Foot orthotics decrease pain but do not improve gait in rheumatoid arthritis patients

OBJECTIVES: Prescribing foot orthotics in rheumatoid arthritis patients with symptomatic forefoot involvement is a standard practice. However, limited research has been reported regarding gait and pain improvement with the use of foot orthotics. PATIENTS AND METHODS: Sixteen patients (13 F, 3 M; mean age: 52 +/- 12 years) with metatarsalgia due to rheumatoid arthritis were included in this prospective, randomized with crossover study, and received foot orthotics. At 1 month follow-up, space and time gait variables with and without foot orthotics were assessed by Bessou's locometer; pain was assessed by visual analogue scale (VAS). RESULTS: Pain levels significantly decreased (P = 0.008) by wearing foot orthotics. Despite a significant step length increase (P = 0.05) with orthotics, there was no significant improvement of stride length, cadence, or walking speed which was the main assessment criterion. CONCLUSIONS: Wearing foot orthotics improves pain, but not sufficiently to improve gait in rheumatoid arthritis patients with metatarsalgia. Foot orthotics improved comfort levels because of a decrease in pain, but was not sufficient to correct gait.     

Infevers: an evolving mutation database for auto-inflammatory syndromes

The Infevers database (http://fmf.igh.cnrs.fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (FMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is FMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation.     

HIV therapy after treatment interruption in patients with multiple failure and more than 200 CD4+ T lymphocyte count

The aim of the study was to investigate the safety and efficacy of a salvage therapy initiated after interrupting treatment in patients with virological failure and more than 200 CD4(+) T lymphocyte count. In this prospective study, 77 patients who received failing regimens had stopped completely all medication for 3 months before starting an optimised regimen consisting of 3-5 drugs. Patients were tested for HIV resistance before and after treatment interruption. Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 1.1 log(10), a median decrease in CD4(+) T cell count of 136 x 10(6)/L and five clinical events related to HIV, but no AIDS-defining event. Eighty-seven percent of patients showed a shift from a drug resistant genotype to a wild-type genotype based on the major resistance mutations. Forty-seven percent of patients with a genotype shift reached fewer than 200 HIV RNA copies/ml of plasma 6 and 12 months after treatment resumption whereas none of those without a genotype shift did so (P = 0.03). However, the genotypic shift was not associated with a sustained virological response by multivariate analysis. The use of a new therapeutic class of compound in the salvage regimen was the only predictor of the sustained virological response. Salvage therapy with 3-5 drugs after interrupting treatment for 3 months can be a safe and effective strategy provided the HIV disease is not too advanced. Randomised trials in this population are needed to assess the clinical benefit of this strategy.     

Partial posttraumatic stress disorder revisited

BACKGROUND: It is thought that the decision rule for a positive diagnosis of Posttraumatic Stress Disorder (PTSD) may be too restrictive, leaving too many victims of a trauma out in the cold for care, compensation, etc. Several authors have proposed the concept of Subthreshold or Partial PTSD (PPTSD). This concept considers that a subject may present a number of symptoms below threshold for criteria C or D (subthreshold syndromes) and may even present without any symptom for one or more of the criteria B, C and D (partial syndromes). METHOD: Data have been collected by means of the Composite International Diagnostic Interview (CIDI) PTSD-module, in a group exposed to two different traumatic events (130 fire victims and 55 car accident victims). The syndrome patterns has been assessed by means of hierarchical class analyses. Each of the criteria B, C and D has been analyzed separately, showing the symptom patterns as hierarchically order clusters. RESULTS: Depending on the threshold used for criterion C (i.e. 3 or 2 symptoms), 18.4 and 22.7% of the subjects respectively satisfy the criteria for PTSD. 8.7% of the subjects show subthreshold syndromes. 60.7% of the subjects show partial syndromes and 16.7% of the subjects have partial syndromes while fulfilling criterion F, i.e. a clinically significant impairment in functioning. CONCLUSIONS: The results show a considerable number of partial and subthreshold syndromes. It is argued that subthreshold syndromes and partial syndromes, which fulfill criterion F, should be regarded as specific nosological categories or as specified PTSD subcategories, i.e. subsyndromal or partial PTSD.     

The anti-inflammatory response dominates after septic shock: association of low monocyte HLA-DR expression and high interleukin-10 concentration

The diminished expression of HLA-DR on monocytes has been proposed as a reliable marker of immunosuppression occuring during septic shock. The objective of the present observational study was to establish the time-dependent relation between plasma cytokines interleukin (IL)-10, transforming growth factor (TGF)-beta1, tumor necrosis factor (TNF)-alpha and monocyte HLA-DR expression in 38 adult patients with septic shock. All patients (mortality at 28 days: 42%, mean admission SAPS II score: 54) had decreased HLA-DR expression. This expression was significantly lower in non-survivors at all time points. All patients had elevated IL-10 concentrations, the highest values were found in non-survivors. IL-10 was the sole cytokine to significantly correlate with HLA-DR expression (r: -0.6, p<0.001). TNF and TGF values did not provide any prognostic information. TGF levels from septic patients were even found to be decreased in comparison with normal values which suggested that IL-10 is likely more important than TGF regarding the immunosuppressive properties of septic patients' plasma. This preliminary work showed that, at the systemic level, the anti-inflammatory response dominated after septic shock. Monocyte HLA-DR expression and IL-10 measurement deserve to be determined in parallel in a larger longitudinal study. They might constitute helpful indicators for staging patients and making a decision about whether to institute a therapy with molecules able of reversing sepsis-induced immunosuppression.     

