Muscle strength and body composition in adult women with Marfan syndrome.

OBJECTIVE: The purpose of this study was to assess skeletal muscle function and body composition in a group of women with Marfan syndrome compared with matched controls. METHODS: The 21 women who were receiving follow-up for Marfan syndrome at our institution, were free of major cardiovascular disease, and consented to the study performed isokinetic and isometric knee extension and flexion maximal strength tests and had their body composition evaluated using dual-energy X-ray absorptiometry (DEXA). The same assessments were done in 19 matched controls. RESULTS: A significant decrease in lean leg mass with no change in total soft-tissue leg mass was noted in the patients compared with the controls. Peak torque values for the quadriceps and hamstring muscle groups were decreased in the patients, but only quadriceps strength was significantly reduced after normalization for lean leg mass. CONCLUSION: The muscle strength reduction in Marfan patients was not fully explained by a decrease in lean leg mass, suggesting qualitative skeletal-muscle alterations related to abnormal fibrillin expression in muscle connective tissue.

[Marfan syndrome]. / Syndrome de Marfan.

Marfan's syndrome is a monogenetic disease with an autosomal dominant transmission generally accompanied by type I fibrillin abnormality. This widely-distributed molecule participates in the structure of connective tissues so that any aberration may result in disease of many systems: skeletal morphology, dislocation of the lens, neurological or cutaneous signs and dilatation of the aorta predisposing to dissection, mitral valve prolapse being a common association. The diagnosis, clinical because of the size of the culprit gene and the multiplicity of the possible mutations, is sometimes difficult, and diagnostic criteria have been proposed. It is important to make the diagnosis because treatment is based on the restriction of violent exercise, betablocker therapy and regular echocardiographic monitoring of the ascending aorta, the region at highest risk of dilatation and dissection. A family enquiry is essential to make the diagnosis before the onset of complications in pauci-symptomatic patients (great intra-familial variability). Pregnancy poses special problems in these patients.

Gastrointestinal tolerability of ibuprofen compared with paracetamol and aspirin at over-the-counter doses.

This multicentre, randomized, investigator-blinded, parallel-group study compared the gastrointestinal (GI) tolerability of ibuprofen, paracetamol and aspirin at over-the-counter doses for common pain indications. Patients (of whom 8633 were evaluable) took either ibuprofen up to 1200 mg daily, or paracetamol or aspirin, each up to 3000 mg daily, for 1-7 days. The main outcome was the proportion of patients with GI adverse events. There were significantly more patients who suffered GI adverse events, principally abdominal pain, dyspepsia, nausea and diarrhoea, with aspirin (18.5%) than with ibuprofen (11.5%), but the difference between ibuprofen and paracetamol (13.1%) was not significant. Significantly more of those patients with a history of non-ulcer GI disease (n = 371) developed GI adverse events than did those with no such history; the incidence of GI adverse events in both groups was lowest with ibuprofen. More women than men experienced GI adverse events (15.5% versus 12.8%). The higher incidence of GI adverse events with aspirin was evident from the first day of treatment. In conclusion, the GI tolerability of ibuprofen, at over-the-counter doses of up to 1200 mg daily for up to 7 days, was at least as good as that of paracetamol and significantly better than that of aspirin.

The cost of osteoporosis in men: the French situation.

The objective of this study was to estimate the annual direct medical costs of osteoporosis and osteoporotic fractures incurred by French men > or =50 years of age. Costs were assessed from a societal perspective for 1999 and expressed in Euros. An expert panel was consulted to identify fractures attributable to osteoporosis according to International Classification of Diseases (ICD)-10 codes. Available age- and gender-specific osteoporosis attribution probabilities (OAP) were used to derive the proportion of health-care utilization for fractures resulting from osteoporosis. Hospital and ambulatory care costs due to fractures were obtained from French databases. A total of 23,260 acute hospitalizations were found to be caused by osteoporosis, 52% of which are for hip fractures. Mean cost per stay varied widely according to the site of fracture, from 1300 (wrist fracture) to 5900 (hip fracture). Consequently, the total cost of acute hospitalization amounts to 97.6 million, with hip fractures accounting for 73.2% of the expenditures. Rehabilitation and convalescence costs were estimated to be 90.8 million, generating a total hospital cost of 188.4 million. The total outpatient costs were estimated to be 9.1 million. Thus, the total medical costs of male osteoporosis amount to 197.5 million. A sensitivity analysis was performed to test the robustness of this figure. We estimate the number of fractures by applying international incidence rates from the literature to the French male population aged > or =50 years, whereas the OAP and unit costs were kept constant. This approach yielded an estimate of 21,857 fractures, which is only 6% below the base case. When compared with values from other countries, our study results appear very conservative.

