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.

[Neuropathology of the cerebral vessels of centenarians]. / Neuropathologie des vaisseaux cérébraux des centenaires.

Neuropathological study of brain and brain vessels was performed in two series of 12 and 20 centenarians, focusing on the prevalence of small vessel lesions, infarction, Alzheimer's changes and mental status. These are discussed as a function of vascular risk factors. In the first series (12 cases), there was no correlation between the severity of small vessel lesions: hyalinosis (12/12), mineralisation (10/12), amyloid angiopathy (9/12), vascular risk factors (high blood pressure or diabetes), Alzheimer's lesions. However, there was a tendency for an association between amyloid angiopathy and high density of neurofibrillary tangles. In the second series (20 cases), small infarcts and lacunes were found in 9/20 cases, neurofibrillary tangles and diffuse deposits of A beta peptide were constant, senile plaques were very frequent (19/20). Five patients were demented (one vascular dementia, one Alzheimer dementia, and 3 mixed dementias). These data indicate that: 1) Lesions of the walls of small cerebral vessels do not seem linked to the vascular risk factors observed at the end of the life of centenarians. 2) Cerebral infarcts and lacunes are frequent in these patients, and are responsible, at least in part, for a high proportion of the cognitive dysfunctions. The study of larger series is needed for a better understanding of relationships between vascular and degenerative lesions in the oldest old.

Plasma fibronectin in French centenarians.

Plasma fibronectin was shown to increase with age, the difference between individuals (the SD of the mean) also increases with age. Fibronectin is highly sensitive to proteolytic degradation and several of the degradation products were shown to have noxious effects as proper proteolytic activity, activation of IL-1 and collagenase expression and also activation of fibronectin biosynthesis. It was therefore interesting to compare the plasma fibronectin values of centenarians in relatively good health with an elderly population in a geriatric hospital, somewhat younger (70-96 years) but with a variety of pathologies. A third population of men and women between 59 and 70 in good health (the EVA-epidemiological study) was also used for comparison. Plasma fibronectin was determined by a specific and highly sensitive Elisa assay. Fibronectin fragments were characterized by immunoblot. It could be shown that plasma fibronectin in centenarians had a lower distribution with lower average values than the geriatric population. Fibronectin fragments could be demonstrated in the plasma of a selection of geriatric patents but not in the plasma of centenarians. These results suggest a more moderate increase of plasma fibronectin in the relatively healthy centenarians as compared to a younger but pathological population. They also show that the plasma fibronectin of the investigated centenarians was better protected from proteolytic degradation than in the geriatric population. The above results also confirm the contention that epigenetic mechanisms such as an age-dependent increase of fibronectin synthesis and degradation and the potential noxious effects of degradation products may well play an important role in the age-dependent decline of physiological functions.

[Causes and consequences of elderly's agitated and aggressive behavior]. / Causes et retentissements des états d'agitation et d'agressivité du sujet âgé.

Agitation and aggressiveness are frequent in the elderly and often related to dementia. As a result of the ageing of the general population this is becoming a major public health concern. No or little epidemiological data, during primary health care, about symptoms, co-morbidity, nor medical and social consequences of elderlys' disruptive behavior have been gathered or published in the French literature. Thus, in order to describe these disorders, a survey in cooperation with general practitioners (GP) was conducted. A representative sample of 212 French GP's, all with preferential geriatric activity were asked to conduct a study by including retrospectively their two most recent patients older than 65, who had exhibited agitation and/or aggressiveness. From this cross sectional study, 410 patients (female: 61%, male: 39%) were included. The mean age was 81 years (sd: 7.65). The patients suffered from change in verbal behavior (80%), verbal aggressiveness (71%), physical agitation (60%), wandering (48%), and/or physical aggressiveness (31%). The average of disruptive behavior symptoms per patient was 2.9. The symptoms appeared progressively in 81% of patients, the mean duration was two years and it was the first episode in 40% of patients. Disruptive behaviors may be explained in view of organic illness in 62% of patients (cardiovascular disease: 37%, neurologic: 12%, diabetes: 7%, dehydratation: 5%), dementia (Alzheimer disease: 20%, vascular dementia: 18%, mixed dementia: 14%). In 54% of patients disruptive behavior may be explained in view of depression: 34%, and anxiety disorder: 31%. A triggering factor was observed in 57% of cases (psychosocial stress: 39%). Somatic consequences of the symptoms were frequently identified: decrease of alimentary intake: 39%, weight loss: 27%, dehydratation: 11%, falls: 32%, and irregular medication intake: 31%. Limitation of daily life activities: 85%, and family life: 97% were also noted. Acceptability of patient's symptoms by the family was good (no discomfort or transitory and mild irritability) in 61% of cases, and very bad (reactions of exhaustion, hospitalization requirement) in 13%. This study carried out during primary care, showed that the elderly's disruptive behaviors cause severe medical consequences and familial and social distress.

