Children with type 2 diabetes mellitus are at greater risk of macrovascular complications

Background:  Type 2 diabetes mellitus (DM) is a risk factor for macrovascular complications in adults. Recently young-onset type 2 DM has increased worldwide and the increase of macrovascular complications in the young is worrisome.
Methods:  Plasma values for plasminogen activator inhibitor-1 (PAI-1) as a marker for promotion, and adiponectin as a marker for inhibition of atherosclerosis, were compared in 33 patients with type 1 DM (16 boys, 17 girls; age 14.9 ± 3.7 years, mean ± standard deviation) with those of 43 patients with type 2 DM (15 boys, 28 girls; age 16.5 ± 3.5 years).
Results:  The PAI-1 level was significantly higher (19.3 ± 8.1 vs 32.9 ± 17.2 ng/ml; P < 0.001) and the adiponectin level was significantly lower (10.1 ± 3.8 vs 7.4 ± 3.7 µg/ml; P < 0.005) in the type 2 DM group. In obese patients, the PAI-1 level was significantly higher ( P < 0.005) and the adiponectin level was lower ( P = 0.15) in the type 2 DM group. Also, in the non-obese subjects, the PAI-1 level was significantly higher ( P < 0.05) and the adiponectin level was lower ( P = 0.11) in the type 2 DM group.
Conclusions:  Even in young patients, type 2 DM is a risk factor for macrovascular complications compared with type 1 DM.     

New criteria for immunofluorescence assay for Q fever diagnosis in Japan

A study was made to evaluate the cutoff value of indirect immunofluorescent-antibody (IFA) test for Q fever diagnosis in Japan. We used 346 sera, including 16 from confirmed Q fever cases, 304 from Japanese pneumonia patients, and 26 from negative cases. Thirteen sera from the confirmed Q fever cases with an immunoglobulin M (IgM) titer of > or =1:128 and/or IgG titer of > or =1:256 by the IFA test were positive by both enzyme-linked immunosorbent assay (ELISA) and Western blotting assay (WBA), whereas 298 sera from pneumonia patients and 26 negative sera with an IgM titer of < or =1:16 and an IgG titer of < or =1:32 by the IFA test were negative by both ELISA and WBA. In the proposed "equivocal area," with an IgM titer of > or =1:32 and < or =1:64 and/or an IgG titer of > or =1:64 and < or =1:128, we found 9 sera, 3 from confirmed Q fever cases and 6 from Japanese pneumonia patients, by the IFA test. Three sera from the confirmed Q fever cases and one of the sera from pneumonia patients were IgM and/or IgG positive by both ELISA and WBA. These results suggest that a single cutoff value for the IFA test may cause false-positive and false-negative results. In conclusion, this study showed that an "equivocal area" should be used for the IFA test rather than a single cutoff value and that sera in the equivocal area should be tested by additional serological assays for confirmation.     

Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: implications for the pathogenesis of human nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease, the pathogenesis of which has not been fully elucidated. Here, we report a molecular aspect of this disease elucidated using rabbits fed a cholesterol-rich high-fat diet and exhibiting insulin resistance. The liver in this model showed steatohepatitis with fibrosis and high mRNA expression for some cytokines, heme oxygenase-1, transforming growth factor-beta1, and collagen alpha1(I). Erythrocytes isolated from the model showed marked fragility and the externalization of phosphatidylserine (PS) on the outer leaflet of the membrane and were frequently engulfed by Kupffer cells/macrophages in the hepatic sinusoids. Expression of milk fat globule-epidermal growth factor (EGF)-factor 8, a PS-binding protein, was augmented in the liver. In culture, RAW 264.7 cells engulfed erythrocytes oxidized by tert-butyl hydroperoxide, a process that was inhibited by anti-milk fat globule-EGF-factor 8 antibody. In addition, PS-positive erythrocytes appeared entrapped in the model liver in ex vivo perfusion experiments. Finally, in specimens from NASH patients, the aggregation of erythrocytes in inflammatory hepatic sinusoids was notable. These results indicate that the engulfment of PS-externalized, apoptotic signal-positive, erythrocytes by hepatic macrophages may lead to the deposition of iron derived from hemoglobin in the liver and be involved in the pathogenesis of steatohepatitis.     

