Cost-effectiveness of primary prophylaxis of febrile neutropenia with pegfilgrastim in docetaxel, cisplatin and 5-fluorouracil therapy for esophageal cancer.

Objective: The efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy in treating esophageal cancer has been reported. However, febrile neutropenia (FN) is a potentially serious adverse event of DCF therapy with an incidence of 10 to 40%. Pegfilgrastim, a granulocyte colony-stimulating factor (G-CSF), has been shown to have a primary prophylactic role in FN. However, it has been suggested that excessive use of expensive G-CSF should be avoided. Therefore, we performed a cost-utility analysis of primary prophylaxis with pegfilgrastim. Design: Cost-effectiveness analysis using decision tree modelling. Methods: We used a decision tree analysis model based on the report of primary prophylaxis with pegfilgrastim. Based on a previous study, the FN incidence rate was set at 40.0% (95% confidence interval (CI): 11.9-68.1) for the pegfilgrastim group and 43.5% (95%CI: 21.6-65.4) for the no pegfilgrastim group. The FN treatment cost was US$726.63, and the duration of FN was 3.65±1.20 days. The utility value of patients who received DCF therapy was 0.643, and the change in utility value at FN onset was -0.15. Expected cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) were calculated, and cost-utility analysis was performed. Results: The ICER of pegfilgrastim was 184,976.75 USD/QALY. As a result of sensitivity analysis, the utility of FN had the greatest impact on the cost-effectiveness analysis, followed by the drug cost of pegfilgrastim. Conclusion: Primary prophylaxis of FN with pegfilgrastim might not be cost-effectiveness. In determining whether to administer pegfilgrastim it is necessary to consider patient factors, not just the incidence of FN.

The second offshore production of methane hydrate in the Nankai Trough and gas production behavior from a heterogeneous methane hydrate reservoir.

Following the first attempt at producing gas from a naturally occurring methane hydrate (MH) deposit in the Daini-Atsumi Knoll in the eastern Nankai Trough area off Honshu Island, Japan in 2013, a second attempt was made in April to June of 2017 at a nearby location using two producer wells sequentially and applying the depressurization method. The operation in the first borehole (AT1-P3) continued for 12 days with a stable drawdown of around 7.5 MPa and 41 000 m3 of methane gas being produced despite intermittent sand-production events. The operation of the other borehole (AT1-P2) followed, with a total of 24 days of flow and 222 500 m3 of methane gas being produced without sand problems. However, the degree of drawdown was limited to 5 MPa because of a higher water production rate than expected in the second hole. The pressure and temperature sensors deployed in the two producers, along with the two monitoring holes drilled nearby, gathered reservoir response data and information about the long-term MH dissociation processes in the vicinity of the production holes in the temporal and spatial domains. Although the ratio of energy return to the input was considerably larger than that for the depressurization operation, some observations (e.g., the high contrast in the production rates between the two holes and the almost constant or slightly reduced gas production rates) were not predicted by the numerical models. This failure in prediction raises questions about the veracity of the reservoir characteristics modeled in the numerical simulations. This paper presents the operation summaries and data obtained with thought-experiment based-anticipated production behaviors and preliminary analysis of the obtained data as the comparison with expected behaviors. Detailed observations of gas and water production, as well as the pressure and temperature data recorded during the gas flow tests, indicate that the heterogeneous MH distribution within the reservoir was mainly responsible for the discrepancies observed between the anticipated and actual behaviors. Furthermore, the motion of the water that does not originate from MH dissociation introduces complexity, such as the occurrence of concentrated water-producing intervals and unexpected gas production responses to decreases in pressure, into the production behavior. The influence of heterogeneity should be clearly understood for the accurate prediction of gas production behavior based on MH reservoirs.

Can digital breast tomosynthesis perform better than standard digital mammography work-up in breast cancer assessment clinic?

