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Biomedical subjects

D Uebelhart

Publications and source records attributed to D Uebelhart.

At least 19 recordsLinked to original sources

Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13 week, randomised, double blind study versus placebo and celecoxib.

OBJECTIVES: To compare the efficacy and safety of lumiracoxib with placebo and celecoxib for osteoarthritis OA in a 13 week, multicentre, randomised, double blind study. METHODS: After a 37 day washout period for nonsteroidal antiinflammatory drugs, 1702 patients with knee OA were randomised to lumiracoxib 200 or 400 mg once daily od, celecoxib 200 mg od, or placebo 2221. A visual analogue scale VAS pain intensity > or =40 mm was required. Primary efficacy variables were OA pain intensity VAS mm in the target knee, patients global assessment of disease activity VAS mm, and WOMAC pain subscale and total scores at 13 weeks. OA pain intensity, patients and physicians global assessment of disease activity, and WOMAC total and all subscale scores were analysed by visit as secondary variables. RESULTS: Lumiracoxib showed significant improvements in all primary and secondary variables compared with placebo. Lumiracoxib 200 mg od and celecoxib 200 mg od achieved similar improvements in OA pain intensity and functional status. Lumiracoxib 400 mg od demonstrated better efficacy for OA pain intensity and patients global assessment of disease activity at weeks 2, 4, and 8 and similar efficacy at week 13 compared with celecoxib 200 mg od. The incidence of adverse events AEs, serious AEs, and discontinuations due to AEs was similar in each group. CONCLUSION: Lumiracoxib demonstrated significant improvement in OA pain intensity, patients global assessment of disease activity, and the WOMAC pain subscale and total scores compared with placebo. Lumiracoxib was well tolerated in this study, with overall tolerability similar to that of placebo and celecoxib.

Adult↗

Hormone replacement therapy: what is the evidence today?

Based on the most recent studies, it clearly appears that long-term hormone replacement therapy (HRT) prevents fractures but does not improve established coronary artery disease. In addition, HRT leads to a small increase in breast cancer incidence and to a decrease in colorectal cancer incidence. HRT increases the incidence of venous thrombosis, pulmonary embolisms and strokes. As a consequence, HRT can no longer be recommended for primary or secondary prevention of cardiovascular diseases. In addition, it was also demonstrated that HRT was not able to improve cognitive functions and prevent dementia. Therefore regarding daily clinical practice, HRT certainly remains useful to control the symptoms of oestrogen deficiency in recently menopausal patients, but it should definitively no longer be recommended for long-term treatment.

Aged↗

[Therapy of osteoporosis: bisphosphonates, SERM's, teriparatide and strontium].

The therapy of osteoporosis is mostly based upon the use of drugs which inhibit bone resorption. Among these, the bisphosphonate family is the best known and mostly used by clinicians. Both second and third generation bisphosphonates, like alendronate and risedronate, are now available as weekly tablets which have facilitated the patient compliance to treatment together with a decreased occurrence of gastrointestinal side effects. These compounds are used efficiently to treat postmenopausal osteoporosis and osteoporosis of men as well. Their use did provide good evidence of increased bone mineral density (BMD) and a reduction in fracture rates. The use of intravenous bisphosphonates such as Zoledronate, Ibandronate and Pamidronate remains in most of the cases limited to special indications such as intolerance to the oral formulations and treatment of patients with bone metastases. The selective estrogen modulators (SERM's) family is limited to a single product on the market as of now, Raloxifene, which does inhibit bone resorption and is well documented by postmenopausal women to increase BMD and reduce vertebral fractures. In addition, a large range of positive nonosseous effects have been documented such as the reduction of the incidence of breast cancer. Other substances do have a strong anabolic effect such as Teriparatide, a recombinant human formulation of PTH 1-34. This compound has demonstrated good efficacy in postmenopausal women, increasing vertebral and hip BMD and reducing the incidence of fractures at both sites. The exact role of Teriparatide in the clinical setting is still open but its overall impact in the therapy of osteoporosis could be major due to its major efficiency over shorter periods of time. Strontium ranelate, a new divalent Strontium salt taken orally, acts both as an anti-catabolic and anabolic agent. The first results provided with strontium ranelate are very promising due to its major effect on the increase in BMD both at the vertebral and hip sites and its ability to reduce the incidence of fractures at both locations. Additional data are awaited to confirm these initial positive results.

