[Prophylaxis and treatment of osteoporosis in patients with rheumatoid arthritis (ORA study)]. / Medikamentöse Osteoporoseprophylaxe und -Therapie bei Patienten mit Rheumatoider Arthritis (ORA-Studie).

OBJECTIVE: The aim of this study was to examine bone mineral density (BMD), frequency of osteopenia and osteoporosis in a representative sample of patients with rheumatoid arthritis (RA) and to describe chemoprophylaxis and treatment of osteoporosis compared to evidence-based guidelines. PATIENTS AND METHODS: In 2005 and 2006, 532 patients with RA (98 men, 434 women) aged 23-87 years were recruited from 9 German rheumatology centers. Clinical examination included a detailed documentation of osteoporosis medication. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD at the lumbar spine and femoral neck. Osteopenia and osteoporosis were defined according to the criteria of the World Health Organization. RESULTS: Of the RA patients 29% had normal BMD at the spine and femoral neck, 49% of the patients had osteopenia and 22% met the criteria for osteoporosis at any site. Of the patients 60% were receiving medication for prophylaxis or therapy of osteoporosis, 38% calcium/vitamin D alone, 20% as combinations mostly of calcium/vitamin D + bisphosphonate, 1% received bisphosphonate only and 1% hormone replacement therapy. Although the frequency of osteoporosis showed no significant differences between male and female patients, women with RA used osteoporosis medication more often than men (63% versus 49%, χ²-test, p <0.05). A total of 101 RA patients (83 menopausal women, 6 premenopausal women, 12 men) received corticosteroids in a daily dose of 7.5 mg or less for at least 3 months and had DXA T-scores below -2.0 at any site. In this patient group 41% of the menopausal women, 17% of the premenopausal women and 42% of the male patients were reported to receive medication with calcium/vitamin D + bisphosphonate. Calcium/vitamin D was used by 35% of the menopausal women, none of the premenopausal women and 50% of the male patients and 18% of the menopausal women, 67% of the premenopausal women and 8% of men received no prophylaxis or treatment for osteoporosis. CONCLUSION: According to the DVO (German Society for Osteoporosis) guidelines for osteoporosis (2009) menopausal women with corticosteroid therapy < 7.5 mg per day for at least 3 months and DXA T-scores below -2.0 should receive treatment with bisphosphonate and calcium/vitamin D. The data show that there were still deficits concerning prophylaxis and treatment of osteoporosis in RA.

[Diagnosis and treatment of osteoporosis and rheumatoid arthritis in accordance with German guidelines. Results of a survey of patients, primary care physicians and rheumatologists]. / Diagnostik und Behandlung der Osteoporose bei rheumatoider Arthritis vor dem Hintergrund der Leitliniennutzung. Ergebnisse einer Befragung von Patienten, Hausärzten und Rheumatologen (ORA-Studie).

In a cross-sectional study the prevalence of osteoporosis and osteopenia in patients with rheumatoid arthritis (ORA study) was investigated. Additionally, patients, their family doctors and rheumatologists were surveyed on their awareness of osteoporosis in RA, prevention, diagnosis, treatment and use of guidelines.In the years 2005 and 2006 a total of 532 patients with RA (98 men, 434 women) aged 23-87 years were consecutively recruited from 9 German centers for rheumatology. Clinical examination included a detailed documentation of osteoporosis medication. Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD) at the lumbar spine and neck of the femur. Questionnaires on osteoporosis were sent to 119 family doctors (87 men, 32 women) and 44 rheumatologists (30 men, 14 women).The survey showed that rheumatologists had a higher awareness of osteoporosis in RA and compared to family doctors they estimated a higher frequency and tested RA patients more often for osteoporosis. In line with osteoporosis guidelines rheumatologists and family doctors saw an indication for densitometry in RA patients on steroid therapy and/or low intensity trauma fractures. In contrast to the 2006 recommendations of osteoporosis guidelines 50% of family doctors and rheumatologists preferred bisphosphonate off-label-therapy for premeopausal women with RA and comorbid glucocorticoid-induced osteoporosis. On the other hand 50% of premenopausal RA patients with osteoporosis did not receive any osteoporosis medication.The survey revealed a high degree of guideline compliance in diagnosing osteoporosis in RA but deficits were observed in the administration of osteoporosis medication, especially in premenopausal women.

Dose-related patterns of glucocorticoid-induced side effects.

