Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.     

Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

Successful choledochojejunostomy for choledochal stricture with preservation of the collateral parabiliary venous system following iatrogenic portal occlusion

We surgically treated a patient with biliary stricture and portal vein occlusion, after operation for gastric cancer with lymphadenectomy along the hepatoduodenal ligament, that had led to choledochal stone formation and a dilatated parabiliary venous system. A 57-year-old man without hepatic dysfunction exhibited hepatic duct dilatation with choledochal stone on ultrasonography and percutaneous transhepatic cholangiography, respectively. Pharmacoportography revealed occlusion of the portal vein and dilatation of the parabiliary venous system. Of various preoperative imaging studies used, enhanced computed tomography was most useful for delineating the surgical anatomy of the hepatoduodenal ligament. Complete preservation of the dilatated vessels, which functioned as the main portal collateral pathway, resulted in a successful choledocho-jejunostomy, with an uneventful postoperative course.     

Adsorption of Human Recombinant Erythropoietin on Dialysis Membranes In Vitro

Abstract: The adsorptive characteristics of 5 dialysis membranes for recombinant human erythropoietin (EPO) were studied in vitro in a closed circuit system. For 120 min, EPO added with bovine serum was significantly adsorbed by polymethylmetacrylate (PMMA) and polyacry–lonitrile (PAN) membranes but not by Cuprophan, ethylene vinyl alcohol (EVAL), or polysulfone (PS) membranes. In addition the EPO adsorptive rate, as well as that of β₂–microglobulin (β₂–MG), was greater with a PMMA membrane than with a PAN membrane. EPO was not detected in the ultrafiltrate at 15 min with 5 membranes. These results indicate that EPO was eliminated by membrane adsorption only with some dialysis membranes.     

Mass Protection Program of Perinatal Hepatitis B Virus Infection in Japan and Impact of an Optional Booster Vaccination on Its Efficacy

We assessed the efficacy of a government-sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow-up procedures in such infants, including an evaluation of anti-HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti-HBs was higher in the standard group than in the follow-up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti-HBs response. In conclusion, we recommend that a follow-up blood test to confirm a response of anti-HBs to HBV vaccine should be performed at 4–8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy.     

Micro-shear bond strength of dual-cured resin cement to glass ceramics.

OBJECTIVES: The aim of this study was to investigate the effects of sandblasting, etching, and a silane coupling agent on the ability of dual-cured resin cement to bond to glass ceramics designed for in indirect adhesive restoration. METHODS: A cast glass ceramic (Olympus Castable Ceramics) with a crystalline phase consisting of mica and beta-spondumene was selected as the substrate material. The glass surfaces, which were sandblasted, polished, or etched with phosphoric acid or hydrofluoric acid (HF), were bonded with a dual-cured resin cement (Panavia Fluoro Cement) using a dentin adhesive system (Clearfil SE Bond), both with and without a silane coupling agent. A micro-shear bond test was carried out to measure the bond strength of the resin cement to the glass surface. Each glass surface was bonded and tested using the shear test. In addition, surfaces with the bonding removed after the shear bond test, the adhesive interface between the glass and cement, and an etched glass surface without any bonding, were studied morphologically using scanning electron microscopy or field emission scanning electron microscopy. RESULTS: Usage of a silane coupling agent effectively raised the bond-strength values of resin cement (Fisher's PLSD, P<0.01). The effectiveness of using phosphoric acid etching to improve bonding was not clear (Fisher's PLSD, P>0.01). HF-etching for 30s seemed to over-etch the glass surface, resulting in adverse effects on bonding (Fisher's PLSD, P<0.01). SIGNIFICANCE: The micro-shear bond strength between Olympus Castable Ceramics and resin cement can be increased by the silane coupling agent used along with an acidic primer.