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Entecavir ( ETV) is reported to result in suppression of hepatitis B virus DNA ( HBV DNA) replication with minimal drug resistance. However, information on the long-term effect of such therapy on serum hepatitis B surface antigen ( HBs Ag) level and elimination of HBs Ag is not available. ETV therapy was started in 553 nucleos(t)ide-naïve patients with chronic hepatitis B infection ( HBe Ag positive: 45%) in our hospital. Serum HBs Ag levels were measured serially by the Architect assay. The median baseline HBs Ag was 2180 IU/mL (0.12-243 000 IU/mL), and median follow-up period was 3.0 years, with 529, 475, 355, 247 and 163 patients followed-up for 1, 2, 3, 4 and 5 years, respectively. At year 5, the mean log HBs Ag decline from baseline was −0.48 log IU/mL, and the cumulative HBs Ag clearance rate was 3.5%. Multivariate analysis identified HBV DNA level at baseline (<3.0 log copies IU/mL, odd ratio = 10.2; 95% confidence interval = 1.87-55.5, P = 0.007) and HBsAg level (<500 IU/mL, odd ratio = 29.4; 95% confidence interval = 2.80-333, P = 0.005) as independent predictors of HBs Ag seroclearance. These results indicate that although serum HBs Ag level declines gradually during ETV therapy, HBs Ag seroclearance remains a rare event. [ABSTRACT FROM AUTHOR]

An impact of serum hepatitis B virus (HBV) DNA on hepatocarcinogenesis has not been investigated in a cohort of patients with non-B, non-C cirrhosis. Eighty-two consecutive Japanese patients with cirrhosis, who showed negative hepatitis B surface antigen and negative anti-hepatitis C virus, were observed for a median of 5.8 years. Hepatitis B virus core (HBc) region and HBx region were assayed with nested polymerase chain reaction. Both of HBc and HBx DNA were positive in 9 patients (11.0%) and both were negative in 73. Carcinogenesis rates in the whole patients were 13.5% at the end of the 5th year and 24.6% at the 10th year. The carcinogenesis rates in the patients with positive DNA group and negative DNA group were 27.0% and 11.8% at the end of the 5th year, and 100% and 17.6% at the 10th year, respectively ( P = 0.0078). Multivariate analysis showed that men ( P = 0.04), presence of HBc and HBx DNA (hazard ratio: 8.25, P = 0.003), less total alcohol intake ( P = 0.010), older age ( P = 0.010), and association of diabetes ( P = 0.005) were independently associated with hepatocellular carcinogenesis. Existence of serum HBV DNA predicted a high hepatocellular carcinogenesis rate in a cohort of patients with non-B, non-C cirrhosis. [ABSTRACT FROM AUTHOR]

Nineteen species of Braconidae have been reared from seeds of Dipterocarpaceae (mainly Shorea species) in West Malaysia. Eleven new species (Brachistinae: Schizoprymnus mesocaudus sp. nov.; Schizoprymnus torreadoroides sp. nov.; Braconinae: Bracon nitidisoma sp. nov.; Bracon rugulifer sp. nov.; Syntomernus shoreatus sp. nov.; Spermatobracon triangulornatus sp. nov.; Cheloninae: Ascogaster cornifera sp. nov.; Ascogaster lamellifera sp. nov.; Phanerotoma divergens sp. nov.; Microgastrinae: Apanteles hemiaurantius sp. nov.; Apanteles striatus sp. nov.) and one new genus (Spermatobracon gen. nov.; type species: Spermatobracon triangulornatus gen. nov. and sp. nov.) are described and illustrated. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) often recurs after surgical or medical treatment.Methods: Eighty consecutive patients with HBV-positive cirrhosis and HCC who underwent potentially curative ablation for HCC were analyzed. Eleven patients received long-term interferon (IFN) therapy. HBV DNA was quantified at the time of HCC treatment. A DNA value of <6.0 log copies/ml was considered low.Results: Initial DNA was low in 39 and high in 41 patients. HCC recurrence rates in the low DNA group and high DNA group were 46.9% and 82.6% at the fifth year, and 73.5% and 91.3% at the tenth year, respectively (P = 0.0103). Similarly, recurrence rates after treatment of HCC in the normal aspartate aminotransferase (AST) group (<38 IU/l, n = 42) and abnormal AST group (n = 38) were 50.6% and 84.0% at the fifth year, and 71.3% and 100% at the tenth year, respectively (P = 0.0003). Six of the 38 patients with abnormal AST, and 5 of 42 patients with normal AST, received IFN after confirmation of tumor ablation. In the subgroup of abnormal AST, tumor recurrence rates in the IFN and untreated groups were 16.7% and 37.9% at the end of the first year, 16.7% and 60.1% at the second year, and 16.7% and 83.4% at the third year, respectively (P = 0.0139). Multivariate analysis revealed that IFN significantly reduced the recurrence rate (hazard ratio = 0.21, P = 0.037) even after adjusting for background characteristics.Conclusions: IFN was inferred to decrease tumor recurrence after treatment of HCC in patients with HBV-related cirrhosis, especially in the subgroup with high AST. [ABSTRACT FROM AUTHOR]

