Chest wall syndrome among primary care patients: a cohort study.

BACKGROUND: The epidemiology of chest pain differs strongly between outpatient and emergency settings. In general practice, the most frequent cause is the chest wall pain. However, there is a lack of information about the characteristics of this syndrome. The aims of the study are to describe the clinical aspects of chest wall syndrome (CWS). METHODS: Prospective, observational, cohort study of patients attending 58 private practices over a five-week period from March to May 2001 with undifferentiated chest pain. During a one-year follow-up, questionnaires including detailed history and physical exam, were filled out at initial consultation, 3 and 12 months. The outcomes were: clinical characteristics associated with the CWS diagnosis and clinical evolution of the syndrome. RESULTS: Among 24 620 consultations, we observed 672 cases of chest pain and 300 (44.6%) patients had a diagnosis of chest wall syndrome. It affected all ages with a sex ratio of 1:1. History and sensibility to palpation were the keys for diagnosis. Pain was generally moderate, well localised, continuous or intermittent over a number of hours to days or weeks, and amplified by position or movement. The pain however, may be acute. Eighty-eight patients were affected at several painful sites, and 210 patients at a single site, most frequently in the midline or a left-sided site. Pain was a cause of anxiety and cardiac concern, especially when acute. CWS coexisted with coronary disease in 19 and neoplasm in 6. Outcome at one year was favourable even though CWS recurred in half of patients. CONCLUSION: CWS is common and benign, but leads to anxiety and recurred frequently. Because the majority of chest wall pain is left-sided, the possibility of coexistence with coronary disease needs careful consideration.

High incidence of childhood hemolytic uremic syndrome in Switzerland is associated with indicators of livestock farming intensity

Background: Hemolytic-uremic syndrome (HUS) is a multisystem disorder associated with significant morbidity and mortality. Typically, HUS is preceded by an episode of (bloody) diarrhea mostly due to Shiga-toxin (Stx) producing Escherichia coli (STEC). The main reservoir for STEC is the intestine of healthy ruminants, mostly cattle, and recent studies have revealed an association between indicators of livestock density and human STEC infection or HUS, respectively. Nationwide data on HUS in Switzerland have been established through the Swiss Pediatric Surveillance Unit (SPSU) [Schifferli et al. Eur J Pediatr. 2010; 169:591-8]. Aims: Analysis of age-specific incidence rate of childhood HUS and possible association of Shiga-toxin associated HUS (Stx-HUS) with indicators of livestock farming intensity. Methods: Epidemiological and ecological analysis based on the SPSU data (1997-2003) and the database of the Swiss Federal Statistical Office (data on population and agriculture). Results: One hundred-fourteen cases were registered, 88% were ≤5 years old. The overall annual incidence rate was 1.42 (0.60-1.91) and 4.23 (1.76-6.19) per 100000 children ≤5 and ≤16 years, respectively (P = 0.005). Stx-HUS was more frequent compared to cases not associated with STEC (P = 0.002). The incidence rate for Stx-HUS was 3.85 (1.76-5.65) in children ≤5, compared to 0.27 (0.00-0.54) per 100'000 children 5-16 years (P = 0.002), respectively. The incidence rate of cases not associated with STEC infection did not significantly vary with age (P = 0.107). Compared to data from Scotland, Canada, Ireland, Germany, England, Australia, Italy, and Austria the annual incidence rate of HUS in young children is highest in Switzerland. Ecological analysis revealed strong association between the incidence rate of Stx-HUS and indicators of rural occupation (agricultural labourer / population, P = 0.030), farming intensity (livestock breeding farms / population, P = 0.027) and cattle density (cattle / cultivated area, P = 0.013). Conclusions: Alike in other countries, HUS in Switzerland is mostly associated with STEC infection and affects predominantly young children. However, the incidence rate is higher compared to countries abroad and is significantly correlated with indicators of livestock farming intensity. The present data support the impact of direct and indirect contact with animals or fecal contaminants in transmission of STEC to humans.

Le multiple evanescent white dot syndrome: une prédisposition génétique [Multiple evanescent white dot syndrome: a genetic predisposition?]

