Remarkable Improvement of Cardiac Function After Pre-emptive Kidney Transplant in a Patient With Severe Mitral Regurgitation Accompanied by Low Cardiac Function: A Case Report.

Patients with end-stage renal disease are at a high risk for cardiovascular diseases. It is controversial whether end-stage renal disease patients with low cardiac function can safely accept kidney transplant. Here, we present a 42-year-old kidney transplant recipient with severe mitral regurgitation accompanied by low cardiac function. He wanted to undergo a pre-emptive kidney transplant from his uncle. We decided to perform living kidney transplant prior to cardiac surgery. Despite adequate ultrafiltration and hemodiafiltration before operation, the patient's ejection fraction still remained 35% 1 day before transplant. He showed complete recovery of cardiac function in only 2 days after pre-emptive kidney transplant, although his body weight did not change before and after the operation. Early removal of the uremic toxin or inflammatory cytokines may play a role in rapid improvement of the cardiac function. Increase of vasoactive substances by improvement of kidney function may lead to reduction of afterload and amelioration of cardiac microcirculation. This report also suggests that optimal timing for operation might be important.

Validation of a new prognostic model to easily predict outcome in renal cell carcinoma: the GRANT score applied to the ASSURE trial population.

Background: Prognostic scores have been developed to estimate the risk of recurrence and the probability of survival after nephrectomy for renal cell carcinoma (RCC). The use of these tools, despite being helpful to plan a customized schedule of follow-up, to the patient's tailored counselling and to select individuals who could potentially benefit from adjuvant treatment, currently is not routine, due to their relative complexity and to the lack of histological data (i.e. necrosis). Patients and methods: We developed a simple score called GRade, Age, Nodes and Tumor (GRANT) based on four easily obtained parameters: Fuhrman grade, age, pathological nodal status and pathological tumor size. Patients with 0 or 1 factor are classified as favorable risk, whereas patients with two or more risk factors as unfavorable risk. The large population of RCC patients from the ASSURE adjuvant trial was used as independent dataset for this external validation, to investigate the prognostic value of the new score in terms of disease-free survival and overall survival and to evaluate its possible application as predictive tool. Statistical analyses were carried out by the Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute (Boston, USA) for the ASSURE trial patients' population. Results: The performance of the new model is similar to that of the already validated score systems, but its strength, compared with the others already available, is the ease and clarity of its calculation, with great speed of use during the clinical practice. Limitations are the use of the Fuhrman nuclear grade, not valid for rare histologies, and the TNM classification modifications over time. Conclusion: The GRANT score demonstrated its potential usefulness for clinical practice. ClinicalTrials.gov Identifier for the ASSURE trial: NCT00326898.

Transient azoospermia following rosuvastatin medication for hypercholesterolemia.

The authors report a case of transient azoospermia following hydroxymethylglutaryl-coenzyme A reductase (HMGCR) inhibitor rosuvastatin medication for hypercholesterolemia. While a primary infertile couple with oligoasthenospermia was preparing for an in vitro fertilization program, the male partner had been diagnosed with hypercholesterolemia in a medical check-up and prescribed four-week oral administration of rosuvastatin. No motile spermatozoa were found in the ejaculated semen and urine on the day of follicular aspiration. Azoospermia was confirmed by reexamination in weeks 3 and 7. Spermatozoa appeared in the ejaculated semen in two weeks of drug withdrawal. In week 16, the sperm count and motility increased to the level where intracytoplasmic sperm injection was available.

Do combined psychological stress examinations predict pregnancy outcome in an assisted reproductive technology program?

PURPOSE OF INVESTIGATION: To investigate prospectively if the pregnancy outcome in infertile women undergoing assisted reproductive technology (ART) is predictable by a combination of psychological stress examinations on the day of embryo/blastocyst transfer. MATERIALS AND METHODS: From April 2012 to May 2012, 114 women aged 42 years old or less underwent transfer of morphologically-good embryo/blastocyst(s) in the present in vitro fertilization (IVF) center. Immediately before the transfer, salivary secretion was obtained and frozen. α-amylase and cortisol concentrations were quantified using biochemical assays. In addition, patients were asked to answer General Health Questionnaire 28 (GHQ28) and Zung's Self Rating Depression Scale (SDS) following transfer. The results were compared between the pregnant group and non-pregnant group. RESULTS: There were no significant differences in the age of the infertile couples between the pregnant group and non-pregnant group as well as body mass index of the infertile women. The GHQ28 and SDS scores were similar between the two groups, as were the salivary α-amylase and cortisol concentrations. CONCLUSION: This prospective study failed to demonstrate the predictivity of the pregnancy outcome by psychological stress examinations in infertile women in an ART program, even though these tests were used in combination.