The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2'-5' oligoadenylate synthetase, dsRNA-activated protein kinase and MxA protein. Among these, MxA protein is assumed to be the most specific surrogate parameter for IFN action. This study was performed to elucidate whether a single nucleotide polymorphism (SNP) (GIT at nt-88) in the promoter region of the MxA gene influences the response to IFN therapy in patients with chronic hepatitis C virus (HCV) infection. Polymorphisms of the MxA gene in 235 HCV patients were determined by polymerase chain reaction- restriction fragment length polymorphism. The frequency of SNP was compared between sustained-responders (n = 78) and nonresponders (n = 1 57), as determined by biochemical and virological responses to IFN. Multivariate analysis showed that among all patients, HCV genotype, HCV RNA level and the SNP of the MxA gene were independent and significant determinants of the outcome of IFN therapy [odds ratio 3.8 (95% confidence interval 2.0-7.0), P < 0.0001; 0.27 (0.15-0.50), P < 0.0001; 1.8 (1.0-3.4), P - 0.0464, respectively]. Furthermore, among patients with a low viral load (≤2.0 Meq/mL), MxA-T-positive patients were more likely to show a sustained response compared with MxA-T- negative patients [2.87 (1.3-6.3); 62% vs 36%; P = 0.0075]. Our findings suggested that the SNP of the MxA gene is one of the important host factors that independently influences the response to IFN in patients with chronic HCV infection, especially those with a low viral load. [ABSTRACT FROM AUTHOR]

Background: Although pegylated interferon (IFN) is now used in many countries as a standard therapy for chronic hepatitis C, the efficacy and safety of combination therapy of high-dose interferon alpha-2b induction with ribavirin are not fully evaluated, especially in Japanese patients infected with hepatitis C virus (HCV) genotype 1b with a high viral load.Methods: Patients ( n = 83) received daily, high-dose induction therapy of interferon alpha-2b (6 million units [MU] once daily for 2 weeks), followed by 6 MU three times weekly for 22 weeks. Oral ribavirin (800 or 600 mg/day) was given daily for 24 weeks, and then the patients were followed up for 24 weeks.Results: Of the 83 patients, 67 (81%) had a biochemical response (BR), and 37 (45%) achieved a sustained BR (SBR). Virologic response (VR; undetectable serum HCV RNA level by polymerase chain reaction [PCR]) was noted in 55 (66%) patients, and sustained VR (SVR) in 16 (19%) patients. Baseline viral load did not influence treatment outcome. There was no significant difference in treatment outcome among treatment-naIve patients, relapsers, and nonresponders to previous IFN monotherapy. Multivariate analyses identified serum ribavirin concentrations at week 8 of therapy (odds ratio [OR], 23.7; 95% confidence interval [CI], 1.84-61.1; P = 0.015) and negativity for serum HCV RNA at week 8 (OR, 22.5; CI, 1.76-57.5; P = 0.017, respectively) as two significant and independent predictors of SVR.Conclusions: The efficacy of 24-week combination therapy of high-dose IFN alpha-2b induction and ribavirin deserves attention in HCV genotype 1b patients with a high viral load, especially in nonresponders to previous IFN monotherapy and patients with a very high viral load. [ABSTRACT FROM AUTHOR]

