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Toward a core nutraceutical program for cancer management.

As previously suggested, it may be feasible to impede tumorevoked angiogenesis with a nutraceutical program composed of glycine, fish oil, epigallocatechin-3-gallate, selenium, and silymarin, complemented by a low-fat vegan diet, exercise training, and, if feasible, a salicylate and the drug tetrathiomolybdate. It is now proposed that the scope of this program be expanded to address additional common needs of cancer patients: blocking the process of metastasis; boosting the cytotoxic capacity of innate immune defenses (natural killer [NK] cells); preventing cachexia, thromboembolism, and tumor-induced osteolysis; and maintaining optimal micronutrient status. Modified citrus pectin, a galectin-3 antagonist, has impressive antimetastatic potential. Mushroombeta-glucans and probiotic lactobacilli can amplify NK activity via stimulatory effects on macrophages. Selenium, beta-carotene, and glutamine can also increase the number and/or cytotoxic activity of NK cells. Cachectic loss of muscle mass can be opposed by fish oil, glutamine, and beta-hydroxy-beta-methylbutyrate. Fish oil, policosanol, and vitamin D may have potential for control of osteolysis. High-dose aspirin or salicylates, by preventing NF-B activation, can be expected to aid prevention of metastasis and cachexia while down-regulating osteolysis, but their impacts on innate immune defenses will not be entirely favorable. A nutritional insurance formula crafted for the special needs of cancer patients can be included in this regimen. To minimize patient inconvenience, this complex core nutraceutical program could be configured as an oil product, a powder, and a capsule product, with the nutritional insurance formula provided in tablets. It would be of interest to test this program in nude mouse xenograft models.

Animals↗

[The health status and morbidity in the crew members of submarines at different periods of combat training activity].

It was found out in the result of complex examination of health status of 2020 enlisted men from 65 submarine crews of the North Fleet, that the inflammatory and infectious morbidity during the post-cruise period was considerably higher than during seagoing period. This morbidity was characterized by seasonal outbreaks. As for the types of the immune dependency, there were no seasonal changes. The peak of infectious morbidity coincides with the pre-cruise preparative period and post-cruise recreation due to "mixing" of the crews and diminishing of the non-specific resistance of an organism.

Chi-Square Distribution↗

Epidemic of adenovirus-induced respiratory illness among US military recruits: epidemiologic and immunologic risk factors in healthy, young adults.

Adenovirus (Ad)-induced acute respiratory illnesses resurged among civilian adults and selected military training populations in the United States during the late 1990s. We examined the epidemiologic and immunologic correlates of Ad-induced respiratory illnesses during a large outbreak at an Army basic training installation in southeast United States during a 9-day period in November 1997. A total of 79 recruits hospitalized with acute respiratory illnesses were evaluated during the outbreak period; confirmation of Ad infection by isolation of Ad-like cytopathic agents from throat cultures was detected in 71 (90%) of these patients. Serotyping of 19 (27%) of these 71 isolates identified the etiologic agent to be Ad type 4 (Ad4). In addition, 30 (81%) of 37 patients in whom paired sera were collected demonstrated significant increases (i.e., 4-fold or higher) in serum anti-Ad4 neutralizing antibodies. Anti-Ad4 immunity in new recruits was found to be very low (15 to 22%). A case-control study involving 66 of the 79 hospitalized cases and 189 non-ill controls from the same units was conducted. A lower risk of hospitalization for acute respiratory illnesses was documented for female recruits (odds ratio[OR] = 0.47, P <.05) whereas, a higher risk was noted for smokers (OR = 1.89, P <.05). Unit (training company) attack rates as high as 8 to 10% per week were documented and the outbreak quickly subsided after live, oral Ad types 4 and 7 vaccination was resumed in November 1997. Re-establishment of a military Ad vaccination program is critical for control of Ad-induced acute respiratory illnesses.

Acute Disease↗

Does glutamine have a role in reducing infections in athletes?

There is an increased risk of infections in athletes undertaking prolonged, strenuous exercise. There is also some evidence that cells of the immune system are less able to mount a defence against infections after such exercise. The level of plasma glutamine, an important fuel for cells of the immune system, is decreased in athletes after endurance exercise; this may be partly responsible for the apparent immunosuppression which occurs in these individuals. We monitored levels of infection in more than 200 runners and towers. The levels of infection were lowest in middle-distance runners, and highest in runners after a full or ultramarathon and in elite rowers after intensive training. In the present study, athletes participating in different types of exercise consumed two drinks, containing either glutamine (Group G) or placebo (Group P) immediately after and 2 h after exercise. They subsequently completed questionnaires (n = 151) about the incidence of infections during the 7 days following the exercise. The percentage of athletes reporting no infections was considerably higher in Group G (81%, n = 72) than in Group P (49%, n = 79, p < 0.001).

Adult↗

Hypnosis as a modulator of cellular immune dysregulation during acute stress.

To assess the influence of a hypnotic intervention on cellular immune function during a commonplace stressful event, the authors selected 33 medical and dental students on the basis of hypnotic susceptibility. Initial blood samples were obtained during a lower stress period, and a second sample was drawn 3 days before the first major exam of the term. Half of the participants were randomly assigned to hypnotic-relaxation training in the interval between samples. Participants in the hypnotic group were, on average, protected from the stress-related decrements that were observed in control participants' proliferative responses to 2 mitogens, percentages of CD3+ and CD4+ T-lymphocytes, and interleukin 1 production by peripheral blood leukocytes. More frequent hypnotic-relaxation practice was associated with higher percentages of CD3+ and CD4+ T-lymphocytes. These data provide encouraging evidence that interventions may reduce the immunological dysregulation associated with acute stressors.

Adult↗

Adverse events associated with intravenous immunoglobulin therapy.

In addition to its U.S. Food and Drug Administration (FDA) approved conditions, immune globulin intravenous (IGIV) is now being used to treat a vast array of autoimmune disorders. Some of the reasons for this overall increase in the use of IGIV include its effectiveness and safety. Despite many years of safe use, side effects and adverse reactions still occur. Common and mild side effects associated with IGIV include: headache, malaise, nausea, low-grade fever, urticaria, arthralgias, and myalgia. These symptoms typically resolve within a few days after their onset. Although rare, the serious and potentially fatal side effects include: anaphylactic reactions, aseptic meningitis, acute renal failure, stroke, myocardial infarction, and other thrombotic complications. Many of these side effects have occurred in patients who have significant, underlying risk factors for the development of the event. Thus, it is vitally important that a thorough and comprehensive medical evaluation be performed on every patient who is being evaluated for potential IGIV therapy. This evaluation can, to some extent, significantly minimize the risk of these side effects. Careful, constant, and close monitoring by trained personnel during the infusion can also result in early detection of such events. Physicians should thoroughly discuss the risks and benefits of IGIV with patients who are being considered for this therapy.

Humans↗

Special feature for the Olympics: effects of exercise on the immune system: infections and exercise in high-performance athletes.

The elite athlete has a potentially increased sensitivity to respiratory infections, rendering protective measures particularly important. Some other infections that may appear in clusters in the sports setting, such as gastroenteritis, leptospirosis, herpes simplex and viral hepatitis, also require special precautionary attention. Strenuous exercise during ongoing infection and fever may be hazardous and should always be avoided. In addition, early symptoms of infection warrant caution until the nature and severity of the infection become apparent. Because myocarditis may or may not be accompanied by fever, malaise or catarrhal symptoms, athletes should be informed about the symptoms suggestive of this disease. Although sudden unexpected death resulting from myocarditis is rare, exercise should be avoided whenever myocarditis is suspected. Guidelines are suggested for the management and counselling of athletes suffering from infections, including recommendations on when to resume training. Acute febrile infections are associated with decreased performance resulting from muscle wasting, circulatory deregulation and impaired motor coordination, which require variable amounts of time to become normalized once the infection is over.

Adult↗

[Microeconomic evaluation of a mass preventive immunisation campaign against meningococcal meningitis and yellow fever in Senegal in 1997].