PURPOSE: To compare the efficacy of use of digital breast tomosynthesis (DBT) with standard digital mammography (DM) workup views in the breast cancer assessment clinic. MATERIALS AND METHODS: The Tomosynthesis Assessment Clinic trial (TACT), conducted between 16 October 2014 and 19 April 2016, is an ethics-approved, monocenter, multireader, multicase split-plot reading study. After written informed consent was obtained, 144 females (age > 40 years) who were recalled to the assessment clinic were recruited into TACT. These cases (48 cancers) were randomly allocated for blinded review of (1) DM workup and (2) DBT, both in conjunction with previous DM from the screening examination. Fifteen radiologists of varying experience levels in the Australia BreastScreen Program were included in this study, wherein each radiologist read 48 cases (16 cancers) in 3 non-overlapping blocks. Diagnostic accuracy was measured by means of sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). The receiver-operating characteristic area under the curve (AUC) was calculated to determine radiologists' performances. RESULTS: Use of DBT (AUC = 0.927) led to improved performance of the radiologists (z = 2.62, p = 0.008) compared with mammography workup (AUC = 0.872). Similarly, the sensitivity, specificity, PPV, and NPV of DBT (0.93, 0.75, 0.64, 0.96) were higher than those of the workup (0.90, 0.56, 0.49, 0.92). Most radiologists (80%) performed better with DBT than standard workup. Cancerous lesions on DBT appeared more severe (U = 33,172, p = 0.02) and conspicuous (U = 24,207, p = 0.02). There was a significant reduction in the need for additional views (χ2 = 17.63, p < 0.001) and recommendations for ultrasound (χ2 = 8.56, p = 0.003) with DBT. CONCLUSIONS: DBT has the potential to increase diagnostic accuracy and simplify the assessment process in the breast cancer assessment clinic. KEY POINTS: • Use of DBT in the assessment clinic results in increased diagnostic accuracy. • Use of DBT in the assessment clinic improves performance of radiologists and also increases the confidence in their decisions. • DBT may reduce the need for additional views, ultrasound imaging, and biopsy.

Verbal instructions influence pain thresholds assessment: A study using manual and electronic mechanical stimulators.

BACKGROUND: Quantitative sensory testing (QST) relies on psychophysical techniques and instructions to test subjects. This study examined the effect of different verbal instructions for mechanical pain thresholds (MPTs) using two different stimulation techniques; weighted pinprick stimulators and an electronic von Frey device (EvF). The test-retest reliability and within session variability in the MPTs for each verbal instruction were compared in addition. METHODS: Sixteen healthy volunteers participated. The MPTs with two different verbal instructions (pinprick and pain) were evaluated with two different stimulation techniques at three test sites: on the skin of the right cheek (face), on the buccal gingival mucosa of the right upper premolar region (gingiva) and on the tip of the tongue (tongue). The exact same protocol was repeated 1-2 weeks later for test-retest reliability. RESULTS: The MPT values with pain instruction were significantly higher than the values with the pinprick instruction for all sites and both stimulation techniques (p < .001). The absolute values of MPT were affected by instruction differences but it did not seem to have a major impact on reliability, and there were no significant differences in within session variability (p > .079) between the two different verbal instructions (pinprick and pain). CONCLUSIONS: The specific wording of standardized QST instructions resulted in significant differences in MPT values regardless of which of the two stimulation techniques were used; pinprick stimulators or EvF. This emphasizes the importance of careful standardization of QST instructions in addition to standardization of the stimulus application. SIGNIFICANCE: Quantitative sensory testing (QST) is a widely accepted tool for somatosensory testing and the reliability and variability in the QST test battery has been found to be acceptable. Changing minor details in the wording of standardized QST verbal instructions resulted in significant differences in mechanical pain thresholds. This emphasizes the importance of careful standardization of QST instructions in addition to standardization of the stimulus application.

CT findings of intraductal papillary neoplasm of the bile duct: assessment with multiphase contrast-enhanced examination using multi-detector CT.