Clinical study of blood purification therapy in critical care in Japan: results from the survey research of the Japan Society for Blood Purification in Critical Care in 2013

To clarify the clinical status of blood purification therapy (BPT) in critical care in Japan, we conducted a cohort study using data from a nationwide registry of the Japan Society for Blood Purification in Critical Care in 2013. We enrolled 2227 patients treated with BPT (female, 39.1%; mean age, 65.5 ± 12.1 years) in the intensive care units of 43 facilities. Patient characteristics, modes of BPT, and survival rate for each disease were investigated. In total, BPT was performed 3053 times. Continuous renal replacement therapy (CRRT) (57.9%) was the most common mode of BPT, followed by intermittent renal replacement therapy (20.2%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX-DHP) (11.5%). Nafamostat mesilate (84.9%) was most frequently used as the anticoagulant. The 28-day survival rate was 56.8% in all patients. The most common mode for acute kidney injury (AKI) and multiple organ failure was CRRT, while PMX-DHP and CRRT were most common for sepsis. There was no significant difference in survival rates among AKI stages 1–3. Survival rate (38.3%) was significantly lower in patients with acute lung injury (ALI) than in those with multiple organ failure (41.8%) and those with sepsis (46.6%). Multivariate regression analysis revealed that the APACHE II score and the presence of acute ALI and acute hepatic failure were significantly associated with death. This large-scale cohort study showed the clinical status of BPT in Japan. Further investigations are required to clarify the efficacy of BPT for critically ill patients.     

Case report of de novo dup(18p)/del(18q) and r(18) mosaicism

This is a report of a 27-year-old woman with an unusual de novo chromosomal abnormality. Mosaicism was identified in peripheral blood cells examined by standard G-bands by trypsin using Giemsa (GTG) analysis and fluorescence in situ hybridization (FISH) analysis with chromosome-18 region-specific probes, 46,XX,del(18)(pter → q21.33:)[41], 46,XX,r(18)(::p11.21 → q21.33::)[8], and 46,XX,der(18)(pter → q21.33::p11.21 → pter)[1]. On the other hand, the karyotype of periodontal ligament fibroblasts was nonmosaic, 46,XX, der(18)(pter → q21.33::p11.21 → pter)[50]. All cell lines appeared to be missing a portion of 18q (q21.33 → qter). The pattern of the dup(18p)/del(18q) in the rod configuration raises the possibility of an inversion in chromosome 18 in one of the parents. However, no chromosomal anomaly was detected in either parent. The most probable explanation is that de novo rod and ring configurations arose simultaneously from an intrachromosomal exchange. The unique phenotype of this patient, which included primary hypothyroidism and primary hypogonadism, is discussed in relation to her karyotype.     

Studies on antibiotic skin testing

Commercially available antibiotics for injection are supplied with test ampules. Users are instructed to dissolve them to make 300 micrograms/ml solution for intradermal pretests to avoid allergic reactions. Sometimes this concentration is too low to prevent anaphylactic reactions. In the present study, we tried to find the maximum concentration for the intradermal tests which would have high sensitivity without giving nonspecific, false positive reactions. We investigated intradermal tests with cephalothin (CET) in a patient who suffered from anaphylaxis after drip infusion with CET, although she was judged to be negative to CET by the usual intradermal test prior to the infusion. Her CET skin test was negative at a concentration of 150 micrograms/ml and positive at 300 micrograms/ml 6 weeks after anaphylaxis, but negative at 300 micrograms/ml and positive at 1000 micrograms/ml 4 and 7 years after anaphylaxis. Prick tests were always negative, even with the maximum soluble concentration of CET, 200 mg/ml. Nonspecific reactions to intradermal tests at concentrations as high as 1000 micrograms/ml were examined with 20 kinds of penicillins and cephems in 51 healthy subjects without histories of drug allergies. Very few false positive reactions were observed, except in 5 out of 24 cases with cefotiam. Intradermal tests at 3000 micrograms/ml, however, frequently resulted in nonspecific reactions. We conclude that 1000 micrograms/ml, not 300 micrograms/ml solutions should be used for intradermal tests to prevent allergic reactions to the injection of antibiotics.     

