Francois Piette

Pharmacologie clinique et vieillissement

Clinicians must be aware that aging can lead to changes in the pharmacokinetics and pharmacodynamics of many drugs. Drug distribution may be modified with aging secondarily to the decrease of serum albumin and to modifications of body composition (increase in the proportion of fat mass and decrease of lean mass). Hepatic metabolism of several drugs is reduced with age, especially drugs which depend of hepatic blood flow or P450 cytochroms. The incidence of renal failure increase largely with age. Glomerular filtration rate should be systematically estimated in older patients and, when needed, the doses of those drugs having significant renal elimination should be adjusted. In older patients, changes in the response to drugs can also develop, concerning specially the central nervous system (increased sensibility to any neurological effect of drugs), the cardiovascular system and the renal management of water and electrolytes. In many cases, the pharmacological changes associated to age are mild and requires no dose adjustment. However, many drugs should be adapted depending on the individual situation of each patient, particularly his renal function and nutritional state. Finally, some drugs should be avoided in older patients because of a bad effectiveness/tolerance ratio compared to alternatives.

Leukocyte Telomere Length in Alzheimer’s Disease Patients with a Different Rate of Progression

BACKGROUNDnAge and short leukocyte telomeres have been associated with a higher risk of Alzheimers disease (AD). Inflammation is involved in AD and it is suggested that anti-inflammatory interleukin-10 (IL-10) may partly antagonize these processes.nnnOBJECTIVEnThe aim is to correlate telomere length (TL) in peripheral blood mononuclear cells (PBMC) from patients with AD to disease progression rate. Moreover, we evaluated whether TL was associated with IL-10 production by unstimulated or amyloid-β (Aβ)-stimulated PBMC.nnnMETHODSnWe enrolled 31 late-onset AD and 20 age-matched healthy elderly (HE). After a two-year follow-up period, patients were retrospectively evaluated as slow-progressing (ADS) (Mini Mental State Examination (MMSE) decline over the two years of follow-up ≤3 points) or fast progressing AD (ADF) (MMSE decline ≥5 points). TL was measured by flow cytometry and in vitro IL-10 production by enzyme-linked immunosorbent assay.nnnRESULTSnTL (mean±SD) for HE, ADS, and ADF was 2.3±0.1, 2.0±0.1, and 2.5±0.1 Kb, respectively. ADS showed a shorter TL compared to HE (pu200a=u200a0.034) and to ADF (pu200a=u200a0.005). MMSE decline correlated with TL in AD (R2u200a=u200a0.284; pu200a=u200a0.008). We found a significant difference in IL-10 production between unstimulated and Aβ-stimulated PBMC from ADS (40.7±13.7 versus 59.0±27.0; pu200a=u200a0.004) but not from ADF (39.7±14.4 versus 42.2±22.4). HE showed a trend toward significance (47.1±25.4 versus 55.3±27.9; pu200a=u200a0.10).nnnCONCLUSIONnPBMC from ADF may be characterized by an impaired response induced by Aβ and by a reduced proliferative response responsible for the longer telomeres. TL might be a contributing factor in predicting the rate of AD progression.

Interleukin-10 Production in Response to Amyloid-β Differs between Slow and Fast Decliners in Patients with Alzheimer’s Disease

We investigated IL-10 and IL-6 production in amyloid-β (Aβ) stimulated peripheral blood mononuclear cells (PBMCs) in twenty Alzheimers disease (AD) patients with slow progression, eleven with fast progression, and twenty age-matched controls. Promoter polymorphisms in IL-10 (position -592, -819, -1082), IL-6 (-174), transforming growth factor-β1 (TGF-β1) (-10, -25), interferon-γ (IFN-γ) (-874), and tumor necrosis factor-α (TNF-α) (-308) genes were analyzed. IL-10 production after Aβ stimulation was high in PBMCs from slow decliners and almost completely abrogated in fast decliners. Association between AA IFN-γ low-producing genotype and fast progression was demonstrated. Investigations in a larger sample will clarify these findings.

Fall related to epileptic seizures in the elderly.

It is well known that both falls and epileptic seizures are very frequent and harmful in the elderly. Moreover, although seizures may cause falls, their relationship is poorly documented in this population. We report four women (mean age: 84.5 years) who presented falls with: late-onset focal seizures of possible parietal (Case 1) or frontal localisation (Case 2), early onset with late aggravation of juvenile myoclonic epilepsy (Case 3), and generalised situation-related myoclonic seizures (Case 4). Falls were presumably associated with tonic posturing of left (Case 1) or right (Case 2) hemibody, to bilateral and massive myoclonic jerks (Cases 3 and 4) with a loss of consciousness (Case 3). The diagnosis of seizures was difficult and routine EEG was unremarkable in Cases 1 and 2, requiring video-EEG monitoring to capture the clinical events. Adequate treatment offered recovery from seizures and falls in all patients. Other mechanisms of seizure-induced falls in older patients and their management are discussed. In conclusion, falls may be caused by different seizure types and appear to be underestimated due to difficulties in seizure diagnosis in the elderly. Recognizing falls related to seizures is important in geriatric practice, as it facilitates adequate management.

Placement of the VenaTech LP Caval Filter in the Elderly: Feasibility and Clinical Benefits of Insertion Via the Arm

PurposeTo evaluate routine use of access sites in the arm for percutaneous caval filter placement (PCFP) in elderly patients. Neck arthritis, patient anxiety, access site thrombosis or fecal/urinary incontinence complicating jugular or femoral access may require alternative access sites in this population.MethodsAccess via the right arm was chosen for PCFP (VenaTech LP). The indication for PCFP was deep vein thrombosis, a history of pulmonary embolism, and a contraindication to anticoagulant therapy. Ultrasound-guided puncture was performed after diameter measurement of the arm veins (ØAV). The filter was inserted with standard imaging procedures. Procedural difficulty was graded and compared with ØAV and the angle from the arm vein to the superior vena cava (αAV/SVC).ResultsOver 2 years, 16 patients (14 women, 2 men) with an average age of 90 years (range 79–97 years) were included in the study. The average ØAV value of the basilic or brachial veins was 4.2 mm (range 3.0–5.1 mm). The minimal ØAV for successful access was determined after the first 15 patients. No hematoma occurred at the puncture sites. The average αAV/SVC value was 62° (range 29°–90°). Arm access was possible in 12 of 16 patients (75%) with ØAV ≥ 3.5 mm and αAV/SVC ≥ 29°. Every procedure via the arm was graded “easy” by the operator, regardless of angulation values. Femoral access was used in one case due to the impossibility of traversing the heart (patient no. 2), and jugular access was used in 3 of 16 (19%) patients due to puncture failure (patient no. 4), small ØAV (3 mm) (patient no. 6), and stenosis of the distal right subclavian vein (patient no.16), respectively.ConclusionPCFP via the arm can be routinely accomplished in patients older than 75 years, provided ØAV ≥ 3.5 mm, and αAV/SVC ≥ 29°.