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Pathophysiology of immune thrombocytopenic purpura.

In 1951, the young hematologist in training, Dr. William Harrington, infused himself with plasma from a patient with immune thrombocytopenic purpura (ITP). He rapidly developed severe, but transient, thrombocytopenia and was at risk for serious hemorrhage. Thus, the humoral autoimmune cause of ITP was established. Since 1953, when Dr. Harrington's in vivo studies ended, in vitro investigations have aimed to determine the molecular and cellular details of immune-mediated platelet destruction.

Animals↗

Does prolonged cycling of moderate intensity affect immune cell function?

BACKGROUND: Prolonged exercise may induce temporary immunosuppression with a presumed increased susceptibility for infection. However, there are only few data on immune cell function after prolonged cycling at moderate intensities typical for road cycling training sessions. METHODS: The present study examined the influence on immune cell function of 4 h of cycling at a constant intensity of 70% of the individual anaerobic threshold. Interleukin-6 (IL-6) and C-reactive protein (CRP), leukocyte and lymphocyte populations, activities of natural killer (NK), neutrophils, and monocytes were examined before and after exercise, and also on a control day without exercise. RESULTS: Cycling for 4 h induced a moderate acute phase response with increases in IL-6 from 1.0 (SD 0.5) before to 9.6 (5.6) pg/ml 1 h after exercise and CRP from 0.5 (SD 0.4) before to 1.8 (1.3) mg/l 1 day after exercise. Although absolute numbers of circulating NK cells, monocytes, and neutrophils increased during exercise, on a per cell basis NK cell activity, neutrophil and monocyte phagocytosis, and monocyte oxidative burst did not significantly change after exercise. However, a minor effect over time for neutrophil oxidative burst was noted, tending to decrease after exercise. CONCLUSIONS: Prolonged cycling at moderate intensities does not seem to seriously alter the function of cells of the first line of defence. Therefore, the influence of a single typical road cycling training session on the immune system is only moderate and appears to be safe from an immunological point of view.

Acute-Phase Reaction↗

A ganglionic model of "learned helplessness".

The phenomenon known as "learned helplessness" (LH) is seen broadly across the animal kingdom. Some of the basic characteristics of this behavior are: failure to escape shock when it is possible to do so following non-escapable shock; reversion to non-escape behavior even after successful escape; if the animal is given escape/avoidance training prior to being given inescapable shocks, the latter will not interfere with its ability to later show normal escape/avoidance behavior (generally described as an immunization effect); following inescapable shock training the animals often become "passive and still" when confronted with an inescapable shock. These behaviors are seen in intact mammals, lower vertebrates, and invertebrates. In fact, the basic characteristics are even seen in a spinal rat and, with the exception of one characteristic not yet examined, in an isolated thoracic ganglion of an insect. The brain is evidently not essential either in mammals or in invertebrates for demonstrating this behavior. Not only can an insect ganglion show the behavioral characteristics of LH, but the neural information underlying the phenomenon of LH can be shown to transfer from one ganglion innervating one pair of legs to another ganglion innervating a different pair of legs. Thus, how CNS information underlying LH is coded and transferred from one site to another within the CNS can be examined in such a system. The LH model has provided valuable insights into the physiology of depression. This model suggests that human depression is caused by one's lack of control over traumatic events. It is supported by a number of parallels between depression and LH behavior. Tricyclic antidepressants, MAO inhibitors, and ECT, which are effective in treating depression, also can prevent and reverse LH in mammals. It would be important to find out if they are also effective in invertebrate models. The fact that the characteristics of the behavior called LH are seen in invertebrates such as slugs, cockroaches, and locusts provokes other intriguing questions about the presence of cognition at these phylogenetic levels, as well as what animal or preparation constitutes an appropriate model for human depression.

Animals↗

Immune effects of relaxation during chemotherapy for ovarian cancer.

BACKGROUND: Psychological interventions, such as relaxation training, have been applied to strengthen resistance to disease. There is evidence that relaxation can modify immune parameters in healthy populations and in chemotherapy naive cancer patients. METHODS: In this study, 22 patients receiving chemotherapy for ovarian cancer were allocated to relaxation training with a clinical psychologist or to a control group. After 2 months' training, blood was sampled 2 days before chemotherapy in the patients' homes, and at the hospital prior to treatment. RESULTS: On average, the intervention group showed higher lymphocyte counts, and a tendency to higher white blood cell numbers as compared to the control group. No significant effects were found in proliferative responses to mitogen and natural killer cell activity after intervention. Relaxation training did not modify the magnitude of changes in immune variables between home samples and at the hospital in anticipation of treatment. CONCLUSIONS: The study suggests that relaxation training can positively affect immune parameters in cancer patients, even if training is performed during myelosuppressive therapy.

