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Abstract: Objective: To identify adequate weight gain ranges during pregnancy in Japanese women. Method: Obstetric records from 2001 to 2002 for 46,659 term, singleton, vaginally delivered live births was used to estimate IUGR and macrosomia risk. Total maternal weight gain was grouped according to gestational age-specific percentile values of weight gain as follows: “very low” (under the 25th), “low” (25th to 49th), “moderate” (50th to 74th), “high” (75th to 89th), and “very high” (90th and over). Results: About 6% of infants were identified as having IUGR and 0.9% as macrosomia. IUGR risk was elevated with low weight gains. Macrosomia risk was related to high weight gains and previous spontaneous abortions. Conclusion: Achieving weight gains between the 50th and 75th percentiles for gestational age was considered adequate for optimal fetal growth in Japanese pregnant women. [Copyright &y& Elsevier]

: The recommended dietary allowance (RDA) for calcium (Ca) of Japanese adults is proposed to be 600 mg/day, which is lower than those of other countries. In this report we estimated the Ca requirement and the RDA for Ca in elderly Japanese utilizing a Ca balance method. Subjects were 10 men aged 65–72 years and 10 women aged 62–77 years. Following a 14 day adaptation period, each participant was subjected to a low Ca diet (Ca 250 mg as a meal) for 6 days. After an interval of 2 weeks or more, another 14 day adaptation period was set and then a high Ca diet (Ca 250 mg as a meal and 600 mg as CaCO3) was served to the subjects for 6 days. Ca balance was calculated at each dose of Ca intake. Ca requirement was estimated by the intersection of the average Ca intake–retention diagram. Daily Ca requirement was 702 mg in the men and 788 mg in the women. The Ca requirement values were multiplied by 1.2 to obtain the RDA for Ca. As a result, RDA for Ca was 842 mg/day for men and 946 mg/day for women. When these values were normalized with the body weight, the RDA for Ca of Japanese and Caucasian women was similar (18.1 and 18.5 mg/kg body weight per day, respectively). Our results suggest the difference in Ca balance between the genders and among populations may be ascribed at least partly to differences in body size. In addition, body weight should be considered when comparing the RDAs among different populations. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the long-term efficacy and safety of growth hormone replacement therapy (GHRT) in Japanese patients with adult growth hormone deficiency (AGHD)., Methods: We conducted a retrospective study. A total of 110 patients with AGHD receiving GHRT were enrolled. Clinical and laboratory data were collected annually from the beginning of the study. Statistical analysis was performed using a linear mixed-effects model., Results: Of all patients, 46.4% were males, 70.9% had adult-onset GHD, and follow-up was up to 196 months, with a median of 68 months. The insulin-like growth factor-1 standard deviation score increased after the start of GHRT and remained constant for more than 11 years. Seventeen patients were followed up for more than 11 years. The body mass index increased. Waist circumference decreased in the short term but increased in the long term. The diastolic blood pressure decreased 1-5 years after the start of GHRT, and the systolic blood pressure increased 11 years after GHRT. Moreover, a long-term decrease in low-density lipoprotein cholesterol, an increase in high-density lipoprotein cholesterol, and a decrease in aspartate aminotransferase and alanine aminotransferase levels were observed. The glycosylated hemoglobin level increased after 3 years. The bone mineral density in the lumbar spine and total hip increased significantly 3 years after the start of GHRT. Finally, the number of adverse events was eight., Conclusion: We demonstrated the metabolic effectiveness and safety of GHRT in Japanese patients with AGHD over a long follow-up period of 16 years., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

One-carbon metabolism (OCM) is a complex and interconnected network that undergoes drastic changes during pregnancy. In this study, we investigated the longitudinal distribution of OCM-related metabolites in maternal and cord blood and explored their relationships. Additionally, we conducted cross-sectional analyses to examine the interrelationships among these metabolites. This study included 146 healthy pregnant women who participated in the Chiba Study of Mother and Child Health. Maternal blood samples were collected during early pregnancy, late pregnancy, and delivery, along with cord blood samples. We analyzed 18 OCM-related metabolites in serum using stable isotope dilution liquid chromatography/tandem mass spectrometry. We found that serum S-adenosylmethionine (SAM) concentrations in maternal blood remained stable throughout pregnancy. Conversely, S-adenosylhomocysteine (SAH) concentrations increased, and the total homocysteine/total cysteine ratio significantly increased with advancing gestational age. The betaine/dimethylglycine ratio was negatively correlated with total homocysteine in maternal blood for all sampling periods, and this correlation strengthened with advances in gestational age. Most OCM-related metabolites measured in this study showed significant positive correlations between maternal blood at delivery and cord blood. These findings suggest that maternal OCM status may impact fetal development and indicate the need for comprehensive and longitudinal evaluations of OCM during pregnancy., Competing Interests: The research fund for this research was a donation from Amway Japan G.K. The funding company played no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Purpose: Pulmonary complications (PC) are a serious condition with a 20% mortality rate. However, few reports have examined risk factors for PC after colorectal surgery. This study investigated the frequency, characteristics, and risk factors for PC after colorectal cancer surgery., Methods: Between January 2016 and December 2022, we retrospectively reviewed 3979 consecutive patients who underwent colorectal cancer surgery in seven participating hospitals. Patients were divided into patients who experienced PC (PC group, n = 54) and patients who did not (non-PC group, n = 3925). Clinical and pathological features were compared between groups., Results: Fifty-four patients (1.5%) developed PC, of whom 2 patients (3.7%) died due to PC. Age was greater (80 years vs 71 years; p < 0.001), frequency of chronic obstructive pulmonary distress was greater (9.3% vs 3.2%; p = 0.029), performance status was poorer (p < 0.001), the proportion of underweight was higher (42.6% vs 13.4%, p < 0.001), frequency of open surgery was greater (24.1% vs 9.3%; p < 0.001), and blood loss was greater (40 mL vs 22 mL; p < 0.001) in the PC group. Multivariate analysis revealed male sex (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.176-3.986; p = 0.013), greater age (OR 3.180, 95%CI 1.798-5.624; p < 0.001), underweight (OR 3.961, 95%CI 2.210-7.100; p < 0.001), and poorer ASA-PS (OR 3.828, 95%CI 2.144-6.834; p < 0.001) as independent predictors of PC., Conclusion: Our study revealed male sex, greater age, underweight, and poorer ASA-PS as factors associated with development of PC, and suggested that pre- and postoperative rehabilitation and pneumonia control measures should be implemented for patients at high risk of PC., (© 2024. The Author(s).)