A pilot survey on obstetric complications in pregnant women with a history of repeated embryo implantation failure and those undergoing single local endometrial injury.

PURPOSE OF INVESTIGATION: To assess if a history of repeated implantation failure (RIF) or local endometrial injury (LEI) for RIF affects the pregnancy course in women who conceived in the subsequent in vitro fertilization (IVF)-embryo/blastocyst transfer (ET/BT) cycle. MATERIALS AND METHODS: Of 42 pregnant women with a history of three consecutive failed ET/BT cycles with negative pregnancy tests, 11 patients had a clinical pregnancy in the immediate subsequent ET/BT cycle following (the RIF group), whereas 31 patients had a clinical pregnancy in the subsequent ET/BT cycle following single curettage LEI in the proliferative phase of the preceding spontaneous cycle (the RIF/LEI group). Information on the obstetric complications were retrieved from medical records and compared with that of women who had a live birth in the first ET/BT attempt (the control group). Results: The clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were significantly higher in the RIF/LEI group than in the RIF group (p < 0.010). There were no significant differences in the incidence of pregnancy of unknown location, ectopic pregnancy, miscarriage, stillbirth, preterm birth, premature rupture of the membranes, placenta previa, placental abruption, preeclampsia, pregnancy-induced hypertension, gestational diabetes, fetal growth restriction, caesarean section, and blood transfusion were similar between the three groups (p > 0.31). CONCLUSION: In this pilot survey, neither a history of RIF nor LEI intervention for RIF increased the incidence of obstetric complications in the women who conceived in the subsequent ET/BT cycle.

Diclofenac suppository pretreatment in prevention of vasovagal reflex-associated complications for infertile women undergoing local endometrial injury.

PURPOSE OF INVESTIGATION: To assess the effects of the diclofenac suppository pretreatment in prevention of vasovagal reflex-associated complications for infertile women undergoing local endometrial injury (LEI). MATERIALS AND METHODS: Eighty-six infertile outpatients with repeated implantation failure following transfer of morphologically good embryos and/or blastocysts underwent single curettage LEI to improve the pregnancy outcome in the subsequent embryo/blastocyst transfer cycle. Of them, 35 patients chose diclofenac suppository administration prior to LEI, whereas 51 patients did not. The occurrence of palpitations, bradycardia, hypotension, presyncope, and requirement of bed rest was compared between the two groups. RESULTS: There were no significant differences in the demographics between the two groups. The prevalence of presyncope and requirement of bed rest was significantly lower in the diclofenac suppository group than in the control group. The pregnancy outcome was similar between the two groups. CONCLUSION: The diclofenac suppository administration is a low-cost effective method to reduce the risk of the vasovagal reflex-associated complications in infertile women undergoing LEI.

Vaginal preparation with povidone iodine disinfection and saline douching as a safe and effective method in prevention of oocyte pickup-associated pelvic inflammation without spoiling the reproductive outcome: evidence from a large cohort study.

PURPOSE OF INVESTIGATION: The aim of this study was to investigate if vaginal preparation procedure affects the occurrence of oocyte pickup-associated pelvic inflammation (OPU-PI) and the reproductive outcome in an in vitro fertilization (IVF) program. MATERIALS AND METHODS: The occurrence of OPU-PI and the reproductive outcome were compared between 956 infertile patients undergoing vaginal preparation with saline douching alone versus 1,216 infertile patients undergoing a combination ofpovidone iodine disinfection and subsequent saline douching in an IVF program. RESULTS: OPU-PI occurred in four patients (0.042%) in the saline douching alone group, whereas there were no cases in the combination group (p = 0.016). There were no significant differences in the rate of fertilization, morphologically good embryo acquisition, clinical and ongoing pregnancy between the two groups (p > 0.23). CONCLUSIONS: This large cohort study demonstrated that a combination of vaginal povidone iodine disinfection and subsequent saline douching is more effective procedure than saline douching alone to prevent OPU-PI, without spoiling the oocyte quality.

Single curettage endometrial biopsy injury in the proliferative phase improves reproductive outcome of subsequent in vitro fertilization-embryo transfer cycle in infertile patients with repeated embryo implantation failure.

