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Background: Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence. Methods: Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users. Findings: During prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p Interpretation: If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has curative potential against hematological malignancies. However, there are concerns about the associated risk of non-relapse mortality (NRM). We performed a retrospective single-center study to assess changes in outcomes after allo-HSCT and causes of NRM over three 5-year periods. The rates of 2-year NRM and overall survival (OS) were 16% and 59%, respectively. We found a significant decrease in NRM (P

Association between pretransplant iron overload determined by bone marrow pathological analysis and bacterial infection

Plasma cell neoplasms can present as a single lesion (solitary plasmacytoma) or as multiple lesions (multiple myeloma). Solitary plasmacytoma is a rare plasma cell neoplasm. There are 2 separate entities, dependent on the location of the lesion originating in either bone or extramedullary soft tissue. It is defined as a proliferation of monoclonal plasma cells without evidence of significant bone-marrow plasma-cell infiltration. We present a 71-year-old woman who was diagnosed with a solitary plasmacytoma of the bone located in the right third rib after surgical resection. A chest roentgenogram showed a solitary expanding lesion in the right third rib. Chest computed tomography (CT) revealed an osteolytic chest wall tumor. Fluorodeoxyglucose positron emission tomography and CT (PET-CT) showed no abnormal uptake in the whole body, except for the third rib lesion. The patient underwent complete en-bloc resection of the chest wall including ribs, muscle, and parietal pleura. The patient is asymptomatic without any recurrence after one and a half years of follow up.

Borderline personality disorder (BPD) is typically characterized by severe affective dysregulation leading to impulsive behaviors. Accordingly, preliminary data suggest the hypothesis that BPD patients could have a specific and altered pattern of subjective emotional response to stimuli. The nature of the emotional response in BPD can be compared with other affective disorders and provide further insight on the nosological proximity with other psychiatric disorders.Subjective emotional response was investigated in 19 patients with DSM-IV BPD with no current depressive episode and in 19 healthy control subjects by using the International Affective Picture System (IAPS). The intensity of arousal, valence and dominance was rated in response to 60 images categorized as pleasant, unpleasant and neutral by using a self-assessment instrument. ANOVA of multiple factors was used for between-groups comparisons.The obtained pattern showed that BPD patients considered the unpleasant and neutral images as less aversive than controls, but the activation that these images induced was higher. Patients showed significantly greater arousal than controls for unpleasant and neutral images (p0.05) but presented greater valence (more positive emotion) for these images (p0.05). In addition, BPD patients showed lower dominance (greater insecurity and dyscomfort) for positive images (p0.05).The subjective emotional response pattern of BPD patients suggests a trait of vulnerability to pleasant stimuli and is similar to the pattern found in depressive patients in previous studies. This supports the evidence that BPD could in part be related with the spectrum of the affective temperament and affective disorders.

Trace elements may play an important role in bipolar disorders. The objective of this study is to determine serum copper and zinc, blood lead and cadmium and urine lead, cadmium and thallium concentrations in patients diagnosed with bipolar disorders and to compare these levels with those of a healthy control group.A total of 25 patients diagnosed with bipolar disorder and 29 healthy subjects participated in this study. Serum copper and zinc concentrations were measured using flame atomic absorption spectrometry; the blood lead and cadmium concentrations were measured by electrothermal atomization atomic absorption spectrometry with Zeeman background correction; urine lead, cadmium and thallium concentrations were measured by inductively coupled plasma mass spectrometry.Median blood and urine lead and cadmium levels were significantly higher among the bipolar patients than among the control group: Blood lead (μg/dL): patient median: 3.00 (IQR: 1.40-4.20); control median (μg/dL): 2.20 (IQR: 0.90-3.00) p=0.040. Blood cadmium (μg/L): patient median: 0.39 (IQR: 0.10-1.15); control median: 0.10 (IQR: 0.10-0.17) p0.001. The median of cadmium (μg/L) in patients who smoked (1.20 IQR: 0.44-2.30) was higher than that in non-smokers (0.12 IQR: 0.10-0.34) p0.001. There was a statistically significant increase (p=0.001) in zinc levels among patients in the manic phase (mean 111.28, SD: 33.36 μg/dL) with respect to the control group (mean 86.07, SD: 12.39 μg/dL).The results suggest that there could be higher levels of some toxic trace elements in the group of patients with bipolar disorder than in the healthy control group.

Background: Cigarette smoking is the major cause of lung cancer (LC). Although the time to first cigarette (TTFC) of the day is a distinct indicator of nicotine dependence, little information is available on its possible relation to LC. Patients and methods: This case-control study includes a total of 1572 incident LC cases and 1572 non-cancer controls visiting for the first time the Aichi Cancer Center Hospital between 2001 and 2005. We estimated the odds ratio (OR) and 95% confidence interval (CI) for TTFC using a logistic regression model after adjustment for several potential confounders. Results: TTFC was inversely associated with the risk of LC. This association was consistent across histological subtypes of LC. For all LCs considered among ever smokers and after accurate allowance for smoking quantity and duration, besides other relevant covariates, compared with TTFC >60 min, the adjusted ORs were 1.08 (95% CI, 0.73-1.61) for TTFC of 31-60 min, 1.40 (0.98-2.01) for 6-30 min and 1.86 (1.28-2.71) for within 5 min (Ptrend < 0.001). Statistically marginally significant heterogeneity by histological subtype was observed (Pheterogeneity, 0.002). Conclusions: Nicotine dependence, as indicated by the TTFC, is associated with increased risk of LC and is therefore an independent marker of exposure to tobacco smoking.