Aged↗

[Physiotherapy interventions in osteoporosis].

Osteoporosis is an increasing public health problem which ultimately causes fractures and a significant reduction in patient's health-related quality of life. In this context, physiotherapists are involved in a wide range of therapies related both to prevention and treatment of osteoporosis. The reduction of the risk of falling by elderly patients with osteoporosis is a very important goal for physiotherapists because it is known to significantly decrease fracture incidence. Indeed, exercise programs including elements of muscle strengthening and better body balance control have a positive effect on the risk of falling, hence reducing the incidence of fractures and increasing the health-related quality of life of osteoporotic patients. As a further consequence, the decreased fracture incidence has a key roll in reducing health care costs. Once a patient presents with an osteoporotic fracture, he may be assisted with various forms of passive, active-assisted and active therapies. This treatment will help reduce pain, increase patient's mobility and prevent the occurrence of additional fractures. In addition, a good and well-balanced education process regarding secondary osteoporosis prevention may also help to modify the behavior of patients and help to improve skeletal health in the longer term. The physiotherapist has definitively a major role to play in the interdisciplinary team aimed at preventing osteoporotic fractures in both primary and secondary prevention levels.

Accidental Falls↗

A comparison of the therapeutic efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis.

OBJECTIVE: To evaluate and compare the efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis of the knee or hip. METHODS: In this 6-week double-blind, active comparator controlled, parallel-group study eligible osteoarthritis patients were randomised to receive either etoricoxib 60 mg once daily (n = 256) or diclofenac 50 mg three times daily (n = 260). The primary study endpoint was the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. Other endpoints included were the WOMAC stiffness and physical function subscales, and the Patient's Global Assessment of Response to Therapy (PGART) questionnaire. Early efficacy was evaluated using WOMAC first question (pain walking on a flat surface) and PGART 4 h after the morning dose of each drug on days 1 and 2. Rescue medication (paracetamol) used was also recorded. The study was designed to show comparable efficacy between etoricoxib 60 mg once daily and diclofenac 50 mg three times daily with respect to the primary endpoint and was conducted outside the United States at 67 centres in 29 countries. RESULTS: Etoricoxib (60 mg once daily) was comparable in efficacy to diclofenac (150 mg daily) on all the above parameters. The one exception was in the assessment of early efficacy where etoricoxib demonstrated significantly greater benefit within 4 h of taking the first dose on the first day of therapy (p = 0.007) as evaluated by the percentage of patients with good or excellent (PGART) responses. The treatment effects of both drugs were similar by the time day 2 was reached and were sustained throughout the 6 weeks of therapy. Both treatments were generally well tolerated. CONCLUSIONS: Etoricoxib is clinically effective in the therapy of osteoarthritis providing a magnitude of effect comparable to that of the maximum recommended daily dose of diclofenac. The onset of clinical benefit with etoricoxib on day one is more rapid than that of diclofenac. Both drugs were generally well tolerated.

Adult↗

Coincidence of Behçet's disease and SAPHO syndrome.

A young woman presented with deteriorated visual acuity due to acute retinal vasculitis. The diagnosis of Behçet's disease was made on the basis of the ophthalmologic findings and recurrent oral and genital aphthous ulcerations. In the past, this young woman had been operated on several times because of progressive aseptic osteitis of the right clavicle. The actual examination revealed chronic osteitis, osteosclerosis and hyperostosis of the anterior chest wall, as well as severe acne papulopustulosa et conglobata. These findings resulted in an additional diagnosis of SAPHO syndrome. This report is the first description of Behçet's disease occurring in association with SAPHO syndrome, both fulfilling the diagnostic criteria.

