Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug‐induced liver injury in rats

Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug‐induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver‐operating characteristic (ROC) curve, using a free‐access database where 142 hepatotoxic or non‐hepatotoxic compounds were administrated to male rats (n = 5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in‐house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. Copyright © 2014 John Wiley & Sons, Ltd.     

Arterial blood pressure response to head-up tilt test and orthostatic tolerance in nurses

Objectives

High tolerance to postural changes was examined in nurses.

Methods

Twelve female nurses and 12 healthy controls underwent a 70° head-up tilt (HUT) test for 10 min. Blood pressure (BP), heart rate (HR), pulse pressure, and hormone levels were measured. Baroreceptor sensitivity (BRS) was calculated using a sequence technique.

Results

HR increased during HUT in both subject groups, with no difference between groups. Systolic BP was rapidly increased by HUT in both subject groups, and was higher in the nurse group than in the control group during the first 2 min of HUT. Pulse pressure decreased during 1–2.5 min of HUT in the control group, but there was no decrease in the nurse group. BRS was decreased by HUT in the nurse group, while it tended to be decreased in the control group. Both during baseline and HUT, BRS was lower in the nurse group than in the control group. Plasma noradrenaline increased with HUT, and the increase was greater in the nurse group than in the control group.

Conclusions

Although nurse subjects had a lower BRS during HUT than control subjects, they were able to effectively maintain BP during HUT, suggesting that nurse subjects had higher orthostatic tolerance. The better maintenance of BP in nurse subjects appeared to be associated with a compensatory mechanism other than the arterial baroreflex and/or a hemodynamic mechanism.     

A case of eosinophilic fasciitis without skin manifestations: a case report in a patient with lupus and literature review

Clinical Rheumatology - Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin...     

Transbronchial Cryobiopsy for Miliary Tuberculosis Mimicking Hypersensitivity Pneumonitis

Miliary tuberculosis is a potentially lethal type of tuberculosis that results from the hematogenous dissemination of Mycobacterium tuberculosis bacilli. We herein describe the case of a 34-year-old man that presented with a one-month history of cough and fever, while his sputum smear results were negative. Chest computed tomography revealed bilateral centrilobular ground-glass opacification (GGO), suggestive of hypersensitivity pneumonitis; thus, bronchoscopy was performed. Cryobiopsy specimens revealed necrotic granulomas. A re-examination of sputum after bronchoscopy identified Mycobacterium tuberculosis, and miliary tuberculosis was diagnosed. A cryobiopsy might be useful for diagnosing miliary tuberculosis pathologically, particularly when miliary nodules may be masked by GGO.     

Successful Catheter Ablation for Multiple Atrial Arrhythmias in a Patient with Situs Inversus Totalis

A 70-year-old woman with situs inversus totalis underwent catheter ablation for atrial fibrillation and atrial flutter. Although her morphologic left atrium (LA) was enlarged, we performed cryoballoon ablation and liner radiofrequency ablation of the cava-tricuspid isthmus without mapping atrial arrhythmias. However, a different form of atrial tachycardia (AT) recurred. We performed catheter ablation a second time using a three-dimensional electroanatomic mapping system. AT was not terminated by the liner ablation at the roof of morphologic LA and mitral isthmus but sustained by changing the atrial activation sequence and cycle length. Multipolar mapping catheter revealed that fractionated low-amplitude potentials were densely located in a limited area of the anterior morphologic LA, and an activation map demonstrated the presence of small-circuit reentry with an extremely slow conduction at the anterior morphologic LA. A single energy application targeting the fragmented potentials successfully terminated the AT. We successfully treated multiple ATs with a complex anatomy using a three-dimensional electroanatomic mapping system.     

Streptococcus oralis Meningitis with Gingival Bleeding in a Patient: A Case Report and Review of the Literature

An 81-year-old man with a history of gingival bleeding presented with a fever, headache, and drowsiness. His mouth and full dentures were unsanitary. Laboratory tests revealed Streptococcus oralis meningitis caused by odontogenic bacteremia. We reviewed eight reported cases, including the present case, because S. oralis meningitis is rare. Our review indicated that S. oralis meningitis needs to be considered when encountering cases of a fever, disturbance of consciousness, and headache with episodes of possible odontogenic bacteremia.     

Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis

Journal of Gastroenterology - Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the...     

Enlargement of Intrathoracic Goiter with Unilateral Phrenic Nerve Paralysis Leading to Cardiopulmonary Arrest

As an intrathoracic goiter expands, it causes airway stenosis and phrenic nerve paralysis, and slight respiratory stimuli can trigger sudden life-threatening hypoventilation. A 78-year-old obese woman with a large intrathoracic goiter was found unconscious with agonal breathing in her room early in the morning. Cardiopulmonary resuscitation restored spontaneous circulation. She underwent surgical removal of the goiter; however, she required long-term mechanical ventilation because of atelectasis due to phrenic nerve paralysis. In patients with large intrathoracic goiters, difficulty breathing on exertion and diaphragm elevation on chest X-ray may be significant findings predicting future respiratory failure.     

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Journal of Gastroenterology - This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease...