Primary high-grade myofibroblastic sarcoma arising from the pericardium.

Primary pericardial sarcomas are very rare. A 62-year-old Japanese man presented with cardiac tamponade. Echocardiography, computed tomography and magnetic resonance imaging revealed massive pericardial effusion and a large tumor in the pericardial cavity, attached to the pericardium of the left ventricular posterolateral free wall. Surgical excision of the tumor was performed and histopathological and immunohistochemical examinations identified high-grade myofibroblastic sarcoma. Because of local recurrence soon after surgery, the patient received adjuvant chemotherapy, including doxorubicin and ifosfamide, and subsequent radiotherapy. As of 6 months after completing radiotherapy, the patient was alive and no disease progression or distant metastases were evident. This may be the first report of primary high-grade myofibroblastic sarcoma arising from the pericardium.     

Frequent loss of heterozygosity in two distinct regions,8p23.1 and 8p22, in hepatocellular carcinoma

AIM: To identify the precise location of putative tumor suppressor genes (TSGs) on the short arm of chromo- some 8 in patients with hepatocellular carcinoma (HCC). METHODS: We used 16 microsatellite markers informative in Japanese patients, which were selected from 61 pub- lished markers, on 8p, to analyze the frequency of loss of heterozygosity (LOH) in each region in 33 cases (56 lesions) of HCC. RESULTS: The frequency of LOH at 8p23.2-21 with at least one marker was 63% (20/32) in the informative cases. More specifically, the frequency of LOH at 8p23.2, 8p23.1, 8p22, and 8p21 was 6%, 52%, 47%, and 13% in HCC cases. The LOH was significantly more frequent at 8p23.1 and 8p22 than the average (52% vs 22%, P = 0.0008; and 47% vs 22%, P = 0.004, respectively) or others sites, such as 8p23.2 (52% vs 6%, P = 0.003; 47% vs 22%, P = 0.004) and 8p21 (52% vs 13%, P = 0.001; 47% vs 13%, P = 0.005) in liver cancer on the basis of cases. Notably, LOH frequency was significantly higher at D8S277, D8S503, D8S1130, D8S552, D8S254 and D8S258 than at the other sites. However, no allelic loss was detected at any marker on 8p in the lesions of nontumor liver tissues. CONCLUSION: Deletion of 8p, especially the loss of 8p23.1-22, is an important event in the initiation or promotion of HCC. Our results should be useful in identi- fying critical genes that might lie at 8p23.1-22.     

Association of distal chromosome 2q with IDDM in Japanese subjects

Summary An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQB1 ^* 0303 and DQB1 ^* 0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDM13 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (< 2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13. [Diabetologia (1998) 41: 228–232] Received: 27 March 1997 and in revised form: 3 October 1997     

Pupillary reflex dilation in response to incremental nociceptive stimuli in patients receiving intravenous ketamine

Pupillometry is a non-invasive monitoring technique, which allows dynamic pupillary diameter measurement by an infrared camera. Pupillary diameter increases in response to nociceptive stimuli. In patients anesthetized with propofol or volatile agents, the magnitude of this pupillary dilation is related to the intensity of the stimulus. Pupillary response to nociceptive stimuli has never been studied under ketamine anesthesia. Our objective was to describe pupillary reflex dilation after calibrated tetanic stimulations in patients receiving intravenous ketamine. After written consent, 24 patients of our pediatric burn care unit were included. They received an oral morphine premedication (0.3 mg kg^?1) 1 h before their scheduled daily dressing change. Just before the procedure, they received 1 mg kg^?1 of intravenous ketamine. Two minutes after this bolus, tetanic stimulations of incremental intensities were performed on the arm of each patient (5–10–20–30–40–60 mA, 60 s interval between stimulations). Pupillary diameter, heart rate and movements were recorded before and after each stimulation. Tetanic stimulations were associated with changes in pupillary diameter and heart rate. The magnitude of these changes was significantly influenced by the intensity of stimulation (ANOVA for repeated measures, p?<?0.001). Movement was associated with a 32% increase in diameter (ROC curves, AUC 0.758) with 65% sensitivity and 77% specificity. In children, pupillary reflex dilation to nociceptive stimuli persists under deep sedation obtained with 1 mg kg^?1 of intravenous ketamine combined with a 0.3 mg kg^?1 oral morphine premedication, and its magnitude depends on the intensity of the stimulation. Our results confirm that pupillometry could be a relevant way to monitor nociception in anaesthetised subjects, including those receiving ketamine. Trial registration clinicaltrials.gov, NCT 02648412     

Accounting for Attribute‐Level Non‐Attendance in a Health Choice Experiment: Does it Matter?

An extensive literature has established that it is common for respondents to ignore attributes of the alternatives within choice experiments. In most of the studies on attribute non‐attendance, it is assumed that respondents consciously (or unconsciously) ignore one or more attributes of the alternatives, regardless of their levels. In this paper, we present a new line of enquiry and approach for modelling non‐attendance in the context of investigating preferences for health service innovations. This approach recognises that non‐attendance may not just be associated with attributes but may also apply to the attribute's levels. Our results show that respondents process each level of an attribute differently: while attending to the attribute, they ignore a subset of the attribute's levels. In such cases, the usual approach of assuming that respondents either attend to the attribute or not, irrespective of its levels, is erroneous and could lead to misguided policy recommendations. Our results indicate that allowing for attribute‐level non‐attendance leads to substantial improvements in the model fit and has an impact on estimated marginal willingness to pay and choice predictions.Copyright © 2014 John Wiley & Sons, Ltd.     

Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol

Antenatal exposure to glucocorticoids, amnionitis, intraamniotic interleukin (IL)-1alpha, or endotoxin can improve postnatal lung function after preterm delivery. The relationship between early lung maturation and the dose and duration of a proinflammatory stimulus has not been evaluated. The effects of proinflammatory stimuli on fetal plasma cortisol also have not been evaluated. We hypothesized that intraamniotic endotoxin would induce early lung maturation in fetal sheep without increasing fetal cortisol. Intraamniotic injections of 1, 4, 20, or 100 mg of Escherichia coli 055:beta5 endotoxin caused 2-fold increases in compliance, 4- to 5-fold increases in lung gas volumes, and 20-fold increases in alveolar saturated phosphatidylcholine (Sat PC) when given 7 d before preterm delivery at 125 d gestation. Animals treated with 20 mg endotoxin for treatment to delivery intervals of 5 h to 15 d had no significant elevations in cord plasma cortisol levels. Increases in Sat PC in lung tissue and alveolar washes were detected 2 d after endotoxin treatment and lung function improved 4 d after endotoxin treatment. Two doses of endotoxin given 3 and 7 d or 7 and 15 d before treatment resulted in lung maturation responses equivalent to single dose comparison groups without elevations in cortisol. Early lung maturation induced by intraamniotic endotoxin in fetal sheep occurred without an increase in fetal plasma cortisol, indicating that endotoxin promoted lung maturation by a mechanism independent of cortisol.     

Ursodeoxycholic acid: Mechanism of action and novel clinical applications.

Ursodeoxycholic acid (UDCA) is used in the treatment of cholestatic liver diseases, gallstone dissolution, and for patients with hepatitis C virus infection to ameliorate elevated alanine aminotransferase levels. The efficacy of UDCA treatment has been debated and the mechanisms of action in humans have still not defined. Suggested mechanisms include the improvement of bile acid transport and/or detoxification, cytoprotection, and anti-apoptotic effects. In this review, we summarize the proposed molecular mechanisms for the action of UDCA, especially in hepatocytes, and also discuss the putative future clinical usage of this unique drug.