Large epidemics of group A meningococcal meningitis occurred in 1995 and 1996 in several countries of the Sub-Saharan Africa zone known as the "meningitis belt", and more particularly in West Africa. Most of these countries affected by the epidemics met difficulties to set up the strategy recommended by the World Health Organization and which includes: Epidemiological surveillance and epidemic incidence threshold calculation to detect early meningitis epidemics and emergency vaccination campaigns with meningococcal A + C polysaccharide vaccine, if possible within the 4-to-6 weeks following the moment the threshold is reached. In this context of epidemics, notably in Mali, and in front of the risk of resurgence of yellow fever, the Ministry of Health of Senegal decided to conduct mass preventive immunization campaigns in 1997 against meningo- coccal meningitis and yellow fever in the districts located in the eastern part of the country and where emergency vaccination would have been difficult in case of epidemic because these area are difficult to reach. A short-term microeconomic evaluation of additional costs that are necessary to organize one of these mass preventive immunization campaigns was conducted in 1997 in the Matam District, in the Northeast part of Senegal. The method rested on value attribution and accounting procedure. The cost was defined as the monetary value of all mobilized resources to product the campaign corresponding to a plurality of charges and representing all of the effective expenses and donations. During this campaign, 85,925 people were vaccinated and a total number of 163,981 doses of both polysaccharide A + C meningococcal and yellow fever vaccines were administered within 3 weeks. Four intervention strategies were involved: Three for vaccination (mobile, fixed and outreach strategy) and one for coordination, information and training. The total cost of the campaign was 55,322.75 euros. Vaccines and solvents represented 60% of the total cost of the campaign, materiel for injection and safety of injection 26%, vaccination staff 7%, and logistics 7%. The mean cost was 0.34 euro per administered dose and 0.64 euro per vaccinee. The mean cost per administered dose of meningococcal vaccine was 0.44 euro. The mean cost of preventive meningococcal immunization was not higher than the mean cost of meningococcal vaccination during mass emergency immunization campaigns in other countries. The addition of yellow fever antigen brought down the campaign mean cost by 0.11 euro and it allowed economies of scales. Direct unit costs per administered dose were higher when people were vaccinated through the outreach strategy (0.35 euro) than when fixed and mobile strategies were used (0.318 and 0.323 euro, respectively). Costs related to transportation and staff were proportionally higher for the outreach strategy. Direct unit costs per administered dose were higher when vaccinations were done in rural areas (0.32 euro) than when done in urban areas (0.31 euro). Direct unit costs increased when the size of target communities decreased (in communities with less than 100 people to vaccinate versus 0.38 euro in communities with more than 2,000 people to vaccinate). This study allowed us to set up a method to measure, describe and analyze the costs of a mass preventive campaign. It demonstrated the economic impact of using multiple antigens during a single preventive campaign.

Costs and Cost Analysis↗

An economic comparison of chloroquine and sulfadoxine-pyrimethamine as first-line treatment for malaria in South Africa: development of a model for estimating recurrent direct costs.

The relative cost-effectiveness of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) as first-line antimalarial therapy in southern Africa is of great interest to policymakers, clinicians and researchers in the subregion. A model was developed to access the cost-effectiveness of replacing CQ with SP as first-line treatment in Mpumalanga, South Africa, where malaria is seasonal and the population is non-immune. In-vivo drug resistance levels were used to derive a 'resistance variable' for each drug, which was used to compare the costs to the public healthcare provider associated with either therapeutic option. Costs including drugs, staff time, transport, maintenance, utilities, training and consumables were determined and subjected to Monte Carlo simulation and subsequent analysis to generate an average cost-effectiveness ratio (ACER) with confidence intervals for each drug. SP was found to be 4.8 (95% CI 3.3-6.7) times more cost-effective than CQ in Mpumalanga at 1997 resistance levels and costs, despite the far greater cost per treatment course of SP (US$ 4.02 as opposed to US$ 0.22 for CQ) in South Africa. At the price of SP in Kenya and Uganda (US$ 0.47-4.80 per treatment course), the ACER for SP does not change materially, increasing to between 5.1 and 5.6. Resistance emerged as the factor that most influenced the ACER of a specific drug. Indirect costs, compliance, changes in effectiveness and costs over time and costs of adverse events were not included in the model owing to paucity of data and logistical difficulties. Since most of these are likely to be similar in both drug models, the relative ACER is unlikely to be significantly altered by their inclusion.

Adult↗

Mini-invasive surgery may be advised in oncology.

