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Caffeine is the most consumed stimulant worldwide, and there is great interest in understanding its neurophysiological effects. Resting-state electroencephalography (EEG) studies suggest that caffeine enhances arousal, which suppresses the spectral power of alpha frequencies associated with reduced alertness. However, it is unclear whether caffeine's neurophysiological effects vary across the human menstrual cycle.The objective of our study was to test whether caffeine's effect on EEG activity differs across the human menstrual cycle.Fifty-six female participants were randomly assigned to complete the experiment while in either their menstrual (n = 21), follicular (n = 19), or luteal (n = 16) phase. Each participant completed two study sessions in the same menstrual phase, approximately 1 month apart, during which they were administered either a caffeine pill (200 mg, oral) or a placebo pill in a counterbalanced order using a randomized double-blinded procedure. We measured their eyes-closed resting-state EEG approximately 30 min after pill administration and conducted a spectral power analysis at different frequency bands.Caffeine reduced EEG power in the alphaWe conclude that when studying caffeine's effects on resting-state EEG, participants' baseline caffeine consumption is more influential than their menstrual cycle phase. This study has important implications for the inclusion of menstruating individuals in neurophysiological studies of caffeine.

Anxiety and obesity are prevalent health concerns that are affected by diet in rodents and humans. How diet influences the development and maintenance of anxiety and obesity has been challenging to characterize, in part, due to methodological differences in chosen experimental and control diets. Within the same experiment, anxiety- and obesity-related effects were characterized in rats fed a Western diet (WD) relative to two control diets. Sixty Long-Evans rats split equally by sex were given standard diet (SD), control (i.e., high-carbohydrate) diet (HCD), or WD from weaning until sacrifice in early adulthood. Anxiety-related behavior was characterized in a modified open field test (mOFT) that allowed for the measurement of defensive behaviors (e.g., hiding within a refuge area), in addition to traditional OF measures (e.g., time in center). Both anxiety-related behaviors and hippocampal CA3 BDNF revealed specific sex differences. Neither adolescent weight gain of male and female rats, nor total body weight in early adulthood, were dependent on administration of HCD or WD, although the WD group consumed the most calories. In males only, administration of either WD or HCD resulted in elevated leptin levels relative to administration of the SD. Results indicate that SDs and HCDs are two distinct types of control diets that can affect comparability of studies and that using an SD might reveal more subtle metabolic changes. Control diet choice should be strongly considered during study design and interpretation, depending on specific research goals. Such studies should include both males and females as these effects are sex-specific.

BACKGROUND AND AIMS Reported rates of cannabis use among Canadian females are increasing. Female cannabis users progress to cannabis use disorder more rapidly than males (telescoping) and have higher rates of emotional disorder comorbidity. Addictive behaviors may change, along with mood and motivations, across the menstrual cycle (MC), particularly for females with pre-menstrual dysphoric disorder (PMDD). This study aimed to determine whether increases in depressed mood and coping motives would predict increased cannabis use pre-menstrually/menstrually, particularly among females with PMDD. We also assessed positive mood and enhancement motive ratings to establish specificity of predicted depressed mood and coping motive results. DESIGN Observational study using data collected across 32 days using electronic daily diary methods. SETTING Nova Scotia, Canada. PARTICIPANTS Sixty-nine naturally cycling female cannabis users (Mean (M) age = 29.25, Standard Deviation (SD) = 5.66) with and without retrospectively identified PMDD (via structured clinical interview) and prospectively identified PMDD (via elevated pre-menstrual depressed mood). Self-reported MC phase was validated using salivary progesterone concentrations. MEASUREMENTS Depressed/positive mood, coping-/enhancement-motivated cannabis use, and cannabis use quantity. FINDINGS Coping motives explained heightened cannabis use pre-menstrually/menstrually in those with retrospectively identified PMDD. Depressed mood explained increased cannabis use menstrually in those with retrospectively/prospectively identified PMDD. Moreover, prospectively identified PMDD significantly moderated the relationship between depressed mood and cannabis use quantity menstrually. In those with prospectively identified PMDD, positive mood and enhancement motives were associated with decreased cannabis use during the follicular/ovulatory phases. Females with versus without retrospectively identified PMDD also displayed greater overall cannabis use quantity (M [SD] = 3.44[2.84] standard joint equivalents versus 1.85[1.82], respectively; U = 277.50, P = 0.008). CONCLUSIONS Depressed mood may explain heightened cannabis use menstrually in females with pre-menstrual dysphoric disorder. Coping motives may explain heightened cannabis use pre-menstrually/menstrually in females with retrospectively identified with pre-menstrual dysphoric disorder.

Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome’s potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects alpha-diversity of the offspring stomach and fecal microbiomes. We provide evidence from beta-diversity analyses that paternal diet and maternal behavior induced community-wide shifts to the adult offspring gut microbiome. Additionally, we show that paternal HFD significantly altered the adult offspring Firmicutes to Bacteroidetes ratio, an indicator of obesogenic potential in the gut microbiome. Additional machine-learning analyses indicated that microbial species driving these differences converged on Bifidobacterium pseudolongum. These results suggest that differences in early-life care induced by paternal diet and maternal care significantly influence the microbiota composition of offspring through the microbiota-gut-brain axis, having implications for adult stress reactivity.

Background and aims Despite increases in female gambling, little research investigates female-specific factors affecting gambling behavior (GB). Although research suggests that some addictive behaviors may fluctuate across menstrual cycle phase (MCP), gambling requires further investigation. In two studies, we examined associations between MCP and three risky GBs: time spent gambling, money spent gambling, and the probability of consuming alcohol while gambling. Associations between MCP and negative affect were also examined in Study 2. We predicted that, consistent with self-medication theory, increases in negative affect (Study 2) and risky GBs (Studies 1 and 2) would occur premenstrually/menstrually relative to other phases. Methods Data were obtained from 33 female gamblers using a retrospective timeline followback procedure (Study 1) and from 20 female gamblers using a prospective 32-day, daily diary method (Study 2). In Study 2, salivary progesterone levels verified self-reported MCP validity. Results Findings revealed significant, but somewhat inconsistent, MCP effects on GBs across studies. The self-medication hypothesis was partially supported. Increases relative to another MCP(s) were found for alcohol consumption while gambling premenstrually, time spent gambling menstrually/premenstrually, money spent gambling menstrually, and negative affect premenstrually. Unexpectedly, findings more consistently indicated that GBs increased during ovulation, suggestive of enhanced reward sensitivity. Progesterone assays validated self-reported MCP (Study 2). Discussion and conclusions The results suggest a role of ovarian hormones on negative affect and GBs in females. This research could lead to the identification of female-specific factors affecting gambling and the development of more effective interventions for females with, or at risk for, problematic gambling.

Extemporaneous compounding in veterinary practice sometimes represents the only possibility for treating animals in the absence of appropriate commercial formulations, especially for particular species. This method involves manipulating pharmaceutical active ingredients to a suitable dosage and formulation for administration to humans or animals. However, veterinarians and pharmacists should focus on the risk of potential incompatibilities and instability of their preparations. To help practitioners in drug compounding, we investigated the stability of oral suspensions of tramadol, fluoxetine, and doxycycline in a commercial ready-to-use vehicle (SyrSpend). A validated high-performance liquid chromatography method was developed to assay these active pharmaceutical ingredients. The oral suspensions were prepared at two concentration ranges and were stored in amber glass bottles under refrigerated conditions and at room temperature. After 90 days, the average recovery rates were between 90% and 110% for tramadol (5 mg/mL to 30 mg/mL) and doxycycline (2 mg/mL to 10 mg/mL) without organoleptic modification. For fluoxetine, only the formulation at 2 mg/mL was stable; at higher concentrations, the uniformity of the suspension was compromised.