AIM: To evaluate multi-detector computed tomography (MDCT) findings of intraductal papillary neoplasm of the bile duct (IPNB), a neoplasm that is considered to be the biliary counterpart of pancreatic intraductal papillary mucinous neoplasm. MATERIALS AND METHODS: Two radiologists retrospectively evaluated multiphase contrast-enhanced CT images with 0.5 or 1mm collimation in 37 consecutive patients with resected IPNB diagnosed by a single pathologist. The CT findings were correlated with the pathological findings concerning invasion of the surrounding organs and vessels. RESULTS: All patients showed bile duct dilatation. An intraductal mass was detected in 36 patients and the following findings were observed: extensive infiltration along the bile duct more than 20mm (n=32), compared with normal hepatic parenchyma, isodense or hyperdense during the late arterial phase (n=31), not hyperdense during the portal-venous and delayed phases (n=36), and intense enhancement rim at the base of the mass during the portal-venous or delayed phase (n=27). Parenchymal invasion of the surrounding organs was seen in eight of 16 tumours showing irregular or bulging margins. Vascular invasion was false positive in four of eight tumours. CONCLUSIONS: IPNB exhibits relatively characteristic findings with multiphase contrast-enhanced examination using MDCT. A tendency to overestimate invasion of the surrounding organs and vessels was seen.

CT findings in autoimmune pancreatitis: assessment using multiphase contrast-enhanced multisection CT.

AIM: To assess the spectrum of findings using multiphase contrast-enhanced computed tomography (CT) in patients with autoimmune pancreatitis (AIP). MATERIALS AND METHODS: Fifty patients (four female and 46 male, mean age 65 years) were retrospectively identified from consecutive patients with abnormal CT findings of the pancreas and negative work-up for known causes. These patients had at least one finding supporting the diagnosis of AIP: serological abnormality, histopathological abnormality, or response to steroid. Two radiologists evaluated multiphase contrast-enhanced CT images in consensus. RESULTS: The pancreas showed diffuse enlargement (n=16; 32%), focal enlargement (n=18; 36%), or no enlargement (n=16; 32%). Forty-nine (98%) patients showed abnormal contrast enhancement in the affected pancreatic parenchyma, including hypoattenuation during the pancreatic phase (n=45; 90%) and hyperattenuation during the delayed phase (n=39; 87%). The following findings were also seen in the pancreas: a capsule-like rim (n=24; 48%); no visualization of the main pancreatic duct lumen (n=48; 96%); ductal enhancement (n=26; 52%); upstream dilatation of the main pancreatic duct (n=27; 54%); upstream atrophy of the pancreatic parenchyma (n=27; 54%); calcification (n=7; 14%); and cysts (n=5; 10%). Forty-two (84%) patients showed one or more of the following extrapancreatic findings: biliary duct or gallbladder abnormality (n=40; 80%); peripancreatic (n=8; 16%) or para-aortic (n=10; 20%) soft-tissue proliferation; and renal involvement (n=15; 30%). CONCLUSION: Patients with AIP presented with a variety of CT findings in the pancreas and the extrapancreatic organs. The present study highlights pancreatic ductal enhancement in a subset of patients with AIP.

Lymphoplasmacytic sclerosing cholangitis: assessment of clinical, CT, and pathological findings.

