[Geriatrics from the 19th to the 21st century. 150 years of geriatric medicine: from increasing life expectancy to improving quality of life for the very old]. / La Gériatrie du 19ième au 21ième siècle.

With the world further aging, geriatric medicine clearly became a necessity: in the 21th century many more people reach older ages by means of continued medical success in expanding lifespan. 150 years ago life expectancy was between 30 to 40 years, but today close to 800 million people are 60 yeas old or more. During the last century aging has been associated with decline and decay, but gradually more people lived ably and healthily in older ages. The expansion in life expectancy has become a synchronism of quality of life: the average 65 year old today is much healthier, physically and mentally fitter, than the average 50 year old 150 years ago, when Alois Alzheimer war born, a period when most nowadays existing geriatric institutions were envisioned and progressively realized over time. Today we strongly believe that a healthy life and, equally, the quality of life of the very old people can be extended with presently existing medical knowledge, based on research, environmental and behavioural changes, by postponing the onset and progression of fatal and disabling diseases and disorders. But very soon ethical considerations concerning all kinds of medical and technological solutions available to maintain or even improve the mental and physical functioning of dependant elderly people will engage our society when deciding how and at what moment in time to make the best decisions and allocate resources. Geriatric medicine will be further challenged by competing and demanding medical and economic needs, when marshalling resources to meet the growing demands of our society for improving care for the very old and often demented adult.

[The reduction of stroke risk, risk of myocardial infarction and death by healthy diet and physical activity]. / Die Verminderung des Schlaganfall-, Herzinfarkt- und Sterblichkeitsrisikos durch gesunde Ernährung und körperliche Aktivität.

There is no doubt that a healthy diet and regular physical activity improve risk factors for cerebro-cardio-vascular disease and death. However, there is less evidence from prospective randomised controlled trials that they also reduce the actual risk of stroke, myocardial infarction and death. The only evidence from randomised controlled trials is, that a mediterranean diet with nuts and/or native olive oil considerably reduces stroke risk by 47% respectively 31%, however not the risk of myocardial infarction and death. A low-fat diet, a low-salt diet, and the addition of omega-3 fatty acids have no influence. In case of severe obesity with a BMI of > 34-38 kg/m2, weight reduction is the priority, if necessary by means of bariatric surgery. In longitudinal studies mortality (-29%), stroke (-34%), and myocardial infarction (-29%) could thus be reduced. Regular physical activity, whether endurance or more intense activity, leads to weight loss and improved vascular risk factors. An independent impact on stroke, myocardial infarction and mortality has not yet been demonstrated in prospective studies (double-blinding being impossible). Nevertheless, several epidemiological meta-analyses with observation durations of 4 to 28 years using data of up to 880 000 persons, indicate that there is a 2-3 fold risk reduction of cerebro-cardio-vascular death and global mortality in people with regular physical activity versus sedentary behaviour.

Risk factors and disease prevalence in 3331 personal check-ups performed in preventive medicine between 2006 and 2011. cross-sectional and follow-up study.

INTRODUCTION: The present data results from a retrospective analysis of 3331 check-ups made in the preventive medicine department of the "ZithaKlinik", named "ZithaGesondheetsZentrum". These check-ups are done for the employee's of several firm's and institutions. According to gender and age, several tests and examinations are performed and the results are given to the person's general practitioner or another doctor of his choice. We will present a global synthesis of all the results but also a follow-up study of persons having performed 2 check-ups or more over a 5-year period. POPULATION: In the cross-sectional part, the analysis is done on 3331 individual check-ups (1447 woman, 1884 men). The average age is 50.3 years +/- 11.4. In the follow-up study, 478 persons (191 women, 287 men) had at least 2 (maximum 5) check-ups in the 5-year period of our observation. Initial age was 54.1 +/- 10.9 years for woman and 51.4 +/- 11.4 for men, respectively 56.4 +/- 10.9 and 53.7+/- 11.2 at their last check-up. RESULTS: An alarming number of persons present with a weight or obesity problem (according to age ranging from 22.0% overweight and 7.3% obese from 18-29 years, respectively 37.5% and 11.3% from 30-49 years, finally 44.0% and 20.6% in the range 50-69 years). Associated risk factors and pathologies (Hypertension, Dyslipidemia, NASH, diabetes type 2 and complete metabolic syndromes) are extremely frequent and getting more so with growing age. Furthermore, physical activity is insufficient in grossly 2/3 of the studied population. The only positive point is a tendency of decreasing tobacco use in all age groups. The follow-up study is frustrating because most of the examined criteria get worse in-between check-ups instead of getting better with changes in lifestyle in an informed population. CONCLUSIONS: Asymptomatic diseases or risk factors for non-communicable diseases are extremely frequent in the population examined. The follow-up data shows that huge parts of this group are not sufficiently conscientious of their problems to act up and change their life-style or seek adapted pharmacological prevention. Absolute number of risk factors (prevalence) or pathologies rise evidently with age but incidence (newly discovered pathologies after a first, second or a record of 21 check-ups with our services) rises less. Life-style changes are rare or insufficient to change the pathological value back to normal or therapeutically range. Even with several biases (retrospective design, selection bias, ...) our study puts similar problems forward in the population as ORISCAV. The astonishing (better than national records) results in tobacco use is probably due to a selection of more health-oriented patients and of a higher socio-educative-economic level. Alcohol abuse was very low but probably due to inadequate screening methods. A better health promotion advocating healthier living must be associated with better communication and new motivational tools. Therapeutical education for patients with chronic non-communicable diseases will be the challenge of the near future as their prevalences increase due to ageing of the population and worse individual lifestyles. In this task, efforts must be made on the personal level (health-team with the individual patient) but also on the national level (legal frame work for patient education by multi-professional teams as they exist already in neighbour states).