Assessment of dementia in elderly outpatients: a comparative study of European centers and consensus statement.

Large numbers of elderly patients, suspected of having dementia, need medical evaluation, often in early phases of their illness. A complete outpatient assessment clearly could be advantageous. Thirty-five centers from 15 European countries, known to their scientific gerontological and geriatric societies to have experience in outpatient care for elderly patients with dementia, participated in an effort to develop a consensus statement for the assessment needs of these patients. The comparison of the centers showed that a wide variety of approaches was currently in practice. Differences appeared to be mainly based on local facilities and organization. A consensus for diagnostic outpatient assessment was easily reached. Diagnosis should be based on DSM-IV criteria, which requires a standardized assessment (including neuropsychological, functional and technical evaluation) and should be multidisciplinary. An assessment of dementia of elderly outpatients appears to be very feasible - a consensus approach with minimum diagnostic requirements is presented.

Sarcopenia, hypermetabolism, and aging.

Sarcopenia is a constant in aging. Observed over long periods, it can reach 1% per year. But it is such a tenuous phenomenon that it cannot be observed over short periods at steady state. The aging phenomenon mainly hits fibers, Type II but on aged muscle thin, normal, and hypertrophic fibers cohabit with sclerosis and fat increases. Sarcopenia is difficult to study, due to the lack of simple clinical, biochemical, or imaging measures. Anthropometric data are largely dependent on water content. DEXA gives better information on appendicular muscle loss. Measures of strength analyze functional outcomes of sarcopenia. Sarcopenia appears largely multifactorial. Hormonal changes, e.g., drop in growth hormone, menopause, and andropause, explain impaired protein synthesis. Disuse (sedentary, bed rest) may explain chronical protein lysis. But the main factors for muscle lysis imply life events and occurring diseases. Cytokines (IL6, TNF alpha) and stress hormones (cortisol) induce quick protein lysis in muscle. Rapid and intensive successive aggressions during life cannot be compensated by slowed synthesis. Harmful consequences of sarcopenia explain many disabilities of old age: loss of strength, inducing itself loss of mobility, falls, equilibrium disorders, poor ADL: loss of nutritional reserves (protein and glycogen) impairing capacities of immune response. Muscle loss spoils vital functions as respiration. Treatment remains rather limited to resistance exercise. Although, these results are thin, they are the only ones to be validated in all the elderly even the frail or the old. However it is not efficient during the evolution of an inflammatory process. The powerful action of cytokine and cortisol on muscular hypermetabolism must be incited for early treatment of any infectious or inflammatory event. Nutritional supplementation has no efficiency in the absence of malnutrition and without exercise. Although mobility impairments mainly due to sarcopenia are the first cause of disablement in the elderly, we lack information on etiology, evolution, and measurement of sarcopenia. We also lack controlled therapeutical studies.

Increased elastase and cathepsin G activity in activated lymphocytes from aged patients: role of denutrition and dementia.

Elastase and cathepsin G activities in cell-lysates and in culture supernates of activated human lymphocytes (incubated for 96 h in the presence of 5 microg/ml of phytohemagglutinin with/without 2 microg/ml of elastin peptides) of 25 old, hospitalized patients (average age: 88.48+/-6.81 years), suffering from vascular-type dementia or denutrition were examined, in comparison with samples of 11 young, healthy donors. Elastase activity was found to be significantly elevated, the excreted fraction of elastase activity strongly decreased in lymphocytes of these patients as compared to young donors. The highest values of enzymatic activities in the culture supernates and also in the cell-lysates were obtained for samples of undernourished patients. Lymphocytes from young, healthy donors showed a significant increase both of excreted and intracellular elastase activity when cultured in presence of elastin peptides. The activation of elastolytic activity by elastin peptides decreased with the age of donors. The results for cathepsin G are essentially similar but the differences between age-categories are less pronounced than for elastase activity.

