Relevance and Feasibility of a Personalized Dietary Intervention in Older People with Meals-On-Wheels: A Randomized Controlled Pilot Trial.

Objective: The present study aimed at assessing the feasibility and the effectiveness of a personalized dietary intervention in a meals-on-wheels service through a randomized controlled pilot trial. Design: Sixty recipients of home-delivered meals (75% of women; 70-97 years old) were recruited and randomly assigned to a control and an experimental group and followed over a period of 4 months. In the experimental group, the nutritional status (Mini-Nutritional Assessment - MNA questionnaire), the food intake and the food preferences were measured for each participant. Based on this screening, participants were provided with dietary guidance and follow-up. Those at risk of malnutrition were proposed enriched home-delivered meals. Enrichment was set up considering food preferences of the participants. Results: Looking at the whole sample at baseline, 80% (n=48/60) were at risk of malnutrition. Furthermore, 55% (n=33/60) ate less than 2/3 of their calorie and/or protein recommended allowances. In the experimental group, the intervention led to an increase of protein intakes and to a lower extent of calorie intake. In the control group, no significant changes were observed. Conclusion: To conclude, this study suggests that providing dietary guidance and adding nutrient-dense food to meals while considering food preferences is feasible and may help older beneficiaries of meals-on-wheels to increase calorie and protein intake and improve their nutritional status. However, there is a need to develop products or recipes to enrich the meals of the elderly more efficiently to achieve the recommended allowance.

Frailty and nutrition: searching for evidence.

Frailty is a geriatric syndrome that predicts disability, morbidity and mortality in the elderly. Poor nutritional status is one of the main risk factors for frailty. Macronutrients and micronutrients deficiencies are associated with frailty. Recent studies suggest that improving nutritional status for macronutrients and micronutrients may reduce the risk of frailty. Specific diets such as the Mediterranean diet rich in anti-oxidants, is currently investigated in the prevention of frailty. The aim of this paper is to summarize the current body of knowledge on the relations between nutrition and frailty, and provide recommendations for future nutritional research on the field of frailty.

Nutrition and immunity in the elderly: modification of immune responses with nutritional treatments.

Nutrition has a strong influence on the immune system of the elderly. Aging induces dysregulation of the immune system, mainly as a result of changes in cell-mediated immunity. Aging is associated with changes to the equilibrium of peripheral T and B lymphocyte subsets, such as decreases in the ratios of mature to immature, naive to memory, T helper 1 subset (TH1) to TH2, and CD5- to CD5+ cells. As a consequence, cell-mediated immune responses are weaker and neither cell-mediated nor humoral responses are as well adapted to the antigen stimulus. Undernutrition, common in aged populations, also induces lower immune responses, particularly in cell-mediated immunity. Protein-energy malnutrition is associated with decreased lymphocyte proliferation, reduced cytokine release, and lower antibody response to vaccines. Micronutrient deficits, namely of zinc, selenium, and vitamin B-6, all of which are prevalent in aged populations, have the same influence on immune responses. Because aging and malnutrition exert cumulative influences on immune responses, many elderly people have poor cell-mediated immune responses and are therefore at a high risk of infection. Nutritional therapy may improve immune responses of elderly patients with protein-energy malnutrition. Supplementation with high pharmacologic doses of a single nutrient (zinc or vitamin E) may be useful for improving immune responses of self-sufficient elderly people living at home. Therefore, nutritional deficiency must be treated in the elderly to reduce infectious risk and possibly slow the aging process.

Myelin basic protein in CSF and blood. Relationship between its presence and the occurrence of a destructive process in the brains of encephalitic patients.

Serum and CSF levels of myelin basic protein (MBP) were measured in 50 patients with encephalitis of various origins and severity. In nearly 50%, the CSF samples were found to display immunoreactivity of MBP. Positivity was found to be correlated with the severity of the clinical signs. More precisely, it corresponded to cases with suspected extensive brain destruction. No relationship could be observed with the cause of disease. Positive tests of sera were infrequent, even from patients whose CSF was rich in MBP. Longitudinal studies performed on 20 patients who were serially investigated during periods ranging from three weeks to 18 months demonstrated that after an attack, MBP liberation into the CSF persists for one to three weeks. The MBP assay should serve as an index for destruction of nervous tissue.