Adult↗

The control of measles in tropical Africa: a review of past and present efforts.

Measles in tropical Africa is endemic and cyclical, with a high incidence that usually peaks during the dry seasons. Measles may be a contributing factor in 10% of all deaths among African children. Several problems have hindered measles immunization programs in Africa; these include difficulties in maintaining the cold chain, poor epidemiologic surveillance, and the logistical problems involved in reaching a population that is 80% rural. The United States Agency for International Development and the World Health Organization both have programs that are helping to increase immunization coverage and to solve the problems just mentioned. Many countries have begun to train their own personnel to administer immunization programs. However, because of limited staff and equipment, a high birth rate, and an uncertain social situation, no firm predictions can be made concerning the permanent control of measles in tropical Africa.

Africa↗

The significance of intensity and duration of exercise on natural immunity in rats.

PURPOSE: The purpose of this study was to examine a) the relationship between running distance (km x d(-1)) and b) the duration of exercise training in weeks on the effects on natural immune function in spontaneously hypertensive rats (SHR). METHODS: Exercise consisted of voluntary running in wheels for 5 or 11 wk. In vivo cytotoxicity was measured as clearance of injected 51Cr-labeled YAC-1 lymphoma cells from the lungs. RESULTS: Increased in vivo cytotoxicity was seen after 5 wk of exercise (P < 0.001) but not after voluntary exercise for 11 wk. If the wheels were locked 3 d x wk(-1) during the last 6 wk of running, thus restricting the exercise to 4 d x wk(-1), the exercise-induced immunoenhancement seen after 5 wk of exercise was maintained also after 11 wk of exercise. When compared with the sedentary controls after 5 wk of exercise, all runners regardless of running distance exhibited significantly higher in vivo clearance of tumor cells from the lungs, and no overall significant correlation was seen between running distance and retained radioactivity. However, the lowest activity runners (< 4 km x d(-1)) exhibited significantly lower in vivo clearance of tumor cells from the lungs when compared with animals running more than 4 km x d(-1). CONCLUSION: We conclude that the duration of exercise training, and to some extent the running distance, has significant effects on the training-induced increase in natural immune function in rats. Furthermore, we conclude that a resting or recovery period during long-term exercise training is important to maintain the immunoenhancing effects in response to exercise.

Animals↗

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↗

The effect of intense interval exercise on iron status parameters in trained men.

Iron and iron-binding proteins play a critical role in the physiology of many human systems, including the immune system. Intense interval exercise in trained men (mean [SD] age = 31.5 [4.5] yr; VO2max = 64.3 [3.8] ml.kg-1.min-1) is associated with significant modulation of iron status parameters. The concentration of red blood cells, hemoglobin, and transferrin all increased significantly immediately post-test (P < 0.01), increases which can largely be attributed to hemoconcentration. Serum iron was elevated by approximately 25% both immediately and 1 h post-test (P < 0.08). Maximum post-test serum iron values (either immediately or 1 h post-test) were significantly elevated with respect to rest (P < 0.01). Transferrin concentration was also significantly elevated at 24 h post-test (P < 0.05). Transferrin saturation was not significantly altered by this protocol (P > 0.10). Despite a trend toward elevation at 24 h post-test, ferritin concentration was not significantly different from the resting value at any sampling point. Intense interval exercise appears to be associated with significant modulation of iron status, the biological importance of which remains to be determined.

Adult↗

[Effect of progressive muscle relaxation using biofeedback on perceived stress, stress response, immune response and climacteric symptoms of middle-aged women].

PURPOSE: This study was aimed to evaluate the effect of progressive muscle relaxation training using biofeedback on perceived stress, stress response, immune response and climacteric symptoms. METHOD: This was a crossover, pre-post test design. The study subjects are 36 middle-aged women who were selected at 2 public health centers. The independent variable was Biofeedback training for 4 weeks, twice a week and home training for 4 weeks. Dependent variables were perceived stress, stress response, immune response, and climacteric symptoms measured with Hildtch's scale (1996). RESULT: Progressive muscle relaxation training using biofeedback was not effective in reducing perceived stress, but it was shown to be effective in reducing physiological stress responses such as pulse rate and EMG. Though blood pressure and skin conductance were repeatedly down, and skin temperature slowly increased, there were no statistically significant differences. Progressive muscle relaxation training using biofeedback was not effective in reducing serum cortisol, enhancing immune responses, or decreasing climacteric symptoms. CONCLUSION: The findings point to a pressing need for further, well-controlled and designed research with consideration in selection of subjects and instruments, frequency of measurements, the sampling method, and intervention modalities.

Adult↗

Effect of a moderate intensity exercise training protocol on the metabolism of macrophages and lymphocytes of tumour-bearing rats.