Background Alcohol use has been reported to fluctuate over women's menstrual cycles (MCs), with increased intake occurring premenstrually/menstrually (phases characterized by heightened negative affect) and during the ovulatory phase (a phase characterized by positive affect). This suggests women may drink for particular emotion-focused reasons at specific points in their cycles. However, no research had yet examined MC variability in drinking motives, or links between cycle-related changes in drinking motives and alcohol consumption. Methods Ninety-four normally cycling women (Mage = 22.9 years old, SDage = 4.7) completed daily diary measures (via Smartphone surveys), with questions pertaining to state drinking motives and quantity of alcohol consumed for the course of a full MC. Results Drinking motives differed by cycle phase. Women reported a slight increase in drinking to self-medicate for negative affect premenstrually, with drinking to cope peaking in the menstrual phase and declining mid-cycle. Women reported a slight increasing trend across the cycle in social motives for drinking, while enhancement motives remained relatively stable across the cycle. Cycle-related changes in drinking motives predicted increases in the quantity of alcohol consumed. Drinking to cope with negative affect predicted a greater number of drinks menstrually (days 1-5). While social motives predicted a greater number of drinks during the follicular and ovulatory phases (days 5-16), enhancement motives were unrelated to drinking quantity across cycle phase. Conclusions Clinicians should be attentive to cycle phase when treating reproductive-aged women with alcohol disorders (e.g., encouraging the use of healthier means of coping with negative affect during menses).

Does heightened stress sensitivity predispose an individual toward disease? Our Society for Neuroscience mini-symposium examines the link between stress and disease onset, exploring sex differences and whether there is an increased female predisposition. This session specifically addresses the

This study aimed to characterize and compare the efficacy profile on six fibromyalgia syndrome (FM) core symptoms associated with pharmacologic and non-pharmacologic treatments. We screened PubMed, Embase and the Cochrane Library for FM articles from 1990 to September 2012 to analyse randomized controlled trials comparing pharmacologic or non-pharmacologic treatments to placebo or sham. Papers including assessments of at least 2 of the 6 main FM symptom domains - pain, sleep disturbance, fatigue, affective symptoms (depression/anxiety), functional deficit and cognitive impairment - were selected for analysis. Studies exploring pharmacologic approaches (n = 21) were mainly dedicated to treating a small number of dimensions, mostly pain. They were of good quality but were not prospectively designed to simultaneously document efficacy for the management of multiple core FM symptom domains. Only amitriptyline demonstrated a significant effect on as many as three core FM symptoms, but it exhibited many adverse effects and was subject to early tachyphylaxis. Studies involving non-pharmacologic approaches (n = 64) were typically of poorer quality but were more often dedicated to multidimensional targets. Pool therapy demonstrated significant effects on five symptom domains, repetitive transcranial magnetic stimulation on four domains, balneotherapy on three domains and exercise, cognitive behaviour therapy and massage on two domains each. Differences between pharmacologic and non-pharmacologic approaches may be related to different modes of action, tolerability profiles and study designs. Very few drugs in well-designed clinical trials have demonstrated significant relief for multiple FM symptom domains, whereas non-pharmacologic treatments with weaker study designs have demonstrated multidimensional effects. Future therapeutic trials for FM should prospectively examine each of the core domains and should attempt to combine pharmacologic and non-pharmacologic therapies in well-designed clinical trials.

There is extensive evidence that sleep restriction alters endocrine function in healthy young men, increasing afternoon cortisol levels and modifying levels of other hormones that regulate metabolism. Recent studies have confirmed these effects in young women, but have not investigated whether menstrual cycle phase influences these responses. The effects on cortisol levels of limiting sleep to 3h for one night were assessed in two groups of women at different points in their menstrual cycles: mid-follicular and mid-luteal. Eighteen healthy, young women, not taking oral contraceptives (age: 21.8±0.53; BMI: 22.5±0.58 [mean±SEM]), were studied. Baseline sleep durations, eating habits and menstrual cycles were monitored. Salivary samples were collected at six times of day (08:00, 08:30, 11:00, 14:00, 17:00, 20:00) during two consecutive days: first after a 10h overnight sleep opportunity (Baseline) and then after a night with a 3h sleep opportunity (Post-sleep restriction). All were awakened at the same time of day. Women in the follicular phase showed a significant decrease (p=0.004) in their cortisol awakening responses (CAR) after sleep restriction and a sustained elevation in afternoon/evening cortisol levels (p=0.008), as has been reported for men. Women in the luteal phase showed neither a depressed CAR, nor an increase in afternoon/evening cortisol levels. Secondary analyses examined the impact of sleep restriction on self-reported hunger and mood. Menstrual cycle phase dramatically altered the cortisol responses of healthy, young women to a single night of sleep restriction, implicating effects of spontaneous changes in endocrine status on adrenal responses to sleep loss.