Acquired Hyperostosis Syndrome↗

[Neurogenic ectopic ossification: a physiatry update].

The first aim of this paper is to present a critical review of the existing literature on neurogenic ectopic ossification. The second aim is to introduce the two papers published in this issue of the journal. In addition, etiopathogenic aspects are described as well as some insights in classical therapies and new therapeutic options which could prove to be useful in the near future.

Anti-Inflammatory Agents, Non-Steroidal↗

The ICIDH-2 as a framework for the assessment of functioning and disability in rheumatoid arthritis.

OBJECTIVE: To investigate by a cross sectional study in patients with rheumatoid arthritis (RA) the relationship between measures of impairment, activity limitation, and participation of the model of functioning and disability (ICIDH-2). METHODS: Inclusion data of patients with RA (n=803) from the Swiss Clinical Quality Management Group were used. Impairments were measured by the Short Form-36 (SF-36) bodily pain scale, rheumatoid arthritis disease activity index (RADAI), disease activity score (DAS28), and radiographic scoring (x ray). Activity limitation was measured with the Health Assessment Questionnaire (HAQ) and the SF-36 physical functioning scale. Participation was measured with the SF-36 role and social functioning scales. Spearman (partial) correlations were used for analysis. RESULTS: Impairment and activity limitation dimensions of the ICIDH-2 model are related; correlations with the HAQ were: SF-36 bodily pain (r(s)=-0.61), RADAI (r(s)=0.58), DAS28 (r(s)=0.49), and x ray (r(s)=0.35). Similar correlations were found for SF-36 physical functioning. Activity limitation and participation restriction dimensions are also related: the HAQ correlates well with SF-36 role-physical (r(s)=-0.53) and SF-36 social functioning (r(s)=-0.43); SF-36 physical functioning correlates similarly. For impairment and participation restriction dimensions only SF-36 bodily pain is substantially correlated (r(s)=0.47 and 0.48) with SF-36 role-physical, after correcting for the influence of the activity limitation dimension (HAQ and SF-36 physical functioning). CONCLUSIONS: In this cross sectional study of patients with RA, impairments are associated with activity limitations, and activity limitations are associated with participation restrictions. Pain is the only impairment directly associated with participation restrictions. Based on the results of this study, it is strongly recommended that the ICIDH-2 framework is used in clinical trials and observational studies including the assessment of disease consequences in RA.

Activities of Daily Living↗

[Medical exercise therapy--indications, tips on individualized prescription].

Medical training therapy (MTT) belongs to the active methods which can be used by physiotherapists under medical prescription. This dynamic method was originally developed by O. Holten in Norway but it has become extremely popular in patients and did also convince a large number of therapists; as a consequence of its success, its prescription increased progressively and actually replaced larger parts of the passive methods used before. The aims of MTT is to work in a pain free environment and increase both muscle resistance, strength and joint mobility as well. The technique does not have any absolute contraindication, but it has to be individually adapted to each single patient. A true advantage of MTT is certainly that the active training sessions can be done in small well controlled groups of patients. As it does also apply for other types of currently used physical therapies, there are only restricted evidence-based proofs of efficacy and therefore scientifically sound studies are still needed in this field.

Clinical Protocols↗

[Conservative treatment of shoulder disorders].

The extreme complexity of the shoulder joint results from the coordinated activity of five different articulations and the supporting soft-tissue girdle. Any perturbation of this system has deleterious biomechanical consequences to the shoulder muscular girdle integrity and will eventually lead to pain and functional limitations. A functional diagnosis of the lesion will always be a prerequisite for a targeted conservative therapy. Treating pain is often the basis of the treatment, but it should rapidly be implemented with a broad range of physiotherapeutic techniques and manual therapy as well when appropriate. The guidelines for therapy include an active stabilisation program in case of joint instability and passive mobilisation whenever functional limitations are present. This paper deals with the different problem-oriented interdisciplinary therapeutic modalities used in frequent shoulder problems.

