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Biomedical subjects

R L Clancy

Publications and source records attributed to R L Clancy.

At least 37 records · Page 2Linked to original sources
PubMed2000

Immune status and respiratory illness for elite swimmers during a 12-week training cycle.

The impact of a 12-week training program by elite swimmers on systemic and mucosal immunity was studied prospectively to examine the relationship between changes in immune parameters and the incidence of respiratory illness. Saliva was collected before and after selected training sessions at 2 weekly intervals. There were significant decreases in salivary IgA (p=0.05) and salivary IgM (p < 0.0001) concentrations after individual training sessions, but no significant changes in salivary IgG or albumin concentrations. Over the 12-week training program there were small but statistically significant increases in pre-exercise concentrations of salivary IgA (p<0.001), IgM (p=0.015) and IgG (p=0.003) and post-exercise salivary IgA (p <0.001). There were no significant trends over the 12 weeks for any class of serum immunoglobulins but a significant fall in NK-cell numbers (p<0.001). There were no associations between serum or salivary immunoglobulin levels or NK-cell numbers and upper respiratory tract illness (URTI) during the 12-week program. The data indicated that despite changes in some immune parameters during this final training program prior to competition there were no associations detected with URTI for this cohort of elite swimmers.

Adolescent↗
PubMed2000

Effects of CH-100, a chinese herbal medicine, on acute concanavalin A-mediated hepatitis in control and alcohol-fed rats.

BACKGROUND: Administration of concanavalin A (Con A) leads to acute hepatitis that involves T-cell activation and inflammatory mediator production in mice and rats. We examined the role of CH-100, a Chinese herbal medicine previously trialed in human hepatitis C, in the prevention of Con A-related, T-cell-mediated, acute liver injury in rats. METHODS: Female Wistar rats were fed 40% ethanol, 2% sucrose, or isocaloric sucrose for 8 weeks. At the same time, these animals were fed either the Chinese herbal medicine CH-100 (4 tablets/kg body weight/ day) or placebo in chow daily. Blood from the tail vein was collected for endotoxin (lipopolysaccharide) assay at 0, 4, and 8 weeks of ethanol consumption. Twenty-four hours after injection of Con A (20 mg/kg body weight) or phosphate-buffered saline, blood from the tail vein was collected for alanine aminotransferase and tumor necrosis factor (TNF)-alpha assays. Liver-associated CD4+ T cells were isolated from liver perfusates and then cultured with Con A (5 microg/ml) at 37 degrees C for 24 hr. Supernatants were harvested for TNF-alpha assay. The proportion of CD4+ T cells in blood and liver perfusates was measured. Liver samples were collected for histopathological analysis. RESULTS: Lipopolysaccharide levels were significantly reduced in CH-100-treated ethanol-fed rats compared with placebo-treated rats. After Con A injection, alanine aminotransferase levels were lower at 12 and 24 hr in herb-treated rats compared with placebo-treated rats. Furthermore, serum TNF-alpha levels were lower in ethanol-fed rats on herbal treatment. A significant decrease in TNF-alpha production by liver-associated CD4+ T cells in culture was observed in CH-100-treated ethanol-fed rats. CH-100 treatment was associated with a decreased percentage of CD4+ cells in both blood and liver perfusate in all groups. Herb-treated rats displayed markedly less hepatic necrosis and a reduced CD4+ T-cell infiltrate in portal areas than did placebo-fed rats. CONCLUSIONS: The results demonstrate that CH-100 modified the T-cell response to Con A injection. The effect was more marked in ethanol-fed rats, which suggests a possible role for CH-100 in treating alcoholic liver disease.

Alanine Transaminase↗
PubMed2000

The measurement of IgA and IgG transglutaminase antibodies in celiac disease: a comparison with current diagnostic methods.