[Development of the medical treatment of diabetes in Luxembourg]. / Evolution du traitement médicamenteux du diabète au Luxembourg.

OBJECTIVES: The aims of the study were to estimate the prevalence of diabetes in Luxembourg in 2002, to compare it to the prevalence reported in 1991 and to evaluate if prescription attitudes have changed since 1991. METHODS: The prevalence of diabetes was estimated using the drug sales data. The key parameters, total amount of antidiabetic drugs sold in one year and the average daily dose or Prescribed Daily Dose (PDD), have been obtained from the National Social Security Organization and by a standardized questionnaire sent to all general practitioners and all internists and endocrinologists of the country. RESULTS: The PDD was calculated on 2,402 questionnaires on individual diabetic patients. By this mean, the proportion of patients only treated with appropriate diet could also be obtained. Compared to 1991, the total amount of antidiabetic drugs showed a four-fold increase in biguanides tablet prescriptions. A high percentage of combined treatments was found. The prevalence of diabetes in Luxembourg was found to be 3.05% of the total population. CONCLUSIONS: Compared to the status in 1991, prevalence of diabetes increased by 63%, which seems mainly due to type 2 diabetic patients as orally-treated diabetic patients almost doubled (2.11% vs 1.16%). A substantial change in prescriptions for diabetes has occurred, suggesting a positive influence of studies like the United Kingdom Prospective Diabetes Study (UKPDS).

Changes in diabetes prevalence and treatment in the last ten years in Luxembourg. A lesson from the United Kingdom prospective diabetes study?

OBJECTIVES: The aims of the study were to estimate the prevalence of diabetes in Luxembourg in 2002, to compare it to the prevalence reported in 1991 and to evaluate if prescription attitudes have changed since 1991. METHODS: The prevalence of diabetes was estimated using the drug sales data. The key parameters, total amount of antidiabetic drugs sold in one year and the average daily dose or Prescribed Daily Dose (PDD), have been obtained from the National Social Security Organization and by a standardized questionnaire sent to all general practitioners and all internists and endocrinologists of the country. RESULTS: The PDD was calculated on 2, 402 questionnaires on individual diabetic patients. By this means, the proportion of patients only treated with appropriate diet could also be obtained. Compared to 1991, the total amount of antidiabetic drugs showed a four-fold increase in metformine tablet prescriptions. A high percentage of combined treatments was found. The prevalence of diabetes in Luxembourg was found to be 3.05% of the total population. CONCLUSIONS: Compared to the status in 1991, prevalence of diabetes increased by 63%, which seems mainly due to type 2 diabetic patients as orally-treated diabetic patients almost doubled (2.11% vs 1.16%). A substantial change in prescriptions for diabetes has occurred, suggesting a positive influence of studies like the United Kingdom Prospective Diabetes Study (UKPDS).

[Lipiwatch: a study of the treatment of dyslipidemias in Luxembourg]. / Lipiwatch: une étude du traitement des dyslipidémies au Luxembourg.

LIPIWATCH is an observational study which has been initiated for 6 months in Belgium and in Luxembourg in 1997 to evaluate if patients treated by lipid-lowering drugs could reach the recommendations of the EAS and NCEP II for LDL-C. 76 patients (31 men) with a mean age of 59.2 +/- 11.39 years were included. 96% of patients had at least one other associated cardiovascular risk factor. After 6 months of treatment, 33% of all patients and only 30% of patients with coronary heart disease or peripheral vascular disease or at least 2 other risk factors reached the recommendations of the EAS. 25% of all patients and only 20% of patients with known coronary heart disease reached the NCEP II recommendations. 55% of patients had a statin prescribed and 38% a fibrate. Mean total cholesterol and mean LDL-C was lowered by 20% and 19% after 6 months. These disappointing results confirmed an insufficient awareness by physicians and patients, inadequate dosages of drugs and a bad compliance by patients.

