Recurrent bilateral metatarsal "stress-and-insufficiency" fractures in a levodopa-treated young woman with Parkinson's disease.

Levodopa treatment of Parkinson's disease is very effective, but many types of adverse events can complicate the disease course, especially dyskinesias. As reported by Lee et al. (Calcif Tissue Int 86:132-41, 2010), levodopa intake is associated with increased homocysteinemia that is known to be linked to poorer bone quality and, consequently, osteoporotic fractures. Herein, we report the case of a young woman who suffered recurrent metatarsal fractures in the context of levodopa-treated early-onset Parkinson's disease.

Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFalpha). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFalpha drug in the treatment of RA, would modulate systemic and local bone resorption and reduce cartilage degradation. METHODS: We performed a prospective study of a multicentric cohort of 48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4 (7.8) years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therapy we measured the following biochemical markers: pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption; serum C-terminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism; and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by dual-energy x-ray absorptiometry (DXA). No patient received bisphosphonates while 77% were under oral glucocorticoids. RESULTS: BMD remained stable over 1 year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (analysis of variance (ANOVA) p = 0.032) values returning to pre-treatment level at week 54. By contrast, ICTP levels progressively declined with a maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodelling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (ANOVA p = 0.041) in those with pre-treatment levels above the upper limit of normal range. CONCLUSIONS: In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.

Total and ultrafiltrable plasma magnesium in hyper- and hypoparathyroidism, and in calcium-related metabolic disorders.

Serum total, ultrafiltrable and protein-bound magnesium, and urinary fractional excretion of magnesium were studied in patients with primary hyperparathyroidism (before and after surgery) and in patients with hyperparathyroidism, malignant hypercalcemia and chronic renal failure with or without hemodialysis. Whereas serum total Mg was unchanged in patients with primary hyperparathyroidism, the ultrafiltrable magnesium concentration was higher than in the control group and higher before than after surgery. The total and the ultrafiltrable magnesium concentrations were highly correlated in the overall patients with Ca-related metabolic disorders, suggesting that renal function had no influence on the relation between these two parameters. Moreover, in malignant hypercalcemia, our results suggested that PTH-like peptides might be less effective than PTH in renal handling of Mg as previously described for Ca.

Effect of megazol on Trypanosoma brucei brucei acute and subacute infections in Swiss mice.

Human African trypanosomiasis (HAT) or sleeping sickness is a major public health problem in 36 sub-Saharan African countries and is caused by Trypanosoma brucei gambiense and T. b. rhodesiense. About 25,000 new cases of the disease are reported annually, and around 50 million people are classed as at risk of contracting the disease. Until now; the only effective drug available for treatment of advanced HAT was the trypanocide melarsoprol. The mortality rate of melarsoprol treated patients is 1-5%. Megazol is a nitroimidazole derivative shown to be effective in vitro against T. b. brucei with an EC50 of 0.01 micrograms.ml-1. When this compound was tested for its in vivo activity in T. b. brucei infected Swiss mice, it was shown to cure the acute disease. However, megazol alone did not cause cure of mice carrying a subacute infection with involvement of the central nervous system (CNS). Combined suramin and megazol treatment did prove effective and the mice were shown to have remission without further relapse from the CNS. The study of three megazol derivatives is also described here. Substitution of a bromine, methyl or trifluoromethyl moiety at the 4 position of the imidazole ring abolished trypanocidal activity both in vivo and in vitro. Intermediates of megazol synthesis (imidazole sulfoxide and imidazole sulfone) were also tested, but were shown not to be active. It is thought that megazol trypanocidal effect may be due to the triggering of radical production by the compound, which have toxic effects on the trypanosomes metabolism. In depth study of megazol is needed to fully elucidate its pharmacokinetics and to precisely pin down its mode of action.

Prospective X-ray densitometry and ultrasonography study of the hand bones of patients with rheumatoid arthritis of recent onset.

OBJECTIVE: Bone demineralization observed in early rheumatoid arthritis is not easily measured. To measure bone loss and to discriminate between rheumatoid arthritis and other rheumatic diseases, we used two methods: dual-energy X-ray absorptiometry and ultrasonography. METHODS: From a population-based recruitment, 32 patients with early peripheral polyarthritis (median disease duration: 4 months) were studied. Clinical, laboratory, functional, hand-bone assessments were made at the entry an at months 6 and 12. Bone X-ray densitometry measurements were made on 16 areas of the hand. Speed of sound was measured across the proximal phalanges of the four fingers. X-rays of both hands were scored according to the modified Sharp's score. At 12 months, patients were classified as rheumatoid arthritis (N = 15; 9 F) or as other rheumatic diseases. RESULTS: We found: 1) significantly decreased bone mineral density (BMD) of the whole hand, in the rheumatoid arthritis group versus the other rheumatic diseases group, at 6 and 12 months (P < 0.05); 2) no significant decrease of bone mineral density (BMD) in other areas in the rheumatoid arthritis group; 3) no significant change of ultrasounds in either group; and 4) no significant correlation between the decrease of BMD in the rheumatoid arthritis group and clinical, biological or radiologic parameters, except for IFNgamma, whose production in whole blood cell culture was lower at entry in the rheumatoid arthritis group. CONCLUSION: DEXA bone assessment in rheumatoid arthritis was able t detect bone loss in the whole hand at 6 months.

