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[Vaccination coverage in the first year of life in 4 cities of the state of São Paulo, Brazil].

Immunization is an important disease prevention measure, and evaluating the effectiveness of immunization programs is crucial to ensuring their success. This study describes the results of a household survey in four cities in the state of São Paulo, Brazil: Francisco Morato, Guarulhos, Osasco, and São Paulo. The survey was done in order to estimate immunization coverage for the cohort of children born in 1996. The city of São Paulo was divided into five strata, according to socioeconomic and living conditions. The survey followed the methodology that the Pan American Health Organization recommends for immunization coverage surveys. The proportion of children who had received a complete set of the recommended vaccinations at the time of the interview, taking into account both oral reports and information recorded on the children's immunization cards, was above 90% for all the cities except Francisco Morato, which had the worst living conditions. In the city of São Paulo, the worst coverage was found in the lowest and highest strata. When only the doses received during the first year of life were considered, the coverage was not adequate to produce herd immunity. The use of private vaccination services was higher in the areas with better living conditions. The difference between the coverage calculated based on data from health services and the coverage calculated based on the survey was inversely proportional to living conditions. Our results suggest that surveys similar to the one described here should be carried out in other cities. Employees who provide vaccination services should be trained to correctly record vaccination data. In addition, it is important to make health professionals aware of the official immunization calendar, and to facilitate the public's access to health services.

BCG Vaccine↗

Psychoneuroimmunology update.

Psychoneuroimmunology is the scientific field that investigates linkages between the brain, behavior, and the immune system and the implications of these linkages for physical health and disease. Recent evidence suggests that both naturalistic and laboratory stressors can alter enumerative and functional aspects of the human immune system. Chronic stress may increase vulnerability to infectious disease; however, the role of stress in the course of inflammatory bowel disease remains unclear. Because there are large individual differences in psychological response to stress, it is important to consider the role of cognitive and affective responses to stress. Depression has been associated with functional immune decrements and immune overactivation. Cognitive states such as perceived control, views of the self, and views of the future have been associated with immune parameters and health in some studies. Very few controlled clinical trials have been conducted to determine if psychosocial interventions can impact the immune system and the progression of medical conditions. There is suggestive evidence for the health benefits of relaxation training, cognitive-behavioral stress management, and support groups; but, there is little research on many other psychosocial interventions in widespread use for medical conditions. An evidence-based discussion of this research literature with interested patients may help them make informed decisions regarding adjunctive treatments.

Affect↗

Behaviour of zinc in physical exercise: a special reference to immunity and fatigue.

The variations in plasma zinc levels is dependent which follows intensivity of exercise. It is clear that there are short-term effects of exercise on zinc metabolism. It has also been shown that a high level of constant exercise can have long-term effects on zinc metabolism. It has been reported that runners have lower plasma zinc levels than controls. Long term endurance training has been shown to significantly decrease resting serum zinc levels in both male and female athletes compared to sedentary controls. Severe zinc deficiency can affect muscle function. One consequence of low serum zinc levels could be a reduction in muscle zinc concentrations. Since zinc is required for the activity of several enzymes in energy metabolism it could be predicted that low muscle zinc levels would result in a reduction in endurance capacity. Zinc may also be acting directly at membrane level; changes in extracellular zinc levels have been reported to influence twitch-tension relationship in muscle. Some investigators have associated acute and exhaustive exercise with decreased immune function. The mechanisms by which physical stress modulates immune competence are complex, involving both immune and neuroendocrine messengers. Muscular fatigue is of critical importance and as such it has been the subject matter of numerous investigators. Although many factors have been identified, a clear cause remains elusive. Factors discussed include: energy supply, the accumulation of metabolites, eccentric work, immune dysfunctions, etc. Recently we have demonstrated that daily high and maintained physical training over a prolonged period of time (7 mo) provokes marked modifications in the immune system of elite sportsmen accompanied by a psychological and biochemical stress level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Assessment of nutritional depletion and immune competence: a comparison of clinical examination and objective measurements.

