Interaction between ACE and ADD1 gene polymorphisms in the progression of IgA nephropathy in Japanese patients

An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and alpha-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; chi2=6.062, P=0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (P=0.0016), but not for those with other ACE genotypes (hazard ratio=0.65, P=0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.     

Clinical significance of left atrial geometry in dilated cardiomyopathy patients: A cardiovascular magnetic resonance study

BackgroundClinical significance of left atrial (LA) function and geometry in patients with dilated cardiomyopathy (DCM) remains uncertain.HypothesisLA geometric parameters assessed by cardiac magnetic resonance (CMR) predict the prognosis in patients with DCM.MethodsThe present study included patients with DCM and sinus rhythm who underwent CMR between December 2007 and April 2018. LA volume was measured using CMR. LA sphericity index was computed as the ratio of the measured maximum LA volume by the volume of a sphere with maximum LA length diameter.ResultsWe included 255 patients in this study. During the mean follow‐up of 3.92 years, hospitalization for HF occurred in 37 patients. The LA sphericity index was significantly higher in patients with hospitalization for HF than in those without (0.78 ± 0.35 vs. 0.58 ± 0.18, p < .001). Multivariable Cox regression analysis identified a higher LA sphericity index as an independent predictor of hospitalization for HF. Patients were categorized based on the median of LA sphericity index. The Kaplan–Meier curve showed that patients with a high LA sphericity index (≥0.57) had a significantly higher risk of hospitalization for HF than those with a low LA sphericity index (<0.57).ConclusionLA sphericity index was an independent predictor of hospitalization for HF. Assessment of LA geometric parameters might be useful for risk stratification in patients with DCM.     

Potential Effect of Prolonged Sevoflurane Anesthesia on the Kinetics of [<Superscript>11</Superscript>C]Raclopride in Non-human Primates

Purpose

Positron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BP_ND) of [¹¹C]raclopride in NHP.

Procedures

Three cynomolgus monkeys underwent two to three PET measurements with [¹¹C]raclopride under continuous sevoflurane anesthesia on the same day. The concentration of sevoflurane was adjusted according to the general conditions and safety parameters of the NHP. Time to peak (TTP) radioactivity in the striatum was estimated from time-activity curves (TACs). The BP_ND in the striatum was calculated by the simplified reference tissue model using the cerebellum as reference region.

Results

In each NHP, the TTP became shorter in the later PET measurements than in the first one. Across all measurements (n = 8), concentration of sevoflurane correlated with TTP (Spearman’s ρ = ? 0.79, p = 0.03), but not with BP_ND (ρ = ? 0.25, p = 0.55).

Conclusions

These data suggest that sevoflurane affects the shape of TACs but has no evident effect on BP_ND in consecutive PET measurements.

     

Type 1 Autoimmune Pancreatitis Extending along the Main Pancreatic Duct: IgG4-related Pancreatic Periductitis

We herein report a unique form of autoimmune pancreatitis (AIP) spreading along the main pancreatic duct (MPD). A 70-year-old man was referred for a small lesion at the pancreatic neck, accompanying an adjacent cyst and dilated upstream MPD. Four years earlier, health checkup images had shown a pancreatic cyst but no mass lesion. Endoscopic ultrasonography showed a contrast-enhanced, tumorous lesion, mainly occupying the MPD. With a preoperative diagnosis of ductal neoplasms mainly spreading in the MPD, Whipple''s resection was performed. The resected specimens showed MPD periductitis with IgG4-related pathology, indicating type 1 AIP. Clinicians should practice caution concerning the various AIP forms.     

Outcomes in Patients with Classic Hodgkin Lymphoma Treated with ABVD: A Single-center Retrospective Study

Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.     

An Irreversible Worsening Cardiac Function after Withdrawing Medical Treatments in a Patient with Dilated Cardiomyopathy: A Pathological Analysis

A 44-year-old man diagnosed with idiopathic dilated cardiomyopathy was admitted to our hospital with acute decompensated heart failure. Seven years before this admission, the first introduction of medication resulted in left ventricular (LV) recovery, which was sustained for several years. However, the patient stopped taking his medication, resulting in worsening of the LV function. Despite the second introduction of medication, the LV function did not improve. We performed cardiac magnetic resonance imaging and an endomyocardial biopsy, which revealed the significant development of cardiac fibrosis that had not been present at the time of the initial diagnosis.     