Comparative tolerability of paracetamol, aspirin and ibuprofen for short-term analgesia in patients with musculoskeletal conditions: results in 4291 patients.

The aim of this blinded, randomised, multicentre study was to compare the tolerability of aspirin, paracetamol and ibuprofen in common pain resulting from musculoskeletal conditions (MSC) in general practice with patients with other non-MSC pain conditions. Patients took aspirin, paracetamol (both up to 3g daily) or ibuprofen (up to 1.2g daily) for up to 7 days. The main outcome was the rate of significant adverse events (SGAE). Four thousand two hundred and ninety one patients with MSC were evaluable (1436 aspirin, 1423 paracetamol, 1432 ibuprofen) and 4101 (95.5%) were per-protocol. A group of 4342 patients included for other (non-MSC) mild to moderate pain conditions was used for comparison. In the MSC group, SGAE were reported by 20.5% of patients with aspirin, 17.0% with paracetamol and 15.0% with ibuprofen. Ibuprofen was statistically equivalent to paracetamol and better tolerated than aspirin (p <0.0001). Ibuprofen was associated with fewer digestive system AE (4.4%) than aspirin (8.6%, p<0.0001) and paracetamol (6.5%, p <0.02). The non-MSC group showed similar intertreatment differences, but experienced fewer SGAE. No serious digestive events were observed with any of the three treatments in either group. These results show that in patients with mild to moderate pain resulting from MSC, ibuprofen given in OTC doses for 6 days is as well tolerated as paracetamol and better tolerated than aspirin.

Tolerability of ibuprofen, aspirin and paracetamol for the treatment of cold and flu symptoms and sore throat pain.

This double-blind randomised study compared the tolerability of ibuprofen (up to 1.2 g daily), aspirin and paracetamol (both up to 3 g daily) for up to seven days, in patients with mild to moderate pain resulting from cold/flu symptoms or sore throat (CF/ST) (n = 2,815). The main outcome was the rate of significant adverse events (SGAE). Rates of SGAE for ibuprofen, aspirin and paracetamol were respectively 12.0%, 15.7% and 12.3%. Ibuprofen was significantly better tolerated than aspirin (p = 0.02) and had comparable tolerability with paracetamol. The latter was also true for total digestive system events and for abdominal pain and dyspepsia. In conclusion, in patients with CF/ST, ibuprofen used at over-the-counter doses is as well tolerated as paracetamol and much better tolerated than aspirin.

Oral meloxicam is effective in acute sciatica: two randomised, double-blind trials versus placebo or diclofenac.

OBJECTIVE: Two randomised, double-blind, double-dummy trials evaluated the efficacy and tolerability of meloxicam compared with placebo or diclofenac in patients with acute sciatica. SUBJECTS: 1021 patients with acute sciatica. TREATMENT AND METHODS: In the first study, 532 patients received meloxicam 7.5 mg, meloxicam 15 mg, or placebo for 7 days. The second study randomised 489 patients to meloxicam 7.5 mg, meloxicam 15 mg, or diclofenac 150 mg for 14 days. RESULTS: Meloxicam 7.5 mg and 15 mg significantly improved overall pain between baseline and day 7 (p < 0.05) compared with placebo. Furthermore, both meloxicam doses showed similar improvements on all primary and secondary efficacy endpoints compared with diclofenac 150 mg. No significant differences in tolerability were observed between any of the treatment groups in either study. CONCLUSIONS: Meloxicam (7.5 mg or 15 mg) was well tolerated and was more effective than placebo, and as effective as diclofenac, in acute sciatica.

