Predictive Value for Outcome and Evolution of Geriatric Parameters after Transcatheter Aortic Valve Implantation.

OBJECTIVES: To identify parameters of comprehensive geriatric assessment (CGA) CGA including ABCDEF score, a multidomain frailty assessment, associated with poor outcome after TAVI and to assess the evolution of CGA parameters at 6-months follow-up. DESIGN: one-year monocentric prospective cohort study. SETTING: Departments of geriatric medicine and cardiology in Rouen University Hospital, Normandy, France. PARTICIPANTS: all patients over 70, selected for TAVI by a multidisciplinary "heart team". MEASUREMENTS: 8-areas CGA was performed before TAVI and at 6-months follow-up. Poor outcome was defined as decrease in 1 BADL or unplanned readmission at 6 months or death within the first year after TAVI. Geriatric characteristics associated with poor outcome were assessed by logistic regression with surgical scores as bivariable. Geriatric characteristics were compared between baseline and 6-months follow-up. RESULTS: 114 patients (mean age 85.8±5.3 years) were included. Mean EuroSCORE was 19.1±10.6%. Poor outcome occurred in 57(50.0%) patients. Loss of one BADL (OR:1.66, 95CI[1.11-2.48]), decrease in IADL (OR:1.41, 95CI[1.14-1.74]), in plasmatic albumin (OR:1.10, 95CI[1.01-1.20]), in MMSe (OR:1.13, 95CI[1.02-1.26]), low walking speed (OR:1.53, 95CI[1.01-2.33]) and ABCDEF score ≥2 (OR:1.63, 95CI[1.09-2.42]) were independently associated with poor outcome. In survivors with complete follow-up (n=80), most geriatric parameters were maintained 6 months after TAVI, but IADL decreased (5.6±1.9 to 4.9±2.2, p<0.001). MMSe increased in patients with previous cognitive impairments whereas it decreased in those without (p<0.001). CONCLUSION: CGA parameters are independently associated with poor outcome after TAVI. These parameters, but IADL, are maintained at 6 months and course of the MMSe depends on previous cognitive status.

Functional outcome 1 year after aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysm in elderly patients.

BACKGROUND: Population aging raises questions about extending treatment indications in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). We therefore assessed functional status 1 year after treatment. METHODS: This study involved 310 patients, aged over 70 years, with ruptured brain aneurysm, enrolled between 2008 and 2014 in a prospective multicentre trial (FASHE study: NCT00692744) but considered unsuitable for randomisation and therefore analysed in the observational arms of the study: endovascular occlusion (EV), microsurgical exclusion (MS) and conservative treatment. The aims were to assess independence, cognition, autonomy and quality of life (QOL) at 1 year post-treatment, using questionnaires (MMSE, ADLI, IADL, EORTC-QLQ-C30) filled in by independent nurses after discharge. RESULTS: The 310 patients received the following treatments: 208 underwent EV (67.1%), 54 MS (17.4%) and 48 were conservatively managed (15.5%). At 1 year, independence rates for patients admitted with good clinical status (WFNS I-III) were, according to the aneurysm exclusion procedure (EV, MS or conservative), 58.9%, 50% and 12.1% respectively. MMSE score was pathological in 26 of the 112 EV patients (23.2%), 10 of the 25 MS patients (40%) and 4 of the 9 patients treated conservatively (44%), without any statistically significant difference [Pearson's Chi2 test, F ratio=4.29; P=0.11]. Regarding QoL, overall score was similar between the EV and MS cohorts, but significantly lower with conservative treatment. CONCLUSION: Elderly patients in good clinical condition with aSAH should be treated regardless of associated comorbidities. Curative treatment (EV or MS) reduced mortality without increasing dependence, in comparison with conservative treatment.

Persistent apathy in Alzheimer's disease as an independent factor of rapid functional decline: the REAL longitudinal cohort study.

OBJECTIVE: To determine the role of persistent apathy in rapid loss of autonomy in Instrumental Activities of Daily Living (IADL) in women with Alzheimer s disease (AD), taking into account the grade of cognitive decline. METHODS: The study was conducted on 272 women from the French REAL cohort. At inclusion patients had a Mini-Mental State Examination (MMSE) score between 10-26. A rapid functional decline was defined as a yearly drop of 4 points or more on the 14-point IADL Lawton scale. Persistent apathy was defined as a frequency score equal to 3 or 4 on the Neuro-Psychiatric Inventory at the three consecutive 6-monthly assessments. RESULTS: 27.6% of women had rapid functional decline in 1 year and 22.1% of them had persistent apathy. A logistic regression analysis showed that, in addition to cognitive decline, persistent apathy plays a role in rapid functional decline in 1 year. For example, for a 3-point decline in MMSE in 1 year, the probability of a rapid loss in IADL is 0.45 for women with persistent apathy compared with 0.28 for those without persistent apathy. CONCLUSIONS: In this study, a rapid loss in IADL score was partly explained by persistent apathy.

