Background characteristics of basic health examination participants: the JPHC Study Baseline Survey

BACKGROUND: Although epidemiologic studies including the Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Disease (JPHC study) have frequently used the basic health examination participants as study subjects, their background characteristics have rarely been investigated. The aim of this study is to clarify the background characteristics of participants and to discuss their impact on epidemiologic studies. METHODS: Subjects were 43,140 (Cohort I) and 34,892 (Cohort II) respondents aged 40-59 years who completed a self-administered questionnaire in 1990 or 1993-94 by the JPHC Study. Respondents whose data of the basic health examination were also available were defined as participants. We compared their sociodemographic factors, personal medical history, and lifestyle-related factors with those of non-participants. RESULTS: Participants tended to be older and less educated. They were more likely to engage in agriculture, forestry and fisheries or to be self-employed persons, or homemakers. Male participants smoked less and were more likely to drink alcohol beverage moderately. Female participants smoked and drank less but tended to participate more in sports and physical exercise in their leisure time. Both male and female participants tended to eat fruits and green vegetables more often than non-participants. In short, participants had a different socioeconomic status from non-participants and a favorable lifestyle profile, especially among women. These findings were principally consistent between the two cohorts. CONCLUSION: These differences between participants and non-participants in the basic health examination might cause a selection bias that limits the application of the results to only participants in the basic health examination.     

The present status of I-131 therapy for Graves' hyperthyroidism in Japan (survey by questionnaire)

A survey on the I-131 therapy of Graves' hyperthyroidism was undertaken by questionnaire in 1,246 hospitals of Japan. One thousand and ninety seven of them (88.0%) responded to the questionnaire. In this paper, we report the results and analysis of the replies to the questionnaire. In the 121 hospitals (11.03%) of the respondents, I-131 therapy is being performed for Graves' hyperthyroidism. A gradual increase was observed in the annual number of I-131 treated Graves' disease patients during the period of 1998-2001, from 1,740 to 2,484. I-131 treatment was selected mainly for the cases with side effects from antithyroid drug (ATD) therapy, followed by the cases with complication of heart or hepatic diseases, recurrences of hyperthyroidism after surgery, radioiodine treatment, and long-term ATD treatment. The 41% of respondents used I-131 in order to restore euthyroidism, 34% aimed for hyperthyroidism and 41% used the dose properly between the two according to the patients. Administration dosage of I-131 was estimated mainly on the basis of thyroid uptake and volume in 93% of the respondents and 48% calculated the radiation dose by also determining the effective half-life in the thyroid gland. Thyroid size was estimated by scintigram (51%), US (33%), CT (22%) and palpation (12%). ATD treatment was used before I-131 administration by 70% of the respondents and 34% after radioiodine therapy. A low-iodine diet was given to the patients for a week (46%) or two weeks (47%) before I-131 administration. However, after treatment only 46% of the respondents continued low-iodine diet for a week.     

Anesthetic management for laparoscopic surgery in a patient with Charcot-Marie-Tooth disease

A 50-year-old woman was scheduled for laparoscopic cholecystectomy under general anesthesia. She was suffering from Charcot-Marie-Tooth (CMT) disease for 21 years, and implanted with a permanent pacemaker for IIIrd degree AV block. Anesthesia was induced with fentanyl and propofol, and maintained with oxygen-air-sevoflurane. Neuromuscular blockade was not used because of the presence of peripheral neuropathy and respiratory muscle weakness. We suggest that sevoflurane anesthesia might be useful for anesthetic management of CMT patient with a risk of postoperative respiratory failure.     

