Patients with ankylosing spondylitis have been breast fed less often than healthy controls: a case-control retrospective study.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and pelvis of young adults. On the HLA-B27 genetic background, the occurrence of AS is influenced by the intestinal microbiota. The goal of our study was to test whether breast feeding, which influences microbiota, can prevent the development of AS. METHODS: First, 203 patients with HLA-B27-positive AS fulfilling the modified New York criteria were recruited in the Department of Rheumatology, Ste Marguerite hospital in Marseilles. A total of 293 healthy siblings were also recruited to make up a control group within the same families. Second, 280 healthy controls, and 100 patients with rheumatoid arthritis and their siblings were recruited. The data collected were age, gender, number of brothers and sisters, age at disease onset, type and duration of feeding (breast or bottle). RESULTS: Patients with AS had been breast fed less often than healthy controls. In families where children were breast fed, the patients with AS were less often breast fed than their healthy siblings (57% vs 72%), giving an OR for AS onset of 0.53 (95% CI (0.36 to 0.77), p value=0.0009). Breast feeding reduced familial prevalence of AS. The frequency of breast feeding was similar in the AS siblings and in the 280 unrelated controls. However, patients with AS were less often breast fed compared with the 280 unrelated controls (OR 0.6, 95% CI (0.42 to 0.89), p<0.01). CONCLUSIONS: Our study suggests a breastfeeding-induced protective effect on the occurrence of AS. To our knowledge, this is the first study of breastfeeding history in patients with AS.

Assessment of proximal femur microarchitecture using ultra-high field MRI at 7 Tesla.

PURPOSE: The purpose of this study was to investigate bone microarchitecture of cadaveric proximal femurs using ultra-high field (UHF) 7-Tesla magnetic resonance imaging (MRI) and to compare the corresponding metrics with failure load assessed during mechanical compression test and areal bone mineral density (ABMD) measured using dual-energy X-ray absorptiometry. MATERIALS AND METHODS: ABMD of ten proximal femurs from five cadavers (5 women; mean age=86.2±3.8 (SD) years; range: 82.5-90 years) were investigated using dual-energy X-ray absorptiometry and the bone volume fraction, trabecular thickness, trabecular spacing, fractal dimension, Euler characteristics, connectivity density and degree of anisotropy of each femur was quantified using UHF MRI. The whole set of specimens underwent mechanical compression tests to failure. The inter-rater reliability of microarchitecture characterization was assessed with the intraclass correlation coefficient (ICC). Associations were searched using correlation tests and multiple regression analysis. RESULTS: The inter-rater reliability for bone microarchitecture parameters measurement was good with ICC ranging from 0.80 and 0.91. ABMD and the whole set of microarchitecture metrics but connectivity density significantly correlated with failure load. Microarchitecture metrics correlated to each other but did not correlate with ABMD. Multiple regression analysis disclosed that the combination of microarchitecture metrics and ABMD improved the association with failure load. CONCLUSION: Femur bone microarchitecture metrics quantified using UHF MRI significantly correlated with biomechanical parameters. The multimodal assessment of ABMD and trabecular bone microarchitecture using UHF MRI provides more information about fracture risk of femoral bone and might be of interest for future investigations of patients with undetected osteoporosis.

[Non-invasive investigation of muscle function using 31P magnetic resonance spectroscopy and 1H MR imaging]. / Explorations de la fonction musculaire par spectrométrie et imagerie de résonance magnétique.

31P MRS and 1H MRI of skeletal muscle have become major new tools allowing a complete non invasive investigation of muscle function both in the clinical setting and in basic research. The comparative analysis of normal and diseased muscle remains a major requirement to further define metabolic events surrounding muscle contraction and the metabolic anomalies underlying pathologies. Also, standardized rest-exercise-recovery protocols for the exploration of muscle metabolism by P-31 MRS in healthy volunteers as well as in patients with intolerance to exercise have been developed. The CRMBM protocol is based on a short-term intense exercise, which is very informative and well accepted by volunteers and patients. Invariant metabolic parameters have been defined to characterize the normal metabolic response to the protocol. Deviations from normality can be directly interpreted in terms of specific pathologies in some favorable cases. This protocol has been applied to more than 4,000 patients and healthy volunteers over a period of 15 years. On the other hand, MRI investigations provide anatomical and functional information from resting and exercising muscle. From a diagnostic point of view, dedicated pulse sequences can be used in order to detect and quantify muscle inflammation, fatty replacement, muscle hyper and hypotrophy. In most cases, MR techniques provide valuable information which has to be processed in conjunction with traditional invasive biochemical, electrophysiological and histoenzymological tests. P-31 MRS has proved particularly useful in the therapeutic follow-up of palliative therapies (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is now an accepted diagnostic tool in the array of tests which are used to characterize muscle disorders in clinical routine. As a research tool, it will keep bringing new information on the physiopathology of muscle diseases in animal models and in humans and should play a role in the metabolic characterization of gene and cell therapy.