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS) is a benign acquired isolated chorioretinal disorder. Symptoms include photopsia, visual blur and scotomas. Ocular examination reveals multiple white dots at the level of the deep retina. A parainfectious disorder was suggested but the exact mechanism of MEWDS is still unknown. Postulating that MEWDS might be an antigen driven inflammatory reaction, we analyzed HLA subtypes in patients with MEWDS. PATIENTS AND METHODS: Sixteen patients were diagnosed with MEWDS in Lausanne from 1985 to 1994. Blood was withdrawn in 9/16 patients. HLA-A, -B and -DR were sought. RESULTS: HLA-B51 was detected in 4/9 patients (44.4%). Other HLA subtypes were detected sporadically. CONCLUSIONS: The frequency of HLA-B51 haplotype was found to be 3.7 times more elevated than in a normal control caucasian group. This suggests the possibility that MEWDS might be a genetically determined disorder as it is the case for other ocular diseases like Birdshot chorioretinopathy (HLA-A29), Harada's disease (HLA-DRMT3), acute anterior uveitis (HLA-B27) or Behçet's disease (HLA-B51). We have no explanation for the presence of HLA-B51 in both Behçet's disease and MEWDS. The association of HLA-B51 and MEWDS needs confirmation by further testing.

Lupus-like syndrome associated with statin therapy.

Statins are among the most widely prescribed drugs. An increasing number of lupus-like syndrome has recently been reported with these lipid-lowering agents. We describe a new case associated with simvastatin therapy. The presence of anti-dsDNA antibodies in the serum is for the first time reported confirming that statins may also induce a systemic autoimmune reaction. Statin-induced lupus-like syndrome is characterized by the long delay between the beginning of therapy and the skin eruption. Antinuclear antibodies may persist for many months after drug discontinuation. The causal relationship may be therefore difficult to establish, and probably many cases are unrecognized. Early diagnosis may avoid unnecessary immunosuppressive therapy.

Validity of the Katz Index to assess activities of daily living by informants in neuropathological studies

Abstract OBJECTIVE To analyze the evidences of construct validity of the Katz Index for the retrospective assessment of activities of daily living (ADL) by informants, to assist neuropathological studies in the elderly. METHOD A cross-sectional study analyzed the functional ability of ADL measure by the Katz Index, of 650 cases randomly selected from the Brazilian Brain Bank of the Ageing Brain Study Group (BBBABSG) database. Sample was divided in two subsamples for the analysis (N=325, each) and then stratified according to cognitive decline assessed by the Clinical Dementia Rating Scale (CDR). Factor analyses with calculations of internal consistency and invariance were performed. RESULTS Factor analysis evidenced a unidimensional instrument with optimal internal consistency, in all subgroups. Goodness of fit indices were obtained after two treatments of covariance, indicating adequacy of the scale for assessing ADL by informants. The scale is invariant to cognitive decline meaning that it can be used for subjects with or without cognitive impairment. CONCLUSION Katz Index is valid for the retrospective assessment of basic ADL by informants, with optimal reliability.

Impairment of JCV-specific T-cell response by corticotherapy: Effect on PML-IRIS management?

OBJECTIVE: To investigate the impact of corticosteroids (CS) on the viral-specific T-cell response, in particular the JC virus (JCV)-specific one, in an attempt to determine the optimal timing of CS in the management of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS). METHODS: A blood draw was performed before and 7 days after the administration of IV CS to 24 patients with relapsing multiple sclerosis (MS). The phenotypic pattern of T cells was determined by CCR7 and CD45RA. To assess the impact of CS treatment on proliferative response of JCV-, influenza-, and Epstein-Barr virus (EBV)-specific T cells, a thymidine incorporation proliferation assay was performed. An intracellular cytokine staining assay was performed to determine the effect of CS treatment on the production of cytokine by virus-specific T cells. JCV T-cell assays were performed only in JCV-infected patients with MS as detected by serologies (Stratify) or detection of JCV DNA in the urine by PCR. RESULTS: CS led T cells, CD4+ and CD8+, toward a less differentiated phenotype. There was a significant decrease of EBV-, influenza-, and JCV-specific T-cell proliferative response upon CS treatment. There was a significant decrease in the frequency of interferon (IFN) γ- and tumor necrosis factor (TNF) α-producing JCV-specific CD8+ T cells, but not EBV- or influenza-specific CD4+ or CD8+ T cells. CONCLUSIONS: CS have a profound impact on the virus-specific T-cell response, especially on JCV, suggesting that when CS are considered, they should not be given before the onset of clinical or radiologic signs of IRIS. Studies addressing directly patients with MS with natalizumab-caused PML are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that methylprednisolone treatment decreases the frequency of JCV-specific CD8+ T cells producing IFN-γ and TNFα, impairing control of JCV, suggesting this should be used to treat but not to prevent PML-IRIS. No clinical outcomes were measured.