OBJECTIVE: To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice. METHODS: Data from 1066 patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5-7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months. RESULTS: The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (<5 mg/day). CONCLUSION: The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.

[Geriatry]. / Gériatrie.

This review discuss several studies published in 2007 that will modify current therapeutic attitudes. New evidence confirm that antipsychotics increase mortality in demented elderly persons with behavioral symptoms. Unfortunately, donepezil was no more effective than placebo to treat agitation in these patients. Aspirine, nonsteroidal anti-inflammatories, as well as supplementation with folate, vitamines B6 and B12 did not prove beneficial to prevent cognitive decline. Hormonal substitution with DHEA, testosterone, and growth hormone is ineffective as anti-aging medicine, while calcium and vitamin d'effectiveness was confirmed in fracture prevention. Finally, several studies report prognostic information that will prove important to improve preparation plan for future heat wave.

[Insufficiency fractures in rheumatology. Case report and overview]. / Insuffizienzfrakturen in der Rheumatologie. Fallbeschreibung und Ubersicht.

Stress fractures occur as insufficiency fractures, with a prevalence of 0.8% in patients with rheumatological illness. The main sites of insufficiency fractures are the pelvis and sacrum, parts of the tibia and fibula that are close to the joints, and the calcaneus and hip. Since the painful symptoms overlap with the clinical picture of the painful joint diseases and because of the low sensitivity of conventional diagnostic X-ray, insufficiency fractures are not diagnosed directly or their diagnosis is delayed. The high sensitivity of computer tomography, skeletal scintigraphy and nuclear magnetic resonance imaging should be exploited in the diagnosis of insufficiency fractures. The case report presented describes insufficiency fractures of the distal right tibia and fibula in an elderly female patient with rheumatoid arthritis being treated with long-term glucocorticoids. In addition to advanced age, female gender, immobility and rheumatoid arthritis requiring long-term cortisone, there are further risk factors for insufficiency fractures: fluoride treatment over many years in the past, hypovitaminosis D3, renal failure. The DXA bone density values of the neck of the femur and the lumbar vertebrae do not show any osteoporosis, and the calcium concentration in the serum is low; phosphate is raised and parathormone is normal; osteocalcin, beta crosslaps and alkaline phosphatase are raised. Bone biopsy specimens taken from the iliac crest and the proximal femur and investigated for the purpose of differential diagnosis revealed renal osteopathy with secondary hyperparathyroidism and osteomalacia. In elderly patients with kidney failure, the possibility of renal osteopathy must be considered as the possible cause of reduced bone quality with a raised risk of insufficiency fractures, even when the parathormone levels are normal. In view of the frequency of osteopathies in rheumatological patients, osteology is of enormous significance in rheumatology.

[Specialties in therapy of osteoporosis in inflammatory joint disease]. / Besonderheiten der Osteoporose-Therapie bei entzündlich-rheumatischen Erkrankungen.

The therapeutic specialties of osteoporosis in inflammatory rheumatic diseases has gained mounting interest in the last year. The paper describes special aspects of osteoporosis in rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematodes. The problems of glucocorticoid therapy are discussed intensively with regard to the recently published recommendations for glucocorticoid-induced osteoporosis. Risk factors of osteoporosis and the therapeutic implications are demonstrated intensively as well as the modifications of the recommendations.

[Osteoporosis in the male]. / Die Osteoporose des Mannes.

BACKGROUND: Osteoporotic fractures occur frequently also in men. Epidemiologic data from Germany indicate that more than 900,000 men are affected by osteoporotic fractures. Diagnosis and therapy of male osteoporosis are hampered by a lack of clinical studies. DIAGNOSIS: Risk factor analysis, conventional spine X-rays, bone densitometry and a limited number of serum and urine analyses contribute to the diagnosis of osteoporosis and the assessment of future fracture risk. Bone densitometry at the femoral neck is superior to measurements at the lumbar spine because of the high prevalence of degenerative changes at the lumbar spine in elderly men. Major risk factors for osteoporosis are hypogonadism, glucocorticoid therapy, hypercalciuria, gastrointestinal disease, and high alcohol consumption. In individual cases, bone histology or additional biochemical studies are needed to establish the cause of osteoporosis. THERAPY: Calcium and vitamin D deficits should be substituted both in prevention and treatment of male osteoporosis. Testosterone replacement therapy is effective in hypogonadism. In primary osteoporosis and in corticosteroid-induced osteoporosis, bisphosphonates (cyclical etidronate, alendronate) and fluorides are therapeutic options. CONCLUSION: Important principles in the care of men with osteoporosis are the transfer of knowledge established for postmenopausal osteoporosis and the rigorous search for secondary osteoporosis aiming at treatment of the underlying cause. Large prospective randomized trials aiming at the reduction of fracture rate in male osteoporosis are missing. They are urgently needed.