The BFI † (Bowel Function Index) is a 3-item questionnaire for assessing opioid-induced constipation (OIC). The aim of this study was to contribute to the validation of the psychometric properties of the BFI by confirming a constipation threshold, and through correlation with other validated tools: KESS (Knowles Eccersley Scott Symptom) score and generic (12-Item Short Form Health Survey, SF-12) and specific (Patient Assessment of Constipation-Quality of Life, PAC-QoL *) quality-of-life scores.A survey on opioid-requiring cancer-patients was carried out in France. A questionnaire was filled out for all patients that recorded their demographic characteristics, an assessment of their constipation using BFI and KESS scores, and included a self-assessment of quality-of-life using PAC-QoL and SF-12. Correlation of BFI with KESS, PAC-QoL, and SF-12 was investigated.Five hundred and twenty patients participated in the entire data collection with no loss. BFI was shown to be statistically correlated (r = 0.571; p 0.0001) with the KESS score and matches up with PAC-QoL and to a lesser extent with the SF-12 generic quality-of-life questionnaire. A BFI threshold of 27-29 to discriminate constipated from non-constipated patients was confirmed.This cross-sectional study in a selected population of cancer pain patients has validated the psychometric properties of the BFI. Further confirmation of the validity of the BFI could be sought through the use of longitudinal studies, and larger populations, such as non-cancer pain patients treated with opioids.This study contributes to the validation of the psychometric properties of the BFI. It confirms the BFI as an easy-to-use tool to assess constipation and its impact on quality-of-life in chronic pain patients.

Few studies have comprehensively assessed the burden associated with fibromyalgia (FM). This cross-sectional, observational study evaluates the impact of FM on patients in France and Germany.A total of 299 FM patients were recruited from 33 physician offices in France and Germany during routine visits. Patients completed a survey that included the Brief Pain Inventory-Short Form (BPI-sf), Fibromyalgia Impact Questionnaire (FIQ), EuroQol 5D (EQ-5D) and the Hospital Anxiety and Depression Scale (HADS) to describe their pain, FM and health-related quality of life (HRQOL). FM severity was defined using patients' FIQ total scores with 0 to39, 39 to59 and 59-100, representing mild, moderate and severe FM, respectively. Site staff completed case report forms using patients' medical records.Mean (standard deviation, SD) age was 54.2 (12.6); 81% of patients were women. The mean (SD) FIQ total score was 53.3 (19.6); 33% and 44% of patients reported moderate and severe FM, respectively. Most patients (91%) were receiving prescription medications for FM during the study. Patients reported a mean (SD) EQ-5D health state valuation of 0.44 (0.33) and a mean (SD) BPI-sf Pain Severity Index score of 4.9 (1.8). Forty-one percent of patients reported some level of disruption in their employment because of FM; employed patients missed a mean (SD) of 2.2 (4.6) workdays during the past 4 weeks. An increase in FM severity was significantly associated with increased pain severity, productivity loss, sleep disturbance and higher anxiety and depression (p0.0001).There is a substantial burden of illness including treatment limitations for FM patients in France and Germany.

We report here a case of chronic inflammatory bowel disease revealed by multiple large cutaneous aseptic distal necrotic ulcers.A 44-year-old male presented with high fever at 40°C associated with multiple necrotic abcesses located on the distal part of his limbs. They were treated successfully by debridment and dressings associated with antibiotics allowing complete healing after 1 month. Six months later, the patient relapsed on his left hand with a short episode of diarrhoea. A total coloscopy revealed a Crohn's disease. Systemic corticotherapy and azathioprine were administered and complete remission was obtained with a 1-year follow-up.Skin manifestations that this patient presented were atypical because of their number, size, and location, exclusively distally on the limbs. This report illustrates an unusual presentation of Crohn's disease with multiple necrotic ulcers only located on the patient extremities.