Purpose: Colorectal cancer is not common in patients under 40 years old, and its associations with clinical features and the prognosis remain uncertain., Methods: Using a multicenter database, we retrospectively reviewed 3015 patients who underwent colorectal surgery between 2016 and 2021. Patients were divided by age into those < 40 years old (young; n = 52), 40-54 years old (middle-aged; n = 254) and > 54 years old (old; n = 2709). We then investigated age-related differences in clinicopathological features, perioperative outcomes and the prognosis., Results: The proportion of young patients increased annually from 0.63% in 2016 to 2.10% in 2021. Female patients were more frequent, the performance status was better, tumors were larger, clinically node-positive and poorly differentiated adenocarcinomas were more frequent, postoperative complications were less frequent, and the hospital stay was shorter in young patients than in older patients. Young age was an independent predictor of a low risk of postoperative complications (odds ratio, 0.204; 95% confidence interval, 0.049-0.849; p = 0.028). With pathologically node-positive status, adjuvant chemotherapy was more frequent in young patients (100%) than in middle-aged (73.7%) or old (51.8%) patients (p < 0.001), and the 3-year relapse-free survival was better in the young group than in others., Conclusion: Despite higher rates of advanced tumors in younger patients, adequate adjuvant chemotherapy appears to improve the relapse-free survival., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: The effect of laparoscopic surgery on short-term outcomes in colorectal cancer patients over 90 years old has remained unclear., Methods: We reviewed 87 colorectal cancer patients aged over 90 years who underwent surgery between 2016 and 2022. Patients were divided into an open surgery group (n = 22) and a laparoscopic surgery group (n = 65). The aim of this study was to investigate the effect of laparoscopic surgery on postoperative outcome in elderly colorectal cancer patients, as compared to open surgery., Results: Seventy-eight patients (89.7%) had comorbidities. Frequency of advanced T stage was lower with laparoscopic surgery (p = 0.021). Operation time was longer (open surgery 146 min vs. laparoscopic surgery 203 min; p = 0.002) and blood loss was less (105 mL vs. 20 mL, respectively; p < 0.001) with laparoscopic surgery. Length of hospitalization was longer with open surgery (22 days vs. 18 days, respectively; p = 0.007). Frequency of infectious complications was lower with laparoscopic surgery (18.5%) than with open surgery (45.5%; p = 0.021). Multivariate analysis revealed open surgery (p = 0.026; odds ratio, 3.535; 95% confidence interval, 1.159-10.781) as an independent predictor of postoperative infectious complications., Conclusions: Laparoscopic colorectal resection for patients over 90 years old is a useful procedure that reduces postoperative infectious complications., (© 2023. The Author(s).)

Introduction: Thirty-day reoperation rate reflects short-term surgical outcomes following surgery. Laparoscopic surgery for colorectal cancer reportedly has positive effects on postoperative complications. This retrospective study investigated risk factors for 30-day reoperation rate among patients after laparoscopic colorectal cancer surgery using a multicenter database., Methods: Participants comprised 3037 patients who had undergone laparoscopic resection of colorectal cancer between April 2016 and December 2022 at the Nagasaki University and six affiliated centers, classified into those who had undergone reoperation within 30 days after surgery (RO group; n = 88) and those who had not (NRO group; n = 2949). Clinicopathological characteristics were compared between groups., Results: In the RO group, anastomotic leakage occurred in 57 patients (64.8%), intestinal obstruction in 12 (13.6%), and intraabdominal abscess in 5 (5.7%). Female patients were more frequent, preoperative treatment less frequent, body mass index (BMI) lower, operation time longer, blood loss greater, and hospital stay longer in the RO group (p < .05 each). Multivariate analysis revealed BMI (odds ratio, 0.415; 95% confidence interval, 0.218-0.787; p = .021) and poor performance status (odds ratio, 1.966; 95% confidence interval, 1.106-3.492; p = .021) as independent predictors of reoperation., Conclusion: Perioperative measures are warranted for patients with low BMI and poor performance status undergoing laparoscopic colorectal surgery., (© 2023 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: We conducted a study to investigate the relationship between optic nerve vertical cup-to-disc ratio (VCDR), body and ocular parameters, and brain lesions in middle-aged and above Japanese subjects, because although various risk factors for glaucoma have been previously characterised, it is theorised that there are unidentified neurological components., Methods: In this population-based, age/gender-stratified, cross-sectional study that involved 2239 Japanese subjects (1127 men and 1112 women) aged 40 years and older (mean age: 59.3±11.7 years) living in the central geographical region of Japan who participated in the National Institute of Longevity Sciences-Longitudinal Study of Aging between 2002 and 2004, 4327 eyes and 2239 obtained MRIs of the head were evaluated. Multivariate mixed model and trend analyses were also performed., Results: No significant relationship between VCDR and brain lesions, other than basal ganglia lesions, was found. VCDR significantly increased with the high grade of basal ganglia infarct lesions (p=0.0193) and high intraocular pressure (p<0.0001) after adjustment for influential factors using a multivariate mixed model. A significant positive linear trend was observed between the predicted VCDR and the degrees of the basal ganglia lesions (p value trend=0.0096)., Conclusion: Our findings suggest that in subjects with higher grades of basal ganglia lesions, strict attention should be paid to elevated VCDR; however, further studies are needed to support/confirm our results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The efficacy of laparoscopic multivisceral resection (Lap-MVR) has been reported by several experienced high-volume centers. The Endoscopic Surgical Skill Qualification System (ESSQS) was established in Japan to improve the skill of laparoscopic surgeons and further develop surgical teams. We examined the safety and feasibility of Lap-MVR in general hospitals, and evaluated the effects of the Japanese ESSQS for this approach., Methods: We retrospectively reviewed 131 patients who underwent MVR between April 2016 and December 2019. Patients were divided into the laparoscopic surgery group (LAC group, n = 98) and the open surgery group (OPEN group, n = 33). The clinicopathological and surgical features were compared between the groups., Results: Compared with the OPEN group, BMI was significantly higher (21.9 vs 19.3 kg/m 2 , p = 0.012) and blood loss was lower (55 vs 380 ml, p < 0.001) in the LAC group. Operation time, postoperative complications, and postoperative hospital stay were similar between the groups. ESSQS-qualified surgeons tended to select the laparoscopic approach for MVR (p < 0.001). In the LAC group, ESSQS-qualified surgeons had superior results to those without ESSQS qualifications in terms of blood loss (63 vs 137 ml, p = 0.042) and higher R0 resection rate (0% vs 2.0%, p = 0.040), despite having more cases of locally advanced tumor. In addition, there were no conversions to open surgery among ESSQS-qualified surgeons, and three conversions among surgeons without ESSQS qualifications (0% vs 15.0%, p = 0.007). Multivariate analysis revealed blood loss (odds ratio 1.821; 95% CI 1.324-7.654; p = 0.010) as an independent predictor of postoperative complications. Laparoscopic approach was not a predictive factor., Conclusions: The present multicenter study confirmed the feasibility and safety of Lap-MVR even in general hospitals, and revealed superior results for ESSQS-qualified surgeons., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Laparoscopic surgery for transverse colon cancer has been excluded from 7 randomized trials for various reasons. The optimal procedure for transverse colon cancer remains controversial., Objective: This study aimed to analyze the patterns of lymph node metastasis in transverse colon cancer and to report short- and long-term outcomes of the treatment procedures., Design: This was a single-center retrospective study., Settings: This study was conducted at Cancer Institute Hospital, Tokyo, Japan., Patients: We enrolled 252 patients who underwent laparoscopic surgery for transverse colon cancer., Interventions: The transverse colon was divided into 3 segments, and the procedures for transverse colon cancer were based on these segments, as follows: right hemicolectomy, transverse colectomy, and left hemicolectomy., Main Outcome Measures: Postoperatively, the surgeons identified and mapped the lymph nodes from specimens and performed formalin fixation separately to compare the results of the pathological findings., Results: For right-sided, middle-segment, and left-sided transverse colon cancers, the frequency of lymph node metastases was 28.2%, 19.2%, and 19.2%. Skipped lymph node metastasis occurred in right-sided and left-sided transverse colon cancers but not in middle-segment transverse colon cancers. The pathological vascular invasion rate was significantly higher in right and left hemicolectomy than in transverse colectomy. For right hemicolectomy, transverse colectomy, and left hemicolectomy, 5-year overall survival rates were 96.3%, 92.7%, and 93.7%, and relapse-free survival rates were 92.4%, 88.3%, and 95.5%. In multivariate analysis, the independent risk factor for relapse-free survival was lymph node metastasis., Limitations: Selection bias and different backgrounds may have influenced surgical and long-term outcomes., Conclusion: Laparoscopic surgery for transverse colon cancer may be a feasible technique. Harvested lymph node mapping after laparoscopic resection based on D3 lymphadenectomy may help guide the field of dissection when managing patients who have transverse colon cancer. The only independent prognostic factor for relapse-free survival was node-positive cancer. See Video Abstract at http://links.lww.com/DCR/B706.MAPEO DE GANGLIOS LINFÁTICOS EN CÁNCER DE COLON TRANSVERSO TRATADO MEDIANTE COLECTOMÍA LAPAROSCÓPICA CON LINFADENECTOMÍA D3ANTECEDENTES:La cirugía laparoscópica en casos de cáncer de colon transverso fué excluida de siete estudios randomizados mayores por diversas razones. El procedimiento más idóneo en casos de cáncer de colon transverso, sigue siendo controvertido.OBJETIVO:Analizar los patrones de las metástasis en los ganglios linfáticos en casos de cáncer de colon transverso y reportar los resultados a corto y largo plazo de los diferentes procedimientos para su tratamiento.DISEÑO:Estudio retrospectivo en un solo centro de referencia.AJUSTE:Estudio llevado a cabo en el Hospital del Instituto del Cancer, Tokio, Japón.PACIENTES:Fueron incluidos 252 pacientes, sometidos a cirugía laparoscópica por cáncer de colon transverso.INTERVENCIONES:El colon transverso fué dividido en tres segmentos y los procedimientos en casos de cáncer se basaron sobre estos segmentos del tranverso, de la siguiente manera: hemicolectomía derecha, colectomía transversa y hemicolectomía izquierda.PRINCIPALES MEDIDAS DE RESULTADO:En el postoperatorio, los cirujanos identificaron y mapearon los ganglios linfáticos de las piezas quirúrgicas y las fijaron con formaldehido por separado para así poder comparar los resultados con los hallazgos histopatológicos.RESULTADOS:En los cánceres de colon transverso del segmento derecho, del segmento medio y del segmento izquierdo, la frecuencia de metástasis en los ganglios linfáticos fue del 28,2%, 19,2% y 19,2%, respectivamente. Las metástasis en los ganglios linfáticos omitidos se produjo en los cánceres de colon transverso del lado derecho y del lado izquierdo, pero no en los cánceres de colon transverso del segmento medio. La tasa de invasión vascular patológica fue significativamente mayor en la hemicolectomía derecha e izquierda que en la colectomía transversa. Para la hemicolectomía derecha, colectomía transversa y hemicolectomía izquierda, las tasas de supervivencia general a cinco años fueron del 96,3%, 92,7% y 93,7%, y las tasas de supervivencia sin recaída fueron del 92,4%, 88,3% y 95,5%, respectivamente. En el análisis multivariado, el factor de riesgo independiente para la sobrevida sin recidiva fue la metástasis en los ganglios linfáticos.LIMITACIONES:El sesgo de selección y los diferentes antecedentes pueden haber influido en los resultados quirúrgicos a largo plazo.CONCLUSIONES:La cirugía laparoscópica en casos de cáncer de colon transverso puede ser una técnica factible. El mapeo de los ganglios linfáticos recolectados después de la resección laparoscópica basada en la linfadenectomía D3 puede ayudar a guiar el campo de la disección en el manejo de pacientes con cáncer de colon transverso. El único factor pronóstico independiente para el SLR fue el cáncer con ganglios positivos. Consulte Video Resumen en http://links.lww.com/DCR/B706. (Traducción-Dr. Xavier Delgadillo)., (Copyright © The ASCRS 2022.)