Acute Disease↗

Non-invasive assessment of equine bone: an update.

This paper summarizes traditional and current methods of non-invasive assessment of bone in the horse. The description and potential clinical utility of two non-invasive technologies with major development in the last decade are presented, namely, (1) serum biochemical markers for bone turnover and (2) quantitative ultrasound. Serum biochemical markers of bone formation valid in horses are osteocalcin, carboxy-terminal peptide of type I procollagen and bone-specific alkaline phosphatase. The cross-linked carboxy-terminal telopeptide of type 1 collagen c-telopeptides of type I collagen and total deoxypyridinoline are the serum markers for bone degradation. These markers respond more rapidly to skeletal changes than other bone assessment techniques, but ideally each horse needs to be compared with itself. Quantitative ultrasound is radiation free and is a well-tolerated technique for measuring bone properties in horses. This device allows bone speed of sound measurements at various sites using the axial transmission mode along the cortex and gives information about stiffness, architecture, porosity and bone mass.A combination of different non-invasive assessment techniques is recommended for the evaluation of bone biphasic modelling-remodelling activity and the mineral phase with its architecture. The potential clinical and research use of these techniques is considered.

Absorptiometry, Photon↗

Modifications of bone and connective tissue after orthostatic bedrest.

Eight male volunteers were submitted to a 6-week anti-orthostatic bedrest trial followed by a 1-month reambulation period. We prospectively monitored whole-body composition by dual-energy X-ray absorptiometry, bone and connective tissue metabolism by biochemical markers and calcium regulating hormones by 1-84 parathyroid hormone and 1,25-dihydroxyvitamin D(3). Bone mineral density (BMD) did not vary significantly; however, a trend toward an increase in head BMD and a decrease in trunk, lumbar vertebrae and lower limb BMD was observed. A decrease in the lower limb lean content occurred by day 27 and was maximum by day 42 after the beginning of bedrest; it normalized by day 30 after bedrest. The serum levels of both osteocalcin and C-terminal crosslinked telopeptide of type I collagen increased as a consequence of bedrest. A slight increase in the serum levels of the N-terminal propeptide of type III collagen, a marker of connective tissue metabolism, was observed during the bedrest period. Except for the C-terminal extension propeptide of type I collagen, all markers decreased to baseline pre-immobilization levels during the 1-month recovery phase. Serum PTH and 1,25-dihydroxyvitamin D(3) levels were low during the bedrest period and rose during the reambulation phase. These results seem to reflect early changes in bone and connective tissue metabolism as a result of bedrest unloading, but their order of magnitude remains moderate, thus emphasizing the necessity to perform longer-duration trials.

Absorptiometry, Photon↗

Expression of the precursor of secretoneurin, secretogranin II, in the synovium of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: Secretoneurin (SN) is a neuropeptide that is chemotactic for mononuclear cells and it has been suggested to be involved in the mediation of pain; there is also evidence that SN is involved in the inflammation process. As secretogranin II (SGII) is the precursor of SN, we investigated expression of SGII mRNA and SN protein in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Snap frozen synovial tissue specimens from 12 patients with RA and 11 patients with OA were examined. RNA was isolated and cDNA copied by reverse transcription. The expression of SGII was determined by polymerase chain reaction and in situ hybridization (ISH). SGII expressing cells were compared with CD68 positive cells stained by immunohistochemistry. SN protein was also detected by immunohistochemistry. RESULTS: A 524 bp SGII-specific fragment could be amplified by PCR from the cDNA of all specimens. ISH showed scattered expression of SGII in both RA and OA synovial tissue; its expression pattern was characterized by positive staining for SGII in both the lining and the sublining layer. Immunohistochemical double labeling with anti-CD68 antibodies revealed expression of SGII in CD68 negative, fibroblast-like cells, whereas CD68 positive macrophages did not. In RA and OA, the SGII staining by ISH was positive with a diffuse staining throughout the entire synovial tissue. SN protein expression was scattered in RA but more intense in OA synovium. CONCLUSION: The expression of SGII mRNA in RA and OA synovial fibroblasts clearly supports the hypothesis that SN is involved in the synovial tissue inflammation in both diseases. The significant lower SN expression in RA could be due to an inhibitory mechanism with respect to the SN levels in synovial fluid. SN might be involved in the modulation of afferent nerve transmission and therefore might play a role in the sensation of pain, especially in patients with OA.

