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Competing Interests: Competing interests: None declared.

Background: Genetic characteristics of polycystic kidney disease (PKD) patients without apparent family history were reported to be different from those with a positive family history. However, the clinical course of PKD patients with no apparent family history is not well documented in the literature., Methods: We evaluated the relationship between genotype and the clinical course of 62 PKD patients with no apparent family history., Results: The annual decline of renal function was faster in the patients with PKD1/PKD2 mutation (PKD1 truncating [-3.08; 95% CI -5.30 to -0.87, p = 0.007], PKD1 nontruncating [-2.10; -3.82 to -0.38, p = 0.02], and PKD2 [-2.31; -4.40 to -0.23, p = 0.03]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, estimated glomerular filtration rate (eGFR), height-adjusted total kidney volume (TKV), and mean arterial pressure (MAP). There was no significant difference in the annual decline of renal function among the different PKD1/PKD2 groups, but Kaplan-Meier analysis showed that progression to eGFR < 15 mL/min/1.73 m2 was significantly faster in PKD1 truncating group (p = 0.05). The annual rate of TKV increase was larger in the patients with PKD1/PKD2 mutation (PKD1 truncating [4.63; 95% CI 0.62-8.64, p = 0.03], PKD1 nontruncating [3.79; 0.55-7.03, p = 0.02], and PKD2 [2.11; -1.90 to 6.12, p = 0.29]) than in the other patients without PKD1/PKD2 mutation. Similar results were obtained after adjustment for gender, age, eGFR, and MAP., Conclusion: Detection of PKD1/PKD2 mutation, especially PKD1 truncating, is useful for predicting the renal outcome and rate of TKV increase in PKD patients with no apparent family history., (© 2019 S. Karger AG, Basel.)

The kidneys consume a large amount of energy to regulate volume status and blood pressure and to excrete uremic toxins. The identification of factors that cause energy mismatch in the setting of chronic kidney disease (CKD) and the development of interventions aimed at improving this mismatch are key research imperatives. Although the critical cellular energy sensor 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is known to be inactivated in CKD, the mechanism of AMPK dysregulation is unknown. In a mouse model of CKD, metabolome analysis confirmed a decrease in AMPK activation in the kidneys despite a high AMP: ATP ratio, suggesting that AMPK did not sense energy depletion. Similar AMPK inactivation was found in heart and skeletal muscle in CKD mice. Several uremic factors were shown to inactivate AMPK in vitro and in ex vivo preparations of kidney tissue. The specific AMPK activator A-769662, which bypasses the AMP sensing mechanism, ameliorated fibrosis and improved energy status in the kidneys of CKD mice, whereas an AMP analog did not. We further demonstrated that a low-protein diet activated AMPK independent of the AMP sensing mechanism, leading to improvement in energy metabolism and kidney fibrosis. These results suggest that a failure to sense AMP is the key mechanism underlying the vicious cycle of energy depletion and CKD progression and direct AMPK activation may be a novel therapeutic approach in CKD., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

In patients with chronic kidney disease (CKD), low body mass index (BMI) is associated with high mortality. This relationship in emergently hospitalized CKD patients is unknown. We investigated the association between obesity and short-term mortality in emergently admitted patients with dialysis-independent CKD (DI-CKD) with and without infection. This retrospective cohort study examined Diagnosis Procedure Combination data of 26103 emergently hospitalized DI-CKD patients. Patients were divided into 8 groups according to their BMI and the presence of infectious diseases. The primary outcome was in-hospital death within 100 days. Cox proportional hazards models adjusted for baseline characteristics showed that low BMI was associated with the outcome both in infected and in non-infected patients (reference group as non-infected and medium BMI [24-26 kg/m2] group): infected and the lowest BMI (≤20 kg/m2) group, hazard ratio (HR) 1.82 (95% confidence interval 1.51, 2.19); non-infected and the lowest BMI group, 1.39 (1.16, 1.67). When patients were stratified according to presence of diabetes mellitus (DM), patients with DM showed that low BMI was associated with the outcome both in infected and in non-infected patients, whereas in non-DM patients, this relationship was attenuated in the non-infected group. For emergently hospitalized CKD patients with infection, high BMI was associated with lower mortality irrespective of the DM status. For non-infected patients, the effects of obesity for in-hospital mortality were modified by the DM status., Competing Interests: The authors have declared that no competing interests exist.