Frailty, osteoporosis and hip fracture: causes, consequences and therapeutic perspectives.

OBJECTIVE: The aim of this review of the literature is to report the factors which both contribute to the frailty syndrome and increase hip fracture risk in the elderly. This work is the fruit of common reflection by geriatricians, endocrinologists, gynecologists and rheumatologists, and seeks to stress the importance of detection and management of the various components of frailty in elderly subjects who are followed and treated for osteoporosis. It also sets out to heighten awareness of the need for management of osteoporosis in the frail elderly. DESIGN: The current literature on frailty and its links with hip fracture was reviewed and discussed by the group. RESULTS: The factors and mechanisms which are common to both osteoporosis and frailty (falls, weight loss, sarcopenia, low physical activity, cognitive decline, depression, hormones such as testosterone, estrogens, insulin-like growth factor-I (IGF-I), growth hormone (GH), vitamin D and pro-inflammatory cytokines) were identified. The obstacles to access to diagnosis and treatment of osteoporosis in the frail elderly population and common therapeutic pathways for osteoporosis and frailty were discussed. CONCLUSION: Future research including frail subjects would improve our understanding of how management of frailty can can contribute to lower the incidence of fractures. In parallel, more systematic management of osteoporosis should reduce the risk of becoming frail in the elderly population.

Tolerance and Long-Term Efficacy of Polyethylene Glycol 4000 (Forlax®) Compared to Lactulose in Elderly Patients with Chronic Constipation.

OBJECTIVES: To assess the tolerance and potential nutritional consequences of long-term repeated doses of PEG 4000 (10 to 30 g/day) in elderly patients with chronic constipation as compared to lactulose (10-30 g/day). DESIGN: Single blind, randomised, multicentre, parallel group comparative study. SETTING: Community-dwelling patients and nursing homes residents aged 70 years and older with a history of chronic constipation. Treatment intervention: PEG 4000 (10-30 g/day) or lactulose (10-30 g/day) for six months. ASSESSMENTS: Clinical nutritional status (Mini Nutritional Assessment), blood and stool samples were taken at baseline and after three and six months for assay of nutritional and absorption parameters. A patient diary documented digestive symptoms and adverse events were recorded. Information on efficacy (stool frequency and consistency) was collected as a secondary outcome measure. RESULTS: Of the 316 patients screened, 245 eligible patients constituted the ITT population (PEG 4000: N = 118; lactulose group: N = 127). The proportion of patients receiving PEG 4000 with abnormal levels of electrolytes, nutritional markers or vitamins did not significantly change in the six months after initiating laxative treatment and do not differ between the two groups. After a D-xylose challenge test, the proportion of patients with abnormally low xylosaemia (suggesting malabsorption) varied from 24.6% at baseline to 35.8% after six months in the PEG 4000 group and from 29.1% to 42.4% in the lactulose group, with no significant between-group or within-group differences. The proportion of patients with poor nutritional status (MNA score <17) varied from 8.5% at baseline to 9.8% after 6 months in the PEG 4000 group and from 3.9% to 5.0% in the lactulose group. No changes in stool fat or total or soluble stool nitrogen were observed in the minority of patients for whom stool analysis was performed. A significantly higher stool frequency (p <0.05) and improved stool consistency (p <0.05) was observed in the PEG 4000 group compared to the lactulose group at each monthly evaluation period. CONCLUSIONS: After six months of treatment with PEG 4000, no clinically relevant changes in biochemical and nutritional parameters and no unanticipated treatment-related adverse events were detected, demonstrating the good clinical tolerance of PEG 4000 in this population of elderly constipated patients. This tolerance was associated with a better clinical efficacy of PEG 4000 compared to lactulose.

The value of clinical characteristics from a standard questionnaire to discriminate cardiac from neurological syncope in the elderly.

