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.

Loss-of-Function Mutations in PTPN11 Cause Metachondromatosis, but Not Ollier Disease or Maffucci Syndrome.

Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a "second hit," that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome.

Syndrome de l'intestin irritable: un diagnostic d'exclusion. [Irritable bowel syndrome: an exclusion diagnosis?].

The irritable bowel syndrome has been considered a diagnosis of exclusion and multiple diagnostic procedures were often performed in order to exclude an organic disorder. Nowadays, studies show that in young patients, who match the clinical criteria of irritable bowel syndrome and show no alarm features, the prevalence of underlying organic disorders is low, or at least not higher than in the general population. Based on these findings, current recommendations suggest that no extra diagnostic tests have to be performed in those patients, apart from the serological tests in search of celiac disease, which are recommended for patients presenting an irritable bowel syndrome with diarrhea or a mixed-type irritable bowel syndrome.

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.

Novel mutation in the tyrosine kinase domain of FGFR2 in a patient with Pfeiffer syndrome.

Mutations in the fibroblast growth factor receptor 2 (FGFR2) cause a variety of craniosynostosis syndromes. The mutational spectrum tends to be narrow with the majority of mutations occurring in either exon IIIa or IIIc or in the intronic sequence preceding exon IIIc. Mutations outside of this hotspot are uncommon and the few identified mutations have demonstrated wide clinical variability, making it difficult to establish a clear-cut genotype-phenotype correlation. To better delineate the clinical picture associated with these unusual mutations, we describe a severely affected patient with Pfeiffer syndrome and a missense mutation in the tyrosine kinase (TK) domain of FGFR2.

Prevalence of Burnout syndrome in health professionals of an onco-hematological pediatric hospital

OBJECTIVE To identify the prevalence of Burnout Syndrome in medical professionals, nurses and nursing technicians working in an Onco-Hematological Pediatric Hospital in São Paulo. METHOD An exploratory, descriptive study with cross-sectional design and quantitative approach, with a sample of 188 health professionals. Data were collected using two self-report instruments: the Maslach Burnout Inventory (MBI-HSS) which is a biosocial data form, and a non-participant observation guide. RESULTS High depersonalization for nurses (29.8%), low job performance for physicians (27.8%), and of nursing technicians (25.5%). High scores were identified in at least two domains of Burnout in 19.2% of nurses, 16.8% of nursing technicians, and 16.6% of doctors. CONCLUSION Health professionals are highly vulnerable to each of the dimensions of Burnout syndrome - namely emotional exhaustion, alienation, and low job performance/satisfaction- in the hospital work.

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.

Mutations in CEP57 cause mosaic variegated aneuploidy syndrome.

Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division.

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.

Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome.

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations.