Protein intake, weight loss, dietary intervention, and worsening of quality of life in older patients during chemotherapy for cancer.

Decreased health-related quality of life (HRQoL) is common in patients with cancer. We investigated the effects of dietary intervention and baseline nutritional status on worsening of HRQoL in older patients during chemotherapy. In this randomized control trial assessing the effect on mortality of dietary advice to increase dietary intake during chemotherapy, this post hoc analysis included 155 patients with cancer at risk of malnutrition. The effects of dietary intervention, baseline Mini Nutritional Assessment item scores, weight loss, and protein and energy intake before treatment on the worsening of HRQoL (physical functioning, fatigue) and secondary outcomes (Timed Up and Go test, one-leg stance time, depressive symptoms, basic (ADL), or instrumental (IADL) activities of daily living) were analyzed by multinomial regressions. Dietary intervention increased total energy and protein intake but had no effect on any examined outcomes. Worsening of fatigue and ADL was predicted by very low protein intake (< 0.8 g kg-1 day-1) before chemotherapy (OR 3.02, 95% CI 1.22-7.46, p = 0.018 and OR 5.21, 95% CI 1.18-22.73, p = 0.029 respectively). Increase in depressive symptomatology was predicted by 5.0-9.9% weight loss before chemotherapy (OR 2.68, 95% CI 1.10-6.80, p = 0.038). Nutritional intervention to prevent HRQoL decline during chemotherapy should focus on patients with very low protein intake along with those with weight loss.

There is no correlation between peripheral inflammation and cognitive status at diagnosis in Alzheimer's disease.

BACKGROUND: Besides the neurofibrillary tangles and amyloid plaques, an inflammatory process is involved at central and peripheral levels in Alzheimer's disease (AD). We aimed to determine whether peripheral inflammatory parameter levels, in plasma and in peripheral blood mononuclear cells (PBMCs), could be correlated with the cognitive status at the time of AD diagnosis. METHODS: Patients were included at diagnosis with MMSE score between 16 and 25 and were naive of symptomatic treatment for AD. C-reactive protein >10 mg/L and any acute or chronic inflammation were considered as exclusion criteria. Cognitive assessment also included the ADAScog scale. Plasma interleukins (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and the chemokine ligand 5 (CCL5) were measured using Luminex(®) X-MAP(®) technology. A subgroup of patients also underwent measures of these parameters in extracellular and intracellular compartments of PBMCs (ancillary study). RESULTS: One hundred and nine patients were included; mean age 79.4 ± 6.8 years with 37 patients in the ancillary study. The mean values of IL-1ß, TNF-α, IL-6 and CCL5 values were 1.49, 7.18, 3.09 and 69,615.81 pg/mL, respectively. No correlation between plasma cytokines or chemokine levels and cognitive scores was found. In PBMCs, the levels of cytokines were detectable but did not either show any correlation with cognitive scores. CONCLUSION: Our data indicate that at diagnosis, peripheral levels of cytokines and CCL5 display low values without any correlation with the cognitive status. Further results of our study will show if these circulating markers are related to the progression of AD.

Prevalence of peripheral artery disease in the elderly population in urban and rural areas of Central Africa: the EPIDEMCA study.

OBJECTIVE: Data on peripheral artery disease in Africa are sparse and limited to urban areas. Given the urban/rural socio-economical gradient in these countries, we sought to determine the prevalence and risk factors of peripheral artery disease in urban and rural areas of two countries in Central Africa. METHODS: Individuals ≥65 years old living in two urban and rural areas of the Republic of Central Africa (ROC) and the Central African Republic (CAR) were invited. Demographic, clinical and biological data were collected. Ankle-brachial index ≤0.90 defined peripheral artery disease. RESULTS: Among the 1871 participants (age 73 years, 62% female) the prevalence of peripheral artery disease was 14.8%, higher in ROC than in CAR (17.4% vs. 12.2%, p = 0.007) and higher in females than males (16.6% vs. 11.9%, p = 0.012). The prevalence of peripheral artery disease increased with age, respectively at 10.9%, 14.9%, 15.1% and 22.2% for age bands of 65-69, 70-74, 75-79 and 80+years (p < 0.001). Higher rates of peripheral artery disease were found in urban areas in ROC (20.7% vs. 14.4% in rural areas, p = 0.011), but not in CAR (11.5% vs. 12.9%, p = NS). In multivariate analysis, peripheral artery disease was significantly associated with age (odds ratio (OR): 1.03; p = 0.004), dyslipidaemia (OR: 1.88; p = 0.003), smoking (OR: 1.78; p = 0.003), obesity (OR: 1.98; p = 0.034) and underweight (OR: 1.49; p = 0.023). Regular alcohol drinking was associated with decreased risk of peripheral artery disease (OR: 0.73; p = 0.044). CONCLUSION: The prevalence of peripheral artery disease in the elderly is high in Africa, especially in females. In ROC, with a higher urban-rural socio-economic gradient, peripheral artery disease is more frequent in the urban areas.