OBJECTIVES: To identify signs and symptoms to differentiate cardiac from neurological syncope in patients over 70 using a standardized questionnaire. DESIGN: Prospective cohort study. SETTING: Five short-stay units in a French university hospital. PARTICIPANTS: One hundred thirty-one in-patients with syncope aged 70 and older. MEASUREMENTS: Patients were interviewed about the signs and symptoms that had been present before, during or after syncope. When possible, a witness who had been present during syncope was also interviewed to compare theirs and the patients' answers. The sensitivity and specificity of 35 questions were calculated among 3 groups defined according to the cause of syncope: cardiac (n = 58), neurological (n = 31) and syncope of unknown origin (n = 42). Statistical analyses were performed to determine discriminating signs and symptoms among the causes and crude agreement was calculated for answers from patients and witnesses. RESULTS: Only 8 and 3 of 35 questions had a sensitivity of at least 0.5 for cardiac and neurological causes respectively. A feeling of impending syncope, thoracic oppression, recall of events preceding syncope and a history of arrhythmia were independently and significantly discriminant among groups. Recall of events preceding syncope (Odds Ratio (OR) = 7.5; 95% confidence interval (CI) = 2.2-25.3) and a personal history of arrhythmia (OR = 4.8; 95% CI = 1.6-14.2) were discriminant between cardiac and neurological causes suggesting mostly a cardiac cause. Agreement between patients and witnesses was only found for questions on the patient's medical history or the circumstances surrounding the onset of syncope. CONCLUSIONS: Recall of events preceding syncope and a history of arrhythmia are strongly suggestive of a cardiac rather than a neurological cause of syncope. Interviews of witnesses are not helpful in suggesting a cause for syncope.

[Sporadic cerebral amyloidotic angiopathy]. / Angiopathie amyloïde cérébrale sporadique.

INTRODUCTION: Sporadic cerebral amyloid angiopathy (CAA) is a microangiopathy identified by neuropathological examination in more than 30 percent of patients over 85 years of age. STATE OF ART: Boston criteria for diagnosis of CAA--related hemorrhage are as follows: "definite CAA", "Probable CAA with supporting pathology", "Probable CAA" and "Possible CAA". Clinical manifestations of CAA are either lobar, cortical, corticosubcortical or cerebellar hemorrhages associated with progressive dementia. Dementia, corresponding either to Alzheimer disease, vascular or mixed dementia, precedes hemorrhages in 25 to 40 percent of cases. Brain MRI can demonstrate microbleeding. PERSPECTIVES: This review compares data regarding CAA prevalence, intracranial hemorrhages, and their risk factors in old patients. Diagnosis and preventive strategies are discussed. It would be useful to identify those affected by CAA among elderly demented patients with atrial fibrillation requiring anticoagulation therapy. CONCLUSIONS: CAA is suspected in the presence of recurrent lobar or cerebellar hemorrhages, and moreover if associated with pre-existing dementia. In elderly demented patients, MRI criteria to detect CAA should be considered in order to prevent hemorrhage risk, particularly after anticoagulation therapy.

Nosocomial febrile illness in the elderly: frequency, causes, and risk factors.

BACKGROUND: Although nosocomial febrile illness (NFI) is common in hospitalized patients, it has been less extensively studied in the elderly. OBJECTIVE: To determine the frequency, causes, and risk factors of NFI in elderly inpatients. METHODS: This prospective study involved 608 patients (> or = 65 years of age) admitted in an acute geriatric unit. Investigators followed this cohort until 1 of the following events occurred: development of NFI, discharge from the geriatric unit, or death. The cause of NFI was classified into 3 groups: infectious, noninfectious, and no apparent diagnosis. We systematically studied 17 comorbid conditions, 6 drugs, and 7 invasive procedures. For comparison, the patients were stratified into 2 groups: patients with NFI and patients without NFI. RESULTS: Sixty-six patients (10.9%) with NFI were identified. They were compared with the remaining 542 patients without NFI. In 49 patients (74%) with NFI, the cause was infectious; in 9 (13.5%), it was noninfectious; and in 8 (12.5%), there was no apparent cause. After multivariate analysis, only fecal incontinence (odds ratio [OR], 5.54; 95% confidence interval [CI], 2.13-14.5), congestive heart failure (OR, 2.97; 95% CI, 1.53-5.76), and pressure ulcers (OR, 2.93; 95% CI, 1.19-7.17) were independent risk factors for NFI. The number of invasive procedures preceding the febrile episode was a significant predictor of infection (OR, 3.68; 95% CI, 1.14-9.21). CONCLUSIONS: Nosocomial febrile illness is a common event in elderly hospitalized patients. In 74% of the patients with NFI, an infection is found. Measures to decrease infectious NFI in the elderly require a reduction in the number of invasive procedures.

