher (P < 0.05) during cycling after eccentric exercise compared with after uphill walking. Increases in plasma catecholamine concentrations and numbers of circulating leucocytes after cycling at 80% VO2 max for 15 min were similar under both experimental conditions, but the delayed leucocytosis (at 150 min post-exercise) was significantly greater (P < 0.01) for the post-eccentric exercise condition. We conclude that dynamic submaximal exercise performed 2 days following exercise with a large eccentric component produces physiological responses that are indicative of a higher relative exercise stress. It is likely that such effects will significantly limit the level and duration of exercise that can be achieved in subsequent training bouts over several days.
The impact of long-term training on systemic and mucosal immunity was assessed prospectively in a cohort of elite swimmers over a 7-month training season in preparation for national championships. The results indicated significant suppression (P < 0.05) of serum IgA, IgG and IgM and salivary IgA concentration in athletes associated with long-term training at an intensive level. There was also a trend towards lower IgG2 subclass levels in serum in athletes compared with controls (P = 0.07). There were no significant changes in numbers or percentages of B or T cell subsets, but there was a significant fall in natural killer (NK) cell numbers and percentages in athletes over the training season (P < 0.05). After individual training sessions there was a significant decrease in salivary IgA levels for athletes compared with controls (P = 0.002). In athletes there was a downward trend in salivary IgA levels over the 7-month training period in both the pre-exercise (P = 0.06) and post-exercise samples (P = 0.04). There were no significant trends in salivary IgG levels over the study period in either athletes or controls. The only significant change in salivary IgM levels was an increase in detection rate in the pre-competition phase in athletes (P = 0.03). The study suggests that training of elite athletes at an intensive level over both short- and long-time frames suppresses both systemic and mucosal immunity. Protracted immune suppression linked with prolonged training may determine susceptibility to infection, particularly at times of major competitions.