Background: Mutations in the precore region and core promoter were compared between patients with acute and chronic hepatitis B. Methods: There were 69 patients with acute self-limited hepatitis B and 210 with chronic hepatitis B who had been followed for >15 years. The hepatitis B virus (HBV) of genotypes A, B and C was detected in 14 (23%), 8 (13%) and 28 (45%) of the patients with acute self-limited hepatitis, respectively, in contrast to 11 (5%), 25 (12%) and 167 (80%) of those with chronic hepatitis. Results: At presentation, hepatitis B e antigen (HBeAg) in serum was the more common (82% versus 65%, P < 0.05), and the wild-type sequences of the precore region (100% versus 74%, P < 0.001) and core promoter (88% versus 36%, P < 0.00001) were more frequent in the 50 patients with acute self-limited hepatitis than the 203 patients with chronic hepatitis B who were infected with HBV of genotype A, B or C. Wild-types of both the precore region and core promoter persisted in acute self-limited hepatitis, while they decreased from 28% to 10% in chronic hepatitis over the course of >15 years. Conclusion: HBV with the wild-type sequences of the precore region and core promoter prevails in patients with acute self-limited hepatitis, unlike in patients with chronic hepatitis. [ABSTRACT FROM AUTHOR]

Although recent papers have suggested that psychological factors are implicated in the experience of infertility, few studies have assessed this relationship in a sample of Japanese infertile women. This study was carried out in order to clarify whether Japanese infertile women experience emotional distress. A cross-sectional questionnaire study was performed to assess the psychological states of 101 infertile women compared to 81 healthy pregnant women. The hospital anxiety and depression scale (HADS) and the profile of mood states (POMS) were administered. These questionnaires produced scores for depression/dejection, anxiety, aggression/hostility, lack of vigour, fatigue, tension anxiety, and confusion. The HADS and the POMS scores of infertile women were significantly higher than those of pregnant women, except for fatigue score. Infertile women with positive HADS indicating emotional disorders (39/101, 38.6%) were significantly (P = 0.0008, chi(2) test) more than those of pregnant women (13/81, 16.0%) when the threshold was set at 12/13 of total HADS scores. The HADS scores were not affected by the women's age, duration of infertility, experience of conception, routine tests, and work states. In this Japanese population, infertile women reported higher levels of emotional distress than pregnant women, suggesting psychological support is needed for infertile women. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to investigate the clinical effectiveness of a structured group intervention program for Japanese patients with breast cancer. Methods. Fifty-seven patients with breast cancer participated in this program. The scores for the Profile of Mood States (POMS) and the Dealing with Illness Inventory were compared before and after intervention. As 5 patients failed to complete the program and 5 did not complete the inventories, the results for 47 patients were analyzed. As intravenous chemotherapy was presumed to cause severe distress, 7 patients who received this treatment during the period covered by the sessions were excluded. The scores of the remaining 40 patients were compared. Results. In the 40 patients, there were significant differences between the before and after intervention scores for Depression, Lack-of-Vigor, Tension-Anxiety, Confusion, and Total Mood Disturbances. Scores for coping strategies and methods, such as passive–resignation, cognitive–passive/ruminative, and avoidance were decreased, as expected; however, scores for active–expressive/information-seeking, and active–reliance on others were, unexpectedly, decreased. Conclusion. This study demonstrated the short-term effectiveness of structured interventions for Japanese patients with breast cancer, especially in alleviating psychological distress. [ABSTRACT FROM AUTHOR]

Recent studies have revealed the evidence for the significance of SV40 genome in human malignancies. In this paper, the presence of SV40-like sequences was investigated in 54 Japanese osteosarcomas in which mutations of the retinoblastoma (Rb), p53, MDM2, and CDK4 genes had been already analysed. Using polymerase chain reaction and Southern hybridization, SV40-like sequences were detected in 25 cases (46.3%). In most cases, only a part of SV40 genome was detected, and the regulatory region containing enhancer sequences was most frequently found (21/54, 38.9%). There was no apparent relationship between the presence of SV40-like sequences and tumour suppressor genes mutations in each tumour. The SV40-like sequences were also detected in peripheral blood cells of substantial proportion of the patients (43.3%), whereas the incidence was much lower (4.7%) in normal healthy controls. This difference is statistically highly significant (P < 0.0001), suggesting that the presence of SV40-like sequences, even if only a part, may play some roles to predispose individuals to osteosarcoma. [ABSTRACT FROM AUTHOR]

