The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients - A pilot study.

Effectiveness of omega-3 supplementation in cystic fibrosis (CF) remains controversial. This study sought to evaluate clinical status, exercise tolerance, inflammatory parameters, and erythrocyte fatty acid profile after 1 year of oral omega-3 supplementation in CF patients. Fifteen ΔF508-homozygous patients undergoing chronic azithromycin were randomized to receive omega-3 fish oil supplementation at a dose of 60mg/Kg/day or placebo. In comparison with the previous year, in the supplemented group, the number of pulmonary exacerbations decreased at 12 months (1.7 vs. 3.0, p<0.01), as did the duration of antibiotic therapy (26.5 days vs. 60.0 days, p<0.025). Supplementation significantly increased the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as early as <3 months of administration, with concomitant decreases in arachidonic acid (AA) levels. This pilot study suggests that long-term omega-3 supplementation offers several clinical benefits as to the number of exacerbations and duration of antibiotic therapy in CF patients.

Prevalence of zinc deficiency and its clinical relevance among hospitalised elderly.

Zinc is an essential trace element, and constituent of many metallo-enzymes required for normal metabolism. Age may be associated with altered metallothionein metabolism related to changes in zinc metabolism. The objectives of this study were: (i) to assess the prevalence of zinc deficiency among hospitalised elderly patients; (ii) to define the social, functional, pathological and nutritional characteristics of zinc deficient elderly hospitalised patients; and (iii) to assess the relationship between the zinc status and humoral immune function among hospitalised elderly patients. Fifty consecutive patients underwent comprehensive geriatric assessments included evaluations of the medical (index of the severity of the disease(s)), psychiatric (Geriatric depression scale (GDS)), therapeutic, social, functional (Katz's scale), and nutritional problems (Mini Nutritional Assessment (MNA) and biochemical markers (zinc, albumin, prealbumin (PAB), cholesterol) before their discharge. Fourteen patients (28%) presented a zinc concentrations lower than 10.7 micromol/l, this value is usually considered as the cut-off level below which a zinc deficient status is possible. Higher proportions of respiratory infections, cardiac failure, and depression were observed among zinc deficient patients as compared with the group of patients with normal zinc status. The other parameters of comprehensive geriatric assessment did not allow to discriminate the zinc deficient patients. The only slight differences (which remained unsignificant) concerned the prealbumin levels which tended to be higher in the group of patients presenting normal zinc status than in the group with poor zinc status (0.208+/-0.062 versus 0.171+/-0.068 g/l respectively, P=0.06), and the IgG2 levels which tended to be lower in the group of patients with normal zinc status than in the group presenting poor zinc status (2.77+/-1.91 versus 4.06+/-2.56, respectively, P=0.057). A negative correlation was observed between the Zn concentrations and the IgG2 levels (Spearman R=-0.311, P=0.028). To the best of our knowledge, this is the first study presenting zinc status according to a comprehensive geriatric assessment among European hospitalised geriatric patients. We decided to perform this study to known whom of our patients needed to be supplemented with zinc administration. Considering the low energy intake of hospitalised patients (confirmed here in regards of the nutritional assessment), and the insufficient trace element density in European foods, the relevance of providing medical supplements or enriched foods to this population has to be evaluated. Although most of the current diseases may be relevant to long-term interactions between nutrition and ageing, certain states observed in the elderly, like impaired immune and cognitive functions, could still benefit from an appropriate nutritional supplementation.

Early effect of ultrarush venom immunotherapy on the IgG antibody response.