"Double-hit" lymphoma (DHL) is a high-grade B-cell lymphoma that harbors concurrent MYC and BCL2 or BCL6 rearrangements. Because cases of MYC / BCL6 DHL are uncommon, most reported conclusions have been based on cases of MYC / BCL2 DHL. Lack of experimental MYC / BCL6 DHL models continues to hinder the pathophysiologic and therapeutic investigations of this disorder. We herein describe a novel MYC / BCL6 DHL cell line, designated DH-My6, carrying both the MYC - IGH and BCL6 - IGH fusion genes. Interruptions of MYC and BCL6 expressions using short interfering RNAs and chemical inhibitors led to significant attenuation of DH-My6 cell growth. Greater antitumor effects were found when the cells were treated with a combination of MYC and BCL6 inhibitors. Moreover, the PLK1 inhibitor volasertib and the HDAC inhibitor vorinostat synergized strongly when combined with the bromodomain inhibitor JQ1. DH-My6 is a new well-validated MYC / BCL6 DHL cell line that will provide a useful model for studies of the pathogenesis and therapeutics for the less common DHL tumor type. The rationale for approaches targeting both MYC and BCL6, and in combination with PLK1 or HDAC inhibitors for superior suppression of the aggressive MYC / BCL6 DHL warrants further in vivo testing in a preclinical model., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interests.

Objective: Metformin is an antidiabetic drug that is widely used to treat patients with diabetes mellitus. Recent studies have reported that treatment with metformin not only improved blood glucose levels but also reduced blood pressure. However, it remains unclear how metformin reduces blood pressure. We hypothesized that metformin affects sodium reabsorption in the kidneys., Methods: Urinary sodium excretion and expression of renal sodium transporters were examined in 8-week-old male C57BL/6 mice with acute and chronic treatment of metformin. In addition, we examined metformin effects using ex vivo preparations of mice kidney slices., Results: In this study, we demonstrated that metformin increased urinary sodium excretion by reducing phosphorylation of the thiazide-sensitive Na-Cl cotransporter (NCC) in acute and chronic metformin administration. We also confirmed reduction of phosphorylated NCC in an ex vivo study. The activity of other renal sodium transporters, such as NKCC2, ENaC, and NHE3 did not show significant changes. WNK-OSR1/SPAK kinase signals were not involved in this inactivation effect of metformin on NCC., Conclusion: Metformin increased urinary sodium excretion by reducing phosphorylation of NCC, suggesting its role in improving hypertension., (Copyright © 2018 Elsevier Inc. All rights reserved.)

With-no-lysine (K) (WNK) kinases, which are mutated in the inherited form of hypertension pseudohypoaldosteronism type II, are essential regulators of membrane ion transporters. Here, we report that WNK1 positively regulates skeletal muscle cell hypertrophy via mediating the function of the pro-longevity transcription factor forkhead box protein O4 (FOXO4) independent of the conventional WNK signaling pathway linking SPS/STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1) to downstream effector ion transporters. Small interfering RNA (siRNA)-mediated silencing of WNK1, but not SPAK/OSR1 kinases, induced myotube atrophy and remarkable increases in the mRNA expression of the muscle atrophy ubiquitin ligases MAFbx and MuRF1 in C2C12 mouse skeletal muscle cells. WNK1 silencing also increased FOXO4 nuclear localization, and co-transfection of Foxo4-targeted siRNA completely reversed the myotube atrophy and upregulation of atrogene transcription induced by WNK1 silencing. We further illustrated that WNK1 protein abundance in skeletal muscle was increased by chronic voluntary wheel running exercise (hypertrophic stimulus) and markedly decreased by adenine-induced chronic kidney disease (atrophic stimulus) in mice. These findings suggest that WNK1 is involved in the physiological regulation of mammalian skeletal muscle hypertrophy and atrophy via interactions with FOXO4. The WNK1-FOXO4 axis may be a potential therapeutic target in human diseases causing sarcopenia.