Fatigue is one of the most frequent symptoms in cancer patients. However, the precise causes of this fatigue are still unknown, and this situation makes it difficult to combat the problem. The present study was conducted to investigate factors correlated with fatigue in disease-free breast cancer patients. A group of 134 randomly selected ambulatory breast cancer patients who had undergone successful surgical treatment participated. They completed the Cancer Fatigue Scale, the Hospital Anxiety and Depression Scale, the Mental Adjustment to Cancer Scale, and an ad hoc questionnaire detailing physical symptoms, social support, and demographic variables at home and returned them by mail the following day. Multiple regression analysis revealed that fatigue was significantly correlated with dyspnea, insufficient sleep, and depression, and that these three variables accounted for a total of 46% of variance in fatigue. Factors concerned with the cancer and treatment, such as disease stage, lymph node metastasis, number of days since operation, past intravenous chemotherapy, radiotherapy, current use of fluoropyrimidine compounds, and current use of tamoxifen citrate were not correlated with fatigue. The results suggest that fatigue in this population is determined by current physical and psychological distress rather than by the cancer itself and prior cancer treatments, and that the management of dyspnea, insomnia, and depression might be important in reducing fatigue in this population. [ABSTRACT FROM AUTHOR]

Fatigue is a common symptom of human immunodeficiency virus (HIV). Little empirical research has focused on its prevalence or characteristics among patients with AIDS. In this study, investigators assessed the frequency of fatigue and its medical and psychological correlates in a cross-sectional survey of ambulatory AIDS patients. Ambulatory patients with AIDS who participated in a study of quality life were classified into fatigue/no fatigue groups based on their responses to fatigue items on the Memorial Symptom Assessment Scale and the AIDS physical symptom checklist. Self-reported inventories were also administered to assess psychological distress, depressive symptoms, and overall quality of life. Medical information was elicited through clinical interview and review of medical chart.

Presents news briefs related to the field of medicine as of May 1999. Significance of chemotherapy for the treatment of cancer; Cause of the occurrence of hot flashes in patients with breast cancer; Effectiveness of the drug tamoxifen to treat hepatocarcinomas.

Background. The purpose of this study was to investigate physicians' perspectives on do-not-resuscitate (DNR) orders at Tokai University hospital, where a euthanasia-like accident occurred several years ago. Methods. A "questionnaire on DNR orders" survey was administered to physicians and the anonymous answers were collected 2 weeks later. Results. Answers were received from 150 of the 400 physicians (37.5%) (surveyed from every department), and revealed that more than 90% of the physicians felt that DNRs were occasionally necessary and that more than 60% of the physicians stated that they had performed DNR. Only 14% of the physicians answered that the patient's consent would be indispensable, and 78% stated that the patient's family and the physician could decide on DNR without the patient's consent being given. Only half of the physicians stated that they regarded it as necessary that DNR order sheets be established hospital policy, and more than 20% of the physicians stated that such an order sheet would not be necessary. Conclusion. There is, in fact, a tacit understanding regarding DNR between physicians and patients/families in medical practice in Japan. However, DNR orders constitute definite medical decisions and procedures. Therefore, such orders should be clearly stated in a standardized format, although such procedures do not seem to be acceptable in the context of the Japanese traditional value system. [ABSTRACT FROM AUTHOR]

In order to investigate the time course change of local cerebral blood flow (1CBF) and local cerebral glucose metabolism (1CGM) and the effect of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose metabolism in a middle cerebral artery occlusion-reperfusion model,14C-Iodo-antipyrine and14C-Deoxyglucose autoradiographic method have been used. The 1CBF was reduced to 0–10% of the control level in the ischaemic core and to 12–40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marked hyperfusion appeared at 15 min and maintained about 30 to 45 min following reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reached to the peak at 60 min after the middle cerebral artery (MCA) occlusion both in the ischaemic core and in the penumbra. The shift from hyper- to hypometabolism was observed during the ischaemia. The reperfusion following 2 hours of MCA occlusion facilitated the decrease of cerebral glucose metabolism in the ischaemic region. The pretreatment of MK-801 (0.4 mg/kg) inhibited both increased glucose metabolism during the ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfusion by MK-801 was remarkable in the ischaemic penumbra. These findings support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion. [ABSTRACT FROM AUTHOR]