Celiac disease (CD) is an inflammatory disorder of the small intestine induced by cereal prolamins. The demonstration of IgA endomysial antibodies (EMA) is currently the most reliable serological screen for CD. The antigenic target is transglutaminase. The aim of this study was to develop an ELISA assay for the detection of antibodies to transglutaminase (TGA), and to assess the sensitivity and specificity of TGA for the detection of celiac disease against the benchmarks of jejunal biopsy, antigliadin antibodies (AGA) and EMA. Sera from 57 patients with celiac disease were tested for IgA and IgG TGA, IgA EMA, IgA and IgG AGA, and the total IgA level. The sensitivity, specificity, predictive value and concordance of AGA, EMA and TGA were assessed against the gold-standard biopsy result. IgG plus IgA TGA offered 100% sensitivity in CD patients for whom no dietary intervention had been commenced, with a specificity of 61%. The sensitivity of TGA dropped from 100 to 79% after dietary restriction. In patients on no gluten restriction, there was 100% agreement between TGA and EMA, and 100% agreement between TGA and AGA for the IgA isotype. The false-positive rate for TGA was 53% in Down's syndrome patients and 25% in patients with systemic autoimmune disorders. We conclude that testing for TGA is a reliable diagnostic serology for celiac disease, with improved sensitivity compared with established methods. The results suggest that serial TGA measurements may be a more and accurate marker for dietary compliance than AGA, but prospective studies are required.

Autoantibodies↗
PubMed2000

Efficacy and safety of prone positioning for patients with acute respiratory distress syndrome.

This article presents an overview of a literature review on how prone positioning can alleviate pathophysiological changes in ARDS and improve ventilation and perfusion. Improvement of gas exchange, efficiency of oxygenation and lung function are emphasized. Literature on the pathophysiology of ARDS, and the physiological effects of prone positioning on haemodynamics and lung function is examined. There are both advantages and disadvantages in turning a patient from the supine to the prone position. There are also contraindications in rotating between the supine and prone positions. Nevertheless, by rotating patients with ARDS, it is possible to achieve a significant improvement in A-aDO2, decrease shunting, and therefore improve oxygenation without use of expensive, invasive and experimental procedures. Placing patients with ARDS in the prone position can reduce inspiratory oxygen concentrations and peak inspiratory pressures, which minimizes the chance for barotrauma and the iatrogenic effects of hyperventilation oxygen toxicity.

Blood Gas Analysis↗
PubMed1999

Increased severity of Candida vaginitis in BALB/c nu/nu mice versus the parent strain is not abrogated by adoptive transfer of T cell enriched lymphocytes.

The role of the host immune system in combating candidal infections in the vagina is poorly understood. A murine model of Candida vaginitis was used to elucidate the role of T cells in a candidal infection. Athymic BALB/c nu/nu mice or normal BALB/c mice were induced into estrus and then infected with 1 x 10(6) Candida albicans intravaginally. The infection was monitored over 1 week. Samples from blood, small intestine, tongue, kidney, spleen, liver, uterus and vagina were tested for recoverable C. albicans. Histology of the vagina was assessed for both inflammation and extent of infection. Results indicated that the BALB/c nu/nu mice had similar levels of vaginal yeast load to the normal BALB/c mice. In 25-30% of nude mice Candida was also recovered from extra vaginal sites (kidney, liver, small intestine), however, extra vaginal dissemination was not observed in any normal BALB/c animals. Histologically, both the nu/nu and control BALB/c had similar levels of vaginal inflammation; however, the nu/nu mice had more florid fungal growth in the vaginal epithelium. Adoptive transfer of either immune or non-immune BALB/c T cells into nude mice had no affect on either infection or vaginal inflammation. Immunohistochemical staining of vaginal tissues from normal BALB/c mice or nude mice adoptively transferred with either immune or non-immune T cells with anti-CD3 monoclonal antibody revealed no significant difference between groups in the numbers of CD3+ vaginal T cells. However, in mice receiving either immune or non-immune T cells no yeast was recovered from any tissues except the vagina. These data show that T cells have a limited role in protecting the vagina from C. albicans infection.

Animals↗
PubMed1999

Salivary IgA subclasses and infection risk in elite swimmers.

The concentrations of total IgA, IgA1 and IgA2 were measured in saliva collected from 25 elite swimmers in the early and late phases of a 7 month training season and compared with the number of respiratory infections during the season. The IgA1 concentrations in the early phase of the training season were significantly associated (P = 0.01) with the number of respiratory infection episodes during the training season. The lower the concentration of IgA1, the greater the number of infection episodes. Swimmers with four or more infections during the training season had significantly lower salivary IgA1 concentrations than those with less than four infection episodes (P = 0.01). The proportion of IgA1 in the saliva of the elite swimmers (80%) was higher than for normal non-exercising adults (60%). A small proportion of athletes had salivary IgA2 concentrations below the detection limit of the assay and the mean concentration of IgA2 was significantly lower than the concentrations for a normal adult population (P = 0.01). This study suggests that measurement of IgA subclasses, in particular IgA1, at the commencement of a training season may predict infection risk in elite swimmers.