Excellent magnetic features make Co-based materials promising candidates as high-performance microwave absorbers. However, it is still a significant challenge for Co-based absorbers to possess high-intensity and broadband absorption simultaneously, owing to the lack of dielectric loss and impedance matching. Herein, microporous Co@C nanoparticles (NPs) with carbon shell thicknesses ranging from 1.8-4.9 nm have been successfully synthesized by dealloying CoAl@C precursors. All of the samples exhibit high microwave absorption performance. The microporous Co@C sample possessing a carbon shell of 1.8 nm exhibits the highest absorption intensity among these samples with a minimum reflection loss (RL) of -141.1 dB, whose absorption bandwidth for RL ≤ -10 dB is 7.3 GHz. As the thickness of the carbon shell increases, the absorption bandwidth of the NPs becomes wider. For the sample with the carbon shell thickness of 4.9 nm, the absorption bandwidth for RL ≤ -10 dB reaches a record high of 13.2 GHz. The outstanding microwave attenuation properties are attributed to the dielectric loss of the carbon shell, the magnetic loss of the Co core, and the cooperation of the core-shell structure and microporous morphology. The strong wideband microwave absorption of the carbon-coated microporous Co NPs highlights their potential applications in microwave absorbing systems.

A 37-year-old Japanese man with a serum creatinine level of 2.5 mg/dL and hepatomegaly was admitted to our hospital for investigation of renal failure. Magnetic resonance imaging (MRI) showed hepatomegaly with small cystic lesions that had high signal intensity on T2-weighted images. There was no splenomegaly, and the kidneys were nearly normal in size with a few small cystic lesions. Renal biopsy revealed that interstitial fibrosis and tubular atrophy affected 60% of the cortex. There was cystic tubular dilation, mainly affecting the distal loop of Henle and distal tubules, since immunohistochemical staining of the dilated tubules was positive for cytokeratin 7 and Tamm-Horsfall protein but was negative for aquaporin 3 and CD10. Immunofluorescence microscopy and electron microscopy did not demonstrate any immune deposits. Genetic analysis identified two different heterozygous missense variants of PKHD1, while the patient's asymptomatic parents were each heterozygous for a single PKHD1 mutation. Accordingly, autosomal recessive polycystic kidney disease (-ARPKD) due to compound heterozygous PKHD1 mutation was diagnosed. The renal biopsy findings of this patient may be nonspecific, but they were different from the typical renal histology of infantile ARPKD. In conclusion, the renal features of adult-onset ARPKD may differ from those of infantile disease.
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Background: The relationship between protein-energy wasting and chronic kidney disease (CKD) progression is unknown. In the present prospective cohort study, we evaluated the hypothesis that a combination of low body mass index (BMI) and serum albumin level is associated with rapid CKD progression., Methods: The study cohort comprised 728 predialysis Japanese patients with CKD (stages 2-5) enrolled from 2010 to 2011. Patients were categorized into four groups according to their serum albumin levels and BMI: group 1, low serum albumin level (<4 g/dL) and low BMI (<23.5 kg/m 2 ); group 2, high serum albumin level (≥4 g/dL) and low BMI; group 3, low serum albumin level and high BMI (≥23.5 kg/m 2 ); and group 4, high serum albumin level and high BMI. The primary outcome was a 30 % decline in estimated glomerular filtration rate (eGFR) or start of dialysis within 2 years. The secondary outcome was an annual GFR decline (mL/min/1.73 m 2 /year)., Results: Logistic regression analysis adjusted for baseline characteristics (reference, group 4) showed that only group 1 was associated with a significant risk of CKD progression, with adjusted odds ratio of 3.51 [95 % confidence interval (CI) (1.63, 7.56)]. A multivariate linear regression analysis adjusted for baseline characteristics showed a significant difference in annual eGFR decline between groups 1 and 4 [coefficients β (standard error) -2.62 (0.75), p = 0.001]., Conclusion: This study suggests that combined effects of low BMI (<23.5 kg/m 2 ) and serum albumin level (<4 g/dL) are associated with CKD progression.

