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.

Aspergillus osteomyelitis after heart-lung transplantation.

Aspergillus osteomyelitis is a severe complication of invasive aspergillosis. Fewer than 15 cases have been observed after solid organ transplantation. We describe a case of Aspergillus osteomyelitis of the ilium after heart-lung transplantation with favorable outcome after medical treatment.

Karyotype and FISH analysis of a newly established cell line derived from a human bladder carcinoma.

A new human malignant urologic cell line was established in vitro from a moderately differentiated transitional cell carcinoma of the bladder and cytogenetically characterized. Repeated chromosome analyses of the cell line using conventional RHG and GTG banding and non-radioactive in situ hybridization showed a stable karyotype with a modal number of 48 and chromosomal rearrangements, some of which have not been previously described. Numerical deviation included three trisomies (+7, +8, +9) and one nullisomy (-19, -19). Structural changes involved a balanced translocation (1;5)(q12;q12), an isochromosome 3q, a 14p+, and two markers. Fluorescence in situ hybridization (FISH), using biotin-labeled alpha satellite probes for chromosome 9 or painting for chromosomes 1 and 8, applied to interphase nuclei or metaphases showed similar results to those found by conventional cytogenetic study. This cell line may be an interesting model for fuller characterization by molecular biology studies and for testing anti-cancer drugs in vitro.

Nonrandom changes of chromosome 10 in bladder cancer. Detection by FISH to interphase nuclei.

Fluorescence in situ hybridization (FISH) to interphase nuclei has been a valuable method for examining the chromosome copies in tumor cells in clinical practice. Twelve cases of transitional cell carcinoma (TCC) of the bladder were investigated with a biotin-labeled repetitive DNA probe to detect numerical aberrations of chromosome 10 in interphase nuclei. The cells containing one fluorescent signal were screened in two of seven non-invasive tumors and in four of five invasive tumors. Two patients presented two FISH spots of different sizes. More than two signals were seen in one invasive tumor. The findings suggest that partial or complete loss of a chromosome 10 is a nonrandom aberration in bladder cancer.

Hepatic hypertrophic osteoarthropathy: the value of liver transplantation.

We describe 4 cases of hepatic hypertrophic osteoarthropathy treated successfully by liver transplantation. Hepatic hypertrophic osteoarthropathy is a rare and disabling condition associated with severe liver diseases. It responds poorly to conservative management, and liver transplantation is the only radical treatment option.

Usefulness of influenza vaccination in the elderly.

Since influenza morbidity and mortality are high in the elderly, the usefulness of vaccination has been evaluated. One hundred and twenty-six older persons aged 60-90 yr were given a vaccine consisting of the 3 antigens Singapore, Shanghaï and Yamagata, the latter 2 being new antigens. Antibody levels for each of the antigens were determined by ELISA calibrated in HA units prior to and 1 month after vaccination. Before vaccination, antibodies to Shanghaï and Singapore antigens were found in practically all sera tested, and antibodies to Yamagata antigen in only 66% of sera. After vaccination, significant levels of antibodies to all 3 antigens were found in sera tested. Thus, it was observed that influenza vaccination proved to be effective in the elderly. The elderly should be immunized against influenza, since this is a safe and efficacious preventive measure. In addition, vaccination should limit the spreading of influenza in nursing homes.

Normocomplementemic urticarial vasculitis inaugurating destructive polyarthritis.

Urticarial vasculitis is an entity characterized by recurrent bouts of urticaria and histological evidence of leukocytoclastic vasculitis. An underlying systemic disease is often present. Joint manifestations occur mainly in cases with hypocomplementemia. We report a case of destructive polyarthritis preceded by urticarial vasculitis without hypocomplementemia.

Interphase cytogenetic studies of bladder cancer.