Background/aim: The effect of neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) for locally advanced rectal cancer (LARC) is not fully understood. This study aimed to identify outcomes following NAC plus AC for LARC., Patients and Methods: We reviewed 252 patients who underwent curative resection for LARC. Propensity score matching matched 51 patients in NAC and non-NAC groups., Results: Operative time (443 min vs. 286 min, p<0.001), blood loss (279 ml vs. 124 ml p<0.001), and number of patients who received AC were higher in the NAC group (74.5% vs. 33.3%, p<0.001). The Disease control rate of NAC group was 98.1%. The NAC group showed better 3-year RFS (86.5% vs. 62.1%, p=0.021). Patients who received both NAC and AC displayed better 3-year RFS (90.2%) compared to the non-NAC group both with (63.8%) and without (60.4%) AC (p<0.05)., Conclusion: NAC and AC for LARC have the potential to improve oncological outcomes., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Hemodialysis patients who undergo surgery have a high risk of postoperative complications. The aim of this study was to determine whether colon cancer surgery can be safely performed in hemodialysis patients., Methods: This multicenter retrospective study included 1372 patients who underwent elective curative resection surgery for colon cancer between April 2016 and March 2020., Results: Of the total patients, 19 (1.4%) underwent hemodialysis, of whom 19 (100%) had poor performance status and 18 had comorbidities (94.7%). Minimally invasive surgery was performed in 78.9% of hemodialysis patients. The postoperative complication rate was significantly higher in hemodialysis than non-hemodialysis patients (36.8% vs. 15.5%, p = 0.009). All postoperative complications in the hemodialysis patients were infectious type. Multivariate analysis revealed a significant association of hemodialysis with complications (odds ratio, 2.9362; 95%CI, 1.1384-7.5730; p = 0.026)., Conclusion: Despite recent advances in perioperative management and minimally invasive surgery, it is necessary to be aware that short-term complications can still occur, especially infectious complications in hemodialysis patients., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The impact of obesity on short-term outcomes after laparoscopic colorectal surgery (LAC) in Asian patients is unclear. The purpose of the present multicenter study was to evaluate the safety and feasibility of LAC in obese Japanese patients., Methods: We retrospectively reviewed 1705 patients who underwent LAC between April 2016 and February 2019. Patients were classified according to body mass index (BMI): non-obese (BMI < 25 kg/m 2 , n = 1335), obese I (BMI 25-29.9 kg/m 2 , n = 313), and obese II (BMI ≥30 kg/m 2 , n = 57). Clinical characteristics and surgical outcomes were compared among the three groups., Results: The proportion of patients with comorbidities (non-obese, 58.1%; obese I, 69.6%; obese II, 75.4%; P < .001) and median operation time (non-obese, 224 minutes; obese I, 235 minutes; obese II, 258 minutes; P = .004) increased significantly as BMI increased. The conversion rate was similar among the groups (P = .715). Infectious complications were significantly high in obese II patients (non-obese, 10.4%; obese I, 8.3%; obese II, 28.1%; P < .001). Multivariate analysis revealed that in obese II patients, BMI was an independent predictive factor of infectious postoperative complications (odds ratio 2.648; 95% confidence interval, 1.421-4.934; P = .002)., Conclusion: LAC has an increased risk of postoperative infectious complications in obese II patients, despite improvements in surgical technique. Management of obese II colorectal cancer patients requires meticulous perioperative management., (© 2020 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Objective: Heterogeneous clinical characteristics are observed in acquired isolated adrenocorticotropic hormone (ACTH) deficiency (IAD); however, its classification remains to be established because of its largely unknown pathophysiology. In IAD, anti-pituitary antibodies have been detected in some patients, although their significance remains unclear. Therefore, this study aimed to classify patients with IAD and to clarify the significance of anti-pituitary antibodies., Design and Methods: We analyzed 46 consecutive patients with IAD. Serum anti-pituitary antibodies were analyzed via immunofluorescence staining using a mouse pituitary tissue. Principal component and cluster analyses were performed to classify IAD patients based on clinical characteristics and autoantibodies., Results: Immunofluorescence analysis using the sera revealed that 58% of patients showed anti-corticotroph antibodies and 6% of patients showed anti-follicular stellate cell (FSC) antibodies. Principal component analysis demonstrated that three parameters could explain 70% of the patients. Hierarchical cluster analysis showed three clusters: Groups A and B comprised patients who were positive for anti-corticotroph antibodies, and plasma ACTH levels were extremely low. Groups A and B comprised middle-aged or elderly men and middle-aged women, respectively. Group C comprised patients who were positive for the anti-FSC antibody and elderly men; plasma ACTH levels were relatively high., Conclusions: Patients with IAD were classified into three groups based on clinical characteristics and autoantibodies. The presence of anti-corticotroph antibody suggested severe injury to corticotrophs. This new classification clearly demonstrated the heterogeneity in the pathogenesis of IAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fujita, Bando, Iguchi, Iida, Nishizawa, Kanie, Yoshida, Matsumoto, Suda, Fukuoka, Ogawa and Takahashi.)

