Biomedical subjects

R L Clancy

Publications and source records attributed to R L Clancy.

At least 19 recordsLinked to original sources

PubMed2006

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

BACKGROUND: Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. OBJECTIVE: To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. RESULTS: The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) gamma from blood CD4 positive T cells. After one month of daily capsules containing 2 x 10(10) colony forming units of L acidophilus, secretion of IFNgamma from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNgamma concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNgamma concentration. CONCLUSION: This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.

Adolescent↗

PubMed2004

In-vivo cell mediated immunity in elite swimmers in response to training.

This study investigated in-vivo cell-mediated immune (CMI) responses in elite swimmers over a 5-month training season, to assess the impact of intense training on changes in T-lymphocyte function. The CMI Multitest was performed early in the season after a period of rest, during peak high-intensity training, and late in the season during the precompetition taper period. The CMI tests were performed at rest prior to a morning training session. There were no significant differences between the swimmers and a control group for any of the seven CMI antigen responses at any of the test points during the season. In the swimmers, there were no significant differences in the number of positive responses to the CMI antigens between the three test points (Friedman's test = 9.6364, p = 0.47) and no significant differences for the CMI cumulative scores (Friedman's test = 11.98, p = 0.29) at each test point. There was no consistent pattern for changes in CMI cumulative scores for individual swimmers over the training season. The findings of this study indicate that, despite reported transient T-lymphocyte immunosuppression immediately after intense exercise, probably associated with acute redistribution and temporary pooling of blood T cell subsets in extremities, the T-lymphocyte function involved in CMI responses is not compromised by extended periods of training at an elite level.

Adult↗

PubMed2004

Clinical investigation of athletes with persistent fatigue and/or recurrent infections.

OBJECTIVE: To investigate whether underlying medical conditions contribute to the fatigue and high incidence of infections that can occur during repeated intense training. METHOD: Forty one competitive athletes (22 male, 19 female) with persistent fatigue and/or recurrent infections associated with performance decrements had a thorough medical examination and a series of clinical investigations to identify potential medical causes. RESULTS: Conditions with the potential to cause fatigue and/or recurrent infections were identified in 68% of the athletes. The most common were partial humoral immune deficiency (28%) and unresolved viral infections (27%). Non-fasting hypoglycaemia was common (28%). Other conditions included allergic disease (15%), new or poorly controlled asthma (13%), upper airway dysfunction (5%), sleep disorders (15%), iron depletion (3%), and one case of a thyroid disorder. A positive antinuclear antibody was detected in 21% of the athletes, without any clinical evidence of autoimmune disorders. Evidence of Epstein-Barr virus reactivation was detected in 22% of the athletes tested. CONCLUSIONS: Athletes with recurrent infections, fatigue, and associated poor performance may benefit from a thorough investigation of potentially reversible underlying medical conditions, especially when these conditions cause disruption to training and competition. Unresolved viral infections are not routinely assessed in elite athletes, but it may be worth considering in those experiencing fatigue and performing poorly.

Adolescent↗

PubMed2003

Helicobacter pylori infection in the Australian community: current prevalence and lack of association with ABO blood groups.

AIMS: To assess the current prevalence of Helicobacter pylori infection in an Australian urban population sample and to relate this to age, gender and ABO and Rhesus blood groups. METHODS: We performed a prospective epidemiological survey of H. pylori serological status in 500 consecutive voluntary blood donors who presented for the purpose of blood donation at the central -Melbourne branch of the Australian Red Cross Blood Service, Victoria, Australia, and gave a Melbourne suburban home address. RESULTS: The overall prevalence of specific anti-H. pylori IgG antibodies in this cohort was 32% (95% confidence interval = 28-36%) and H. pylori sero-positivity increased with age. The rate of H. pylori infection was not significantly different in men and women, with anti-H. pylori IgG anti-bodies detected in 35% (97/277) of men compared with 28% (63/233) of women (P = 0.12). Similarly, H. pylori serological status was not significantly different between subjects of different ABO (P = 0.18) or Rhesus blood groups (P = 0.55). CONCLUSION: This study showed that, contrary to expectation, the updated prevalence of H. pylori seropositivity (32%) in this Melbourne sample is at least as high as that found in previous Australian studies over the past 19 years. Seropositivity increased with age, and was not related to gender, confirming the infection pattern seen in other developed nations. Despite epidemiological evidence of increased peptic ulcer disease in ABO blood group O subjects, and recent evidence that H. pylori adhesion to gastric epithelial cells is mediated by blood group epitopes, no significant association between blood groups and H. pylori serological status was detected.