Rheumatoid factors, anti-filaggrin antibodies and low in vitro interleukin-2 and interferon-gamma production are useful immunological markers for early diagnosis of community cases of rheumatoid arthritis. A preliminary study.

OBJECTIVE: To determine whether measurements of different autoantibodies (Ab) and cytokines are useful to distinguish very early rheumatoid arthritis (RA) from other inflammatory rheumatisms. METHODS: From a population-based recruitment, 32 patients with very early polyarthritis (median duration: 4 months) were studied. Evaluations at entry (M0), and at 6 (M6) and 12 months (M12). Ab tested: rheumatoid factors (RF) by agglutination methods and ELISA, antiperinuclear factor (APF), antikeratin Ab (AKA), anti-Sa and antinuclear Ab. Cytokine production (TNFalpha, IL2, IFNgamma, IL1beta, IL10) in whole blood cell culture (WBCC) was determined at M0. At M12, patients were classified as having RA (N = 15) or other rheumatic diseases. RESULTS: At M0, AKA/APF and anti-Sa Ab frequencies were low, 13% and 7%, respectively. While most Ab detected at M0 persisted, others appeared during follow-up, particularly APF, which rose from 13 to 40% at M12. At M6, IgM-RF was detected in two RA patients exclusively by ELISA. AKA/APF were found to be highly specific markers for RA (100% specificity). At some time during follow-up, two RF-negative RA patients were AKA-positive. In two patients, AKA and APF were present at M0 before they satisfied ACR criteria. IL2 and IFNgamma production was significantly lower (P < 0.05) for RA patients. CONCLUSION: AKA/APF and anti-Sa Ab were detected in community cases of very early RA. AKA/APF and RF detected by ELISA might contribute to an earlier diagnosis of RA. Low production of IFNgamma and IL2 in WBCC constituted a distinct immunopathological feature in very early RA patients.

[An efficacy trial on Trypanosoma brucei brucei of molecules permeating the blood-brain barrier and of megazol]. / Essais d'efficacité sur Trypanosoma brucei brucei de molécules franchissant la barrière hématoméningée et du mégazol.

Human African trypanosomiasis (HAT) is a major public health problem in 36 sub-Saharan African countries and around 50 million people are classed as "at risk". About 25,000 new cases of the disease are reported annually by the World Health Organisation (WHO). This disease is fatal if untreated. As for now, chemotherapy is unsatisfactory and relies on a few drugs which show two major problems. The first is pharmacokinetics involving the passage through the blood-brain barrier. The second concerns toxicity and adverse side-effects of drugs used to treat this disease. New trypanocides should be safe, effective without toxicity. This study reports the action of 45 drugs, known to pass through the blood-brain barrier and belonging to different therapeutic classes, and also the megazol, a nitrothiadiazole derivative, on Trypanosoma brucei brucei AnTat 1-9 in vitro in acellular semi-defined medium. Results showed that some drugs did not modify the parasitic growth, and others were either trypanostatic or trypanocide. These last drugs were tested in vivo on T. b. brucei An-Tat 1-9 infected Swiss mice. Only megazol was shown to be effective and trypanocide. This compound might trigger the production of oxygen derivatives and free radicals-which have toxic effects on the trypanosome metabolism.

[Remission under treatment of cutaneous xanthomatosis disclosing myeloma: apropos of a case with a three-year course]. / Régression sous traitement d'une xanthomatose cutanée révélatrice d'un myélome: à propos d'un cas avec 3 ans d'évolution.

We report a case of IgG lambda multiple myeloma with inaugural cutaneous xanthomatosis. A three years follow up showed parallel evolution of xanthomatosis and monoclonal gammapathy during therapy suggesting that the association is not coincidental. A decrease in IDL catabolism could be responsible. The monoclonal gammapathy could react with IDL and disturb the recognition of apolipoprotein E by its hepatic receptor.

[Correlation between the serum level of soluble CD16 and the staging of myeloma: study of 214 serums]. / Corrélation entre le taux sérique du CD16 soluble et le stade du myélome: étude de 214 sérums.