Purpose: To evaluate the microorganism detection and contamination rate of donor eyes., Study Design: Retrospective study., Methods: In this retrospective study, we reviewed all donor cornea data collected from Kyoto Prefectural University of Medicine (KPUM) Eye Bank, Kyoto, Japan from April 2015 to June 2018, including microbiologic data obtained from conjunctival swabs and preservation medium and findings of postoperative infection from the medical records., Results: During the study period, 77 eyes from 44 deceased individuals (mean age at time of death: 75 ± 17.3 years [range, 30-102 years]) were donated to the KPUM Eye Bank after being harvested using standard safety precautions and disinfection procedures. In 49 of the 77 eyes (63.6%), the conjunctival-swab culture revealed microorganisms, with the 3 most commonly detected being methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-sensitive S aureus (MSSA), and methicillin-resistant S aureus (MRSA). The data revealed positive microorganism detection in only 4 (5.2%) of the 77 donor-cornea storage-medium cultures. Positive microorganism detection was found in all the age groups, with no statistical difference between the groups (P > .05). In the eyes enucleated ≥ 2.5 h postmortem, a higher positive microorganism detection occurred (P = .03). During the postoperative follow-up period, there was no record of corneal infection., Conclusions: The preenucleation conjunctival-swab-culture findings revealed that the rate of positive microorganism detection was similar for advanced-age and younger-age donors and that a shorter elapsed time from donor death to postmortem enucleation resulted in less donor-microorganism contamination.

Background: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients., Methods and results: Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m 2 ), and cardiac index (CI; L/min/m 2 ). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group., Conclusions: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

Background: Plasma renin activity (PRA) is generally increased in patients with pheochromocytoma (PCC) due to low circulating plasma volume and activation of β-1 adrenergic receptor signaling. However, there has been no study on the aldosterone renin ratio (ARR) in patients with PCC. To elucidate the issue, this study aimed to determine the PRA, plasma aldosterone concentration (PAC), and ARR in patients with PCC and compare them with those in patients with subclinical Cushing's syndrome (SCS) and non-functioning adrenal adenoma (NFA)., Methods: In this retrospective single-center, cross-sectional study, 67 consecutive patients with adrenal tumors (PCC (n = 18), SCS (n = 18), and NFA (n = 31)) diagnosed at Kobe University Hospital between 2008 and 2014 were enrolled., Results: PRA was significantly higher in patients with PCC than in those with SCS and NFA (2.1 (1.3 ~ 2.8) vs. 0.7 (0.5 ~ 1.8) and 0.9 (0.6 ~ 1.4) ng/mL/h; p = 0.018 and p = 0.025). Although PACs were comparable among the three groups, ARR was significantly lower in patients with PCC than in those with SCS and NFA (70.5 (45.5 ~ 79.5) vs. 156.0 (92.9 ~ 194.5) and 114.9 (90.1 ~ 153.4); p = 0.001 and p < 0.001). Receiver operating characteristic curve analysis demonstrated that, in differentiating PCC from NFA, PRA > 1.55 ng/mL/h showed a sensitivity of 70.0% and specificity of 80.6%. Interestingly, ARR < 95.4 showed a sensitivity of 83.3% and specificity of 86.7%, which were higher than those in PRA., Conclusions: ARR decreased in patients with PCC, which was a more sensitive marker than PRA. Further study is necessary to understand the usefulness of this convenient marker in the detection of PCC., Trial Registration: This study was not registered because of the retrospective analysis.

"Total" folate in blood has usually been measured to evaluate the folate status of pregnant women. However, folate is composed of many metabolites. The main substrate is 5-methyltetrahydrofolate (5-MTHF), with folic acid (FA) representing a very small component as an unmetabolized species in blood. We longitudinally evaluated 5-MTHF, FA and total homocysteine in maternal and cord blood from Japanese pregnant women. Subjects were 146 pregnant women who participated in the Chiba study of Mother and Child Health (C-MACH) prospective cohort study. Sera were obtained in early and late pregnancy, at delivery, and from cord blood. Species levels were measured by isotope-dilution mass spectrometry. Both 5-MTHF and FA levels were lower than reported levels from pregnant women in populations from countries with mandatory FA fortification. As gestational age progressed, serum 5-MTHF levels decreased, whereas serum FA levels were slightly reduced only at delivery compared to early pregnancy. A significant negative association between serum 5-MTHF and total homocysteine was shown at all examined times, but no associations with FA were evident. At delivery, cord 5-MTHF was significantly higher than maternal levels, while FA again showed no significant correlation. These results suggest that 5-MTHF is actively transported to the fetus through placental transporters and may reflect folate status during pregnancy as a physiologically important species.

Background: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD., Methods: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans., Results: We identified 3 new loci on chromosome 1q21 ( CTSS ), 10q26 ( WDR11-FGFR2 ), and 11q22 ( RDX - FDX1 ). Quantitative trait locus analyses suggested the association of CTSS and RDX - FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans., Conclusions: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.

Although acromegaly has been reported in patients with Neurofibromatosis type 1 (NF1), these cases have not been associated with growth hormone (GH)-producing somatotroph adenoma, but with optic pathway glioma. A 68 year-old Japanese woman, who had been clinically diagnosed with NF1, was referred to our hospital due to a thyroid tumor and hypercalcemia. Acromegaly was suspected due to her facial features, and subsequent examinations revealed the presence of GH excess with a pituitary tumor, leading to the diagnosis of acromegaly. Histological and immunohistochemical analysis demonstrated an eosinophilic pituitary adenoma with diffuse positivity for GH, indicating typical somatotroph adenoma. In addition, her thyroid tumor was diagnosed histologically as follicular thyroid carcinoma (FTC) with primary hyperparathyroidism (PHPT). To investigate the pathogenesis of this untypical multiple endocrine tumor case of NF1, genetic analysis was performed using peripheral leukocytes and tissue of resected tumors. A heterozygous novel germline nonsense mutation (p.Arg1534*) in exon 35 of the NF1 gene was detected from peripheral leukocytes, which results in a truncated protein lacking the critical domain for GTPase activity, strongly suggesting its causal role in NF1. The loss of heterozygosity (LOH) in exon 35 of the NF1 gene was not detected in the somatotroph adenoma, parathyroid adenoma, and FTC. Although any mutations of the following genes; MEN1, CDKN1B, and PAX8-PPARγ were not detected, a heterozygous GNAS R201C mutation was detected in the somatotroph adenoma. To our knowledge, this is the first rare MEN1-like case of genetically diagnosed NF1 complicated with acromegaly caused by a somatotroph adenoma.

Background: We previously reported that an index of afterload-related left ventricular diastolic function, operant diastolic elastance (Ed)/effective arterial elastance (Ea) = E/e'/(0.9 × systolic blood pressure), was significantly higher in elderly hypertensive women. We aimed to determine sex-related differences in the E/e'-related indices for left ventricular diastolic function and their related factors during admission in patients with heart failure with preserved ejection fraction (HFpEF)., Hypothesis: Elderly HFpEF women exhibit severe left ventricular diastolic dysfunction associated with different left atrioventricular volume ratio., Methods: We divided 267 patients with HFpEF (men/women, 116/151) into two groups by age (≥75 years, n = 212; <75 years, n = 55). We examined the alterations of E/e', E/e'/stroke volume index = Ed, and Ed/Ea, and cardiac structure during admission., Results: Ed and Ea were significantly higher in women than in men, at admission, especially in patients ≥75 years. Before discharge, not only Ed and Ea but also Ed/Ea was significantly higher in women than in men, especially in patients ≥75 years. Elderly female patients had larger left atrial than left ventricular volume., Conclusions: Higher afterload-related left ventricular diastolic elastance, Ed/Ea, in association with higher arterial elastance, Ea, accompanied by left atrioventricular volume mismatch was observed in elderly HFpEF women., (© 2018 Wiley Periodicals, Inc.)