AIM: To assess the clinical, computed tomography (CT), and pathological findings in patients with lymphoplasmacytic sclerosing cholangitis. MATERIALS AND METHODS: Fifteen consecutive patients (four women and 11 men, mean age 71 years) with lymphoplasmacytic sclerosing cholangitis and without the characteristic features of underlying disorders causing benign biliary strictures were retrospectively recruited. Two radiologists evaluated multiphase contrast-enhanced CT images acquired with 0.5 or 1-mm collimation. One pathologist performed all histological examinations, including IgG4 immunostaining. RESULTS: The intrahepatic biliary ducts showed dilatation in all 15 patients, but only seven presented with jaundice. Although laboratory data were not available in all patients, serum gammaglobulin and IgG levels were elevated in five of six patients and six of eight patients, respectively. Anti-nuclear antibody was detected in three of six patients. The involved biliary ducts showed the following CT findings: involvement of the hilar biliary duct (14/15), a mean wall thickness of 4.9 mm, a smooth margin (10/15), a narrow but visible lumen (6/15), hyper-attenuation during the late arterial phase (9/15), homogeneous hyper-attenuation during the delayed phase (11/11), and no vascular invasion (14/15). Abnormal findings in the pancreas and urinary tract were detected in eight of 15 patients. In 13 patients with adequate specimens, moderate to severe lymphoplasmacytic infiltration associated with dense fibrosis was observed. Infiltration of IgG4-positive plasma cells was moderate or severe in nine patients and minimal or absent in four patients. CONCLUSION: Lymphoplasmacytic sclerosing cholangitis exhibits relatively characteristic clinical and CT findings, although they are not sufficiently specific for differentiation from other biliary diseases.

Predictability of investment behavior from brain information measured by functional near-infrared spectroscopy: a bayesian neural network model.

In line with previous studies using fMRI and as is apparent from experimental results, cerebral blood flow (oxygenated hemoglobin (oxyHb) concentration) in the medial prefrontal cortex (MPFC) and orbital cortex (OFC) as is observed with fNIRS (functional near-infrared spectroscopy) is presumed to be closely related to reward prediction and risk prediction as part of decision-making under risk. Results of analysis using a predictive model with a three-layer perceptron revealed that changes in the oxyHb concentration in cerebral blood as indicated by fNIRS observation include information to effectively predict investment behavior. This paper indicates that adding oxyHb concentration at the aforementioned sites in the brain as a predictive factor allows prediction of subjects' investment behavior with a considerable degree of precision. This fact indicates that information provided by fNIRS allows valid analysis of investment behavior and it also suggests a wide-ranging practical applicability for this information like investment assistance using fNIRS.

Focal inflammation in the embryological ventral pancreas: assessment using CT and MRI.

AIM: To identify the characteristic computed tomography (CT) and magnetic resonance imaging (MRI) findings of nonuniform inflammation between the posterior aspect of the head and the remainder of the pancreas. MATERIALS AND METHODS: Two radiologists retrospectively evaluated images of 19 patients in whom the degree of attenuation in the CT images and/or the signal intensity in the MRI images differed between the posterior aspect of the head (ventral primordium) and the remainder of the pancreas (dorsal primordium) due to benign disorders other than uneven fatty replacement. Multiphase, contrast-enhanced CT examinations were performed in 17 patients. In five, T1- and T2-weighted images with and without fat suppression were obtained using a 1.5 T superconducting MRI system. RESULTS: The lesions were localized in the posterior aspect of the head in 17 patients. In two patients, the lesions occupied the posterior aspect of the head and extended to the neck. The lesions exhibited the following findings: inhomogeneous hypoattenuation (with spotty areas of relatively well-maintained contrast enhancement) during the pancreatic phase (17/17) and no intense peripheral enhancement or central necrotic areas (17/17) in CT images, hypointensity in T1-weighed images (5/5), hyperintensity in T2-weighed images (4/5), no vascular invasion (19/19), failure to depict the entire course of Wirsung's duct (17/19), and calcification (13/19). Santorini's ducts were depicted in all but three patients. CONCLUSION: Focal inflammation in the embryological ventral pancreas exhibits a unique anatomical distribution and characteristic findings.

Temporal dynamics of dairy health and production in rural smallholder communities in Northern Vietnam.

The objective of this field study was to describe the temporal pattern of dairy cattle health and production and associated risk factors in rural small-holder communities in northern Vietnam, one of the target areas of the government's dairy development programme. A total of 99 dairy farms (11 per commune) were recruited from 9 of 32 communes in Ba Vi District, Ha Tay Province, using random two-stage cluster sampling. All dairy cattle present on the selected farms were included. After the initial questionnaire survey was conducted, farms were visited to collect follow-up information at 3-monthly intervals over a period of one year. The results suggest that offtake as well as mortality are important productivity indices because farmers sell or slaughter dairy cattle that are in poor health at low prices during summer months. Changes in relation to the farming operation suggest that for the farmers adopting dairy production it has become one of the main agricultural activities.

