Early diagnosis of recurrent hepatocellular carcinoma with 18F-FDG PET after radiofrequency ablation therapy

The aim of this study was to evaluate the role of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in the restaging of hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA). This study was performed on 33 lesions in 24 patients with HCC. 18F-FDG PET and computed tomography (CT) studies were performed in all patients before treatment. PET acquisition was started 50-60 min after injection of 18F-FDG (5-6 MBq/kg). Semi-quantitative analysis using Standardized Uptake Value (SUV) was measured for the evaluation of tumour 18F-FDG uptake. All patients underwent RFA treatment and were followed up at least 2 years with 18F-FDG PET, CT and clinical evaluation in the interval of every 3 months in the first year and every 6 months in the second year. 18F-FDG PET detected recurrence earlier than CT between 4-6 months in 2 patients and between 7-9 months in 6 patients whereas CT was positive in 4 patients. Overall detection rate of recurrence with 18F-FDG PET was 92% which was higher than that of CT (75%). Statistically significant difference in the SUV was observed between well and moderately differentiated HCC (p=0.033) and also between well and poorly differentiated HCC (p=0.037). The size of tumours showed a significant correlation with the time of recurrence (p<0.00033, r=0.8601, n=12). The results of this study indicate that 18F-FDG PET could detect recurrence earlier in patients with HCC treated with RFA, as compared with CT and could diagnose extrahepatic lesions. SUV showed a significant correlation with time of recurrence after RFA. 18F-FDG PET may be a dominant imaging modality as a follow-up procedure of HCC after RFA, in terms of early detection of recurrence.     

Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy

PURPOSE: To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa. PATIENTS AND METHODS: In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin > or =100 ng/ml or transferrin saturation > or =15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal. RESULTS: One hundred twenty-nine patients were evaluable for efficacy (FG, n = 41; oral iron, n = 44; no iron, n = 44). Mean increase in Hb was 2.4 g/dl (95% confidence interval [CI], 2.1-2.7) for FG (p = .0092 vs. oral iron; p = .0044 vs. no iron), 1.6 g/dl (95% CI, 1.1-2.1) for oral iron (p =.7695 vs. no iron), and 1.5 g/dl (95% CI, 1.1-1.9) for no iron. Hb response (increase > or =2 g/dl) was 73% for FG (p = .0099 vs. oral iron; p = .0029 vs. no iron), 46% for oral iron (p = .6687 vs. no iron), and 41% for no iron. FG was well tolerated. CONCLUSION: For cancer patients with chemotherapy-related anemia receiving epoetin alfa, FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron, supporting more aggressive treatment with IV iron supplementation for these patients.     

Monitoring sheet covering long-term chemotherapy to predict individual adverse reaction patterns for patients with gynecologic chemotherapy

Monitoring the adverse reaction patterns specific to individual patients is important to avoid subsequent reactions. Gynecologic cancer chemotherapy is often implemented repeatedly with an altered protocol during prolonged terms. The purpose of this study was to develop and assess the efficacy of a worksheet that pharmacists can use to analyze adverse reaction patterns in individual patients with gynecologic chemotherapy. The worksheet which we developed consisted of multiple sections. One section is for necessary drug information for the proper use of antineoplastic agents. Another section is for the following items recorded by the pharmacists: a) patients' basic information such as stage of disease and protocol, b) state of implementation and break of chemotherapy and supportive therapy on calendar, and c) laboratory data and symptoms. We arranged the last item below the calendar and enabled pharmacists to easily assess individual adverse reactions coupled with the treatment course. Reviews of the developed worksheet indicated that the worksheet led to the convenient detection of individual adverse reaction patterns and effective prevention of additional adverse reactions. This monitoring sheet covering long-term chemotherapy which was designed to predict individual adverse reaction patterns will improve the individualization and safety of gynecologic chemotherapy.     

A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder

Rationale Nitrous oxide (N₂O) can initially lower core temperature (T _core), but hypothermic tolerance develops with chronic administration. Therefore, one or both of T _core’s controlling determinants, heat production (HP) and heat loss (HL), must adapt across repeated N₂O administrations. Simultaneous measurements of HP, HL, and T _core during chronic N₂O administrations will elucidate this adaptive process and constitute a rigorous model for studying the systems-level dynamics of tolerance in both mature and young animals. This approach is justified by the need to better understand the increased vulnerability to addiction associated with adolescent drug use. Objectives The objective of the study was to measure HL and HP across repeated steady-state administrations of 60% N₂O in young and mature rats. Materials and methods Synchronous measurements of HP (indirect calorimetry), HL (direct calorimetry), and T _core (telemetry) were obtained during 60% N₂O administrations in adolescent (28–45 days, n = 11) and mature rats (>90 days, n = 8). Rats received five 90-min drug exposures (every other day). Results Compared to mature rats, adolescents initially exhibited greater hypothermia, but acquired tolerance more rapidly and actually developed hyperthermia during the fifth administration. In both groups, N₂O consistently increased HL, but progressive increases of intrasessional HP over repeated administrations prevented hypothermia and subsequently promoted hyperthermia in adolescent rats. Conclusions Adolescent rats hyper-adapt to N₂O hypothermia. Increases of intrasessional HP across N₂O administrations explained both tolerance to N₂O hypothermia and the unexpected hyperthermia observed in adolescents. These findings raise the possibility that the increased vulnerability to addiction associated with adolescent drug use involves a hyper-adaptive tolerance mechanism.     

