Utility of the Berlin Initiative Study-1 equation for the prediction of serum vancomycin concentration in elderly patients aged 75 years and older.

Accurate assessment of renal function is essential for determining serum vancomycin (VCM) concentration. Creatinine clearance (Ccr)-calculated using the Cockcroft and Gault (CG) equation-can be used to evaluate renal function for determining VCM dosage. However, Ccr-based evaluation may not be an accurate representation of the renal function in the elderly. Herein, we examine the effectiveness of estimated glomerular filtration rate (eGFR) calculated using the Berlin Initiative Study-1 (BIS1) equation, for predicting the serum VCM concentration. Herein, we retrospectively analyzed patients (aged ≥ 75 years) who had received VCM. Serum VCM concentration was predicted based on Ccr and eGFR. eGFR was calculated using the Japanese equation for eGFR (eGFRJAP), Modification of Diet in Renal Disease (MDRD) equation (eGFRMDRD), chronic kidney disease epidemiology collaboration (CKD-EPI) equation (eGFRCKD-EPI), and BIS1 equation (eGFRBIS1). The predicted serum VCM concentration was compared with the measured values. Prediction bias, accuracy, and precision were evaluated by calculating the mean prediction error (ME), mean absolute prediction error (MAE), and root mean squared prediction error (RMSE). Our results showed that the ME between the measured and the predicted values calculated using Ccr and each eGFR was the largest and smallest when calculated based on Ccr and eGFRMDRD, respectively. MAE and RMSE were the largest and smallest when calculated based on Ccr and eGFRBIS1, respectively. A significant difference was observed in the MAE associated with eGFRJAP, eGFRMDRD, and eGFRCKD-EPI compared to that associated with eGFRBIS1. In conclusion, our results suggest that the BIS1 equation might be useful for determining the VCM dosage in the elderly.

Effects of convective drying assisted by ultrasound and osmotic solution on polyphenol, antioxidant and microstructure of murtilla (Ugni molinae Turcz) fruit.

The effects of pretreatment with ultrasound and an osmotic solution combined with hot air convection drying on the total polyphenol content (TPC), antioxidant activity and microstructural of murtilla skin fruit were evaluated. The effects of ultrasound frequency (0 and 130 kHz), osmotic solution concentration (0 and 70 °Brix) and time (60 or 120 min) on the TPC and the antioxidant activities as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays were evaluated. The TPC and DPPH antioxidant activity decreased significantly (p < 0.05) when ultrasound was applied at 0 °Brix for 60 min. Higher FRAP activity was obtained upon treatment with ultrasound and an osmotic solution for 60 min. The ORAC values did not significantly differ based on the pretreatment methods but decreased when an osmotic solution was applied for 120 min without ultrasound. When ultrasound and the osmotic solution were applied, the skin cells of the dried murtilla fruit became more distorted, resulting in larger spaces between them and causing loss of shape. Although the application of pretreatment procedures before murtilla fruit drying did not positively affect the TPC, DPPH or ORAC individually, the application of a Global Standardized Response based on the followed by a mathematical model adjustment indicated that a 70 °Brix osmotic solution applied for 60 min was the best treatment for preparing murtilla fruit aiming a high antioxidant activity in dried product.

Safety evaluation of the use of calcineurin inhibitor to prenatal and postpartum women in Japan from a health administrative database.

BACKGROUND: To investigate the use of calcineurin inhibitors (CNIs) in pregnant Japanese women and to evaluate their safety in infants. METHODS: Data were extracted from the claims database of the Japan Medical Data Center. The prevalence of CNIs was evaluated 180 days before pregnancy onset, during pregnancy, and within180-days post partum. We investigated the characteristics of the infants, including the presence of major malformations and their diagnoses, for 1 year after birth. RESULTS: A total of 91,865 pregnancies in 80,049 women were included. Fifty-three women were prescribed CNIs between 180-day before pregnancy onset and 180-day postpartum; 35 of the 53 women were prescribed the drugs during pregnancy, and 10 of their infants were born preterm. Three were diagnosed with major congenital malformations, such as patent ductus arteriosus. Six preterm infants presented with infant respiratory distress syndrome. CONCLUSIONS: No congenital anomalies were clearly attributable to the use of CNIs during pregnancy.