Nutritional influences on immune response in healthy aged persons.

Healthy elderly (80+/-5 years) with different nutritional status were compared to young healthy adults (25+/-5 years) to quantify the relative influences of aging and nutrition on immune response. Aged persons, without alteration of their nutritional status, had lower CD3+, CD8+, and CD45RA+ as well as higher CD2+CD3-, CD2+CD4-CD8-, and CD45RO+ T cell subsets and IL-6 release than their younger counterparts. T cell proliferation and IL-2 production were comparable in the two healthiest groups. Aged subjects with low nutritional status expressed similar but more marked changes in immune response while nutritional status did not influence the immune response in young subjects. Furthermore, lower nutritional status was associated with lower CD4+ counts and lower T cell functions in aged persons. These results indicate that the influences of aging and undernutrition in humans are cumulative and suggest that some changes in immune response that have been attributed to aging may, in fact, be related to nutrition and not aging.

Respective roles of immune and nutritional factors in the priming of the immune response in the elderly.

Ninety-six institutionalized elderly (greater than 70 years old) (mean age: 82 +/- 7 years) subjects, negative for tetanus toxoid antibodies were primed with tetanus toxoid vaccination and dinitrochlorobenzene (DNCB). Correlations were studied between some immunological parameters, nutritional parameters prior to immunization and the immune response intensity after it. Levels of tetanus toxoid specific IgG (ELISA assay) were positively correlated with monocyte phagocytosis, DNCB response and prealbumin levels, and negatively correlated with total IgG, monocyte immune degradation and tetanus toxoid lymphocyte stimulation. No correlation was observed with IgA, IgM, PHA stimulation. Tetanus toxoid lymphocyte stimulation correlated positively with response to DNCB, and negatively with tetanus toxoid IgG as well as total IgG. DNCB response correlated with prealbumin, tetanus toxoid IgG and tetanus toxoid lymphocyte stimulation. Therefore, it appears that malnutrition, as measured by prealbumin level, is one of the main factors contributing to the inconstant senile immunodeficiency. Monocyte antigenic degradation function unaltered with age can impair immune response while conserved or increased phagocytosis enhances immune response in the elderly. High total IgG levels were linked with low specific responses to priming antigens. High specific antibody levels also correlated negatively with cellular specific response. It is assumed that regulatory IgG antibody accumulation, likely anti-idiotypic antibodies, play an important role in senile immunological depletion.

Cell mediated immunity changes in ageing, relative importance of cell subpopulation switches and of nutritional factors.

Decreased T-cell functions with ageing have been extensively described. This review focuses on recent data on changes in T-cell subpopulations related to ageing and their consequences on T-cell proliferation. Increase of immature T cells CD2+ CD3- is an ageing phenomenon related to T-cell declining proliferation. Recently it was shown that increase of immature T cells was due to an increase in different subtypes of the CD2+ CD3- population, double-negative CD2+ CD4- CD8- and double-positive CD2+ CD4+ CD8+ subpopulations, the former being associated with nutritional deficit, the latter with associated diseases. Other authors have focused on decreases of native T cells with parallel increase of memory T cells; such a switch is also relevant to declining T-cell proliferation. This review focuses on two major factors which influence immune ageing; nutritional parameters and antigen exposure.

IGF-I, IGF-I-binding proteins and GH-binding protein in malnourished elderly patients with inflammation receiving refeeding therapy.

