Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge

Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3alpha,6,7alpha,12alpha-tetrol (3alpha,6,7alpha,12alpha-tetrahydroxy-5beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.

[Body-packer ; body-stuffer - a medical challenge]

Since the seventies, the practice of drug smuggling in the form of body packing has increased in the Western world. The goal of our study was to present an algorithm for the safe management of intracorporal drug transport based on clinical experience and current evidence. The retrospective study, conducted over the past four years in our hospital prison, analyzes and discusses the diagnostic and therapeutic concepts. Thirty-four patients hospitalized 37 times in a 48-month period were included. In 28 patients drug packages were identified. Only two patients suffered from serious complications. The study demonstrates that following a specifically designed management algorithm based on clinical experience and principles of evidence-based medicine can optimize risk management, improve quality assurance and patient safety.

Neck treatment and shoulder morbidity: Still a challenge

Shoulder complaints and functional impairment are common sequelae of neck dissection. This is often attributed to injury of the spinal accessory nerve by dissection or direct trauma. Nevertheless, shoulder morbidity may also occur in cases in which the spinal accessory nerve has been preserved. In this article, the physiology and pathophysiology of the shoulder are discussed, followed by a consideration of the impact of neck dissection on shoulder complaints, functional impairment, and quality of life. Finally, rehabilitation will be considered. © 2010 Wiley Periodicals, Inc. Head Neck, 2010.

"Drug mules" as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

PURPOSE: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox(®)) in the detection of internal cocaine containers. METHODS: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16-45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT=35, nDR=70, nLSDR=30. An overall calculation of all "drug mules" and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. RESULTS: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. CONCLUSIONS: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

Malignant pheochromocytomas and paragangliomas: a diagnostic challenge

Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare disorders arising from the adrenal gland, from the glomera along parasympathetic nerves or from paraganglia along the sympathetic trunk. According to the WHO classification, malignancy of PCCs and PGLs is defined by the presence of metastases at non-chromaffin sites distant from that of the primary tumor and not by local invasion. The overall prognosis of metastasized PCCs/PGLs is poor. Surgery offers currently the only change of cure. Preferably, the discrimination between malignant and benign PCCs/PGLs should be made preoperatively.

Mannitol dry powder challenge in comparison with exercise testing in children

Rationale Mannitol dry powder (MDP) challenge is an indirect bronchial provocation test, which is well studied in adults but not established for children. Objective We compared feasibility, validity, and clinical significance of MDP challenge with exercise testing in children in a clinical setting. Methods Children aged 6–16 years, referred to two respiratory outpatient clinics for possible asthma diagnosis, underwent standardized exercise testing followed within a week by an MDP challenge (Aridol™, Pharmaxis, Australia). Agreement between the two challenge tests using Cohen's kappa and receiving operating characteristic (ROC) curves was compared. Results One hundred eleven children performed both challenge tests. Twelve children were excluded due to exhaustion or insufficient cooperation (11 at the exercise test, 1 at the MDP challenge), leaving 99 children (mean ± SD age 11.5 ± 2.7 years) for analysis. MDP tests were well accepted, with minor side effects and a shorter duration than exercise tests. The MDP challenge was positive in 29 children (29%), the exercise test in 21 (21%). Both tests were concordant in 83 children (84%), with moderate agreement (κ = 0.58, 95% CI 0.39–0.76). Positive and negative predictive values of the MDP challenge for exercise-induced bronchoconstriction were 68% and 89%. The overall ability of MDP challenge to separate children with or without positive exercise tests was good (area under the ROC curve 0.83). Conclusions MDP challenge test is feasible in children and is a suitable alternative for bronchial challenge testing in childhood. Pediatr. Pulmonol. 2011; 46:842–848. © 2011 Wiley-Liss, Inc.

The challenge of triaging chest pain patients: the bernese university hospital experience

Accurate diagnosis of the causes of chest pain and dyspnea remain challenging. In this preliminary observational study with a 5-year follow-up, we attempted to find a simplified approach to selecting patients with chest pain needing immediate care based on the initial evaluation in ED. During a 24-month period were randomly selected 301 patients and a conditional inference tree (CIT) was used as the basis of the prognostic rule. Common diagnoses were musculoskeletal chest pain (27%), ACS (19%) and panic attack (12%). Using variables of ACS symptoms we estimated the likelihood of ACS based on a CIT to be high at 91% (32), low at 4% (198) and intermediate at 20.5-40% in (71) patients. Coronary catheterization was performed within 24 hours in 91% of the patients with ACS. A culprit lesion was found in 79%. Follow-up (median 4.2 years) information was available for 70% of the patients. Of the 164 patients without ACS who were followed up, 5 were treated with revascularization for stable angina pectoris, 2 were treated with revascularization for myocardial infarction, and 25 died. Although a simple triage decision tree could theoretically help to efficient select patients needing immediate care we need also to be vigilant for those presenting with atypical symptoms.