Objectives: Methotrexate (MTX) is used for the treatment of polyarticular juvenile idiopathic arthritis (JIA), and an anti-interleukin-6 receptor monoclonal antibody (tocilizumab: TCZ) is also used and added for the treatment of intractable JIA. It has been reported that MTX might induce Epstein-Barr virus (EBV)-associated lymphoma, but the discussion about the effect of MTX and/or TCZ against reactivation of EBV in pediatric patients has been incomplete., Methods: The EBV loads in four polyarticular JIA and three systemic arthritis JIA patients treated with MTX and/or TCZ, and the percentage of EBV-specific killer T cells (EBV-CTLs) in some patients were prospectively monitored., Results: No patients had EBV-associated symptoms during the observation period. EBV loads in all patients were not significantly increased, and the levels of EBV loads were the same as EBV-seropositive healthy children following the administration of MTX and/or TCZ. EBV-CTLs were detectable during the observation period, but some patients had slightly low levels of EBV-CTLs., Conclusion: Treatment with MTX and/or TCZ did not severely affect EBV load and prevent induction of EBV-CTLs in JIA patients.

25 nm carbon-coated microporous Co/CoO nanoparticles (NPs) were synthesized by integrating chemical de-alloying and chemical vapor deposition (CVD) methods. The NPs possess micropores of 0.8-1.5 nm and display a homogeneous carbon shell of about 4 nm in thickness with a low graphitization degree. The saturation magnetization (M S ) and coercivity (H C ) of the NPs were 70.3 emu g -1 and 398.4 Oe, respectively. The microporous Co/CoO/C NPs exhibited enhanced microwave absorption performance with a minimum reflection coefficient (RC) of -78.4 dB and a wide absorption bandwidth of 8.1 GHz (RC ≤ -10 dB), larger than those of the nonporous counterparts of -68.3 dB and 5.8 GHz. The minimum RC values of the microporous Co/CoO/C NPs at different thicknesses were much smaller than the nonporous counterparts. The high microwave absorption mechanism of the microporous Co/CoO/C nanocomposite can be interpreted in terms of the interfacial polarization relaxation of the core/shell and micropore structures, the effective permittivity modification of the air in the micropores and the polarization relaxation of the defects in the low-graphitization carbon shell and the porous Co NPs. Our study demonstrates that the microporous Co/CoO/C nanocomposite is an efficient microwave absorber with high absorption intensity and wide absorption bandwidth.

Background: A reduction in medical staff such as occurs in hospitals during nights and weekends (off hours) is associated with a worse outcome in patients with several unanticipated critical conditions. Although difficult airway management (DAM) requires the simultaneous assistance of several appropriately trained medical caregivers, data are scarce regarding the association between off-hour presentation and endotracheal intubation (ETI)-related adverse events, especially in the trauma population. The aim of this study was to determine whether off-hour presentation was associated with ETI complications in injured patients with a predicted difficult airway., Methods: This historical cohort study was conducted at a Japanese community emergency department (ED). All patients with inhalation burn, comminuted facial trauma (Abbreviated Injury Scale Score Face ≥3), and penetrating neck injury who underwent ETI from January 2007 to January 2016 in our ED were included. Primary exposure was off-hour presentation, defined as the period from 6:01 PM to 8:00 AM weekdays plus the entire weekend. The primary outcome measure was the occurrence of an ETI-related adverse event, including hypoxemia, unrecognized esophageal intubation, regurgitation, cardiac arrest, ETI failure rescued by emergency surgical airway, cuff leak, and mainstem bronchus intubation., Results: Of the 123 patients, 75 (61.0 %) were intubated during off hours. Crude analysis showed that off-hour presentation was significantly associated with an increased risk of ETI-related adverse events [odds ratio (OR), 2.5; 95 % confidence interval (CI), 1.1-5.6; p = 0.033]. The increased risk remained significant after adjusting for potential confounders, including operator being an anesthesiologist, use of a paralytic agent, and injury severity score (OR, 3.0; 95 % CI, 1.1-8.4; p = 0.034)., Conclusions: In this study, off-hour presentation was independently associated with ETI-related adverse events in trauma patients with a predicted difficult airway. These data imply the need for more attentive hospital care during nights and weekends.