Context: Pheochromocytoma and paraganglioma are catecholamine-producing tumors that often impair glucose tolerance. The effects of these tumors on insulin sensitivity and insulin secretion in patients have remained unclear, however., Objective: To characterize the influence of pheochromocytoma or paraganglioma on glucose tolerance, we comprehensively analyzed various parameters related to insulin secretion or insulin sensitivity in patients with these tumors., Design: Hyperglycemic and hyperinsulinemic-euglycemic clamps, as well as an oral glucose tolerance test (OGTT), were performed in patients before and after tumor excision., Setting: Patients underwent metabolic analyses on admission to Kobe University Hospital., Patients: Eleven patients with pheochromocytoma and two with paraganglioma were examined., Intervention: None., Main Outcome Measures: We evaluated various parameters related to insulin secretion or insulin sensitivity as determined by an OGTT and by hyperglycemic and hyperinsulinemic-euglycemic clamp analyses., Results: Surgical treatment of the tumor reduced urinary catecholamine excretion and improved glucose tolerance. The insulinogenic index, but not total insulin secretion, measured during the OGTT as well as the first phase, but not the second phase, of insulin secretion during the hyperglycemic clamp were improved after surgery. The insulin sensitivity index determined during the hyperinsulinemic-euglycemic clamp remained unchanged after surgery., Conclusion: These results suggest pheochromocytoma and paraganglioma impair glucose tolerance primarily through impairment of insulin secretion-in particular, that of the early phase of the insulin secretory response. A prospective study with more patients is warranted to further confirm these results., (Copyright © 2017 Endocrine Society)

This study was conducted to determine the effects of depression and/or insomnia on masked hypertension (MHT) compared with other types of HT and on variability in home-measured blood pressure (HBP) and clinic BP (CBP). Three hundred and twenty-eight hypertensives (132 women) aged 68±10 years were classified into four BP types: controlled HT (CHT), white-coat HT, MHT and sustained HT (SHT), based on CBP (140/90 mm Hg) and morning HBP (135/85 mm Hg) measurements. A score of ⩾16 on the Center for Epidemiologic Studies Depression Scale (CES-D) was defined as depression. The mean values and s.d. of BP were calculated from measurements taken during the 14 consecutive days just before the CES-D evaluation. Compared with the CHT group, the risk of depression was 2.77-fold higher in the SHT group and even higher in the MHT group (7.02-fold). The association between depression and MHT was augmented in the presence of insomnia and was somewhat stronger in women. A HBP variability index defined as s.d./mean BPs in both morning and night time was significantly higher in MHT than in the other BP types, whereas that of CBP was not. Both morning and night-time HBP variability were significantly higher in depressive patients than in non-depressives. These suggest that depression is associated with MHT and that increases both morning and night-time HBP variability but not CBP variability. Physicians should be mindful of mental stresses such as depression in their hypertensive patients when forming strategies to control BP over the diurnal cycle.

Background: The current state of eye diseases and treatments in the elderly as well as the relationships between dementia and systemic diseases remain unclear. Therefore, this study evaluated the prevalence of eye diseases, visual impairment, cognitive impairment, and falls (which are an important health issue and are considered one of the Geriatric Giants) in super-elderly people in Japan., Methods: The subjects were 31 elderly people (62 eyes; mean age: 84.6 ± 8.8 years; age range 61-98 years) who were admitted to a geriatric health services facility. Eye treatment status, systemic diseases, dementia, and recent falls were investigated. Eye examinations including vision and intraocular pressure measurement, and slit-lamp biomicroscopy were conducted., Results: Mean best corrected visual acuity (logMAR) was 0.51 ± 0.56, and mean intraocular pressure was 13.7 ± 3.5 mmHg. Approximately half of the subjects exhibited excavation of the optic nerve head including cataracts and glaucoma. Ten subjects had visual impairment (i.e., visual acuity of the eye with the better vision <20/40). The mean Hasegawa dementia scale scores between the visually impaired and non-visually impaired groups were 10.2 ± 6 and 16 ± 8 points, respectively (p < 0.05). Furthermore, 70% of subjects with visual impairment experienced a fall in the past year compared to 48% of those without visual impairment, although the difference was not significant. Regarding systemic diseases, there were 6, 5, and 15 cases of diabetes, hyperlipidemia, and hypertension, respectively. There was no significant difference between these systemic diseases and visual function after adjusted for age and gender., Conclusions: The percentages of patients with age-related eye diseases and poor visual acuity in a geriatric health services facility were extremely high. Compared to those without visual impairment, those with visual impairment had lower dementia scores and a higher rate of falls.

Purpose: Colorectal neoplasms are well known to be a complication in cases of acromegaly; however, data on the prevalence of colorectal neoplasms in Asian patients with acromegaly are limited. Further, the factors associated with colorectal neoplasms in cases of acromegaly are controversial. Therefore, we aimed to clarify the prevalence of and factors associated with colorectal neoplasms in Japanese patients with acromegaly in a single center., Methods: We analyzed consecutive 57 patients who had undergone full-length colonoscopy at the time of diagnosis at Kobe University Hospital between 1986 and 2012., Results: Of the 57 patients, 22 (38.6%), 18 (31.6%) and 3 (5.3%) patients were diagnosed with hyperplastic polyps, adenomas, and adenocarcinomas, respectively and the prevalence was significantly higher than in a historical control group, Chinese patients with irritable bowel syndrome (The odds ratio was 4.0, 8.7, and 17.5, respectively). The prevalence of adenocarcinomas was also significantly higher in these patients than in the general Japanese population (odds ratio 14.5). Patients with acromegaly who had colorectal neoplasms had longer disease duration than those without colorectal neoplasms. Of note, the area under the growth hormone (GH) concentration-time curve (GH AUC) during the oral glucose tolerance test was significantly higher in patients with adenocarcinomas than in those with no colonic lesion or those with hyperplastic polyps., Conclusion: Japanese patients with acromegaly exhibited an increased risk of colorectal neoplasms, especially colorectal adenocarcinomas. An increased GH AUC was associated with an increased risk for colon adenocarcinomas in patients with acromegaly.

Poor growth in utero has been suggested to be associated with adverse levels of serum cholesterol concentrations in later life. In Asia, there have only been a limited number of studies examining the relationship between fetal status and serum lipids, especially in adolescents. The objective of this study was to examine the relationships between birth weight and serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels; adjusting for current physical status including percent body fat, physical activity and nutrient intake in healthy Japanese late adolescents. The data of 573 late adolescents with an average age of 17.6 (287 boys and 286 girls) who underwent physical examinations which included blood sampling and who had all the required data, were analyzed. Birth weight was obtained from their maternal and child health handbook. Multiple regression analysis showed that birth weight was positively associated with serum HDL in girls, independently of percent body fat or fat intake, when adjusted for current body height and weight. There were no associations between birth weight and serum HDL in boys, or serum LDL in either sex.