A comprehensive model for reproductive and developmental toxicity hazard identification: I. Development of a weight of evidence QSAR database

A weight of evidence (WOE) reproductive and developmental toxicology (reprotox) database was constructed that is suitable for quantitative structure-activity relationship (QSAR) modeling and human hazard identification of untested chemicals. The database was derived from multiple publicly available reprotox databases and consists of more than 10,000 individual rat, mouse, or rabbit reprotox tests linked to 2134 different organic chemical structures. The reprotox data were classified into seven general classes (male reproductive toxicity, female reproductive toxicity, fetal dysmorphogenesis, functional toxicity, mortality, growth, and newborn behavioral toxicity), and 90 specific categories as defined in the source reprotox databases. Each specific category contained over 500 chemicals, but the percentage of active chemicals was low, generally only 0.1-10%. The mathematical WOE model placed greater significance on confirmatory observations from repeat experiments, chemicals with multiple findings within a category, and the categorical relatedness of the findings. Using the weighted activity scores, statistical analyses were performed for specific data sets to identify clusters of categories that were correlated, containing similar profiles of active and inactive chemicals. The analysis revealed clusters of specific categories that contained chemicals that were active in two or more mammalian species (trans-species). Such chemicals are considered to have the highest potential risk to humans. In contrast, some specific categories exhibited only single species-specific activities. Results also showed that the rat and mouse were more susceptible to dysmorphogenesis than rabbits (6.1- and 3.6-fold, respectively).     

In Vitro-In Vivo Correlation of Blood–Brain Barrier Permeability of Drugs: A Feasibility Study Towards Development of Prediction Methods for Brain Drug Concentration in Humans

Pharmaceutical Research - In vitro human blood–brain barrier (BBB) models in combination with central nervous system-physiologically based pharmacokinetic (CNS-PBPK) modeling, hereafter...     

Longitudinal neuroendocrine changes assessed by dexamethasone/CRH and growth hormone releasing hormone tests in psychotic depression

Although psychotic depression has been reported to exhibit a greater degree of dysregulation of hypothalamic-pituitary-adrenocortical (HPA) function than non-psychotic depression, little is known concerning hypothalamic-pituitary-somatotropic (HPS) function in psychotic depression and how neuroendocrine function changes after treatment. To investigate the longitudinal changes in HPA and HPS system function in psychotic depression, we performed repeated dexamethasone/corticotropin releasing hormone (DEX/CRH) tests and growth hormone (GH) releasing hormone (GHRH) tests in inpatients with major depressive disorder. The psychotic depression group exhibited greater elevation of ACTH responses to the DEX/CRH test and stronger decreases in GH responses to the GHRH test than the non-psychotic depression group at admission. At discharge, the neuroendocrine responses to the DEX/CRH test of the psychotic depression group were still stronger than those of the non-psychotic depression group, though there were no significant differences in severity of depression between the groups. There were significant longitudinal changes in neuroendocrine responses to the DEX/CRH test between admission and discharge. The psychotic depression group exhibited increased GH responses to GHRH at discharge compared with those at admission, whereas no significant longitudinal change in GH response was found in the non-psychotic depression group. Consequently, there were no significant differences in GH responses to GHRH between the psychotic and non-psychotic depression groups at discharge. The results of GHRH test showed no significant relationships with severity of depression except psychotic features and the results of the DEX/CRH test. Our findings suggest that the HPS axis may be associated with psychotic features rather than general severity of depression. Further longitudinal studies are needed to clarify the role of HPS function in psychotic depression and whether sustained dysregulation of HPA function in psychotic depression is associated with a poor outcome after discharge.     

Level, distribution and correlates of platelet-derived microparticles in healthy individuals with special reference to the metabolic syndrome

Platelet-derived microparticles (PDMPs), a procoagulant factor, are reportedly elevated in type 2 diabetes mellitus and acute coronary syndrome. The metabolic syndrome (MS) is strongly associated with cardio- and cerebrovascular disease-related atherothrombotic events. To clarify the level, distribution and correlates of PDMPs with special reference to MS, we conducted a cross-sectional study of 467 healthy Japanese volunteers without signs, symptoms, or a history of cardio- or cerebrovascular disease. They were 211 men and 256 women (median age 39 and 35 years, respectively). Using an ELISA kit and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX) we assayed the PDMP levels. Total cholesterol, low-density and high-density lipoprotein cholesterol, remnant cholesterol, triglycerides, C-reactive protein, and traditional cardiovascular risk factors were also recorded. There was a significant difference in the level of PDMPs between men and women. The median value and the interquartile range of PDMPs was 8.3 IU/ml and 6.2-10.5 IU/ml and 6.8 IU/ml and 5.2-8.6 IU/ml, respectively, in men and women. PDMPs were significantly associated with MS criteria in men (p < 0.001) and women (p = 0.040). Logistic regression analysis revealed a significant odds ratio of 3.9 [95% confidence interval (CI): 1.4-10.5] in men and of 4.2 [95% CI: 1.6-10.7] in the entire study population. Our results suggest that PDMPs identified by glycoprotein CD42b and CD42a are positively associated with MS.     

Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study

BACKGROUND: Trichotillomania (repetitive hair-pulling) is an Axis I psychiatric disorder whose neurobiological basis is incompletely understood. Whole-brain trichotillomania neuroimaging studies are lacking. AIMS: To investigate grey and white matter abnormalities over the whole brain in patients with trichotillomania. METHOD: Eighteen patients with DSM-IV trichotillomania and 19 healthy controls undertook structural magnetic resonance imaging after providing written informed consent. Differences in grey and white matter were investigated using computational morphometry. RESULTS: Patients with trichotillomania showed increased grey matter densities in the left striatum, left amygdalo-hippocampal formation, and multiple (including cingulate, supplementary motor, and frontal) cortical regions bilaterally. CONCLUSIONS: Trichotillomania was associated with structural grey matter changes in neural circuitry implicated in habit learning, cognition and affect regulation. These findings inform animal models of the disorder and highlight key regions of interest for future translational research.