Background: Despite the oncogenic potential of Merkel cell polyomavirus (MCPyV), it has been found in the normal skin of healthy individuals; however, little is known about geographical variations in the ecology of MCPyV in this tissue., Methods: This study included 284 Japanese participants. Sun-unexposed arm and sun-exposed forehead skin swab samples were obtained and analyzed for MCPyV infection, using quantitative polymerase chain reaction. Phylogenetic analyses were also conducted, based on the full-length genes encoding MCPyV large T antigen and viral protein 1., Results: This study provides the first analyses of the age-specific prevalence and levels of MCPyV infection in normal skin. Steep increases in prevalence and viral load were observed in individuals aged >40 years. MCPyV infections with a high viral load were predominantly observed in the foreheads of subjects aged >60 years, among whom a high burden of MCPyV tended to persist. Phylogenetic analyses showed that all of the gene sequences obtained in this study clustered in a major clade, suggesting the existence of an Asian/Japanese genotype., Conclusions: This large study suggests that MCPyV infection with high viral loads is prevalent in the sun-exposed skin of elderly adults, making it necessary to follow up this cohort for possible transformation of MCPyV to a pathogenetic form., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Granulomatous interstitial nephritis (GIN) is one of the renal pathological manifestations of sarcoidosis. It is usually clinically silent, but may present occasionally as acute kidney injury (AKI). AKI caused by sarcoid GIN without extrarenal manifestations is extremely rare. We report a case of a 70-year-old man with a history of type 2 diabetes mellitus admitted with progressively worsening kidney function. The patient also exhibited anorexia, malaise and weight loss. Laboratory tests showed an elevated serum lysozyme level, but the serum angiotensin-converting enzyme (ACE) and serum calcium levels were normal. Increased uptake was evident only in kidney on gallium 67 scintigraphy. Although typical organ involvement of sarcoidosis was not evident, a renal biopsy showed granulomatous interstitial nephritis with non-caseating granulomas. No medications had been added in the 3 years preceding renal function deterioration. Following a bronchoalveolar lavage that revealed a high CD4:CD8 ratio, and a skin test that showed negative for tuberculin, a diagnosis of renal sarcoidosis was established. On diagnosis, oral prednisolone was initiated and renal function improved. The anorexia and malaise also disappeared. This is the extremely rare case of AKI caused by sarcoid GIN without extrarenal manifestations or elevated serum ACE level.

Purpose: Airway management in severe bronchial asthma exacerbation (BAE) carries very high risk and should be performed by experienced providers. However, no objective data are available on the association between the laryngoscopist's specialty and endotracheal intubation (ETI)-related adverse events in patients with severe bronchial asthma. In this paper, we compare emergency ETI-related adverse events in patients with severe BAE between anesthesiologists and other specialists., Methods: This historical cohort study was conducted at a Japanese teaching hospital. We analyzed all BAE patients who underwent ETI in our emergency department from January 2002 to January 2014. Primary exposure was the specialty of the first laryngoscopist (anesthesiologist vs. other specialist). The primary outcome measure was the occurrence of an ETI-related adverse event, including severe bronchospasm after laryngoscopy, hypoxemia, regurgitation, unrecognized esophageal intubation, and ventricular tachycardia., Results: Of 39 patients, 21 (53.8 %) were intubated by an anesthesiologist and 18 (46.2 %) by other specialists. Crude analysis revealed that ETI performed by an anesthesiologist was significantly associated with attenuated risk of ETI-related adverse events [odds ratio (OR) 0.090, 95 % confidence interval (CI) 0.020-0.41, p = 0.001]. The benefit of attenuated risk remained significant after adjusting for potential confounders, including Glasgow Coma Score, age, and use of a neuromuscular blocking agent (OR 0.058, 95 % CI 0.010-0.35, p = 0.0020)., Conclusions: Anesthesiologist as first exposure was independently associated with attenuated risk of ETI-related adverse events in patients with severe BAE. The skill and knowledge of anesthesiologists should be applied to high-risk airway management whenever possible.