Flow microcalorimetric study of butyrylcholinesterase kinetics and inhibition.

The enzymatic hydrolysis of butyrylcholine, catalyzed by horse serum butyrylcholinesterase (EC 3.1.1.8), was studied at 37 degrees C in Tris buffer (pH 7.5) by flow microcalorimetry. A convolution procedure, using the Gamma distribution to represent the impulse response of the calorimeter, was developed to analyze the microcalorimetric curves. After correction for buffer protonation, the hydrolysis reaction was found to be slightly endothermic, with Delta H=+9.8 kJ mol(-1). Enzyme kinetics was studied with both the differential and integrated forms of the Michaelis equation with equivalent results: Michaelis constant K(m)=3.3mM, catalytic constant k(cat)=1.7 x 10(3)s(-1), bimolecular rate constant k(s)=5.1 x 10(5)M(-1)s(-1). The reaction product, choline, was found to be a competitive inhibitor with a dissociation constant K(i)=9.1mM. Betaine had a slightly higher affinity for the enzyme, but the inhibition was only partial. This study confirms the usefulness of microcalorimetry for the kinetic study of enzymes and their inhibitors.

Predicting and preventing adverse drug reactions in the very old.

The size of the elderly population has been increasing steadily for several years. Individuals in this age group often have several concomitant diseases that require treatment with multiple medications. These drugs, for various reasons and especially as a consequence of potential accumulation, may be associated with adverse reactions. Of the numerous factors that can favour the occurrence of these adverse drug reactions, the most important are the pathophysiological consequences of aging, particularly as these apply to the very old. Although absorption of drugs is not usually reduced in the elderly, diffusion, distribution and particularly elimination decline with age. Furthermore, while hepatic metabolic function is fairly normal, renal function is usually markedly depressed in very old individuals, and this can translate into clinical consequences if it is not taken into account. This is why, before administration of any drug in the elderly, evaluation of glomerular filtration rate is essential. Validated estimations such as those obtained from the classical Cockcroft-Gault formula or from more recent methodologies are required. In addition to reductions in various organ functions, factors connected with very old age such as frailty, falls, abnormal sensitivity to medications and polypathology, all of which tend to be more common in the last years of life, all directly impact on adverse drug reaction occurrence. Given these characteristics of the elderly population, the best way to reduce the prevalence of adverse drug reactions in this group is to limit drug prescription to essential medications, make sure that use of prescribed agents is clearly explained to the patient, give drugs for as short a period as possible, and periodically re-evaluate all use of drugs in the elderly.

Inhibition of human serum arylesterase by metal chlorides.

The inhibition of arylesterase (paraoxonase, EC 3.1.8.1) by metal chlorides was studied with both pooled human serum (A phenotype) and purified enzyme, using phenyl acetate as substrate. Inhibition data were analysed with the Hill equation. Results obtained with whole serum and purified enzyme were very similar. On the basis of the Hill coefficient, n(H), three groups of inhibitors were distinguished: (1) Cu(2+) and Hg(2+) for which n(H)=1, suggesting a single binding site (probably the free cysteine at position 283); these metals were mixed inhibitors, with more affinity for the free enzyme than for the enzyme-substrate complex; (2) Mn(2+), Co(2+), Ni(2+), Zn(2+), and Cd(2+) for which n(H)>1, suggesting several cooperative binding sites; (3) La(3+), for which n(H)<1. Within groups (1) and (2) the inhibiting potency followed the order of the periodic table. For the 3d elements the inhibiting order followed the Irving-Williams series, with the classical exception of Cu(2+). Only Zn(2+) was inhibitory at its physiological concentration.