Summary Objective Apoptosis of chondrocytes plays a pivotal role in cartilage degeneration. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine and has been assumed to cause the degradation of human cartilage. To investigate the mechanisms of TNF-α-mediated apoptosis of human chondrocytes from a point of view of the balance between the caspase-cascade and the expression of inhibitor of apoptosis proteins (IAPs), although both of them are induced with TNF-signals. Methods The expression of TNF-receptors (TNF-Rs) in normal human articular chondrocyte (NHAC-kn) was examined with immunocytochemistry. Subconfluent cultures of NHAC-kn were tested with TNF-α and/or actinomycin D (actD), and the induction of apoptosis was evaluated by the frequency of apoptotic cells visualized with nuclear staining using Hoechst 33342. The activation of caspases and the expression of IAPs were examined with Western blot analyses. Results NHAC-kn expressed TNF-R1 and -R2. When NHAC-kn was treated with TNF-α (10ng/ml) and actD (0.2μg/ml) for 24h, the frequency of apoptotic cells increased to more than 25%. TNF-α alone, however, induced the apoptosis insufficiently (up to 8.3%), even when used at the concentration of 100ng/ml for 48h. In apoptotic human chondrocytes induced with TNF-α (10ng/ml) and actD (0.2μg/ml), the caspase-3, -8, and -9 were activated and the protein expression of XIAP and c-IAP1 decreased. Conclusions In apoptotic human chondrocytes induced with TNF-α and actD, the balance between caspase activation and IAPs' expression lay with the executioner caspase (caspase-3) and led to decreased expression of XIAP and c-IAP1.

In esophageal squamous cell carcinoma (SCC), we used immunohistochemical analysis to further elucidate the correlation of p53 protein expression with clinicopathological factors, as well as with risk factors, such as tobacco smoking, alcohol consumption and a family history of cancer, using odds ratios (ORs). The expression of p53 protein was demonstrated in 55.1% of 89 esophageal SCC cases examined by immunohistochemistry. The expression of p53 protein did not correlate with gender, age, histological grading, lymph node metastasis, or TNM stage. The prevalence of p53 expression was significantly higher in patients with multiple primary esophageal cancers (P0.05). p53 expression did not correlate with prognosis in univariate survival analysis. The esophageal SCC in either smokers or alcohol users was 4.67-5.83 times more likely to express p53 protein, while the likelihood of p53 expression in patients who use both tobacco and alcohol was more than 14.0 times. However, a significant association was not found between p53 expression and a family history of cancer, this having an OR as low as 1.85. The expression of p53 protein did not correlate with clinicopathological factors and prognosis in univariate and multivariate survival analyses. In contrast, tobacco smoking and alcohol consumption were shown to be strongly associated with p53 mutations in esophageal carcinogenesis.

To investigate risk modification for lung cancer with diet in Japanese, we conducted a hospital-based case–control study and evaluated variation in influence with the histological type. We recruited 367 male and 240 female cases with adenocarcinomas, and 381 male and 57 female cases with squamous cell and small cell carcinomas. Controls comprised 2964 male and 1189 female cancer-free outpatients matched for sex and age with the cases. Odds ratios (ORs) and their 95% confidence intervals (CIs) for lung cancer were calculated with adjustment for potential confounding factors, using an unconditional logistic model. We found decreased ORs for adenocarcinomas in both males (OR = 0.51, 95% CI 0.31–0.84) and females (OR = 0.48, 95% CI 0.24–0.94) who consumed cooked/raw fish, but not dried/salted fish at the highest quartile frequency, compared with the lowest. Soybean curd consumption was associated with a decreased OR for female adenocarcinomas. Decreased ORs for squamous cell and small cell carcinomas were observed in males with frequent consumption of raw and green vegetables, fruit and milk, but consumption of carrot, pumpkin, egg and coffee was associated with increased ORs. This study suggests cooked/raw fish consumption lowers the risk of adenocarcinoma of the lung in Japanese. © 2001 Cancer Research Campaign http://www.bjcancer.com

We have examined the expression of nitrotyrosine, a marker of peroxynitrite formation, in 55 esophageal cancers by immunohistochemistry. Nitrotyrosine was detected in 21 of 55 (38.2%) esophageal cancers. Comparison of nitrotyrosine expression and the pathological findings showed that there was a significant association between the expression of nitrotyrosine and each of the depth of tumor invasion (P

To describe epidemiological features on HIV prevalence among female commercial sex workers (CSWs), a cross-sectional study on sexual behaviour and serological prevalence was carried out in Cambodia. The CSWs were interviewed on their demographic characters and behaviour and their blood samples were taken for testing on sexually transmitted diseases, including HIV, Chlamydia trachomatis, syphilis, and hepatitis B. Associations between risk factors and HIV seropositivity were analysed. High seroprevalence of HIV and Chlamydia trachomatis IgG antibody (CT-IgG-Ab) was shown among the CSWs (54 and 81·7%, respectively). Univariate logistic regression analyses showed an association between HIV seropositivity and age, duration of prostitution, the number of clients per day and CT-IgG-Ab. Especially, high-titre chlamydial seropositivity showed a strong significant association with HIV prevalence. In multiple logistic regression analyses, CT-IgG-Ab with higher titre was significantly independently related to HIV infection. These suggest that existence of Chlamydia trachomatis is highly related to HIV prevalence.

Myoclonus is defined as shock-like, brief involuntary abnormal movements in muscle jerking caused by external stimuli; and it arises from progressive myoclonus epilepsy, post-anoxic encephalopathy and Alzheimer's disease, causing disabling symptoms. It is a rare syndrome but very difficult to control. Piracetam (2-oxo-1-pyrrolidineacetamide, Myocalm) was developed more than 30 years ago as a cyclic derivative of gamma-aminobutyric acid (GABA); it has been used in European countries for the treatment of memory loss and other cognitive defects in patients. Some reports have suggested that piracetam has anti-myoclonus activities, but the mechanisms of myoclonus are not well-identified, and thus there have been few preclinical studies on piracetam for the treatment of myoclonus. We investigated the effect of piracetam and clonazepam, an anti-epileptic drug, on high dosage urea-induced myoclonus using an electromyogram in rats. The incidence of myoclonus induced by urea 4.5 g/kg (i.p.) was significantly reduced by piracetam at 300 mg/kg (i.p.) and by clonazepam at 0.3 mg/kg (p.o.). The coadministration of piracetam 100 mg/kg (i.p.) and clonazepam at 0.03-0.1 mg/kg (p.o.) significantly reduced the incidence of myoclonus, although separate administration was not effective. After oral administration of piracetam, it is rapidly and completely absorbed and excreted almost unchanged in the urine; however, it does show a little binding to human serum protein. Repeated oral administration of piracetam for 7 days in phase-I trials did not show any accumulation of the drug. In the placebo-controlled double-blind crossover trial of piracetam conducted in the UK, there was a significant improvement in cortical myoclonus. In phase-II trials, piracetam inhibited myoclonus and showed an improvement in the quality of life (QOL) of the patients. These results show that piracetam has a beneficial use in clinics for severe myoclonus patients when it is combined with anti-epileptic drugs, demonstrating an improvement in the myoclonus and QOL of patients.