Insufficiency and stress fractures of the long bones occurring in patients with rheumatoid arthritis and other inflammatory diseases, with a contribution on the possibilities of computed tomography.

In patients with long standing rheumatoid arthritis and other rheumatoid disorders, stress fractures and insufficiency fractures are not uncommon. The cause may be osteoporosis due to rheumatoid arthritis, corticosteroid therapy, joint stiffness, and deformity of the joints caused by the inflammatory process. Also, unaccustomed exercise after reconstructive joint surgery may be a cause of fractures in these patients. Fractures can be documented on conventional X-ray-pictures and tomograms. Computed tomography can show the medullary extent of these fractures and gives, in several cases, additional information showing the combination of insufficiency fractures with fragmentations of parts of the involved bone. Reconstructive surgery with total joint replacement may be another cause of the development of these fractures. This unaccustomed increase in ambulation may lead to stress fractures in other joints of the same extremity or of contralateral extremity. Pain beginning in joint of the lower extremity in a patient with chronic rheumatoid arthritis should, besides arthritis, raise the possibility of a stress fracture. Also with cases of angular deformity of a joint and unaccustomed exercise after reconstructive surgery patients stress fractures may be seen and can be established by Plainfilm, Computed Tomography scintimetric bone scanning and MRI.

Eyeglass MEDRETE: practical considerations (a user's guide).

This article presents the experiences of two independent practitioners who participated in eyeglass-dispensing medical readiness training exercises (MEDRETEs) in Central America. It explains the importance of defining personnel policies, having the proper equipment, utilizing the retinoscopists optimally, and having an adequate supply of eyeglasses with plus lens power for indigenous persons in this geographic area. To maximize the effectiveness of a MEDRETE, a dispensing optician and two teams of translators are needed. Triage of patients will permit the optimal number of refractions and distribution of corrective lenses to those most in need. Fitting indigenous patients with corrective lenses in one of the more tangible and lasting effects of a MEDRETE. It contributes not only to patient satisfaction but possibly to improved relationships with the host nation.

[L-tryptophan-associated chronic eosinophilia-myalgia syndrome treated with cyclosporin]. / L-Tryptophan-assoziiertes chronisches Eosinophilie-Myalgie-Syndrom behandelt mit Ciclosporin.

After 2 weeks of ingestion of 130 g L-Tryptophan a 52 year old female develops an Eosinophilia Myalgia Syndrome with acute onset of deep venous thrombosis of forearm and possible initial cardiac manifestation featuring intermittent sinustachykardia. This is followed by a severe chronic disease (follow-up 15 months) with diffuse scleroderma and sensomotoric polyneuropathia. The deep muscle biopsy-specimen shows mononuclear infiltration of fascia and interstitial myositis with rare eosinophils. A blood eosinophilia (900/ul) occurs only in the initial acute onset of the illness. Plasma level of Kynurenine is significantly high (4000 pmol/ml), collagenneosynthesis is activated (Procollagen type III peptid 0.927 U/ml). No significant clinical improvement was seen with Acathioprine (100 mg/d) and Prednisolon (40-60 mg/d), after treatment with Ciclosporin scleroderma regresses completely, polyneuropathy is persisting.

[Isolation of H. pylori proteins and support for their suitability in serologic diagnoses]. / Isolierung von H.pylori-Proteinen und Beurteilung ihrer Eignung für den Einsatz in serologischen Diagnosesystemen.

H.pylori-proteins were separated using gel chromatographic methods. These antigens were tested for their suitability to detect H.pylori-specific antibodies. A complex of two proteins (62 kDa and 30 kDa) was a strong and specific antigen. A third protein (13 kDa) was a good but nonspecific antigen. Concerning these facts we compared two often used antigen preparations for serodiagnosing H.pylori-specific antibodies (acid-glycine preparation and sarcosyl-insoluble outer membrane proteins). The sarcosyl-insoluble material contains more specific antigens and lower levels of nonspecific proteins compared to the acid-glycine preparation. Based on these results we conclude that the outer membrane preparation seems to be more suitable for the serodiagnosing of H.pylori-specific antibodies.