A 76-year-old man with a history of type 2 diabetes mellitus was admitted with cholangitis caused by cholangiocarcinoma. Cholangitis with Escherichia coli (E. coli) bacteremia recurred due to the unstable bile drainage. At 1 month after recurrence, rapidly progressive glomerulonephritis with nephrotic syndrome was manifested. Renal biopsy findings were consistent with immunoglobulin A (IgA)-dominant postinfectious glomerulonephritis (PIGN). After ensuring that the recurrent cholangitis was controlled by drainage and antibiotic therapy, oral prednisolone was initiated, and the patient's renal function and proteinuria subsequently gradually improved. This is the first case report of IgA-dominant PIGN associated with cholangitis caused by E. coli infection.

A 76-year-old woman with a history of lumbar fracture and marked proteinuria, bilateral pitting edema, malaise and pruritus was referred for an evaluation of an impaired renal function. A renal biopsy led to a tentative diagnosis of acute interstitial nephritis (AIN) with minimal change disease caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Following the discontinuation of oral NSAIDs, the patient's symptoms disappeared spontaneously. However, nephrotic-range proteinuria relapsed one month after discharge, following loxoprofen patch use. The withdrawal of the topical loxoprofen patches once again resulted in the disappearance of all symptoms. This is the first case report of nephrotic-range proteinuria and AIN secondary to topical NSAID patch use.

A novel free-energy perturbation method is developed for the computation of the free energy of transferring a molecule between fluid phases. The methodology consists in drawing a free-energy profile of the target molecule moving across a binary-phase structure built in the computer. The novelty of the method lies in the difference of the definition of the free-energy profile from the common definition. As an important element of the method, the process of making a correction to the transfer free energy with respect to the cutoff of intermolecular forces is elucidated. In order to examine the performance of the method in the application to fluid-phase equilibrium properties, molecular-dynamics computations are carried out for the evaluation of gas solubility and vapor pressure of liquid n-hexane at 298.15 K. The gas species treated are methane, ethane, propane, and n-butane, with the gas solubility expressed as Henry's constant. It is shown that the method works fine and calculated results are generally in good agreement with experiments. It is found that the cutoff correction is strikingly large, constituting a dominant part of the calculated transfer free energy at the cutoff of 8 A.

We report a 67-year-old man with highly symptomatic polycystic liver disease. Fenestration was selected to treat symptoms because the cysts were scattered diffusely and the normal liver volume was limited. Although this patient was relieved from symptoms of liver cysts consequently, several severe postoperative complications including disseminated intravascular coagulation, respiratory failure, liver failure, and biliary leakage occurred resulting in a 6-month postoperative hospital stay. Although various treatments for symptomatic adult polycystic liver disease have been advocated, a definitive treatment remains controversial, especially in diffuse adult polycystic liver disease. Fenestration is one of the alternative treatments for the patients whose cysts are difficult to resect. However high morbidity rate should be carefully assessed, if extensive fenestration is needed to treat diffuse adult polycystic liver disease. Further consideration of appropriate treatments for diffuse adult polycystic liver disease is needed.