Marfan syndrome and fibrillin disorders.

Marfan syndrome is the second most common inherited connective tissue disorder after osteogenesis imperfecta. Musculoskeletal abnormalities are at the forefront of the clinical picture and count among the major diagnostic criteria for Marfan syndrome, together with cardiovascular and ocular system involvement. Early diagnosis is of the utmost importance since preventive measures significantly increase life expectancy and prevent the occurrence of impairments and disabilities. Marfan syndrome is due to mutations within the fibrillin-1 gene, which is the main protein of the microfibril network. Microfibrils play a crucial role in the trophicity and function of elastic tissue. Multidisciplinary management of the patients and their families is vital.

Magnetic resonance imaging changes in periarticular soft tissues during flares of medial compartment knee osteoarthritis. Preliminary study in 10 patients.

OBJECTIVE: To quantify changes in magnetic resonance imaging signals from the deep and superficial capsulo-ligamentous planes and the medial collateral ligament in flares of knee osteoarthritis. PATIENTS AND METHODS: Preliminary prospective study of ten patients with medial compartment knee osteoarthritis meeting American College of Rheumatology criteria and associated with a Lequesne index of 5 or more. A grid was used to evaluate signal changes as compared to the opposite (asymptomatic) knee. Magnetic resonance images were read independently by two radiologists blinded to clinical data. RESULTS AND DISCUSSION: In all ten patients the capsulo-ligamentous planes and medial collateral ligament generated low signal on T1 images and high signal on T2 images. No significant changes were seen in the asymptomatic knee. The evaluation grid produced satisfactory interobserver agreement. CONCLUSION: Flares of medial compartment knee osteoarthritis are associated with changes in magnetic signal as compared to the contralateral asymptomatic osteoarthritic knee. The grid developed for this study could be used to evaluate the effects of treatment in a larger number of patients.

Bone mineral density in sixty adult patients with Marfan syndrome.

Sixty adult patients (40 women, 20 men) with Marfan syndrome (MFS) according to the Berlin criteria had a full clinical examination and bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry of the hip and nondominant forearm. BMD was expressed as a Z-score and compared with the reference population of the Hologic database. In MFS men, BMD (g/cm(2)) was compared with the BMD of 45 normal tall Caucasian adults. Osteocalcin was measured by radioimmunoassay. In patients with MFS, BMD was compared between patients with and without previous fractures and according to the phenotypic severity of MFS. The mean age of the patients was 32.9 +/- 9.3 years (women 32.5 +/- 9.7, men 33.4 +/- 8.6), mean height was 180.3 +/- 10.3 cm (women 176.3 +/- 9.2, men 188.1 +/- 7.5) and mean body mass index 20.9 +/- 3.6 kg/m(2) (women 20.8 +/- 3.4, men 20.95 +/- 3.97). Hyperlaxity score (Beighton criteria) was 6.9 +/- 1. 1. Six patients (10%) had a previous fracture. Thirty per cent of patients had had at least one previous operation for scoliosis, aortic dilatation or eye problems. BMD values in the 60 patients were as follows: Z-score of the hip, -1.26 +/- 0.93, p<10(-9) (neck, -0.93 +/- 1.09, p<10(-9); trochanter, -1.31 +/- 0.85, p<10(-9); intertrochanter, -1.39 +/- 0.99, p<10(-9); Ward's triangle, -0.93 +/- 1.88, p<10(-9)); Z-score of the radius: -1.6 +/- 1.06, p<10(-9) (1/3 proximal, -1.29 +/- 1.03; mid-radius, -1.94 +/- 1.04; ultradistal, -0.68 +/- 1.1, p<10(-9)). The decrease in BMD was similar in men and women at both the hip and the radius. BMD in MFS patients was significantly decreased at cortical compared with trabecular sites (radius 1/3 proximal vs ultradistal, p<0.0001; total femur vs Ward's triangle, p<0.0005). No difference in BMD was found between MFS patients with or without previous fractures and those with severe or less severe phenotypic expression of MFS. An influence of height and weight in MFS on BMD is suspected. Osteocalcin was not increased in our group of MFS patients. Thus both men and women with MFS have a significant deficit of BMD at the hip and radius. The decrease in BMD is present equally in both sexes and is more pronounced at predominantly cortical sites. In our group of patients we found no increase in fractures and no relation between decreased BMD and phenotypic expression of the syndrome.

