Evaluation of 25 years of Uterine Cervical Cancer Screening at Tokai University Hospital Health Evaluation and Promotion Center.

The total number of persons who underwent uterine cervical cancer screening at the Tokai University Hospital Health Evaluation and Promotion Center during the 25-year period from January 1976 to March 2001 was 30,173 (gross number: 111,181). Since 1995, more than 6,500 females have visited the center annually, and more than 70% were 40-59 years of age. Among these females, 849 exhibited atypical changes higher than class IIIa in the cytological examination (class IIIa: 779, IIIb: 43. IV: 14 and V: 13), and the detection rate was 0.76%. In examining the relationship between the age and number of visits to the center and the detection rate of atypical changes observed in the cytological examination, patients in their 40s exhibited the highest detection rate (1.31%), and the rate at the first screening was 1.19%. Analysis of the age distribution for the detection rate of atypical changes in the cytological examination before 1989 and after 1990 showed that persons in their 40s and 50s had high rates (1.62% and 1.69%, respectively) before 1989, but since 1990 persons in their 20s, 30s and 40s exhibited high rates (2.86%, 2.16% and 2.61%, respectively) (p ＜ 0.001). This suggests a lowering of the age at which atypical changes are observed in the cytological examination.

Progression of 189 women diagnosed with uterine cervical dysplasia based on abnormal results in mass screening.

During the five-year period from January 1997 to December 2001, cytological abnormalities in the uterine cervix were confirmed in 189 women (class IIIa: 172, class IIIb: 9, class IV: 7, and class V: 1) who underwent cytology screening of the uterine cervix at the Tokai University Health Evaluation and Promotion Center. Biopsy samples from the uterine cervix showed that the 172 women categorized into class IIIa based on cytology included 28 with no atypical lesions, 53 with mild dysplasia, 24 with moderate dysplasia, 3 with severe dysplasia; and the 9 women in class IIIb included 2 with mild dysplasia, 5 with moderate dysplasia, 1 with carcinoma in situ, and 1 with invasive carcinoma. The conformity rates between the cytology data and the biopsy samples were 71.3% and 11.1% in class IIIa and class IIIb, respectively. A three-year followup survey of the class IIIa and class IIIb subjects confirmed progression (PRO) in 8 (4.7%), continuous (CON) symptoms in 48 (27.9%), and regression (REG) in 116 (67.4%) in class IIIa, and PRO, CON and REG in 3 (33.3%), 4 (44.4%), and 2 (22.2%), respectively, in class IIIb; the percentage of subjects in the CON+REG group was significantly higher than in the PRO group (p = 0.0052). Twelve subjects underwent resection because uterine carcinoma was suspected in the punch biopsy; these subjects have remained under observation and have now made a complete recovery. Our results suggest that patients with uterine abnormal cells should undergo regular cytology and colposcopy for detection of high-risk patients and to allow treatment at an early stage.

Uterine body cancer mass screening at Tokai University Hospital.

A total of 1,512 women participated in mass screenings for uterine body cancer (UBC) from 1998 to 2003 at Tokai University Hospital. Their rate in the examinees of uterine cervical cancer (UCC) mass screenings was 4.7%. Among the 1,512 examinees, endometrial cytological abnormalities (class III or higher) were found in 17 (1.1%) cases. As a result, UBC was detected in two patients (0.13%). One case was diagnosed as class V, adenocarcinoma, and she underwent hysterectomy. In another case, adenocarcinoma was found to be associated with atypical endometrial hyperplasia in hysterectomy specimens. For the remaining 15 cases diagnosed as class III, the cytological abnormalities disappeared after a follow-up except for 3 patients who were not followed at Tokai University Hospital. In a comparison of the examinees with or without genital bleeding, the cytological abnormalities were more frequently detected in the former group; 4.2% (6/142) vs. 0.6% (5/819) (p < 0.05). We recommend examinees aged 40 years or higher with a complaint of genital bleeding to participate in UBC mass screening for detection of endometrial adenocarcinoma at early stages.

Platelet inhibition by single low-dose aspirin, using the newly developed aggregometry with the laser light scattering method.