The ability of two surgeons to assess accurately nutritional depletion and immune state in surgical patients by clinical examination has been studied. The clinical status of all the surgical patients (198) in a large teaching hospital was assessed by two surgeons without knowledge of the results of objective testing. One of the surgeons had had a formal training in nutritional assessment techniques, the other had not. Each was asked to make two clinical assessments, one of nutritional depletion the other of immune competence. On the same day each patient also had an objective assessment of nutritional depletion (relative weight index) and immune competence (delayed hypersensitivity skin testing to four antigens). While the two surgeons identified more than 80% of the patients objectively assessed as being not depleted, they could pick only 40% of the patients who were depleted. Similarly, they identified 60% of the patients who reacted normally to the skin tests but they picked only 31% of the patients with impaired reactivity. The surgeon with nutritional training performed better than the untrained surgeon. This study suggests that malnourished patients cannot be adequately identified by clinical examination

Adult↗

Notch pathway defines an aggressive and immune-suppressive phenotype associated with checkpoint inhibitor resistance in pan-gastrointestinal adenocarcinomas.

The Notch pathway regulates the homeostasis and tumorigenesis of gastrointestinal epithelium. Given its roles in cancer stem cell capacity and cancer immunity, we hypothesized that Notch activation can predict poor prognosis and resistance to immune checkpoint inhibitors (ICIs) in gastrointestinal adenocarcinoma (GIAC). The mRNA expression and genomic alterations of Notch pathway were characterized in esophagus (ESAD), stomach (STAD), colon (COAD), or rectum (READ) adenocarcinomas from The Cancer Genome Atlas (TCGA) dataset. The prognostic model (mRNA-score) was constructed using the TCGA dataset (the training set) and was validated in 3 independent sets (GSE19417 [ESAD], GSE84437 [STAD], and GSE40967 [COAD]). The associations of the mRNA-score with drug sensitivity, immune cell infiltration, and immunotherapy efficacy were, respectively, analyzed using the Genomics of Drug Sensitivity in Cancer (GDSC) database, the TCGA dataset, and multiple clinical cohorts including GSE165252, PRJEB25780, IMvigor210, and CheckMate-009/010/025. Notch pathway genes exhibited conserved genomic/transcriptomic features across four GIAC subtypes. Three pan-GIAC clusters were determined by unsupervised clustering, and the cluster with higher expression of the Notch pathway genes had shorter overall survival (OS), immunosuppressive microenvironment, and higher scores of the signatures concerning angiogenesis, cell cycle, PI3K-AKT-mTOR, TGF-&#x3b2;, glycolysis, etc. A prognostic algorithm (mRNA-score) was constructed, which was correlated with poor OS in the training set (TCGA, P&#x2009;<&#x2009;0.001) and three validation sets (GSE19417, P&#x2009;=&#x2009;0.025; GSE84437, P&#x2009;=&#x2009;0.001, GSE40967, P&#x2009;=&#x2009;0.007). A high mRNA-score was linked with more "resting"/ "anti-inflammatory" rather than "activated"/ "pro-inflammatory" tumor-infiltrating immune cells and ICI resistance in GIACs (GSE165252, P&#x2009;=&#x2009;0.047; PRJEB25780, P&#x2009;=&#x2009;0.047) and other solid tumors such as urothelial carcinoma and clear cell renal cell carcinoma. Our findings demonstrate the utility of the Notch pathway in predicting prognosis and ICI resistance. Further studies are warranted to explore the efficacy of Notch inhibitors as immunotherapeutic adjuvants to overcome ICI resistance.

Humans↗

[Fitness in the elderly].

A healthy way of growing old is supposed to postpone for as long as possible the physiological loss of functional organ capacity and preserve a high quality of life. While the individual predisposition depends on genetic variables, behavioral and environmental influences have a strong modulating effect on the aging process. According to our current knowledge, there is no doubt that physical fitness prolongs life and prevents cardiovascular diseases in particular. Physical activity and sports have many positive effects, which are well proven. In addition to the cardiovascular system, bone metabolism and immune status should be mentioned here. Furthermore, the increase in quality of life through physical training is undisputed, with positive effects for persons of any age. Current data prove that regular moderate training provides the greatest benefits.