[Value of multidisciplinary consultation in diagnosis and survival of Marfan syndrome]. / Apport d'une consultation multidisciplinaire dans le diagnostic et le suivi d'un syndrome de Marfan.

OBJECTIVES: To facilitate diagnosis, define a strategy for prevention and treatment and obtain further insight concerning Marfan's disease, we conducted a series of multidisciplinary consultations in French clinics. PATIENTS AND METHODS: Five specialists (a genetics specialist, a pediatrician or a rheumatologist, an ophthalmologist, and a psychologist) saw all the patients successively in the same clinic. A synthesis of the clinical files was prepared for analysis. Since the first consultation on 1 January 1995 and the study end on 30 June 1997, 494 patients (67% adults) participated in primary consultations, 143 were seen at follow-up consultations. RESULTS: The diagnosis of Marfan's disease was affirmed in 41% of the patients, disaffirmed in 48% and uncertain in 11%. Among the Marfan's patients, 75% were seen again within the framework of a multidisciplinary follow-up consultations. Annual work-up included cardiology (echocardiography with measurement of the proximal aorta diameter in search for indication for beta-blocker therapy or preventive valve replacement), ophthalmology (lens, retina) and rheumatology examinations (skeletal involvement). CONCLUSION: Early diagnosis and rigorous follow-up can help prevent ocular and cardiac complications in Marfan's disease. The multidisciplinary approach provides more precise data for diagnosis and possible phenotype-genotype correlations.

Spontaneous epidural hematoma discovered upon evaluation of a calcified disk herniation.

A female renal transplant recipient had intractable femoral neuralgia due to a large calcified disk herniation. She then developed an anterior epidural hematoma above the herniation, from T12 to L2, in the absence of clotting disorders. Spontaneous resorption of the hematoma occurred. The femoral neuralgia resolved after surgical treatment of the herniation. The location of the hematoma suggests that the calcified disk may have torn the fragilized epidural venous network.

Destructive polyarthritis due to a group B streptococcus.

A new case of destructive polyarthritis due to a Group B streptococcus is reported. The patient was a 55-year-old male whose predominantly axial manifestations in the absence of evidence of an infection initially suggested psoriatic arthritis. Although rare, Group B streptococcal arthritis has been reported outside the postpartal and neonatal periods. Monoarthritis with a favorable outcome has been the most common clinical pattern. Several cases of destructive polyarthritis with axial involvement have been reported in which the joint destruction and longer time to diagnosis as compared with monoarticular forms resulted in permanent functional impairment.

Chemodectoma of the cauda equina.

We report a new case of chemodectoma of the cauda equina, in a 52-year-old male who presented with low back pain and sciatica, then rapidly developed cauda equina syndrome. Magnetic resonance imaging demonstrated a tumor at the L2-L3 level. Complete excision was performed and the tumor was found to be a chemodectoma. Chemodectomas are rare neural crest tumors that are usually located at the neck. About 70 cases involving the cauda equina have been reported. Most are benign, although local recurrences occur in 4% of cases. A case with a cerebellar metastasis has been reported. Long-term follow-up should be provided.

Late onset spondylarthropathy: clinical and biological comparison with early onset patients.