Sarcomatoid carcinoma is a rare variant of malignant tumor arising from the urinary tract. This tumor had been termed carcinosarcoma because of its carcinomatous and sarcomatous components. There is still some confusion in the terminology between true carcinosarcoma and sarcomatoid carcinoma; however, the latter is now regarded as primarily a malignant epithelial tumor with pseudosarcomatous transformation. Four cases of sarcomatoid carcinoma arising from the urinary tract are reported. The patients were a 77 year old female, and three males aged 62, 69 and 80 years. All but the eldest patient complained of gross hematuria. Surgical removal was performed in the younger three cases, and an autopsy was done in the remaining case. All the tumors were macroscopically polypoid. Histopathologic examination revealed fasciculated spindle-cell tumors with myxoid stroma or malignant fibrous histiocytoma-like spindle cell tumors. The epithelial nature was proven in these sarcomatous cells by immunohistochemical and/or electron-microscopic examinations. Only a small amount of squamous cell carcinoma components was also evident in the latter three cases. Although the younger three patients were alive at 44, 23 and 39 months' follow-up, respectively, constant careful monitoring is recommended.

The incidence of immune-mediated anaphylaxis during anesthesia ranges from 1 in 10,000 to 1 in 20,000. Neuromuscular blocking agents are most frequently incriminated, followed by latex and antibiotics, although any drug or substance used may be a culprit. Diagnosis relies on tryptase measurements at the time of the reaction and skin tests, specific immunoglobulin E, or basophil activation assays. Treatment consists of rapid volume expansion and epinephrine administration titrated to symptom severity.

The use of antidepressant drugs in fibromyalgia is extensive despite small evidence of the real impact in the clinical practice setting. This study was aimed to evaluate the long-term efficiency of antidepressant treatment in fibromyalgia and the role of psychosocial factors in treatment response.A total of 102 consecutive patients with fibromyalgia from primary health care centers were studied with psychopathological and psychological assessment interviews and questionnaires. Sustained release venlafaxine was added to previous treatments in flexible doses from 150 to 300 mg daily for a 6-month period. Efficacy measures included the Clinical Global Impression (CGI) scale (patient and clinician versions) and the Fibromyalgia Impact Questionnaire (FIQ) score reduction.At 6 months, 48% patients were considered responders to treatment (CGI change score 1 or 2) and 23.5% had a mild response. Of note, 57.8% had less fatigue and 31.4% had less pain. The proportion of responders was greater in the group with major depression (65%) than in those without depression (45%), but the difference did not reach statistical significance. However, the reduction of FIQ scores was significantly greater in depressed (21.1; IQR: 1.4-42.0) than in non-depressed patients (41.4; IQR: 23.6-52.6) (P0.05). FIQ score reduction was significantly smaller in patients taking concomitant opiate treatment (P0.01) and in patients seeking incapacitation (P0.01).Antidepressant treatment in fibromyalgia was effective in patients with and without major depression, but the functional response was greater in depressed patients. Treatment response to antidepressants might be significantly influenced by attitudinal and psychosocial factors of the disease.

Schizophrenic treatment was developed during the second half of the last century, mainly within the context of the development of antipsychotic drugs. Even though there has been significant progress due to the availability and use of multiple drugs, these can still be classified into three basic groups of antipsychotic drugs (atypical antipsychotics, typical antipsychotics and dopamine partial agonist antipsychotics). Their primary antipsychotic mechanism is still the action on the dopamine systems. Many of the second-generation antipsychotics are believed to offer advantages over first-generation agents in the treatment for schizophrenia. However, the drug properties that provide the different therapeutic effects from those of the first generation are not clear and some adverse effects may still affect the patient's health and quality of life. Furthermore, the efficacy of the antipsychotics is limited. This has led to the use of adjuvant medications to strengthen the treatment effects. On the other hand, work is being done on the development of new research lines to develop new non-dopaminergic antipsychotic drugs, with not very successful results. The aim of this paper is to make a brief review on the current therapeutic armamentarium for schizophrenia, the strategies to develop drugs, and theories of mechanisms of action of antipsychotics. Emphasis is placed on the new therapeutic targets for the development of future treatments.

We present a case of successful surgical ablation of an oblique epicardial accessory pathway on the right coronary artery in a 56-year-old female patient with Wolff-Parkinson-White (WPW) syndrome, for which the radio-frequency (RF) catheter ablation had not been effective 3 times. The heart was exposed via a T-shaped sternotomy, and positioned for adequate exposure using a suction device. Epicardial mapping was performed with a multi-electrode catheter fixed on the atrioventricular sulcus. The epicardium just above the right coronary was dissected with an ultrasonic scalpel and we confirmed complete electrophysiological block of the accessory pathway. For 3 years since the surgery, there has been no recurrence of arrhythmia in the patient. Although an RF ablation through a transcutaneous intrapericardial approach can be an alternative, surgical ablation seems to be a safer and more curative approach to failed RF catheter ablation of accessory pathway. Such surgical skills should be maintained.

DSM-IV defines Borderline personality disorder (BPD) as a personality disorder that can be primarily characterized by emotional instability, extremely polarized thought and chaotic interpersonal relations. It is the most common personality disorder. Its prevalence is estimated to be from 0.2% to 1.8% of the general population, and the 76% of them are women. However, despite these data and the different biologic findings, there are few publications on neuroimage about this nosologic entity. Recent studies suggest that a dual cerebral disorder, including frontal and limbic circuits, could be present in characterize BPD. These cerebral areas would also be involved in the serotonergic dysfunction that seems to be related to the impulse dyscontrol and self-aggressive behaviour, characteristic of these patients. Most authors point out the importance of traumatic precedents in the BPD genesis, with a direct relation between stress and the neurobiological findings observed, including the neuroimage changes. The aim of this article is to make a revision of the main neuroimage data found in BPD, including the new techniques such as functional MRI, diffusion tensor MRI and spectroscopy.