Clustering of cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null mice.

AIMS/HYPOTHESIS: The metabolic syndrome comprises a clustering of cardiovascular risk factors but the underlying mechanism is not known. Mice with targeted disruption of endothelial nitric oxide synthase (eNOS) are hypertensive and insulin resistant. We wondered, whether eNOS deficiency in mice is associated with a phenotype mimicking the human metabolic syndrome. METHODS AND RESULTS: In addition to arterial pressure and insulin sensitivity (euglycaemic hyperinsulinaemic clamp), we measured the plasma concentration of leptin, insulin, cholesterol, triglycerides, free fatty acids, fibrinogen and uric acid in 10 to 12 week old eNOS-/- and wild type mice. We also assessed glucose tolerance under basal conditions and following a metabolic stress with a high fat diet. As expected eNOS-/- mice were hypertensive and insulin resistant, as evidenced by fasting hyperinsulinaemia and a roughly 30 percent lower steady state glucose infusion rate during the clamp. eNOS-/- mice had a 1.5 to 2-fold elevation of the cholesterol, triglyceride and free fatty acid plasma concentration. Even though body weight was comparable, the leptin plasma level was 30% higher in eNOS-/- than in wild type mice. Finally, uric acid and fibrinogen were elevated in the eNOS-/- mice. Whereas under basal conditions, glucose tolerance was comparable in knock out and control mice, on a high fat diet, knock out mice became significantly more glucose intolerant than control mice. CONCLUSIONS: A single gene defect, eNOS deficiency, causes a clustering of cardiovascular risk factors in young mice. We speculate that defective nitric oxide synthesis could trigger many of the abnormalities making up the metabolic syndrome in humans.

Structural variation-associated expression changes are paralleled by chromatin architecture modifications.

Copy number variants (CNVs) influence the expression of genes that map not only within the rearrangement, but also to its flanks. To assess the possible mechanism(s) underlying this "neighboring effect", we compared intrachromosomal interactions and histone modifications in cell lines of patients affected by genomic disorders and control individuals. Using chromosome conformation capture (4C-seq), we observed that a set of genes flanking the Williams-Beuren Syndrome critical region (WBSCR) were often looping together. The newly identified interacting genes include AUTS2, mutations of which are associated with autism and intellectual disabilities. Deletion of the WBSCR disrupts the expression of this group of flanking genes, as well as long-range interactions between them and the rearranged interval. We also pinpointed concomitant changes in histone modifications between samples. We conclude that large genomic rearrangements can lead to chromatin conformation changes that extend far away from the structural variant, thereby possibly modulating expression globally and modifying the phenotype. GEO SERIES ACCESSION NUMBER: GSE33784, GSE33867.

