Possible involvement of TNF-alpha in left ventricular remodeling in hemodialysis patients

BACKGROUND: Tumor necrosis factor (TNF)-alpha causes hypertrophic as well as negative inotropic effects on cardiac myocytes. Circulating TNF-alpha levels are reported to be elevated in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). We investigated whether increased circulating TNF-alpha is associated with left ventricular remodeling against pressure and/or volume overload in HD patients with or without diabetes mellitus. METHODS: Echocardiography and the measurement of plasma TNF-alpha and B-type natriuretic peptide (BNP) concentrations, one of the parameters indicating left ventricular wall stress, were performed on 176 ESRD patients undergoing maintenance HD (88 non-diabetic and 88 diabetic patients). RESULTS: The mean plasma TNF-alpha concentrations were high, but did not differ between non-diabetic and diabetic patients (9.8 +/- 4.3 pg/mL vs. 9.9 +/- 5.4 pg/mL). In non-diabetic patients, plasma TNF-alpha concentration correlated positively with interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), and inversely with left intraventricular dimensions, but did not correlate with left ventricular mass index (LVMI). In contrast, in diabetic patients, plasma TNF-alpha concentration correlated positively with plasma BNP concentration (r=0.821, p=0.0001) and left intraventricular dimensions, and inversely with rLVWT (r=-0.407, p=0.0001) and left ventricular fractional shortening (r=-0.445, p=0.0001). CONCLUSIONS: Circulating TNF-alpha is possibly involved in concentric left ventricular remodeling in non-diabetic HD patients, whereas it is associated with eccentric left ventricular remodeling against sustained pressure and/or volume overload in diabetic HD patients.     

Different remodelling against left ventricular overload between diabetic and non-diabetic haemodialysis patients

1. Diabetes mellitus is significantly associated with the occurrence of congestive heart failure in end-stage renal disease patients undergoing maintenance haemodialysis. In the present study, we asked whether the left ventricular remodelling against sustained pressure and/or volume overload to the left ventricle may be different between diabetic and non-diabetic haemodialysis patients. 2. Left ventricular parameters, including left ventricular mass index (LVMI), interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), were assessed in 486 patients receiving maintenance haemodialysis (145 diabetic and 341 non-diabetic patients) using transthoracic echocardiography. Plasma concentrations of B-type natriuretic peptide (BNP), measured with an immunoradiometric assay, were used as a humoral parameter indicating left ventricular wall stress. 3. In non-diabetic patients, the plasma BNP concentration correlated with LVMI (r = 0.245; P = 0.0001), IVST (r = 0.250; P = 0.0001) and rLVWT (r = 0.149; P = 0.006). Furthermore, LVMI was correlated with mean blood pressure and pulse pressure and IVST and rLVWT were correlated with pulse pressure. 4. In contrast, none of the measured factors was correlated with LVMI and IVST in diabetic patients. Plasma BNP concentrations were positively correlated with end-systolic and end-diastolic left intraventricular dimensions and were inversely correlated with rLVWT and left ventricular fractional shortening in diabetic patients, but not in non-diabetic patients. 5. In conclusion, a sustained increase in left ventricular wall stress is likely to elicit eccentric left ventricular remodelling in diabetic haemodialysis patients, whereas it causes concentric left ventricular remodelling in non-diabetic haemodialysis patients. This difference in left ventricular remodelling against left ventricular overload may be associated with the high incidence of congestive heart failure in diabetic haemodialysis patients.     

Leydig cell tumor of the testis presenting male infertility: a case report

A 33-year-old male was referred to our hospital for male infertility with painless swelling of the left scrotal content. Left high orchiectomy was performed under the diagnosis of left testicular tumor. Histologically, this testicular mass was a Leydig cell tumor. We reviewed 55 cases of Leydig cell tumor of the testis previously reported in Japan, and reported the hormonal profile in our case before and after surgery.     