Aged↗

Salivary IgA response of triathletes participating in the French Iron Tour.

Athletes are susceptible to upper respiratory tract infections (URTI) during intense training and after major competitions. Secretory IgA, which is the predominant antibody of the mucosal immune system, is the major effector of host-resistance to many microorganisms causing URTI. Previous studies have shown that salivary IgA-mediated immunity decreases after a single short distance triathlon, but the effect of repeated triathlon competitions on secretory IgA levels remains unknown. The purpose of this study was to examine the salivary IgA response of elite triathletes in repeated triathlon races during the 2001 French Iron Tour (FIT). Eight triathletes participated in this study. Saliva samples were collected daily after waking up (fasting basal state), before (pre-race) and after (post-race) each day's competition. Salivary IgA, total protein, and flow rate were measured. Salivary IgA concentrations were measured by an enzyme-linked immunosorbent assay. The salivary flow rate was significantly decreased after each race compared with the fasting basal state (p < 0.01). The salivary IgA concentration of the fasting basal state decreased over the FIT and was even lower than that of the post-race values (p < 0.05). The salivary IgA secretion rate of the fasting basal state decreased by 51.9% over the FIT (p < 0.05). Our data suggest that intense exercise repeated daily has a cumulative negative effect on basal levels of salivary IgA.

Adult↗

Beta-hydroxy-beta-methylbutyrate ingestion, part II: effects on hematology, hepatic and renal function.

PURPOSE: The purpose of this investigation was to examine the effects of differing amounts of beta-hydroxy-beta-methylbutyrate (HMB), 0, 36, and 76 mg x kg(-1) x d(-1), on hematology, hepatic and renal function during 8 wk of resistance training. METHODS: Thirty-seven, untrained collegiate males and were randomly assigned to one of the three groups, 0, 38, or 76 mg x kg(-1) x d(-1). Resistance training consisted of 10 exercises, performed 3 d x wk(-1) for 8 wk at 80% of their 1-repetition maximum. Blood and urine was obtained before training, 48 h after the initial session, 1 wk, 2 wk, 4 wk, and at 8 wk of resistance training. Blood was analyzed for glucose, blood urea nitrogen, hemoglobin, hepatic enzymes, lipid profile, total leukocytes, and individual leukocytes. Urine was analyzed for pH, glucose, and protein excretion. RESULTS: The 38 mg x kg(-1) x d(-1) group had a greater increase in basophils compared with 0 or 76 mg x kg(-1) x d(-1) groups (P < 0.05). No difference occurred in any other blood and urine measurements. CONCLUSION: These data indicate that 8 wk of HMB supplementation (< or = 76 mg x kg(-1) x d(-1)) during resistance training had no adverse affects on hepatic enzyme function, lipid profile, renal function, or the immune system.

Adolescent↗

[Generation of suppressive protein after heavy physical stress in athletes].

Our previous work showed that under the condition of restraint stress and the control of central nervous system, a suppressive protein (neuroimmune protein, NIP) was generated in peripheral lymph tissue and released into the blood stream, which acts as an immune suppressor. In the present study the serum from the athletes performed a heavy athletic training for 18 days was also able to suppress the lymphocyte proliferation of normal mice. The molecular weight at the suppressive factor in athlete serum determined by gel filtration HPLC was similar to that in mice and rats. In vitro experiment, the normal human lymphocytes were incubated with the serum from restraint stressed rats for 12 h and then the extract of human lymphocyte was made for testing the effect on normal lymphocyte proliferation. The result showed that it suppressed normal mouse lymphocyte proliferation. This result was similar to our previous experiment by using normal mouse lymphocyte incubated with the rat serum treated with restraint stress. It was also found that the serum and the extract of lymph node from restraint stressed mice suppressed human lymphocyte proliferation induced by PHA. The results suggest that suppressive protein induced by stress in mice and rats could also be induced in human beings and there is no distinct species specificity among them.

