Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis obliterans

BACKGROUND: Measles virus infection may progress to a chronic obstructive process including bronchiolitis obliterans (BO). This study investigates pulmonary cellular profiles and interleukin (IL)-8 levels in patients with BO following the measles. METHODS: BAL fluid was obtained from 12 children with BO who had a history of measles pneumonia during an outbreak in 2000 and 2001. BAL cell counts and differentials were compared to control patients as well as BAL IL-8 levels, which were measured by enzyme-linked immunosorbent assay. Immunohistochemical staining of BAL cells and three open-lung biopsy specimens were also analyzed for T-cell surface markers CD3, CD4, and CD8. RESULTS: BAL cellular profiles were characterized by a significantly increased percentage of neutrophils in the measles BO group (median, 16.0%) compared to the control group (2.3%) [p < 0.01]. BAL IL-8 levels were also markedly increased in the measles BO group (mean +/- SD, 418.6 +/- 286.0 pg/mL) compared to the control group (92.8 +/- 126.7 pg/mL) [p < 0.01]. BAL IL-8 levels correlated significantly with neutrophil percentages in both the measles BO group (r = 0.86, p = 0.000) and the control group (r = 0.79, p = 0.007). The lymphocyte subsets were characterized by a significantly increased number of CD8+ cells, resulting in a decreased CD4/CD8 ratio in the BAL and the biopsy specimens. CONCLUSION: These results suggest that pulmonary neutrophils and IL-8, along with CD8+ T lymphocytes may play an important role in the pathogenesis of BO after measles virus infection.     

Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma

From June 1997 to August 2005, 52 consecutive newly diagnosed stage 4 neuroblastoma patients over 1 year of age were assigned to receive tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) as consolidation therapy. Fifty of the 52 patients underwent a first HDCT/ASCR and 44 patients underwent a second HDCT/ASCR. Eight patients (15.4%) died from treatment-related toxicity (seven during the second HDCT/ASCR). Total body irradiation (TBI) in the first HDCT/ASCR and a shorter interval (< 12 weeks) between the first and second HDCT/ASCR were associated with a higher rate of treatment-related death in the second HDCT/ASCR (P = 0.032 and 0.095, respectively). The tumor relapsed or progressed in 11 patients, and 33 patients remained event free with a median follow-up of 53 months (range 19-117) from diagnosis. The 5-year event-free survival (EFS) (+/- 95% confidence interval) for all 52 patients was 62.1+/-13.7%. The application of TBI and local radiotherapy, and a longer interval between the first and second HDCT/ASCR were independently associated with a better EFS (P = 0.026, 0.007 and 0.020, respectively). However, further studies will be needed to decrease the toxic death rate in the second HDCT/ASCR while reducing the relapse rate.     

Divergent effect of cyclosporine on Th1/Th2 type cytokines in patients with severe, refractory rheumatoid arthritis

OBJECTIVE: To investigate the effect of cyclosporine on cytokine production, especially on T helper 1 (Th1) and T helper 2 (Th2) type cytokines, in patients with rheumatoid arthritis (RA). METHODS: A 16 week randomized, double blind, placebo controlled study of cyclosporine (2.5 to 4 mg/kg/day) was conducted in 40 patients with severe, refractory RA who had residual inflammation and disability despite partial responses to prior maximal tolerated dose of methotrexate (MTX; < 15 mg/week) and low dose prednisone (< 10 mg/day). Clinical and laboratory variables, and circulating levels of interleukin 2 (IL-2), IL-4, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) measured by ELISA were compared between patients (cyclosporine group) treated with cyclosporine plus MTX and those (placebo group) treated with placebo plus MTX at entry and at 16 weeks. RESULTS: At 16 weeks, the cyclosporine group (n = 17), compared with the placebo group (n = 17), had greater decreases in tender joints, swollen joints, patient global assessment, patient self-assessed disability, and C-reactive protein, as well as having more patients with > 20% improvement. Comparison of circulating cytokines at entry and at 16 weeks showed significant decreases of IL-2 (median -61 vs 7 pg/ml; p = 0.004) ("+" denotes increase, "-" denotes decrease), IL-12 (median -313 vs -14 pg/ml; p = 0.002), TNF-alpha (median -55 vs 5 pg/ml; p < 0.001), and IFN-gamma (median -21 vs 5 pg/ml; p = 0.003), and a significant increase of IL-10 (median 55 vs -12 pg/ml; p < 0.001) in the cyclosporine group compared with the placebo group. The degree of IL-10 increases correlated strongly with the degree of IL-12 decreases in the cyclosporine group (r = 0.572, p = 0.016). However, there was no change in circulating IL-4 between the 2 groups. Within the cyclosporine group, the improved patients (n = 10) compared to the non-improved patients (n = 7) had a greater increase in circulating IL-10 (median 172.0 vs 85.2%; p = 0.01). The rate of increase of IL-10 strongly correlated with the rate of improvement of joint scores (r = 0.718, p = 0.001) after administration of cyclosporine. CONCLUSION: Our results suggest that the therapeutic effect of cyclosporine is achieved by correcting a Th1/Th2 imbalance (a shift of Th1 type to Th2 type), which may be involved in the pathogenesis of RA; and that circulating IL-10 is useful to assess the clinical improvements in patients with RA after administration of cyclosporine.     