In vitro and ex vivo effects of a selective nociceptin/orphanin FQ (N/OFQ) peptide receptor antagonist,CompB, on specific binding of [3H]N/OFQ and [35S]GTPgammaS in rat brain and spinal cord

1. A novel selective nociceptin/orphanin FQ (N/OFQ) peptide receptor antagonist, 1-[(3R,4R)-1-cyclooctylmethyl]-3-hydroxymethyl-4-piperidyl)-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (CompB), inhibited specific binding of [(3)H]N/OFQ to crude membranes from the rat brain and spinal cord in a concentration-dependent manner and their K(i) values were 7.11 and 4.02 nM, respectively. Rosenthal analysis indicated that there was a significant increase in the K(d) value for [(3)H]N/OFQ binding in the brain and spinal cord in the presence of CompB (10 nM). 2. There was a dose-dependent increase in K(d) values for [(3)H]N/OFQ binding in the brain and spinal cord following i.v. injection of CompB at relatively low doses (0.69-6.88 micro mol kg(-1)), compared with the control values. In the spinal cord, enhancement with each dose was constantly greater and the duration of enhancement (6.88 micro mol kg(-1)) was significantly longer. 3. The degree of increase in K(d) values for [(3)H]N/OFQ binding after i.v. injection of CompB (6.88 micro mol kg(-1)) was significantly larger in the lumbar region of the spinal cord compared to other regions. 4. CompB (0.1, 0.3 micro M) shifted the concentration-effect curves of N/OFQ-stimulated [(35)S]GTPgammaS binding in the brain and spinal cord to the right. 5. The i.v. injection of CompB (6.88 micro mol kg(-1)) significantly suppressed the N/OFQ-stimulated [(35)S]GTPgammaS binding in the rat spinal cord and shifted the concentration-effect curve to the right, while it produced little inhibitory effect in the brain. The present study has shown that CompB may exhibit pharmacological effects through a predominant blockade of N/OFQ peptide receptors in the spinal cord under in vivo conditions.     

Living‐donor single‐lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins

This is a case report of a successful single‐lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6‐year‐old boy underwent living‐donor single‐lobe transplantation with the right lower lobe from his 31‐year‐old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO₂/FiO₂ in the intensive‐care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT‐guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.     

Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients

Objectives

The purpose of this study was to evaluate the effect of early tracheostomy in patients following lung transplantation and to determine its optimal timing and influence on clinical outcomes.

Methods

We retrospectively reviewed records of 96 adult patients who underwent lung transplantation at our institution between August 2008 and January 2016. Time-to-tracheostomy was defined based on timing of the procedure: “early” if less than 3 days or “late” if 3 or more days after lung transplantation.

Results

Forty-nine patients (51%) underwent tracheostomy 3.2?±?1.8 days after lung transplantation. Among these patients, 21 patients (42.9%) underwent early tracheostomy and 28 patients (57.1%) underwent late tracheostomy. Multivariable logistic regression analysis indicated that preoperative performance status was a significant predictor for tracheostomy (p?=?0.006, odds ratio 2.72). Patients in the early tracheostomy group began walking (p?=?0.003) and oral feeding (p?=?0.0006) earlier and had a shorter duration of mechanical ventilation (p?=?0.04) and shorter length of intensive care unit (p?=?0.01) and hospital stay (p?=?0.04) than patients in the late tracheostomy group. No significant differences in postoperative walking (p?=?0.06), oral feeding (p?=?0.17), or length of hospital stay (p?=?0.37) were observed between patients who underwent early tracheostomy and those who did not undergo tracheostomy.

Conclusions

Early tracheostomy following lung transplantation decreased both intensive care and hospital stay, due to improved postoperative recovery, even in patients with poor preoperative conditions. Furthermore, length of hospital stay in patients with early tracheostomy was similar to that of patients without tracheostomy after lung transplantation.

     

Effects of immunization of pregnant guinea pigs with guinea pig cytomegalovirus glycoprotein B on viral spread in the placenta

Background

Cytomegalovirus (CMV) is the most common cause of congenital virus infection. Infection of guinea pigs with guinea pig CMV (GPCMV) can provide a useful model for the analysis of its pathogenesis as well as for the evaluation of vaccines. Although glycoprotein B (gB) vaccines have been reported to reduce the incidence and mortality of congenital infection in human clinical trials and guinea pig animal models, the mechanisms of protection remain unclear.