Relationship between the combination of polyunsaturated fatty acids intake and psychological distress during pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

No studies have examined the association of the combination of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs intake with psychological distress during pregnancy. To examine these associations, we divided Japanese pregnant women into 25 groups based on combining quintiles of n-3 PUFAs intake and quintiles of n-6 PUFAs intake. We conducted multivariable logistic regression analyses to assess the risk of psychological distress during pregnancy (Kessler Psychological Distress Scale ≥ 5 or 13). Compared to the third quintile of both n-3 PUFAs and n-6 PUFAs intake, the groups with unbalanced intake, high intake of both, and low intake of both were associated with a higher risk of both Kessler Psychological Distress Scale ≥ 5 and 13 in early and mid-pregnancy. Further research is needed to identify the precise combination of n-3 PUFAs and n-6 PUFAs intake associated with the lowest psychological distress during pregnancy.

Natural history of branch duct intraductal papillary-mucinous neoplasms of the pancreas without mural nodules: long-term follow-up results.

BACKGROUND AND AIMS: Although branch duct intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas without mural nodules are frequently observed in asymptomatic subjects, the natural history of these lesions has never been studied. The aim of this study was to elucidate the natural history of branch duct IPMNs without mural nodules. METHODS: Eighty-two patients who had no apparent mural nodules on initial examination were selected for follow-up. All subjects underwent examinations by imaging modalities including endoscopic retrograde pancreatography, and were followed-up by regular examinations once or twice a year. Serial changes of the maximum cystic diameter and the appearance of mural nodules were studied during the observation periods ranging from 14 to 148 months (median, 61 months). RESULTS: Nine (11.0%) of 82 patients exhibited obvious progression of cystic dilatation (median, 59 months). Of these nine patients with cystic enlargement, six continued with regular follow-up examinations. Three cases underwent surgical resection, and were pathologically diagnosed as adenoma in two and borderline in one. Four patients (4.9%) showed newly developed mural nodules in dilated branch ducts (median, 105 months). Histological analysis revealed three cases classified as adenoma and one as carcinoma in situ. None of the remaining 69 patients (84.1%) showed any changes in dilated branch ducts (median, 57 months). CONCLUSIONS: Most branch duct IPMNs without mural nodules remained unchanged during long-term follow-up. Although follow-up with careful examination is required to detect newly developed mural nodules in dilated branch ducts, branch duct IPMNs without mural nodules can be followed-up without surgery.

Home blood pressure measurements associated with better blood pressure control: the J-HOME study.

The usefulness of self-measurements of blood pressure (BP) at home (home BP measurements) in hypertensive patients has been reported by many studies. Several national guidelines recommend the use of home BP measurements to achieve better hypertension control. The objective of this study was to clarify the association between home BP measurements and hypertension treatment among 2363 essential hypertensive patients taking antihypertensive drugs. Compared to the 543 (23.0%) patients who had not taken home BP measurements, the 1820 (77.0%) patients who had taken home BP measurements were significantly older, included a higher proportion of males, included a higher proportion with a family history of hypertension, took a greater number of antihypertensive drugs and alpha blockers and took antihypertensive drugs more often in the evening. Home BP measurements were associated with significantly better control of home and office BP levels. Compared to patients who had not taken home BP measurements, the adjusted odds ratios for good control of morning home BPs, evening home BPs and office BPs in patients who had taken home BP measurements were 1.46 (95% confidential interval (CI) 1.33-1.57), 1.35 (95% CI 1.21-1.47) and 1.23 (95% CI 1.06-1.37), respectively. Home BP measurements were associated with good hypertensive management. Our findings suggest that it is important that physicians recommend home BP measurements to their patients.

[Multiple calcifying fibrous pseudotumor of the pleura].

A newly recognized distinctive fibrous soft tissue lesion called "calcifying fibrous pseudotumor" (CFPT) was recently described in the soft tissue of the extremities, trunk, scrotum, groin, neck, or axilla. But CFPT orgining from the pleura is rare. A 44-year-old woman was admitted to our hospital for an investigation of a chest radiographic abnormality. The complete resection was performed through mini-thoracotomy utilizing video assisted thoracoscopic surgery. Microscopically, the lesion was mostly composing dense collagenous tissue and scattered calcifications. The postoperative course was uneventful and no recurrence is observed 18 months after operation. We report succsessful surgical treatment for multiple CFPTs.

[Adult Bochdalek hernia with volvulus of the stomach].

We report a rare case of Bochdalek hernia, congenital posterolateral diaphragmatic hernia with volvulus of the stomach, in an adult A 74-year-old man was admitted to our hospital complaining of sudden abdominal pain and vomiting. Roentgenologic examination of the chest showed air above the left diaphragm, and the mediastinum was displaced to the right. Upper gastrointestinal series revealed volvulus of the stomach in which the pylorus was displaced to the left. The surgical repair was done through left thoracotomy with combining laparoscopy and thoracoscopy without surgical complications, 1 year later the patient is asymptomatic.

Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification.