ABO Blood-Group System↗

PubMed2002

Primary role for CD4(+) T lymphocytes in recovery from oropharyngeal candidiasis.

Oropharyngeal candidiasis is associated with defects in cell-mediated immunity and is commonly seen in human immunodeficiency virus positive individuals and AIDS patients. A model for oral candidiasis in T-cell-deficient BALB/c and CBA/CaH nu/nu mice was established. After inoculation with 10(8) Candida albicans yeasts, these mice displayed increased levels of oral colonization compared to euthymic control mice and developed a chronic oropharyngeal infection. Histopathological examination of nu/nu oral tissues revealed extensive hyphae penetrating the epithelium, with polymorphonuclear leukocyte microabscess formation. Adoptive transfer of either naive or immune lymphocytes into immunodeficient mice resulted in the recovery of these animals from the oral infection. Reconstitution of immunodeficient mice with naive CD4(+) but not CD8(+) T cells significantly decreased oral colonization compared to controls. Interleukin-12 and gamma interferon were detected in the draining lymph nodes of immunodeficient mice following reconstitution with naive lymphocytes. This study demonstrates the direct requirement for T lymphocytes in recovery from oral candidiasis and suggests that this is associated with the production of cytokines by CD4(+) T helper cells.

Adoptive Transfer↗

PubMed2001

Irradiation-induced oral candidiasis in an experimental murine model.

The aim of this experiment was to establish a mouse model of irradiation-induced oral candidiasis and to explore the cellular populations and mechanisms by which the infection is cleared from the oral mucosa. BALB/c mice received irradiation to the head and neck equivalent to 800 Rad using a Cobalt 60 gamma source. Both irradiated and non-irradiated mice were infected orally with 1 x 10(8) Candida albicans yeasts. Compared with untreated controls, irradiated animals developed a more severe infection of longer duration, with hyphae penetrating the oral mucosa. Monoclonal antibody depletion of CD4+ but not CD8+ T cells from the systemic circulation prolonged the infection in irradiated mice, but not in controls. Supernatants of submandibular and superficial cervical lymph node cultures from irradiated animals demonstrated significantly higher titers of interleukin-12, but similar levels of interferon-gamma compared with controls. Screening for cytokine production by an RNase protection assay detected only macrophage migration inhibition factor in irradiated and non-irradiated oral tissues from day 8 onwards. The results of this study demonstrate a requirement for CD4+ T cells in the recovery from oral candidiasis induced by head and neck irradiation in mice, and are consistent with a role for Th1-type cytokines in host resistance.

Analysis of Variance↗

PubMed2001

Is there another chapter in the Helicobacter pylori/peptic ulcer disease story?

The role of Helicobacter pylori in the production of mucosal damage has largely been considered within a simple infection paradigm, because to date eradication has appeared to be a predictable outcome of antibiotic therapy. Changes in the epidemiology and management of peptic ulcer disease, however, require a more comprehensive framework to understand these shifting clinical patterns. The present review examines mucosal damage as an outcome of a complicated host-parasite relationship, with alterations in both parasite physiology and host defence mechanisms being keys to understanding disease patterns.

Anti-Bacterial Agents↗

PubMed2001

Effects of hypoxia on diaphragm activity in anesthetized rats.