Transitional cell carcinomas of human urinary bladder were studied by interphase fluorescence in situ hybridization (FISH). With current hybridization to isolated nuclei, 26 tumors were investigated and nonrandom +7, -9 and -10 were identified. Monosomy 11, tetraploidies and polyploidies were detected in invasive and poor-differentiated tumors. Hybridization on frozen sections offers another means of analysing surgical samples. FISH to vesical washings can be applied to monitor tumor progression. Hybridizations on paraffine sections and on tissues previously stored in liquid nitrogen allow retrospective studies of the archived materials. Our data suggest that the interphase FISH can become a powerful tool for cytogenetic studies of bladder cancer.

Pelvic lymphadenoscopy. A simple reliable method for the staging of pelvic cancers.

The staging of pelvic cancers using imaging techniques is not very precise, even with the most recent methods. However, optimal treatment depends on the results of this staging. In our experiment, we carried out a pelvioscopy prior to any curative treatment on all our patients who had had pelvic cancer for at least three years. Seventy-eight pelvioscopies were performed with 48 patients, entailing minimum morbidity and no mortality. For 23 patients, the lymph nodes were metastasized even though the C.T. were considered normal. With this simple method, staging of pelvic cancers can be improved and this extensive, unnecessary surgery can be avoided in many cases.

[An increase of choleresis in secondary biliary cirrhosis in rats is caused by bile duct secretion]. / L'augmentation de la cholérèse au cours de la cirrhose biliaire secondaire chez le rat est due à une sécrétion par les voies biliaires.

Bile flow may be considerably increased in human cirrhosis. The mechanism of this increase has not been established. Two mechanisms have been proposed: a) increased canalicular filtration because of sinusoidal hypertension, or b) secretion by proliferated bile ductules. To distinguish between these two possibilities, we examined the determinants of bile secretion in rats with secondary biliary cirrhosis after bile duct obstruction. Sham-operated animals served as controls. Four weeks after bile duct ligation, all animals had cirrhosis. Bile flow was significantly higher and bile salt secretion significantly lower in cirrhotic animals than in controls. Biliary bicarbonate concentration was significantly higher in cirrhotic animals than in controls. Bile-to-plasma concentration ratio of erythritol was significantly lower in cirrhotic animals than in controls, suggesting a dilution of erythritol by a secretion distal to bile canaliculi. Bile-to-plasma ratio of sucrose was not significantly different in cirrhotics and controls, suggesting that paracellular permeability was not modified. Secretin, at the dose of 3 clinical units/100 g, induced an increase of approximately 75 percent in bile flow, and 70 percent in biliary bicarbonate concentration in cirrhotics. In conclusion, bile flow was increased in biliary cirrhosis in rats. The dilution of erythritol, the increase in biliary bicarbonate concentration and the increased response to secretin strongly suggest that increased choleresis was due, at least in part, to secretion by bile ductules or ducts. These results confirm that secondary biliary cirrhosis is a good experimental model for the study of alterations of bile secretion in cirrhosis.

[Effect of chronic administration of cyclosporin A on choleresis in rats]. / Effet de l'administration chronique de ciclosporine A sur la cholérèse chez le rat.

The effect of therapeutic doses of cyclosporine A (CyA) on bile flow and bile salt output was studied in the rat. Thirty male Sprague-Dawley rats (250 to 380 g) were injected intraperitoneally with CyA (n = 15) or vehicle (n = 15) at the dose of 10 mg.kg-1 for 3 weeks. The effect of CyA on basal and taurocholate-induced bile flow, on basal bile salt output and bile salt output under taurocholate infusion, and the effect of chronic administration of CyA on bile salt-independent bile flow was evaluated. Administration of CyA was associated with a decrease in basal bile flow (5.6 +/- 0.7 vs 6.7 +/- 0.7 microliters.min-1.100 g-1; p less than 0.001) and bile flow under taurocholate infusion (8.0 +/- 0.8 vs 10.9 +/- 1.1 microliters.min-1.100 g-1; p less than 0.001). Basal bile salt output (133.9 +/- 48.2 vs 173.8 +/- 53.6 nmol.min-1.100 g-1; p less than 0.003) and bile salt output under the infusion of taurocholate were significantly lower in cyclosporine-treated rats than in controls (443.3 +/- 48.2 vs 617.2 +/- 172.7 nmol.min-1.100 g-1; p less than 0.001). There was no significant difference in bile salt-independent bile flow between the 2 groups. There was no modification of seric alanine aminotransferase activity or hepatic histology. This study confirms that chronic administration of CyA at therapeutic doses can induce cholestasis. Cholestasis is related mainly to a decrease in bile salt secretion and bile salt-dependent flow.