Parafibromin is a protein product derived from the hyperparathyroidism 2(HRPT2) tumor suppressor geneand its inactivation has been coupled to familial and sporadic forms of parathyroid malignancy. In this study, we have conducted immunohistochemistry on 33 parathyroid carcinomas (22 unequivocal and 11 equivocal) using four parafibromin antibodies directed to different parts of the protein. Furthermore, for a fraction of cases, the immunohistochemical results were compared with known HRPT2 mutational status. Our findings show that 68% (15 out of 22) of the unequivocal carcinomas exhibited reduced expression of parafibromin while the 25 sporadic adenomas used as controls were entirely positive for parafibromin expression. Additionally, three out of the six carcinomas with known HRPT2 mutations showed reduced expression of parafibromin. Using all four antibodies, comparable results were obtained on the cellular level in individual tumors suggesting that there exists no epitope of choice in parafibromin immunohistochemistry. The results agree with the demonstration of a approximately 60 kDa product preferentially in the nuclear fraction by western blot analysis. We conclude that parafibromin immunohistochemistry could be used as an additional marker for parathyroid tumor classification, where positive samples have low risk of malignancy, whereas samples with reduced expression could be either carcinomas or rare cases of adenomas likely carrying an HRPT2 mutation.

Stimulation by thyroid-stimulating hormone and Grave's immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo.

To elucidate the pathogenesis of thyroid gland hypervascularity in patients with Graves' disease, we studied the expression of mRNAs for vascular endothelial growth factor (VEGF) and its receptor, Flt family, using human thyroid follicles in vitro and thiouracil-fed rats in vivo. Human thyroid follicles, cultured in the absence of endothelial cells, secreted de novo-synthesized thyroid hormone in response to thyroid-stimulating hormone (TSH) and Graves' IgG. The thyroid follicles produced VEGF mRNA but not flt-1 mRNA. The expression of VEGF mRNA was enhanced by insulin, tumor-promoting phorbol ester, calcium ionophore, dibutyryl cAMP, TSH, and Graves' IgG. When rats were fed thiouracil for 4 wk, their serum levels of TSH were increased at day 3. VEGF mRNA was also increased on day 3, accompanied by an increase in flt family (flt-1 and KDR/ flk-1) mRNA expression. These in vitro and in vivo findings suggest that VEGF is produced by thyroid follicles in response to stimulators of TSH receptors, via the protein kinase A and C pathways. VEGF, a secretable angiogenesis factor, subsequently stimulates Flt receptors on endothelial cells in a paracrine manner, leading to their proliferation and producing hypervascularity of the thyroid gland, as seen in patients with Graves' disease.

[Esophago-bronchial fistula confirmed with bronchoscopy utilized an indocyanine green].

The patient was a 54-year-old female with both headache and vomit presented to the emergency room. Endoscopic examination revealed an advanced esophageal cancer located on the middle thoracic esophagus. Histological analysis revealed squamous cell carcinoma. The clinical stage was diagnosed as T4N2M0 and this case was treated by the chemoradiation. She presented progressive moist cough after chemoradiotherapy. Esophagography demonstrated esophago-bronchial fistula (EBF). EBF was not detected by routine broncoscopy. To confirm fistula, we were performed the bronchoscopy which utilized an indocyanine green. Contrast media colored green were over from the superior segmental bronchus in a bronchoscope. The bronchoscope which utilized an indocyanine green is effective for EBF.

Effects of phenobarbital and secondary bile acids on liver, gallbladder, and pancreas carcinogenesis initiated by N-nitrosobis (2-hydroxypropyl)amine in hamsters.

The effects of dietary administration of phenobarbital [(PB) CAS: 50-06-6] or the secondary bile acids, deoxycholic acid [(DCA) CAS: 83-44-3] and lithocholic acid [(LCA) CAS: 434-13-9], on tumorigenesis in the liver, gallbladder, and pancreas were investigated in male Syrian golden hamsters after carcinogenic initiation by N-nitrosobis(2-hydroxypropyl)amine [(BHP) CAS: 53609-64-6]. BHP [500 mg/kg (body wt)] was injected sc once weekly for 5 weeks. The animals were then maintained on a basal diet or a diet containing either 0.05% PB, 0.1% DCA, 0.5% DCA, or 0.5% LCA for 30 weeks. DCA enhanced the development of cholangiocarcinomas without influencing that of hepatocellular lesions. PB promoted the induction of hepatocellular carcinomas but not that of cholangiocarcinomas. LCA was without effect on the induction of either hepatocellular carcinomas or cholangiocarcinomas. DCA at a dose of 0.5% enhanced the induction of polyps in the gallbladder. Both DCA, at a dose of 0.1%, and LCA significantly enhanced the induction of pancreas carcinomas. PB had no effect on the induction of polyps in the gallbladder or of pancreas carcinomas. These data document that different tumors may be differentially promoted following initiation with a common carcinogen.