Adult↗

[Plasma exchanges (author's transl)].

Therapeutic plasma exchanges (PE) represent a new approach to the management of numerous immune diseases and are in full development. In practice, however, they require sophisticated equipment, heavy investments and fully trained staff, and they are not as free from dangers as was initially assumed. A rational appraisal of the results therefore is desirable, but prospective comparative studies are scarce, and the present indication all too often rest upon non-scientific criteria, such as the need to slow down the course of an allegedly severe disease or the subjective impressions of the therapeutic team. In spite of these uncertainties, it would seem that PE deserves a major place in the treatment of diseases due to auto-antibodies or circulating immune complexes, as well as in that of malignant monoclonal gammapathies with hyperviscosity of the blood, some acute or chronic metabolic disorders and occasional intoxications with substances highly bound to serum proteins, which constitute the usual indications. The indications proposed in this review paper are based on the most representative publications in this particular field and on the own experience of the authors, who have performed 1200 PEs between 1978 and 1980.

Autoimmune Diseases↗

Relationship between primary payer and use of proactive immunization practices: a national survey.

OBJECTIVE: To quantify the national use and determinants of proactive immunization practices by examining the relationship to the primary practice payer. STUDY DESIGN: A standardized survey was conducted in 1995 by trained personnel using computer-assisted telephone interviewing. PATIENTS AND METHODS: A stratified random sample of family physicians, pediatricians, and general practitioners across the United States was selected from the American Medical Association master file of physicians list, which included nonmembers. The main outcome measures were use of reminder systems and assessment of immunization rates. RESULTS: Of the 1769 physicians who were contacted, 1236 participated. Use of reminder systems varied by the practice's primary payer: 31% of health maintenance organization (HMO), 41% of Medicaid, 27% of fee-for-service (FFS), and 28% of no predominant payment source physicians reported using a reminder system (P < 0.01). Use of computerized reminders also varied according to practice primary payer (HMO, 68%; Medicaid, 34%; FFS, 51%; and no predominant payment source, 42%; P < 0.01) as did assessment of immunization rates in the practice (HMO, 57%; Medicaid, 40%; FFS, 28%; and no predominant payment source, 30%; P < 0.01). A majority of Medicaid physicians (84%) required a physical examination before immunization, compared to 49% of HMO, 56% of FFS, and 63% of no predominant source physicians (P < 0.01). CONCLUSIONS: The primary payment source of a practice appears to influence use of proactive immunization practices.

Child↗

Influence of iron status and iron supplements on natural killer cell activity in trained women runners.

Twenty-two trained women runners (.VO2peak 48.1 + 1.2 ml x kg -1 x min -1) were divided into an iron supplement (n = 13) or placebo group (n = 9) based on initial serum ferritin concentration (24.2 +/- 2.9 and 58.5 +/- 4.0 microg x l -1, respectively). Exercise consisted of a 35-min run (80 % .VO2peak) and was performed at week 0 (WK0), after two weeks of intensified training (WK2) and after eight weeks recovery training (WK10). The eight weeks recovery training were concomitant with subjects taking iron supplements or placebo in a double blind fashion. Concentrations of serum ferritin, serum iron and total iron binding capacity were assessed pre-exercise and complete blood count, natural killer cell activity (NKACT), and cell surface markers for CD3+, CD4+, CD3+,CD8+, CD3-, CD16+, CD56+ cells were determined both pre- and post-exercise. Serum ferritin concentrations were significantly (p < 0.05) increased on WK10 compared to WK2 (time effect). NKACT (%lysis) and NK cell number was lower (p < 0.05) at WK0 for supplement (42.9 +/- 1.9 % and 305.5 +/- 15.0 x 10 6 x l -1, respectively) compared to placebo groups (50.9 +/- 2.0 and 406.1 +/- 25.6, respectively). Two weeks of intensified training did not alter indices of host defense. In conclusion, NKACT and NK cell numbers were lower in subjects with greater body mass and lower iron stores (p < 0.05), but were not significantly altered after two weeks of intensified training or when serum ferritin levels increased.