Borderline personality disorder is a disorder with important social and clinical repercussions, which has been treated mainly by psychotherapy. In recent years, the syndromic analysis of this disorder has allowed us to identify different symptoms capable of being improved with psychopharmacology treatment. Thus, its complex symptomatology could be included in four clinical dimensions: impulsive-aggressive, affective instability, cognitive- perceptive and anxiety-inhibition. Antidepressants, mood stabilizers, antipsychotics, anxiolytics, or more recently omega-3 fatty acids have shown efficacy in the treatment of symptomatic dimensions of this disease. We have reviewed scientific articles (reviews, clinical trials or clinical guidelines) published over the last ten years and have proposed therapeutic algorithms for psychopharmacology management in these patients.

OBJECTIVE: To determine the aetiological relationship between human T cell leukaemia virus type-I (HTLV-I) and arthritis, by performing an epidemiological study of the inhabitants of Tsushima, an island northwest of the main island of Kyushu, Japan, which is an endemic area of HTLV-I. METHODS: A total of 7087 people underwent an annual health check, and those with arthropathy had further physical and radiological examinations by rheumatologists. The presence of HTLV-I antibody was determined by the particle agglutinin method, and integration of the proviral DNA in peripheral lymphocytes was confirmed by polymerase chain reaction. RESULTS: HTLV-I was positive in 26.1% of inhabitants; the incidence increased to 37.0% in patients with symptoms of polyarthritis. The prevalence of rheumatoid arthritis (RA) was significantly different between HTLV-I carriers (0.56%) and non-carriers (0.31%). The stage of bone destruction in HTLV-I carriers with articular symptoms was milder than that in RA patients without HTLV-I. The relative risk of HTLV-I infection for polyarthritis was 1.66 (p < 0.05). CONCLUSION: This is the first epidemiological report clarifying the association between HTLV-I and polyarthritis. Our results suggest that this viral infection has a relationship to RA.

Because the epithelial cell adhesion molecule (Ep-CAM) is expressed in almost all carcinomas and human leucocyte antigen (HLA)-A*2402 is the most common allele in many ethnic groups, including Japanese, the identificationof peptide sequences, which elicit HLA-A*2402-restricted Ep-CAM-specific cytotoxic T-lymphocyte (CTL) responses, would facilitate specific immunotherapy for various histological types of carcinomas. An epitope was identified through the following steps: (i) computer-based epitope prediction from the amino acid sequence of Ep-CAM, (ii) major histocompatibility complex (MHC) stabilization assay to determine the affinity of the predicted peptide with HLA-A*2402 molecules, (iii) stimulation of CDB + T cells with peptide-pulsed dendritic cells and (iv) testing the CTL specificity by means of enzyme-linked immunospot (ELISPOT) assays, CTL assays and MHC/peptide-tetramer staining. Peripheral CD8 + T cells of four of five healthy donors after three rounds of stimulation with the peptide Ep-CAM 1 7 3 - 1 8 1 (RYQLDPKFI) secreted interferon-γ in ELISPOT assays when exposed to the peptide. A CTL clone specific to the peptide efficiently lysed Ep-CAM-expressing cancer cell lines in an HLA-A*2402-restricted fashion. Endogenous processing and presentation of the peptide in a lung cancer cell line were confirmed by means of cold target inhibition assays. The CTL clone was also lyric to normal bronchial epithelial cells but to a lesser extent at low effector: target ratios. All these data suggest that the peptide-specific CTL responses may play some roles both in anti-cancer and autoimmune reactions. The peptide should prove useful to study anti-Ep-CAM CTL responses among population possessing HLA-A*2402.

There is accumulating evidence that peptides derived from the catalytic subunit of human telomerase reverse transcriptase (hTERT) are specifically recognized by CD8+ cytotoxic T lymphocytes. We investigated the cytotoxicity of a human leukocyte antigen (HLA)-A*2402-restricted hTERT-derived peptide 461-469 (hTERT461)-specific CD8+ T-cell clone, designated as K3-1, established from a healthy donor by repetitive peptide stimulation. This clone exhibited cytotoxicity against 4 out of 6 HLA-A24-positive lung cancer cell lines with positive telomerase activity but not 4 HLA-A24-negative examples. When the target cells were pretreated with 100 U/ml of interferon (IFN)-gamma for 48 hr, the susceptibility to K3-1 increased with PC9 cells but unexpectedly decreased with LU99 cells. However, in both cell lines, the expression of molecules associated with epitope presentation such as HLA-A24, transporters associated with antigen processing, low molecular weight polypeptide 7 and proteasome activator 28 was similarly increased after IFN-gamma treatment. Results of CTL assays using acid-extracted peptides indicated that the epitope increased on PC9 cells but not on LU99 cells after IFN-gamma treatment. Semi-quantitative reverse transcriptase polymerase chain reaction disclosed that the expression of hTERT was attenuated in LU99 but not in PC9 cells, accounting for the decreased cytotoxicity mediated by K3-1. The attenuation of the hTERT expression and K3-1-mediated cell lysis after IFN-gamma treatment was also observed in primary adenocarcinoma cells obtained from pulmonary fluid of a lung cancer patient. Our data underline the utility of peptide hTERT461 in immunotherapy for lung cancer, as with other malignancies reported earlier, and suggest that modulation of hTERT expression by IFN-gamma needs to be taken into account in therapeutic approach.

Little information is available on the clinical characteristics of infectious complications that occur in the early period after reduced-intensity stem cell transplantation (RIST). We retrospectively investigated the clinical features of neutropenic fever and infectious episodes within 30 days after RIST in 76 patients who had received fluoroquinolones as part of their antibacterial prophylaxis. Preparative regimens included cladribine 0.66 mg/kg or fludarabine 180 mg/m2 plus busulfan 8 mg/kg. All but 1 patient survived 30 days after transplantation, and 75 patients (99%) became neutropenic within a median duration of 9 days. Neutropenic fever was observed in 29 patients (38%), and bacterial infection was confirmed in 15 (20%) of these, including bacteremia (n = 13), bacteremia plus pneumonia (n = 1), and urinary tract infection (n = 1). The causative organisms were gram-positive (n = 9) and gram-negative organisms (n = 7), with a mortality rate of 6%. Neither viral nor fungal infection was documented. Multivariate analysis showed that the presence of neutropenia at the initiation of preparative regimens was an independent risk factor for subsequent documented bacterial infections (P = .026; 95% confidence interval, 1.25–35.1). We conclude that neutropenic fever and bacteremia remain common complications in RIST.