OBJECTIVE: To investigate the mechanisms determining the success or failure of refeeding therapy in malnourished elderly patients with inflammation by studying changes in plasma IGF-I, GH-binding protein (GHBP) and IGF-binding protein (IGFBP) levels and IGFBP-3 proteolysis. DESIGN AND METHODS: We studied 15 severely malnourished hospitalized elderly patients. Weight, food intake, plasma albumin, transthyretin, C-reactive protein (CRP), orosomucoid, interleukin-6 (IL-6), IGF-I, intact and proteolytically degraded IGFBP-3 and GHBP levels were determined on admission and during refeeding therapy designed to increase food intake to 40 kcal/kg body weight per day (15% protein). RESULTS: Plasma IGF-I, IGFBP-3 and GHBP levels were significantly low for age on admission in all malnourished elderly patients. They increased in nine patients as nutritional status improved (albuminemia >30 g/l; transthyretinemia >200 mg/l or weight gain >5% of initial body weight) and levels of inflammation markers decreased (group 1). In contrast, plasma IGF-I, IGFBP-3 and GHBP levels remained low in six patients in whom nutritional status failed to improve and levels of inflammation markers increased (group 2). IGF-I showed greater variations than IGFBP-3 or GHBP with respect to nutritional status. High plasma CRP and IL-6 levels were associated with high levels of IGFBP-3 proteolysis. CONCLUSION: Efficient refeeding therapy was associated with a significant increase in IGF-I plasma levels. In patients with severe and persistent inflammation, high levels of proteolysis of IGFBP-3 may have contributed to the low plasma IGF-I levels, persistence of hypercatabolism and lack of improvement in nutritional status.

Immune responses during recovery from protein-energy malnutrition.

Protein-energy malnutrition (PEM) is a worldwide problem. Infants and children from developing countries and elderly people from all around the world are the two main groups suffering from PEM. PEM induces profound immunodeficiency, characterized mainly by decreased cell-mediated immunity, and also by decreased humoral and non-specific immunity. Non-specific immune deficiency is of particular importance for defences against infections and its decrease in PEM may further deteriorate nutritional and immune status, pushing patients into a vicious and dramatic circle. Refeeding such patients and the restoration of their nutritional status lead to improvement in all immune responses: a strong association between the evolution of these two responses is always observed during refeeding. The need for specific nutrients to restore immune functions during refeeding of PEM patient has been extensively studied in the past years. This review describes the pathophysiological mechanisms of immune consequences of PEM and of immune restoration with refeeding, and in addition focuses upon some nutrients of particular importance, namely glutamine, zinc and vitamin E. Particular attention is directed at the elderly patients with PEM, a growing population for which the importance of undernutrition on prognosis is not yet fully recognized.

Longitudinal changes in iron and protein status of elderly Europeans. SENECA Investigators.

OBJECTIVE: Describe the iron and protein status of European elderly people studied in 1993, together with changes observed in the previous four years. DESIGN: Two optional designs: (1) A transversal study from a randomly selected group of female and male elderly subjects born between 1913 and 1914. (2) A longitudinal study including base-line measurements in 1988/1989 in subjects born in 1913-1918, which were repeated and extended in 1993. SETTING: Nineteen towns in 12 European countries participated in the baseline study in 1988/ 1989. Eleven centres in nine countries completed the follow-up study in 1993, and two new towns joined in 1993. The study included blood sampling for analysis of markers of nutritional status. RESULTS: The mean haemoglobin (Hb) values during the follow-up study for the different town populations ranged from 142 to 159 g/l for men and from 129 to 146 g/l for women. Prevalences of anaemia, based on WHO criteria (Hb < 130 g/l for men, and Hb < 120 g/l for women), amounted to 6.0% and 5.0% for men and women, respectively, and were very close to the baseline prevalences of 5.6% and 5.5%. A small decrease in Hb was observed after 4y in men. The mean haematocrit (Hct) values for the different towns ranged from 42% to 48% in men and from 39% to 44% in women. For both sexes, a decrease in Hct was observed. White blood cell (WBC) counts and differentials were measured in the follow-up study only. Mean WBC counts ranged from 5.8 x 10(3)/microliter to 7.1 x 10(3)/microliter in men and from 5.6 x 10(3)/microliter to 6.7 x 10(3)/microliter in women. Mean lymphocyte counts ranged from 1.6 x 10(3)/microliter to 2.4 x 10(3)/microliter in men and from 1.7 x 10(3)/microliter to 2.3 x 10(3)/microliter in women and mean neutrophile counts ranged from 3.4 x 10(3)/microliter to 4.4 x 10(3)/microliter and from 3.1 x 10(3)/microliter to 4.0 x 10(3)/microliter, respectively. The mean serum albumin values for the different towns varied from 39.9 g/l to 43.2 g/l for men, and from 39.3 g/l to 42.4 g/l for women, quite similar to the baseline study. In 25 subjects (2.2%) only serum albumin level was below 35 g/l and five subjects (0.4%) had a serum albumin level below 30 g/l. No albumin changes were detected for either sex over the four year period. The group of survivors in the follow-up study had higher mean albumin concentrations at baseline than the group of subjects who had died between the baseline and the follow-up study. CONCLUSION: In this population of elderly subjects in their seventies, Hb, Hct and albumin showed little change over the 4 year follow-up period. The prevalence of anaemia and low serum albumin values was relatively low, which is indicative of a relatively good health.