Osler's maneuver: absence of usefulness for the detection of pseudohypertension in an elderly population.

PURPOSE: To investigate the prevalence and clinical relevance of Osler's maneuver for detecting pseudohypertension in the elderly. PATIENTS AND METHODS: Osler's maneuver was performed by one investigator in 205 consecutive inpatients of a French geriatric hospital (40 men and 165 women; mean age 84.2 +/- 6.2 years). In 12 Osler-positive and 12 Osler-negative patients matched for age, sex, and presence of hypertension, the blood pressure values measured directly at the radial artery were compared to those measured indirectly with a standard mercury sphygmomanometer. Aortic and upper limb pulse wave velocities (PWV) were also measured in these 24 patients. RESULTS: Twenty-three of 205 patients (11%) were Osler-positive. Age, sex ratio, and prevalence of hypertension or other cardiovascular diseases did not differ significantly in Osler-positive and Osler-negative patients. Systolic blood pressure (SBP), measured by standard mercury sphygmomanometer, was significantly greater in Osler-positive than Osler-negative patients (157 +/- 37 versus 132 +/- 28 mm Hg; P < 0.01). Diastolic blood pressure (DBP) did not differ significantly (78 +/- 18 versus 74 +/- 14 mm Hg). Interobserver agreement concerning Osler's sign, studied in 40 patients, was good (kappa = 0.72). In 12 Osler-positive and 12 Osler-negative patients, the mean differences between SBP obtained by cuff-manual indirect blood pressure and direct measurements were -3.71 +/- 22.85 mm Hg and -8.59 +/- 14.40 mm Hg (P = NS). For DBP, these differences were 18.40 +/- 15.72 and 12.01 +/- 5.80 mm Hg (P = NS). The differences between the indirect and direct blood pressure measurements were significantly correlated to upper limb PWV, but not aortic PWV, for both SBP and DBP. Pseudohypertension, defined as the indirect measurement overestimation of SBP or DBP by 10 mm Hg or more, was found in 15 of the 24 patients (63%). In these patients, upper limb PWV was significantly greater than in those with no pseudohypertension (7.0 +/- 2.2 versus 5.4 +/- 1.3 m/s; P < 0.05). CONCLUSION: The Osler-positive maneuver is frequently found in elderly hospital inpatients, but its ability to detect pseudohypertension in clinical practice is poor. Measurement of upper limb PWV might be a more appropriate way of screening for this condition.

Prevalence of associated diseases in different types of dementia among elderly institutionalized patients: analysis of 3447 records.

OBJECTIVE: To determine the prevalence of dementia in a population of hospitalized or institutionalized elderly patients, and that of associated diseases according to dementia type. DESIGN: Retrospective analysis of a database of diagnostic codes. SUBJECTS: All patients admitted to 1 of the 4 geriatric units participating in the study at the Charles Foix Hospital between 1980 and 1989. MEASUREMENTS: All diagnoses mentioned in the discharge summary that could cause or contribute to hospitalization were recorded for each patient. A final list of 54 different diagnoses could be recorded for each patient. Dementia was subdivided into 3 subtypes: Alzheimer dementia (DAT), vascular dementia (VD), and other types of dementia (unclassifiable dementia). MAIN RESULTS: The study involved 3447 patients aged 81.0 +/- 8.3 years, of whom 27.7% were men. Dementia was the most frequent disease in this population (34.3%); Alzheimer disease was responsible for 15%, vascular dementia for 9.5%, and other types for 9.8%. The average number of associated diseases was 3.23 +/- 2.10 in the Alzheimer dementia group, 4.73 +/- 2.38 in the vascular dementia group, and 3.96 +/- 2.26 in the nondemented group. Parkinson disease was present in 15.5% of patients with unclassifiable dementia, compared with 7.6% in the nondemented group (P < 0.001). There were significantly more diseases commonly seen in bedridden patients in the group of patients with both other types of dementia and Parkinson disease than in the group of other types of dementia patients without Parkinson disease (P < 0.01). CONCLUSION: Dementia was the most common disease observed in our elderly institutionalized population. Alzheimer patients had significantly fewer associated diseases than nondemented patients, whereas the reverse was found in the vascular dementia group. The co-existence of Parkinson disease and dementia in our population was associated with the poorest health status, as these patients were more likely to present simultaneously such conditions as pressure sores, incontinence, dehydration, or iatrogenesis.