Modelling number of services per conception of Japanese Black cattle by random regression.

Repeated records of number of services per conception (NSC) were collected on 607 Japanese Black cows. Data were analysed by random regression (RRM) and multiple trait (MTM) models, considering NSC in each parity as a separate trait. The chosen RRM included additive genetic and permanent environmental effects fitted with a third-order Legendre polynomials of parity. Heritabilities (h2) estimated by RRM decreased along the NSC trajectory from 0.15 in the first parity to 0.04 in the sixth parity and then increased up to 0.22 in the 10th parity. The corresponding estimates obtained by MTM ranged between 0.04 in parity 9 and 0.13 in parity 1. Permanent environmental proportions (p2) of the total phenotypic variance estimated by RRM showed similar pattern and magnitude to those of h2 estimated by the same method. On the contrary, the p2 estimated by MTM ranged between 0.04 in the first parity and 0.11 in the 10th parity. Additive genetic (r(G)), permanent environmental (r(P)) and phenotypic (r(PH)) correlations were also estimated. The values estimated by RRM between adjacent parities were higher than those of parities far apart. The corresponding values estimated by MTM were lower than those estimated by RRM with no certain trend. The results indicated that NSC in heifers is more heritable than NSC in cows with different parities. Reproductive traits are economically important traits and hence, they should be considered in breeding goals.

Intrapulmonary metastasis of non-small cell lung cancer: a prognostic assessment.

OBJECTIVE: According to the revised TNM classification in 1997, intrapulmonary metastasis within the same lobe of the primary tumor is designated as T4 and intrapulmonary metastasis in a different lobe is M1. However, their prognostic implications remain unclear. To assess their prognoses, we retrospectively analyzed the postoperative survival of patients with and without intrapulmonary metastasis. METHODS: From January 1982 to December 1996, 2340 patients with non-small cell lung cancer underwent surgical resection. The survival of patients having complete resection (n = 1534) was analyzed according to their intrapulmonary metastasis status: patients without intrapulmonary metastasis (n = 1393), those with metastasis in the same lobe (n = 105), and those with metastasis in a different lobe (n = 18). For comparison, patients with T4 disease without intrapulmonary metastasis in the same lobe (n = 54) and those with M1 disease without metastasis in a different lobe (distant M1, n = 18) were also analyzed. RESULTS: The overall 5-year survivals were as follows: no intrapulmonary metastasis, 60%; stage T4 disease with no intrapulmonary metastasis, 34%; pulmonary metastasis in the same lobe, 34%; pulmonary metastasis in a different lobe, 11%; and distant M1, 6%. The differences in survival between patients with no pulmonary metastasis and those with metastasis in the same lobe (P <.001, log-rank test) and between patients with metastasis in the same lobe and those with distant M1 (P <.001) were significant. In contrast, there was no significant difference between patients with metastasis in the same lobe and those with T4 disease and no intrapulmonary metastasis or between patients with metastasis to a different lobe and those with distant M1. CONCLUSIONS: Prognostically, intrapulmonary metastasis within the same lobe of the primary tumor was comparable with T4 and that in a different lobe was comparable with M1. In terms of postoperative prognosis, the revised TNM classification for intrapulmonary metastasis seems to be appropriate.

Ultrasonographic assessment of the risk of injury to branches of the middle hepatic vein during laparoscopic cholecystectomy.

