[Effect of age on the natural history of the shoulder: a clinical and radiological study in the elderly]. / Etude du vieillissement naturel de l'épaule: étude clinique et radiographique d'une population de personnes âgées.

PURPOSE OF THE STUDY: Classically, the shoulder joint is thought to age more by its tendons than by its cartilages, the incidence of rotator cuff tears being considered to increase with age. The purpose of this work was to assess the natural history of the shoulder joint based on a clinical and radiological study of 200 patients aged 70 to 101 years. MATERIAL AND METHODS: The cohort was composed of 48 men (34%) and 152 women (76%), aged 84.25 +/- 6.7 years. All patients underwent a physical examination and the Constant score was established. The radiographic examination included an AP view in neutral rotation of both shoulders. The Hamada classification was used to stage full thickness cuff tears. The glenohumeral compartment was analyzed to search for osteophyte formation and joint narrowing. RESULTS: The subacromial height was greater than 6 mm, mean 9.89 +/- 2 mm, in 349 shoulders (87.25%), corresponding to stage I in the Hamada classification; it measured less than 6 mm, mean 3.08 +/- 1.7 mm in 51 shoulders (12.75%) in 38 subjects (19% of the total cohort). The Hamada classification for the other shoulders was stage II (n = 21 shoulders, 5.25%), and stage III (n = 16 shoulders, 4%), stage IV (n = 5, 1.25%) and stage V (n = 5, 1.25%). The Hamada stage could not be determined for four shoulders. There was a strong statistical correlation between the Constant score and Hamada stage. The glenohumeral space was normal in 288 shoulders (72%). Ninety-three shoulders (23.25%) in 62 patients (31%) presented humeral and/or inferior glenoid osteophytes without glenohumeral impingement and 19 shoulders (4.75% in 14 patients (7%) presented complete glenohumeral impingement. There was a significant correlation between the Constant score and severity of the glenohumeral degradation. The proportion of subacromial impincement increased significantly and regularly with degradation of the glenohumeral space (p < 104). For half of the shoulders, glenohumeral impingement was associated with subacromial impingement (eccentric osteoarthritis). DISCUSSION: The results of this study confirm that the frequency of rotator cuff tears increases with age. One out of five patients aged 70-90 years presented subacromial impingement versus one out of three among patients aged over 90 years. Clinical tolerance of subacromial impingement or subacromial osteoarthritis is good. Glenohumeral impingement, associated or not with subacromial impingement, is poorly tolerated, the patients presenting shoulder pain and marked stiffness. CONCLUSION: Our results demonstrate that the natural history of the shoulder does not exhibit a regular linear relationship with the Hamada radiological classification.

Emergency hospitalization in the elderly in a French university hospital: medical and social conditions and crisis factors precipitating admissions and outcome at discharge.

Emergency admissions of elderly patients constitute a major management issue due to the complexity of their problems. The aim of this retrospective observational study was to identify medical and social characteristics and crisis factors for emergency department (ED) hospitalization in elderly patients, and to evaluate the influence of these factors on the length of stay and outcome at discharge. During a 4-month period, 396 patients aged 70 years and older were referred to the ED of a University Hospital (Hjpital Edouard Herriot) in Lyon, France. A questionnaire specifically designed for the study was completed for each patient using the information in the patients' files previously filled in by the "Rapid Geriatric Assessment Team" of the ED. We described civil and marital status, living conditions, reason for admission to ED and other associated pathologies according to the ICM-9, crisis factors, length of stay (LOS) and outcome at discharge. The mean age was 81.9 years (SD 6.5); two thirds (66.7%) of the study subjects were female, and 46.7% were widowed; the majority (68.7%) lived in their own homes. The main reasons for admission were cardiopulmonary diseases in 31.6% of cases, followed by neuropsychiatric disorders in 28.2%, and falls in 8.3%; a final category (31.8%) included subjects admitted for general, non-specific symptoms. Among the crisis factors observed, 49.4% presented an acute episode of a chronic illness, 33.6% lived alone, and 20.9% had been hospitalized during the 6-month period preceding the study. The average LOS was 3.15 days. The multivariate model showed that falls increase LOS by 74%, dementia by 65%, and depression by 21%. Upon discharge, 13% returned to their residence before hospitalization, 55% were transferred to a medical speciality ward, and 4% to other facilities, whereas only 19% were transferred to a geriatric ward, and 9% died during their stay in the ED. The multinomial model showed that outcome at discharge was influenced by functional dependency, dementia, depression, and acute episodes of a chronic illness. For many elderly, the ED remains a critical point of access to more complete managed care. This elderly population is comprised of polypathological, frail persons whose morbid state requires multidisciplinary management in geriatric units. The findings of this study suggest that interventions of multidisciplinary networks, such as home health care programs aimed at detecting crisis factors and establishing early prevention of crisis states, may improve unfavorable medical and social conditions and reduce hospitalization in geriatric patients.