Adolescent↗
PubMed1999

Fish oil feeding delays influenza virus clearance and impairs production of interferon-gamma and virus-specific immunoglobulin A in the lungs of mice.

Ingestion of fish oil can suppress the inflammatory response to injury and may impair host resistance to infection. To investigate the effect of a diet containing fish oil on immunity to viral infection, 148 BALB/c mice were fed diets containing 3 g/100 g of sunflower oil with either 17 g/100 g of fish oil or beef tallow for 14 d before intranasal challenge with live influenza virus. At d 1 and d 5 after infection, the mice fed fish oil had higher lung viral load and lower body weight (P < 0.05). In addition to the greater viral load and weight loss at d 5 after infection, the fish oil group consumed less food (P < 0.05) while the beef tallow group was clearing the virus, had regained their preinfection weights and was returning to their preinfection food consumption. The fish oil group had impaired production of lung interferon-gamma (IFN-gamma), serum immunoglobulin (Ig) G and lung IgA-specific antibodies (all P < 0. 05) although lung IFN-alpha/beta and the relative proportions of bronchial lymph node CD4+ and CD8+ T lymphocytes did not differ between groups after infection. The present study demonstrates a delay in virus clearance in mice fed fish oil associated with reduced IFN-gamma and antibody production and a greater weight loss and suppression of appetite following influenza virus infection. However, differences observed during the course of infection did not affect the ultimate outcome as both groups cleared the virus and returned to preinfection food consumption and body weight by d 7.

Animals↗
PubMed1999

Helicobacter pylori infection in intensive care: increased prevalence and a new nosocomial infection.

OBJECTIVE: The pathogenesis of acute gastric stress ulceration in the seriously ill is uncertain, and any role of Helicobacter pylori infection is unknown. We aimed to assess the relationship between H. pylori serological status and stress ulceration in seriously ill patients, as well as H. pylori serological status in intensive care nurses as a marker for nosocomial infection. DESIGN: Prospective epidemiologic survey. SETTING: Adult intensive care unit in a university teaching hospital. PATIENTS: One hundred patients, 100 nurses, and 500 blood donors as community controls. INTERVENTIONS: H. pylori serological status was measured in patients, staff, and controls using a rapid whole blood test. Upper gastrointestinal bleeding and risk factors for acute stress ulceration were recorded. MEASUREMENTS AND MAIN RESULTS: In seriously ill patients, H. pylori seropositivity (67%) was significantly higher than in the control group (39%) (p < .001). In patients, seropositivity was not related to age, country of birth, diagnostic category, severity of illness, or risk score for stress ulceration. There was a trend toward increased macroscopic gastric bleeding in seropositive patients. In intensive care nurses, H. pylori seropositivity (40%) was significantly higher than in age-matched controls (19%) (p < .001). Only duration of intensive care nursing was significantly associated with seropositivity (p = .02). CONCLUSIONS: The unexpectedly high H. pylori seropositivity rate in this seriously ill cohort raises the possibility that under intensive care conditions, H. pylori infection may modulate responses to illness and injury, with consequent clinical implications. Furthermore, the elevated seropositivity rate in intensive care nurses suggests that H. pylori can be nosocomially transmitted.

Adult↗
PubMed1999

Salivary IgA levels and infection risk in elite swimmers.