Evaluation of psychometric properties of Japanese version of international prostate symptom score and BPH impact index

PURPOSE: To evaluate psychometric properties of the Japanese version of International Prostate Symptom Score (IPSS) and BPH Impact Index (BII). METHODS: The translated IPSS and BII questionnaires were administered to 103 patients with benign prostatic hyperplasia and 23 asymptomatic men. In 82 patients the questionnaires were repeated 2 weeks later to examine reproducibility. Further 2 weeks later 21 out of 82 patients responded to the questionnaires asking symptoms during the last week rather than during the last month. To evaluated responsiveness the questionnaires were repeated after treatment in 22 patients. Internal consistency, construct validity and criterion validity were examined by proper statistic methods. RESULTS: Reproducibility was good to excellent with weighted kappa more than 0.62 for all items. It was not significantly affected by age, symptom severity, institution type, or whether the patients were asked symptoms during the last week or during the last month. Internal consistency was also good with Cronbach's alpha more than 0.83. Principle component analysis identified 2 components in IPSS and a single component in BII, with all the items contributing to the first component. Most items had significant correlation with external criteria including maximum flow rate, residual urine volume or prostate volume. The scores of patients were clearly larger than asymptomatic men and obviously reduced after receiving therapies. CONCLUSION: Japanese translations of IPSS and BII were shown to be reliable, valid and one-dimensional instruments in the Japanese patients. They would be equivalent to the original English questionnaires.     

Long-lasting gene expression by particle-mediated intramuscular transfection modified with bupivacaine: combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at a distant site

The immune response is modulated by genetic adjuvants using plasmid vectors expressing cytokines. Skeletal muscle can express a foreign gene intramuscularly administered via a needle injection, and the potential of muscle as a target tissue for somatic gene therapy in treating cancer has been explored. In the present study, we investigated the efficacy of particle-mediated intramuscular transfection modified with a local anesthetic agent, bupivacaine, on luciferase and green fluorescent protein. The results indicate that these proteins are more efficiently expressed and persist longer in muscle modified in this way compared with the needle-injection method. Using an established rat sarcoma model, particle-mediated intramuscular gene-gun therapy with a combination of IL-12 and IL-18 cDNA was conducted. Growth of the distant sarcoma was significantly inhibited by particle-mediated intramuscular combination gene therapy, and the survival rate was also improved. Furthermore, the combination gene-gun therapy maintained significant levels of interferon-gamma and induced a high activity of tumor-specific cytotoxic T lymphocytes. These results suggest that the sustained local delivery of IL-12 and IL-18 cDNA using intramuscular gene-gun therapy modified with bupivacaine can induce long-term antitumor immunity, and can provide the great advantage of inhibiting the disseminated tumor.     

Tumor response to chemotherapy: the validity and reproducibility of RECIST guidelines in NSCLC patients

We investigated the validity and inter-criteria reproducibility between RECIST (Response Evaluation Criteria in Solid Tumors) guidelines and WHO (World Health Organization) criteria, considering the decrease in patient numbers resulting from inclusion of the minimum lesion size criterion introduced in RECIST guidelines. RECIST guidelines are based on unidimensional measurement and exclusion of small lesions from measurement. The aims of the study were to examine: (1) the effect of the minimum lesion size criterion, (2) the validity of unidimensional and bidimensional measurements, i.e., their relationship with tumor volume, (3) the inter-criteria reproducibility between current RECIST guidelines and previous WHO criteria. One hundred and twenty patients with non-small cell lung cancer (NSCLC) in clinical trials were evaluated. By applying the minimum lesion size criterion, six cases became ineligible without any influence on precision of tumor volume measurement. In the validity study, actual tumor volume was regarded as the gold standard. Although the unidimensional measurement had a lower correlation with tumor volume value than the bidimensional measurement, both the unidimensional measurement and bidimensional measurement correlated sufficiently well with tumor volume changes and the assessed tumor volume response. In the inter-criteria reproducibility study between RECIST guidelines and WHO criteria, the response rate assessed by RECIST guidelines (19.3%) was almost the same as that assessed by WHO criteria (20.0%). In conclusion, RECIST guidelines are adequate for evaluating tumor response to chemotherapy in terms of both validity in relation to tumor volume and inter-criteria reproducibility with the WHO criteria.     