Nutritional status: haematology and albumin. Euronut SENECA investigators.

In the context of the Euronut SENECA study of nutrition and the elderly, performed in 19 towns situated in 12 European countries, blood haemoglobin and haematocrit, and serum albumin were measured in a large sample of 70-75-year-old subjects. The mean haemoglobin (Hb) values for the different towns ranged from 144 g l-1 to 157 g l-1 for men and from 131 g l-1 to 150 g l-1 for women. The town haematocrit (Hct) means ranged from 43.0% to 48.9% for men and from 39.7% to 46.4% for women. No clear geographical pattern emerged for either Hb or Hct. The 95% ranges (2.5-97.5 percentile intervals) for Hb and Hct for all towns combined (without any claim of being representative of Europe) were very similar to those reported in the NHANES II study of the USA. Prevalences of anaemia, using the WHO definition (Hb less than 130 g l-1 for men and Hb less than 120 g l-1 for women) were 5.2% for men and 5.7% for women. The town mean serum albumins ranged from 40.3 g l-1 to 44.3 g l-1 for men and from 40.3 g l-1 to 43.2 g l-1 for women. No clear geographical pattern emerged. Mean values were somewhat lower than for younger adults and comparable to other published data. Most albumin values were in the normal range, with only 2.0% of both men and women having levels below 35 g l-1 and only 0.4% of men and no women having levels below 30 g l-1. These results show that these 70-75-year-old subjects who chose to participate in the study were in relatively good health as judged from their haemoglobin, haematocrit and serum albumin levels.

Nutrition: a major factor influencing immunity in the elderly.

This paper reviews recent findings on immune ageing. Ageing per se affects mainly cell-mediated immunity: decreases in mature T-cells (CD3+) partly compensated with increases in less mature T-cells (CD2+CD3-) are observed. In addition antigen pressure throughout life induces increases in memory T-cells (CD45R0+) and borderline decreases in CD8+ subsets. Those changes lead to lower proliferative ability. In contrast B-cell subsets and innate immunity are less affected with ageing. These changes are mainly related to health status and are less important in very healthy elderly. Such changes are more important in undernourished elderly, and in elderly who exhibit decreases in micronutrient status. They are even stronger in elderly patients with protein energy malnutrition (PEM). In seniors with PEM, decreased immune functions, for all aspects of immunity, i.e. T-cell, B-cell subsets and functions and innate immunity, are strongly related to protein nutritional status. Refeeding can boost immune response but at a lower speed in patients exhibiting inflammatory process. The disequilibrium between normal macrophage functions and decreased T-cell functions is partly responsible for long-lasting inflammatory process in stressed patients. Therefore acute phase responses are more detrimental on nutritional status and nutrient reserves in aged patients than in adults. Such disequilibrium, stress after stress, pushes the elderly to frailty state.