In vivo hippocampal (31)P NMR metabolites in Alzheimer's disease and ageing.

Memory loss is the most common early symptom of Alzheimer's disease (AD). For this study, we chose the hippocampi as regions of interest. The hippocampus, which is closely associated with memory processing, is known to be vulnerable to damage in the early stage of AD. We considered both inter-group (patients vs controls) and intra-group (right vs left hippocampus) comparisons. We examined seven patients meeting the DSM-III-R criteria of senile dementia and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS - ADRDA) criteria of probable AD, and II aged controls. This study focused on the measurement of phosphorus 31 ((31)P) Nuclear Magnetic Resonance (NMR) spectroscopy metabolites in each hippocampus. We found significant differences in phosphorus metabolites for both intra-group comparison (pH shifted towards relative alkalosis in the left hippocampus of patients) and inter-group consideration (reduced phosphodiesters [Pde]and elevated gamma adenosine triphosphate (ATP) in the right hippocampus, higher inorganic phosphate (pHi) in the left hippocampus for patients as compared to controls). We suggest energy failure and membrane functional breakdown in patients compared to aged controls.

[Adaptive control of therapeutics using amikacin in very old patients: retrospective analysis of efficacy and toxicity]. / Contrôle adaptatif des thérapeutiques par l'amikacine chez des patients très âgés: analyse rétrospective de l'efficacité et de la toxicité.

UNLABELLED: The authors previously showed the precision of adaptive control of amikacin therapy in elderly patients. The present retrospective study evaluated the effects of such therapy on outcomes. 48 patients, aged 80 +/- 5 years, with estimated creatinine clearance (eCCR) of 48 +/- 15 ml/mn, received amikacin initial dosage of 13.3 +/- 3.5 mg/kg/d, alone or with other drugs. Efficacy outcomes were: E1 = changes in dosage during therapy; E2 = fever reduction within 3 days after therapy; E3 = eradication of infection by culture data; E4 = reduction of white blood cell count (WCB) to normal; E5 = overall recovery. Toxicity outcomes were: T1 = subjective ototoxicity; T2 = nephrotoxicity, variation of serum creatinine low (between 18 et 44 mumol/l) or high (over 0.5 mg/dl). RESULTS: E1: final dose = 11.8 +/- 5.1 mg/kg/d (NS), 57% reduced, 33% increased, during 15.1 +/- 9.3 days in therapy, with 88% having effective peaks over 15 micrograms/ml. E2: fever reduced within 3 days 16/37; after 12/37; no change, 9/37. E3: cultures became negative, 13/28. E4: WBC fell early, 10/21; late, 7/21; no change, 2/21. E5: recovery 36; death, 8; change in therapy, 3. T1: no clinical signs of ototoxicity. T2: low(+), 9/51; low(-), 11/51; high(-), 7/51. final eCCR: 48 +/- 14 ml/mn (NS); no nephrotoxicity. These results suggest that adaptive control of amikacin regimens yields good efficacy and avoid toxicity in the Elderly. However, prospective controlled clinical trials should be done for confirmation.

Functions and tocopherol content of blood platelets from elderly people after low intake of purified eicosapentaenoic acid.