BACKGROUND: Although hemorrhage from the gallbladder bed during laparoscopic cholecystectomy is one of main reasons for conversion to open cholecystectomy, the cause of this life-threatening complication is unclear. PATIENTS AND METHODS: Color Doppler ultrasound was used to examine the cause of venous hemorrhage from the gallbladder bed during laparoscopic cholecystectomy in 4 patients postoperatively and to examine the anatomic relationship between the gallbladder bed and branches of the middle hepatic vein in 50 healthy volunteers. RESULTS: Injury to a large branch of the middle hepatic vein adjacent to the gallbladder bed was diagnosed in all 4 patients. One patient required conversion to open cholecystectomy while the bleeding in 2 patients was immediately controlled by direct pressure with the gallbladder. The branch of the middle hepatic vein was completely adherent to the gallbladder bed in 5 of the 50 volunteers, and in 1 the diameter of the branch was as large as 3.5 mm. In 3 volunteers branches 3.0 to 3.8 mm in diameter traversed as close as 1.0 mm from the gallbladder bed. CONCLUSIONS: Patients with large branches of the middle hepatic vein close to the gallbladder bed are at risk of hemorrhage during laparoscopic cholecystectomy and should be identified preoperatively with ultrasound.

Clinical potential of intravascular ultrasound for physiological assessment of coronary stenosis: relationship between quantitative ultrasound tomography and pressure-derived fractional flow reserve.

BACKGROUND: Little is known regarding intravascular ultrasound (IVUS) criteria to determine the functional severity of coronary stenosis. Recently, fractional flow reserve (FFR) has emerged as a lesion-specific index of the functional severity of a coronary stenosis that is independent of systemic hemodynamic variability. The present study was undertaken to determine the IVUS parameters for the physiological severity of coronary stenosis. METHODS AND RESULTS: Fifty-one lesions in 42 patients were evaluated by means of quantitative coronary angiogram, IVUS, and intracoronary pressure measurements. The FFR was calculated as the ratio of the distal coronary pressure divided by the proximal coronary pressure under hyperemia. We considered a value of the FFR <0.75 as significant in determining inducible ischemia, according to the previous studies. The minimal luminal area (MLA) and the area stenosis were measured by IVUS. By regression analysis, the MLA showed a positive correlation with the FFR value (r(2)=0.62, P<0.0001). The area stenosis had a significant inverse correlation with the value of FFR (r(2)=0.60, P<0.0001). The IVUS thresholds that maximized the sensitivity and specificity were MLA <3.0 mm(2) (sensitivity, 83.0%; specificity, 92.3%) and area stenosis >0.6 (sensitivity, 92.0%; specificity, 88.5%). The combination of both criteria (MLA <3.0 mm(2) and area stenosis <0.6) without exception met a value of the FFR <0.75. CONCLUSIONS: Anatomic parameters obtained by IVUS showed a significant correlation to the FFR values. The present study demonstrated that the combination of the MLA and area stenosis measured by IVUS can be an anatomic predictor for the physiological impact of coronary epicardial stenosis.

Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma.

PURPOSE: To investigate the importance of preirradiation mental and endocrinological evaluation, and the effectiveness of involved-field radiotherapy following neoadjuvant chemotherapy. METHODS AND MATERIALS: Following etoposide and cisplatin with or without ifosfamide, 13 patients with nondisseminated disease received involved-field irradiation of 24 Gy in 12 fractions within 3 weeks and 2 patients with disseminated germinoma received 24 Gy craniospinal irradiation (CSI). CT simulation was used to cover the tumor bed. RESULTS: Full-scale intelligence quotient (IQ) tests given at the time of the initial radiotherapy showed less than 90 in 7 of 11 patients who had tumors involving the neurohypophyseal region, but the 4 patients who had solitary pineal tumors showed higher scores. Panhypopituitarism was observed in 9 patients with tumors involving the neurohypophyseal region. All patients are alive without disease, with a median follow-up period of 40 months. No in-field relapse was noted after the involved-field radiotherapy. One patient experienced a recurrence outside of the planning target volume. CONCLUSION: Decline of neurocognitive and endocrine functions were often seen in patients with tumors involving the hypophyseal region, but not in patients with solitary pineal germinoma before radiotherapy. Involved-field radiotherapy using 24 Gy is effective with the help of CT simulation and neoadjuvant chemotherapy.