No one would argue that men and women differ, not only in features we consider to be related to reproductive function, but also in ways we do not directly connect to reproduction. Although the results of research designed to examine sex differences are always a hot topic of conversation, there are important reasons to understand as much as we can about each sex, from the level of the genome to behavior. There is strong evidence for sex differences in the incidence and presentation of most disease processes (1) in addition to a long-standing knowledge that men and women differ in the most basic metabolic processes, having serious consequences for pharmacological treatments (2). Despite this, there remains an underrepresentation of female subjects in basic research and clinical trials. For example, although the National Institutes of Health (NIH) has had an official policy to increase the inclusion of women in research since 1993, as recently as 2005, only 3% of all NIH grants have been awarded for work that considers that results may differ according to the sex of the research subjects (3). The excuse for this has always been the cyclical nature of female gonadal steroid levels, which potentially impact on sexually dimorphic measures, making the results from females inherently more variable. Nonetheless, the message that “sex matters” is slowly getting through to the research community, as evidenced by funding agencies, such as the Canadian Institutes of Health Research (http:// www.cihr-irsc.gc.ca/e/25499.html#2.1.2.), mandating that research be performed in both sexes. The study in the current issue of Endocrinology by van Nas et al. (4), in which the authors incorporated the use of powerful molecular techniques (global network and linkage analysis tools) and a solid neuroendocrine approach to understand the role of gonadal hormones and sex chromosomes in sexually dimorphic gene expression, is an excellent example. Sex differences are the result of sexual differentiation, a process that is initiated by the presence/absence of a Y-chromosomeencoded testis-determining factor called SRY in humans (Sry in mice), and then mediated by the presence of Xvs. Y-chromosomes and gonadal steroids (5). The sexual differentiation process, which begins early in development and continues throughout adolescence, results in massive sex differences in phenotype. Most of these differences are the result of natural and/or sexual selection for traits that affect the fitness of each sex differentially (6). Despite the fact that males and females differ so drastically phenotypically, they are almost identical genetically. Thus, the majority of sexually dimorphic traits are the result of sex differences in expression of the same genes. Of relevance, sex-related differences in gene expression have been noted in insects, nematodes, birds, and mammals (6). Mammalian sex differences at the transcriptional level have been known for over 20 yr, with the initial discovery that a number ofcytochromeP450enzyme(Cyp450)genes in rat liverare sexually dimorphic (7). Although not yet documented, it is likely that there are human Cyp450s that are transcribed in a sex-specific manner, thuscontributingtoobserveddifferences inCyp450substrateclearance rates (2). Recently, the application of microarray technologies has allowed for the systematic investigation of sex differences in gene expression in a number of somatic tissues in addition to liver, including kidney, muscle, adipose, whole brain, hypothalamus, myocardium,andheart (reviewed inRef.8).However, themajority of these studies have been hampered by relatively small sample size, resulting in limited power to fully explore tissue specificity in sexually dimorphic gene expression. A previous high-density expression array analysis of 23, 574 transcripts in mice (derived from an intercross between two inbred mouse strains) revealed thousands of genes in liver and adipose tissue showing sexual dimorphism, as well as hundreds in the brain (9). The authors concluded that the extent of sex differences in gene expression is larger than previously realized and that sexually dimorphic genes are highly tissue specific. This report set the stage for the present study by van Nas et al. (4), the goal of which was to investigate sexual dimorphism at the molecular level and explore gene coexpression networks that are preserved between the two sexes or are sex-specific in mice. The authors used a rigorous neuroendocrine experimental design that included intact males and females, gonadectomized (GDX) males and females, administered either placebo, dihydrotestosterone (DHT) or estradiol replacement, and GDX “four core

