Effects of preemptive analgesia with intravenous acetaminophen on postoperative pain relief in patients undergoing third molar surgery: a prospective, single-blind, randomized controlled trial.

BACKGROUND: The efficacy of preemptive analgesia in managing postoperative pain remains controversial. The aim of this study was to compare the efficacy of intravenous (IV) acetaminophen administered before or immediately after the surgical extraction of an impacted mandibular third molar. MATERIAL AND METHODS: This prospective randomized clinical trial included 120 patients. The patients were assigned to one of three groups: the preoperative-treatment group (pre-group), which received 1000 mg of IV acetaminophen 20 min before surgery; the postoperative-treatment group (post-group), which received 1000 mg of IV acetaminophen after surgery; the no-treatment group (control-group), which did not receive any analgesic. Rescue analgesic (60 mg loxoprofen) was issued to each patient, with instructions on self-administration if needed. For the rescue medication usage, the time of first loxoprofen usage and the total amount of loxoprofen consumption were obtained for a 17-hour period after surgery. We measured pain using the visual analogue scale at 1 hour and at 2, 3, 4, 5, and 15 hours after surgery. RESULTS: There was no significant difference in pain level among the three groups at any time interval. However, the pre-group demonstrated significantly lower rescue analgesic consumption and longer time until initial administration. CONCLUSIONS: Administration of IV acetaminophen before third molar surgery provides more effective pain control than postoperative administration and no treatment.

TTF-1/NKX2-1 binds to DDB1 and confers replication stress resistance to lung adenocarcinomas.

TTF-1, also known as NKX2-1, is a transcription factor that has indispensable roles in both lung development and physiology. We and others have reported that TTF-1 frequently exhibits high expression with increased copy number in lung adenocarcinomas, and also has a role as a lineage-survival oncogene through transcriptional activation of crucial target genes including ROR1 and LMO3. In the present study, we employed a global proteomic search for proteins that interact with TTF-1 in order to provide a more comprehensive picture of this still enigmatic lineage-survival oncogene. Our results unexpectedly revealed a function independent of its transcriptional activity, as TTF-1 was found to interact with DDB1 and block its binding to CHK1, which in turn attenuated ubiquitylation and subsequent degradation of CHK1. Furthermore, TTF-1 overexpression conferred resistance to cellular conditions under DNA replication stress (RS) and prevented an increase in consequential DNA double-strand breaks, as reflected by attenuated induction of pCHK2 and γH2AX. Our findings suggest that the novel non-transcriptional function of TTF-1 identified in this study may contribute to lung adenocarcinoma development by conferring tolerance to DNA RS, which is known to be inherently elicited by activation of various oncogenes.

Lung cancer associated with an azygos lobe successfully treated with video-assisted thoracoscopic surgery.

Primary lung cancer associated with an azygos lobe is extremely rare. Herein, we report the case of a 64-year-old woman with lung adenocarcinoma arising in the right upper lobe with an azygos lobe. The patient underwent a right upper lobectomy and lymph node dissection with video-assisted thoracoscopic surgery. Video-assisted thoracoscopic surgery lobectomy for lung cancer of this variant has yet to be reported. We demonstrate the intraoperative findings and the resected pulmonary lobe. This is the first case of primary lung cancer associated with the azygos lobe treated by lobectomy with video-assisted thoracoscopic surgery.

Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid.

AIM: Tumour necrosis factor-alpha (TNF-alpha) is one of the major inflammatory cytokines involved in the pathogenesis of various vitreoretinal diseases. The authors investigated the effect of hypoxia, TNF-alpha and dexamethasone on vascular endothelial growth factor (VEGF) expression by cultured hyalocytes. METHODS: Hyalocytes were isolated from bovine vitreous. Hypoxic and TNF-alpha-dependent effects on cultured hyalocytes were investigated using several assays to determine VEGF protein expression, hypoxia-inducible factor (HIF)-1alpha protein levels, HIF-1alpha-DNA-binding ability and VEGF mRNA stability. The effects of dexamethasone on VEGF expression and its intracellular signalling under hypoxic or TNF-alpha stimulated conditions were also examined. RESULTS: Hypoxic conditions and TNF-alpha stimulation induce VEGF expression in hyalocytes. These stimuli also stabilise HIF-1alpha protein and increase its DNA-binding ability. Dexamethasone significantly inhibits both HIF-1alpha protein levels and HIF-1alpha-DNA-binding activity, and also decreases the hypoxic- and TNF-alpha -dependent induction of VEGF expression in hyalocyte. However, dexamethasone has no significant effect on the stability of VEGF mRNA. CONCLUSIONS: Hyalocytes may be involved in various vitreoretinal diseases by increasing HIF-1alpha protein stability and HIF-1alpha-DNA binding, and thus increasing VEGF production under pathological conditions. Dexamethasone seems to be capable of inhibiting hypoxic and TNF-alpha dependent VEGF production, presumably via its inhibitory effects on HIF-1alpha protein levels and its DNA-binding activity.