[Aortic dissection and Horton arteritis]. / Dissection aortique et artérite de Horton.

Aortic dissection in a 61-year-old woman treated symptomatically and with a fatal outcome within three months by extension to the arch of the aorta and its major vessels, and as a direct result of haemopericardium. The association with temporal arteritis, presenting before the aortic complication by prolonged headache with raised sedimentation rate and painful inflammation of both temporal arteries, was confirmed by histopathological examination of the aorta. This revealed giant cell arteritis independent of atheromatous lesions. The association of aortic dissection and temporal arteritis is very rare. Clinical and pathological examination of the smaller arteries and in particular the craniocephalic arteries is therefore justified in all cases of aortic dissection. When it affects the aorta, temporal arteritis may favor aortic dissection as a result of changes in the media.

[Mediastinal adenopathy and cancer of the prostate]. / Adénopathies médiastinales et cancer de la prostate.

The authors report a case of metastases from a carcinoma of prostate producing mediastinal adenopathy with compression. The clinical presentation was unusual as this is an unusual area for lymphadenopathy and an abnormal lymphatic pattern was invoked as a possible cause or that the lymphatic channels communicating with these nodes had an abnormal thoracic duct. The aetiological diagnosis was facilitated by the presence of a specific prostatic antigen on the lymph node biopsy which allowed one to use an effective androgen suppression therapy.

[Preoperative localization of parathyroid adenomas. Role of cervical ultrasonography]. / Localisation pré-opératoire des adénomes parathyroidiens. Place de l'échographie cervicale.

OBJECTIVES: We evaluated the sensitivity and specificity of cervical ultrasonography for the detection of primary parathyroid adenomas. METHODS: From January 1990 to May 1992, ultrasonography was performed before exploratory cervicotomy in 30 patients (10 males, 20 females, mean age 56.3 yr) whose diagnosis was primary hyperparathyroidism based on radioimmunoassay of parathyroid hormone. The same trained operator performed all the ultrasonographic examinations. RESULTS: Twenty-six parathyroid tumours were detected in 23 of the 30 patients examined by ultrasonography. The four standard localizations and one ectopic tumour were visualized. At surgery 37 tumours were found in 30 patients. Among the 11 false negatives, the operator had identified an abnormal tumour incorrectly as a cervical lymph node in 2. Most of the false negatives occurred early in the study. The sensitivity of ultrasonography was thus 70 % with a 100% specificity. CONCLUSIONS: Cervical ultrasonography is a reliable, non-invasive and relatively inexpensive examination which should be used as a first-line test for the aetiological assessment of hyperparathyroidism.

[Treatment of cerebral aging disorders with Ginkgo biloba extract. A longitudinal multicenter double-blind drug vs. placebo study]. / Traitement des troubles du vieillissement cérébral par l'extrait de Ginkgo biloba. Etude longitudinale multicentrique à double insu face au placebo.

The effectiveness of Ginkgo biloba extract in the treatment of cerebral disorders due to ageing was evaluated in a multicentric, double-blind, drug versus placebo trial involving 166 patients. In this study carried out under strict methodological conditions a specially devised geriatric clinical evaluation scale was used. The results confirmed that Ginkgo biloba extract is effective against cerebral disorders due to ageing. The difference between control and treatment groups became significant at 3 months and increased during the following months. These results were concordant with the overall clinical assessment made by the specialist in charge.