Elderly people present an increased incidence of atherosclerosis and vascular cerebral damages, associated with blood platelet hyperactivity and a stimulation of arachidonic acid metabolism in vivo. The effects of a low intake of purified eicosapentaenoic acid (EPA) on platelet hyperactivity in old human subjects has been investigated. In a randomized, double blind study, 8 people took during 2 months a daily intake of 100 mg of eicosapentaenoic acid (EPA) given as a triglyceride (1,3-dioctanoyl,2-eicosapentaenoyl-glycerol), and 8 other subjects ingested a placebo. A slight, but significant reduction of platelet-rich plasma aggregation in response to epinephrine and arachidonic acid occurred after EPA intake, as well as a decreased aggregation of washed platelets induced by thrombin, although collagen- and U-46619-induced aggregations were not significantly modified. EPA intake failed to affect arachidonic acid metabolism in thrombin-stimulated platelets or in clotted venous blood. The urinary excretion of thromboxane, 6-keto-PGF1 alpha and their 2,3-dinor-metabolites was also not modified. Similarly, no change in the plasma and platelet lipid fatty acid compositions could be observed. Platelet, but not plasma, alpha- and gamma-tocopherol were enhanced by EPA intake. An increase of platelet vitamin E has been associated with a decrease of aggregation, especially in vitamin E-deficient subjects, like elderly people. Therefore, low intake of EPA might have contributed to inhibit platelet aggregation by increasing cellular vitamin E.

Age-related changes in cancellous bone structure. A two-dimensional study in the transiliac and iliac crest biopsy sites.

In 94 pairs of large sections of normal iliac bone (53 men, 41 women, aged 20-80 years) we confirmed trabecular bone area (B.Ar) and the mean number of trabeculae per mm (Tb.N) to decline with age, in areas representative of the transiliac (TI) and iliac crest (IC) biopsy in both sexes, whereas mean trabecular width (Tb.Wi) did not decrease. Our data also confirm that disappearance of entire elements is the main event in age-related loss of trabecular bone. In addition, our study demonstrated that Tb.Wi is lower in women than in men in the IC site, and a preferential loss of the thinner trabeculae could be seen in this group. Up to 50 years, Tb.N was found higher in women in both sites. B.Ar and Tb.Wi values are markedly higher in the TI site (+/- 15%); Tb.N values were similar. Measured and calculated Tb.Wi values show systematic differences. In a pilot study in 14 IC biopsies with widely diverging B.Ar values, we tested the validity of several equations currently used for derived parameters in the structural analysis of cancellous bone sections. The equation for mean trabecular number passed the test, whereas the validity of the equations for mean trabecular separation and Tb.Wi appeared limited. We found anisotropy of iliac bone to increase as B.Ar decreases.

Platelets and aging. I--Aggregation, arachidonate metabolism and antioxidant status.

Platelet functions were investigated in sixteen old (78-94 years) and eight young (25-35 years) subjects. Whole blood platelet aggregation induced by collagen was higher in the elderly. Similarly, aggregation of platelet rich plasma and plasma-free platelets induced by various agents was increased but the collagen-induced release of ATP was reduced. In agreement with the enhanced platelet aggregability, the increase of thromboxane formation (under thrombin stimulation) was also noted in platelets from elderly people. To further assess platelet and vascular function in vivo, we measured the excretion of urinary TXB2, 2,3-dinor TXB2, 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha. The four metabolites were all increased in the elder population. In addition, a significant reduction of platelet vitamin E was observed in the elderly people, although the plasma content was normal. These results indicate numerous modifications of platelet behaviour with aging. They include the increased platelet susceptibility to aggregation, and the depletion of ATP granule content, which could reflect an activation in vivo in agreement with the enhanced urinary excretion of thromboxane and prostacyclin metabolites. We hypothesize that platelet hyperactivity associated with the enhanced oxygenated metabolism of arachidonic acid could be linked to vitamin E depletion. These changes may reveal a prethrombotic state in the elderly population.

Effects of linoleic acid and gamma-linolenic acid intake on platelet functions in elderly people.

Sixteen old subjects were given daily dietary supplement of lg of linoleic acid and lg of gamma-linolenic acid (primerose oil) or 2g of linoleic acid (sunflower oil) for periods of two months. Haemostatic parameters, platelet aggregation, exogenous and endogenous arachidonic acid metabolism were investigated before and after the intake. Diets did not induce any significant change in haemostatic parameters (bleeding time, levels of anti-thrombin III, plasminogen and plasma beta-TG and PF4). Platelet rich plasma aggregation induced by collagen and arachidonic acid were significantly reduced after linoleic acid (18:2n-6) intake. In contrast, gamma-linolenic acid (18:3n-6) supplement did not alter aggregation. However, thromboxane B2 formation (under stimulation) and vitamin E level in platelets (but not in plasma) were decreased after 18:3n-6 as compared to 18:2n-6 intake. The mechanism of thromboxane B2 decrease is unclear. Nevertheless, we may speculate that beneficial effect of this decrease could be counterbalanced by the decreased platelet vitamin E. We conclude that intake of 18:2n-6 or 18:3n-6 does not affect much platelet functions in elderly people.