Estimation of estrogenic and antiestrogenic activities of selected pesticides by MCF-7 cell proliferation assay.

Estrogenic activities of 20 selected pesticides-which are used for agricultural production as insecticides, fungicides and herbicides-were examined by estrogen receptor (ER)-dependent MCF-7 cell proliferation assay. Among them, chlordecone, dicofol, methoxychlor, gamma-HCH, fenarimol, EPN, triadimefon, and triadimenol had estrogenic activities, all of which were suppressed by the addition of pure antiestrogen ICI 182,780. The first 5 compounds exhibited binding capacities to ERalpha. The antiestrogenic activity of a compound was examined by estimating its suppressive effect on cell proliferation induced by 30 pM 17beta-estradiol. Strongly suspected antiestrogens were captan and myclobutanil, both of which were found to have the capacity to bind to ERalpha and which might exert their activities by competing at the level of ERalpha. Antiestrogenic activities of nitrofen, fenitrothion, fenarimol and triadimefon were also suggested. Affinities of the compounds for ERalpha and/or androgen receptor (AR) were lower than those of synthetic estrogen (diethylstilbestrol) and testosterone (mibolerone), respectively. Fenitrothion had the highest affinity to AR. Chlordecone, dicofol, methoxychlor, nitrofen, fenarimol, myclobutanil and pyridate had capacities to bind both ERalpha and AR. Chlordecone and pyridate were much more effective as competitors of estrogen binding to ERalpha than androgen binding to AR and, conversely, nitrofen was a more effective competitor of androgen binding to AR.

Cell death induced by the phenolic antioxidant tert-butylhydroquinone and its metabolite tert-butylquinone in human monocytic leukemia U937 cells.

2-tert-Butyl-4-hydroquinone (TBHQ), a phenolic antioxidant used as a food additive, and its metabolite 2-tert-butyl-1,4-benzoquinone (TBQ) were both cytotoxic in human monocytic leukemia U937 cells, TBQ being the more strongly cytotoxic. Both compounds induced caspase activity towards DEVD-MCA as a substrate and the cleavage of poly(ADP-ribose) polymerase in cells. Enzyme activities of caspase-3,-7,-6 and -9 seemed to be induced, and procaspases-3 and-7 were processed to active forms in cells treated with TBHQ and TBQ. They induced nuclear condensation and fragmentation in some cells. Electron microscopic examination revealed severe disruption of mitochondrial structure and the formation of intracellular vacuoles. Morphological changes were more marked in the cells treated with TBHQ than TBQ. Mitochondrial transmembrane potential was disrupted. Cytochrome c was released from mitochondria to cytosol and ATP level was moderately decreased by the treatment of cells with these chemicals. Cellular glutathione (GSH) appeared to contribute to defense against cell death induced by TBQ, but its contribution was not marked in the case of TBHQ. TBHQ and TBQ exhibited the apoptotic features in various assays, but the mode of cell death may not be defined as a typical apoptosis or necrosis.

ER-dependent estrogenic activity of parabens assessed by proliferation of human breast cancer MCF-7 cells and expression of ERalpha and PR.