Hypoxia is one of the most common conditions observed by PACU nurses after surgery. It may be caused by a reduced functional residual capacity, hypoventilation, and/or ventilation-perfusion mismatch. Hypoxia can also affect diaphragm contractility, making it difficult to wean postoperative patients from mechanical ventilation. Clinically, however, there is no method to directly measure diaphragm contractility; therefore, indicators of intrathoracic pressure such as tidal volume are used. The purpose of this study was to directly measure the effects of diaphragm shortening in 12 anesthetized Sprague-Dawley rats before, during, and after induced hypoxia. A miniaturized ultrasonic sensor was used to measure changes in diaphragm thickness as an index of diaphragm shortening. A stainless steel electrode was attached adjacent to the ultrasonic sensor and used to measure the electromyogram (EMG) of the diaphragm. After normoxic measurements were recorded, hypoxia was initiated by connecting the tracheal cannula to a latex balloon containing 7.4% oxygen in nitrogen. During the first 5 minutes of hypoxia, diaphragm shortening, EMG, and intrathoracic pressure increased. Over the next 30 to 100 minutes, EMG and intrathoracic pressure remained elevated, whereas diaphragm shortening decreased to 50% of control, which was defined as diaphragm fatigue. The mean time for hypoxia-induced diaphragm fatigue to occur was 63 minutes. These results indicate that hypoxia-induced decline in diaphragm shortening was not caused by a decrease in muscle excitation as measured by EMG. These data suggest that impairment in mechanical-chemical coupling (diaphragm shortening) could be a result of decreased oxygen availability associated with the lower arterial blood oxygen content. Thus, the increase in intrathoracic pressure throughout hypoxia suggests that intrathoracic pressure is not always a consistent index of the contractile state of the diaphragm.

Analysis of Variance↗

PubMed2001

Redistribution of pulmonary blood flow during hypoxic exercise.

Pulmonary blood flow (PBF) distribution was studied at rest and during exercise in rats acclimatized to chronic hypoxia (barometric pressure [PB] 370 Torr for 3 weeks, A rats) and non-acclimatized (NA) littermates. Both A and NA rats exercised in hypoxia (inspired O2 pressure [PIO2] approximately 70 Torr) or in normoxia (PlO2 approximately 145 Torr). PBF distribution was determined using fluorescent-labeled microspheres injected into the right atrium. The lungs were cut into 28 samples to determine relative scatter of specific PBF ([sample fluorescence intensity/sample dry weight)/(total lung fluorescence intensity/total lung dry weight]). Exercise produced redistribution of PBF both in NA and A rats, and this effect was larger in hypoxia than in normoxia, with minimal redistribution occurring during normoxic exercise in NA rats. The pattern of distribution varies considerably among individual animals. As a result of distribution, the previous high flow areas would be overperfused during hypoxic exercise in some rats. The results support the concept that hypoxic pulmonary vasoconstriction is not uniform and suggest that the combination of hypoxia and exercise may lead to overperfusion and capillary leak in some individuals.

Acclimatization↗

PubMed2001

Mucosal immunity, respiratory illness, and competitive performance in elite swimmers.

PURPOSE: Exercise and training are known to elicit changes in mucosal humoral immunity, but whether these alterations have any impact on competitive performance remains unclear. This investigation examined relationships between salivary immunoglobulin (Ig) concentration, the incidence of respiratory tract illness (RTI), and competitive performance in elite swimmers. METHODS: Forty-one members of the Australian Swimming Team (21 males and 20 females) aged 15-27 yr were monitored during preparations for the 1998 Commonwealth Games. Twenty-five coaches and staff (19 males and 6 females) aged 32-65 yr, serving as "environmental controls," were also monitored. Salivary IgA, IgM, and IgG and albumin concentration (mg.L-1) were measured in both groups in May 1998 and again in August 1998, 17 d before competition. Subjects were categorized as "ill" (at least one RTI) or "healthy". RESULTS: There were no significant changes in salivary IgA, IgM, or IgG concentration in the swimmers between May and August, nor were there any differences between healthy (N = 23) and ill (N = 18) swimmers. There was a significant positive relationship between IgM and performance in the male swimmers (r = 0.85, P < 0.001) but not for any other parameter. There was no significant difference in performance between ill and healthy swimmers (P = 0.11). Gold medal winners (N = 9) had higher IgM levels than other swimmers (N = 32) in May (P = 0.02) and higher IgG in August (P = 0.02). CONCLUSION: These data indicate that a season of training by elite swimmers did not alter salivary immunoglobulin concentrations, and the presence of RTI had no significant impact on competitive performance.