High bacterial titers in urine are predictive of abnormal postvoid residual urine in patients with urinary tract infection.

Urine bacterial titers (BTs) are influenced by bacterial and host factors. The impact of an abnormal postvoid residual (PVR) on BT in urine was investigated. A total of 103 inpatients with a urine growing Enterobacteriacae (≥ 10(2) CFU/mL) and a PVR measure were analyzed, mostly female (62%), elderly (mean age: 72 years), with urinary tract infection (25% of asymptomatic bacteriuria) due to Escherichia coli (85%). Fifty-two subjects (56%) had BT ≥ 10(6) CFU/mL; 48 (53%) had a PVR ≤ 100 mL, while 26 (25%) had a PVR >250 mL. PVR increased with BT, and a significant (P<0.0001) threshold was reached for 10(6) CFU/mL: 100mL mean PVR for patients with BT ≤ 10(5) CFU/mL versus 248 mL for patients with BT >10(5) CFU/mL. High PVR and BT were associated with complicated infections, concomitant bacteremia, and delayed apyrexia. Screening for patients with BT ≥ 10(6) CFU/mL is an easy way to identify patients at high risk for acute retention and voiding disorders.

Fecal incontinence in the institutionalized elderly: incidence, risk factors, and prognosis.

PURPOSE: This study was conducted to evaluate the incidence, identify the risk factors, and assess the prognosis of elderly institutionalized patients who develop fecal incontinence. PATIENTS AND METHODS: We enrolled 1,186 patients 60 years of age and older living in long-term care facilities who did not have fecal incontinence. We assessed their medical history, treatment, mobility, and cognitive function. Patients were followed up for 10 months to determine the incidence of fecal incontinence, defined as at least one involuntary loss of feces. Independent risk factors associated with fecal incontinence were identified using Cox proportional hazards models. The prognosis of incontinent patients was assessed by comparing their survival rate with that in the continent patients. RESULTS: Fecal incontinence occurred in 234 patients (20%), and was usually associated with acute diarrhea or fecal impaction. We identified five risk factors for the development of fecal incontinence: a history of urinary incontinence (rate ratio [RR]: 2.0, 95% confidence interval [CI] 1.5 to 2.6); neurological disease (RR: 1.9, 95% CI 1.0 to 3.4); poor mobility (RR: 1.7, 95% CI 1.2 to 2.4); severe cognitive decline (RR: 1.4, 95% CI 1.1 to 1.9); and age older than 70 years (RR: 1.7, 95% CI 1.0 to 2.8). Ten-month mortality in the 89 patients with long-term (> or = 8 days) incontinence was 26%, significantly greater than that observed in the continent group (6.7%) or in the 145 patients with transient incontinence (10%). CONCLUSIONS: Long-lasting or permanent fecal incontinence was associated with increased mortality, suggesting that this symptom is a marker of poor health in older patients. Actions that improve mobility might help prevent fecal incontinence in elderly patients.

Is presentation of bacteremia in the elderly the same as in younger patients?

OBJECTIVE: To compare the presentation of bacteremia in young and elderly patients. PATIENTS AND METHODS: Seventy-one elderly (mean age 80.4 years) and 34 younger inpatients (mean age 45.7 years) with bacteremia were prospectively studied. These were compared with a control group of 187 geriatric patients (mean age 81.3 years) with clinical signs of bacteremia but in whom blood cultures were negative. Bacteremia was defined as one or more positive blood cultures showing a pathogenic bacteria in patients with clinical signs of bacteremia. In all 105 patients with bacteremia, 16 common clinical or biological signs of the disease were immediately investigated after blood culture. Patients were classified into three groups: elder patients and young patients with bacteremia and elderly patients without bacteremia. RESULTS: Only three clinical findings of the 16 studied were found in at least 70% of the bacteremic elderly patients: fever, increased erythrocyte sedimentation rate, and a clinical indication of the source of infection. These three signs were found statistically more often in bacteremic elderly compared with nonbacteremic elderly patients (P < 0.01). Seven other signs (hypothermia, altered mental state, leukopenia, and lymphopenia) had a specificity above 80%. On a logistic regression analysis, four variables were significantly and independently associated with bacteremia in the elderly: rapid onset of infection (defined as a period < or = 48 hours between the earliest manifestation of bacteremia and the time of blood blood sample), fever, altered general state, and clinical indication of the source of infection. Younger infected patients had more chills, sweating, alter general state, altered mental state or lymphopenia than did the bacteremic elderly patients. Bacteremic elderly patients had statistically few symptoms than the young infected patients (P < 0.001). CONCLUSIONS: In elderly patients with early stage bacteremia, most of the signs or symptoms that are considered typical in the literature appear irregularly. None appeared pathognomonic. Elderly patients with bacteremia had fewer signs or symptoms than younger infected patients.