Estrogenic activities of the phenolic preservatives methylparaben, ethylparaben, propylparaben, butylparaben, isopropylparaben and isobutylparaben were examined by assaying estrogen-receptor (ER)-dependent proliferation of MCF-7 cells. All the compounds stimulated the proliferation to about the same level as the maximal cell yield attained with 3x10(-11) M 17beta-estradiol, but at a concentration in the order of 10(5) to 10(7) higher than 17beta-estradiol. The cell-proliferative effects of parabens were completely suppressed by anti-estrogen ICI 182,780. MCF-7 cells treated with butylparaben and isobutylparaben exhibited a decrease in gene expression of ERalpha and an increase in that of progesterone-receptor (PR), but the effects of these parabens were not as prominent as those of 17beta-estradiol. Western blot analysis indicated that these parabens caused a slight decrease in expression of ERalpha protein. Competitive binding to human ERalpha and ERbeta in vitro revealed that the parabens with longer side-chains showed greater affinity for estrogen receptors, and that they had similar relative binding affinity (RBA) values to both ERalpha and ERbeta. RBA values were much smaller than that of diethylstilbestrol. In conclusion, parabens have ER-dependent estrogenic activities, and their effects on the intracellular signaling pathway might be different from that of 17beta-estradiol.

Structure of a quinohemoprotein amine dehydrogenase with an uncommon redox cofactor and highly unusual crosslinking.

The crystal structure of the heterotrimeric quinohemoprotein amine dehydrogenase from Paracoccus denitrificans has been determined at 2.05-A resolution. Within an 82-residue subunit is contained an unusual redox cofactor, cysteine tryptophylquinone (CTQ), consisting of an orthoquinone-modified tryptophan side chain covalently linked to a nearby cysteine side chain. The subunit is surrounded on three sides by a 489-residue, four-domain subunit that includes a diheme cytochrome c. Both subunits sit on the surface of a third subunit, a 337-residue seven-bladed beta-propeller that forms part of the enzyme active site. The small catalytic subunit is internally crosslinked by three highly unusual covalent cysteine to aspartic or glutamic acid thioether linkages in addition to the cofactor crossbridge. The catalytic function of the enzyme as well as the biosynthesis of the unusual catalytic subunit is discussed.

Urinary 17-hydroxycorticosteroids and 17-ketosteroid sulfates in normal children and in children with atopic dermatitis or renal disease.

We measured both urinary 17-hydroxycorticosteroids(17-OHCS) and 17-ketosteroid sulfates(17-KS-S) in normal children and in children with some diseases to evaluate adaptation to stress in children. 17-OHCS and 17-KS-S values were measured in morning urine from 60 normal children(3-18 years old) and 24 children with atopic dermatitis or renal disease. In normal children, the 17-OHCS/creatinine showed no difference by age, but both 17-KS-S/creatinine and 17-KS-S/17-OHCS showed significant positive correlation with age. No sex differences were significant. In children with atopic dermatitis or with renal disease treated with cyclosporine A, 17-OHCS/creatinine was significantly higher and the 17-KS-S/17-OHCS ratio was significantly lower than in age-matched controls. These values returned to normal as the conditions improved or as treatment ended. In patients who underwent renal biopsy, both 17-OHCS/creatinine and 17-KS-S/creatinine values were significantly higher after biopsy than before because of the stress caused by pain and complete bed rest. Measurement of urinary 17-OHCS and 17-KS-S in children can be useful for evaluation of adaptation to stress as well as in adults.

Age-period-cohort analysis of lung cancer mortality in Japan, 1960-1995.

The mortality data on lung cancer in Japan from 1960 to 1995 was analysed based on an age-period-cohort (APC) model. Though the APC model has an 'identifiable problem' caused by the relationship of age, period and cohort parameters, non-linear components of them revealed their original (separated) effects. They were: (1) non-linear age effects had a peak in 55-59 and 60-64 years old in males and 50-54 in females, (2) non-linear period effects were very small in both genders, (3) non-linear age and period effects were small enough to neglect compared with their linear effects, and (4) there were five parts of trends in Japanese lung cancer mortality in both genders in the non-linear birth cohort effects. The 1961-65 birth cohort effect seemed to increase differently from previous birth years. This trend should be monitored carefully.

DNA damage induced by red food dyes orally administered to pregnant and male mice.