Anti-myeloma effect of homoharringtonine with concomitant targeting of the myeloma-promoting molecules, Mcl-1, XIAP, and β-catenin

Since a variety of cell intrinsic and extrinsic molecular abnormalities cooperatively promote tumor formation in multiple myeloma (MM), therapeutic approaches that concomitantly target more than one molecule are increasingly attractive. We herein demonstrate the anti-myeloma effect of a cephalotaxus alkaloid, homoharringtonine (HHT), an inhibitor of protein synthesis, through the induction of apoptosis. HHT significantly reduced Mcl-1, a crucial protein involved in myeloma cell survival, in all three myeloma cell lines examined, whereas certain BH3-only proteins, such as Bim, Bik, and Puma, remained unchanged following HHT treatment, and their expression levels depended on the cell type. HHT also reduced the levels of c-FLIP(L/S), activated caspase-8, and induced active truncated-Bid. Thus, HHT-induced apoptosis appears to be mediated via both intrinsic and extrinsic apoptosis pathways, and the resultant imbalance between BH3-only proteins and Mcl-1 may be pivotal for apoptosis by HHT. In addition, HHT treatment resulted in reduced levels of beta-catenin and XIAP proteins, which also contribute to disease progression and resistance to chemotherapy in MM. In combination, HHT enhanced the effects of melphalan, bortezomib, and ABT-737. These results suggest that HHT could constitute an attractive option for MM treatment though its ability to simultaneously target multiple tumor-promoting molecules.     

Imaging of pulmonary emphysema: A pictorial review

The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological – pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease.     

Effects of movement duration on error compensation in periodic bimanual isometric force production

Recent studies using bimanual force production have examined how factors influence redundancy in the nervous system. The present study examined effects of different movement durations on bimanual force control strategies. Ten healthy male participants produced periodic isometric forces such that the sum of two finger forces was a target cycling between 5 and 10 % of maximum voluntary contraction during five movement durations (500, 750, 1,000, 1,250, and 1,500 ms). Correlations between the two finger forces changed from positive to negative with an increase in duration. The polynomial regression analysis indicates that while the correlations between two finger forces were most negative at the target duration of 1,250 ms, they became more positive as the durations deviated from 1,250 ms. Similarly, while force variability was smallest at the target duration of 1,250 ms, it increased as the durations deviated from 1,250 ms. These findings suggested that while the duration of 1,250 ms might be a natural frequency of both fingers, bimanual force strategies changed from force error compensation to force coupling as the durations deviated from 1,250 ms. In addition, while the variance in the sum of two finger forces (the task-relevant variance) decreased with movement duration, the difference between both the finger forces (the task-irrelevant variance) did not change with the duration. Thus, a decrease in the task-relevant variance with movement duration resulted in the negative correlation between the two finger forces and the small force variability.     

Ultra-Early Induction of General Anesthesia for Reducing Rebleeding Rates in Patients with Aneurysmal Subarachnoid Hemorrhage

ObjectiveRebleeding of aneurysmal subarachnoid hemorrhage (aSAH) is one of the significant risk factors for poor clinical outcome. The rebleeding risk is the highest during the acute phase with an approximate rebleeding rate of 9-17% within the first 24 h. Theoretically, general anesthesia can stabilize a patient's vital signs; however, its effectiveness as initial management for preventing post-aSAH rebleeding remains unclear. The purpose of this study was to determine the feasibility and safety of ultra-early general anesthesia induction for reducing the rebleeding rates among patients with aSAH.Materials and methodsWe retrospectively evaluated patients with aSAH who were admitted to our department between January 2013 and December 2019. All the patients underwent ultra-early general anesthesia induction as initial management regardless of their severity. We evaluated the rebleeding rate before definitive treatment, factors influencing rebleeding, and general anesthesia complications.ResultsWe included 191 patients with two-third of them having a poor clinical grade (World Federation of Neurological Society [WFNS] grade IV or V). The median duration from admission to general anesthesia induction was 22 min. Rebleeding before definitive treatment occurred in nine patients (4.7%). There were significant differences in the Glasgow Coma Scale score (p = 0.047), WFNS grade (p = 0.02), and dissecting aneurysm (p <0.001) between the rebleeding and non-rebleeding patients. There were no cases of unsuccessful tracheal intubation or rebleeding during general anesthesia induction.ConclusionUltra-early general anesthesia induction could be performed safely in patients with aSAH, regardless of the WFNS grade; moreover, it resulted in lower rebleeding rate than that reported in previous epidemiological reports.