Differences in the signs and symptoms of hyperthyroidism in older and younger patients.

OBJECTIVES: To determine if aging modifies the clinical presentation of hyperthyroidism and the signs of thyrotoxicosis in older people. DESIGN: Prospective cohort study. SETTING: A French university hospital. SUBJECTS: Eighty-four new patients with overt hyperthyroidism confirmed chemically between January 1992 and January 1993. Controls were 68 older euthyroid patients matched to the older hyperthyroid patients. MEASUREMENTS: Comparison of 19 classical signs of hyperthyroidism between 34 older patients (> or = 70 years; mean age 80.2) and 50 younger patients (< or = 50 years; mean age 37.4). Older patients were also compared with controls (mean age 81.3). RESULTS: Three signs were found in more than 50% of older patients: tachycardia, fatigue, and weight loss. Seven signs were found significantly less frequently in older patients (P < .001): hyperactive reflexes, increased sweating, heat intolerance, tremor, nervousness, polydipsia, and increased appetite. Only anorexia (32% vs 4%) and atrial fibrillation (35% vs 2%) were more found frequently in older people (P < .001). A goiter was present in 94% of the younger and in 50% of the older patients (P < .001). The mean number of clinical signs found in the older subjects was significantly smaller than the number found in younger patients (6 vs 10.8; P < .001). Comparison with older controls showed three signs that were highly associated with thyrotoxicosis in older people: apathy (Odd ratio (OR): 14.8), tachycardia (OR: 11.2), and weight loss (OR: 8.7). CONCLUSION: This study confirms the paucity of clinical signs of hyperthyroidism in older adults. These results suggest the necessity of routine screening for thyroid disease in this age group.

Does age play a role in clinical presentation of hypothyroidism?

OBJECTIVE: To determine if aging modifies the clinical presentation of hypothyroidism. DESIGN: Comparison of 24 clinical signs of hypothyroidism between elderly patients (> or = 70 years of age) and younger patients (< or = 55 years of age). SETTING: Prospective study of patients with chemically confirmed overt hypothyroidism. PATIENTS: Sixty seven elderly patients (79.3 +/- 6.7 years) and 54 younger patients (40.8 +/- 9 years) were included in the study. RESULTS: Neither mean duration of evolution nor mean thyroid-stimulating hormone (TSH) level were different between the 2 groups. Two signs were found in more than 50% of the elderly patients (fatigue and weakness). Four signs were significantly less frequent in elderly patients (chilliness, paresthesiae, weight gain, and cramps). Mean number of clinical signs in the elderly (6.6 +/- 4) was significantly smaller than in young patients (9.3 +/- 4.7) (P < 0.01). CONCLUSIONS: Our results suggest that the presentation of hypothyroidism is altered in the elderly in comparison with young patients in that there are (1) fewer signs or symptoms and (2) diminished frequency of some classical signs. Our results underline the importance of TSH measurement in the elderly.

Drug-drug interactions related to hospital admissions in older adults: a prospective study of 1000 patients.

OBJECTIVE: To investigate the frequency, nature, and side effects of drug-drug interactions (DDI) in a group of geriatric inpatients. DESIGN: Study of drugs administered at home in the 2 weeks preceding hospitalization. SETTING: Evaluation of patients admitted to a geriatric unit from the emergency unit. PATIENTS: One thousand inpatients more than 70 years of age (83.0 +/- 7.1 years), admitted consecutively to a hospital for acute illness. MEASUREMENTS: All possible two by two combinations of drugs administered at home were considered to determine whether these associations could lead to a DDI and whether side effects resulted from these interactions. RESULTS: Five hundred thirty-eight patients were exposed to 1087 DDI. The most frequently involved drugs were cardiovascular and psychotropic medications. There were 189 side effects observed in 130 patients. The most frequent side effects were neuropsychological impairment, arterial hypotension, and acute renal failure. The number of side effects did not differ between the 66 contraindicated drug associations and the 1021 associations that only required precautionary use. CONCLUSIONS: DDI frequently lead to side effects in older adults. Classifications of DDI must be adapted to increased DDI sensitivity in this population. Nevertheless the frequency of side effects might be reduced by limiting the prescription of the most frequent and dangerous DDI.