We determined the genotoxicity of synthetic red tar dyes currently used as food color additives in many countries, including JAPAN: For the preliminary assessment, we treated groups of 4 pregnant mice (gestational day 11) once orally at the limit dose (2000 mg/kg) of amaranth (food red No. 2), allura red (food red No. 40), or acid red (food red No. 106), and we sampled brain, lung, liver, kidney, glandular stomach, colon, urinary bladder, and embryo 3, 6, and 24 h after treatment. We used the comet (alkaline single cell gel electrophoresis) assay to measure DNA damage. The assay was positive in the colon 3 h after the administration of amaranth and allura red and weakly positive in the lung 6 h after the administration of amaranth. Acid red did not induce DNA damage in any sample at any sampling time. None of the dyes damaged DNA in other organs or the embryo. We then tested male mice with amaranth, allura red, and a related color additive, new coccine (food red No. 18). The 3 dyes induced DNA damage in the colon starting at 10 mg/kg. Twenty ml/kg of soaking liquid from commercial red ginger pickles, which contained 6.5 mg/10 ml of new coccine, induced DNA damage in colon, glandular stomach, and bladder. The potencies were compared to those of other rodent carcinogens. The rodent hepatocarcinogen p-dimethylaminoazobenzene induced colon DNA damage at 1 mg/kg, whereas it damaged liver DNA only at 500 mg/kg. Although 1 mg/kg of N-nitrosodimethylamine induced DNA damage in liver and bladder, it did not induce colon DNA damage. N-nitrosodiethylamine at 14 mg/kg did not induce DNA damage in any organs examined. Because the 3 azo additives we examined induced colon DNA damage at a very low dose, more extensive assessment of azo additives is warranted.

Preliminary report: effect of adrenal androgen and estrogen on bone maturation and bone mineral density.

To clarify the independent physiological roles of adrenal androgen and estrogen on bone growth, we compared the lumbar spine bone mineral density (BMD) in prepubertal girls with virilizing congenital adrenal hyperplasia (CAH) (n = 17) and girls with central precocious puberty (CPP) (n = 18). When BMD was analyzed according to chronologic age, no significant differences were found between CPP and CAH patients. However, when adjusted to bone age, BMD was statistically higher in CAH than in CPP subjects. This finding suggests that adrenal androgen, as well as estrogen, plays an important role in increasing BMD. Adrenal androgen may act on bone not only as androgen, but as estrogen after having been metabolized into an aromatized bone-active compound in peripheral tissues, such as bone and fat. Therefore, adrenal androgen may have a more important role in increasing BMD than previously realized.

A necessary and sufficient condition of comparability for using standardized mortality ratio (SMR).

A necessary and sufficient condition of comparability for using SMR was studied mathematically by considering the equivalence between SMR and CMF, as CMF was a perfectly comparable index. This condition was expressed by either proportionality of mortality vectors or proportionality of projected person-years to the plane spanned by mortality vectors of reference and index groups. We could obtain another expression of the condition, in which affect of distortions were easily understood, which consist of three factors: distortion of proportionality of mortality, distortion of person-years and similarity of distortions. Our results were applied to study the mortality of biliary tract cancer in Ibaraki Prefecture. Places where absolute difference between CMF and SMR exceeds some criterion (say, 0.15) were Satomi, Ushiboiri, Nihari in males and Gozenyama, Suifu and Asahi in females. All three distortion indices exceeded their upper 95% percentiles in Satomi in males.

Assessment of smoking related risks for respiratory symptoms among elderly people.

Disease risk among elderly smokers is considered to be doubled due to their smoking habits and age as compared with elderly non-smokers. The investigators conducted risk assessments of smoking for respiratory symptoms among elderly people.A questionnaire survey on smoking habits and respiratory symptoms was conducted among 3,000 persons of 56 years of age and over who were randomly selected from suburban residents in a prefecture in Japan in October, 1997. A total 1,954 or 65.1%, of individuals responded, consisting of 42.8% for men and 57.2% for women, with an average age of 73.6 years.In addition to descriptive analysis, multiple logistic regression analysis was conducted. The results are summarized as follows: Smokers accounted for 28.1% of men and 3.6% of women. Among all age-groups, the highest rate of smokers was observed in men of 56-69 years old (34.7%) which was lower than the national average rate for the 60-69 year-old group (56.1% of men and 14.5% of women in '97). The odds ratios and 95 percent confidence interval (95%CI) for "having phlegm every day" and "having phlegm for more than 4 days a week" among smokers were 2.06 (95%CI=1.41-3.01) and 2.77(95%CI=1.80-4.27). Significantly higher odds ratios among smokers were also observed for "wheezing" and "shortness of breath when hurrying".Odds ratios for some respiratory symptoms including "having phlegm for more than 4 days per week" among inhalers were significantly high compared with non-smokers, whereas those among non-inhalers were not significantly different from 1.0. Odds ratios for symptoms of phlegm and wheezing were significantly higher (Odds ratio≥2.0) among heavy smokers (Brinkman Index [B.1] >900) compared to non-smokers, while odds ratios of the same symptoms were not different from 1.0 among light smokers (B. I. ≤500).