Adaptation, Physiological↗

Immunological responses of breast cancer patients to behavioral interventions.

This article reports the results of an 18-month study of immune system and psychological changes in stage 1 breast cancer patients provided with relaxation, guided imagery, and biofeedback training. Thirteen lymph node negative patients who had recovered from a modified radical mastectomy were randomly assigned to either an immediate treatment or a delayed treatment control group. Multiple pre-post psychological measures were performed. Significant effects were found in natural killer cell (NK) activity (p < .017), mixed lymphocyte responsiveness (MLR) (p < .001), concanavalin A (Con-A) responsiveness (p < .001), and the number of peripheral blood lymphocytes (PBL) (p < .01). No significant psychological changes were detected; however, reductions were seen in psychological inventory scales measuring anxiety. The results show that behavioral interventions can be correlated with immune system measures, thereby replicating the results of an earlier pilot study from our Center. Discussion is provided on differential T-cell and B-cell responsiveness to behavioral interventions.

Adult↗

Cocaine vaccines: antibody protection against relapse in a rat model.

The efficacy of active immunization with the cocaine immunogen GNC-keyhole limpet hemocyanin (KLH) in preventing cocaine self-administration reinstatement was assessed in rats. An animal model of relapse was used where rats were trained to self-administer cocaine, subjected to a period of extinction by substituting the drug for saline, vaccinated, and re-exposed to cocaine. Compared with controls, animals immunized with GNC-KLH did not reinstate cocaine self-administration behavior when given a noncontingent cocaine infusion on two consecutive days. Upon double and triple infusions, 38-62% of vaccinated animals failed to reinstate as compared with full reinstatement in all control animals. Exposure to ad libitum cocaine reinstated baseline values in control animals and resulted in double to triple the baseline values of self-infusions in vaccinated animals, suggesting a partial antibody-mediated blockade of cocaine access to the central nervous system. This compensating effect was blocked by passive immunization pretreatment with the monoclonal IgG GNC92H2 in both vaccinated and control groups. To further assess the surmountability potential of GNC-KLH-induced antibody titers by cocaine self-administration, and the capacity of these titers to block the reinforcing effects of the drug, rats were tested at various doses of cocaine (0.015-0.5 mg/infusion). Active immunization with GNC-KLH produced approximately an 8-fold rightward shift of the dose-effect function for cocaine. The results reported suggest that immunopharmacotherapy may offer a promising means to treat cocaine abuse by aiding in the prevention of relapse.

Animals↗

Impact of free vaccine and insurance status on physician referral of children to public vaccine clinics.

CONTEXT: Concerns about financial barriers to vaccination led to the development of the Vaccines for Children (VFC) program, which provides free vaccines to states for children who are uninsured, Medicaid eligible, or Native American or Native Alaskan. OBJECTIVE: To understand the effect of economic factors on physician likelihood of referring children to public vaccine clinics for immunizations and to evaluate the VFC program. DESIGN: A standardized survey was conducted in 1995 by trained personnel using computer-assisted telephone interviewing. SETTING AND PARTICIPANTS: A stratified random sample of family physicians, pediatricians, and general practitioners younger than 65 years who were in office-based practices across the United States. MAIN OUTCOME MEASURES: Likelihood of referral of a child to a health department for vaccination by child's insurance status and by the physician's receipt of free vaccines. RESULTS: Of the 1769 physicians with whom an interviewer spoke, 1236 participated. Most respondents (66%) were likely to refer an uninsured child to the health department for vaccination, whereas only 8% were likely to refer a child who had insurance that covers vaccination. The majority (58%) of physicians reported differential referral based on insurance status. Among physicians who received free vaccine supplies from the VFC program or elsewhere, 44% were likely to refer an uninsured child whereas 90% of those not receiving free vaccine were likely to refer the same child (P<.001). In regression analysis, the receipt of free vaccine supplies accounted for 24% of the variance in the likelihood to refer an uninsured child for vaccination. CONCLUSIONS: Physicians receiving free vaccine supplies report being less likely to refer children to public clinics for vaccinations.