[Evolution and weight and body composition determination after therapy for pathological obesity for measuring compliance in (re)-education]. / Evolution du poids et de la composition corporelle à moyen terme après une cure pour obésité pathologique selon la compliance à la (ré)-éducation.

Obesity, and its associated complications, is one of the most costly diseases in modern civilisations. Dieting alone rarely gives good long-term results. The effect of the combination of nutritional education and moderately intensive physical exercise on the evolution of weight and Body composition has been analysed by bio-impedancemetry over a one-year period. Patients could be divided into four groups: patients lost after the 3-week nutritional course, patients neither dieting nor exercising, patients dieting and patients both dieting and exercising. The results for the four groups were the following: undeterminably, 5% loss compared to initial weight (and nearly 10% compared to reported maximum weight). 10% loss and 15% loss over one year. In the last group, Body composition showed a relative increase in muscle mass, which explains the lack of a drop in basal metabolic rates seen in the diet-alone group. This maintained metabolic rate probably prevented patients from weight cycling (yo-yo phenomenon). This result can be compared to other life-style changing studies or pharmacological treatments (Orlistat, sibutramine) of obesity, which resulted in an approx. 10% weight reduction.

Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus.

BACKGROUND: Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes. METHODS: As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-level scale (none to proliferative). FINDINGS: The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p = 0.2). Patients on lisinopril had significantly lower HbA1c at baseline than those on placebo (6.9% vs 7.3 p = 0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p = 0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p = 0.06). Lisinopril also decreased progression by two or more grades (0.27 [0.07-1.00], p = 0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p = 0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p = 0.4). INTERPRETATION: Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.

Genetic variability of the CYP 2D6 gene is not a risk factor for sporadic Parkinson's disease.

Genetic studies of the frequencies of mutant alleles for coding cytochrome P-450 monooxygenase (CYP 2D6) in Parkinson's disease (PD) patients have been inconsistent. We studied the mutants A and B in 80 strictly defined sporadic PD patients divided into young age onset of the disease (< 40 years, N = 20), mid age onset (40-50 years, N = 12), and older age onset (> 50 years, N = 48). They were compared with 108 controls from the same geographic area. There were no significant differences in allele or genotype frequencies between PD patients and controls. Future genetic studies in PD should focus on other alleles or other areas of the genome.

Epirubicin cardiotoxicity: a study comparing low- with high-dose-intensity weekly schedules.

Epirubicin is one of the less cardiotoxic alternatives to doxorubicin. We were interested in studying the cardiotoxic effect of the total cumulative dose, and weekly schedules of low compared to high dose intensity. Fifty-seven patients were treated with different epirubicin-containing regimens. We confirm the classical notion that total cumulative doses of less than 600 mg/m2 do not induce significant cardiotoxicity, whereas doses above 600 mg/m2 are associated with a trend towards cardiotoxicity. Patients receiving a high weekly dose intensity (> 40 mg/m2), however, did have a significantly lower incidence of cardiotoxicity than those receiving a low dose intensity per week (< 40 mg/m2) (22.8% versus 50%; P < 0.05). We identified the association of a dose intensity of more than 40 mg m-2/ week-1 and a cumulative dose of 400-899 mg/m2 or a dose intensity of less that 40 mg m-2/week-1 and a cumulative dose of less than 400 mg/m2 to have the lowest incidence rate of cardiotoxicity. We conclude from this study that epirubicin in weekly schedules of high dose intensity is not more cardiotoxic than in weekly schedules of low dose intensity.

[Clozapine in the treatment of mental manifestations of Parkinson disease]. / La clozapine dans le traitement des manifestations psychiatriques de la maladie de Parkinson.

