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SummaryMemory 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 (31P) 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.

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.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.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 (p104). For half of the shoulders, glenohumeral impingement was associated with subacromial impingement (eccentric osteoarthritis).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.Our results demonstrate that the natural history of the shoulder does not exhibit a regular linear relationship with the Hamada radiological classification.

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).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.

8532 Background: To assess the prevalence of malnutrition in elderly patients (pts) with cancer and to determine the effect of malnutrition on Overall Survival (OS). Methods: Cancer pts aged 65 and older underwent a multidimensional geriatric assessment at our institution. Data were collected for calorie and protein intakes, Mini Nutritional assessment (MNA Nestlé), functional status (ADL score), and comorbidity (CIRS-G). Survival time was defined as the time from geriatric assessment to date of death or last follow-up. A Cox regression model was used to estimate the hazards ratio (HR) and 95 percent confidence intervals (95%CI) of risk factors for death. Results: 133 consecutive pts (68% male, 50% hospitalized) were evaluated from 05/1999 to 08/2002. Median age was 78 years (range: 66–92). Main tumour sites were prostate (36%), breast (15%), bladder (12%) and Head and Neck (10%). Forty eight pts (36%) had metastatic disease. Only 55 pts (43%) were fully independent in ADLs (score = 6), and 15 pts were completely independent in IADLs (score = 14). Fifty one pts (43%) had mild to severe disability/morbidity status (CIRS-G severity index ≥2). Regarding nutritional status, only 34% were estimated well nourished with MNA >23.5, 54% had calorie intake ≤1500 kcal/day and 38% had body weight loss > 5% in the last 3 months. Survival analysis was performed with a 16-month median follow up. Median survival time was 7 months (95%CI 6–9 months). In the univariate analysis, male gender, metastatic stage, MNA, ADL score and CIRS-G severity index were significantly correlated with OS. In the multivariate analysis, male gender (HR=2.3, 95% CI: 1.3–4.1), metastasis (HR=1.6, 95% CI: 1.0–2.6), MNA No significant financial relationships to disclose.

8172 Background: Increased age-related prevalence of co-morbidity and functional impairment promote the risk of treatment intolerance and mortality in elderly cancer patients (pts). Clinical studie...

Measurement by an image analysing computer of two parameters indicating the amount of bone tissue in transfixing iliac biopsies has been performed in 34 osteoporotic females having at least one crush vertebral fracture and in a normal population of 25 females. The comparison of both groups has shown that the percentage of bone tissue in the spongy space (trabecular bone volume) gives a much better indication of osteoporosis than the percentage of bone tissue between periosteal surfaces which takes into account the amount of both cortical and trabecular bone (total bone density).

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.

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.

Bone histomorphometry consists of measuring the bone tissue components and of counting the bone cells. The tetracycline double labelling process also permits quantitation of dynamics phenomenons such as the calcification rate of osteoid or the osteoblastic appositional rate. Thus, these methods are able to furnish vital information on the amount and the dynamics of bone tissue, but they have not yet demonstrated all their possibilities for the following reasons: a) too few normal values have been collected for each parameter taking into account age and sex. b) the representativness of a bone biopsy sample in comparison to the bone biopsied, the opposite bone and the whole skeleton is not well-established. c) a diversity of parameters is being measured by different groups and a sometimes confusing vocabulary is being used producing a dynamic language to describe morphological changes. d) the limited use of the tetracycline double labelling process proposed by Frost (5).

The effect on the bones of immobilization was studied by means of quantitative histological methods on 34 biopsies of the iliac crest after different periods of immobilization in 28 patients, 22 of whom were immobilized by medullary lesions. At the same time a biochemical study was carried out on 68 immobilized patients over a 52-week period. This histomorphometric study included measurements of the absolute volume of trabecular bone, the volume of the osteoid matrix, the osteoclastic resorption surfaces, the size of the osteocyte lacunae, the thickness of the iliac cortical zones and the medullary adipose volume. 19 subjects received in addition double labeling with tetracycline with the object of carrying out a histodynamic study of the osteoblastic activity. The decrease in the absolute volume of the trabecular bone reached 33 percent of its original value and continued up to the 25th week, and was followed by stabilization at a value slightly higher than the vertebral fracture limit. Immobilization also led to an increase in the osteoclastic resorption surfaces and, secondarily, to an increase in the periosteocyte lacunae, a thinning of the iliac cortical zones, and a decrease in the volume of the osteoid matrix. Calciura increased as did total hydroxyprolinuria in parallel with an increase in the resorption surfaces. The histological and biochemical changes suggest a histodynamic hypothesis, according to which the longevity of the basic multicellular bone unit increases, leading to a new equilibrium characterized by very slow renewal of the bone.

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.

The diphosphonates are analogues of the pyrophosphates that are capable of resisting enzymatic destruction and they become fixed in the bone tissue where they have a powerful inhibitory action on osteoclastic resorption and on osteoid mineralization. Ethane-1-hydroxy-1, 1-diphosphonate (EDHP) was administered by mouth at the dose of 20 mg/kg/day over a period of 3 to 6 months to 11 patients with painful Paget's disease. A marked analgesic effect was noted in 7 of the 11 patients. Spectacular metabolic effects were noted with return to normal of the total hydroxyprolinuria/24 h and of the alkaline phosphatases 3 months after treatment in 6 of the 11 treated subjects and a marked improvement in these parameters in 4 other patients. Histologically, there was almost total disappearance of osteoclasia and of osteoblastosis in the affected areas. Clinically, the secondary effects presented in some cases as diarrhoea, and an early and marked rise in phosphoraemia was recorded. Histologically, hyperosteoidosis was seen, equally in the affected and nonaffected zones. This resulted from an almost complete stoppage in the calcification of the osteoid as indicated by the double labelling by tetracycline. The review of the literature shows that considerable therapeutic effects are obtained even with very small doses of EHDP, e.g., 10 mg/kg/day for 3 months, but that these are often accompanied by more marked secondary effects. The diphosphonates appear to be a promising treatment for Paget's disease.

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.

The effect of immobilization on human bone was studied through a longitudinal, as well as cross-sectional, quantitative and dynamic histological analysis of 34 decalcified and undecalcified iliac crest biopsies. They were obtained at various times after the onset of immobilization in 28 patients of which 22 were suffering from post-traumatic spinal cord lesions. Trabecular bone volume, osteoid volume, trabecular osteoclastic resorption surfaces, size of the periosteocytic lacunae, thickness of iliac cortices and volume of the cell population of the marrow were measured. The histodynamic study was made by double tetracycline labeling in 19 patients. The histological data were compared with biological data from another group of 68 immobilized patients including 22 of the patients undergoing biopsy. Calcemia, phosphoremia, alkaline phosphatase, calciura, phosphaturia and hydroxyprolinuria were measured. The decrease of the trabecular bone volume averaged 33% over 25 weeks and then stabilized. Immobilization also caused an early increase in the trabecular osteoclastic resorption surfaces and later in the size of periosteocytic lacunae, an early depression of osteoblastic bone formation and a thinning of the cortices. Calciuria was high, as was hydroxyprolinuria which correlates with resorption surfaces. The histological and biochemical changes suggest an histodynamic hypothesis according to which the global lifespan of the BMU (Basic Multicellular Unit from Frost) would be increased. These changes reflect atransient, leading to a newsteady state: rarefied bone with a low rate of subsequent turn-over. They emphasize the importance of mechanical factors in the development of bone cells.

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.