UNLABELLED: The effects of exercise on the immune system has been shown to be dependent on the level of fitness of the subjects, the degree of intensity, and the duration of the exercise. A reduction in salivary IgA levels occurs after individual sessions of exercise. PURPOSE: The purpose of this study was to assess the relationship between changes in salivary IgA and training volume, psychological stress, and infection rates in a cohort of 26 elite swimmers over a 7-month training period and to compare the changes with a group of 12 moderately exercising controls. METHODS: Salivary IgA concentrations were measured by an electroimmunodiffusion. Exercise gradings were assessed by a standardized aerobic-anaerobic rating system. Psychological stress/anxiety was evaluated by the Spielberger State-Trait Anxiety Inventory. Infections were physician-verified. RESULTS: Salivary IgA levels showed an inverse correlation with the number of infections in both elite swimmers and moderately exercising control subjects. The pretraining salivary IgA levels in swimmers were 4.1% lower for each additional month of training and 5.8% lower for each additional infection. The posttraining salivary IgA levels in swimmers were not significantly correlated with infection rates but were 8.5% lower for each additional 1 km swum in a training session and 7.0% lower for each additional month of training. The number of infections observed in the elite swimmers was predicted from regression models by the preseason (P = 0.05) and the mean pretraining salivary IgA levels (P = 0.006). The trends in pretraining salivary IgA levels over the 7-month season, calculated as individual slopes of pretraining IgA levels over time, were also predictive of the number of infections (P = 0.03) in the swimmers. CONCLUSIONS: These results indicate that measurement of salivary IgA levels over a training season may be predictive for athletes at risk of infection.

Adolescent↗
PubMed1999

Protection against Helicobacter pylori infection by intestinal immunisation with a 50/52-kDa subunit protein.

A mouse model of Helicobacter pylori infection was used to evaluate the vaccine antigen potential of the citrate synthase homologue protein purified from the H. pylori NCTC 11637 strain. Mice were immunised with the protein by intra-Peyer's patch immunisation. This route gives maximal intestinal immunisation and was used to screen oral vaccine candidate antigens without the added complication of simultaneously testing oral delivery systems. Two weeks post-immunisation mice were infected with Sydney strain H. pylori and 4 weeks after infection the mice were killed and the level of H. pylori infection in the stomach determined. Pre-immunisation with the 50/52-kDa protein led to a 84-91% reduction in H. pylori infection compared to unimmunised controls.

Animals↗
PubMed1999

Effect of chronic sodium cyanate administration on O2 transport and uptake in hypoxic and normoxic exercise.

Systemic O2 transport during maximal exercise at different inspired PO2 (PIO2) values was studied in sodium cyanate-treated (CY) and nontreated (NT) rats. CY rats exhibited increased O2 affinity of Hb (exercise O2 half-saturation pressure of Hb = 27.5 vs. 42.5 Torr), elevated blood Hb concentration, pulmonary hypertension, blunted hypoxic pulmonary vasoconstriction, and normal ventilatory response to exercise. Maximal rate of convective O2 transport was higher and tissue O2 extraction was lower in CY than in NT rats. The relative magnitude of these opposing changes, which determined the net effect of cyanate on maximal O2 uptake (VO2 max), varied at different PIO2: VO2 max (ml. min-1. kg-1) was lower in normoxia (72.8 +/- 1.9 vs. 81. 1 +/- 1.2), the same at 70 Torr PIO2 (55.4 +/- 1.4 vs. 54.1 +/- 1.4), and higher at 55 Torr PIO2 (48 +/- 0.7 vs. 40.4 +/- 1.9) in CY than in NT rats. The beneficial effect of cyanate on VO2 max at 55 Torr PIO2 disappeared when Hb concentration was lowered to normal. It is concluded that the effect of cyanate on VO2 max depends on the relative changes in blood O2 convection and tissue O2 extraction, which vary at different PIO2. Although uptake of O2 by the blood in the lungs is enhanced by cyanate, its release at the tissues is limited, probably because of a reduction in the capillary-to-tissue PO2 diffusion gradient secondary to the increased O2 affinity of Hb.

Animals↗
PubMed1999

Is there a role for a mucosal influenza vaccine in the elderly?

Influenza infection is an acute respiratory disease with a high morbidity and significant mortality, particularly among the elderly and individuals with chronic diseases. The majority of countries now recommend annual influenza vaccination for all people aged 65 years or older, and for those with high risk conditions. Most commercially available influenza vaccines are administered systemically and while these are effective in children and young adults, efficacy levels in elderly individuals have been reported to be much lower. Mucosal vaccines may offer an improved vaccine strategy for protection of the elderly. As the influenza virus causes a respiratory infection, it is potentially more beneficial to administer a vaccine that will boost protection in the mucosal surfaces of the upper and lower respiratory tract. Mucosal influenza vaccines are aimed at stimulating protective immunity in the respiratory tract via oral or intranasal immunisation. This review examines our present knowledge of mucosal immunity and current strategies for mucosal vaccination. It also stresses that the use of serum antibody levels as a 'surrogate marker' for protection against influenza is potentially misleading; serum antibody, for example, may be a quite inappropriate marker to assess a mucosal vaccine. This marker does not reflect other immune responses to vaccination that are crucial for protection.