It is commonly accepted that moderate intensity exercise is beneficial to the immune system. We tested the influence of a moderate intensity training protocol (8 weeks) upon immune system function in Wistar tumour-bearing (TB) rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, together with some functional parameters (hydrogen peroxide production and lymphocyte proliferative response). These substrates were chosen since they represent the most important energetic and synthetic metabolites for these cellular types. The training protocol caused a decrease of 17.4 per cent in the production of H(2)O(2) by macrophages, as well as a decrease in glucose consumption (25 per cent) and lactate production (47.1 per cent), and an increase in the production of labelled CO(2) from the oxidation of [U-(14)C]-glucose, in TB rats. The training protocol was also able to induce changes in the maximal activity of some key enzymes in the metabolism of glucose and glutamine, a reduction of hexokinase (68.8 per cent) activity and an increase in the activity of citrate synthase (10.1 per cent) in TB rats. The training protocol increased the proliferative response of lymphocytes cultivated in the absence of mitogens (75 per cent), of those cultivated in the presence of ConA (38.2 per cent) and in the presence of LPS (45.0 per cent). These cells also showed an increase in the maximal activity of some key enzymes of the glycolytic and glutaminolytic pathways. Our data demonstrated that the training protocol was able to induce an increase in aerobic utilisation of both substrates in lymphocytes and macrophages. The training protocol was also able to prevent several changes in glucose and glutamine metabolism that are normally present in sedentary TB rats. These changes in immune cell metabolism induced by the training protocol were able to increase TB rat survival.

Animals↗

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↗

Immunological effects of competitive versus recreational sports in cross-country skiing.

For a period of two months during the competitive season the effects of endurance training in cross-country skiers were evaluated in order to compare the adaptive and innate immune systems between 10 competitive athletes, 10 moderately trained athletes and 10 untrained healthy controls. The main results were as follows: the peripheral T-lymphocyte count of the competitive athletes was decreased. In contrast the number of peripheral blood NK cells was increased in this group. These data imply a diminution of the adaptive immune system due to repeated bouts of intense exercise and contemporaneous reinforcement of the innate immune response. Moreover the inducible IL-12-expression following monocyte stimulation was significantly decreased in competitive athletes. Compared with the other two groups, the moderately trained athletes showed a significantly increased production of IFN-gamma upon T-cell stimulation. These data suggest that the immune system may profit from moderate endurance training by an increased capacity to generate IFN-gamma while the immune situation following repeated exhausting exercise of competitive athletes tends to deteriorate through downregulation of IFN-gamma and IL-12.

Adaptation, Physiological↗

Anabolic steroids and lymphocyte function in sedentary and exercise-trained rats.

The effects of the administration of suprapharmacological doses of anabolic steroids (AASs) on the immune system were examined in sedentary and exercise-trained rats by testing mobility and proliferative response in cultures of thymus and spleen-derived lymphocytes. Male Wistar rats were exercise-trained following two programmes of treadmill running of 3 months duration, differing in intensity, in the absence of treatment or with simultaneous i.m. administration of a suprapharmacological dose (10 mg/kg/week) of nandrolone decanoate (ND) or stanozolol (ST) during the past two months. At this dose ND reduced body weight gain, promoted a redistribution of immune cells from thymus to spleen, impaired lymphocyte mobility and inhibited the mitogen-induced proliferative response (about 90% inhibition for thymus-derived cells). Stanozolol (ST) treatment was without effect on body weight gain, but it also induced a redistribution of lymphocytes and modified the in vitro lymphocyte activity, although less severely than ND. Application of the high-intensity training programme reduced lymphocyte mobility and proliferation in vitro and a simultaneous treatment with anabolic steroids further impaired some of the immune cell responses. Application of the endurance-directed training programme, however, did not reduce mobility or mitogen-induced proliferation of lymphocytes, and normalized the activity of these cells in anabolic steroid-treated rats. So, endurance exercise, contrary to high-intensity training, could counteract the apparent negative effects of high doses of androgens on lymphocyte function.

Adrenal Glands↗

Evaluating children with respiratory tract infections: the role of immunization with bacterial polysaccharide vaccine.

Antibody deficiency syndromes are an important cause of recurrent infections in children. Today it is possible to perform a complete evaluation of antibody-mediated immunity leading to a definitive diagnosis of either normal or abnormal immunity in most patients. However, the interpretation of the results of IgG subclass determinations and specific antibody responses is still being defined. At this time our recommendation is that patients who meet the criteria for an evaluation of antibody-mediated immunity be referred to subspecialists trained in this evaluation until better criteria for normal have been developed. The possibility that protective amounts of antibodies against pneumococcal serotypes may develop only transiently must be considered in patients with recurrent infections after initial improvement after immunization, especially if IgG2 subclass deficiency is also present. In the future it may be possible to use a faster and more economical approach to evaluate patients with recurrent infections by immunization with pneumococcal vaccine and then measuring IgM, IgG and IgA along with postimmunization specific antipneumococcal antibody titers 4 to 6 weeks later. For this approach to become feasible, further studies comparing the information obtained from the evaluation of pre- and postimmunization antibody concentrations with that obtained from the evaluation of postimmunization concentrations alone are needed.