Methods

To understand the gB vaccine protection mechanisms, we analyzed the spread of challenged viruses in the placentas and fetuses of guinea pig dams immunized with recombinant adenoviruses expressing GPCMV gB and β-galactosidase, rAd-gB and rAd-LacZ, respectively.

Results

Mean body weight of the fetuses in the dams immunized with rAd-LacZ followed by GPCMV challenge 3 weeks after immunization was 78% of that observed for dams immunized with rAd-gB. Under conditions in which congenital infection occurred in 75% of fetuses in rAd-LacZ-immunized dams, only 13% of fetuses in rAd-gB-immunized dams were congenitally infected. The placentas were infected less frequently in the gB-immunized animals. In the placentas of the rAd-LacZ- and rAd-gB-immunized animals, CMV early antigens were detected mainly in the spongiotrophoblast layer. Focal localization of viral antigens in the spongiotrophoblast layer suggests cell-to-cell viral spread in the placenta. In spite of a similar level of antibodies against gB and avidity indices among fetuses in each gB-immunized dam, congenital infection was sometimes observed in a littermate fetus. In such infected fetuses, CMV spread to most organs.

Conclusions

Our results suggest that antibodies against gB protected against infection mainly at the interface of the placenta rather than from the placenta to the fetus. The development of strategies to block cell-to-cell viral spread in the placenta is, therefore, required for effective protection against congenital CMV infection.     

Pharmaceutical evaluation of steroidal ointments by ATR-IR chemical imaging: distribution of active and inactive pharmaceutical ingredients

We recently used micro attenuated total reflection infrared (ATR-IR) spectroscopy to conduct imaging analysis of ointments and evaluate the distributions of the active pharmaceutical ingredient (API) and excipients. An alclometasone dipropionate (ALC) ointment was used as a model product. Almeta, a brand-name product, had a domain with absorbance at 1656 cm(-1) attributable to the carbonyl group of ALC, the API. Absorbances at 1040 and 3300 cm(-1) were also noted in this domain, indicating the presence of the solubilizer, propylene glycol. Data also suggested the presence of benzyl alcohol in this domain. More detailed analysis showed the distribution of surfactants and other excipients in the base. Similar results were obtained for Vitra, a generic version of Almeta. Imaging analysis with micro ATR-IR confirmed that both ointments are liquid droplet dispersions with ALC dissolved in propylene glycol and dispersed in a base. However, minor differences in the ingredient distributions of the two ointments were detected and reflect differences in excipient concentrations and type, or manufacturing differences. In summary, we used micro ATR-IR for imaging analysis of an original ointment, Almeta, and its generic form Vitra, and established a method for visually evaluating the distributions of the API and excipients in these ointments.     

Usefulness of the MOSAIC (measurement of stenosis by aliasing coronary flow) method using transthoracic color Doppler echocardiography in unstable angina patients

Background

The aim of this study was to investigate the significance of the MOSAIC (measurement of stenosis by aliasing coronary flow) method for the detection of proximal left coronary stenosis in patients with unstable angina (UA) using transthoracic Doppler echocardiography (TTDE).

Methods

Patients (n = 107) with UA were evaluated. Proximal left coronary flow was sought in the short axis (SAX) at the aortic root level using color Doppler guidance. When detected coronary flow showed color aliasing, the color velocity range was gradually increased until color aliasing nearly disappeared. Then, the color baseline was shifted until the color flow showed “isovelocity”.

Results

Proximal coronary flow was detected in 86 (80.4%) of 107 patients. In these 86 patients, an optimal cutoff value of isovelocity ≥ 47.5 cm/s predicted significant coronary stenosis (percent diameter stenosis ≥ 70%) of the proximal left anterior descending (AHA segment 6) or left main coronary artery with a sensitivity of 88%, specificity of 97%, positive predictive value of 98%, and negative predictive value of 86%. In all 107 patients, the same cutoff value predicted significant coronary stenosis with a sensitivity of 78%, specificity of 98%, positive predictive value of 98%, and negative predictive value of 81%.

Conclusions

The MOSAIC method may play a complementary role in expeditious risk stratification and decision making in patients with UA.