Fatal case of Epstein-Barr virus primo-infection, haemophagocytic syndrome in a 26-year-old patient treated with azathioprine for Crohn's disease: an autopsy case

Objective: A 26-year-old man with a history of Crohn's disease, treated with azathioprine since 2 years, presented an Epstein-Barr virus (EBV) primo-infection and exacerbation of digestive symptoms. Method: An ileo-colectomy was performed, which showed a fatal EBV lymphoproliferation disorder along with a haemophagocytic syndrome. EBV DNA load in the peripheral blood persisted to be high loaded during hospitalisation (479,000 copies per milliliter) despite triple antiviral treatment. Results: Autopsy revealed a systemic lymphoproliferation involving lymph nodes, gastrointestinal mucosa and solid viscera (heart, kidney, lungs, prostate, brain). This was compounded of a population of large polymorphic B cell, hypertrophic macrophages and T lymphocytes, associated to haemophagocytosis. These massive infiltrations mimicked macroscopically as ulcers in the intestinal mucosa and ranged from polymorphic with plasmocytic differentiation to monomorphic large cells. Autopsy results confirmed the absence of Crohn's disease reactivation. The EBV infection was observed in all organs within the large images of the B cell lymphoproliferations. Further postmortem investigations revealed a deficit of the azathioprine's metabolisation enzyme thiopurine methyltransferase (TPMT). Conclusion: We report and discuss herein the observations of a complete autopsy case along with the postmortem identification of the EBV infection type and TPMT mutation in a patient treated by azathioprine for Crohn's disease. Autopsy findings and further investigations helped explain the complicate clinical evolution and the fatal issue of the patient.

Syndrome de l'artère poplitée piégée [Popliteal artery entrapment syndrome].

Popliteal entrapment is a rare compression syndrome involving vascular (and neurologic) structures of the popliteal fossa. In this article we review the popliteal artery entrapment syndrome (PAES). PAES is a cause of intermittent claudication that can be, although rarely, complicated with acute limb-threatening ischemia. PAES occurs more often in young adult. Concerning pathophysiology, PAES is provoked by an abnormal relationship between popliteal artery and muscular-tendon structures within the popliteal fossa. A surgical repair is usually required to resolve mechanical compression or vascular damage.

Skin problems associated with pegylated liposomal doxorubicin-more than palmoplantar erythrodysesthesia syndrome.

Liposomal pegylated doxorubicin is an encapsulation form of doxorubicin, with an improved pharmacokinetic profile and the ability to selectively accumulate into tumor tissue. As a result, the tolerated dose of the drug can be increased, followed by a reduced incidence of neutropenia and cardiotoxicity in comparison to doxorubucin treatment. However, a common adverse dose-schedule limiting effect of the treatment is palmoplantar erythrodysesthesia syndrome. In this retrospective study we included six patients hospitalised in the University Hospital of Zurich during the last 2 years, in connection with side effects caused by pegylated liposomal doxorubicin. These patients received this chemotherapeutic agent for treatment of various malignancies such as breast cancer, ovarian cancer, mycosis fungoides and cutaneous B-cell lymphoma. Three of six patients in this study developed classical palmoplantar erythrodysesthesia, one developed palmoplantar erythrodysesthesia associated with extensive bullous disease, one developed eruption of lymphocyte recovery syndrome and one developed intertrigo like dermatitis with stomatitis. Pegylated liposomal doxorubicin induces various skin reactions including palmoplantar erythrodysesthesia syndrome. However, the exact clinical presentation might depend on pre-existing skin diseases.

Prevalence of restless legs syndrome in female blood donors 1 week after blood donation.

BACKGROUND AND OBJECTIVE: Restless legs syndrome (RLS) is a frequent condition with a prevalence of 5-15% in the general population. Clinical and genetic observations have shown that iron deficiency, highly prevalent among blood donors, can be related to RLS. The objective of this study was to assess the prevalence of RLS in female blood donors 1 week after blood donation. METHODS: One week after blood donation, 291 female blood donors, aged <50 years, self-responded to all four RLS questions defined by the 1995 International RLS study group. Blood donation rate, fatigue, aerobic capacity, menstruation, mood disorder and quality of life were also assessed along with haemoglobin and ferritin blood concentrations. RESULTS: Prevalence of RLS in female blood donors 1 week after blood donation was 6·9% (CI 95% 4·2-10·4%). Female blood donors with RLS had a higher prevalence of hyper-menorrhaea (P = 0·033) and were significantly more tired (P = 0·001). We observed no associations between RLS and number of previous donations (P = 0·409), aerobic capacity (P = 0·476), mood disorder (P = 0·169), quality of life (P = 0·356), haemoglobin (P = 0·087), and serum ferritin level (P = 0·446). CONCLUSION: Restless legs syndrome prevalence in female blood donors is not as important as described in some other studies, which could reassure blood donors. The prevalence of hypermenorrhaea and fatigue is higher in RLS blood donors. Therefore, screening for fatigue and hypermenorrhaea could be considered as these symptoms are associated with RLS in female blood donors.

