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.     

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.     

Alcohol dependence syndrome and BDIM (before-discharge intervention method)--report 4, the family members' self-reports about BDIM]

One hundred fifty-three inpatients with alcohol dependence syndrome were treated with the structured BDIM (Before-Discharge Intervention Method). 82 patients of them have participated to self-help group meetings or kept having therapy as our outpatients or inpatients during the study period. We chose the families of the 82 patients as our study subject Out of the study subjects who took part in BDIM, 64 families (117 persons) answered our questionnaire. Among them 63 families (101 persons) gave their described answers of impressions and opinions about BDIM, which were summarized as follows. (1) Through BDIM the family members gained second thought on their alcoholic family member (IP: identified patient) and they could tell their new view to IP. BDIM enabled them to tell IP their sincere feeling and hope for recovery of IP. BDIM empowered both IP and IP's family members. (2) The family members became to know IP's orientation on his or her disease. They came to know IP's denial and understand him or her as he or she was. (3) The family members felt emotional ties among themselves and IP through BDIM. When the family members of a dysfunctional family took part together in BDIM, they could know the feelings, thoughts, experiences and hopes one another. The family members had a precious experience of mutual understanding among themselves and IP to hope for recovery together. (4) The family members appreciated BDIM as a effective therapy. In BDIM many of them regarded highly of giving their letters to IP as a useful method to convey their feeling and thoughts calmly to IP. (5) On the other hand some family members pointed out the difficulty for themselves to write on BDIM. For family members who are not good at writing a letter or tend only to blame IP through their letters, writing and giving letters to IP is not appropriate as a therapy. If family members feel strong anxiety or fear, it is safe not to practice BDIM.     

Stereoselectivity of a potent calcium antagonist, 1-benzyl-3-pyrrolidinyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism.     

Minimum incision endoscopic nephrectomy for giant hydronephrosis

Five consecutive patients with symptomatic giant hydronephrosis underwent minimum incision endoscopic nephrectomy. The originally huge renal specimen was retroperitoneally mobilized using both of endoscopy and direct vision, without the use of trocar ports or gas insufflation, via a single minimum incision that narrowly permitted extraction of the specimen. The specimen was successfully extracted from the incision in all patients. Technically, proper deflation of the hydronephrotic sac facilitates mobilization and enables extraction of the specimen. Median (range) size of incision, operative time, and estimated blood loss were 4 cm (3-5), 205 min (156-222), and 210 mL (110-350), respectively. No patient required blood transfusion or encountered operative complications. Postoperative convalescence was short and uneventful; all patients resumed oral intake and ambulance on the day following surgery, and were physically dischargeable from hospital after 2-3 postoperative days. Thus, this technique is a feasible, minimally invasive and safe procedure for symptomatic giant hydronephrosis.     

Sequential bilateral minimum incision endoscopic radical nephrectomy in dialysis patients with bilateral renal cell carcinomas

Since 1998, we have performed minimum incision endoscopic surgery (MIES) for renal cell carcinoma (RCC). For seven dialysis patients with bilateral RCC, we have performed sequential bilateral MIES radical nephrectomy. It was carried out by retroperitoneal approach through a single minimum incision that narrowly permitted extraction of the specimen using endoscopy and direct stereovision, without trocar ports, without gas insufflation and without the insertion of the hands of operators into the operative field. Although six of the seven patients had multiple complications in addition to chronic renal failure (CRF), bilateral kidneys were successfully removed by sequential MIES radical nephrectomy without major operative complication. Postoperative recovery was prompt with all patients resuming oral feeding and walking by the second postoperative day. Sequential bilateral MIES radical nephrectomy, leaving the peritoneal cavity intact and without imposing circulatory stress caused by gas insufflation, is a feasible treatment for bilateral RCCs in dialysis patients.