Child↗

Risk factors for improper vaccine storage and handling in private provider offices.

CONTEXT: Preventing loss of vaccine potency during storage and handling is increasingly important as new, more expensive vaccines are introduced, in at least 1 case requiring a different approach to storage. Little information is available about the extent to which staff in private physicians' offices meet quality assurance needs for vaccines or have the necessary equipment. Although the National Immunization Program at the Centers for Disease Control and Prevention (CDC) in 1997 developed a draft manual to promote reliable vaccine storage and to supplement published information already available from the CDC and the American Academy of Pediatrics, the best ways to improve vaccine storage and handling have not been defined. OBJECTIVES: To estimate the statewide prevalence of offices with suboptimal storage and handling, to identify the risk factors for suboptimal situations in the offices of private physicians, and to evaluate whether the distribution of a new National Immunization Program draft manual improved storage and handling practices. DESIGN: Population-based survey, including site visits to a stratified, random sample of consenting private physicians' offices. At least 2 months before the site visits, nearly half (intervention group) of the offices were randomly selected to receive a draft CDC manual entitled, "Guideline for Vaccine Storage and Handling." The remainder was considered the control group. Trained graduate students conducted site visits, all being blinded to whether offices were in the intervention or control groups. Each site visit included measurements of refrigerator and freezer temperatures with digital thermometers (Digi-thermo, Model 15-077-8B, Control Company, Friendswood, TX; specified accuracy +/- 1 degrees C). Their metal-tipped probes were left in the center shelf of cold storage compartments for at least 20 minutes to allow them to stabilize. The type of refrigerator/freezer unit, temperature-monitoring equipment, and records were noted, as were the locations of vaccines in refrigerator and freezer, and the presence of expired vaccines. Other information collected included the following: staff training, use of written guidelines, receipt of vaccine deliveries, management of problems, number of patients, type of office, type of medical specialty, and the professional educational level of the individual designated as vaccine coordinator. PARTICIPANTS: Two hundred twenty-one private physicians' offices known by the Georgia Immunization Program in 1997 to immunize children routinely with government-provided vaccines. OUTCOME MEASURES: Estimates (prevalence, 95% confidence interval [CI]) of immunization sites found to have a suboptimally stored vaccine at a single point in time, defined as: vaccine past expiration date, at a temperature of </=1 degrees C or >/=9 degrees C in a refrigerator or >/=-14 degrees C (recommended for varicella vaccine) in freezer, and odds ratios (ORs) for risk factors associated with outcomes. We performed chi(2) analysis and Student's t tests to compare the administrative characteristics and quality assurance practices of offices with optimal vaccine storage with those with suboptimal storage, and to compare the proportion of offices with suboptimal storage practices in the groups that did and did not receive the CDC manual. RESULTS: Statewide estimates of offices with at least 1 type of suboptimal vaccine storage included: freezer temperatures measuring >/=-14 degrees C = 17% (95% CI: 10.98, 23.06); offices with refrigerator temperatures >/=9 degrees C = 4.5% (95% CI: 1.08, 7.86); offices with expired vaccines = 9% (95% CI: 4.51, 13.37); and offices with at least 1 documented storage problem, 44% (95% CI: 35.79, 51.23). Major risk factors associated with vaccine storage outside recommended temperature ranges were: lack of thermometer in freezer (OR: 7.15; 95% CI: 3.46, 14.60); use of freezer compartment in small cold storage units (OR: 5.46; 95% CI = 2.70, 10.99); lack of thermometer in refrigerator (OR: 3.07; 95% CI: 1.15,8.20); and failure to maintain temperature log of freezer (OR: 2.70; 95% CI: 1.40, 5.23). Offices that adhered to daily temperature monitoring for all vaccine cold storage compartments, compared with those that did not, were 2 to 3 times more likely to assign this task to staff with higher levels of training, have received a recent visit from the state immunization program, and be affiliated with a hospital or have Federally Qualified Health Center status. In addition, sites using >1 refrigerator/freezer for vaccine storage were more likely to have at least 1 cold storage compartment outside recommended temperature ranges. We found no significant differences in the data reported above between the intervention group (received copy of the draft manual) and the control group (did not receive copy of draft manual), even when controlling for the annual number of immunizations given or the type of office. (ABSTRACT TRUNCATED)