Low-dose aspirin (acetylsalicylic acid 81 mg/day, LDA) is often used as an antiplatelet drug in the treatment of cardiovascular and cerebrovascular diseases as well as for patients with anti-phospholipid antibody syndrome. In this study, we explored the duration of the inhibitory effect of a single LDA on platelet aggregation, using the newly developed aggregometry with the laser light scattering method. Five healthy volunteers (females between 23 and 30 years old) ingested 81 mg of buffered aspirin. Platelet aggregation was measured with adenosine 5'-diphosphate before the ingestion and at the 1st, 2nd, 4th, 6th, and 8th day thereafter. The results showed that the effect of 81 mg of aspirin continues for at least 8 days, which suggested that the intermittent administration of 81 mg of aspirin (a few times a week) might be an alternative way to induce the anti-platelet effect.

Beta-naphthoflavone disturbs astrocytic differentiation of C6 glioma cells by inhibiting autocrine interleukin-6.

Regulation of astrocyte differentiation is a key process in the development of the central nervous system (CNS), and disturbance of the differentiation can lead to brain system dysfunction. Here we show that beta-naphthoflavone (betaNF), an agonist of the aryl hydrocarbon receptor (AhR), disturbed the cAMP-induced astrocytic differentiation of C6 glioma by inhibiting autocrine interleukin-6 (IL-6). Treatment of cells with betaNF reduced the induction of an astrocyte marker glial fibrillary acidic protein (GFAP). This was caused by the inactivation of its upstream transcription factor signal transducer and activator of transcription 3 (STAT3) by betaNF. In addition, betaNF attenuated the induction of the IL-6 gene, which leads to the activation of STAT3. Most importantly, the inhibitory effect of betaNF on GFAP promoter activity was recovered by the addition of recombinant IL-6. Taken together, these results indicate that the inhibitory effect of betaNF on IL-6 induction suppresses STAT3 activation. These processes subsequently lead to the attenuation of GFAP induction.

cAMP-induced astrocytic differentiation of C6 glioma cells is mediated by autocrine interleukin-6.

Elevation in the level of intracellular cAMP is known to induce the astrocytic differentiation of C6 glioma cells by unknown mechanisms. In this report, we show that cAMP-induced autocrine interleukin 6 (IL-6) promoted astrocytic differentiation of C6 cells. Treatment of cells with N(6),2'-O-dibutyryl cAMP (Bt(2)AMP) and theophylline caused the delayed phosphorylation of signal transducer and activator of transcription 3 (STAT3), as well as the expression of an astrocyte marker, glial fibrillary acidic protein (GFAP). Overexpression of the dominant-negative form of STAT3 leads to the suppression of GFAP promoter activity, suggesting that STAT3 activity was essential for cAMP-induced GFAP promoter activation. On the other hand, the IL-6 gene was quickly induced by Bt(2)AMP/theophylline, and subsequent IL-6 protein secretion was stimulated. In addition, recombinant IL-6 induced GFAP expression and STAT3 phosphorylation. Most importantly, treatment with IL-6-neutralizing antibody dramatically reduced the cAMP-induced GFAP expression and STAT3 phosphorylation and reversed the cellular morphological changes that had been caused by Bt(2)AMP/theophylline. Taken together, these results indicated that Bt(2)AMP/theophylline lead to delayed STAT3 activation via autocrine IL-6. These processes subsequently led to the induction of GFAP. IL-6 secretion is thus thought to be a key event in controlling the astrocytic differentiation of C6 cells.

Preservation of tubal function following methotrexate treatment for ectopic pregnancy.

To evaluate methotrexate (MTX) administration as a conservative treatment for ectopic pregnancy, we reviewed the medical records of 248 cases (210 patients) of MTX treatment for tubal pregnancies at our department between December 1985 and December 2003, and compared its pregnancy prognosis with that of laparoscopic salpigotomy (59 patients). With the MTX treatment, 185 patients were successfully treated, and the subsequent pregnancy rate and ectopic pregnancy rate were 48.4 % and 18.4 %, respectively, while those rates were 49.2 % and 18.6 %, respectively, after the salpigotomy. These results suggest that MTX treatment is comparable to the more conservative operation. To clarify the (dys/) function of the ectopic implantation tubes and MTX-treated tube (s), we excluded patients who had a contra-lateral healthy tube, and extracted 40 patients as "the affected tube group", where the pregnancy-related parameters were not adversely affected. The findings suggest that MTX is not necessary to preserve tubal function.