Decreased maturation of T-cell populations in the healthy elderly: Influence of nutritional factors on the appearance of double negative CD4-, CD8-, CD2+ cells.

Aging is characterized by decreased T-cell functions partly related to increase of T-cell immature subsets. In carefully selected populations we explored influences of decreased nutritional levels and/or diseases on the appearance of T-cell immaturity in elderly persons. Decrease of nutritional status is associated in healthy elderly fitting the "SENIEUR" protocol with decreased mature T-cells (CD3+), (CD8+) and increased immature double-negative T-cells (CD2+CD4-CD8-). Diseased undernourished patients express the same variations in T-cell subsets plus decreased CD4+ and increased double-positive T-cells (CD2+CD4+CD8+). This seems to indicate that aging-associated immature T-cells in peripheral blood are generated at two different, thymic and extra-thymic sites of maturation.

Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX.

A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.

[Immunologic aging. Effect of denutrition]. / Le viellissement immunologique. Influence de la dénutrition.

Ageing leads to decrease of immune functions. The T lymphocyte is more susceptible to ageing than the B lymphocyte for which in vitro functions are almost preserved. All functions of cell mediated immunity are decreased in elderly. T lymphocyte are less mature, present decreased T helper and T suppressive functions, decreased T proliferative ability responses to stimuli and lower interleukin synthesis. T dependent antibody responses are also decreased: primary responses are diminished and secondary responses less specific. Nevertheless in healthy elderly such immune deficiency remains minor. Underdiminution whatever it concerns (mostly proteins but also vitamin or trace elements) also leads to immunodeficiency. When it occurs in aged individuals, undernutrition rapidly induces a profound immunodeficit. Prevention of prompt treatment of all undernutrition states is a major concern in geriatrics.

[An unusual variant of urothelial carcinoma: the "nested variant of urothelial carcinoma." Report of two cases]. / Une variante particulière de carcinome urothélial: le "nested variant of urothelial carcinoma". A propos de deux cas.

We report two cases of a poorly known variant of transitional cell carcinoma, the "nested variant of urothelial carcinoma". This tumor is composed of small islands or nests of transitional cells, presenting little atypia and mimicking von Brünn's nests. This low grade tumoral variant seems to behave as a high grade tumor of the same stage. Deep biopsies are necessary to display tumoral invasion, which allows the diagnosis. Importance of the knowledge of this entity is highlighted in order to avoid misdiagnoses that could delay appropriate therapy.

[Immune status in infantile autism. Correlation between the immune status, autistic symptoms and levels of serotonin]. / Etat immunitaire dans l'autisme infantile. Corrélations entre état immunitaire, symptômes autistiques et taux de sérotonine.

In sixteen autistic children high values of IgG and a high level of lymphocyte stimulation with PHA were observed. Principal component analysis showed: 1) a significant correlation between basic lymphocyte mitogenic activity and the clinical symptoms opposition and hyperactivity, 2) a significant correlation between high Ig levels, high PHA stimulation responses and the main autistic symptoms (withdrawal, inaffectivity, hypoactivity, mannerism, stereotypy and negatively echolalia), 3) a significant correlation with serotonin uptake by platelets and high immunological responses. Such correlations are strongly in favor of an immunologic component in autistic disease.

[Malnutrition in the elderly. Clinical consequences]. / Dénutrition du sujet âgé. Conséquences cliniques.