[Neuropathology of 20 centenarians. I. Clinical data]. / Neuropathologie de 20 centenaires. I. Données cliniques.

We report a clinical study of 20 patients aged more than 100 years, and deceased in Charles Foix Hospital, Ivry/Seine, France, where they had stayed for 10 days to 16 years (mean: 3.3 years, median: 4 years). Each of them was studied neuropathologically (the results of this study will be published later on). The case selection excluded only those patients whose neuropathological study could not be complete. The prevalence of sensorial deficits was high: 15/20 patients had deterioration of hearing, 8 of them were deaf; 14/20 patients had deterioration of sight, 4 of them were blind. Motor deficits were numerous: 15 patients were not ambulatory. The patients were classified as demented or not, according to the criteria of the DSMIII R (American Psychiatric Association 1987), on the basis of a retrospective evaluation of clinical records, and of an inquiry among the caring staff. Their mental status was also evaluated by the Global Deterioration Scale of Reisberg et al (1985). Five patients had been demented, four had been intellectually normal, and 11 had suffered from mild disturbances of memory or cognitive functions. This series was not representative of the general population of centenarians, but probably of those institutionalized in France. We observed a low proportion of demented patients despite the prevalence expected from epidemiological studies. This is difficult to interpret. The low proportion of dementia in this small sample is not due to the short duration of the course of diseases responsible for dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

[Medicalization of information systems in Internal Medicine and Geriatrics: a true medical challenge]. / Médicalisation des systèmes d'information en Médecine Interne et Gériatrie: un véritable enjeu médical.

Elderly people constitute an ever growing part of short-stay hospital patients. At the moment, 25% of these patients age aged 75 or more. The demographic curve, the effect of public health policies favouring treatment at home and the new characteristics of demand for care by the oldest patients will undoubtedly result in an increasing number of these hospitalizations. This tendency has repercussions on the organization of hospital structures, but it also raises the problems of specificity of consumption of goods and medical hospital units by elderly patients and of their financing as part of budget allotments. The progressive but imperative installation, forced on us by decrees, of medicalized management tools (e.g. the Information System Medicalization Programme) in public hospitals and some private clinics throws doubt on the value of this tool to describe the stays of elderly people.

Effect of two French nurses' strikes on mortality in a geriatric hospital.

PURPOSE: To study the influence of the 1988 French nurses' strikes on mortality in a geriatric hospital. MATERIALS AND METHODS: Two nurses' strikes affected the Charles Foix Hospital near Paris from June 29 to July 31 and from September 17 to October 22, 1988. Mortality was studied in nine geriatric wards of this hospital, including two rehabilitation units comprising 187 beds, and seven long-term care units comprising 1,132 beds. Monthly mortality rates were calculated from the hospital's administrative registers and expressed as deaths per 1,000 patient-days. These rates were calculated in each of the aforementioned nine units for the 36 months preceding the first strike (control period) and for the 12 months following it (study period). RESULTS: Over the control period, monthly mortality was significantly higher in rehabilitation units than in long-term care units (2.46 +/- 1.21 versus 0.83 +/- 0.47, p less than 0.001), but mortality rates among rehabilitation units, as well as among long-term care units, were comparable. Also, during the control period, large seasonal fluctuations in monthly mortality rates were observed in both rehabilitation units and long-term care units (peak in winter and nadir in summer). These rates tended to decrease from year to year in rehabilitation units but not in long-term care units. A statistical model based on time-series analysis of the control period data was used to calculate the expected monthly mortality rates for the study period in rehabilitation units and in long-term care units, respectively. Three of the 12 actual monthly mortality rates exceeded the upper limit of the 95% confidence interval of the 12 expected monthly mortality rates, in the units where the more severe care disruption occurred. A detailed analysis of discharge summaries of these units failed to identify a possible link between some of these deaths and a possible absence of care. CONCLUSIONS: The nurses' strikes did not induce a clear-cut increase in mortality in this population of elderly patients. However, we cannot exclude the possibility that these strikes had some negative effects on health. Our results fail to provide answers to the difficult ethical problems created by such stoppages.