The conventionnal tools used for virological diagnosis include direct antigen detection by immunofluorescence (IFA) or an immunoenzymatic test (EIA), and viral isolation technique (VIT). In most cases, IFA and EIA have a slightly lower sensitivity than VIT but are also able to detect some VIT-negative samples. Results of several teams using RT-PCR technologies show that the molecular methods detect more positive cases than the conventional tools. Work is under way to expand the number of viruses detected by multiplex RT-PCR and to determine wether newly discovered viruses, such as human metapneumovirus, contribute to burden of paediatric lower respiratory infections. In conclusion, according to requirements of speed, low cost of the methods, and to achieve the highest rate of detection of respiratory viruses, the combined use of IFA and multiplex RT-PCR is today likely to be the best way to improve diagnosis of respiratory illnesses in children.

Objective:To develop evidence-based recommendations for the management of fibromyalgia syndrome.Methods:A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords “fibromyalgia”, “treatment or management” and “trial”. Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literature, a Delphi process was used to provide basis for recommendation.Results:146 studies were eligible for the review. 39 pharmacological intervention studies and 59 non-pharmacological were included in the final recommendation summary tables once those of a lower quality or with insufficient data were separated. The categories of treatment identified were antidepressants, analgesics, and “other pharmacological” and exercise, cognitive behavioural therapy, education, dietary interventions and “other non-pharmacological”. In many studies sample size was small and the quality of the study was insufficient for strong recommendations to be made.Conclusions:Nine recommendations for the management of fibromyalgia syndrome were developed using a systematic review and expert consensus.

We review the current knowledge about fibromyalgia, adding to the clinical aspects, the nosology, epidemiology and pathogenesis. The therapeutic and social management of these suffering patients are discussed.The limitations of the American College of Rheumatology classification criteria used as diagnostic criteria are discussed. Fibromyalgia is not a simple psychiatric disorder, even if psychiatric symptoms are constantly found. Based on functional brain imaging, there is some evidence pointing to an abnormal function of the supra-spinal centres for pain regulation.Fibromyalgia is a clinical autonomous entity. Physiopathology knowledge is improving, but must be confirmed by new research. Patients will take profit of multimodal individualized treatment programs, including explanations about the diagnosis. In most cases, fibromyalgia is compatible with the maintenance of a professional activity, possibly adapted to the patient. Recognized disability requiring compensation is infrequent.

We report on five cases of associated systemic sclerosis and sarcoidosis (associated connective tissue diseases). The special peculiarities of this association are emphasized with a review of the literature (14 other cases reported). The clinical aspects, the prognosis, the role of silica, the likelihood of a chance association and the need (in our opinion) to reconsider the name 'sarcoidosis' are discussed.

Low or high dosage heparin adjuvant therapy for Erysipelas (E) has become frequent, especially in France.Publications on erysipelas complications were reviewed, and 2 studies were found in which the detection of deep venous thrombosis (DVT) was systematically performed: Mahe A (6DVT/40E), and Perrot JL (4DVP/155E). We calculated the relative incidence (CRI) at 4.9 p. 100, for all studies systematically detecting the DVT (whether symptomatic or not). The other studies reported clinical DVT. CRI was at 0.7 p. 100 without heparin adjuvant therapy. CRI was at 0, not statistically significant, with low or high dosage heparin adjuvant therapy. The most frequent complications for heparin treatment were: thrombocytopenia (5.7 and 0.9 p. 100 respectively with standard and low weight heparin), and hemorrhage (less than 3 p. 100 for DVT treatment).The risk of DVT associated with E is inferior to 10 p. 100 (the level of risk for DVT is small according to consensus conferences on thromboembolism). The incidence of asymptomatic DVT is superior to that of symptomatic DVT. But we do not know if asymptomatic DVT is equivalent to symptomatic DVT. Consensus conferences on thromboembolism do not recommend the preventive administration of heparin to bedfast patients with a low risk of DVT.There is no indication of adjuvant anticoagulant therapy for erysipelas. There is no indication for systematic prophylactic anticoagulant therapy for erysipelas. Prophylactic anticoagulant therapy is used depending on other risk factors of DVT. Wearing stockings may be another indication for patients.