Total cost minimization control scheme for biological wastewater treatment process and its evaluation based on the COST benchmark process.

This paper proposes a new cost minimisation control scheme for a predenitrification type of biological wastewater treatment process and evaluates the validity of the control scheme based on the benchmark process presented by Copp. The control scheme adopting a hierarchical control structure incorporates lower-level controllers that consist of a set of local dynamic controllers and a higher-level static optimiser that provides the set points of the lower-level controllers based on the total cost index of Vanrolleghem and Gillot. Prior to benchmarking, this paper derives a simplified process model used for the optimiser, which is able to approximate the benchmark process model effectively as well as is simplified sufficiently for faster set point optimisation for on-line purposes. Numerical experiments evaluate the effectiveness of the proposed control scheme from various viewpoints including process operational and optimisation viewpoints.

Activation of peroxisome proliferator-activated receptor gamma by troglitazone inhibits cell growth through the increase of p27KiP1 in human. Pancreatic carcinoma cells.

In the present study, we examine whether human pancreatic carcinoma cells express peroxisome proliferator-activated receptor gamma (PPARgamma) and the effect of PPARgamma activation by its selective ligand on cellular growth in pancreatic cancer cells. Immunohistochemical study of resected human pancreata using a polyclonal PPARgamma antibody revealed that PPARgamma protein expression in the nuclei of carcinoma cells was observed in 9 of 10 pancreatic adenocarcinomas. In contrast, normal pancreatic duct epithelial cells in the samples expressed no PPARgamma. Reverse transcription-PCR and Northern blot analysis demonstrated that all four tested human pancreatic cancer cell lines, PK-1, PK-8, PK-9, and MIA Paca-2, expressed PPARgamma mRNA. Luciferase assay in PK-1 cells showed that troglitazone, a selective ligand for PPARgamma, transactivated the transcription of a peroxisome proliferator response element-driven promoter in a dose-dependent fashion. Troglitazone inhibited the growth of all four pancreatic carcinoma cell lines in a dose-dependent manner. Cell cycle analysis by flow cytometry demonstrated that troglitazone induced G1 arrest in PK-1 cells. To examine the role of cyclin-dependent kinase inhibitors in the G1 arrest by troglitazone, we determined p27KiP1, p21CiP1/Waf1, or p18Ink4c protein expression by Western blot analysis in troglitazone-treated PK-1 cells. Troglitazone increased p27Kip1 but not p21Cip1/Waf1 or p18Inkc protein levels in time- and dose-dependent manners. To clarify the functional importance of p27Kip1 in the cell growth inhibition by troglitazone. All these results suggest that PPARgamma could be considered as a possible target molecule for treatment in human pancreatic carcinomas.

Effects of transforming growth factor-beta released from gastric carcinoma cells on the contraction of collagen-matrix gels containing fibroblasts.

To investigate the mechanisms underlying contraction of the stomach wall in cases of gastric scirrhous carcinoma, we have developed an in vitro model for gastric cancer, in which both fibroblasts and gastric carcinoma cells are embedded within a collagen matrix. Gastric carcinoma cells of the scirrhous type (KATO-III) but not the nonscirrhous type (MKN-28) markedly enhanced the ability of human intestine, human lip, and mouse kidney fibroblasts to contract collagen gels. KATO-III cells released transforming growth factor-beta (TGF-beta) into culture media in an activated form, whereas the MKN-28 cells produced a latent form. The role of TGF-beta produced by gastric cancer cells from the scirrhous type was clarified by adding TGF-beta (receptor grade) into collagen gels embedded with fibroblasts, contraction being enhanced. Other growth factors tested, including transforming growth factor-alpha and epidermal growth factor, did not enhance the contraction of collagen gels containing embedded human and rodent fibroblasts. These results suggest that the activated form of TGF-beta released from gastric scirrhous carcinoma cells stimulates fibroblasts to contract the collagenous stroma of the stomach wall, which leads to the so-called "linitis plastica" stomach condition.

Preneoplastic and neoplastic growth of xenotransplanted lung-derived human cell lines using deepithelialized rat tracheas.

