Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.</p

Visualization of coronary plaque in type 2 diabetes mellitus patients using a new 40MHz intravascular ultrasound imaging system

SummaryBackgroundPrevious epidemiological studies demonstrated plaque vulnerability to be high in diabetic patients. iMap-intravascular ultrasound (IVUS) is a recently developed radiofrequency 40MHz IVUS imaging system for tissue characterization. This study aimed to characterize coronary plaque in target lesions of diabetic patients using iMap-IVUS.MethodsWe studied 175 treated vessels in 146 patients with stable angina pectoris and analyzed plaque components of culprit lesions by iMAP-IVUS. Patients were divided into 2 groups: non-diabetic (non-DM: 112 vessels, 93 patients) and diabetic (DM: 63 vessels, 53 patients).ResultsIn gray-scale IVUS 2D analysis, there were no differences in IVUS parameters. In 3D analysis, the DM group tended to have a larger plaque volume (p=0.07) and plaque burden (p=0.10). At minimum lumen sites, the absolute lipidic and necrotic areas (0.84±0.44mm2 vs. 0.58±0.41mm2, p<0.001, and 2.42±1.65mm2 vs. 1.46±1.76mm2, p<0.001, respectively) and percent lipidic and necrotic areas were significantly greater in the DM than in the non-DM group (8.39±3.38% vs. 5.25±2.30%, p<0.0001, and 23.65±11.54% vs. 12.99±10.71%, p<0.0001, respectively). In addition, the absolute lipidic and necrotic volumes (11.75±10.59mm3 vs. 8.18±6.24mm3, p<0.01, and 29.99±28.90mm3 vs. 19.44±19.35mm3, p<0.01, respectively) and percent lipidic and necrotic volumes were significantly greater in the DM than in the non-DM group (6.27±1.92% vs. 5.13±1.82%, p<0.0001, and 16.54±7.56% vs. 12.08±6.05%, p<0.0001, respectively).ConclusionCharacterization of coronary plaque by iMAP-IVUS in diabetic patients showed increased lipidic amount and necrotic plaque volume relative to subjects without DM

Preoperative Use of Alpha-1 Receptor Blockers in Male Patients Undergoing Extracorporeal Shock Wave Lithotripsy for a Ureteral Calculus

In this retrospective single-center cohort study, we investigated the impact of preoperative use of an alpha-1 adrenergic receptor (AR) blocker on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) in 193 male patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blockers. The primary outcome was treatment success after single-session SWL. We performed a multivariable logistic regression analysis adjusting for clinically important confounders to examine the association between preoperative use of alpha-1 AR blockers and the treatment success of SWL. Among the 193 patients, 15 (7.8%) were taking an alpha-1 AR blocker preoperatively. A multivariable analysis showed that preoperative use of an alpha-1 AR blocker was a significant negative predictor for treatment success of SWL (adjusted odds ratio 0.17; 95% confidence intervals, 0.04-0.74). Our findings suggest that the preoperative use of an alpha-1 AR blocker was a negative predictor of treatment success of SWL in male patients with a single ureteral calculus. Clinicians should pay more attention to the preoperative drug use in determining an appropriate stone therapy modality

Formation of meso, N-diphenylprotoporphyrin IX by an aerobic reaction of phenylhydrazine with oxyhemoglobins.

Administration of phenylhydrazine to rabbits resulted in the denaturation of hemoglobins in erythrocytes, causing the formation of intracellular precipitates known as Heinz bodies, severe hemolytic anemia, and reticulocytosis. To elucidate the molecular mechanism of the destabilization, we allowed human oxyhemoglobins to react aerobically with phenylhydrazine. After treatment with acetic acid/HCl and H2SO4/methanol, the chloroform extract contained blue-green pigments of major products accompanied by different minor products. Each product was isolated by column chromatography. By fast-atom-bombardment mass spectrometry (FAB-MS) and proton nuclear magnetic resonance (1H-NMR) spectrometry, dimethyl esters of N-phenylprotoporphyrin IX and meso, N-diphenylprotoporphyrin IX were determined. Other major products also were determined to be dimethyl esters of triphenyl-and tetraphenyl-substituted protoporphyrins by FAB-MS. The formation of meso, N-diphenylprotoporphyrin indicated that the addition of a phenyl radical to the meso-carbon atom of the protoporphyrin ring occurred. Triphenyl and tetraphenyl adducts also indicated the formation of phenyl radicals in the aerobic reaction of phenylhydrazine with oxyhemoglobins. From these results, we suggest that the formation of phenyl radicals and the replacement of heme with phenyl-substituted protoporphyrins cause the destabilization of hemoglobins to induce Heinz bodies and hemolytic anemia with phenylhydrazine.</p