[Clinical results of selective laser trabeculoplasty].

PURPOSE: Selective laser trabeculoplasty (SLT) is a new laser procedure using a frequency-doubled Q-switched Nd: YAG laser (wavelength: 532 mm). The laser parameters are set to selectively target pigmented trabecular meshwork (TM) cells without coagulative damage to the TM structure or non-pigmented cells. We investigated the safety and efficacy of SLT in lowering intraocular pressure (IOP). SUBJECTS AND METHOD: Sixty-seven eyes of 67 patients with uncontrolled open angle glaucoma were treated with the Coherent Selecta 7000 (Coherent Inc., Palo Alto, CA). Nineteen of 67 patients had previously received argon laser trabeculoplasty (ALT). A total of approximately 60 non-overlapping spots were placed over 180 degrees of the TM ranging from 0.5 to 1.0 mJ per pulse. The maximum energy level at which no bubble formation was observed determined choice. RESULTS: The average preoperative IOP was 22.4 mmHg. Six months after the operation, mean IOP reduction was 4.4 mmHg, and mean outflow pressure (OP) reduction was 38.1%. One month after the operation 68.7% of patients responded to treatment with an OP reduction of at least 20% ("responders"). Transient IOP elevation of 5 mmHg or greater was seen in 25.4% of patients. The success rate at 6 months after operation was 64.6% for all patients (67 eyes) and 78.2% for the responders (46 eyes). An analysis using a Cox proportional hazard model showed that a low preoperative IOP was the significant determinant for success, and the hazard ratio for the IOP increase of 5 mmHg was 2.12. Other factors such as age, gender, past history of ALT, and goniopigment were not significantly related to success. CONCLUSION: SLT appears to be a safe and effective way to lower IOP.

[The critical appraisal of QOL questionnaire for prostate cancer patients].

BACKGROUND: Prostate cancer is a common malignancy that affects Japanese elderly men. Its incidence is increasing, recently, and its treatments are various. The measurement of quality of life (QOL) has become important for the evaluation of and selection of treatments. In Japan, however, there is no standard way of measuring QOL for prostate cancer patients, except the Japanese version of the EORTC QOL questionnaire for prostate cancer patients. We examined the validity and feasibility of this translated EORTC QOL questionnaire for prostate cancer patients. METHODS: Sixty-nine prostate cancer patients who were under treatment in 4 hospitals were selected for this study. We applied the content validity, the factorial validity which was analyzed by the oblique principal component cluster analysis, the internal consistency analyzed by the alpha coefficient of Cronbach, the convergent validity which was used GHQ, IPSS and PS as external measures, and the feasibility. RESULTS: This questionnaire showed good internal consistency, as the alpha coefficient was 0.61 to 0.90 in all domains, except for sex life, which was the lowest. This questionnaire was classified into 7 clusters by the oblique principal component cluster analysis. Consequently, the factorial validity was good, except for items regarding sex life. As domains correlate well with external measures except in sex life, the convergent validity was good. It was suggested that only two items were not acceptable in regard to the content validity and the feasibility, and that the translation into Japanese of 2 items was inadequate. CONCLUSIONS: Our study suggests that the Japanese version of the EORTC QOL questionnaire for prostate cancer patients demands improvement for the practical employment in clinical trials, as there is a problem of translation and feasibility.

[Clinical experiences and problems with home medical treatment in an orthopedic clinic].