Child↗

Mucosal (secretory) immune system responses to exercise of varying intensity and during overtraining.

Athletes are susceptible to upper respiratory tract infection (URTI) during intense training and after major competition; high rates of URTI have also been associated with the overtraining syndrome (staleness). Secretory immunoglobulin A (IgA), the predominant immunoglobulin in mucosal secretion, is a major effector of resistance against pathogenic microorganisms causing URTI. Previous work has shown that salivary IgA levels decrease after a single bout of intense prolonged exercise. The purpose of these studies was to examine the IgA response to various exercise conditions. Whole, unstimulated saliva was obtained before and after exercise. IgA concentration (microgram.mg protein-1) was measured by ELISA and IgA secretion rate (microgram.min-1) calculated. Study 1: Recreational joggers ran on a treadmill for 40 min at 55% and 75% VO2peak and competitive distance runners ran for 90 min at the same intensites. In both groups, IgA secretion rate did not change significantly after exercise at either intensity. Study 2: Competitive runners ran on a treadmill for 90 min at 75% VO2peak on 3 consecutive days. IgA secretion rate decreased 20 to 50% after exercise (p < .001). Post-exercise IgA secretion rates were significantly lower (p < .05) on days 2 and 3 compared with day 1. Study 3: Elite swimmers were followed over a 6 month season, with IgA concentration measured at 5 times. Throughout the season, IgA concentration was significantly (p < .05) lower in stale compared with well-trained swimmers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Tumor growth retardation, cure, and induction of antitumor immunity in B16 melanoma-bearing mice by low electric field-enhanced chemotherapy.

PURPOSE: The exposure of cells in vitro to trains of low voltage-pulsed electric fields in the range of 20-100 V/cm was previously shown to induce an efficient uptake of macromolecules with molecular weight in the range of M(r) 300-2,000,000 via an endocytic-like process. This study examines the antitumor effectiveness of treatment based on similar exposure of solid tumors in mice to low electric fields (LEFs) in the presence of chemotherapeutic agents. EXPERIMENTAL DESIGN: LEF was applied to approximately 5 mm in diameter (60-70 mm(3)) s.c. B16-F10.9 melanoma tumors by percutaneously placed electrodes after intratumoral injection of either cis-platinum(II) diamminedichloride, Taxol, 5-fluorouracil, or bleomycin. RESULTS: Significant eradication of primary tumors, prolongation of survival, and complete cure of some of the C57Bl/6 mice from both primary tumors and metastases were achieved using this technique with cis-platinum(II) diamminedichloride, bleomycin, and Taxol (13.5, 8, and 26% cure rate, respectively). Mice cured by LEF-enhanced chemotherapy and challenged with a tumorigenic dose of B16-F10.9 cells lived significantly longer than first time inoculated ones, and 23.5% of the challenged mice did not develop tumors at all. Spleen cells from the cured mice that were inoculated together with B16-F10.9 cells inhibited the primary tumor growth in intact mice. Histological analysis of tumor sections of LEF-enhanced chemotherapy-treated mice revealed multiple necrotic areas, apoptosis, and massive infiltrates of T lymphocytes and macrophages. Low voltage electrochemotherapy with Taxol was shown to be more effective than surgical removal of the tumor with Taxol. CONCLUSIONS: These findings indicate that LEF-enhanced chemotherapy is an effective treatment of animals bearing metastatic melanoma.

Animals↗