The main risk factors for developing chronic low back pain are related to comorbidity, the social circle of the patient and family status, the patient's concept of his health status, the patient's profession and the interval before medical treatment. For patients undergoing surgery, the same risk factors for chronic low back pain are found, with a predominance of professional status and age of the patient. On the contrary, the initial handicap and the type of management are of little importance in patient outcome. It is important to detect early the factors that risk to favour the transition to chronicity of low back pain. The effectiveness of both medical and socio-professional approaches to prevention remains to be evaluated and defined in prospective studies.

Irrespective of the underlying mechanisms, joint pain usually originates in activation of nociceptors, or free nerve endings. Nociceptive signals release a large number of neuromediators, such as substance P and the calcitonin gene-related peptide. Complex neuronal activation occurs, which involves not only local sensitization of joint nociceptors but also modifications in central pain pathways. Additional complexity results from the ability of numerous environmental, psychological, and constitutional factors to influence joint pain.

Emboli in the upper limb occur much less often than in other territories. They usually cause subacute ischaemia due to the importance of the arterial anastomotic network. Medical treatment is thus often sufficient. An analysis of the data in the literature show that medical treatment can give results comparable to surgery. Medical management should only be proposed as a complementary treatment when acute sensitivomotor acute ischaemia threatens the upper limb since priority must be placed on immediate restoration of the arterial flow.

Symphysitis of the pubis due to Streptococcus occurred after endoscopic resection of the prostate in a 69-year-old man. Despite a well conducted antibiotic regimen, signs persisted one year later and required arthrography that showed a prostato-symphysis fistula. This procedure might be used to find an explanation of certain persistent cases of symphysitis. Fistulization between the prostate and the pubic symphysis would be a new pathogenic hypothesis for symphysitis of the pubis.

The medical treatment of sclerotic arterial disease in the lower limbs is only one facet in the management of generalized arterial disease. Clinical and ancillary investigations estimate not only the severity of arterial insufficiency, but also the diffusion of arterial disease and the existence of threatening lesions. Medical treatment has 2 essential aims: to limit the progression of lesions by risk factor control and antithrombotic drugs; to improve arterial insufficiency using adapted rehabilitation and, if necessary, drugs with vasodilatating or haemorrheological properties.

SUMMARY Recent work in onr laboratory has revealed that enucleated patients produce large lateral and vertical head movements during visually guided grasping. These movements may allow them to maximise the use of retinal motion cues in planning and controlling their grasp. The aim of the present study was to determine whether the tendency to produce these adaptive head movements increases as a function of time since enucleation. We tested a group of 12 enucleated patients in whom the time between surgery and testing varied from 2 weeks to 35 years (mean = 11.2 years). These patients were required to reach out and grasp oblong blocks of different sizes at different distances. Correlational tests revealed an increase in the proportion of self-generated lateral and vertical head movements versus forward head movements as a function of post-enucleation time (r(s)(12) = 0.68, p

The authors report the cases of two patients who had chronic incapacitating heel pain unresponsive to standard therapy. They were both found to have Paget's disease of the calcaneus. The diagnosis was difficult because the typical roentgenological changes required time to develop and because no other sites were involved. Local corticosteroid injections, elimination of weight-bearing, and standard analgesic therapy were ineffective. Bisphosphonate therapy (pamidronate) given as intravenous infusions ensured prompt lasting pain relief, making ambulation possible.

In most cases, the treatment of adult's Still disease presents difficulties, in view of its undesirable side-effects. For this reason, we made an open trial of the effects of high-dose intravenous immunoglobulins (IVIg), a therapy with low iatrogen risk, and whose effectiveness in the treatment of other multisystemic diseases has been acknowledged. Seven patients suffering from adult Still's disease were given between one and eight IVIg infusions with a dose of 1 g/kg/day for two consecutive days. All seven responded positively, with clinical improvement. It lasted between 1 and 90 days in three patients, who subsequently relapsed; it has been continuing for an average of 13 months (2 to 24 months) in the other four patients. There were no clinical features making it possible to distinguish, after the trial, the patients who responded positively to intravenous immunoglobulins. This data, which needs to be confirmed with a controlled trial, provides hope of improved therapy for the one half of patients suffering from adult Still's disease who respond positively to intravenous immunoglobulins.