Adolescent↗

PubMed2001

T cells augment monocyte and neutrophil function in host resistance against oropharyngeal candidiasis.

The purpose of this study was to identify the cell populations involved in recovery from oral infections with Candida albicans. Monoclonal antibodies specific for CD4+ cells, CD8+ cells, and polymorphonuclear leukocytes were used to deplete BALB/c and CBA/CaH mice of the relevant cell populations in systemic circulation. Monocytes were inactivated with the cytotoxic chemical carrageenan. Mice were infected with 10(8) C. albicans yeast cells and monitored for 21 days. Systemic depletion of CD4+ and CD8+ T lymphocytes alone did not increase the severity of oral infection compared to that of controls. Oral colonization persisted in animals treated with head and neck irradiation and depleted of CD4+ T cells, whereas infections in animals that received head and neck irradiation alone or irradiation and anti-CD8 antibody cleared the infection in a comparable fashion. The depletion of polymorphonuclear cells and the cytotoxic inactivation of mononuclear phagocytes significantly increased the severity of oral infection in both BALB/c and CBA/CaH mice. High levels of interleukin 12 (IL-12) and gamma interferon (IFN-gamma) were produced by lymphocytes from the draining lymph nodes of recovering animals, whereas IL-6, tumor necrosis factor alpha, and IFN-gamma were detected in the oral mucosae of both naïve and infected mice. The results indicate that recovery from oropharyngeal candidiasis in this model is dependent on CD4+-T-cell augmentation of monocyte and neutrophil functions exerted by Th1-type cytokines such as IL-12 and IFN-gamma.

Animals↗

PubMed2001

Living and training in moderate hypoxia does not improve VO2 max more than living and training in normoxia.

The objective of these experiments was to determine whether living and training in moderate hypoxia (MHx) confers an advantage on maximal normoxic exercise capacity compared with living and training in normoxia. Rats were acclimatized to and trained in MHx [inspired PO2 (PI(O2)) = 110 Torr] for 10 wk (HTH). Rats living in normoxia trained under normoxic conditions (NTN) at the same absolute work rate: 30 m/min on a 10 degrees incline, 1 h/day, 5 days/wk. At the end of training, rats exercised maximally in normoxia. Training increased maximal O2 consumption (VO2 max) in NTN and HTH above normoxic (NS) and hypoxic (HS) sedentary controls. However, VO2 max and O2 transport variables were not significantly different between NTN and HTH: VO2 max 86.6 +/- 1.5 vs. 86.8 +/- 1.1 ml x min(-1) x kg(-1); maximal cardiac output 456 +/- 7 vs. 443 +/- 12 ml x min(-1) x kg(-1); tissue blood O2 delivery (cardiac output x arterial O2 content) 95 +/- 2 vs. 96 +/- 2 ml x min(-1) x kg(-1); and O2 extraction ratio (arteriovenous O2 content difference/arterial O2 content) 0.91 +/- 0.01 vs. 0.90 +/- 0.01. Mean pulmonary arterial pressure (Ppa, mmHg) was significantly higher in HS vs. NS (P < 0.05) at rest (24.5 +/- 0.8 vs. 18.1 +/- 0.8) and during maximal exercise (32.0 +/- 0.9 vs. 23.8 +/- 0.6). Training in MHx significantly attenuated the degree of pulmonary hypertension, with Ppa being significantly lower at rest (19.3 +/- 0.8) and during maximal exercise (29.2 +/- 0.5) in HTH vs. HS. These data indicate that, despite maintaining equal absolute training intensity levels, acclimatization to and training in MHx does not confer significant advantages over normoxic training. On the other hand, the pulmonary hypertension associated with acclimatization to hypoxia is reduced with hypoxic exercise training.

Altitude↗

PubMed2001

Exercise training alters the effect of chronic hypoxia on myocardial adrenergic and muscarinic receptor number.