Cancer/testis (CT) antigens are considered promising candidates for vaccine-based immunotherapy. The aim of this study was to investigate which CT antigens should be targeted in immunotherapy of Japanese lung cancer. To determine the expression of 12 CT antigens in Japanese primary lung cancers and cell lines, a reverse-transcription polymerase chain reaction (RT-PCR) analysis was performed. Among 46 primary lung cancers, high expression rates were found for MAGE-3 (41%, 19/46), and SSX-4 (35%, 16/46). A similar pattern of CT antigen expression was observed in 29 lung cancer cell lines. The expression frequency of a certain CT antigen, namely NY-ESO-1, in Japanese cases was drastically different from that in Caucasians. Polyvalent CT antigen vaccine may be effective to increase the number of lung cancer patients eligible for cancer-specific immunotherapy. Vaccination with MAGE-3 and SSX-1 would cover 57% of all patients, with three antigens, MAGE-3, SSX-1, and MAGE-4, would cover 65%, and with four antigens, MAGE-3, SSX-1, MAGE-4 and SSX-4, would cover 70%. Simultaneous expression of two or more CT antigens was observed in 25/46 (54%) primary lung cancers and 18/29 (62%) lung cancer cell lines. Polyvalent CT antigen vaccines may be also effective to reduce a chance of emergence of antigen loss variants, thus preventing tumors from escaping from the immune system. For this purpose, vaccination with combinations of MAGE-3 with MAGE-6, SSX-4, MAGE-1 or BAGE may be effective for a quarter of Japanese lung cancer patients. In addition, in silico surveys of dbEST database were used for identification of new CT antigens. We identified a novel gene, TES101RP, expressed only in some small cell lung cancers (SCLC) and in testis, as confirmed by RT-PCR analysis.

Malignant lymphoma may present prominent peripheral nervous system disorders with variable etiologies. We describe a patient who presented with chronic relapsing polyradiculoneuropathy accompanied by right facial nerve palsy. Gadolinium enhancement of the right facial nerve and cervical spinal roots was noted on magnetic resonance imaging (MRI). Sural nerve biopsy specimens showed mononuclear cell infiltration around the vessels in the epineurium. Histopathological and immunohistochemical investigations of sural nerve specimens revealed perivascular infiltration of lymphocytes with T-cell dominancy. No apparent direct invasion of lymphoma cells was seen. The results of nerve conduction studies, sural nerve biopsy and cerebrospinal fluid examination were suggestive of immune-mediated inflammatory demyelinating neuropathy. The chronic and relapsing fashion and unique radiological findings in our patient expand on the previously reported features of peripheral neuropathy associated with peripheral T-cell lymphoma.

Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking.

Associations between Helicobacter pylori (HP) infection and lifestyle factors have been demonstrated by several studies, but there are very few reports on links with host factors, especially concerning genetic polymorphisms for inhabitants of large city. The present investigation was conducted to determine the HP infection rate with reference to the Interleukin-1 beta gene (IL-1B) polymorphism and assess the interactions with smoking reported for outpatients.The subjects were 468 participants in a health-check-up program of law of health for aged conducted by Nagoya Nishi Health Center. The participants were asked to permit use of their residual blood drawn during a health-check-up program and written informed consent was obtained for gene polymorphism tests. Data on smoking habit were obtained by self-administered questionnaire. The IL-1B C-to-T polymorphism at -31 was genotyped by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) and an anti-HP IgG antibody test was used for detecting HP infection. Differences in values were assessed by a chi 2 test. An unconditional logistic model was applied for estimating odds ratios with the computer program STATA Version 6. This study was approved by the Ethical Committee at Aichi Cancer Center in 2000 before it was commenced (Ethical Committee Approval Number 11-12)The HP infection rate was 52.6% (61/116) for the C/C genotype of IL-1B-31, 48.6% (89/183) for the C/T, and 63.2% (103/163) for T/T; the difference were not statistically significant. However, when non-current smokers were excluded, the rate were 47.8% (11/23), 52.9% (18/34), and 72.7% (16/22), respectively, indicating the T/T genotype to have a higher infection rate. The age-sex-smoking adjusted odds ratio (OR) relative to the C/C genotype were 0.97 (95% confidence interval, 0.59-1.57) for the T/C genotype and 1.73 (1.04-2.87) for the T/T genotype. Among current and former smokers the age-sex adjusted OR were 1.68 (0.50-5.71) for the T/C genotype and 5.29 (1.11-25.1) for the T/T genotype, suggesting a effect of this polymorphism prominent in smokers.An association between the IL-1B-31 polymorphism and persistent HP infection was observed for inhabitants with a smoking habit, indicating that this polymorphism is one genetic trait conferring an increased likelihood of persistent HP infection.

To determine the impact of family history (FH) on anthropometric and reproductive risk factors for breast cancer, a case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan.In total, 1584 breast cancer cases were included and 15,331 women, confirmed as free of cancer, were recruited as the referents. Odds ratios and 95% confidence intervals were determined by logistic regression analysis. Separate analyses were performed for premenopausal and postmenopausal women.Height, weight, and current body mass index (BMI) were positively associated with postmenopausal breast cancer regardless of FH, while these anthropometric factors did not alter risk in premenopausal women. The impacts of height and weight on postmenopausal breast cancer were more pronounced among FH women. There was little association with reproductive risk factors for premenopausal or postmenopausal breast cancer in FH cases, in clear contrast to the non-FH cases.These findings suggest some differences in risk impact of common etiologic factors between familial breast cancer and sporadic cases that may give pointers to further analysis of host-specific factors. They imply that avoidance of obesity after menopause may reduce the risk of breast cancer, regardless of FH.