Intra- and inter-operator reproducibility of automated cloud-based carotid lumen diameter ultrasound measurement

Background: Common carotid artery lumen diameter (LD) ultrasound measurement systems are either manual or semi-automated and lack reproducibility and variability studies. This pilot study presents an automated and cloud-based LD measurements software system (AtheroCloud) and evaluates its: (i) intra/inter-operator reproducibility and (ii) intra/inter-observer variability. Methods: 100 patients (83 M, mean age: 68 ± 11 years), IRB approved, consisted of L/R CCA artery (200 ultrasound images), acquired using a 7.5-MHz linear transducer. The intra/inter-operator reproducibility was verified using three operator's readings. Near-wall and far carotid wall borders were manually traced by two observers for intra/inter-observer variability analysis. Results: The mean coefficient of correlation (CC) for intra- and inter-operator reproducibility between all the three automated reading pairs were: 0.99 (P &lt; 0.0001) and 0.97 (P &lt; 0.0001), respectively. The mean CC for intra- and inter-observer variability between both the manual reading pairs were 0.98 (P &lt; 0.0001) and 0.98 (P &lt; 0.0001), respectively. The Figure-of-Merit between the mean of the three automated readings against the four manuals were 98.32%, 99.50%, 98.94% and 98.49%, respectively. Conclusions: The AtheroCloud LD measurement system showed high intra/inter-operator reproducibility hence can be adapted for vascular screening mode or pharmaceutical clinical trial mode

Renal Function after Nephrectomy Influences the Risk of Cardiovascular Events

We retrospectively analyzed the factors related to postoperative cardiovascular (CV) events in patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1 renal cell carcinoma (RCC). We identified 570 patients who underwent PN or RN for T1 renal cell carcinoma between January 1998 and December 2009 at our institution and related hospitals. We determined the cumulative incidence rate of CV events and overall survival (OS) using Kaplan-Meier survival curves with a log-rank test, and we evaluated the risk for an increase in CV events and OS using Cox proportional hazard regression. Of the 570 patients, 171 underwent PN and 399 underwent RN. The type of surgery was not significantly related with CV events. The only factor that significantly increased the risk of CV events in both the univariate (HR 2.67, p=0.006) and multivariate analyses (HR 2.14, p=0.044) was a postoperative estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Postoperative eGFR was also a significant risk factor for OS in the univariate analysis (HR 2.38, p=0.0104), but not in the multivariate model. Postoperative renal function was a significant independent predictor of the incidence of subsequent CV events

A low-cost machine learning-based cardiovascular/stroke risk assessment system: integration of conventional factors with image phenotypes

Background: Most cardiovascular (CV)/stroke risk calculators using the integration of carotid ultrasound image-based phenotypes (CUSIP) with conventional risk factors (CRF) have shown improved risk stratification compared with either method. However such approaches have not yet leveraged the potential of machine learning (ML). Most intelligent ML strategies use follow-ups for the endpoints but are costly and time-intensive. We introduce an integrated ML system using stenosis as an endpoint for training and determine whether such a system can lead to superior performance compared with the conventional ML system.Methods: The ML-based algorithm consists of an offline and online system. The offline system extracts 47 features which comprised of 13 CRF and 34 CUSIP. Principal component analysis (PCA) was used to select the most significant features. These offline features were then trained using the event-equivalent gold standard (consisting of percentage stenosis) using a random forest (RF) classifier framework to generate training coefficients. The online system then transforms the PCA-based test features using offline trained coefficients to predict the risk labels on test subjects. The above ML system determines the area under the curve (AUC) using a 10-fold cross-validation paradigm. The above system so-called "AtheroRisk-Integrated" was compared against "AtheroRisk-Conventional", where only 13 CRF were considered in a feature set.Results: Left and right common carotid arteries of 202 Japanese patients (Toho University, Japan) were retrospectively examined to obtain 395 ultrasound scans. AtheroRisk-Integrated system [AUC=0.80, P&lt;0.0001, 95% confidence interval (CI): 0.77 to 0.84] showed an improvement of similar to 18% against AtheroRisk-Conventional ML (AUC=0.68, P&lt;0.0001, 95% CI: 0.64 to 0.72).Conclusions: ML-based integrated model with the event-equivalent gold standard as percentage stenosis is powerful and offers low cost and high performance CV/stroke risk assessment