Does age play a role in mylohyoideus muscle function?

Because swallowing disorders are frequent in the elderly, we assessed the relationship between age and mylohyoideus muscle contraction, which is an important component of the initial step in swallowing. In a prospective study, 120 subjects without any personal history of diseases associated with swallowing disorders underwent electromyographic recording (EMG) of mylohyoideus muscle activity. Four groups of equal size (n = 30) were defined according to age (< or = 50, 51-70, 71-85, >85 years). The frequency and duration of mylohyoideus muscle asynchronisms were compared among the four groups. The comparison of mylohyoideus muscle EMG among groups did not show a significant difference in the mean number of asynchronisms, in duration per subject or in the frequency of long-lasting asynchronisms. Asynchronisms were a very frequent event, observed in 98% of subjects, and were mostly short, lasting less than 0.1 s in 90% of subjects. In healthy elderly patients, there was no linear relationship between the mean duration of asynchronisms and ageing. The occurrence of one or more long-lasting asynchronisms or of at least six asynchronisms during a sequence of 10 successive swallows should be considered to be abnormal.

[Cancer of the cervix. Dictionary of complications]. / Cancer du utérin. Glossaire ou lexique des complications.

This glossary of the complications of carcinoma of the cervix was evaluated by the review of more than 1 000 medical records at the Gustave-Roussy Institute. It is the fruit of the practical experience over several years of a team combining of the disciplines of radiotherapy, surgery, gynaecology and computer techniques. It has no pretense at universality. It greatly simplifies, and always in terms of practice and not theory. It was established for the purpose of computerised recording and hence statistical study. It is inadequate for detailed studies in depth of individual complications.

[Prevalence of anal incontinence in adults]. / Etude de la prévalence de l'incontinence anale chez l'adulte.

Inquiries were conducted to determine the prevalence of anal incontinence in a) the general population over 45 by a gallup poll studying 1,100 persons (A); b) 3,914 patients seen by their general practitioner or their gastroenterologist during the same week (B); c) 500 patients consulting for urinary stress incontinence (C1); d) 1,136 neurological patients suffering from micturation disorders (C2); and e) 10,157 elderly persons living in retirement homes or in hospital (D). In the general community (A), the prevalence of anal incontinence, including gas and stool incontinence, was 11 percent, the prevalence of fecal incontinence, 6 percent, the prevalence of daily or weekly fecal incontinence, 2 percent; prevalences were respectively 15.5 percent, 7.9 percent, and 3.2 percent in group B, and 27 percent, 9 percent and 3.8 percent in group C1. The prevalence of fecal incontinence was 18 percent in group C2 and 33 percent in group D. Prevalence did not depend on age in group A and C1, but was twofold higher in group C1 than in group A. The prevalence increased with age in groups B and D.

[Vasoactive factors of endothelial origin]. / Les facteurs vasoactifs d'origine endothéliale.

The discovery of powerful vasoactive compounds synthetized by the vascular endothelium has led to the elaboration of new physiopathological concepts. We review the present state of knowledge about the role, potential therapeutic virtues, and physiopathological consequences of the three major endothelial vasoactive factors: 1. Prostacyclin (PG12), a powerful vasodilator, and the most potent known inhibitor of platelet aggregation, derived from arachidonic acid metabolism: 2: Endothelium-derived relaxing factor (EDRF) a powerful vasodilator thought to be a short-acting nitroxide; 3: Endothelin, a 21 amino-acid peptide with potent vasoconstricting properties.

[Methotrexate. Pharmacology applied to the treatment of rheumatoid arthritis]. / Méthotrexate. Pharmacologie appliquée au traitement de la polyarthrite rhumatoïde.

Methotrexate (MTX) is used increasingly for the treatment of rheumatoid arthritis (RA). It is an antagonist of folic acid. For the low doses used in RA (less than 15 mg/week), MTX is completely and rapidly absorbed with an active process membrane transport. The frequent toxic effects of this drug (hepatotoxicity, hematologic or possible long-term oncogenicity) limit its widespread use. MTX is as effective in treating RA as the other second line drugs and always more rapidly effective, perhaps because of anti-inflammatory properties. MTX must at the present time be used only in severe RA, refractory to more than one classical slow acting drug. Despite this, it is an extremely promising new agent in the therapy of rheumatic diseases.