Chronic hypoxic exposure results in elevated sympathetic activity leading to downregulation of myocardial alpha(1)- and beta-adrenoceptors (alpha(1)-AR, beta-AR). On the other hand, it has been shown that sympathetic activity is reduced by exercise training. The objective of this study was to determine whether exercise training could modify the changes in receptor expression associated with acclimatization. Four groups of rats were studied: normoxic sedentary rats (NS), rats living and training in normoxia (NTN), sedentary rats living in hypoxia (HS, inspired PO(2) = 110 Torr), and rats living and training in hypoxia (HTH, inspired PO(2) = 110 Torr). Training consisted of running in a treadmill at 80% of maximal O(2) uptake during 10 wk. Myocardial receptor density was measured by radioactive ligand binding. Right ventricular (RV) hypertrophy occurred in HS but not in HTH. No effect of exercise was detected in RV weight of normoxic rats. Acclimatization to hypoxia (HS vs. NS) resulted in a decrease in both alpha(1)- and beta-AR density, whereas muscarinic receptor (M-Ach) expression increased. Hypoxic exercise training (HS vs. HTH) moderated beta-AR downregulation and M-Ach upregulation and prevented the fall in alpha(1)-AR density. Normoxic training (NS vs. NTN) did not change beta-AR density. On the other hand, densities of alpha(1)-AR in both ventricles as well as RV M-Ach increased in NTN vs. NS. The data show that exercise training in hypoxia 1) prevents RV hypertrophy, 2) suppresses the downregulation of alpha(1)-AR in the left ventricle (LV) and RV, and 3) attenuates the changes in both beta-AR and M-Ach receptor density in LV and RV. Exercise training in normoxia increases M-Ach receptor expression in the RV.

Animals↗

PubMed2000

Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus.

The effect of a fish oil diet on virus-specific cytotoxicity and lymphocyte proliferation was investigated. Mice were fed fish oil (17 g fish oil and 3 g sunflower/100 g) or beef tallow (17 g tallow and 3 g sunflower/100 g) diets for 14 days before intranasal challenge with influenza virus. At day 5 after infection, lung virus-specific T lymphocyte, but not macrophage or natural killer (NK) cell, cytotoxicity was significantly lower in mice fed fish oil, while bronchial lymph node cell proliferation to virus was significantly higher. In mice fed fish oil, spleen cell proliferation to virus was also significantly higher following immunization. The results showed that, despite improved lymphocyte proliferation, fish oil impairs primary virus-specific T lymphocyte cytotoxicity. This impairment may explain the delayed virus clearance that we have previously reported in infected mice fed the fish oil diet.

Animals↗

PubMed2000

Effects of pressure support ventilation and continuous positive airway pressure on diaphragm performance.

Many patients who are on mechanical ventilation are on ventilator modes called pressure support ventilation (PSV) and continuous positive airway pressure (CPAP) particularly when they are being weaned. As the diaphragm is responsible for approximately 75% of breathing, it is important to promote diaphragm shortening to optimize weaning from mechanical ventilation. The purpose of our 1998 quasi-experimental study was to explore the effects of PSV and CPVP on diaphragm shortening. An animal model was utilized using four Sprague-Dawley rats from the same litter purchased from Sasco (Kansas City, USA). Also measured in this study were intrathoracic pressure (DeltaITP), positive inspiratory pressure, respiratory rate, tidal volume, end-tidal carbon dioxide, central venous pressure (CVP) and mean arterial pressure (MAP). Pressure support was increased in increments of 5 cm H2O at CPAP levels of 0, 2 and 4 cm H2O. A direct assessment of diaphragm shortening was achieved through the adherence of a miniaturized ultrasonic sensor to the inferior surface of the middle costal surface of the right hemidiaphragm of four Sprague-Dawley rats. Limitations of this study included a small sample size, anaesthetized rats and abdominal dissection for insertion of the ultrasonic sensor. As PSV was increased, there was a decrease in MAP, CVP, respiratory rate and end-tidal CO2. When increasing levels of CPAP were added to PSV, a decrease in diaphragm shortening was observed. These results support that higher levels CPAP may hinder diaphragmatic function thus prolong mechanical ventilation. The purpose of this pilot study was to explore the effects of PSV and CPAP on diaphragm shortening. Also measured were DeltaITP, positive inspiratory pressure, respiratory rate, tidal volume, end-tidal carbon dioxide, CVP and MAP. Pressure support was increased in increments of 5 cm H2O at CPAP levels of 0, 2 and 4 cm H2O. A direct assessment of diaphragm shortening was achieved through the adherence of a miniaturized ultrasonic sensor to the inferior surface of the middle costal surface of the right hemidiaphragm of four Sprague-Dawley rats. Limitations of this study included a small sample size, anaesthetized rats and abdominal dissection for insertion of the ultrasonic sensor. As PSV was increased, there was a decrease in MAP, CVP, respiratory rate and end-tidal CO2. When increasing levels of CPAP were added to PSV, a decrease in diaphragm shortening was observed.