BACKGROUND: We have previously shown in several allergy models that allergic and tolerance status with respect to allergens is associated with a somewhat different dominant specificity of IgG antibodies. The objective was to test this hypothesis in the compelling model of ultrarush venom immunotherapy (VIT), which induces clinical tolerance after only a few hours of treatment. METHODS: Antibody titers and specificity were evaluated through solid-phase ELISA using streptavidin-biotin technology in 12 patients allergic to wasp venom before and during the ultrarush procedure (at 12 h, 24 h, and 15 days). The results were compared with those from another group of 20 patients treated with venom injections for at least 2 years. RESULTS: No significant change was observed in IgG titers during the early phase of VIT. The capacity of individual sera to prevent the antigen binding of pooled IgG from allergic patients changed rapidly, with mean percentage inhibitions falling from 80+/-15%, before starting VIT, to 26+/-14%, 35+/-15%, and 34+/-5% after 12 h, 24 h, and 15 days of treatment, respectively (P<0.001 by one-way ANOVA). The capacity of individual sera to prevent the antigen binding of pooled IgG from patients receiving prolonged VIT changed, with mean percent inhibitions increasing from 47+/-8%, before starting VIT, to 76+/-7%, 83+/-6%, and 87+/-6% after 12 h, 24 h, and 15 days of treatment, respectively (P<0.001 by one-way ANOVA). CONCLUSIONS: During the initial phase of ultrarush VIT, a change in IgG specificity, i.e., a change in the set of epitopes dominantly recognized by IgG on wasp-venom antigens, occurred concomitantly with early clinical tolerance and was already detectable a few hours after the onset of treatment. Although it may be an epiphenomenon, this change represents the earliest humoral modification described so far during this procedure. The mechanism is unknown, but it appears to be a selective depletion of the highest avidity antibody fraction by the venom injected in large doses at this stage of therapy. Finally, our data now show the previously documented association between a particular IgG specificity and the clinical status (allergy vs tolerance) to be true also with ultrarush VIT, a model in which the clinical ability to display allergic symptoms is rapidly reversed.

Relationship between allergic status and specificity of IgG antibody to inhaled allergens: the grass pollen model.

BACKGROUND: We have previously reported that IgG antibodies from healthy individuals and patients suffering from non-seasonal mite allergy bind to different sets of epitopes on Der p 1, allowing almost complete discrimination of the populations. OBJECTIVES: To confirm this observation in a seasonal allergy model where a clear relationship between allergic symptoms and exposure to the offending agent is established. To investigate whether the pattern of modified specificity is related to the differences in IgG subclass hierarchy usually exhibited by nonallergic and allergic populations. METHODS: The capacity of individual sera from patients allergic to grass pollen and healthy individuals, including grass pollen-sensitized subjects, to prevent the binding of pooled IgG, IgG1, and IgG4 fractions from grass pollen-allergic patients and healthy individuals to solid-phase bound grass pollen antigen was evaluated in enzyme-linked immunosorbent assay (ELISA) using streptavidin-biotin technology. Specificity controls were performed using sera from patients allergic to cat dander and house dust mite. RESULTS: The capacity of sera to prevent the antigen binding of allergic IgG averaged 84 +/- 5% for allergic sera and 53 +/- 6% for healthy sera (P < 0.001 by one-way anova). Conversely, using the antigen-binding capacity of healthy control IgG as reference, percentage inhibitions averaged 46 +/- 9% in grass pollen-allergic subjects compared with 80 +/- 4%, 82 +/- 2% in healthy individuals, and mite- and cat-allergic patients, respectively, resulting in two well-separated populations (P < 0.0001 by one-way anova). Similar results were found regardless of whether pooled IgG1 or IgG4 were used. CONCLUSION: Together with previous data, our results define a new type of humoral signature in the immune response to inhaled allergens. Allergic and healthy status differ not only in the presence or absence of specific IgE antibody but also in the preferential expression of distinct IgG specificities that are better correlated with clinical manifestations and are unrelated to subclass distribution.

Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation.

Strenuous exercise may be associated with immune suppression. However, the underlying mechanism is not known. A decrease in the plasma level of glutamine, which is utilised at a high rate by cells of the immune system, and an increase in the plasma level of some cytokines may impair immune functions such as lymphocyte proliferation after prolonged, exhaustive exercise. In two separate studies of the Brussels marathon, using similar protocols, the time course of the changes in the plasma concentrations of some amino acids (glutamine, glutamate, alanine, tryptophan and branched chain amino acids), acute phase proteins and cytokines (interleukins IL-1 alpha, IL-2, IL-6, tumour necrosis factor type a) was measured in male athletes. The numbers of circulating leucocytes and lymphocytes were also measured. Amino acid and cytokine concentrations have not previously been measured concomitantly in marathon runners; the measurement of some of these parameters the morning after the marathon (16 h) is novel. Another novel feature is the provision of glutamine versus placebo to marathon runners participating in the second study. In both studies the plasma concentrations of glutamine, alanine and branched chain amino acids were decreased immediately after and 1 h after the marathon. Plasma concentrations of all amino acids returned to pre-exercise levels by 16 h after exercise. The plasma concentration of the complement anaphylotoxin C5a increased to abnormal levels after the marathon, presumably due to tissue damage activating the complement system. There was also an increase in plasma C-reactive protein 16 h after the marathon. The plasma levels of IL-1 alpha were unaffected by the exercise, while that of IL-2 was increased 16 h after exercise. Plasma IL-6 was increased markedly (approximately 45-fold) immediately after and at 1 h after exercise. Neopterine, a macrophage activation marker, was significantly increased post-exercise. There was a marked leucocytosis immediately after the marathon, which returned to normal 16 h later. At the same time there was a decrease in the number of T-lymphocytes, which was further reduced within 1 h to below pre-exercise levels. Glutamine supplementation, as administered in the second study, did not appear to have an effect upon lymphocyte distribution.