[Diffuse bone metastases revealing pleural mesothelioma. Case report]. / Métastases osseuses diffuses révélatrices d'un mésothéliome pleural. Rapport d'un cas.

A 76 year old man, presenting with symptoms of general malaise alone, had a marrow biopsy which showed and undifferentiated carcinoma. A subsequent autopsy revealed a multi-nodular pleural mesothelioma, which was not seen radiologically, presumably because of the small size of the nodule. There were bilateral adrenal metastases and diffuse bony metastases involving the marrow. An occupational contact with asbestos was retrospectively confirmed. It is rare that a pleural mesothelioma does not exhibit thoracic signs and very uncommon that bony metastases should give the diagnosis in such a tumour.

[Resection of the prostate after 75 years]. / La résection de prostate après soixante-quinze ans.

The authors report a series of 100 endoscopic resections performed in patients over the age of 75 years. In patients with no risk factors, there was no mortality and the morbidity was 5%. In patients with one risk factor, mortality was 5% and morbidity was 10%.

[Chromosomal analysis of bladder tumors. Technical aspects, anatomoclinical correlations and perspectives. Report of 18 cases]. / Analyse chromosomique des tumeurs de vessie. Aspects techniques, corrélations anatomocliniques et perspectives. A propos de 18 cas.

The course of bladder tumours is difficult to predict. The most reliable prognostic factor at the present time is histological grade. Cytogenetic subclasses of bladder tumours can be distinguished on the basis of the demonstration of karyotype anomalies in bladder tumour cells. Eighteen patients underwent cytogenetic examination of their bladder tumour and were followed for an average of 35 months. Multivariate analysis of the clinical and laboratory parameters studied revealed the importance of age and the absence of trisomy 7 in the tumour on patient survival. The presence of trisomy 7 in a bladder tumour may therefore constitute a factor of poor prognosis. This hypothesis needs to be confirmed by further studies in larger populations. The search for this anomaly can be performed by fluorescent in situ chromosomal hybridisation, a technique which transforms cytogenetics from an experimental procedure into a routine complementary investigation. These techniques can be performed on urine samples, suggesting the possibility of their application to screening or follow-up of bladder tumours.

Generic drug prescriptions following hospital discharge: a prospective study in France.

AIMS: Systematic generic prescription at discharge could reduce confusion on drug-name usage, decrease commercial influence on medicine, and reduce drug-related expenditures. This study aimed to analyze generic drug prescriptions at discharge from hospital and to estimate the potential savings associated with a total substitution policy (substitution of every substitutable drug for its cheapest generic counterpart). METHODS: Drug prescriptions before admission and at discharge of all patients from three medical units of a university hospital were prospectively collected for five weeks without informing prescribers. RESULTS: Prescriptions from 85 patients were analyzed. On admission, 68 patients (80%) received 413 drugs; 141 were substitutable brand-name drugs and 23 (16%), which were directly prescribed as generics. At discharge, 488 drugs were prescribed to the 85 patients; 180 were substitutable drugs but only 5 (2.8%) were written as generics on prescription pads, a decrease of 78% (p<0.0001) compared to admission. In average, generics were 18% less expensive than brand-name drugs. Some common therapeutic classes offered even greater price difference, such as proton-pump inhibitors (42%), statins (32%), or antihypertensive agents (28%). Potential savings from a total substitution policy at discharge were estimated to €1512 per 1000 patients per week; for lifetime drugs, savings amounted to €18,960 per 1000 patients per year. CONCLUSIONS: Very few drugs are written as generics on medical forms at discharge in France. Hospital practitioners should be encouraged to prescribe generics, particularly in chronic diseases. A broad generic prescription policy at hospital discharge would result in substantial savings for health insurance.