Antibody Formation↗

Exercise does not modify spatial memory, brain autoimmunity, or antibody response in aged F-344 rats.

Old F-344 rats were given endurance training over a 10-week period on a motorized treadmill. This treatment resulted in substantial heart-to-body weight ratio increases, indicative of effective training. To determine whether endurance training might alter some of the known immune system and cognitive changes observed during aging, exercised old rats were compared to nonexercised old and young controls on three variables: in vivo antigen-specific immune activity, brain-reactive antibody formation, and spatial memory. The exercise training did not influence any of these measures in the old rats. Both groups of old rats showed poorer antibody response to a specific antigen, more brain-reactive antibody formation, and poorer spatial memory than the young controls. There was, however, a significant relationship between brain-reactive antibody formation and spatial memory performance, regardless of training condition.

Aging↗

Iron status and resting immune function in female collegiate swimmers.

Iron deficiency may lead to anemia and may result in compromised endurance exercise performance. Iron deficiency has also been reported to adversely affect the immune system and has been associated with attenuation of natural killer cell (NK) activity. This study was conducted to examine the relationship between iron status and NK activity in highly conditioned female athletes. Ten collegiate female swimmers (SWM) and 9 inactive females (SED) participated in this investigation. Resting blood samples were obtained and analyzed for serum iron and ferritin. NK activity (% lysis) was determined using a whole blood method (51Cr release assay). No significant relationship was found between iron and NK activity (r = 0.55, p =.09), nor between serum ferritin and NK activity (r = 0.33, p =.35) for SWM. ANOVA revealed significantly greater NK activity for SWM (51.63 +/- 15.79%) versus SED (30.34 +/- 13.67%). Serum ferritin levels were not significantly different between SWM (20.38 +/- 8.62 hg á ml-1) and SED (16.79 +/- 10.53 hg á ml-1), nor were iron values different between groups (16.54 +/- 2. 17 mmol á L-1 SWM; 11.92 +/- 2.61 mmol á L-1 SED). A significant relationship between iron status and resting immune function could not be established. Exercise training may affect NK activity; however, the influence of iron status on immune function requires further evaluation.

Adult↗

Patients' acceptance of traditional and nontraditional immunization providers.

OBJECTIVE: To examine patients' acceptance and reported use of traditional and nontraditional immunization providers and settings. DESIGN: Survey. SETTING: Stratified sample of private family physician clinics, family medicine residency training programs, community pharmacies that provide immunizations under standing order protocols, and nonimmunizing community pharmacies, all located in Iowa. PATIENTS OR OTHER PARTICIPANTS: Individuals presenting for medical care or pharmacy services. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sources of past immunizations, 'access to immunizations, importance of immunization records, and future use of different health care providers and settings for immunizations. Univariate and multivariate analyses were performed to examine the relationships between patient demographics and recruitment site on the question responses. RESULTS: 420 surveys were returned (67% response rate). Respondents frequently received immunizations at sites other than physician offices. Younger patients and those living in smaller towns were more likely to report receiving an immunization from a nonphysician. Patients recruited in immunizing pharmacies more often reported previous immunization by a pharmacist (P < .001), most often for influenza. Respondents often reported that it was more convenient to receive an immunization outside a physician office. Greater support was noted for receiving adult immunizations from nonphysicians and in nontraditional settings, whereas traditional settings and providers (physician offices, community health departments) were preferred for childhood immunizations. CONCLUSION: Iowans report accessing different health care providers and settings for their routine immunizations. In general, they are more likely to support using traditional immunization providers and settings for childhood immunizations but are less exclusive about where they receive adult immunizations. Pharmacists should consider focusing initial efforts on administering adult immunizations, due to greater patient acceptance of nontraditional immunizers for adult immunizations.

Adult↗

Measurement of mortality from neonatal tetanus in Burma.

Surveys to determine mortality from neonatal tetanus were conducted in March and April 1985 in accessible areas of Burma, where pregnant women had been immunized with tetanus toxoid and, for comparison, also in areas where such immunization had not been given. Neonatal mortality rates were three times greater in areas where tetanus toxoid immunization had only recently or had not yet been introduced by the national expanded programme on immunization. Analysis of the data indicates that the impact on reduction of neonatal mortality from tetanus of three interventions (immunization of pregnant women with tetanus toxoid; delivery in hospital; or birth at home attended by a trained health worker) was greatest for immunization.

Health Surveys↗