Age Factors↗
PubMed1999

Alcoholic hepatitis as a T-cell mediated disorder: an hypothesis.

BACKGROUND: The mechanism by which alcohol induces alcoholic hepatitis, the precursor lesion for cirrhosis, has never been elucidated. In particular, direct toxicity has not been proven. This article reviews the hypothesis that a primary target of chronic alcohol ingestion is the T lymphocyte. The lesion in the T lymphocyte is characterized by reduced baseline secretion of cytokines, including tumor necrosis factor-alpha; although characterized by an exaggerated release of cytokines when stimulated by polyclonal activators such as endotoxin. High concentrations of cytokines, especially tumor necrosis factor-alpha, within the liver induce necrosis/apoptosis of hepatocytes. METHODS: Data supporting this hypothesis in rodent models are reviewed. CONCLUSION: A strategic approach for testing this concept in man is defined.

Animals↗
PubMed1998

The effect of successful contact lens wear on mucosal immunity of the eye.

OBJECTIVE: This study aimed to assess the effect of contact lens wear on the mucosal defenses of the outer eye against infection. DESIGN: A case-controlled study of daily contact lens wearers in their initial 6 months of contact lens wear. PARTICIPANTS: Contact lens wearers (mean age, 23.1 years; 47 subjects) were compared with age-matched control subjects (mean age, 24.7 years; 44 subjects). INTERVENTION: Outer eye defenses were studied by assay of tear constituents and quantitative conjunctival microbiology. MAIN OUTCOME MEASURES: Antimicrobial activity of tears was studied by assay of total immunoglobulin A (IgA), IgA isotype-specific antibodies reactive with Escherichia coli, Haemophilus influenzae, Staphylococcus epidermidis, albumin and lysozyme, and the ocular surface microbial load determined using quantitative microbiology of the conjunctival sac. RESULTS: The IgA isotype-specific antibodies reactive with E. coli (P = 0.03) and S. epidermidis (P = 0.068) were lower in contact lens wearers, but antibody:albumin ratios were not significantly different in the two groups. Contact lens wear also had no significant effect on tear IgA, albumin, or lysozyme or its ratios with albumin. Bacterial numbers and colonization rates for coagulase-negative staphylococci were greater in contact lens wearers than in age-matched control subjects. Corynebacterium sp. and non-Enterobacteriaceae (P = 0.007) were isolated more frequently and in greater numbers from contact lens wearers. Colonization rates were increased for Corynebacterium sp., but non-Enterobacteriaceae were transient. In both daily contact lens wearers and age-matched control subjects, most conjunctival flora were transient rather than colonizing, and no subject developed an outer eye infection during the study. CONCLUSION: These results suggest that daily contact lens wear does not significantly alter the mucosal defenses of the outer eye that function to eliminate organisms from the conjunctival sac and prevent outer eye infection.

Adult↗
PubMed1998

Diaphragm shortening and intrathoracic pressure during hypercapnia in rats.

The purpose of this study was to determine the relationship between intrathoracic pressure (delta ITP) and diaphragm shortening (DS) during the development of diaphragm fatigue. Fatigue of the diaphragm was produced by having rats breath 15% CO2 in O2. Diaphragm shortening increased significantly to 178% of control during the first 5 min of hypercapnia and then decreased to 86% of control at approximately 80 min. Twenty minutes after terminating hypercapnia, DS increased to 115% of the prehypercapnic value. delta ITP increased to 199% of control following 5 min of hypercapnia and continued to increase, reaching 267% of control at the end of the hypercapnic period. Twenty minutes later, delta ITP was 147% of control. These results illustrate that during increased respiratory work, DS can decrease while intrathoracic pressure remains increased. These findings suggest that intrathoracic pressure may not always reflect the contractile status of the diaphragm. These findings are consistent with other studies indicating that as the diaphragm fatigues, accessory respiratory muscle activity increases to maintain delta ITP.

Animals↗