PURPOSE OF INVESTIGATION: To evaluate the effectiveness of single curettage endometrial biopsy injury (EBI) in the proliferative phase for in vitro fertilization-embryo transfer (IVF-ET) outcome of the subsequent cycle in infertile patients with repeated embryo implantation failure (EIF). MATERIALS AND METHODS: Of 89 patients who repeated EIF three times following transfer of morphologically good embryos and/or blastocysts, 40 patients chose curettage EBI prior to the subsequent IVF-ET cycle. Using a three-mm wide curette, EBI was performed once between days 6 and 12 of the spontaneous cycle. Their IVF-ET outcomes in the subsequent cycle were compared with those in 49 patients who did not opt for EBI. RESULTS: The clinical pregnancy rate (37.5% vs 12.2%), embryo implantation rate (23.6% vs 6.3%), and ongoing pregnancy rate (25.0% vs 8.2%) were significantly higher in the EBI group than in the non-EBI group. No serious complaints and complications were noted. CONCLUSION: Single curettage EBI in the proliferative phase of the preceding cycle significantly improved IVF-ET outcome in infertile patients with repeated EIF.

Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice.

In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression.

Feasibility and efficiency of indirect lifestyle interventions in offspring of type 2 diabetic patients.

INTRODUCTION: Individuals genetically predisposed to type 2 diabetes represent an important target for preventive strategies. Genetic screening, based on information about individual genetic variants, will be possible technically, but translational research in this field is still insufficient. Family history thus represents a useful tool for detecting genetically high-risk populations in this post-genomic era. OBJECTIVES: The purpose of this pilot study was to investigate the feasibility and efficiency of indirect lifestyle interventions in offspring of type 2 diabetic patients. METHODS: Offspring were recruited from 74 diabetic (Group 1) and 39 non-diabetic (Group 2, control group) patients. A lifestyle intervention was conducted by mail, a total of 3 times, every 3 months. Lifestyle related to diet and physical activity was assessed using a self-administered questionnaire. RESULTS: Ten offspring of type 2 diabetic and 6 of non-diabetic patients participated in this study. Total energy intake decreased after 3 interventions in both of the groups (Group 1: 305 ± 228.8 kcal/day, p = 0.004; Group 2: 82 ± 65.6 kcal/day, p = 0.04); however, the effect of intervention was significantly greater in Group 1 compared to Group 2 (p = 0.021). Physical activity and other physical outcomes were stable in normal levels during the study period in both of the groups. CONCLUSIONS: The intervention program helped to reduce total energy intake in offspring of type 2 diabetic patients more than in the control group, but the acceptance rate of the intervention program was disappointingly low. Further consideration is required to access and motivate offspring to develop precautionary lifestyle principles.

Comparison of oral falecalcitriol and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism: a randomized, crossover trial.

BACKGROUND: Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral falecalcitriol treatment with those of intravenous calcitriol treatment. METHODS: Twenty-one patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. RESULTS: Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, -200.1 +/- 107.0 with falecalcitriol vs. -200.8 +/- 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, -137.1 +/- 73.1 with falecalcitriol vs. -120.4 +/- 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral falecalcitriol treatment did not change any bone metabolic marker level. CONCLUSION: The present study showed that oral falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.

Correlation of dystrophin-glycoprotein complex and focal adhesion complex with myosin heavy chain isoforms in rat skeletal muscle.

AIM: The dystrophin-glycoprotein complex (DGC) and focal adhesion complex (FAC) are transmembrane structures in muscle fibres that link the intracellular cytoskeleton to the extracellular matrix. DGC and FAC proteins are abundant in slow-type muscles, indicating the structural reinforcement which play a pivotal role in continuous force output to maintain posture for long periods. The aim of the present study was to examine the expression of these structures across fast-type muscles containing different myosin heavy chain (MHC) isoform patterns which reflect the fatigue-resistant characteristics of skeletal muscle. METHODS: We measured the expression of dystrophin and beta1 integrin (representative proteins of DGC and FAC respectively) in plantaris, extensor digitorum longus, tibialis anterior, red and white portions of gastrocnemius, superficial portion of vastus lateralis and diaphragm, in comparison with soleus (SOL) and cardiac muscle from rats. RESULTS: The expression of dystrophin and beta1 integrin correlated positively with the percentage of type I, IIa and IIx MHC isoforms and negatively with that of type IIb MHC isoform in fast-type skeletal muscles, and their expression was abundant in SOL and cardiac muscle. CONCLUSION: Our results support the idea that DGC and FAC are among the factors that explain the fatigue-resistant property not only of slow-type but also of fast-type skeletal muscles.