Recent studies suggest that smoking habit may relate to genetic traits. This study examines the association with a polymorphism (C-31T) of interleukin 1B (IL-1B), which encodes IL-1beta, a multifunctional pro-inflammatory cytokine. Since the T allele makes a TATA box, the allele is thought to be responsible for a higher potency of IL-1B expression, indicating that individuals harboring the T allele are prone to inflammation. The study subjects were two different populations; 241 non-cancer outpatients (118 males and 123 females) at a cancer hospital and 462 examinees (127 males and 335 females) of a health checkup program provided by a local government. Current smokers were 36.4% for the male outpatients, 9.8% for the female outpatients, 38.6% for the male examinees, and 5.6% for the female examinees. The sex-age-adjusted odds ratios of current smokers were calculated for the genotypes with the T allele relative to the CC genotype by an unconditional logistic model. The estimate was 0.45 (95% confidence interval, 0.21-0.97) for the outpatients, and 0.83 (0.42-1.61) for the examinees. Although not significant for the examinees, the observed associations suggest that this polymorphism may influence smoking behavior through an inflammatory response of the respiratory tract to cigarette smoke.

The functional polymorphisms regulating immunologic responses may influence the proliferation or suppression of malignant lymphoma. We examined the association between malignant lymphoma risk and the polymorphisms of the IL-1 gene family [IL-1B -31 C/T, IL-1A -889 C/T, and IL-1RN 86-bp variable number of terminal repeat (VNTR)] and myeloperoxidase (MPO -463 G/A).The hospital-based case-control study was conducted in Japan. Genotypes were examined in a total of 372 lymphoma cases and 241 non-cancer control subjects. The relative risks were estimated by unconditional logistic regression analysis.The overall allele distribution of these polymorphisms did not differ substantially between patients and controls; the odds ratios were 0.73 (95% confidence interval, 0.48-1.11) for the T allele carriers of IL-1B relative to the non-carriers, 1.01 (0.56-1.82) for the 2-repeat allele (allele 2) carriers of IL-1RN, 0.96 (0.62-1.48) for the T allele carriers of IL-1A, and 1.04 (0.70-1.57) for the A allele carriers of MPO. Subgroup analyses according to histology [diffuse large B-cell lymphoma (DLBL), follicular lymphoma, low-grade lymphoma of mucosa associated lymphoid tissue, and others] failed to illustrate differences except for DLBL which showed a possible association with IL-1A and IL-1B polymorphisms.Our data show a limited association between these polymorphisms and malignant lymphoma risk in total. The possible association of the IL-1A and IL-1B polymorphisms with DLB-needs further clarification.

A 9-year-old boy underwent biopsy of the tumor at the external auditory meatus under general anesthesia with a laryngeal mask airway(LMA). During emergence from anesthesia, laryngospasm with marked inspiratory effort and cyanosis occurred. The LMA was removed and the patient was orotracheally intubated following vecuronium administration. In spite of controlled ventilation with 100% oxygen, oxygen saturation remained at low 90s and pink frothy sputum appeared in the tracheal tube. We suspected negative pressure pulmonary edema and treated him with mechanical ventilation with positive end-expiratory pressure. Seventeen hours later the pink frothy sputum decreased and he was extubated. Laryngospasm during emergence from anesthesia with an LMA can induce negative pressure pulmonary edema, especially in pediatric patients.

In general, the incidence and mortality rates for lymphoid and hematopoietic malignancies in Oriental countries, including Japan, are lower than in Western Europe and the U.S. However, those of lymphoid malignancies (ML) are clearly increasing in Japan, especially in the older generations. The main cause of the recent increment might be explained by compensation for risk reduction of infectious diseases in the old generations, so that their life span is extended rather than increment in exposure to specific risk factors. With regard to change in diagnostic criteria for ML, the geographical distribution of ML death rates by subtype shows variation over the last 20 years. In Japan, ML is more prevalent in southwestern districts, attributed to ATL caused by HTLV-I, and this high incidence of ATL should disappear with the HTLV-I eradication in the future. On the other hand, further diagnostic techniques might be developed and it is conceivable that a unique geographical distribution of new subtypes of lymphoid and hematopoietic malignancies may thereby be generated.

Two cases of renal pelvis rupture caused by urolithiasis are reported. The first case was in a 62-year-old male who had left flank pain. Urological examination including drip infusion pyelography (DIP) and abdominal computed tomography (CT) revealed a spontaneous rupture of the left renal pelvis. The rupture was assumed to have been caused by a small ureteral stone. The stone passed spontaneously, and the extravasation disappeared with conservative therapy. The second case was in a 84-year-old male who was admitted with high fever. Urological examination including DIP and abdominal CT showed a suspected rupture of the left renal pelvis due to a renal stone at the ureteropelvic junction. Percutaneous nephrostomy was performed and antegrade pyelography showed extravasation from the left renal pelvis. Extravasation disappeared on the 12th postoperative day. Extracorporeal shock wave lithotripsy was performed three times. The renal stone was completely discharged and the nephrostomy tube was removed successfully.

We recently identified 3 fractions of human peripheral blood (PB) dendritic cells (DC), including the monocyte-associated fractions 1 and 2 (CD1a+,CD11c+ and CD1a-,CD11c+, respectively) and the lymphoid-associated fraction 3 (CD1a-,CD11c-). We attempted to determine whether these fractions were altered in Sjögren's syndrome (SS).We examined 23 patients with primary SS and 22 normal control subjects. DC were purified from PB and analyzed by flow cytometry. Immunohistochemical staining of labial salivary glands of SS patients was performed with monoclonal antibodies against fascin, which is known to be specific for DC.The total numbers of PB DC and fraction 1 DC were decreased in SS. Immunohistochemical staining demonstrated that fascin+,CD11c+,HLA-DR+ mononuclear cells were present and scattered among numerous fascin-hyperfiltrating cells in SS patients. Interferon-gamma (IFNgamma)-producing Th1 cells were shown to be increased in both PB and salivary glands of patients, indicating the presence of general IFNgamma-producing Th1 polarization in SS. Furthermore, numbers of Thl cells were increased when naive T cells were cocultured with fraction 1 DC in vitro.These findings suggest selective trafficking of fraction 1 DC into focal sites of inflammation and subsequent promotion of Th1 balance, suggesting a novel pathogenesis of SS.