Audiological assessment before and after fractionated stereotactic irradiation for vestibular schwannoma.

PURPOSE: To find the audiological outcome after LINAC-based fractionated stereotactic irradiation (STI). MATERIALS AND METHODS: Twenty-four patients with vestibular schwannoma treated by fractionated STI between 1991 and 1997 had measurable hearing before STI and were followed audiologically for more than 6 months. The pure tone average (PTA) was measured by averaging the air-conduction threshold for five main frequencies (250-4000 Hz) before and periodically after STI in the 24 patients. Several possible prognostic factors for hearing preservation (defined as a PTA change at the last follow-up of less than 10 dB) were investigated. The median follow-up time was 22 months, ranging from 5 to 69 months. The irradiation schedule was 36 Gy in 20 fractions in 5 weeks to 44 Gy in 22 fractions in 6 weeks followed by 4 Gy/1 fraction boost. RESULTS: The pure tone average before STI was distributed from 7 to 73 dB. Fifty percent of patients showed a change in PTA of less than 10 dB, 79.2% of patients showed a change in PTA of less than 20 dB and 20.8% of patients showed a change in PTA of more than 21 dB at the last follow-up. Only one patient (4%) became deaf. Cases with a sudden loss of hearing were more likely to experience hearing preservation than those with gradual loss of hearing (P<0.05). The mean age was younger in patients whose hearing was preserved (P<0.05). Poor pretreatment PTA appeared to linearly correspond to the changes in PTA (regression coefficient 0.78). The size of the tumor was not related to the change in PTA. No relationship was observed between the maximum or peripheral dose and the PTA change. The real benefit of stereotactic boost after small-field fractionated irradiation was not certain. CONCLUSION: Fractionated STI produced a hearing preservation rate compatible with meticulously collimated multi-spots single fraction irradiation. Further follow-up is required to confirm the long-term benefits of fractionation.

Substituted 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase.

A series of 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives have been synthesized and evaluated for their ability to selectively inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The 1-phenyl moiety participates in a hydrophobic interaction where an optimum size is required. At this position, 3,4-dimethylphenyl is the best moiety for inhibiting chymase and showed high selectivity compared with chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrogen-bond acceptors such as nitrile and methoxycarbonyl enhances its activity. Molecular-modeling studies on the interaction of 3-[(4-chlorophenyl)sulfonyl]-1-(4-chlorophenyl)-imidazolidine-2,4-dione (29) with the active site of human heart chymase suggested that the 1-phenyl moiety interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, and the 4-carbonyl of the imidazolidine ring and sulfonyl group interact with the oxyanion hole and the His-45 side chain of chymase, respectively. The complex model is consistent with the structure-activity relationships.

[Assessment of left ventricular function by pressure-volume loop in VSD and TOF before and after operation].

This study estimates the perioperative left ventricular function of VSD and TOF by using Pressure-Volume (PV) loop. The most characteristic hemodynamic change of VSD is a decreased volume load. Although ejection fraction significantly decreased after the operation, this change did not mean a deteriorated left ventricular contractility. Emax, which is an index of left ventricular contractility on PV loop, improved and pressure-volume area (PVA) which is correlated with 02 consumption of left ventricule was reduced. Mechanical efficiency of left ventricular energetic state did not significantly change. Left ventricular volume and ejection fraction in TOF slightly increased after the operation. Increased ejection fraction reflected a compensation to volume overload after surgery. Emax slightly decreased and PVA increased. Meanwhile mechanical efficiency increased after the operation indicating well preserved ventricular contractility. In particular, the shape of PV loop of both VSD and TOF eventually became usual square after operation due to recover of the isovolumic contraction and relaxation phase. These characteristics had better to be concerned for improvement of surgical techniques as in conotruncal repair, particularly in TOF in the setting of better quality of life with low atrial pressure.