A case of Calmette-Guérin bacillus (BCG) infection of a knee implant during intravesical BCG-therapy is reported. The course was favorable after replacement of the implant and administration of antituberculous agents. This case of septic osteoarthritis due to the BCG is different from cases of reactive polyarthritis reported after intravesical instillations of BCG. It probably resulted from diffusion of the BCG via the bloodstream.

Four patients who developed unilateral reflex sympathetic dystrophy of a lower limb associated with a bout of sciatica due to lumbar disc herniation are reported herein. In two cases, reflex sympathetic dystrophy developed after resolution of the sciatica, whereas the two conditions were concomitant in the two other patients. In all four patients, the diagnosis of reflex sympathetic dystrophy was missed. Surgery to release the root was considered in two cases. The reflex sympathetic dystrophy resolved within 1 to 3 months in every case. In view of the incidences of these two conditions, their concomitant occurrence seems rare. To avoid unwarranted therapeutic procedures, reflex sympathetic dystrophy should be considered in patients with chronic painful manifestations accompanying root involvement.

The authors report on a 24-year old patient with Blackfan-Diamond syndrome who developed a Hodgkin's disease. This patient became transfusion-dependent at the age of 10, after an initial period of corticosensitivity, and after failure of androgens. He developed hemochromatosis despite from parenteral chelation therapy. He died of infectious complications 4 months after the diagnosis of Hodgkin's lymphoma. A review of the literature shows an increased incidence of malignancies in Blackfan-Diamond syndrome (three cases of leukemia), and in similar disease (thalassemia and sickle cell disease), but not in other patients with hemosiderosis (primitive hemochromatosis, end-stage renal failure under dialysis). Etiopathogenic hypotheses are discussed.

Alexander disease, or hypoproconvertinemia is a rare autosomic recessive coagulation disorder. The features include familial and/or personal history of bleeding, with an abnormal prothrombin period and a normal activated partial thromboplastin period. Coagulation and genetic studies allow subclassification with prognosis incidence for this disease. The authors report on a case of one family with Alexander disease.

We describe a case of tenosynovitis of tibialis posterior due to Yersinia enterocolitica occurring after injury by a plant thorn in a 55-year-old man. The illness was chronic with 2 recurrences in spite of antibiotic treatment. Full recovery was obtained only after surgical intervention. Our patient's chronic course was fostered by the persistence of thorn fragments in the infected area and the exceptionally pathogenic character of the isolated colony of Yersinia.

The oscillometric method records arterial wall oscillations during pulse wave and index pressure. Sensitivity increases with reactive hyperemia but many artefacts influence his technic. Electronic oscillography is more sensitive but has similar limits and a very high cost. This two methods detect easily arterial occlusive lesions but give only few information about the severity of arterial disease. On the opposite, Irrigraphy (impedance plethysmography) is a functional non invasive technic. Perfected by R. Sarrazin, J. F. Picard and A. Franco, it consists in recording the signal generated by electrical impedances variations related to pulse volume and heart rate. The pulse volume curve is recorded at six different positions of the leg. This method permits the evaluation of collateral vessels. Automatization of this non invasive technic increased reliability, and saves time examination.

The sickle cell trait may result in recurrent macroscopic haematuria which can cause severe anaemia. Despite normal intravenous urography and CAT, the haemorrhage probably occurs in the renal medulla due to the operative physiopathogenic conditions. A proliferative mesangial glomerulonephritis with IgG, IgA, IgM and complement deposits, which has a controversial relationship with sickle cell disease, may be discovered by renal biopsy. The severity of the anaemia may necessitate treatment with epsilon-aminocaproic acid which cures the haematuria but may provoke rhabdomyolysis. This case report is followed by a review of the literature of the different types of renal involvement in sickle cell trait and sickle cell anemia.