[Physiological osteopenia: histomorphometric findings]. / L'ostéopénie physiologique: données histomorphométriques.

The construction of bone results from the collaborative work of functional constituents; destructive cells or osteoclasts, the activity of which induces that of other, constructive cells, the osteoblasts. During the whole period of growth, construction surpasses destruction. During the rest of life the destructive process predominates, whence a physiological osteopenia, which affects man as well as woman, but which accelerates in the latter during the postmenopausal years. The measurement of this physiological osteopenia by bone biopsy shows clearly that it is due to a simultaneous diminution of these two processes. Common osteoporosis, of early appearance, presents in 50% of cases as the chemical and biological expression of an acceleration of normal processes. 30% of them, on the contrary, are accompanied by an excess of destruction, whereas the rate of construction remains normal. In about 20% of cases it is the constructive phase which is depressed, destruction remains normal.

Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial.

After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however, substantial increases in iliac trabecular bone volume: the mean increase, confirmed by repeat blind measurements, was 70% above mean baseline volume. The new bone was histologically normal. Those patients who had the largest increases in 47Ca-kinetic and histomorphometric indices of new bone formation showed the greatest increases in trabecular bone volume, suggesting that treatment with human parathyroid hormone fragment caused a dissociation between formation and resorption rates that was confined to trabecular bone. Since vertebrae are four-fifths composed of trabecular bone, this hormone fragment may prove useful in treating patients with the crush fracture syndrome.

Niflumic acid-induced skeletal fluorosis: iatrogenic disease or therapeutic perspective for osteoporosis?

A case of skeletal fluorosis induced by prolonged treatment with niflumic acid, a fast-acting non-steroid antiinflammatory agent, is reported in a 35-year-old woman suffering from rheumatoid arthritis and treated, in addition, with corticosteroids. The case report discussed is, to our knowledge, the third of its kind regarding bone fluorosis resulting from use of this nicotinic derivative. This clinically asymptomatic case of skeletal fluorosis was discovered, as in the 2 previously reported cases, by the examination of bone X-ray (performed as part of the routine work-up for rheumatoid arthritis) which showed evident osteosclerosis. Quantitative histologic study of iliac crest biopsy revealed marked increase in trabecular bone volume and osteoid volume, suggestive of fluorosis. Abnormally high urine and bone fluoride confirmed the diagnosis. After ruling out a hydrotelluric source of fluorine, the patient's fluorosis was linked to chronic use of niflumic acid, following the publication in 1978 of the 2 previously reported cases affected by this drug. The fluorine contained in niflumic acid induced a marked densification of trabecular bone in all 3 cases. Long-term clinical and pharmacokinetic studies will be required to determine whether or not niflumic acid can be employed in the prevention or treatment of both of apparently idiopathic osteoporosis or corticosteroid-induced osteoporosis.

Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age.

The mean wall thickness (MWT) of packets of trabecular bone was measured in undecalcified iliac crest bone samples of 36 normal subjects (14 female and 22 male) under polarized light. The mean wall thickness was 49.7 +/- 8.7 microns at a mean age of 50.9 years. There existed a significant decrease of MWT with advancing age. With an appositional rate of 0.72 micron/day, the mean formation time of iliac trabecular bone packets is 69 days. The decrease of MWT with age corresponds to a decrease in bone formation at the basic multicellular unit (BMU) level with aging and can partly explain the physiological senile osteopenia.

Serum alpha-fetroprotein concentration in adult patients under corticoid, estroprogestative or androgen therapy.

The serum alpha-fetoprotein concentration was measured by radioimmunoassy in 41 women with or without hormonal contraception, 21 patients with rheumatoid arthritis given corticosteroids or not, and 6 patients under androgen therapy for aplastic anemia. None of these therapies induced any significant variation of the serum alpha-fetoprotein level. More extensive studies are needed to investigate the possible effect of these hormones on the metabolism of this protein at a cellular level.

PIP: Serum alpha-fetoprotein concentration was measured by radioimmunoassay in 41 women with or without hormonal contraception, 21 pateints with rheumatoid arthritis given corticosteroids or untreated, and 6 patients under androgen therapy for aplastic anemia. The various therapies were ineffective in inducing any change in alpha-fetoprotein level. Future research should focus on the metabolism of this protein at a cellular level in the presence of these hormones.