Antigens, CD↗

Intravenous pamidronate attenuates bone density loss after acute spinal cord injury.

OBJECTIVE: To compare the effects of a 6-month treatment with intravenous pamidronate (30-mg infusion once per month) to conventional rehabilitation without pamidronate on bone density of the spine and leg bones and on the excretion rate of N-telopeptide, a urinary marker of bone catabolism, in acutely spinal cord injured patients. DESIGN: A nonrandomized control trial in which 24 spinal cord injured subjects entered the study within 6 weeks of their injury. Fourteen subjects received pamidronate; 10 did not. OUTCOME MEASURES: Bone density measurements by dual x-ray absorptiometry were performed before the initial treatment (within 6 weeks of the injury) and at 3, 6, and 12 months postinjury and was the primary efficacy parameter. Urine for N-telopeptide levels was the secondary efficacy parameter. RESULTS: After acute spinal cord injury, patients treated with intravenous pamidronate had significantly less bone density loss compared with those who did not receive pamidronate (parametric ANOVA, p<.02). Also, ambulatory subjects had significantly less bone density loss over the study period (p<.05) than nonambulatory subjects. In general, a high excretion level of the urinary bone-breakdown product N-telopeptide was found before intravenous pamidronate treatment, followed by a dramatic reduction in excretion after pamidronate treatment. Ambulatory subjects excreted significantly less N-telopeptide than motor-complete subjects at all time points. CONCLUSION: Intravenous pamidronate treatment and ambulatory ability in the first 6 months after an acute spinal cord injury prevents bone density loss.

Acute Disease↗

Shoulder pain and dysfunction in hemiplegia: effects of functional electrical stimulation.

OBJECTIVE: To determine the influence of functional electrical stimulation (FES) on subluxation and shoulder pain in hemiplegic patients. DESIGN: Controlled study of 24 months' duration beginning in the first month after onset of stroke. SUBJECTS AND SETTING: One hundred twenty hemiplegic patients with both subluxed and painful shoulder were followed for rehabilitation before and after discharge between 1989 and 1993. All subjects received conventional rehabilitation based on the Bobath concept. In addition, patients were alternately assigned to a control group or to receive additional FES for 5 weeks on muscles surrounding their subluxed and painful shoulder. MAIN MEASURES: Clinical examinations, including range of motion, pain assessment, and x-rays, were performed at the start of the study, between the second and fourth weeks after onset of stroke, and subsequently at 6, 12, and 24 months. RESULTS: The FES group showed significantly more improvement than the control group in both pain relief (80.7% vs. 55.1%, p<.01) and reduction of subluxation (78.9% vs. 58.6%, p<.05). Furthermore, recovery of arm motion appeared to be significantly improved in the FES group (77.1% vs. 60.3% in the control group, p<.01). CONCLUSION: The FES program was significantly effective in reducing the severity of subluxation and pain and possibly may have facilitated recovery of the shoulder function in hemiplegic patients.

Adult↗

Parenchymatous cerebral neurocysticercosis in a quadriplegic patient.