Background: A metabolomic approach using umbilical cord blood from infants at birth has not been studied widely yet., Aim: We examined changes in metabolite levels in umbilical cord blood at birth via gas chromatography/mass spectrometry (GC/MS)-based metabolomics, with the aim of achieving a detailed understanding of fetal stress during labor., Study Design: All procedures were reviewed and approved by the Institutional Review Board of Kobe University School of Medicine. This was a cohort study of pregnant women based in Palmore Hospital, which is located in an urban area of Japan, and was carried out between December 2010 and May 2011., Subject: Umbilical cord arterial blood samples were obtained from 41 infants immediately after delivery., Outcome Measures: Metabolites in the blood samples were measured using GC/MS to investigate whether the delivery method (spontaneous onset of labor, induction of labor or elective cesarean section) affected the metabolite profile in umbilical cord blood., Results: Elective cesarean section without labor led to lower levels of isoleucine, fructose, mannose, glucose, allose, glucuronic acid, inositol and cysteine in comparison with vaginal delivery following spontaneous labor and without medication., Conclusion: It is proposed that the stress associated with labor be involved in alterations in the levels of metabolites, particularly saccharides such as glucose, in umbilical cord blood., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Chemerin, a recently discovered adipocytokine plays an important role in obesity and obesity-associated metabolic complications. However, the role of chemerin in the pathogenesis of type 2 diabetes mellitus (T2DM) has not fully been elucidated. We compared the serum chemerin levels and metabolic parameters between 88 control subjects, 86 patients with metabolic syndrome (MS), and 147 patients with T2DM in a Japanese population and further analyzed their correlation. Enzyme-linked immunosorbent assay was used to measure the serum chemerin levels. The chemerin levels were significantly higher in male than in female control subjects (p < 0.005), with significant decreases in patients with T2DM compared with those with MS and control subjects (164.9 ± 6.3 ng/mL vs. 209.8 ± 7.7 and 218.7 ± 7.3 ng/mL; p < 0.0001 vs. p < 0.0001, respectively) but no significant differences in female subjects. The multiple regression analysis revealed that the chemerin levels negatively correlated with the fasting glucose and HbA1c levels in total and male subjects. In the patients with T2DM, the chemerin levels negatively correlated with fasting glucose and high-density lipoprotein cholesterol but positively correlated with body mass index (BMI), and total cholesterol and triglyceride levels. The negative correlation between the chemerin and fasting glucose levels remained significant after adjustment for age, sex, and BMI in the total and male subjects and those with T2DM. These results suggest the role of chemerin in sex dimorphism and a potential link between chemerin levels and T2DM pathogenesis in a Japanese population.

Background/aims: The present study aimed to elucidate the relationship between microvessel count (MVC) according to CD34 expression and clinicopathological characteristics or prognosis in pancreatic carcinoma (PC) patients who underwent hepatectomy., Methodology: CD34 expression was analyzed using immunohistochemical methods. Mean MVC in 5 areas per specimen and clinicopathological factors were consecutively examined in 42 PC patients., Results: Median MVC for PC patients was 123/mm2, which was applied as a cut-off value. Higher MVC was significantly associated with the advanced Japanese tumor-node-metastasis stage IVa and IVb (p=0.034). Univariate survival analysis identified higher carcinoembryonic antigen (CEA) and CA19-9 level, infiltrative type on macroscopic examination, invasive ductal carcinoma, node metastasis and higher tumor-node-metastasis classification were significantly associated with poor survival. The 5-year overall survival rate in the higher MVC group tended to be lower than that in the higher MVC group (37 vs. 55%), but not statistically significant (p=0.15)., Conclusions: Tumor MVC might be a candidate prognostic marker of PC patient survival after pancreatectomy and further investigation in a larger series is warranted to clarify the significance of this marker.

Background: Nocturnal and early morning hypertension are both significant risk factors for cardiovascular events. It remains unclear whether anxiety disorder affects nocturnal blood pressure (BP), early morning BP, or BP pattern in hypertensive patients., Methods and Results: One hundred and twenty consecutive hypertensive outpatients (77 men and 43 women; mean age, 66±11 years) were divided into 2 groups based on Hospital Anxiety and Depression Scale (HADS) score: a control group (n=78; HADS ≤10) and an anxiety group (42 patients; HADS ≥11). Nocturnal BP, early morning BP, morning BP surge (defined as BP rise ≥50 mmHg), and BP pattern (extreme-dipper/dipper/non-dipper/riser) were measured on ambulatory BP monitoring. Clinical characteristics and BP were also evaluated at physician check-up. There was no significant difference between the 2 groups for BP check-up, but nocturnal and early morning BP were significantly higher in the anxiety group (142±16 mmHg and 152±21 mmHg) than in the control group (126±14 mmHg and 141±18 mmHg). With regard to patients with morning BP surge, nocturnal and early morning BP were also significantly higher in the anxiety group. The relative risk of existing anxiety disorders in riser-type hypertension was 4.48-fold higher (95% confidence interval: 1.58-12.74; P<0.005) than in dipper-type hypertension., Conclusions: Anxiety disorder is associated with nocturnal and early morning hypertension, and may be a risk factor for cardiovascular events.

Aim: Greater antenatal weight or body mass index (BMI) gains may lead to larger fetuses and thus increase the risk for operative deliveries, such as cesarean deliveries. In order to examine the effect of weekly maternal weight and BMI changes on large-for-gestational-age (LGA) infants and cesarean delivery, delivery records from overall healthy women were analyzed., Materials and Methods: Singleton, term delivery records from January to December 2003, at three obstetric departments (urban, suburban, rural) in Japan (1617 records) were analyzed. Multivariate logistic regression analyses were applied in order to estimate the effect of maternal pre-pregnancy body size, higher maternal weight or BMI gains by calculating the odds ratios for LGA infants and cesarean deliveries., Results: Maternal pre-pregnancy overweight, primiparity, and BMI gains of more than 0.13 per week were independent factors positively related to LGA, and maternal underweight was negatively related. Urban hospital setting, maternal age 35 years or older, primiparity, and BMI gains of more than 0.13 per week independently increased the odds ratios for cesarean delivery. Weight or BMI gains between two-week intervals (26-28 weeks, 32-34 weeks) were not useful for predicting either LGA or cesarean delivery. LGA was unrelated to cesarean delivery risk., Conclusions: Applying BMI gains per week enables target weight gains to be set according to the mother's height, which may be useful in reducing risks for LGA and cesarean delivery, especially in shorter women. Further investigation may be needed to explore the practicality and effectiveness of advising women to gain weight according to their body height., (© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.)

Hepatocellular carcinoma (HCC) patients often have esophagogastric varices due to portal hypertension by chronic hepatitis or cirrhosis. Surgical treatment for gastric varices is necessary when the patient undergoes hepatic resection for HCC, simultaneously. We examined the clinical demographics, surgical records and outcome in 7 patients undergoing both hepatectomy and Hassab's operation (=decongestion of upper gastric veins and splenectomy) between 1994 and 2007. All patients had HCC, including chronic injured liver diseases. Preoperative liver functions were well preserved in all patients. Right hepatectomy was performed in two patients and limited resections in 5. Three patients had postoperative complications and the in-hospital death by hepatic failure was observed in one. Four patients had tumor recurrence within one year and 3 were dead, while, two patients had long-term survival with or without recurrence of HCC. Following Hassab's operation, gastric varices dramatically disappeared. Portal hypertension and hypersplenism were significantly improved. Simultaneous operation with Hassab's procedure and hepatectomy is useful and can be safely performed in HCC patients with gastric varices.

Background: Inadequate folate status has been associated with many negative reproductive outcomes, such as neural tube defects (NTD), low birth weight and placental abruption., Aim of the Study: The objectives of this study were to evaluate the levels of dietary folate intake during pregnancy in Japanese women and the subsequent birth weight of their babies., Methods: A longitudinal prospective study was conducted with 197 women with a singleton pregnancy in 2005. Dietary folate was investigated 3 times: in the first trimester at 12 weeks, in the second trimester at 20 weeks and in third trimester at 32 weeks using a diet history questionnaire (DHQ). Non fasting blood samples were collected from the women for measurement of homocysteine, hemoglobin, ferritin, unbound iron-binding capacity (UIBC) and total iron-binding capacity (TIBC)., Results: Energy intake increased as pregnancy advanced, but not significantly. The daily intake of folate increased from 248.5 +/- 113.1 microg/d in the first trimester to 275.4 +/- 100.2 microg/d in the third trimester (P = 0.04). This was well below the recommended level of 440 microg/d and only 10% of mothers were above the levels. In the third trimester, plasma homocysteine concentration was significantly higher in the low folate group of less than 250 microg/d (P = 0.02), but not the first and second trimesters. Dietary folate intake and plasma homocysteine concentrations were not likely to be predictors of birth weight in our subjects., Conclusions: Our study shows that Japanese women's energy and folate intakes do not meet their energy needs during pregnancy and are at an extremely low recommended dietary allowance level throughout pregnancy.