In the last decade mini-invasive surgery has consistently developed with good results, but also with some unjustified clinical applications. This review is aimed at defining evidence based indications and procedures ('clinical practice') and those still worthy of controlled studies in oncologic centers with expertise in mininvasive surgery ('clinical research'). At present, diagnostic and staging laparoscopy and thoracoscopy represent the 'standard' for different tumors. Conversely, therapeutic indications according to evidence based medicine criteria are still limited. Tumors treatment by mini-invasive surgery requires 'expertise' on the part of the surgical team; this can be achieved by extensive training of a correct use of instruments and methods following the general surgical principles of traditional 'open surgery'.

Diagnostic Equipment↗

The terrible twos--anger and anxiety. Hazardous to your health.

Anxiety and anger are hazardous to health. This article offers a selective review of research that illustrates how anxiety and anger increase vulnerability to illnesses, compromise the immune system, increase lipid levels, exacerbate pain, and increase the risk of death from cardiovascular disease and from all sources of death. Possible mechanisms for such effects are identified, including the role of cardiovascular reactivity. Finally, data are provided on Anxiety Management Training, a brief, structured psychological intervention that has proven effective in anxiety as well as anger management.

Anger↗

Large epidemic of respiratory illness due to adenovirus types 7 and 3 in healthy young adults.

After 25 years of successful control through immunization, respiratory infections due to adenoviruses have reemerged to threaten the health of young adults in the military. Shortly after the loss of adenovirus vaccine supplies, a large outbreak of respiratory illness was observed at the United States Navy's sole basic training center. Laboratory testing confirmed 541 cases of adenovirus infection, including 378 cases due to serotype 7 and 132 cases due to serotype 3. This outbreak was remarkable because of its unique serotype distribution and the large amount of data available to describe demographic factors associated with infection. This was the largest outbreak of respiratory illness due to adenovirus types 7 and 3 documented in recent history, and it portends even greater challenges for young adults in the military in the postvaccine era.

Adenovirus Infections, Human↗

[Effects of acute endurance exercise and 8 week training on the production of reactive oxygen species from neutrophils in untrained men].

We investigated the effects of acute endurance exercise and habitual physical activity for health maintenance on human neutrophil function in 12 untrained men. The acute exercise condition was a continuous exercise for 90 minutes at the intensity of 50% and 55% of maximal oxygen uptake (VO2max) on an ergometer. The training program was 3 km jogging three times per week for 8 weeks. The capacity of neutrophils to produce reactive oxygen species (ROS) was detected with lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent chemiluminescence (LmCL) on stimulation with opsonized zymosan (OZ) and phorbol myristate acetate (PMA). As for the acute exercise effects, both LgCL and LmCL responses of neutrophils, stimulated using PMA consistently increased after exercise at 50%VO2max, whereas those stimulated with OZ remained unchanged. At 55%VO2max, LgCL responses to both stimulants increase maximally 1 h after exercise, and then decreased 3 h after exercise, whereas LmCL responses to both stimulants increased continuously after exercise at 55%VO2max. These phenomena observed at 55%VO2max compared to 50%VO2max suggests the improved capacity of producing ROS neutrophils after exercise. The number of neutrophils also increased maximally 1 h after exercise, due to the mobilization of band neutrophils (shift to the left), suggesting that functional changes was associated with cell mobilization. The increase in the capacity of neutrophils to produce ROS and marked neutrophilia following the acute endurance exercise suggests that a large quantity of ROS may be produced in vivo. As for the training effects, the LgCL and LmCL responses were maintained in the exercise group as compared to the decreased ones in the control group. The difference between the exercise group and the control group was observed only in LgCL response to OZ. Humoral immune factors (IgG, IgA, IgM, C3, C4) and serum opsonic activity were also unaltered. These phenomena suggest that homeostasis might be kept constant in terms of immunity through regular physical activity.

Adult↗

Circulating immunoreactive proANP(1-30) and proANP(31-67) in sedentary subjects and athletes.