Traditional and new types of spondarthritis with special consideration of spondylodiscitis.

In rheumatology the so-called "seronegative spondarthritis" is a group of diseases characterized by the presence of HLA-B 27. This group includes the typical ankylosing spondylitis as well as atypical spondylopathies such as those occurring in psoriasis, Reiter's disease and chronic inflammatory enteropathies, which attack mainly the spine and secondarily the peripheral joints. In some severe cases, non-infectious, sterile spondylodiscitis was observed. These can lead to instability and fracture, followed by pseudarthrosis of the involved segment of the spine. In contrast to these traditional spondarthritides three new types are marked by the lack of HLA-B 27. 1) "Spondarthritis hyperostotica pustulo-psoriatica" (F. Schilling), a very rare variation of psoriatic spondylopathy, sometimes accompanied by spondylodiscitis. 2) Arthritis and spondarthritis in acne fulminans. 3) Destructive arthropathy and spondylopathy in long-term hemodialysis, occasionally occurring with spondylodiscitis, a very new type of spondarthritis. The amyloid B (beta-2-micro-globulin), discovered only four years ago, plays a dominant role in the pathogenetic chain of this disease. Details of the etiology of these very impressive diseases are presented. Destructive spondylodiscitis will no doubt be a challenge to neurosurgeons.

Sudden visual loss associated with clostridial bacteraemia.

A patient with endogenously acquired Clostridium septicum panophthalmitis is presented. The patient exhibited a striking sequence of signs and symptoms associated with this devastating ocular infection. Intensive antibiotic therapy was ineffective and enucleation of the globe was required. The microscopic pathology of the enucleated globe showed extensive infarction and necrosis of ocular structures in association with the panophthalmitis. In addition thrombosis of the central retinal artery and of choroidal vessels was observed.

Multilayered keratinocyte culture used for in vitro toxicology.

Human keratinocytes are the most appropriate target cells for evaluating mechanisms of skin cytotoxicity and pharmacology of chemical agents. After having formed a confluent stratified epithelium with proliferating basal cells and differentiated cell layers, human keratinocytes were harvested after enzymatic detachment as stable, three-dimensional cell aggregates or used as adherent multilayers in microtiter plates to study the local cytotoxicity of different toxic compounds. The advantage of this test is that it uses the adequate target cells and that it evaluates both the ability of the test chemical to penetrate several cellular layers as well as the ability to interfere with cellular function. The end points are cell viability and cell metabolism, which are determined by neutral red uptake and MTT reduction, respectively. For the 13 chemicals evaluated in this study we found good correlation (r = .819) between the potency rankings of keratinocyte NR 50 values and in vivo irritancy data. There was also good agreement (r = .945) between ranking of these chemicals according to midpoint toxicity of both the 3T3 assay and the keratinocyte assay. This test system might be at the present stage a supplementation of the current test battery, which shall replace in vivo irritation tests like the Draize test.

The association reaction of yeast alcohol dehydrogenase with coenzyme is partly diffusion-controlled in solvents of increased viscosity.

The steady-state kinetics of the yeast and liver alcohol dehydrogenase catalyzed reduction of aldehydes were examined in solvent mixtures of increased viscosity. This was done to investigate the effects of diffusion control on the fast association of NADH with the enzymes. Both glycerol and sucrose were unsatisfactory as viscosogens, as they inhibited the enzyme, but poly(ethylene glycol)/water mixtures were satisfactory. The 5-fold faster reaction of yeast alcohol dehydrogenase with NADH is partly diffusion controlled, whereas the slower liver alcohol dehydrogenase reaction showed no diffusion effects. These results are consistent with a yeast alcohol dehydrogenase active site that has relatively little steric hindrance to NADH binding. It is estimated that contributions to this association reaction from diffusion control and chemical activation control are equal at a solvent viscosity of 10 cP. Thus, under physiological conditions of increased viscosity the NADH association may be significantly affected by diffusion effects. In order to estimate accurately the maximum diffusion-controlled rate constant from diffusion theory, the diffusion coefficients of NADH were measured in poly(ethylene glycol)/water mixtures and were found to vary inversely as the solvent viscosity raised to the power of 0.5. The non-Stokesian behaviour of molecules as large as NADH in polymer/water mixtures may be a serious limitation to the routine use of poly(ethylene glycol) as a viscosogen for diffusion studies.