OBJECTIVE: To compare the clinical, radiological, and biological profile of patients presenting late onset spondylarthropathy (LOSPA) with patients with early onset spondylarthropathy (EOSPA). METHODS: During the period April 1987 to April 1995 a retrospective chart review of inpatients and outpatients identified eight patients with LOSPA. They were matched with 32 patients with EOSPA examined during the same period of time. Clinical, radiological, and biological signs were compared. All patients fulfilled Amor criteria for spondylarthropathy. RESULTS: Mean age of patients with LOSPA was 65.1 years (range 58-72), and 26.6 years (range 11-40) in patients with EOSPA. The sex ratio (female/male) was 5/3 in LOSPA and 9/23 in EOSPA (p = 0.007). Patients with LOSPA had more significantly cervical and dorsal pain (p = 0.002, p = 0.02 respectively), anterior chest wall involvement (p = 0.04), number of peripheral arthritis (p = 0.04), aseptic osteitis (p = 0.004), and systemic symptoms: fever, fatigue, weight loss (p = 0.04). Mean (SD) erythrocyte sedimentation rate was 87 (24) in LOSPA and 24 (35) in EOSPA patients (p = 0.001). Inflammatory bowel disease was diagnosed in three patients with EOSPA. A definite family history of SPA was found in 50% of patients with LOSPA and in 31% of patients with EOSPA. A clear response to NSAID was obtained in 62% of LOSPA patients and in 90.6% of EOSPA patients (p = 0.05). Three LOSPA patients (two with Crohn's disease) not responding to NSAID were successfully treated with prednisone. CONCLUSION: The onset of spondylarthropathy is uncommon after 55 years. Patients with LOSPA, according to accepted international criteria present a different clinical and biological profile when compared with younger patients. These results suggests that age may influence the presentation of SPA at onset.

Osteonecrosis of the hip in renal transplant recipients. Changes in functional status and magnetic resonance imaging findings over three years in three hundred five patients.

OBJECTIVE: to conduct a retrospective study of the appearance and course of magnetic resonance imaging abnormalities in avascular osteonecrosis of the femoral head in renal transplant recipients and of potential relations between these abnormalities and the functional outcome. PATIENTS AND METHODS: among 305 renal transplant recipients, patients with pain in the hips or knees underwent radiographs and magnetic resonance imaging studies of the hips and, if appropriate, of the knees. The mean time interval between these studies and transplantation was 8.9 months. The outcome was evaluated based on the Lequesne index and findings from a repeat magnetic resonance imaging study after a mean follow-up of 33 months since transplantation. The criteria developed by Mitchell et al. were used to diagnose osteonecrosis on magnetic resonance images. The size of the necrotic area was estimated using the tracing paper method as < 25%, 25-50%, > 50% of the surface of the femoral head. Eleven patients were treated by elimination of weight-bearing and conservative treatments and 15 underwent core decompression (radiographic stage I or II). RESULTS: Fourteen patients (4.5%) developed osteonecrosis of the femoral head, which was bilateral in 12 patients and unilateral in two: thus, the total number of hips with osteonecrosis was 26. The first magnetic resonance imaging study disclosed a crescent-shaped area of low signal intensity in 25 cases, most of which were mild in severity as assessed on radiographs (Arlet and Ficat stage I or II). Extensive necrosis was found in most cases at the first evaluation (> 25% in 15 cases and > 50% in eight). The surface of the necrotic area (as assessed irrespective of the treatment used) remained unchanged in 20 cases and decreased in six. In half the cases the hyperintense signal from the sequestrum converted to a hypointense signal after a mean follow-up of 39 years. A poor functional outcome (Lequesne's index > 7 or total hip arthroplasty) was seen in 61.5% of cases, irrespective of the treatment used. CONCLUSION: Avascular osteonecrosis of the femoral head precipitated by corticosteroid therapy in renal transplant recipients occurred in 4.5% of patients immediately involved a large segment of the epiphysis, and usually remained stable over time, although a decrease in the size of the lesion was seen in a few cases. Overall, the functional prognosis was poor, with a Lequesne's index greater than 7 or total hip arthroplasty in two thirds of cases after three years' follow-up. The incidence of avascular osteonecrosis of the hip in renal transplant recipients has decreased since 1980, when cyclosporin was introduced and doses of corticosteroids used to treat rejection episodes were diminished.