Effects of selenium supplementation on immune parameters in gut failure patients on home parenteral nutrition.

The relationships between some parameters of the immune response and selenium were investigated in five patients receiving home parenteral nutrition for short-bowel syndrome. They were first submitted to a relative depletion by providing 20 micrograms selenium/day as L-selenomethionine for 1 mo. Then, daily selenium intake was raised to 200 micrograms for 2-4 mo. On entering the study, the patients presented a relatively good health status, and immunological parameters were at the lowest limit of the normal range. Four patients rapidly responded to the 200-micrograms supplementation by a continuous increase in their plasma selenium levels, whereas the fifth patient showed a moderate and late increase. At the end of the trial, there was an improvement in the lymphocyte response to pokeweed and phytohemagglutinin mitogens in four patients and to CD3 in three patients. The response to two of three antigens (Candidin, Varidase) tested was also enhanced in the same patients, but the response to the third antigen (tetanus toxoid) was uniformly low in all patients. The only patient showing essentially no immune improvement after selenium supplementation was the one with a low and delayed increase in plasma selenium. This study supports a role for selenium in the maintenance of an optimal immune response in humans.

Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast.

The effect of selenium supplementation on plasma selenium concentrations and lymphocyte-proliferation responses to mitogens was investigated in 22 elderly institutionalized subjects. Subjects were assigned to a 6-mo trial with either 100 micrograms Se/d (as selenium-enriched yeast) or a placebo. Plasma selenium concentrations of the selenium-supplemented group increased from 0.84 +/- 0.26 to 1.55 +/- 0.33 mumol/L (mean +/- SD) after 2 mo and the values plateaued thereafter. The mean response of lymphocytes to mitogens in elderly subjects tended to be lower than responses in healthy adults, although responses remained within the 5-95% confidence-interval limit for healthy adults. During selenium supplementation the proliferative response to pokeweed mitogen increased significantly (+79% of baseline concentrations after 4 mo, P less than 0.01) and reached the upper limit of the usual range for adults after 6 mo (+138%, P less than 0.001). In accordance with previous studies in animals and in vitro, this investigation demonstrates for the first time immunostimulatory properties of selenium-enriched yeast in elderly humans.

Autotransfusion during aorto-iliac surgery.

Red blood cell (RBC) quality and function during autotransfusion with the Solcotrans system were studied. Up to 64% (mean 999.5 +/- 310 ml) of the total volume of blood lost (mean 1895 +/- 707 ml) during operation in 10 patients undergoing elective abdominal aortic surgery was salvaged. No patient received homologous blood during surgery. Haemoglobin (Hb) and Haematocrit (PCV) values decreased but within acceptable limits. No evidence of DIC was found and renal function was unaffected. Mechanical and functional damage to the RBC was minimal and erythrocyte oxygen-carrying capacity was excellent. 2,3-DPGRBC concentration and RBC reduced glutathion were normal. The device was easy to handle and technical problems were not encountered. It was accurate in salvaging blood although the need for homologous blood was not entirely eliminated since four patients received homologous blood products in the postoperative period. No adverse clinical events occurred.

Training effects of sub-maximal electrostimulation in a human muscle.