31P magnetic resonance spectroscopy study of phosphocreatine recovery kinetics in skeletal muscle: the issue of intersubject variability.

We have analyzed by (31)P MRS the relationship between kinetic parameters of phosphocreatine (PCr) recovery and end-of-exercise status under conditions of moderate and large acidosis induced by dynamic exercise. Thirteen healthy subjects performed muscular contractions at 0.47 Hz (low frequency, moderate exercise) and 0.85 Hz (high frequency, heavy exercise). The rate constant of PCr resynthesis (k(PCr)) varied greatly among subjects (variation coefficients: 43 vs. 57% for LF vs. HF exercises) and protocols (k(PCr) values: 1.3+/-0.5 min(-1) vs. 0.9+/-0.5 min(-1) for LF vs. HF exercises, P<0.03). The large intersubject variability can be captured into a linear relationship between k(PCr), the amount of PCr consumed ([PCr(2)]) and pH reached at the end of exercise (pH(end)) (k(PCr)=-3.3+0.7 pH(end)-0.03 [PCr(2)]; P=0.0007; r=0.61). This dual relationship illustrates that mitochondrial activity is affected by end-of-exercise metabolic status and allows reliable comparisons between control, diseased and trained muscles. In contrast to k(PCr), the initial rate of PCr recovery and the maximum oxidative capacity were always constant whatever the metabolic conditions of end-of-exercise and can then be additionally used in the identification of dysfunctions in the oxidative metabolic pathway.

Gender modulates the energy cost of muscle contraction in untrained healthy subjects. A 31P magnetic resonance spectroscopy analysis.

The forearm flexor muscles of 56 untrained volunteers (26 women and 30 men) were examined by 31P magnetic resonance spectroscopy, during a rest-exercise-recovery protocol, in order to document the impact of gender on muscle energetics. Absolute concentrations of high-energy phosphate compounds, intracellular pH and rates of aerobic and anaerobic ATP production were calculated. An inverse correlation was found between body mass index (BMI) and power output in women but not in men. After correcting for power output and BMI, the measured energy cost of contraction was twice larger for women than for men. This increase was also reflected in larger ATP production from aerobic and anaerobic pathways. This higher energy cost might be explained in part by differences in local muscle mass, a higher impact of fatness, but also by a reduced metabolic efficiency of muscle fibers in untrained women.

Reduced metabolic efficiency of skeletal muscle energetics in hyperthyroid patients evidenced quantitatively by in vivo phosphorus-31 magnetic resonance spectroscopy.

Skeletal muscle energetics of seven hyperthyroid patients were investigated throughout a rest-exercise-recovery protocol using phosphorus-31 magnetic resonance spectroscopy (31P MRS) to quantitatively document in vivo the metabolic bases of impaired muscle performance in hyperthyroidism. The contributions of the main pathways of adenosine triphosphate (ATP) synthesis to energy production and proton efflux were measured and compared with results from normal muscle. At rest, a reduced concentration of phosphocreatine (PCr) was calculated for hyperthyroid patients when compared with controls, whereas pH and concentrations of inorganic phosphate (Pi) and phosphomonoesters (PME) were not different from controls. During exercise, the analysis of changes in pH and PCr concentration demonstrated that (1) at the onset of exercise, the magnitude of glycolysis activation is significantly larger for patients, resulting in a marked pH decrease; (2) the energy cost of exercise is higher for patients as compared with controls performing the same amount of work; and (3) both anaerobic and aerobic pathways are significantly more activated in the hyperthyroid group throughout the 3 minutes of exercise. During recovery, the rates of proton efflux and PCr resynthesis were similar in both groups, excluding any alteration in oxidative function and proton handling as a cause of initial glycolytic hyperactivation. The increased energy cost measured for patients during exercise evidences an increased need for energy, which is (1) probably linked to the existence of additional ATP-consuming mechanism(s), and (2) supported by hyperactivation of both aerobic and anaerobic pathways. These findings imply that, all things equal, a hyperthyroid muscle requires more energy to function than normal, and as a result is potentially more fatiguable.