[Treatment of a massive tracheal bleeding with percutaneous cardiopulmonary support].

A 69-year-old woman was admitted to our hospital with heart failure. Echocardiography demonstrated severe mitral valve regurgitation due to chordae rupture of the posterior mitral leaflet. Although she was intubated and ventilation was initiated, her condition did not improve. On the 17th hospital day, she was scheduled to undergo mitral valve plasty. After induction of anesthesia, massive bleeding occurred from the tracheal granuloma (diameter, 3 cm), which had developed at the tip of the tracheal tube, and the airway was obstructed. Emergency percutaneous cardiopulmonary support (PCPS) was then introduced. Thereafter, endoscopic hemostasis was performed, followed by the excision of the granulation tissue using a gastric fiberscope. After excising the tissue, the patient could be ventilated; therefore, she was weaned from PCPS. The maximum PCPS flow was 4.0 l/min, and it was conducted for a 210-minutes duration. Her respiratory condition improved, and she was weaned from the ventilator 3 days after surgery. Mitral valve plasty was performed 55 days after the first operation, and she was discharged from the hospital in good health.

Investigation of formaldehyde pollution of tap water and rain water using a novel visual colorimetry.

The pollution of tap water and rain water with formaldehyde in Toyama Pref., Japan was investigated by means of a simple, rapid and cost-effective visual colorimetry developed by us. The levels of formaldehyde in three tap waters from different sources of dams on mountainside and a well-water pumped in urban area in Toyama Pref. were lower than 0.01 mg L(-1) that was the detection limit of the colorimetry. On the other hand, rain waters were seriously polluted with formaldehyde. Rain waters were sampled from three different sites (urban area, top of hill and industrial area) in Toyama Pref. from autumn to winter in 2006. The levels of formaldehyde in the rain waters ranged from 0.07 to 0.30 mg L(-1). The analytical results by the visual colorimetry were in good agreement with those obtained by GC-MS method. It was confirmed that the colorimetry is excellent for practical use for the determination of formaldehyde. It must be concerned about the pollution of rainwater with formaldehyde, when rain water is applied for tap water and miscellaneous purpose.

[Unruptured aneurysm of the sinus of Valsalva associated with right ventricular outflow tract stenosis; report of a case].

A 51-year-old female was referred to our hospital for heart murmur and was diagnosed with right ventricular outflow stenosis by echocardiography. Six years later, follow-up echocardiogram revealed that the stenosis was caused by an aneurysm of the sinus of Valsalva (2 cm in diameter) originated from the right coronary sinus. Resection and patch closure of the aneurysm were carried out under complete cardiopulmonary bypass. The aneurysm was not associated with ventricular septal defect and was categorized as Sakakibara-Konno type I. Postoperative state was uneventful. Systolic murmur disappeared and pressure difference in the right ventricular outflow was normalized.

Tranilast inhibits glucose-induced insulin secretion from pancreatic beta-cells.

Tranilast, N-(3,4-demethoxycinnamoyl)-anthranilic acid, is an anti-allergic agent identified as an inhibitor of mast cell degranulation. Recently, tranilast was shown to decrease albuminuria in a rat model of diabetic nephropathy and to ameliorate vascular hypertrophy in diabetic rats, suggesting that it may be clinically useful in the treatment of diabetic complications. However, the effects of tranilast on glucose tolerance have not been elucidated. Thus, the aim of this study is to investigate the effect of tranilast on insulin secretion in pancreatic beta-cells. Treatment with tranilast significantly suppressed insulin secretion in INS-1E cells and rat islets induced by 16.7 mmol/l glucose. Furthermore, tranilast inhibited tolbutamide-induced insulin secretion. Treatment with tranilast increased (86)Rb (+) efflux from COS-1 cells in which pancreatic beta-cell-type ATP-sensitive K (+) (K (ATP)) channels were reconstructed and suppressed the cytosolic ATP/ADP ratio in INS-1E cells. Interestingly, treatment with tranilast enhanced glucose uptake in INS-1E cells. In the present study, we demonstrated that tranilast inhibited glucose- and tolbutamide-induced insulin secretion through the activation of K (ATP) channels in pancreatic beta-cells.