Glucocorticoid hormones are known to enhance gonadotropin/cAMP-induced steroidogenesis in rat and human granulosa cells. As glucocorticoids induce apoptosis in numerous cell types, we investigated the role of glucocorticoids in the control of apoptosis in immortalized human granulosa cells (HO-23) transfected with a temperature-sensitive mutant of p53 (Val(135)). When HO-23 were incubated with forskolin in the presence or absence of dexamethasone (Dex) at 32 or 37 C, progesterone production was higher by 4- and 8-fold in the presence of Dex at 37 or 32 C, respectively (P:0. 01). The expression of adrenodoxin (ADX), which is an intrinsic part of the cytochrome P450 side-chain cleavage enzyme system, remained the same in the presence or absence of Dex in forskolin-stimulated cells. Dex reduced apoptosis (to 33% of control) in cultures after activation of p53 by shifting the temperature from 37 to 32 C. Moreover, Dex suppressed apoptosis induced by serum deprivation (to 40% of control) or forskolin stimulation (to 28% and 40% at 37 and at 32 C, respectively). The protective effect of Dex on cAMP-, p53-, and serum deprivation-induced apoptosis was confirmed by both 4',6-diamido-2-phenylindole hydrochloride DNA staining and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling with an ED(50) of 7 nM Dex. Hydrocortisone showed a similar antiapoptotic effect. The protective effect of glucocorticoids against apoptosis was completely abolished by RU486 when cells were coincubated with 10 nM Dex and 10-100 nM RU486. The protection against apoptosis by glucocorticoid involved a sharp elevation in intracellular levels of Bcl-2 (3-7.6 fold; P:0.01). In contrast to the effect of Dex in the prevention of apoptosis in HO-23 granulosa cells, Dex dramatically stimulated apoptosis by 3-fold in LTR-6 myeloid leukemia cells expressing the same temperature-sensitive mutant (Val(135) p53) and the same amount of glucocorticoid receptor-alpha. Forskolin did not stimulate apoptosis when incubated with these cells. However, it augmented by 1.2-fold the p53-induced apoptosis in cells shifted from 37 to 32 C. Dex further enhanced apoptosis by 1.9-fold in p53-activated cultures (32 C). Incubation of the cells with Dex dramatically reduced Bcl-2 levels to 15% of control at 37 C (P:0.01) or 32 C in the presence or absence of forskolin (P:0.01). Our data suggest that glucocorticoids exert a protective effect against induced apoptosis in immortalized granulosa cells and a stimulatory effect on apoptosis in myeloid leukemia cells. Moreover, modulation of Bcl-2 levels plays an important role in mediating the glucocorticoid effect on cell survival. The opposite effect of glucocorticoids on Bcl-2 levels in the two cell lines may be due to the different ontogeneses of the two cell types: epithelial for granulosa cells vs. mesenchymal for myeloid cells studied in the present work.

Human T-cell leukemia virus type I (HTLV-I) carriers are clustered in limited groups in the world. One of these groups is the Andean native population of South America. As part of an international collaborative study devoted to explore the clustering of HTVL-I carriers in different countries, the aim of this paper was to evaluate the seroprevalence of HTLV-I/II virus in the native population of Puna Argentina in Jujuy. Blood samples of individuals of three populations of Puna Jujeña (Susques, Rinconada, Cochinoca) were screened with particle agglutination (PA), immunofluorescence (IF) and western immunoblotting analysis (WB) tests. Two out 86 (2.32%) individuals examined in the Puna Jujeña showed positive results for HTLV-I antibodies. It is concluded that the Province of Jujuy, in particular its less miscegenated highest altitude areas, constitute the northern and southern Andean natural geographical clustering of HTLV-I. This distribution is probably linked both to a history of prehistoric human dispersal in the Andes and to high mother- to-child transmission of the virus under close conditions of each group.

A 61-year-old man and a 59-year-old woman were referred to our hospital because of lower abdominal pain and discomfort, pollakisuria and a lower abdominal mass. In both patients, radiological studies and cystoscopy caused us to suspect a urachal abscess. We performed operations transperitoneally. In the male patient, fish bones were detected between the mass and ileum. A partial cystectomy was performed on the female patient, and the histological diagnosis was Sparganosis mansoni. In both cases, it was very difficult to make a correct diagnosis before the operations, but surgical treatment was successfully performed.

Adult T-cell leukemia (ATL) is associated with human T-cell leukemia virus type 1 (HTLV-1) and is known to be a refractory disease of highly poor prognosis. We describe a case of ATL treated with allogeneic bone marrow transplantation (allo-BMT). The allo-BMT successfully induced complete remission in the patient. Currently, at 24 months post BMT, there has been no evidence of minimal residual disease (MRD) detected by polymerase chain reaction (PCR) assay for the T-cell receptor gamma chain gene. By contrast, PCR analysis demonstrated the reappearance of the cells harboring the integrations of the HTLV-1 proviral DNA 9 months after the BMT. These findings may imply a reversion to the carrier state rather than the recurrence of the leukemia from the MRD. The clinical consequence of our case illustrates that allo-BMT is an effective therapy, at least for achieving longer disease-free survival in ATL.

A 39-year-old man was admitted with massive ascites. Specimens of ascitic fluid contained numerous cells with a FAB-L3 appearance, and small noncleaved cell lymphoma morphology. These cells expressed CD10, CD19, CD20, CD38, CD45, HLA-DR, and IgM antigens, and were positive for IgM and c-myc protein in cytoplasmic immunostaining tests. Clonal rearrangements of IgH and c-myc genes were detected by Southern blot analysis. No mass lesions were found by physical examination, and systemic computed photography did not reveal enlargement of lymph nodes, spleen, or liver. Bone marrow aspiration showed no infiltration of malignant cells. Ga scintigraphy indicated hot lesions only in the abdomen. These findings suggested that Burkitt's lymphoma had developed in the peritoneal cavity as a primary lymphomatous effusion. Chemotherapy with methotrexate, cyclophosphamide, vincristine, doxorubicin, etoposide, and dexamethasone was effective, and the patient has been free from the disease for 1 year since completion of consolidation treatment with autologous peripheral blood stem cell transplantation.

Cell cycle-associated proteins, p16, pRb, p21 and p53 are important in regulating the G1-S checkpoint in the cell cycle, and their functional alterations play key roles in carcinogenesis and cell proliferation.We immunohistochemically examined the expression of p16, pRb, p21 and p53 proteins by using surgically resected tissues from 35 patients with primary esophageal cancers.In 35 esophageal cancers, the expressions of p16, pRb, p21 and p53 proteins were detectable in 4(11.4%), 25(71.4%), 11(31.4%) and 20(57.1%) respectively. Interestingly, 24 of 25 pRb positive cancers (96.0%) had negative p16, whereas three of ten pRb-negative cancers (30.0%) had high levels of p16 (p0.05). In 11 cases of p21 positive immunostaining, there was lymph node metastasis (pN1) in 9 (81.8%).These results suggest that abnormalities of p16 protein may be closely associated with the carcinogenesis or cell proliferation of esophageal cancers.