Twenty-five patients who received home medical treatment were reviewed. There were 11 males and 14 females, with a mean age of 77 years. In an orthopedic clinic, it is difficult to secure the time for to visit a patient's home. Another problem for doctor is that the medical fee for home treatment is very low. To promote home treatment by orthopedists, it is important to secure the time to visit a patient's home, to improve the fees for home treatment, and to establish a connection with a visiting nurse care station and visiting rehabilitation workers.

Timing of menopause, reproductive years, and bone mineral density: a cross-sectional study of postmenopausal Japanese women.

Age at menopause has been found to be associated positively with bone mineral density, and age at menarche has been found to be associated negatively with bone mineral density. However, there have been few studies on the relations of timing of menopause and length of the reproductive period with bone mineral density. The purpose of this study was to examine the relations of timing of menopause and reproductive years (calculated as age at menopause minus age at menarche) with mineral density of the second metacarpal bone in postmenopausal Japanese women. The study population consisted of 1,035 naturally menopausal women aged 40-70 years who were screened in 1996-1997. Using computed x-ray densitometry, the authors measured bone mineral density by analyzing radiographic films of the right second metacarpal bone. Using the women with early menopause (age < 49 years) as the reference group and adjusting for age, subjects with late menopause were at decreased risk for low bone mineral density (odds ratio (OR) = 0.69, 95% confidence interval (CI) 0.49-0.97). After adjustment for additional covariates (grip strength, physical activity, body mass index, smoking, and calcium intake), the association was unchanged (OR = 0.70, 95% CI 0.50-0.99). Postmenopausal women with more reproductive years (> or = 40 years) were at decreased risk for low bone mineral density compared with those with fewer reproductive years, after adjustment for age (OR = 0.73, 95% CI 0.40-1.30) and potentially confounding factors (OR = 0.76, 95% CI 0.41-1.37); the p-value for trend was not statistically significant. In multiple linear regression analysis, early menopause and fewer reproductive years were independent predictors of low bone mineral density. In this study, postmenopausal Japanese women who had a late menopause and more reproductive years were at decreased risk for low bone mineral density, and may therefore be less prone to osteoporosis.

The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme.

The Ras target AF-6 has been shown to serve as one of the peripheral components of cell-cell adhesions, and is thought to participate in cell-cell adhesion regulation downstream of Ras. We here purified an AF-6-interacting protein with a molecular mass of approximately 220 kD (p220) to investigate the function of AF-6 at cell-cell adhesions. The peptide sequences of p220 were identical to the amino acid sequences of mouse Fam. Fam is homologous to a deubiquitinating enzyme in Drosophila, the product of the fat facets gene. Recent genetic analyses indicate that the deubiquitinating activity of the fat facets product plays a critical role in controlling the cell fate. We found that Fam accumulated at the cell-cell contact sites of MDCKII cells, but not at free ends of plasma membranes. Fam was partially colocalized with AF-6 and interacted with AF-6 in vivo and in vitro. We also showed that AF-6 was ubiquitinated in intact cells, and that Fam prevented the ubiquitination of AF-6.

Physical activity and the risk of breast cancer: a case-control study of Japanese women.

A case-control study was conducted in Ibaraki, Japan. Cases were 148 women aged 26-69 diagnosed with breast cancer at Tsukuba University Hospital or Tsukuba Medical Center Hospital between January 1990 and March 1997. Two controls were individually matched to cases by age (within 1 year) and residence (municipalities). A self-administered questionnaire was used to obtain information on physical activity and the effects of potential confounding factors. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95 percent confidence intervals (95% CIs). After adjustment for potential confounding factors (height, body mass index (BMI), family history of breast cancer, education, age at menarche, age at first birth, parity, menopausal status), recreational physical activity was associated with a reduced risk of breast cancer (p for trend = 0.005). OR for breast cancer among women who played regular sport or exercise more than 15.3 METs per week was 0.35 (95% CI = 0.17, 0.73), as compared to women with no sport or exercise. The risk of breast cancer was also reduced in women with higher occupational physical activity levels, but it was not significant (p for trend = 0.223). The adjusted OR among the highest quartile level was 0.55 (95% CI = 0.27, 1.12) with the lowest quartile level as reference. Our findings support a protective effect of recreational physical activity on breast cancer in Japanese women.