Twenty-six cases with spontaneous carotid-cavernous fistulas were followed up for periods ranging between 4 months and 9 years 8 months. A complete regression of symptoms without reappearance for more than 6 months was noted in 19 cases, a marked improvement in 2 cases, and a moderate regression in 3 cases. In 2 cases, symptoms have continued for 9 years 8 months and for 1 year. The regression of symptoms was usually delayed in patients less than 60 years old, in cases in which the symptoms developed slowly, and in cases with multiple draining veins. According to our observations a regression of symptoms may occur after very slight changes of haemodynamics. Compression of the cervical carotid artery for a short time or a temporary occlusion of the carotid artery by a balloon catheter should be considered as the treatment of choice in the first instance in cases with spontaneous carotid-cavernous fistulas showing relatively low pressure and low flow shunt. [ABSTRACT FROM AUTHOR]

Based on the work by Fawzy on a structured psychiatric intervention for malignant melanoma patients, the author developed a modified version for Japanese cancer patients. This program is a series of five one-hour sessions including psychoeducation, problem-solving, psychological support, relaxation training (progressive muscle relaxation and autogenic training) and guided imagery. In this preliminary study, 10 breast cancer patients received individual interventions and another 10 were divided into two groups for group therapies. Comparing the results of POMS and Dealing With Illness Inventory scores between pie- and poste-interventions, both the individual and the group interventions were definitely effective in improving psychological distress but less effective for changing coping styles for Japanese patients with breast cancer. The subjects receiving individual intervention were also interested in the group sessions because they wanted to share their knowledge on breast cancer. On the other hand, the patients assigned to the group intervention were hesitant to talk each other in the earlier sessions. These impressions imply that this structured intervention should be modified to include both individual and group sessions. [ABSTRACT FROM AUTHOR]

The sulfonylurea receptor 1 (SUR1) is an essential regulatory subunit of the beta-cell ATP-sensitive K+ channel (K[ATP]). The possible role of SUR1 gene mutation(s) in the development of NIDDM remains controversial as both a positive association and negative linkage results have been reported. Therefore, we examined the SUR1 gene at the single nucleotide level with single strand conformation polymorphism analysis in 100 Japanese NIDDM patients. We identified a total of five amino acid substitutions and 17 silent mutations by examining all 39 exons of this gene. Two rare novel mutations, D811N in exon 20 and R835C in exon 21, were identified in the first nucleotide-binding fold (NBF), a functionally important region of SUR1, in one patient each, both heterozygotes. To analyze possible functional alterations, we reconstituted the mutant K(ATP) by coexpressing beta-cell inward rectifier (BIR) (Kir 6.2), a channel subunit of K(ATP), and mutant SUR1 in HEK293T and COS-7 cells. As demonstrated by the patch clamp technique and rubidium (Rb+) efflux studies, neither mutation alters the properties of channel activities. Two other rare missense mutations, R275Q in exon 6 and V560M in exon 12, were also identified. The R275Q substitution was not found in 67 control subjects, and V560M was present in three control subjects. Neither of these substitutions appeared to cosegregate with NIDDM in the probands' families. A previously reported S1370A substitution located in the second NBF was also common in the Japanese subjects (allelic frequency 0.37), and was found at an equal frequency in nondiabetic control subjects. In conclusion, SUR1 mutations impairing K(ATP) function do not appear to be major determinants of NIDDM susceptibility in Japanese. [ABSTRACT FROM AUTHOR]

Research interest in psychosocial predictors of the onset and course of cancer has been active since the 1950s. Investigators aimed to systematically obtain data on psychosocial factors associated with human response to illness in this prospective study. The change of estrogen function, represented by amenorrhea or hot flashes, that results from breast cancer treatment may increase the risk of major depressive disorder in those women undergoing treatment for breast cancer. One hundred twenty-five patients with metastatic melanoma completed questionnaires measuring cognitive appraisal of threat, coping, psychologic adjustment, perceived aim treatment, social support and quality of life.