A 54-year-old man had received low anterior resection for rectal carcinoma and extended right hepatectomy for a metastatic liver tumor. One year later, imaging studies disclosed a metastatic liver tumor in segment 2 of the liver. The residual left hepatic vein was completely invaded by the tumor from the root of the hepatic vein to the confluence of several branches by intraoperative ultrasonography. To resect partial liver with the involved hepatic vein was deemed impossible. Microwave coagulation therapy was performed on the tumor and the involved hepatic vein, as we had established the safety of microwave irradiation to the main hepatic vein without interference of the hepatic venous flow in an experimental study. The patient remains well 40 months after the surgery without recurrent signs. The hepatic venous flow of the irradiated hepatic vein is maintained well according to serial examination of Doppler ultrasonography.

The patient was a 74-year-old female. Type 1 undifferentiated carcinoma (non-small cell type) was detected in the middle of the thoracic esophagus in August 1999. Although the lesion was diagnosed as T2, N0, and Stage II, the patient was judged to be a poor risk, inoperable case because of a complex past history of renal and respiratory dysfunctions, and dysbasia. Intravenous administration of nedaplatin at 15.8 mg/m2 and 5-FU 590.6 mg/m2 were carried out for 5 consecutive days as chemotherapy. The second cycle of chemotherapy was performed with nedaplatin reduced to 11.8 mg/m2 on the basis of the adverse reactions observed after the first cycle, and PR was attained. As for radiotherapy, additional extracorporeal irradiation was judged to be too dangerous from her history, so endoesophageal brachytherapy alone was added, and CR was obtained. The patient has maintained a CR for more than 2 years after discharge. In this poor risk case with a highly malignant undifferentiated carcinoma, an "individualization strategy" was effective.

This study evaluated the efficacy of adding pioglitazone 30 mg to the therapy of patients with type 2 diabetes mellitus whose glycaemic control was poor on an alpha-glucosidase inhibitor (alpha-GI) alone or in combination with a sulphonylurea (SU). The patients (n = 20) had a HbA(1c) level between 7.0 and 12.0% and the fasting plasma glucose was 7.8 mmol/l or higher. They were treated with 30 mg pioglitazone once daily for 16 weeks. The decrease in HbA(1c) at week 16 of treatment was 0.8% (7.8% at baseline dropping to 7.1% at week 16; p < or = 0.01). An increase in leptin was observed 4 weeks after starting the post-study period (p < or = 0.05). Tumour necrosis factor-alpha (TNF-alpha) and body fat percentage did not show any significant alterations. Correlations between the decrease in HbA1c at week 16 and characteristic variables of patients were examined. A correlation with leptin (p = -0.5632, p < or = 0.05) levels was found. Five patients experienced adverse drug reactions, such as oedema, hypoglycaemia and increased creatine phosphokinase (CK), all of which were mild in severity. The addition of pioglitazone in diabetics whose glycaemic control was poor on a alpha-GI alone or with a alpha-GI and SU combination resulted in a significant decrease in HbA1c, and the treatment was well-tolerated. Our findings also suggest that leptin levels could be useful for assessing responders to pioglitazone.

We have already reported that the ratio of portal venous flow 30 min after oral intake of glucose 75 g to that before intake (PVFR30), measured using pulsed-Doppler ultrasonography (US), correlated significantly with other indicators of liver function and that it could be used to estimate hepatic function before surgery, including liver resection. In this study, to assess the disadvantages of pulsed-Doppler ultrasonography, PVFR30 was measured using two-dimensional (2D) phase-shift (PS) magnetic resonance imaging (MRI). PVFR30 was measured in 17 patients and 7 volunteers: 13 with liver cirrhosis (LC) and 11 without LC (non-LC). Portal venous flow could be measured in all patients without any disturbance of intestinal gas or patient fat, or the high degree of technical skill that Doppler US requires. PVFR30 was significantly lower in the LC group than in the non-LC group. In addition, it correlated significantly with other indicators of liver function, including the indocyanine green clearance test, prothrombin time, hepaplastin test, and cholinesterase activity. These results suggest that PVFR30 measured by 2D PS MRI can be used to estimate liver function, and that this MRI method can be performed more easily than pulsed-Doppler US.