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At present, for adults with chronic hepatitis B virus (HBV) infection, two new analogues, entecavir (ETV) and tenofovir, are recommended as the first-line therapy by the EASL (European Association for the Study of the Liver), AASLD (American Association for the Study of Liver Diseases), and APASL (Asian Pacific Association for the Study of the Liver) guidelines. The use of pegylated interferon-α (PEG IFN-α) is recommended as the first-line therapy instead of standard IFN-α according to the above 3 guidelines. In this paper, the aim was to assess: (1) the long-term efficacy and safety as well as the resistance to ETV and tenofovir disoproxil fumarate (TDF); (2) the efficacy of PEG IFN-α; (3) the role of combination therapy with IFN plus two analogues, such as lamivudine and ETV; (4) the efficacy and safety of two analogues with cirrhosis, and (5) suppression of hepatocellular carcinoma (HCC) by ETV and IFN treatment. The results are as follows: (1) both ETV and TDF showed long-term efficacy and safety; (2) PEG IFN-α resulted in a greater decline in HBV DNA levels and a higher rate of HBeAg seroconversion; (3) combination therapy with IFN plus two analogues did not elevate the rate of sustained responses; (4) both ETV and TDF showed efficacy and safety with cirrhosis (ETV especially displayed efficacy and safety with decompensated cirrhosis), and (5) suppression of HCC was observed by ETV and IFN.

Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non–small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion–positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.

There have been several reports about associations of serum leptin or adiponectin with bone mineral density and biochemical markers of bone turnover. However, the precise roles of adipocytokines in bone metabolism have not been fully elucidated. We investigated the associations of serum level of leptin or adiponectin with bone mineral density, serum osteocalcin, and urinary N-terminal telopeptide of type I collagen (NTX) in 40 Japanese patients with type 2 diabetes mellitus. Bone mineral density was measured by using dual-energy x-ray absorptiometry at different sites (distal radius, femoral neck, and lumbar spine) and was expressed as z score. Multiple regression analysis revealed that there were significant positive correlations between serum leptin or adiponectin level and z score at the distal radius, but not at the femoral neck or the lumbar spine. Although no correlation was observed between serum leptin and serum osteocalcin, there was a significant negative correlation between serum leptin and urinary NTX, a marker of bone resorption. No correlation was observed between serum adiponectin and serum osteocalcin or urinary NTX. These results indicate that leptin and adiponectin may have a protective effect on bone metabolism in patients with type 2 diabetes mellitus.

Objective To evaluate the effectiveness of the Semmes–Weinstein monofilament examination (SWME) for diabetic peripheral neuropathy (DPN) screening at an outpatient clinic. Methods Eighty-two type 2 diabetic outpatients were questioned about 13 subjective symptoms and tested for deep reflexes. They were examined using two types of quantitative sensory testing: SWME (using 4.31/2 g and 5.07/10 g monofilaments) and vibration testing (using the C-64 quantitative tuning fork). The patients were diagnosed with DPN when two of the following three criteria from both legs were met: (1) the presence of either pain, numbness, or paraesthesia; (2) a diminished or absent ankle reflex; or (3) a scale below 4 for their vibration perception thresholds (VPT). Results The most common subjective symptoms were muscle cramps and numbness in the extremities. SWME 4.31/2 g at the great toe or the plantar aspect of the fifth metatarsal was the most useful diagnostic test for DPN, providing 60.0% sensitivity and 73.8% specificity. SWME 4.31/2 g was correlated with lower limb VPT ( P =.029) and three subjective symptoms including fainting. SWME 5.07/10 g was correlated with lower limb VPT ( P =.011), the ankle reflex ( P =.013), the knee reflex ( P =.031), and two subjective symptoms. However, the sensitivity to diagnose DPN was low (30.0%). Conclusions The abnormalities indicated by SWME correlated well with those identified by lower limb VPT. Moreover, SWME 4.31/2 g correlated with fainting, suggesting that it could detect abnormalities in the small fibers. Considering the minimal time for this examination, SWME 4.31/2 g is a useful examination in an outpatient setting along with lower limb VPT and ankle reflex testing.

Controversy remains regarding the optimal dose calculation with radioiodine therapy for patients with Graves' disease. Here, we focused our analysis on data concerning the patient's pretreatment background, an empirically set dose of radioiodine and the post-treatment thyroid function, and investigated those factors that affected the outcome. The subjects consisted of 38 patients diagnosed as having Graves' disease. All patients were hospitalized to undertake radioiodine therapy between 1989 and 1998 at our hospital. At the follow-up periods of 6-, 12-, and 36-months after therapy, we divided the patients into two groups: one group those who had hypothyroid function, and the other those who had normal or hyperthyroid function. At 6- and 12-months, 50% of the patients belonged to the hypothyroid function group, whereas at 36-months, 55% of them had hypothyroid function. Logistic regression analysis, with the objective variable being the post-treatment hypothyroidism after 12 months, revealed that the significant factor was the onset age. We suggested that the age at onset should be considered in patients with Graves' disease to determine the optional radioiodine dose for the therapy.

We sought to establish the clinical utility of the Pentax-AWS Airway Scope(®) (AWS) when used by paramedics to intubate the trachea, and to evaluate whether their performance was influenced by previous clinical experience with the Macintosh laryngoscope (ML).Twenty paramedics attempted tracheal intubation using the AWS in five patients each in the operating room. We recorded the success rate, the number of intubation attempts, and the time for intubation and adverse events, and compared these based on the paramedics' previous clinical experience with the ML. Ten paramedics had no prior clinical experience of the ML (group A) and 10 had used it on more than 30 occasions (group B).The intubation success rate was 99 % (99/100). Notably, 96 % (47/49) of intubations were achieved on the first attempt by the inexperienced paramedics in group A, compared with 64 % (32/50) by the experienced paramedics in group B (p = 0.0001). The time to intubation (mean ± SD) was significantly shorter in group A than in group B (37 ± 24 vs. 48 ± 21 s, p = 0.002). There were marked variations in the times taken to intubate, but no apparent improvement as the intubators gained experience between their first and fifth cases. No complications were encountered in either group.We found that paramedics could achieve a high tracheal intubation success rate using the AWS independent of previous airway management experience. Better intubation performance with the AWS was observed in paramedics without clinical experience with the ML.