Metabolic determinants of the onset of acidosis in exercising human muscle: a 31P-MRS study.

Onset of intracellular acidosis during muscular exercise has been generally attributed to activation or hyperactivation of nonoxidative ATP production but has not been analyzed quantitatively in terms of H(+) balance, i.e., production and removal mechanisms. To address this issue, we have analyzed the relation of intracellular acidosis to H(+) balance during exercise bouts in seven healthy subjects. Each subject performed a 6-min ramp rhythmic exercise (finger flexions) at low frequency (LF, 0.47 Hz), leading to slight acidosis, and at high frequency (HF, 0.85 Hz), inducing a larger acidosis. Metabolic changes were recorded using (31)P-magnetic resonance spectroscopy. Onset of intracellular acidosis was statistically identified after 3 and 4 min of exercise for HF and LF protocols, respectively. A detailed investigation of H(+) balance indicated that, for both protocols, nonoxidative ATP production preceded a change in pH. For HF and LF protocols, H(+) consumption through the creatine kinase equilibrium was constant in the face of increasing H(+) generation and efflux. For both protocols, changes in pH were not recorded as long as sources and sinks for H(+) approximately balanced. In contrast, a significant acidosis occurred after 4 min of LF exercise and 3 min of HF exercise, whereas the rise in H(+) generation exceeded the rise in H(+) efflux at a nearly constant H(+) uptake associated with phosphocreatine breakdown. We have clearly demonstrated that intracellular acidosis in exercising muscle does not occur exclusively as a result of nonoxidative ATP production but, rather, reflects changes in overall H(+) balance.

Three cases of arthritis after BCG therapy for bladder cancer.

The authors report three cases of arthritis occurring after treatment with BCG immunotherapy for bladder disease. This complication is observed in 0.5 to 1% of treated patients and affects the small joints within 1 to 5 months of the first BCG injection. The clinical outcome is favourable with non-steroidal antiinflammatory drugs. This form of arthritis may be attributable to a cross-reaction between antigenic components of cartilaginous proteoglycan and BCG, influenced by a particular HLA-DR pattern, and with the intervention of a heat shock protein.

Aetiologies of male osteoporosis: identification procedures.

Secondary causes and risk factors assume far greater importance in male osteoporosis than in female osteoporosis. The principal problem in dealing with male osteoporosis, above all in young men, is the difficulty to find a curable aetiology. Six groups of aetiologies can be drawn up: toxic causes or causes due to a change in the general state of health, drug-induced causes, renal causes, hormonal causes, exceptional causes and lastly the idiopathic form. The minimum number of investigations necessary so as to be quite sure not to overlook these various aetiologies is proposed.

Surgical management of calcific tendinitis of the shoulder: an analysis of 26 cases.

Chronic calcific tendinitis of the shoulder has good results after medical treatment in most cases. Around 10% of the patients resistant to medical treatment require surgery. We report 22 patients operated on using an open procedure. The operation included removal of the calcific deposit and an acromioplasty. The patients were rated preoperatively and postoperatively for pain, limitations in activities of daily living, range of movement and power according to a questionnaire and the Constant assessment. Globally the average score increased from 52.2 points out of 100 at the preoperative examination to 89.3 postoperatively with a mean follow up of 23 months. The most favourable results are obtained in patients with the longest interval between onset of disease and intervention (over 1 year) and with a progressive course of disease. Different techniques are discussed. Arthroscopically assisted procedures and open techniques are compared.

Magnetic resonance imaging of the wrist in rheumatoid arthritis: comparison with other inflammatory joint diseases and control subjects.