Regulation of DARPP-32 Thr75 phosphorylation by neurotensin in neostriatal neurons: involvement of glutamate signalling

Neurotensin is a neuropeptide involved in dopaminergic signalling. We have recently reported that neurotensin stimulates the phosphorylation of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa) at Thr34 (PKA-site) by activating dopamine D1-type receptors in neostriatal neurons. DARPP-32 is also phosphorylated by cyclin-dependent kinase 5 on Thr75, and the phosphorylated form of DARPP-32 at Thr75 inhibits protein kinase (PKA) activity. In this study, we examined the effect of neurotensin on DARPP-32 Thr75 phosphorylation using mouse neostriatal slices. Neurotensin decreased the level of phospho-Thr75 DARPP-32 at 2 min of incubation, maximally to about 50% of control at a concentration of 1 micro m. Pretreatment with a combined neurotensin receptor type 1 (NTR1)/type 2 (NTR2) antagonist, SR142948, reduced the basal level of phospho-Thr75 DARPP-32 and abolished the ability of neurotensin to decrease DARPP-32 Thr75 phosphorylation. However, neither an NTR1 antagonist, SR48692, an NTR2 antagonist, levocabastine, nor the two combined affected the basal level and the neurotensin-mediated decrease in DARPP-32 Thr75 phosphorylation. The effect of neurotensin was abolished by tetrodotoxin (TTX) or MK801 plus CNQX, but not by SCH23390 or raclopride. These results indicate that neurotensin stimulates the release of glutamate by activating a hypothesized unidentified neurotensin receptor, resulting in the dephosphorylation of DARPP-32 at Thr75 by activating NMDA and AMPA receptors expressed at medium spiny neurons. Thus, neurotensin, by removing the inhibition of PKA by phospho-Thr75 DARPP-32, potentiates its signalling via the dopamine/D1 receptor/PKA/phospho-Thr34 DARPP-32/PP-1 cascade.     

Cholinergic mechanism in the lateral septal area is involved in the stress-induced blood pressure increase in rats

Previously, we demonstrated that the rostral part of the ventral zone of the lateral septal area (LSV) was involved in the restraint stress-induced pressor response. It is suggested that there exist acetylcholine receptors responsible for blood pressure increase in the caudal part of the lateral septal area. In this study, we examined whether acetylcholine receptors responsible for pressor responses also exist in the rostral part of the LSV and whether these acetylcholine receptors are involved in the stress-induced pressor response in rats. Microinjection of either carbachol (10-100pmol) or physostigmine (0.46 and 1.5nmol) into the LSV caused a dose-dependent increase in blood pressure. The pressor response to carbachol (30pmol) was inhibited by the M1 antagonist pirenzepine and the M3 antagonist 4-DAMP mustard but not by the M2 antagonist methoctramine injected into the LSV. Bilateral microinjections of the M1/M3 antagonist 4-DAMP (1nmol) inhibited the restraint stress-induced pressor response. These findings suggest that M1/M3 muscarinic receptors responsible for blood pressure increase exist in the rostral part of the LSV and they are partly involved in the stress-induced pressor response.     

Association of total and central obesity with mortality in postmenopausal women with coronary heart disease

Overweight and abdominal obesity increase mortality risk, although the risk may be mediated by traditional cardiac risk factors. The authors assessed the association of baseline measures, change in overall body weight and abdominal obesity (waist circumference), and weight and waist circumference cycling with total mortality among postmenopausal women with known heart disease. They used data from 2,739 US women who participated in the Heart and Estrogen/progestin Replacement Study between 1993 and 2001. Over 6.8 years of follow-up, 498 women died. In adjusted Cox models that included either baseline waist circumference or body mass index (BMI), each was associated with mortality. However, after further adjustment for diabetes, hypertension, and lipoproteins, these associations disappeared. In models including both waist circumference and BMI, larger waist circumference (hazard ratio=1.40 per standard deviation, 95% confidence interval: 1.16, 1.68) was associated with increased risk and higher BMI (hazard ratio=0.81 per standard deviation, 95% confidence interval: 0.67, 0.97) was associated with decreased risk of total mortality, independent of cardiac risk factors. Weight and waist circumference cycling were not associated with mortality. Results show that both BMI and waist circumference are associated with mortality among postmenopausal women with established heart disease, but waist circumference may be more important than BMI, and their effects may be largely mediated by other cardiac risk factors.