This paper compares the effects of 6 wk of sub-maximal training by electrostimulation (100 Hz) and voluntary contractions on the contractile properties of the adductor pollicis muscle in intact man. The daily training program consisted of ten series of twenty 1-s isotonic contractions (60 to 65% of maximum) separated by 1-s intervals. The observed increase in muscle force, tested in maximal voluntary and electrically evoked contractions, appears to be significantly smaller during electrostimulation than during a training session performed by voluntary contractions. The increase in force recorded during electrostimulation is not associated with changes in the tetanus rates of tension development and tension relaxation (dP0/dt). Conversely, the tetanus time course is found to be significantly accelerated in muscles trained by voluntary contractions. No change of the surface action potential total area was observed during both training procedures. Furthermore, electrostimulation does not improve muscle resistance to fatigue, which is observed to be significantly increased after training by voluntary contractions. This study indicates that electrostimulation augments the muscle force of contraction by changing peripheral processes associated with intra-cellular events, without modifying the nervous command of the contraction. The comparison of the peripheral changes recorded during sub-maximal training by electrostimulation and voluntary contractions suggests that electrostimulation is less efficient, but complementary to voluntary training because the number and the type of trained motor units are different in the two procedures.

Demonstration of auto-anti-idiotypic antibody cross-reacting with public idiotypic determinants in the serum of rye-sensitive allergic patients.

The present study documents the presence, in the serum of one allergic individual, of auto-anti-idiotypic antibodies cross-reacting with public idiotypic determinants expressed on human IgE and IgG anti-Rye I antibodies. Sera from rye-sensitive patients were tested for specific IgG and IgE antibodies to Rye I by double antibody. The IgG fraction, isolated from the serum of a patient with a history of previous hyposensitization therapy, was repeatedly absorbed on Rye-I-Sepharose as well as on IgM- and IgG-Sepharose to remove anti-Rye I antibodies as well as any possible anti-heavy or light chain activity. This IgG fraction, named anti-idiotypic fraction (a-IdF), blocked in a dose-dependent fashion the reaction of IgG and IgE anti-Rye I antibodies with Rye I antigen. The a-IdF also blocked the binding of anti-rye antibodies to Rye I antigen in the serum of 20 unrelated allergic patients, indicating that these anti-Rye I antibodies bore public idiotypic determinants.

Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial.

22 cirrhotic patients with chronic encephalopathy were given oral zinc supplementation or placebo in a double-blind randomised trial. In the group which received zinc acetate 600 mg a day for 7 days, serum zinc had been restored to normal by day 8. On day 8 hepatic encephalopathy, as assessed by a trailmaking test, was improved in the supplemented group but not in the placebo group. There was also a significant increase in blood urea nitrogen in the supplemented group. Short-term oral zinc supplementation probably improved hepatic encephalopathy by correcting the zinc deficiency that compromises conversion of ammonia to urea. The duration of this improvement requires further investigation.

Beneficial effects of oral zinc supplementation on the immune response of old people.

Zinc is known to have beneficial effects on the immune response. In an attempt to modify age-associated immune dysfunction, supplemental zinc was administered to 15 subjects over 70 years of age (220 mg zinc sulfate twice daily for a month). As compared to 15 controls, matched for age and sex, there was a significant improvement in the following immune parameters in the treated group: (1) number of circulating T lymphocytes; (2) delayed cutaneous hypersensitivity reactions to purified protein derivative, Candidin and streptokinase-streptodornase; (3) immunoglobulin G (IgG) antibody response to tetanus vaccine. Zinc treatment had no influence on the number of total circulating leukocytes or lymphocytes, or on the in vitro lymphocyte response to three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). The data suggest that the addition of zinc to the diet of old persons could be an effective and simple way to improve their immune function.

Influence of oral zinc supplementation on the lymphocyte response to mitogens of normal subjects.

Oral zinc sulfate was given for 1 month to 83 normal subjects distributed in four groups according to age (20 to 40; 40 to 60), sex, and oral contraception. Their in vitro lymphocyte response to phytohemagglutinin and Concanavalin A, and their serum zinc and copper levels were measured before and after treatment. They were compared in 20 untreated subjects. Zinc treatment significantly increased the lymphocyte response to phytohemagglutinin and Concanavalin A. In the group of women aged 40 to 60, this resulted in a normalisation of the response to Concanavalin A. The response to zinc was related to the starting value of lymphocyte stimulation obtained by phytohemagglutinin, i.e., in low responders this was enhanced whereas in high responders it tended to be reduced. Treatment increased serum zinc and had no effect on serum copper. There was no correlation between serum zinc or copper and the lymphocyte response. The beneficial effect of zinc supplementation on the lymphocyte response does not result from a correction of latent zinc deficiency.