Background and Purpose: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma., Materials and Methods: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23-76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors., Results: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (< or =2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163-29.788), maximum rCBV (4.739; 95% CI, 1.950-11.518), extent of surgery (2.692; 95% CI, 1.196-6.061), and sex (2.632; 95% CI, 1.153-6.010)., Conclusion: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

Mouse mammary tumor virus (MMTV) is the causative agent of breast tumors in mice. Recently, DNA sequences homologous or closely related to MMTV env gene have been specifically detected in breast cancer tissue from significant numbers of American, Australian, and Tunisian women, suggesting a viral etiology for at least a part of human breast cancer. However, the viral sequences have not been detected from any of breast cancer samples in several subsequent studies. Thus, whether MMTV-related retrovirus is a causative agent of human breast cancer remains controversial. To demonstrate if MMTV-related retrovirus is involved in Japanese cases of breast cancer, breast tissue specimens from 46 breast cancer patients and 3 patients with benign mammary tumors were investigated. Extensive analysis using PCR and Southern blot hybridization, however, could not detect the MMTV env gene-like sequence in any of the samples tested as well as in MCF7 cells that has previously been described as a positive control. Thus, MMTV itself or MMTV-related retrovirus is not associated with breast carcinogenesis in Japanese women, and it is unclear whether this conclusion is merely a reflection of regional differences in its epidemics.

Discovery of deafness genes has progressed but clinical application lags because of the genetic heterogeneity. To establish clinical application strategy, we reviewed the frequency and spectrum of mutations found in Japanese hearing loss patients and compared them to those in populations of European ancestry. Screening revealed that in Japanese, mutations in GJB2, SLC26A4, and CDH23, and the mitochondrial 12S rRNA are the major causes of hearing loss. Also, mutations in KCNQ4, TECTA, COCH, WFS1, CRYM, COL9A3, and KIAA1199 were found in independent autosomal dominant families. Interestingly, spectrums of GJB2, SLC26A4, and CDH23 mutations in Japanese were quite different from those in Europeans. Simultaneous screening of multiple deafness mutations based on the mutation spectrum of a corresponding population using an Invader panel revealed that approximately 30% of subjects could be diagnosed. This assay will enable us to detect deafness mutations in an efficient and practical manner in the clinical platform. We conclude that specific racial populations may have unique deafness gene epidemiologies; therefore, ethnic background should be considered when genetic testing is performed. Simultaneous examination of multiple mutations based on a population's spectrum may be appropriate and effective for detecting deafness genes, facilitating precise clinical diagnosis, appropriate counseling, and proper management.

A mass screening of subjects for prostate specific antigen (PSA) was conducted to investigate whether this method is effective in detection of early stage prostate cancer. From 2001 to 2005, 1022 patients in Yokosuka City with pathologically diagnosed prostate cancer by using prostate needle biopsy were divided into screened (S: 276 patients) and non-screened (NS: 746 patients) groups. Clinical factors (mean age, PSA at diagnosis, clinical stage, Gleason score, WHO classification, cases of radical prostatectomy) were evaluated and analyzed. Statistical significance was analyzed by Mann-Whitney's U-test. The mean age was 70.7 and 72.7 (p<0.0001) in the S group and NS group, respectively; mean PSA at diagnosis was 10.5 and 18.6 ng/ml (P=0.0139); percentage of organ-confined disease (T2b or lower clinical stage), 75 and 55 (p<0.0001); percentage of non-metastatic diseases was 92 and 77 (p<0.001) and percentage of pathologically poor-risk cancer (8 or more Gleason score) was 22 and 38 (p=0.0004), respectively. In conclusion, PSA mass screening was found useful to detect early stage prostate cancer in Yokosuka City. Further studies should be conducted to determine whether PSA mass screening will be able to decrease mortality of prostate cancer.

Background: The purpose of the paper was to determine the risk factors for small-for-gestational-age (SGA) infants at full term, in Japan., Methods: The study was conducted at four hospitals and clinics in the Tokyo metropolitan area. A retrospective review of 2972 mothers and their infants born from singleton pregnancies at any time during the years 2002 and 2003 was conducted., Results: Of these women, 8.4% gave birth to SGA infants. The proportion of SGA infants was significantly higher among heavy smokers (>10 cigarettes/day; 13.7%, P < 0.01). The odds ratio (OR) for SGA decreased significantly in proportion to the pregnancy body mass index (OR, 0.89; 95% confidence interval [CI]: 0.84-0.94, P < 0.001). The OR of SGA for stratified maternal weight gain was 1.79 (95%CI: 1.24-2.58, P 12 kg., Conclusion: The present study clearly confirms the detrimental effect of a low prepregnancy body mass index, low maternal weight gain and maternal smoking during pregnancy on the incidence of SGA infants.

Mutations in the CDH23 gene are known to be responsible for both Usher syndrome type ID (USH1D) and non-syndromic hearing loss (DFNB12), and the molecular confirmation of the CDH23 gene has become important in the diagnosis of these conditions. The present study was performed to find whether the CDH23 mutations are also responsible for non-syndromic hearing loss in patients in the Japanese population. A total of 51 sequence variants were found in 64 Japanese probands with non-syndromic sensorineural hearing impairment from autosomal recessive families. Among them, at least four missense mutations in six patients from five families were confirmed to be responsible for deafness by segregation study. All mutations detected were missense mutations, corroborating the previous reports regarding DFNB12. The present data confirmed that CDH23 mutations are frequently found and significantly responsible in Japanese. Interestingly, the CDH23 mutation spectrum in Japanese is very different from that found in Caucasians. This Japanese spectrum may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of DFNB12 and USH1D.

Background: Adequate folate status in pregnancy is important for satisfactory pregnancy outcome., Aim of the Study: The objective of the present study was to evaluate folate status in healthy pregnant women by assessing dietary folate intakes and measuring changes in folate-related biomarkers including plasma tHcy, serum vitamin B(12) (B(12)), and serum and RBC folate concentrations in each trimester and to examine their relation to fetal growth., Methods: From 94 pregnant women, 3-day-dietary records were obtained and blood was collected for plasma total homocysteine (tHcy), serum B(12), and serum and red-blood cell (RBC) folate measurements. Infant anthropometric measurements were made immediately after birth., Results: Average folate intake was less than 300 microg/day with a mean energy intake of about 1800 kcal. Mean serum and RBC folate concentrations declined significantly during gestation (p < 0.05). Mean serum B(12) also significantly decreased (p < 0.01), whereas plasma tHcy increased from 5.1 in the first trimester to 5.9 micromol/l in the third trimester (p < 0.01). Multiple regression analyses, after controlling for maternal age, parity and pre-pregnancy body-mass index indicated that a 1.0 micromol/l increase in plasma tHcy in the third trimester corresponded to a 151 g decrease in birth weight (p < 0.01). Neither B(12) nor folate concentrations in all three trimesters showed any significant associations with birthweight. Plasma pyridoxal-5'-phosphate concentrations were markedly low, and were consistent with low intake of vitamin B(6) in our population., Conclusion: Our data suggest that higher plasma tHcy in the third trimester is a predictor of lower birth weight. In general, the dietary intake of B-vitamins and energy may be inadequate in our population, suggesting intervention is necessary.