BACKGROUND: Medical treatment of Parkinsonian syndromes is often complicated by psychiatric side effects such as confusional states, hallucinations and psychosis. Recent pilot studies report good clinical results with the atypical neuroleptic clozapine. PATIENTS AND METHODS: We report on 15 patients with Parkinsonian syndromes: 11 with idiopathic Parkinson's disease (IPD), 3 with multiple system atrophy (MSA) and 1 with postencephalitic Parkinsonism (SPP). The mean age was 68.8 +/- 10 years; the mean duration of Parkinsonian symptoms was 6.8 +/- 5.7 years. The Hoehn & Yahr grade was: 3.5 +/- 0.8. Eleven patients were suffering from psychotic episodes, 10 from hallucinations, 8 from confusional states. Clozpine was introduced at nighttime and dosage was modified until the appearance of clinical effect or intolerable side effects. RESULTS: We report on an observed cumulative duration of clozapine treatment of 13 patient-years. The average treatment duration was 10.5 +/- 10.4 months. The mean daily dose was 33.3 +/- 30 mg (range: 6.2-100). There was at least transitory improvement of psychiatric symptoms in all patients. There was constant and complete improvement in 7 patients (46%) and satisfactory improvement in 5 patients (33.3%). The levodopa dosage was unchanged (mean dosage 563 +/- 232 mg), and the dosage of dopamine agonists was significantly increased. None of our patients experienced motor deterioration. Side effects comprised sialorrhoea, sedation, orthostatic hypotension, and delirium tremens and an epileptic seizure in one patient each. Two patients died suddenly at the 63rd and at the 86th day of treatment respectively, outside the hospital. These deaths seemed to be unrelated to the treatment. There was no agranulocytosis. CONCLUSION: Clozapine is an efficient antipsychotic drug in Parkinsonian patients with no motor side effects in the dosages used. The effective dosage is very low in comparison to psychiatric patients. However various side effects may occur and close monitoring is required.

[Biochemistry and medical value of NO. Physiology and physiopathology of nitric oxide]. / Biochimie et intérêt en médecine du NO. Physiologie et physiopathologie des oxydes nitriques.

The metabolism of nitric oxide (NO) and its derivatives has the advantage of ubiquitarian distribution and these compounds have multiple biological effects. The way of synthesis is simple and this biochemistry produces many variable products in normal physiological conditions. The way of synthesis is simple and this biochemistry produces many variable products in normal physiological conditions. The way of transportation and the pH (giving a particular redox condition) determine its half-life, the function of the molecule and its transmitted message. The advantage of the general distribution of this synthesis is probably a disadvantage in pharmacological approaches. Drugs which will increase or decrease the NO production have to act in a very precise location in a complex physiology so as not to produce more adverse side-effects in another location than benefit effects on the target. This review is a synthesis of the physiology and pathology of this biological information transmitting system.

[Implantable insulin pumps: evaluation after more than 3 years experience]. / Les pompes à insuline implantables: bilan après plus de trois ans d'expérience.

Since the beginning of insulin therapy the improvement of treatment in IDDM is mainly for acute metabolic complications than for chronic degenerative complications. The DCCT could recently prove for the first time that the incidence of chronic complications (retinopathy, nephropathy and neuropathy) could be diminished by reaching glycemic control in more than 700 patients. One of the problems explaining the failure of classical treatment is due to the variability of absorption in the sub-cutaneous tissue. The patients treated by insulin pumps are all IDDM. The aim of this study is to evaluate safety and feasibility of implantable programmable pumps with intraperitoneal insulin infusion. We found three cases of irreversible catheter obstruction. Defects of external communicators and the slow-downs of insulin infusion in infusaid pumps were observed. No acceleration in insulin infusion was found. Acute metabolic complications were two severe hypoglycemic events, but no acito-cetosis. After more than two years for most of the patients we observed a global improvement in glycemic control, demonstrated by a better mean glycemia and lower HbA1c values. The standard deviation of the glycemia was lowered significantly, this value reflects daily fluctuability. The number of hypoglycemias was also lowered. Our study shows a more stable glycemic control than the one in the DCCT study. The safety and feasibility seem to be highly satisfying.

Of the British coastline and the interest of fractals in medicine.

We review a certain number of medical applications of a new non-euclidean geometry: the fractal geometry described by Mandelbrot. Examples come from anatomy, cytology, general physiology and physiopathology. Furthermore, real clinical applications are shown, in particular, in cardiology, neurology, ophtalmology, radiology and other imaging techniques. An easy reading mathematical approach is added. Some of the fractal images will certainly capture your attention and spur your interest for further applications of this new concept.

Diffusion properties of an artificial membrane used for Langerhans islets encapsulation: an in vitro test.

Glucose and insulin permeability of an artificial membrane (AN69, HOSPAL, Sweden) used for Langerhans islets encapsulation were investigated. In vivo, a 1 and 7 d intraperitoneal implantation of the AN69 membrane in rats induced a loss of permeability towards glucose and insulin probably due to a protein-coating performed after implantation. In vitro, a protein-coating of the AN69 membrane with fetal calf serum solution reproduced similar results. Thus this in vitro test which mimicks in vivo conditions should be proposed to evaluate rapidly the physicochemical properties of a membrane suitable for pancreatic islets encapsulation.