Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of Ullrich disease with distinct pathological change of muscular dystrophy

A case of Ullrich disease was presented. The patient was a 3-year-old girl with torticollis, generalized muscle weakness and acroatonia since birth. High-arched palate, protruded calcaneus, and mild contracture of proximal joints were also recognized. Intellectual development was normal. Serum level of CPK was slightly increased. In histological and histochemical examinations of quadriceps femoris muscle, proliferated connective tissue, marked variation in the muscle fiber diameter, and a lot of degenerated and regenerated fibers were recognized. Minimal injury easily causes subcutaneous hemorrhage, but no abnormality was found in the structure of collagen.     

Changes in immune regulation in response to examination stress in atopic and healthy individuals

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.     

Molecular basis of severe myoclonic epilepsy in infancy

Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies.     

Cross-cultural invariance of the Academic Expectations Stress Inventory: Adolescent samples from Canada and Singapore

We provide further evidence for the two-factor structure of the 9-item Academic Expectations Stress Inventory (AESI) using confirmatory factor analysis on a sample of 289 Canadian adolescents and 310 Singaporean adolescents. Examination of measurement invariance tests the assumption that the model underlying a set of scores is directly comparable across groups. This study also examined the cross-cultural validity of the AESI using multigroup confirmatory factor analysis across both the Canadian and Singaporean adolescent samples. The results suggested cross-cultural invariance of form, factor loadings, and factor variances and covariances of the AESI across both samples. Evidence of AESI's convergent and discriminant validity was also reported. Findings from t-tests revealed that Singaporean adolescents reported a significantly higher level of academic stress arising from self expectations, other expectations, and overall academic stress, compared to Canadian adolescents. Also, a larger cross-cultural effect was associated with academic stress arising from other expectations compared with academic stress arising from self expectations.     

Modified Epworth Sleepiness Scale in Chinese children with obstructive sleep apnea: a retrospective study

Background and objective  The purpose of this study is to assess whether Chinese children with high apnea–hypopnea index (AHI) are sleepier by a modified Epworth Sleepiness Scale (ESS). Materials and methods  Records were retrospectively reviewed. We included children who were between 3 and 12 years old, admitted for overnight polysomnogram because of suspected obstructive sleep apnea syndrome (OSAS). A modified ESS was used to assess excessive daytime sleepiness (EDS) of the children. Results  One hundred ninety-two Chinese children were included. Children with high AHI, defined as AHI > 5.0, were sleepier than children with AHI less than or equal to 5. After adjustment by age, gender, and obesity, children with high AHI remained significantly sleepier. Modified ESS was significantly correlated with AHI (rho = 0.124, 95% CI = 0.004–0.281). Modified ESS score of >8 was the best cutoff point with the sensitivity and specificity of 0.29 and 0.91, respectively. The odds ratio of children with modified ESS > 10 having high AHI was 4.231 (95%CI = 1.248 to 14.338) and children with modified ESS > 8 had the highest odds ratio, 4.295(95%CI = 1.66 to 11.1), of having high AHI. Conclusion   Chinese children with high AHI appear to be sleepier than children with low AHI. Children with suspected OSAS and high modified ESS, i.e., ESS > 8, had significantly higher odds ratio of having high AHI. Increased sleepiness is a specific but not a sensitive symptom in snoring children with high AHI. Screening for EDS in snoring children may help us identify those with high AHI and prioritize the management of those children. All authors worked and the study was carried out in Kwong Wah Hospital in Hong Kong. There was no conflict of interest and no specific source of funding for the study.