The aim of this study was to evaluate magnetic resonance images (MRI) of the wrist of rheumatoid arthritis (RA) patients. MRI and plain X-ray of the wrists were performed in 15 patients with RA, 7 patients with another chronic inflammatory joint disease (CIJD), and 10 control subjects. Patients had only minor changes on plain X-ray. Coronal T1 weighted spin echo sequences were performed before and after an intravenous pulse of gadolinium (GD). Contiguous 3 mm thick slices were obtained. Synovitis was frequently objectivized in the two groups of patients. MRI detected far more erosions and central bone geodes than plain X-ray. Geodes were frequent among controls while cortical bone erosions were frequent in patients. Most of the erosions were enhanced after GD injection in the RA patients but not in the 2 other groups. Thus MRI is not only useful in diagnosing inflammatory changes of the wrist but also in distinguishing early stage RA from other CIJD.

Antiphospholipid syndrome and factor V Leiden. Three cases with recurrent venous thrombosis.

Recurrent thrombosis is a common complication of various rheumatic disorders and is part of the definition of antiphospholipid syndrome. We report three cases of recurrent venous thrombosis due not only to antiphospholipid syndrome with a normal activated partial thromboplastin time but also to resistance to activated protein C caused by the factor V Leiden mutation. These three cases confirm that thrombotic disease is frequently multifactorial and suggest that resistance to activated protein C should be looked for routinely in patients with suggestive clinical manifestations, particularly when standard clotting tests are normal.

Serum and synovial fluid osteocalcin in rheumatic diseases.

The mechanisms involved in juxta-articular bone destruction are poorly understood. Osteocalcin or gamma-carboxyglutamic acid (GLA) protein is a small non-collagenous bone protein. It is a sensitive marker of osteoblastic bone formation. Its seric variations in the serum in such rheumatisms as rheumatoid arthritis remain unclear. Further information on local osteoblastic activity may be obtained by assaying the level of osteocalcin in the synovium. Its serum level can be evaluated by radioimmunoassay. The same method can be used in the synovial fluid. Paired serum and synovial fluid samples have been assayed from 63 patients, 33 patients with inflammatory arthritis (rheumatoid arthritis, psoriasis, chondrocalcinosis, pyogenic arthritis) and 30 patients with mechanical joint effusion (osteoarthritis, meniscal lesions). Serum levels of osteocalcin were the same in the inflammatory group (m: 8.69 +/- 0.68 ng/ml) and in the mechanical group (m: 10.2 +/- 0.67 ng/ml). In the synovial fluid, the levels of osteocalcin were significantly lower in the inflammatory group (m: 3.27 +/- 0.40 ng/ml) than in the mechanical group (m: 6.91 +/- 0.47 ng/ml). The same results were obtained with the ratio of synovial fluid osteocalcin on serum osteocalcin. There was a significant correlation between serum and synovial fluid osteocalcin and an inverse correlation between synovial fluid osteocalcin and the number of synovial fluid cells. The present study suggests that periarticular osteoblastic depression, among patients with inflammatory arthritis, is likely.

[Non invasive investigation of muscle diseases using 31P magnetic resonance spectroscopy: potential in clinical applications]. / Spectrométrie de résonance magnétique du phosphore-31 et maladies musculaires. Avantages, limites et perspectives en clinique.

P-31 MRS has become in a very short time, a major new tool to explore muscle metabolism for clinical diagnostic purposes, while offering a unique non-invasive way to conduct advanced basic research in muscle physiopathology. The comparative analysis of normal and diseased muscle remains a major requirement to further define metabolic events surrounding muscle contraction and the metabolic anomalies underlying pathologies. Also, standardized rest-exercise-recovery protocols for exploration of muscle metabolism by P-31 MRS in healthy volunteers as well as in patients with intolerance to exercise need to be developed. Our protocol is based on a short term intense exercise which is very informative and well accepted by volunteers and patients. Invariant metabolic parameters have been defined to characterize the normal metabolic response to the protocol. Deviations from normality can be directly interpreted in terms of specific pathologies in some favorable cases. In most cases, P-31 MRS provides valuable information which has to be processed in conjunction with traditional invasive biochemical, electrophysiological and histoenzymological tests. For malignant and exercise hyperthermias, P-31 MRS constitutes a diagnostic tool with 100p.cent sensitivity, as compared to contracture tests on muscle biopsies. P-31 MRS has proved particularly useful in the therapeutic follow-up of palliative therapies (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is now an accepted diagnostic tool in the array of tests which are used to characterize muscle disorders in clinical routine. As a research tool, it will keep bringing new information on the physiopathology of muscle diseases in animal models and in humans and should play a role in the metabolic characterization of gene therapy.