The Airway scope® (AWS), the KingVision® (KV) and the McGRATH® (MG) are new indirect video laryngoscopes designed to facilitate effective and safe tracheal intubation under various conditions. However, there are few comparative studies as for performance in tracheal intubation attempted by inexperienced personnel. The purpose of this study was to evaluate success rates, time to intubation with use of these devices by inexperienced personnel in a simulated manikin difficult airway.

Background & Aims : Zinc (Zn) deficiency cause a variety of disorders including dermatological, neurological and immunologic abnormalities.Methods : To investigate the relation between serum levels of Zn ion and suppression of protective immunity, we measured the levels of Zn of 10 elderly patients with repeated infections (group 1), and compared with those of other 10 elderly without infections (group 2).Results and conclusions : The levels of serum Zn in group 1 were higher than those in group 2 (58.0±5.2μg/dl vs. 72.3±4.1μg/dl, P=0.0375 ; n=10, 10, respectively). Our result suggested that Zn deficiency might be a risk factor of infections in elderly.

Although bystander cardiopulmonary resuscitation (CPR) can improve survival from cardiac arrest, the reported prevalence of bystander CPR remains low in most countries. This study was performed to investigate factors affecting laypersons' willingness in performing CPR.

The Airway Scope (AWS) (Pentax-AWS, Hoya Corp., Tokyo, Japan) and the Airtraq (ATQ) (Prodol, Vizcaya, Spain) have similarities in the novel structures of their blades. In this study, we evaluated the ease of use of the AWS and ATQ compared with the Macintosh laryngoscope (ML) by inexperienced personnel in a simulated manikin difficult airway.Twenty-four fifth-year medical students with no previous experience in tracheal intubation participated in this study. We used an advanced patient simulator (SimMan(R), Laerdal Medical, Stavanger, Norway) to simulate difficult airway scenarios including cervical spine rigidity, limited mouth opening, and pharyngeal obstruction. The sequences in selecting devices and scenarios were randomized. Success rates for tracheal intubation, and the time required for visualization of the glottis, tracheal intubation, and inflation of the lungs, and the number of optimization maneuvers and dental click sounds were analyzed. The 3 different intubation devices were tested in 4 different scenarios by 24 students.Both the AWS and ATQ had very high success rates of tracheal intubation compared with the ML (AWS 100%*; ATQ 98%*; and ML 89%; *P0.05 AWS, ATQ versus ML). The time to intubation with the AWS was significantly shorter than with the ATQ and ML (AWS 11 +/- 6 seconds; ATQ 16 +/- 12 seconds; and ML 16 +/- 11 seconds; *P0.05 AWS versus ATQ, ML). The number of optimization maneuvers with the AWS was significantly lower than with the ATQ and ML. There were significantly more audible dental click sounds with the ML than with the AWS and ATQ.Both the AWS and ATQ may be suitable devices for difficult intubation by inexperienced personnel in this manikin simulated scenario. Further studies in a clinical setting are necessary to confirm these findings.

An acute in vivo model for drug-induced torsades de pointes (TdP) for use in safety evaluation of drugs was developed using dogs with acute complete atrioventricular (AV) block. In order to study the effects of anesthetic agents on the inducibility of TdP, arrhythmias were induced by programmed electrical stimulation (PES) before and after cumulative intravenous administration of quinidine under anesthesia with sodium pentobarbital, halothane, or isoflurane. Both prolongation of the QTc and the incidence of TdP were greatest in dogs anesthetized with halothane and were smallest in those given pentobarbital, suggesting that halothane is the most suitable anesthetic for this TdP model. To further validate this model, astemizole was administered intravenously to other dogs under halothane anesthesia. Astemizole at 0.3 mg/kg caused slight prolongation of the QT interval but did not induce any arrhythmias. At 1 mg/kg, however, TdP were induced in 5 of 10 animals and in an additional 2 animals at 3 mg/kg. Single and multiple ectopic beats preceded the induction of TdP, and the ectopic beats were observed in a dose-dependent manner. The plasma concentrations of quinidine in dogs with TdP were equivalent to or less than quinidine levels in humans with TdP, while those of astemizole were higher in dogs. In conclusion, this acute canine model of TdP with halothane anesthesia, complete AV block, PES, and simultaneous measurements of plasma drug concentration would be valuable for assessing the risk of drugs, especially I(Kr) blockers, to induce TdP in humans.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen of hospital-acquired pneumonia. The difference in outcome between patients with imported and newly-isolated MRSA in the ICU has not been well investigated. The aim of our study was to explore the incidence, risk factors and outcome in patients with imported and newly-isolated MRSA.

Bronchial asthma (BA) often develops in children with atopic dermatitis (AD). To clarify the usefulness of AD in infants as a predictor for the later development of BA, we examined the prevalence of and the risk factors for the later development of BA in infants with AD in four prefectures in Japan. We registered 157 infants with AD (100 boys and 57 girls) for the study and 151 infants (95 boys and 56 girls) were successfully followed up for a mean duration of 1 year. Atopic dermatitis was cured and improved in 23 and 70% of the patients, respectively, during the follow-up period. Boys developed mite allergy more frequently than did girls during the follow-up period (P