[Potentially inappropriate medications in the elderly: a list adapted to French medical practice]. / Médicaments potentiellement inappropriés aux personnes âgées: intérêt d'une liste adaptée à la pratique médicale française.

Drug induced adverse effects are frequently encountered in geriatrics. Their occurrence can be limited by an adapted prescription. Potentially inappropriate medications are drugs with an unfavourable benefit to risk ratio when other safer or more efficient therapeutic alternatives are available. An expert consensus allowed us to establish a new list of potentially inappropriate medications for people aged 75 or over, taking into account French prescribing habits. The drugs or the drug-classes proposed in this list are, generally speaking, and when possible, to be avoided in the elderly, but can be prescribed at times, under special clinical conditions, provided that the benefit to risk ratio is assessed. The French list proposed here could be considered as (i) an epidemiological tool for evaluating the quality of drug prescription in geriatrics and as (ii) a prescription guide suggesting an alternative treatment whenever a therapeutic alarm is raised. This guide could be used both as a base for the education of prescribers and as a way of increasing patients awareness. This French list should be kept up-to-date so as to remain adapted to the evolution of the knowledge on the effect of drugs in the elderly and of the pharmaceutical market.

[Age and management decisions in patients with primary lung cancer]. / Age et décision de prise en charge des patients atteints d'un cancer pulmonaire primitif.

INTRODUCTION: Therapeutic decisions are difficult in elderly patients because of the heterogeneity of this population. Our objective was to evaluate the role of age in the management of patients suffering from primary lung cancer seen in the department of respiratory diseases of the Limoges regional teaching hospital between 2002 and 2004. METHODS: A cross sectional study analysed the management of 363 patients suffering from primary lung cancer. The patients were divided into two groups according to their age (less than seventy or seventy and over). A comparison was made between the management of the two groups. RESULTS: The comparisons according to age produced evidence of reduced activity, greater dependence, an increased Charlson score, less frequently administered radiotherapy and chemotherapy, and more frequent symptomatic treatment in the elderly group (p<0.001). CONCLUSIONS: The geriatric assessment of patients suffering from primary lung cancer should make allowance for the physiological age of the patient and adapt the management to ensure the best quality of life.

Modification of HLA expression on peripheral lymphocytes and monocytes during aging.

Immunosenescence involves modifications of humoral and cellular immunity. Here we report the analysis of human leukocyte antigen (HLA) expression on T lymphocytes, B lymphocytes and monocytes of 58 healthy subjects aged 23-95 years old. Using a double staining immunofluorescence and flow cytometry analysis, we have determined the percentages of cells expressing HLA class-I and HLA-DR antigens. The number of antigenic sites expressed per cell were evaluated for HLA-ABCw, HLA-A, HLA-B, HLA-DR locus with a flow cytometry quantification technique. With advancing age, we observed: (i) a significant decrease of the percentage of T cells and B cells expressing HLA-A products; (ii) a decrease of the number of HLA class-I antigenic sites expressed per cell on the three populations tested, predominantly on B cells and in a locus-dependent fashion; (iii) a decrease of the number of HLA-DR molecules expressed per T cell, although the percentage of T cells expressing DR products was increased; (iv) a significant diminution of the percentage of B cells expressing HLA-DR molecules, without changes of the number of HLA-DR antigenic sites per cells. These changes in HLA expression with increasing age could contribute to the decreased level of immunologic responsiveness observed with ageing and contribute to the modification of antigen recognition.

Age-associated changes in mitochondrial parameters on peripheral human lymphocytes.

Among theories of aging, mitochondria are believed to be involved in senescence. Alterations of respiratory chain function and accumulation of various mitochondrial DNA mutations have been reported in mammalian postmitotic tissues. Because mitochondria have a central role in apoptosis and in adenosine triphosphate production, alteration of mitochondria function could contribute to immune senescence. We searched for alterations of mitochondrial parameters in peripheral lymphocytes with aging. Comparisons of respiratory chain activities of complex II+III, III, and IV were carried out in two populations of healthy volunteers with average ages of 35.3 +/- 6.7 years and 80.8 +/- 8.7 years. No difference was observed in complex IV activity between each group, whereas a significant decrease of complex II+III and a nonsignificant decrease of complex III activity were observed with aging. Alterations in mitochondrial functions can result from mutations in mitochondrial DNA (mtDNA), the most common being the 4977-bp deletion (mtDNA(-4977)). In either group we observed many deletions of mtDNA on peripheral blood lymphocytes by large-fragment polymerase chain reaction. This result suggests that alterations of respiratory chain activities observed with aging in lymphocytes could be the result of nuclear DNA dysfunction, with consequences on immune function (reduced responsiveness to antigen). Its possible implication on the recent observation of increased apoptosis of CD45RA+ RO- T cells with aging is discussed.

Hypokalemic quadriplegia and respiratory arrest revealing primary Sjögren's syndrome.

We report a case of hypokalemic flaccid quadriplegia with sudden respiratory arrest in a 38-year-old woman discovered to have distal renal tubular acidosis which lead to the diagnosis of primary Sjögren's syndrome. This case is compared to 8 similar cases previously described in the literature.

Population pharmacokinetics of amikacin in geriatric patients studied with the NPEM-2 algorithm.

