[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.

[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.

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.

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.

Decrease of serum paraoxonase activity in chronic renal failure.

Paraoxonase is an esterase that hydrolyzes organophosphate compounds. The enzyme is associated with HDL and could protect LDL against peroxidation, which suggests a possible involvement of paraoxonase in the antiatherogenic properties of HDL. Paraoxonase activity has been shown to be low in patients with myocardial infarction, diabetes mellitus, or familial hypercholesterolemia. Because cardiovascular disease is the main cause of death in chronic renal failure, serum paraoxonase activity was measured by spectrophotometry using three synthetic substrates (phenyl acetate, paraoxon, and 4-nitrophenyl acetate) in 305 patients with kidney disease, including 47 patients with non-end-stage chronic renal failure, 104 patients treated with hemodialysis, 22 patients treated with peritoneal dialysis, and 132 renal transplant patients. Patients were compared with two groups of aged-matched control subjects (total number = 195). Especially with 4-nitrophenyl acetate, paraoxonase activity was lower in patients with some degree of renal insufficiency (chronic renal failure [P < 0.05], chronic hemodialysis [P < 10(-4)], chronic peritoneal dialysis [P < 10(-4)]) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure could be an essential factor of premature vascular aging, especially when dialysis is used. Renal transplantation seems to restore paraoxonase activity.

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.

Calcium oxalate crystalluria in elderly patients and treatment with naftidrofuryl oxalate.

Crystalluria is important in the evaluation of patients with urinary stone and is more frequently encountered in elderly than in younger adults. After noting that calcium oxalate monohydrate crystalluria was higher in elderly patients, we undertook a study to determine if oral treatment with naftidrofuryl oxalate, a drug frequently prescribed for elderly patients in France, was associated with crystalluria. The presence of early morning crystalluria was assessed in non-stone-forming patients hospitalized in a geriatric department. We studied 251 patients without a history of nephrolithiasis (mean age; 81.6 +/- 8.5 years) of whom 49 had been treated orally with naftidrofuryl oxalate at a mean dosage of 485 +/- 120 mg/24h. We identified and quantified the crystals in one early morning urine sample kept at room temperature. The frequency of crystalluria in elderly patients without stones who were not taking naftidrofuryl oxalate was 31.7% compared with only 6% in the general adult population. In this group, mainly calcium phosphate crystals were found. In patients who received naftidrofuryl oxalate, the frequency of crystalluria was 51% of which the major component was calcium oxalate monohydrate and not calcium phosphate. Naftidrofuryl oxalate may enhance crystal formation in elderly patients. This should be taken into account, particularly when other predisposing factors for nephrolithiasis are present, and a preventive increase in fluid intake considered.

[Peritoneal dialysis in people more than 75 years old]. / Dialyse péritonéale chez les personnes âgées de plus de 75 ans.

Over 75 years old peritoneal dialysis patients can be treated with at least as good results as those of hemodialysis. Peritoneal dialysis is the only method used to treat old patients at home with psychological profits. Regarding the lack of references on nutritional state of uremic old patients and on early death forecast factors geriatric peritoneal dialysis knowledges are not yet well established.

[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.

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.

[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.