OBJECTIVE: To present and discuss a case of cerebral neurocysticercosis in a quadriplegic patient. DESIGN: Case report of a case of neurocysticercosis in a high level spinal cord injury (SCI) patient who developed episodes of autonomic dysreflexia and orthostatic hypotension associated with transient neurologic deficits and seizures. SETTING: Spinal Cord Unit of the University Hospital of Geneva, Switzerland. SUBJECT: Single patient case report. MAIN OUTCOME MEASURE: Clinical and radiological magnetic resonance imaging follow-up of the patient between July 1995 and October 1997. RESULTS: Treatment of cysticercosis with praziquantel relieved the patient from autonomic dysreflexia, symptomatic orthostatic hypotension, transitory neurological deficits and seizures. CONCLUSION: Diagnosis of neurocysticercosis in a quadriplegic patient might be difficult because of frequent overlaps with some usual symptoms occurring in high level SCI, mostly autonomic dysreflexia and orthostatic hypotension. Neurocysticercosis should be kept in mind when a SCI patient living in, or coming from endemic zones presents with new neurological abnormalities and seizures. Magnetic resonance imaging appears to be more sensitive than computerised tomography to confirm the diagnosis of active cysticercosis. Treatment with praziquantel associated with cimetidine to increase the drug bioavailability and prednisone to reduce the inflammatory reaction gives good results.

Animals↗

Effects of hyaluronic acid on cartilage degradation.

Based on the published literature available so far, it appears that naturally derived hyaluronic acid (HA) and newer formulations available on the market belong to the pharmacologic class of slow-acting drugs for the treatment of osteoarthritis. These compounds seem to have the potential to modulate the painful symptoms of osteoarthritis as well as to improve the function of the osteoarthritis joint. Positive clinical consequences are based on direct and indirect effects of viscosupplementation associated with a normalization of the rheologic properties of the osteoarthritic synovial fluid, decreased inflammation, and end-coating of the pain receptors in the osteoarthritis joint. Few in vivo data exist in humans to support the concept that HA formulations could have a structure-modifying effect on human osteoarthritis cartilage. Animal-based studies have demonstrated positive effects of exogenous HA on pain in the joint, heat shock proteins, and in models of osteoarthritis. Although many promising effects of exogenous HA have been reported, there remains uncertainty as to the effectiveness of reversing cartilage injury and other manifestations of joint diseases with exogenous HA because of difficulties in interpreting and unifying results of these studies. This is due largely to differences of cartilage source in models of joint/cartilage injury, multiple end points, the controls employed, analytical techniques, and the molecular weight of exogenous HA used. There exists a need for uniform agreement as to the choice of injury model, time points of the study, evaluation tools, and source and molecular weight of the HA used if we are to determine whether exogenous application of HA has a truly beneficial role in the reversal of cartilage injury.

Animals↗

Effect of calcitonin on bone and connective tissue metabolism in hemiplegic patients: a two-year prospective study.

OBJECTIVES: To test the effects of 200 IU/day of a nasal spray of salmon calcitonin in modulating the increased bone tissue metabolism observed in hemiplegic patients. DESIGN: A two-year, prospective, randomized, double-blind, placebo-controlled study. PATIENTS: Thirty-four patients with hemiplegia due to a cerebrovascular accident were included in the study during the first month after onset of hemiplegia after giving their informed consent. All patients followed a suitably planned course of active rehabilitation according to Bobath. They were randomly allocated to either the calcitonin or the placebo group but all of them received a daily oral calcium supplementation of 1000 mg. RESULTS: Biochemical markers of bone formation, serum total alkaline phosphatase, osteocalcin and type I procollagen did not vary during the two years of follow-up. Cross-linked carboxy-terminal telopeptide of type I collagen, a biochemical marker of bone resorption, was elevated initially after stroke and then decreased significantly (p <0.001), stabilizing as of month 12. Urinary calcium/creatinine and total hydroxyproline/creatinine ratios presented with similar profiles. The serum levels of the type III procollagen, a marker of connective tissue metabolism, were also elevated upon entry and decreased thereafter. No significant difference could be found between the calcitonin-treated and the placebo group for any of the biochemical markers at any time point. CONCLUSION: This prospective study demonstrated that biochemical markers of bone and connective tissue metabolism were elevated shortly after the occurrence of stroke and then gradually decreased during the first two years after injury. The daily administration of 200 IU of intranasal calcitonin did not influence the levels of these markers.

Administration, Intranasal↗