[Open clinical study of liposomal superoxide dismutase in severe rheumatoid arthritis. Study of a series of 7 cases]. / Etude clinique ouverte de la superoxyde dismutase liposomale dans la polyarthrite rhumatoïde sévère. Etude d'une série de 7 cas.

An open clinical study of treatment of severe rheumatoid arthritis (7 cases) with liposomal bovine copper superoxide dismutase is described. The drug was administered by intramuscular injection twice a week for three months and was well tolerated. Of the seven cases five showed good or very good results with significant amelioration. The absence of toxicity indicates that liposomal superoxide dismutase may be used in future trials with a greater number of patients.

P-31 magnetic resonance spectroscopy. A tool for diagnostic purposes and pathophysiological insights in muscle diseases.

31P Magnetic Resonance Spectroscopy (MRS) is a potent tool allowing the investigation of muscle energetics in a noninvasive manner in humans. This review details the contribution of 31P MRS to the diagnosis of metabolic myopathies and provides some clues for the use of this technique in a clinical perspective. Finally, the contribution of 31P MRS to our understanding of the physiopathology of several other diseases is highlighted.

[Pseudodementias. Clinical and pathogenic problems]. / Les pseudo-démences. Problèmes cliniques et pathogéniques.

Since the initial description by Ganser and Wernicke at the beginning of the century, two types of problems have appeared in the history of the concept of pseudo-dementia. The clinical ones have been at the root of careful descriptions of the pseudodemential syndrome by the Anglo-Saxon authors of the sixties, and have emphasized the psychiatric etiology and the reversible aspect of the disorders. The others are concerned with the pathogenic problems coming from pseudodementia and take in consideration -- on the basis of bringing together the clinical and neuropsychological sides with subcortical dementia -- the mechanisms that could be common to the physiopathology of the degenerating, demential and psychoneurotic disorders. This article analyses the concept of pseudementia in this double view, dwelling on the clinical and diagnostic problems.

[Posture and movement analysis and sports medicine]. / Analyse de la posture et du mouvement et médecine du sport.

The use of posture and movement analysis methods has developed during the past 15 years. These methods are of special interest in the field of sport sciences and have allowed to improve the understanding of physiology of posture and movement in athletes. More recently these methods have been used in the field of sport medicine. In some cases, they have helped to identify abnormalities which cannot be seen on standard clinical examination and to understand the mechanism of lesions occurring during sport activities. For the future these methods should provide useful information for understanding the physiopathology of lesions, for developing prevention of pathologies related to sport and for elaborating and assessing new treatment protocols in the field of sport medicine.

[Abdominal actinomycosis. Apropos of a case]. / Actinomycose abdominale. A propos d'un cas.

Abdominal actinomycosis is a chronic suppurating granulomatosis caused by a Gram positive germ, Actinomyces. Manifestations of this rare disease are usually pseudotumoral syndrome leading to surgical exeresis. The diagnosis is obtained from the pathology report. We report a pseudotumor of the transverse colon which invaded the greater omentum and the anterior abdominal wall. From a review of the recent literature, we observed that most papers deal essentially with a relatively new entity, pelvic actinomycosis related to prolonged use of an intra-uterine device without medical surveillance.

[Intestinal metastases of bronchopulmonary cancer. Apropos of a case]. / Métastases intestinales du cancer broncho-pulmonaire. A propos d'un cas.

Intestinal metastases are relatively frequent in lung cancer (4.7 to 14% in autopsy series) but rarely recognized clinically before severe complications due to hemorrhage or occlusion. We report a new case and review the literature. Digestive tract localizations should always be searched in case of bronchogenic cancer as prognosis is very poor. Mean survival is 4-8 weeks requiring adapted approach to the primary tumor.