BACKGROUND: Atrial natriuretic peptide (ANP) is synthesized and stored in myocytes as prohormone(1-126), which upon release is cleaved into proANP(1-98) and alpha-ANP(99-126). In addition, cleavage of proANP(1-98) produces proANP(1-30), proANP(31-67), and proANP(79-98) fragments. ProANP(1-30) and proANP(31-67) have roles in fluid and electrolyte homeostasis. The aim of the present study was to develop a plasma assay for proANP(1-30) and proANP(31-67) and to compare results in trained athletes and sedentary subjects. METHODS: Two competitive enzyme immunoassays were established with affinity-purified sheep antiserum against synthetic ANP fragments. The immunoreactivity (ir) of proANP(1-30) and proANP(31-67) was measured in 10-microL plasma samples without extraction in a microwell-based assay. Plasma concentrations in sedentary male subjects (n = 22) and male endurance athletes (n = 14) were examined. RESULTS: In the assay for ir-proANP(1-30) and ir-proANP(31-67), the concentrations at 95% B/B(0) were 4.7 and 14.2 pmol/L, respectively. Within-run CVs were 4-6% and 5-6%, and between-run CVs were 9% for both assays. Both assays were linear on dilution (y = 0.9945x - 0. 7291 and y = 1.0001x - 3.428), and the recoveries were 102-112% and 102-106%, respectively. In the sedentary and athletic groups, the ir-proANP(1-30) concentrations were similar: 318 +/- 38 pmol/L and 312 +/- 25 pmol/L (mean +/- SE), respectively, whereas the ir-proANP(31-67) was higher in the rowers (713 +/- 81 pmol/L) than in the sedentary subjects (387 +/- 71 pmol/L; P <0.005). CONCLUSIONS: The proANP fragment assays are precise (CV <10%) and exhibit nearly quantitative recovery (102-112%). Only ir-proANP(31-67) responds to physical training.

Animals↗

Effectiveness of the meningococcal vaccination programme for British Armed Forces recruits.

After several clusters of meningococcal disease arose among recruits to the British Armed Forces, vaccination against A + C meningococcal disease was introduced for military recruits in 1992. From 1993 onwards, no further clusters of group C infection were reported and incidence of meningococcal disease among trained soldiers fell, but there was no significant reduction in the overall incidence of meningococcal disease in recruits.

Humans↗

[Immunological criteria for the selection of servicemen for service under extreme conditions].

The paper deals with the results of the comparative immunological survey of three groups: group I (450 persons), a special unit "Quarantine" undergoing training for hostilities in Afghanistan; group II (800 persons), an armored regiment assigned for home service; and group III (578 persons), students of a vocational technical school. Among the members of all three groups disturbances in the systems of humoral and local immunity were detected, but the number of immunodeficiency cases in group I considerably exceeded that in groups II and III, which correlated with considerably greater morbidity figures registered in group I. On the basis of these data immunological risk groups were formed and immunocorrective measures were recommended.

Adaptation, Physiological↗

Measuring state expenditures for core public health functions.

In 1993, the U.S. Public Health Service, with the assistance of the Public Health Foundation (PHF), launched a pilot study to develop state and national expenditure estimates for the core functions of public health. The core public health functions selected for the data collection effort were (1) health-related data, surveillance, and outcomes monitoring; (2) investigation and control of diseases, injuries, and response to natural disasters; (3) immunizations, family planning, and STD and TB clinical services; (4) protection of environment, housing, food, water, and the workplace; (5) laboratory services; (6) public information and education and community mobilization; (7) targeted outreach and linkage to personal services; (8) accountability/quality assurance; (9) training and education; and (10) leadership, planning, policy development, and administration. State health officials from Connecticut, Iowa, Missouri, Oregon, and Rhode Island helped develop a methodology and a set of guidelines for estimating expenditures on core functions and used this methodology to report expenditure data. Three additional states--Illinois, New York, and Texas--joined in a second phase of the pilot study, one that included collecting data on personal health services and total agency expenditure data. The eight states' combined per capita core function expenditures were $44 in fiscal year (FY) 1993. This included expenditures by state and local public health agencies and state substance abuse, mental health, and environmental health agencies. Expenditures for core public health functions accounted for 27% of these agencies' total expenditures. The largest core function expenditure accounting for approximately 30% of the total was for the protection of environment, housing, food, water, and the workplace. Extrapolating the eight states' expenditure estimates to the national level, spending for core public health functions in FY 1993 totaled $11.4 billion, or 1.3% of total U.S. health spending. The pilot project demonstrates that with appropriate guidance, including an estimating methodology and uniform definitions, categorical program data can be reported by function. The results of the data collection effort also demonstrate the potential utility of examining expenditures by core functions for state planning and policy making. The methodology allows states to distinguish core functions from other responsibilities, providing states with quantified information useful for reform efforts.

Data Collection↗