In October 1996, a 26-year-old woman was given a diagnosis of acute myeloblastic leukemia, FAB subtype M1. Treatment with combined chemotherapy achieved a complete remission (CR). In May 1997, the patient received an allogenic bone marrow transplant (BMT) from an HLA-identical sibling donor. Cyclosporine (CsA) and short-term methotrexate were given for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment was obtained and signs of acute or chronic GVHD never developed. Five months after BMT, the patient experienced low-grade fever and blurred vision. Retinal examination demonstrated intraretinal hemorrhages, cotton-wool spots, and retinal detachments, which were presumably attributable to multiple thrombosis of retinal microvessels. The patient also exhibited hemolytic anemia with red cell fragmentation, thrombocytopenia, elevated lactate dehydrogenase, and renal impairment, and was thus given a diagnosis of BMT-associated thrombotic microangiopathy (BMT-TM). Discontinuation of CsA and administration of ticlopidine and prednisolone induced successful recovery from BMT-TM. Three months after the onset of BMT-TM, however, the patient experienced generalized clonic-tonic seizures with consciousness loss. Single-photon-emission computed tomography revealed blood-flow disturbances in the brain, suggesting the recurrence of microthrombosis. Accordingly, multiple transfusions of fresh frozen plasma were administered together with dipyridamole and aspirin. The patient gradually recovered and remained asymptomatic through the following 13 months. Currently, early diagnosis of BMT-TM is considered to be difficult. We suggest that careful examination of the ocular base may be useful for the early detection of BMT-TM.

A 71-year-old man was referred to our hospital complaining of urinary retention. He noticed a small mass on his buttocks about one year ago. Computed tomographic (CT) scan and magnetic resonance imaging (MRI) showed a large mass of 10 cm in diameter located in the retrovesical space. The mass extended to the surface of his buttocks and contained many calcified deposits, and was accompanied with a sacral bone fracture. Transdermic biopsy revealed the presence of sacral chordoma. Chordoma is a rare tumor, arising from remnants of the notochord and is locally progressive. Both tumor resection and diverting colostomy were performed at another hospital. In that operation his spinal cord was protected down to the second sacral level. Unfortunately after the operation, the patient suffered total urinary incontinence. At 15 months after surgical treatment, the patient presented with lung and bone metastases, and at 2 years after his initial operation, he had local recurrence.

The main form of cytotoxic treatment for multiple myeloma (MM) is conventional dose chemotherapy at present.Between November 1989 and December 1991, a multicenter phase II study of alternating conventional dose combination chemotherapy (CCT) with COP (cyclophosphamide, vincristine, prednisone) and MP (melphalan and prednisone) to evaluate its clinical usefulness for overt MM patients was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG).Eighty-one previously untreated patients were enrolled in the study. For 69 eligible patients, the response rate was 50.7% [95% confidence interval (CI) 38.4-63.0%]. The median survival time was 38.5 (95% CI 32.0-44.4) months. The survival rate at 3 and 5 years was 50.7 and 27.3%, respectively. Grade 4 toxicity by the criteria of the World Health Organization consisted of anemia in eight patients, leucocytopenia in three, cardiac in one and hepatic in two, but there was no treatment-related death.The COP-MP regimen for overt MM is thought to be one of the effective CCTs according to the results of the present phase II study.

To clarify the validity of the health habit index, we evaluated risk of death by health habit index in residents in Aichi Prefecture. Subjects were 7,662 residents aged 40-79 years living in a rural area of Aichi Prefecture who responded to a questionnaire in 1988, that included 12 health habit items on diet, physical activity, rest, mental health, smoking, drinking and regular health check. Data on death and migration in this cohort group was collected from 1990 to 1997. The risk ratios (RRs) of death for all causes, cancer and cardiovascular diseases were estimated by Cox's proportional hazard model. The number of all causes of death, cancer and cardiovascular diseases was 650, 240 and 197, respectively. Proper health habits of adequate but not over eating, regular physical activity, properly managing stress, non-smoking or smoking cessation for one year or more and regular health examinations in men and regular physical activity and non-smoking in women related to lower age-adjusted RR of death for all causes, while smoking cessation of less than one year in men with increased RR. Lower RR of cancer was observed for non-smoking men, and for women who occasionally have enough sleep. Proper health habits on adequate but not overeating, enjoying mealtime, regular physical activity, properly managing stress, moderate drinking (2 "go"/day) or occasional heavy drinking and regular health examinations related to lower RR of cardiovascular diseases in men, while regular physical activity related to lower RR in women. Multivariate analysis for the RR of death for all causes showed similar results, except higher RR in the men who avoided excess salt consumption, and decreased RR in the women who occasionally have enough sleep. In conclusion, the present study suggested that regular physical activity is associated with decreased risk from death for all causes, especially for cardiovascular diseases. Health habit index in the present study included various items with or without association to risk for death. It is important to apply this index to health promotion on the basis of its specific characteristic.

A residual ventricular septal defect as part of the tetralogy of Fallot (TOF) is often difficult to close when a long interval has elapsed after a radical operation or the position of the defect is problematic.When an accurate diagnosis and closure of a residual ventricular septal defect (VSD) were not obtainable through right atriotomy and right ventriculotomy, the ascending aorta was opened. The smooth surface of the left ventricular septum makes it possible to find the position of the defect, and close it accurately and safely.Three consecutive patients were operated upon using this method. They had undergone repair of tetralogy of Fallot anomalies 8 years, 26 years, and 21 years prior to this surgery, respectively. All patients survived the operation and were discharged from the hospital. None of the patients had residual defects, aortic regurgitation, or new atrioventricular block.This transaortic approach for closing residual ventricular septal defects related to the tetralogy of Fallot offers an alternate method when either the right atrial or right ventricular approach cannot be performed successfully. This approach may make it possible to close such defects directly.