Clinical reference values for laboratory hematology tests calculated using the iterative truncation method with correction: Part 1. Reference values for erythrocyte count, hemoglobin quantity, hematocrit and other erythrocyte parameters including MCV, MCH, MCHC and RDW

Age and sex dependent differences in the clinical reference values for erythrocyte count (RBC), hemoglobin quantity (Hb), hematocrit (Ht) and other erythrocyte parameters including MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), were calculated by the iterative truncation method with correction (Usui's method) using the results from tests on 6,300 patients' specimens obtained at Kyoto University Hospital. For RBC, Hb and Ht, the data obtained from the individuals below 13 years old showed the normal or sometimes log-normal distribution, but adjustment by the Xn-type variable transformation was often necessary to obtain the normal distribution for the data taken from the populations containing individuals over the age of 14. For the clinical reference values of RBC, Hb and Ht, no sex difference was observed below the age of 12. The values for males were significantly higher than those of females in the age range 13-79, and the values showed no significant sex-dependent difference at ages above 80. In females, age-dependent change of values for RBC, Hb and Ht was less prominent than in males; especially the upper limit values for females were very stable for all ages. MCV and MCH gradually increased with age both in males and females, and the MCHC remained constant in all age populations of male and female. The reference value for RDW was generated by the percentile method instead of the iterative truncation method because of the strong deviation in the distribution pattern, and the RDW values showed a gradual increase with age in both males and females.     

Semiquantitative analysis of C-11 methionine PET may distinguish brain tumor recurrence from radiation necrosis even in small lesions

Objective

¹¹C-Methionine positron emission tomography (MET-PET) has been used to distinguish brain tumor recurrence from radiation necrosis. Because the spatial resolution of conventional PET scanners is low, partial volume effect (PVE) may decrease the detectability of small tumor recurrence. The aim of this study is to investigate the diagnostic value of MET-PET upon semiquantitative analyses in particular PVE-affected small lesions.

Methods

First, we performed a phantom experiment to investigate what size lesion is affected by PVE. This study included 29 patients (33 lesions) suspected of recurrent brain tumors by magnetic resonance imaging (MRI) after radiation therapy. All of them received MET-PET. Semiquantitative analysis was performed using maximum standardized uptake value (SUVmax) and lesion-versus-normal ratio (L/N ratio). ROC analysis was also assessed about the diagnostic value of MET-PET.

Results

From the result of the phantom experiment, lesions smaller than 20 mm in brain mode or smaller than 30 mm in whole-body mode were defined as PVE-affected lesions. Histological analysis or clinical follow-up confirmed the diagnosis of tumor recurrence in 22 lesions, and radiation necrosis in 11 lesions. L/N ratios of recurrence and necrosis for overall lesions were 1.98 ± 0.62 and 1.27 ± 0.28, respectively (p < 0.01). In the PVE-affected lesions, L/N ratio for recurrence (1.72 ± 0.44) was also significantly higher than that for necrosis (1.20 ± 0.11) (p < 0.01). On the ROC analysis for the PVE-affected lesions, the area under the curve for L/N ratio (0.897) was significantly higher than that for SUVmax (0.718) (p < 0.05). These areas under the curve were almost equal to that of overall lesions for L/N ratio (0.886) and for SUVmax (0.738).

Conclusions

Semiquantitative analysis of MET provided high diagnostic value even for PVE-affected small lesions. MET-PET enables early diagnosis of recurrence of brain tumor in the follow-up after the radiation therapy.     

Anatomical characterization of PDF‐tri neurons and peptidergic neurons associated with eclosion behavior in Drosophila

The peptidergic Pigment‐dispersing factor (PDF)‐Tri neurons are a group of non‐clock neurons that appear transiently around the time of adult ecdysis (=eclosion) in the fruit fly Drosophila melanogaster. This specific developmental pattern points to a function of these neurons in eclosion or other processes that are active around pupal–adult transition. As a first step to understand the role of these neurons, we here characterize the anatomy of the PDF‐Tri neurons. In addition, we describe a further set of peptidergic neurons that have been associated with eclosion behavior, eclosion hormone (EH), and crustacean cardioactive peptide (CCAP) neurons, to single cell level in the pharate adult brain. PDF‐Tri neurons as well as CCAP neurons co‐express a classical transmitter indicated by the occurrence of small clear vesicles in addition to dense‐core vesicles containing the peptides. In the tritocerebrum, gnathal ganglion and the superior protocerebrum PDF‐Tri neurites contain peptidergic varicosities and both pre‐ and postsynaptic sites, suggesting that the PDF‐Tri neurons represent modulatory rather than pure interneurons that connect the subesophageal zone with the superior protocerebrum. The extensive overlap of PDF‐Tri arborizations with neurites of CCAP‐ and EH‐expressing neurons in distinct brain regions provides anatomical evidence for a possible function of the PDF‐Tri neurons in eclosion behavior.