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos)

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large‐scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30‐day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30‐day mortality among patients with Grade I or Grade III AC, but significantly lower 30‐day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.     

Focal eosinophilic infiltration of the liver: a mimick of hepatic metastasis

We present three cases of focal eosinophilic infiltration in the liver that mimicked hepatic malignancy on computed tomography during hepatic arteriography (CTHA) and computed tomography during arterial portography (CTAP). In all patients, focal eosinophilic liver infiltration appeared as a solitary nodule or as two nodules without hepatosplenomegaly and showed homogeneous hyperattenuation on CTHA and hypoattenuation on CTAP. Received: 10 June 1998/Revision accepted: 26 August 1998     

Effects of Coffee Intake on Incident Chronic Kidney Disease: A Community-Based Prospective Cohort Study

Background

Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population.

Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha‐2‐HS‐glycoprotein

Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2‐HS‐glycoprotein gene (AHSG) and its protein, fetuin‐A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA‐dependent manner. In HepG2 cells treated with 300 μmol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 μmol/L of melatonin. However, melatonin did not improve insulin resistance in FETUA‐overexpressing cells, indicating that improvement in insulin resistance by melatonin was dependent on downregulation of FETUA. Moreover, melatonin decreased palmitic acid‐induced ER stress markers, CHOP, Bip, ATF‐6, XBP‐1, ATF‐4, and PERK. In addition, in the high‐fat diet (HFD) mice, oral treatment with 100 mg/kg/day melatonin for 10 weeks reduced body weight gain to one‐third of that of the HFD group and hepatic steatosis. Insulin sensitivity and glucose intolerance improved with the upregulation of muscle p‐AKT protein expression. FETUA expression and ER stress markers in the liver and serum of HFD mice were decreased by melatonin treatment. In conclusion, melatonin can improve hepatic insulin resistance and hepatic steatosis through reduction in ER stress and the resultant AHSG expression.     

Severe hematuria in a hematopoietic cell transplant recipient caused by Ureaplasma urealyticum not by BK virus or adenovirus infection

A 17‐year‐old male with acute lymphoblastic leukemia developed severe hematuria and scrotal swelling after haploidentical hematopoietic cell transplantation (HCT). Urine culture was negative. BK virus and adenovirus were negative. However, Ureaplasma urealyticum was detected. He showed dramatic improvement after doxycycline treatment. This is the first report in the literature of hemorrhagic cystitis caused by U. urealyticum in a HCT recipient. In HCT recipients with hemorrhagic cystitis, U. urealyticum should be considered as a potential cause.     

Time course of the changes in right and left ventricle function and associated factors after transcatheter closure of atrial septal defects

Objective

The purpose of this study was to evaluate the changes in right ventricle (RV) and left ventricle (LV) function after transcatheter atrial septal defect (ASD) closure and to assess the influence of the age and the amount of shunt.

Design

Retrospective study

Patients

Fifty‐three adult patients who underwent transcatheter closure were enrolled, then divided into subgroups according to the age (< 40 years vs ≥ 40 years), and the amount of shunt flow (QpQs < 2.5 vs QpQs ≥ 2.5).

Outcome Measures

Two‐dimensional tissue Doppler imaging was performed in a four‐chamber view at the basal ventricular septum (VS) and tricuspid valve annulus (TVA) before and at 1 month and 6 months after closure. Myocardial velocities, the myocardial performance index (MPI), and isovolumic acceleration (IVA) were assessed.

Results

At the TVA, the MPI decreased slightly and then greatly increased at 6 months after closure (P = .002). The IVA improved in all patients (P < .001), and the E′/A′ ratio decreased, especially in the old age group (P = .031) and larger shunt group (P = .035). At the VS, S′ and the IVA decreased and had not recovered until 6 months in the old age (P = .02) and larger shunt (P = .02). The Qp/Qs showed a significant reverse correlation with a decrease in the E′/A′ at the TVA (r = ?0.37, P = .008), and age of patient was correlated with a decrease in the IVA at the VS (r = ?0.32, P = .019). The age at closure (β = ?0.36, P = .002), the Qp/Qs ratio (β = ?0.45, P = .01), and RV MPI changes (β = ?7.64, P < .001) were found to be associated factors with IVA decrease at the VS.

Conclusions

After ASD closure, RV global function might be impaired. In elderly patients and patients with a large shunt, impairment of LV contractility developed until 6 months after closure. Close long‐term observation is required after closure, especially in old‐age patients with a large shunt.