Reproductive immunology 2003: reassessing the Th1/Th2 paradigm?

We briefly review the history of concepts (some of which are still valid) which have lead to the present situation where pregnancy is viewed as being a Th2 phenomenon. We recall some of the early evidence which has been taken as supporting the general validity of this concept in murine and human pregnancy. We then recall some of the recent data dealing with "newer" cytokines and the role of uterine natural killer (NK) cells at the feto-maternal interface which fit neither with a steady-state concept nor with inflammatory cytokines, being solely "bad guys" as the paradigm would predict, nor with the concept of reduction of NK "activity" being required for successful pregnancy. As an example of the newer complexity, we briefly recall some of our recent micro-array studies in mice, and describe briefly our most recent data in human pointing out the importance of the tripod IL-12/IL-18/NK in successful or failed pregnancy in human, perhaps under IL-15 control. We conclude by a repeated warning against the so-called rationales of lymphocyte alloimmunization for therapy of recurrent spontaneous abortion and improvement of implantation rates.     

Characterization of iron deposition in endometriotic lesions induced in the nude mouse model

BACKGROUND: Pelvic endometriotic lesions are often laden with hemosiderin. In order to investigate the potential source of such iron deposits, we examined whether the seric and erythrocyte fractions of menstrual effluent might influence the occurrence of iron deposition within lesions in a murine model of endometriosis. METHODS: Endometriosis was induced in 57 nude mice by intraperitoneal injection of unfractionated human menstrual effluent, endometrial fragments plus serum, endometrial fragments plus erythrocytes or endometrial cell fraction alone. The number of implants, histologic aspect, proliferative activity and iron deposition in lesions was assessed. RESULTS: On day 5, lesions were evidenced in all 10 mice receiving menstrual effluent, in 9/13 of those injected with the cellular fraction, in 10/13 with the cellular fraction plus serum and in 10/12 with the cellular fraction plus erythrocytes. Iron conglomerates were observed at the interface between the lesion and peritoneum when menstrual effluent (47 deposits/mm(2)) and the cellular fraction with erythrocytes (20 deposits/mm(2)) were injected, but were scarce when the cellular fraction was injected without erythrocytes, either alone (4 deposits/mm(2)) or with serum (2 deposits/mm(2)) (P < 0.05). CONCLUSIONS: Iron conglomerates, typically found in the stroma of endometriotic lesions, were induced by erythrocytes present in menstrual effluent. This may be one of the factors triggering oxidative damage and chronic inflammation.     

Distraction from chronic pain during a pain-inducing activity is associated with greater post-activity pain

The aim of this study was to investigate the effects of distraction from pain during and after a pain-inducing lifting task in a sample of chronic low back pain (CLBP) patients. Fifty-two CLBP patients (25 males, 27 females; mean age=46.30 years) performed a pain-inducing lifting task twice, once alone and once with a simultaneous cognitive distraction task. The results revealed that (1) distraction had no effect upon self-reported pain during the lifting task, (2) distraction had a paradoxical effect of more pain immediately after the lifting task, (3) both pain-related fear and pain catastrophizing did not moderate the effects of distraction on pain, but (4) catastrophic thinking about pain during the lifting task was related to more vigilance to pain and less engagement in the distracting task. Further investigation of the catastrophizing data showed that the effect of catastrophizing about pain during the lifting task on the cognitive distraction task was mediated by the amount of attention paid to pain. Clinical implications of these findings are discussed.     

Trends in the treatment of orthopaedic prosthetic infections

The most commonly used therapy for prosthetic joint infection is a two-stage prosthetic exchange separated by 6 weeks of intravenous antibiotic therapy. This often results in long periods of hospitalization, morbidity, severe functional impairment and sometimes increased mortality. Therefore novel and challenging therapeutic approaches have been attempted, particularly in hip prosthetic infection. This includes, whenever possible, according to the type of microorganism, antibacterial susceptibility and clinical presentation (including age and comorbidities): (i) less aggressive surgical techniques (debridement and prosthesis retention, or re-implantation with a single-stage exchange arthroplasty); and (ii) antibiotic combinations active against biofilm-associated bacteria, including rifampicin (particularly with quinolones) with excellent bio-availability which allow prolonged and efficient oral therapy.