Proximal 11p deletion syndrome (P11pDS): additional evaluation of the clinical and molecular aspects.

The combination of multiple exostoses (EXT) and enlarged parietal foramina (foramina parietalia permagna, FPP) represent the main features of the proximal 11p deletion syndrome (P11pDS), a contiguous gene syndrome (MIM 601224) caused by an interstitial deletion on the short arm of chromosome 11. Here we present clinical aspects of two new P11pDS patients and the clinical follow-up of one patient reported in the original paper describing this syndrome. Recognised clinical signs include EXT, FPP, mental retardation, facial asymmetry, asymmetric calcification of coronary sutures, defective vision (severe myopia, nystagmus, strabismus), skeletal anomalies (small hands and feet, tapering fingers), heart defect, and anal stenosis. In addition fluorescence in situ hybridisation and molecular analysis were performed to gain further insight in potential candidate genes involved in P11pDS.

Prévention du syndrome post-thrombotique [Prevention of post-thrombotic syndrome].

Post-thrombotic syndrome (PTS) is the most frequent chronic complication of deep vein thrombosis (DVT) with an estimated prevalence of 30-50%. PTS is a significant cause of disability, especially when complicated by venous ulcers. Therefore, PTS has important socio-economic consequences for both the patient and the health care system. Actually, the efficacy of PTS treatment is very limited; therefore, best treatment remains prevention. Compression therapy, particularly by graduated compression stockings (GCS) has a pivotal role in PTS prophylaxis. Aim of this article is to resume state of the art literature on this subject. Recommendations on PTS prevention have even been reported.

Tubular Dysfunction in Idiopathic Nephrotic Syndrome

Objectives: To evaluate the degree of tubular involvement in INS at various stage of the disease. Methods: 19 patients with INS were studied. 13 were steroid responders (group 1). 5 of them had biopsy which showed MCD. 6 patients were non responder to steroid or were steroid dependant with frequent relapses (group 2). Biopsies showed 3 FSGS and 3 MCD. They were treated with prednisone, ciclosporin and/ or mycofenolate mofetil. Protein, microalbumin (ALB), alpha-microglobulin (AMG), N-acetyl-beta-D-glucosaminidase (NAG) and creatinine (cr) were measured in each urine sample. Patients were considered in remission if prot/ cr ratio (g/mol) was < 20 (group 1a and 2a), and in relapse if the ratio was > 200 (group 1c and 2c). Some patients in group 1 had non nephrotic proteinuria (group 1b). Tubular dysfunction was defi ned by NAG/cr ratio (mg/mmol) > 0.86 or by AMG/cr ratio (mg/mmol) > 1.58. Results: Prot/cr ALB/cr NAG/cr AMG/cr Group 1a 10.3 ± 4.1 1.1 ± 1.0 0.19 ± 0.12 1.40 ± 0.97 Group 1b 60.4 ± 63.4 42.8 ± 66.7 0.39 ± 0.21 1.20 ± 0.56 Group 1c 713.3 ± 276.8 799.8 ± 534.9 2.25 ± 1.86* 4.25 ± 2.09* Group 2a 11.3 ± 6.1 4.7 ± 5.7 0.26 ± 0.19 1.18 ± 0.60 Group 2c 914.9 ± 718.6 682.9 ± 589.3 3.00 ± 2.72* 5.47 ± 4.30* Results are mean ± SD, p < 0.001 compared to group 1a and 2a No difference was observed between group 1 and group 2 neither in remission nor in relapse. Conclusions: These data indicate that tubular dysfunction occurs in INS but only in patients in relapse. In this population, tubular dysfunction was independent of the severity of the nephrotic syndrome, the treatment protocol and the histopathology.