Objective: To evaluate the effectiveness of restricting weight gain during pregnancy to reduce perinatal complications., Study Design: The study was conducted in the Tokyo metropolitan area, and reviewed 3071 mothers and their infants born from singleton pregnancies retrospectively. To examine the influence of increased maternal weight gain on perinatal complications, we performed five-category stratification for weight gain: less than 8.0, 8.0-10.0, 10.1-12.0, 12.1-14.0 and over 14.0 kg., Results: Total weight gains less than 8.0 kg significantly increased the risk of low birth weight (LBW) and small for gestational age (SGA) infants (OR=2.19, 95% CI; 1.36-3.52, OR=1.76, 95% CI; 1.23-2.51) and total weight gain over 14.0 kg significantly increased the risk of large for gestational age (LGA) infants and pregnancy induced hypertension (PIH) (OR=3.06, 95% CI; 1.88-4.98, OR=2.87, 95% CI; 1.86-4.42, respectively), compared with women with weight gain of 10.1-12.0 kg. The groups with weight gains of 8.0-10.0 kg and 12.1-14.0 kg did not show adverse perinatal outcomes, including gestational diabetes (GDM), cesarean delivery, postpartum hemorrhage and laceration, significantly different from the 10.1 to 12.0 kg gain group., Conclusion: Strict restriction of weight gain during pregnancy is not effective in reducing perinatal complications.

Mutations in WFS1 are reported to be responsible for two conditions with distinct phenotypes; DFNA6/14/38 and autosomal recessive Wolfram syndrome. They differ in their associated symptoms and inheritance mode, and although their most common clinical symptom is hearing loss, it is of different types. While DNFA6/14/38 is characterized by low frequency sensorineural hearing loss (LFSNHL), in contrast, Wolfram syndrome is associated with various hearing severities ranging from normal to profound hearing loss that is dissimilar to LFSNHL (Pennings et al. 2002). To confirm whether within non-syndromic hearing loss patients WFS1 mutations are found restrictively in patients with LFSNHL and to summarize the mutation spectrum of WFS1 found in Japanese, we screened 206 Japanese autosomal dominant and 64 autosomal recessive (sporadic) non-syndromic hearing loss probands with various severities of hearing loss. We found three independent autosomal dominant families associated with two different WFS1 mutations, A716T and E864K, previously detected in families with European ancestry. Identification of the same mutations in independent families with different racial backgrounds suggests that both sites are likely to be mutational hot spots. All three families with WFS1 mutations in this study showed a similar phenotype, LFSNHL, as in previous reports. In this study, one-third (three out of nine) autosomal dominant LFSNHL families had mutations in the WFS1 gene, indicating that in non-syndromic hearing loss WFS1 is restrictively and commonly found within autosomal dominant LFSNHL families.

Objective: To assess the status of dietary folate intake, serum and red blood cell (RBC) folate, and related nutritional biomarkers in healthy Japanese women in early pregnancy., Design: A cross-sectional, observational study., Subjects: Pregnant women in the first trimester, at 7-15 weeks gestation (n=70), who were not consuming any folate supplements or folate fortified foods., Methods: Three-day dietary records were obtained from each subject to assess dietary folate intake. Blood samples were collected for measurement of biomarkers. Biomarkers and nutrient intake were analyzed in two groups defined by their serum folate concentrations: the low folate group (serum folate < 9 ng/ml) and the high folate group (serum folate > or = 9 ng/ml)., Result: Mean serum and RBC folate concentrations in all subjects were 10.3 and 519 ng/ml, respectively. These levels were remarkably higher than the reported values from many other countries despite our subjects receiving no folic acids supplements. However, mean folate intake by our subjects from natural foods was 289 microg/day, which is thought to be low according to the Japanese dietary recommendation specified for pregnant women. The intake of spinach and fruits was significantly greater in the high folate group than in the low folate group., Conclusion: Folate intake was thought to be adequate to maintain a desirable level of serum folate concentration in Japanese pregnant women in the first trimester, although the intake of folate from natural food was not high enough to meet the recommended daily intake.

Background: We previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection., Methods: We compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II)., Results: By a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3)., Conclusions: The modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.

Aim: To investigate possible factors related to the recent rise in prevalence of low-birth-weight (LBW) infants in Japan., Methods: A data set comprising 11,746 infants from the Children and Infant Growth Surveys (1980, 1990, and 2000) was analyzed., Results: The proportion of LBW infants was 4.2% in 1980, 6.1% in 1990, and 8.3% in 2000. The maternal smoking prevalence increased from 6.5% in 1990 to 10.9% in 2000. When multivariate logistic regression analysis was applied to estimate the risk for LBW from 1990 to 2000, the following were selected as independent factors: preterm delivery, early term delivery, female sex of the infant, maternal primiparity, multiple gestation, maternal short stature, older maternal age (>24 years), and maternal smoking. The population attributable fraction (PAF) of preterm plus early term delivery and multiple gestations to LBW was 85.1% in 1990, and 89.3% in 2000. The PAF of maternal smoking was 6.4% in 1990, and 7.4% in 2000., Conclusions: The increase in preterm deliveries and multiple gestations were found to be the important factors with regard to the increase in LBW infants in Japan. The increased prevalence of maternal smoking was not substantially associated with the increase in LBW infants.

This study evaluated the effect of the implementation of game on mental health among participants in a bedrest (BR) experiment. Subjects were 12 healthy males aged 20-26, who participated in a 20-day 6-degrees head-down tilting BR experiment. The participants were asked to complete psychometrical questionnaires before, during, and after the experiment. We entrusted the participants to manage their leisure time and they intended a game in which all of them could take part over the experiment period. The general conversation and light-hearted mood among the subjects continued during the experimental period. Longitudinal data analysis showed that levels of neurosis and mood status did not deteriorate during the experiment, while our previous experiments, which were performed under the same protocol as this study except for the implementation of the game showed a distinct deterioration in psychosocial status. We consider that the implementation of game autonomously contributes to the positive effects on the mental health among the participants., (c2004 Elsevier Ltd. All rights reserved.)

This study evaluated changes of mood status and depressive and neurotic levels in nine young male subjects during a 20-day 6 degrees head-down tilting bed rest and examined whether exercise training modified these changes. Participants were asked to complete psychometrical inventories on before, during, and after the bed rest experiment. Depressive and neurotic levels were enhanced during bed rest period according to the Japanese version of Zung's Self-rating Depression Scale and the Japanese version of the General Health Questionnaire. Mood state "vigor" was impaired and "confusion" was increased during bed rest and recumbent control periods compared to pre-bed rest and ambulatory control periods according to the Japanese version of Profiles of Mood State, whereas the mood "tension-anxiety", "depression-dejection", "anger-hostility" and "fatigue" were relatively stable during experiment. Isometric exercise training did not modify these results. Microgravity, along with confinement to bed and isolation from familiar environments, induced impairment of mental status., (c2002 Elsevier Science Ltd. All rights reserved.)

All cases of primary adrenocortical tumors, including those found incidentally, recorded in the Pathological Autopsy Case Annuals of Japan during a 12 year period from 1973 to 1984 were surveyed. Age- and sex-specific incidences of lesions were estimated from the population, mortality and autopsy statistics for the same period. There were 101 adenomas, 77 of which were presumed to be non-functional, and 222 carcinomas. The age-specific distribution profiles of both the benign and malignant tumors showed single peaks in the sixties and could not be distinguished from one another. The estimated age-specific distribution of morbidity of the non-functional adenomas showed a peak at about 10 years younger than that found in the autopsy records, although it was again similar to that of carcinoma derived from various clinical reports. The morbidity of the non-functional adenomas per 100,000 population was almost equal to that of breast cancer in Japan, being highest in the fifties age group with more than 4,000 people a year being suggested to have adenoma in this age bracket.