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.     

A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

Hematoma Size in Deep Intracerebral Hemorrhage and its Correlation with Dot-Like Hemosiderin Spots on Gradient Echo T2*-Weighted MRI

BACKGROUND AND PURPOSE: Dot-like low intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted MRI have been histologically diagnosed to represent old cerebral microbleeds associated with microangiopathies. They have also been correlated to the fragility of small vessels and the tendency to bleed. Therefore, a substantial number of dotHSs might be associated with a large-sized, deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old microbleeds that did not enlarge to symptomatic size. METHODS: To investigate how dotHSs are related to the size (maximal diameter) of primary deep ICH, we analyzed the diameter and the number of dotHSs in 151 patients with deep ICH not associated with subarachnoid hemorrhage or intraventricular hemorrhage (75 males and 76 females, age ranged from 37 to 90 [65.7 +/- 11.3 years old] who were consecutively admitted to Hakodate Municipal Hospital. The hazard ratio (HR) for a maximal diameter of deep ICH < or =2 cm was estimated, using the number of dotHSs and risk factors for stroke. RESULTS: The number of dotHSs associated with the diameter < or =2 cm was 9.2 +/- 11.5, significantly larger than that with the diameter > or =2 cm (4.7 +/- 7.0, P= .012). Multivariate analysis revealed that a maximal diameter of deep ICH of < or =2 cm was found in patients with dotHS (HR, 3.7; 95% confidence interval [CI], 1.4-10.1; P= .009). CONCLUSION: Though small sample size limited the power of our analyses, these findings suggest that the number of dotHSs may be associated with a small diameter of deep ICH.     

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.     

Objective assessment of nerve injury after greater saphenous vein stripping.

AIM: The complication of nerve injury after greater saphenous vein stripping for varicosity is subjective, and a method for objective evaluation has never been established. The aim of this study was to evaluate postoperative sensory changes by quantitative assessment of current perception threshold (CPT), and to clarify the relation between CPT and symptoms. PATIENTS AND METHODS: Between January 2003 and August 2005, 27 limbs in 18 patients were enrolled. Quantitative sensory function was determined through CPT using a Neurometer (Neurotron, Inc., USA), with which saphenous nerve neural fiber selective minimum sensing values against three electrical stimuli (2000, 250, 5 Hz) were measured. CPT measurements were scheduled on the day before the operation, and 2-7 days, 1, 3, and 6 months after the operation. RESULTS: An increase in CPT value of more than 20% or decrease to below 50% compared to the preoperative value with at least two stimuli was defined as CPT abnormality. Subjective symptoms were observed in 13 limbs in the early postoperative period, and 10 limbs showed CPT abnormality. In 6 limbs with a CPT increase over 20% with all three stimuli, neurological symptoms continued for 6 months. CONCLUSIONS: CPT evaluation provides an objective indication of neurological symptoms in the lower limb following varicose vein surgery.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

Successful treatment with balloon dilatation using a double‐balloon enteroscope for a stricture in the small bowel of a patient with Crohn's disease

The requirement for endoscopic access to a stricture is a major limitation of the endoscopic dilatation for the treatment of strictures in the gastrointestinal tract. We have developed the double‐balloon enteroscopy method that enables visualization of the entire small bowel. In addition, double‐balloon enteroscopy has a potential for the interventional therapy including dilatation of strictures. We present here a case of jejunal strictures in a 47‐year‐old woman with Crohn's disease successfully treated with a balloon catheter in combination with double‐balloon enteroscopy. Balloon dilation with double‐balloon enteroscopy is a promising method for the treatment of small bowel strictures in Crohn's disease.