Animals↗

PubMed2000

One year in Antarctica: mucosal immunity at three Australian stations.

The effect of a year's isolation in Antarctica on the human mucosal immune system was assessed during the winter of 1992 at three Australian Antarctic stations: Casey, Davis and Mawson. Saliva samples were collected from each expeditioner prior to their departure from Australia and during each month in Antarctica. The concentrations of salivary immunoglobulins IgA and IgG were significantly different between the three stations, but there were no differences for salivary IgM and albumin. The mean concentrations of IgA were higher at Mawson (P < 0.008), and the mean concentrations of IgG were lower at Davis (P < 0.001) compared with the other stations. Ranges of values observed at the stations over the 12-13 months were similar. The variability of values within individuals showed station differences for salivary IgM and IgG only. The study revealed significant changes in salivary immunoglobulin values over the period in Antarctica, with similar patterns at the three Australian stations. The salivary IgA and IgM levels were lower in the first 4 months in Antarctica (January-April) and increased to maximum values in July-August, before returning to mean levels when isolation was broken in October-November. The patterns of salivary IgA and IgM suggest that stressors due to isolation may play a role in alterations of mucosal immunity in expeditioners in Antarctica.

Adult↗

PubMed2000

Effects of positive end-expiratory pressure on diaphragm function.

Patients admitted to the PACU after surgery may require mechanical ventilation. Knowledge about the anatomy and physiology of the diaphragm and its association with ventilator modes may be helpful in the management of this patient. As the acuity of PACU patients increase, more patients may also be on higher levels of positive end-expiratory pressure (PEEP), requiring PACU nurses to understand the relationship between PEEP and diaphragm function to facilitate weaning. This article provides a review of the mechanical ventilation mode of PEEP and its relationship to diaphragmatic performance. The physiological effects associated with the use of PEEP are also reviewed.

Diaphragm↗

PubMed2000

Training strategies to maintain immunocompetence in athletes.

Clinical experience and empirical evidence have led to the modeling of exercise and training as a form of stress on the immune system. Coaches, athletes, and medical personnel are seeking guidelines on ways to reduce the risk of illness that compromises training or competitive performance. The immune system is influenced by a wide range of physical, environmental, psychological, and behavioural factors which, combined with clinical assessment, collectively form the basis of the following intervention strategies: 1) training: careful management of training volume and intensity, variety to overcome training monotony and strain, a periodised approach to increasing loads, and provision of adequate rest and recovery periods; 2) environmental: limiting initial exposure when training or competing in adverse environmental conditions (heat, humidity, altitude, air pollution) and acclimatising where appropriate; 3) psychological: teaching athletes self-management and coping skills and monitoring of athletes' responses to the psychological and psychosocial stresses of high-level training and competition; 4) behavioural: adopting a well-balanced diet with adequate intake of macro- and micro-nutrients, limiting transmission of contagious illnesses by reducing exposure to common infections, airborne pathogens, and physical contact with infected individuals; and 5) clinical considerations: medical screening, pathology testing, immunization and prophylaxis, and routine management of illness-prone athletes. Future experimental studies are required to develop and enhance the effectiveness of these strategies in reducing illness in athletes.

Australia↗