Analysis and assessment of the capacity of neutrophils to produce reactive oxygen species in a 96-well microplate format using lucigenin- and luminol-dependent chemiluminescence.

The chemiluminescence (CL) assay has been used to measure the reactive oxygen species (ROS)-generating capacity of phagocytes. To achieve more optimal measurement conditions for a multi-channel microplate photon-counting CL analyzer with the cooled charge-coupled device (CCD) camera which offers enhanced sensitivity, we investigated factors affecting the variability in lucigenin-dependent CL (LgCL) measurement of human neutrophils stimulated with either opsonized zymosan (OZ) or phorbol myristate acetate (PMA). We obtained sensitive LgCL responses with good reproducibility and rapid data-acquisition using 50 microl neutrophils (3 X 10(6) cells/ml) and 50 microl of 0.5 mM lucigenin per well, in addition to either 100 microl of OZ (5 mg/ml) when zymosan was opsonized with 10-20% serum or 100 microl of PMA solution (1 X 10(-6) M) with automatic regular intervals of mixing and detection during the continuous measurement at 37 degrees C. Furthermore, we studied the contribution of various ROS to LgCL and luminol-dependent CL (LmCL) using modulators of ROS metabolism including superoxide dismutase (SOD), catalase, deferoxamine and sodium azide (NaN3). LgCL was inhibited by SOD but not by the other agents, whereas LmCL was inhibited by NaN3 and deferoxamine. Thus, it was demonstrated that LgCL detects the superoxide anion with high selectivity whereas the LmCL assay measures myeloperoxidase (MPO)-mediated formation of hypochlorous acid. Such microplate-based multiple measurements facilitate the accurate assessment of phagocytic function.

HLA affinities of Iyers, a Brahmin population of Tamil Nadu, South India.

Seventy-four randomly sampled Iyers, a Brahmin population of Tamil Nadu and preachers and followers of the Advaita philosophy, living in Madurai, were studied for their HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, C4A, C4B, and BF polymorphisms and compared with other populations. HLA alleles A1, A11.1, A24, A33, B35, B44, B51, B52, B57, Cw4, Cw6, Cw7, DR4, DR7, DR8, DR10, DR11, DR15, and DQ1 and C4A*3, C4A*4, C4A*6, C4A*Q0, C4B*1, and BF*S were represented in 15% of the samples studied. HLA alleles A25, A69, Cw3, Cw8, B45, B14, B39, B18, B50, and B56 were not identified. Various populations of Tamil Nadu were compared, but the Iyers of Madurai formed a separate cluster with Sourashtrans of Madurai and major group 4 (various Brahmin populations of Tamil Nadu); hill tribes (Irulas, Malayalis, and Badagas) and caste groups in the plains (Kallars and Nadars) formed distinct clusters. Comparison of the Iyers with other Indian and world populations revealed that Iyers form a distinct branch of the Indo-European and Central Asian tree. The Bhargavas of Lucknow, another Brahmin caste group from Uttar Pradesh, did not cluster with the Iyers but clustered with Central Asian populations. The Punjabis of Delhi clustered with European and Middle Eastern populations. Studies on two-locus haplotypes of Iyers revealed unique haplotypes in them (A26-B8, A33-B44, A33-Cw7, A1-B57, B8-DR3, B44-DR7, DR7-DQ2, C4A*32-C4B*Q0, and C4A*6-C4B*2), most of which were not identified in the Bhargavas of Lucknow and the Punjabis of Delhi. Thus it is possible that various Brahmin populations of India differ in their origin, migration, and settlement, although all of them adopted Hinduism in ancient times. A comparison of haplotypes in Iyers with the world population reveals a sharing of haplotypes with Southeast Asian populations. This implies that the ancestors of the Iyers of Madurai, who originated in the Eurasian steppes or Central Asia, might have migrated to India through Southeast Asia, thus developing the prevalent haplotypes en route.