The population pharmacokinetics of amikacin were studied in 40 geriatric medicine patients (aged 59-95 years, average 78 years) by the NPEM-2 algorithm, using a 2-compartment model. The fitted parameters were: renal clearance of amikacin, expressed as a fraction of creatinine clearance (CLS) and volume of the central compartment, expressed as a fraction of body weight (VS). The nonrenal clearance of amikacin (CLi) and the transfer constants between the 2 compartments (k12 and k21) were held constant. The distribution of each pharmacokinetic parameter was characterized by the median and the 50% dispersion factor (DF50) which is the interval between the 25th and 75th percentiles, divided by 1.32. The parameters were thus estimated by the following values: CLs = 0.91 +/- 0.45 and Vs = 0.29 +/- 0.10 l x kg-1. The volume of distribution was increased with respect to the usual value of 0.20 l x kg-1. The interindividual variability was high, particularly for clearance. Although the median value of CLs was close to unity, indicating that for most patients the elimination kinetics of amikacin followed that of creatinine, there was a slight probability to observe much higher values of CLs (up to 5), indicating that for some aged patients the elimination of amikacin was less altered than that of creatinine. These parameters were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 20 patients by the Bayesian method, with 2 blood samples per patient. For each patient the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 hours with no significant bias and a precision of 3.5 mg x 1(-1). This study confirms the ability of the NPEM-2 algorithm to provide reference population values for use in Bayesian monitoring of aminoglycoside therapy.

[Chronology of vascular access in hemodialysis. Apropos of 244 accesses in 150 hemodialysis patients]. / Chronologie des abords vasculaires en hémodialyse. A propos de 244 abords chez 150 hémodialysés.

Out of an experience of 244 vascular access in 150 patients the authors try do find the best chronology of the angioaccess procedures. 68% of the patients see their need in vascular access definitely resolved by the first classical forearm internal arterio-venous fistula and everything must be done in the dialysis population to avoid the failure of the fistula. This would lead to internal shunt procedures using graft materials of which we know the limited potency, leading to periodic operations. Emergency situations are approached by use of the femoral vein catheterization for hemodialysis. Only the impossibility of femoral or jugular catheterization would lead to the use of the external A.V. Shunt which would be placed on the leg to preserve the vessels of the arms. For some patients the repeated failure of the successive A.V. fistula and shunts have drived us towards either peritoneal dialysis or "hemasite" vascular access system.

[From organophosphate compound toxicity to atherosclerosis: role of paraoxonase 1]. / De l'intoxication par les composés organophosphorés à l'athérosclérose: rôles de la paraoxonase 1.

PURPOSE: Paraoxonase 1 is an ubiquitous human serum and tissue esterase known to hydrolyse organophosphorous compounds. It seems to be implicated in various vascular diseases. CURRENT KNOWLEDGE AND KEY POINTS: Recently paraoxonase has been located on the surface of High Density Lipoproteins (HDL) which has directed studies towards its involvement in atherosclerosis. An antioxidant effect has been suggested from its structure rich in reducing amino acids (cysteine), which was confirmed on low density lipoproteins (LDL) first in vitro and then in vivo. Paraoxonase 1 hydrolyses an arachidonic acid derivative found on the surface of oxidised LDL known to participate in the essential initial step of atherogenesis. Clinically paraoxonase 1 activity is low when pathological vascular ageing occurs early (myocardial infarction) and when cardiovascular risk is high (diabetes mellitus, chronic renal failure, analphalipoproteinemia). FUTURE PROSPECTS AND PROJECTS: The genetic polymorphism of this enzyme is one of the determinants of serum paraoxonase 1 activity variations. It could explain sensitivity differences in chronic organophosphate intoxications and has been suspected as a risk factor of vascular injury. A decrease of this enzyme activity with ageing could play a part in the high prevalence of cardiovascular diseases in the aged.

[Multiple autoimmune syndrome]. / Syndrome auto-immun multiple.

Report a case of multiple auto-immune syndrome with auto-immune thyroiditis, Sjögren's syndrome, primary biliary cirrhosis. Moreover the patient suffered from neuropsychiatric symptoms and anti-cardiolipid antibodies were significantly elevated.

[The heart in chronic kidney failure patients]. / Le coeur de l'insuffisant rénal chronique.

Risk factors for heart disease in patients with chronic renal failure (CRF) are the same as in general population; moreover CRF and renal replacement therapies (dialysis, immunosuppressive drugs for kidney transplantation) induce further specific cardiac risks. In practice, the commonest heart diseases associated with CRF are coronary artery diseases, myocardiopathies from various aetiologies, valve diseases and arrhythmias. Uremic pericarditis are quite unusual nowadays. Advances in therapy authorize easier control of congestive heart failure, the major complication of heart disease in CRF patients. Furthermore, it was observed that correction of anemia with erythropoietin therapy or kidney transplantation can ameliorate or reverse partially some cardiac diseases.

[Is kidney transplantation justified after 65 years?]. / La transplantation rénale est-elle licite après 65 ans?

According to literature kidney transplantation in patients above 65 years of age is justified. It is justified for selected patients with perfect cardiovascular status and several years of life expectancy. However it would be better not to enlarge these indications since there are not enough kidney transplants.