The human lung tumor-derived cell lines A549, Calu-1, Calu-3, HuT292, and SW900 and the transformed human bronchial epithelial cell line TBE-1, that was transfected with the v-Harvey-ras oncogene, were inoculated into deepithelialized Fisher 344 rat tracheas (5 X 10(5) cells/trachea). After the ends of the tracheas were sealed, the tracheas were transplanted into s.c. tissues of nude mice. In a parallel experiment, 1 X 10(6) cells from each of these cell lines were injected s.c. Histological examination of the tracheal transplants 2, 4, 8, 12, and 16 weeks after cell inoculation proved to be of greater usefulness than either clinical or histological observation of the s.c. injection sites. A549, Calu-1, and TBE-1 produced intratracheal neoplastic nodules as early as 2 weeks after cell inoculation. Calu-3, HuT292, and SW900 grew relatively slowly in the tracheas, and simple or stratified epithelia with slight or moderate atypia (preneoplastic lesions) were seen at 2 weeks. After the 4th week, they produced tumor nodules in the tracheal transplants, whereas no tumor cells could be seen at the s.c. injection sites. The human derivation of the cells was confirmed by in situ hybridization using human-specific DNA probes. The intratracheal inoculation and xenotransplantation of human-derived cell lines offers a time-saving alternative to the s.c. inoculation assay for tumorigenicity and is at the same time a potentially valuable approach to studying preneoplastic and neoplastic progression with human cell subpopulations.

[New forceps for a sutureless patch technique using sheet materials].

Intraoperative air leaks are often treated by a sutureless patch technique using a fibrin tissue-adhesive collagen fleece or synthetic materials with fibrin sealant. Intraoperatively, the technique of using these materials has been troublesome, therefore air leaks fail to close. Akicette has been applied as an easy sutureless patch technique for air leaks. Seven air leaks (5 were lung cancers, 2 were spontaneous pneumothorax) were treated with Akicette. Akicette is simple to operate with, and can easily carry sheet materials. Using Akicette, the sheet materials tightly adhered onto surrounding the pleural defect without any sliding on the wet lung surface. Akicette is feasible tool for a sutureless patch technique and is useful to easily place the sheet materials.

Importance of ornithine transcarbamylase (OTC) deficiency in small intestine for urinary orotic acid excretion: analysis of OTC-deficient spf-ash mice with OTC transgene.

We report the effect of the ornithine transcarbamylase (OTC) transgene composed of 1.3 kb of the 5' flanking region of the rat OTC gene fused to rat OTC cDNA on urinary orotic acid excretion in OTC-deficient spf-ash (sparse-fur with abnormal skin and hair) mice during overnight-starvation and nitrogen loading. During starvation, spf-ash mice with about 6% and 2% of control levels of OTC activity in the liver and small intestine excreted a large amount of orotic acid in the urine. Transgenic spf-ash mice with about 10% and 30% of the control OTC activities in the liver and small intestine did not excrete more than the normal level of orotic acid. Accidental parasitization of transgenic spf-ash mice with ticks (Myocoptes musculinus) resulted in decrease of the OTC activities in the liver and small intestine to the levels in spf-ash mice, and increased excretion of orotic acid. During extermination of the ticks, the mice showed varied levels of OTC activity and orotic acid excretion. On nitrogen loading, transgenic spf-ash mice as well as spf-ash mice excreted larger amounts of orotic acid, while control mice showed no increase in its excretion. The levels of urinary orotic acid were inversely correlated to the logarithms of the OTC activities in the liver and small intestine, the correlation being significantly higher with intestinal OTC than with hepatic OTC activity. These results suggest that the level of OTC activity in the small intestine is important for production of orotic acid.

Low density lipoprotein receptor activity in the guinea pig adrenal cortex. I. Zonal characterization and response to adrenocorticotropin.

The binding of [125I]iodo-low density lipoprotein ([125I]iodo-LDL) to isolated membranes was determined for the outer (glomerulosa/fasciculata) and inner (reticularis) zones of the guinea pig adrenal cortex. Binding of [125I]iodo-LDL to membranes from both zones was found to be highly specific and dependent on the presence of divalent cations, such as calcium. Saturation analysis revealed that the maximum high affinity binding capacity was similar for both zones under control conditions (approximately 400 ng/mg protein). When ACTH was administered, however, the maximum high affinity binding capacity increased in the outer zone by at least 3-fold, while there was no significant change for the inner zone. It was also noted that dexamethasone administration decreased [125I]iodo-LDL high affinity binding activity to less than half the control level in the outer zone without altering the binding activity in the inner zone. The cholesterol content in the outer zone was 2-3 times greater than that in the inner zone. When ACTH was administered, the concentration of cholesterol decreased significantly in both zones. Thus, ACTH appeared to influence cholesterol metabolism in the outer and inner adrenocortical zones, but was able to modulate LDL receptor activity only in the outer zone.