Soluble CD16 (sCD16) are soluble part of Fc receptor for IgG which control in mice, proliferation of hybridoma B cells and IgG production. The levels of sCD16 in 165 myeloma patients and 29 patients with MGUS appear significantly different:25a.u./ml versus 144a.u./ml and values of stage I are significantly higher than those of stages II + III.sCD16 might be a prognosis factor in myeloma.

[Postpartum septic arthritis. Two case reports]. / Arthrites septiques du post-partum. A propos de deux cas.

Nongonococcal septic arthritis can occur during the postpartum period. We report two cases, one involving the wrist and the sacroiliac joints and the other the pubic symphysis. The difficulty of initial diagnosis in the postpartum period is emphasized. This pathology is uncommon and may begin insidiously. The sacroiliac joint is particularly at risk for postnatal sepsis, but its deep localization hinders investigations. Besides the classical obstetrical infectious assessment (blood cultures, urine culture, vaginal sample, white blood cell count and CRP) and radiological investigations, joint puncture is needed to isolate the causal infectious agent. Joint immobilization in combination with major 3-month antibiotic therapy is usually successful, generally with no sequellae.

[Infectious spondylodiscitis after a cure for genital prolapse. 5 cases]. / Spondylodiscites infectieuses après cure de prolapsus génital. A propos de 5 cas.

Bacterial osteitis of the discs and the vertebrae is rare after fixing the uterus to the promontary of the sacrum. Only 30 cases have been reported in the literature. Twelve cases were found in a Rheumatology Unit over a period of 12 years from 1975-1987. The initial symptoms of septic osteitis were low back pain or sciatica, and fever. They were confirmed by radiological evidence. Bacteriological diagnosis was obtained in every case by fine needle aspiration of the disco-vertebral space retrieving staphylococci or gram-negative bacilli. The same agent was found in blood cultures in four or five cases. Potentiating pathogenic factors include urinary tract infections, prosthetic material, and surgical errors.

[Osteoporosis in the elderly. Practical prevention and treatment]. / Ostéoporose du sujet âgé. Prévention et traitement en pratique.

A MAJOR PUBLIC HEALTH ISSUE: Osteoporosis in the elderly limits independence and quality of life. Preventive and curative treatment should be adapted to the patient's age. THERAPEUTIC OBJECTIVES: The goal of preventive like curative treatment is to reduce the risk of fracture. Risk can best be assessed from personal history of fracture or with bone densitometry. THERAPEUTIC METHODS: Non-drug methods are based on physical activity, diet, reduction of alcohol intake or smoking, and limiting the risk of falls. Drugs used include calcium, vitamin D, hormone replacement therapy and bisphosphonates. THERAPEUTIC STRATEGY: Prevention programs should focus first on non-drug methods, adapted to the patient's age. For drug regimens, hormone replacement therapy is rarely used after 70 years of age while calcium and vitamin D are widely used. Drugs inhibiting bone resorption, e.g. bisphosphonates, are added on for curative treatment. After the age of 80 years, the calcium vitamin D combination alone is useful. FOLLOW-UP: A simple surveillance scheme should include a check-up of renal function every year in patients taking bisphosphonates. It is most difficult to assess treatment efficacy on an individual basis.

[Experimental study of the stabilization capability of upper metaphyseal tibial fractures by different types of external fixators]. / Mesure expérimentale de la capacité de stabilisation des fractures metaphysiares supérieures de jambe par différents types de fixations externes.

PURPOSE OF THE STUDY: The major problem in external fixation of upper metaphyseal tibial fractures with a double-frame Hoffmann device is poor healing. With a dynamic fixation, it would be possible, with no change in technique, to compress the fracture site in a second phase, and therefore to facilitate the healing process. However, a new fixation device should not compromise the primary stability of the fixation. The aim of this experimental study on cadavers was to compare, in conditions very close to a clinical situation, the initial stabilization capability of five types of external fixation. MATERIAL: Five types of external fixators were tested on cadavers specimens: 1. a standard double-frame Hoffmann device; 2. a double-frame Hoffmann's device sagittaly reinforced with two additional anterior-posterior half-pins; 3. a type-1 axial dynamic fixation device using 6-mm conical pins; 4.a type-2 dynamic axial fixation device with 5-mm cylindrical pins; and 5. a mixed device including an lizarov-type epiphyseal fixation and a monoplane diaphyseal fixation. METHODS: The metaphyseal fracture was simulated by a transversal resection of a 20-mm segment. Specimens received by increments a load of up to 310 N, with which it was possible to determine stiffness components in valgus/varus, flexion/extension, rotation around the vertical axis and axial vertical displacement. The bone mineral content of the specimens was measured by Di Energy X-ray Absorptiometry. RESULTS: The stabilization characteristics of type-1 axial dynamic fixation were identical to those of the standard Hofmann's device in flexion/extension and in rotation as well as axially, but a greater mobility in valgus/varus was observed. The sagittal reinforcement of Hoffmann's device increased its rigidity in flexion/extension. The mixed lizarov fixation was stiffer than the standard Hoffmann's device in rotation; it was equivalent in valgus/varus and flexion/extension and less stiff in axial vertical displacement. In this study it was showed that the individual variability of bone mineral content is a negligible parameter. DISCUSSION: The experimental behaviour of the mixed Ilizarov device gives to assume that it may facilitate the healing process without endangering the primary stability of the fixation. However, this theoretical advantage should be validated in a randomized prospective clinical study.

[Erosive arthropathies in Crohn disease. Apropos of 3 cases]. / Arthropathies érosives au cours de la maladie de Crohn. A propos de 3 observations.

Three unusual cases of destructive joint lesions in patients with Crohn's disease are reported. One patient with chronic enteropathic polyarthritis developed erosions of the wrists. The other two patients had spondyloarthropathic disease; erosions developed in the right hip in one and in the hips, knees and tibiotarsal joints in the other. The few similar cases reported in the literature are reviewed.

[Still disease in the adult and in pregnancy]. / Maladie de Still de l'adulte et grossesse.

The interactions between pregnancy and adult-onset Still's disease are unclear. Nine pregnancies which occurred from 1983 through 1991 in seven women (mean age 27.7 years; range 23-40) were studied retrospectively. Five patients had one pregnancy and two had two pregnancies. Onset of the joint disease occurred before or during pregnancy. The joint disease occurred at the 5th or 6th month of the first pregnancy in two patients; one of these patients had a second pregnancy which was not associated with a flare. In five patients, onset of the joint disease occurred 4, 15, 42, 44 and 58 months before the first pregnancy, respectively; any effects of the joint disease on the pregnancy were extremely variable. 6 infants were full-term and two were premature (35 weeks); the remaining pregnancy was electively terminated; Apgar scores were normal in all eight infants, who were all male. Adult-onset Still's disease did not influence the outcome of the pregnancy in our patients; no clear-cut effects of pregnancy on adult-onset Still's disease were seen.

[Aspergillus spondylodiscitis. Apropos of 3 cases]. / Spondylodiscite aspergillaire. A propos de trois observations.

Three cases of Aspergillus discitis are reported in immunodepressed patients. Vertebrae osteomyelitis was preceded in 2 cases by pulmonary infection. The diagnosis was established in every case by disc aspiration or closed-needle-biopsy and mycological examination of the material. Aspergillus fumigatus was identified in two cases; in one case itroconazole led to recovery within three months.

[Usefulness of magnetic resonance imaging in Churg-Strauss syndrome related cardiac involvement. A case series of three patients and literature review]. / Intérêt de l'imagerie par résonance magnétique nucléaire au cours de l'atteinte cardiaque du syndrome de Churg-Strauss. Trois observations et revue de la littérature.

PURPOSE: The reported prevalence of cardiac complications is variable in patients with Churg-Strauss syndrome (15-92%) and depends on diagnostic tools. Diagnosis at early stage of heart involvement is crucial, resulting in appropriate management. METHODS: We report three patients who developed cardiac manifestations, revealing Churg-Strauss syndrome. The diagnosis of cardiac involvement was obtained using cardiac magnetic resonance imaging (MRI). RESULTS: Two patients were males and the remaining one was a female. Presenting clinical manifestations were: cardiac failure (n=1) and retrosternal pain (n=2). Laboratory findings disclosed: high blood count of eosinophils (range: 6000-11,000/mm(3)); antineutrophil cytoplasmic antibodies were positive in a single patient. Cardiac MRI demonstrated: (1) late gadolinium enhancement (n=3), involving mainly the apical and mid-cavity left ventricular segments; (2) impaired left ventricular function (n=2), mean left ventricular ejection fraction being: 51%; and (3) pericardial effusion (n=3). Outcome was favourable after institution of combined therapy with prednisone and cyclophosphamide (n=2); one patient also underwent plasma exchanges. CONCLUSION: Our case series underlines that MRI is a helpful tool in the diagnosis of Churg-Strauss syndrome-related cardiac complications. We further suggest that clinical assessment of patients with Churg-Strauss syndrome should include cardiac MRI, in order to detect cardiac involvement at an early stage; indeed, because cardiac manifestations are predictive factors of poor prognosis, diagnosis at early stages of cardiac involvement may result in improvement of patients management.