UNLABELLED: A COMMON PROBLEM: Undernutrition occurs when nutrient intake does not meet nutritional needs. Selective food intake induced micronutrient deficits (moderate undernutrition) and can later lead to protein calorie malnutrition (PCM). PCM is often discovered during acute illness (increased nutritional needs). PCM is observed in 30 to 50% of the institutionalized population and in 2-4% of the elderly living at home. Micronutrient deficits are far more frequent and concern 4 million elderly persons in France. AGE-RELATED CHANGES: Decreased smell and taste capacities and the inability to modify eating habits in stress conditions are mainly responsible for low food intake. Low intake leads to immunodeficiency, and subsequent frailty. Any intercurrent illness aggravates both undernutrition and immunodeficiency, creating a disease-to-disease spiral (undernutrition-immunodeficiency) that is difficult to inverse. SIGNS OF PCM: Early signs of protein-calorie malnutrition are nonspecific: fatigue, apathy, decline in muscle strength. It is important to diagnose undernutrition at this stage before more specific symptoms develop: anorexia, weight loss, infection. Metabolic disorders occur at a later stage, generally during an acute illness, leading to overt PCM with perturbed glucose metabolism, recurrent infection, dehydration, impaired wound healing and calcium bone loss. The length of refeeding therapy depends on the intensity of the clinical signs, weight loss, dehydration, glucose metabolism disorder and/or on the severity of clinical complications such as infection or bone fractures. PRACTICAL ATTITUDE: Under nutrition must be recognized early at the stage of nonspecific clinical expression. Practitioners must be constantly aware of the risk of undernutrition and search for nonspecific signs in the elderly.

[Discovery of a renal chromophobe cell carcinoma in a pregnant woman. Apropos of a case]. / Découverte d'un carcinome rénal à cellules chromophobes chez une femme enceinte. A propos d'un cas.

We report the case of a young pregnant woman with a malignant tumour of the kidney suggestive of oncocytoma. Because of the pregnancy, preoperative staging consisted of abdominal ultrasound and magnetic resonance imaging. Caesarean section was performed. Several days later, surgical exploration of the kidney was performed with tumourectomy and frozen section analysis: radical nephrectomy was finally performed. The definitive histology was chromophobe renal cell carcinoma. This is a rare tumour of the kidney, with its own characteristics allowing histopathological diagnosis and with a better prognosis than renal cell carcinoma. In the literature, pregnancy, a situation of immune depression, does not increase the prevalence of malignant neoplasms.

[Aging and the immune system. Experimental aspects]. / Vieillissement et système immunitaire. Quelques aspects expérimentaux.

So far no comparative studies have been conducted to know whether physiological influences related to sex hormonal differences affect the age-related changes of the immune system. The aim of this study was to investigate whether pregnancies and sex influence the age-related changes in the peripheral lymphoid compartment and functions of T cells in mice. Using flow cytometry, we examined changes in (Thy1.2+) T cells, (B220+) B cells and (CD11b/Mac-1+) macrophages in the spleen of multiparous and virgin females and males at 2, 8, 15 and 23 months of age. The development of naive (CD44low) and memory (CD44high) cells were investigated in CD4+ and CD8+ T cell subsets. To analyze the age-related changes in functions of T cells, we examined the secretion of some T cell immunoregulatory cytokines (IL-2, IL-4, gamma-interferon and GM-CSF) of in vitro Concanavalin A-activated spleen cells of C57BL/6 mice. Both short term (8 months) and long term (15-23 months) effects of pregnancies were obvious in the age-related changes of the immune system. Short term effect included delayed appearance of memory CD4+ cells and the preserved IL-2 production. At eight months, shortly after pregnancies, both parameters were higher in multiparous females. Later effects of pregnancies were evidenced by a higher level of macrophages (Mac-1+) than in other groups throughout life. The increased gamma-interferon, IL-4 and GM-CSF productions appeared earlier, at 15 months, IL-4 and GM-CSF levels remained higher in multiparous females than in virgin females and males in late adulthood. Sex differences were also noticed: males exhibited lower macrophage levels after one year and gamma-interferon secretion capacity than females in late life. This study underlines that the onset, magnitude and kinetics of the age-related changes in the distribution of immune cells and T cell functions are parity- and sex-dependent. These changes may influence the incidence of age-related diseases and may explain the greater longevity of women, especially the multiparous ones.