How frequent are invasive therapies required in patients receiving tamsulosin for benign prostatic hyperplasia? A retrospective long‐term study

Three hundred Japanese patients with benign prostatic hyperplasia (BPH) who started an alpha1-adrenoceptor blocker, tamsulosin, between 1993 and 1996 were followed for 3.0+/-3.3 years (mean+/-SD) to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented. Patients with a lower quality of life (QOL) index or maximum urinary flow rate (Qmax) were transferred for invasive therapy earlier than those with less severe BPH. The International Prostate Symptom Score (I-PSS) was also associated, but apparently to a lesser extent, with the timing of the invasive therapy. Finally, the overall severity evaluated using all of the above three indices, I-PSS, QOL index, and Qmax, in accordance with the 'Severity Criteria for BPH' issued by the Japanese Urological Association, was found to be a good measure for predicting the prognosis of patients with BPH treated with tamsulosin.     

Bisphosphonate induces apoptosis and inhibits pro-osteoclastic gene expression in prostate cancer cells

AIM: Bisphosphonates are well established for the management of cancer-induced skeletal complications. Recent studies suggest that bisphosphonates promote apoptosis of cancer cells as well as osteoclasts in bone metastatic sites. To determine the direct effects of bisphosphonate on prostate cancer, we examined the effects of minodronate on prostatic cancer cell growth and the expression of apoptosis-related proteins and osteoclastogenic factors. METHODS: PC-3, DU145 and LNCaP cells were treated with amino-bisphosphonate minodronate. Then proliferation, apoptosis and expression of bcl-2, bax, poly (ADP)-ribose polymerase (PARP), caspase-3, receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinases-2 (MMP-2), and parathyroid hormone related protein (PTHrP) were assessed. RESULTS: The proliferation of prostatic cancer cells was inhibited by minodronate. DNA fragmentation and TUNEL-positive nuclei were observed in minodronate-treated PC-3 cells. Minodronate decreased bcl-2 expression and induced bax expression, caspase-3 activity and degradation of PARP in DU145 and PC-3 cells. Minodronate decreased expression of RANKL, PTHrP and MMP-2 in PC-3 cells. CONCLUSIONS: Our results suggest that bisphosphonate not only promotes apoptosis directly but also decreases pro-osteoclastic gene expression in prostate cancer cells.     

Liver cell adenoma: A case report and a review of 30 cases reported in Japan

A 38 year old man with a huge liver cell adenoma extending to the pelvis was treated by left lateral lobectomy. The tumour, which was well-encapsulated by fibrous membrane, was 18 × 19 × 6 cm in size and weighed 1500g. Histopathologically, this tumour was composed of well-differentiated liver cell trabeculae and a small number of pseudobiliary ducts, but no Glisson sheaths. For the past 4 years 8 months he has remained asymptomatic. Thirty cases of liver cell adenoma found in Japanese literature are reviewed here and possible pathogenic implications are discussed.     

Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma

To assess the characteristics of intrahepatic metastatic lesions (IML) in hepatocellular carcinoma (HCC), we analysed both the histological features and proliferative activities of 15 resected cases of HCC accompanied by IML. The histological features of the IML were essentially the same as those observed in the main nodules in 12 (80%) of 15 cases. In 13 (87%) of 15 cases, the labelling index of proliferating cell nuclear antigen (PCNA) in the IML was either higher than or the same as in the main nodules. In 10 (77%) of 13 cases, the MIB-1 labelling index in the IML was either higher than or the same as in the main nodules. The results indicate that the histological features of the IML are essentially the same as those of the main nodules, while the proliferative activities in the IML were generally higher than those in the main nodules. Such characteristics may thus provide a clue to help distinguish intrahepatic metastasis from the multicentric occurrence of HCC.     

LONGITUDINAL STUDY OR SERUM THYROID HORMONES, CHORIONIC GONADOTROPHIN AND THYROTROPHIN DURING AND AFTER NORMAL PREGNANCY

Measurements of serum levels of thyroxine (T4), free T4, 3,5,3'-triiodothyronine (T3), free T3, 3,3',5'-triiodothyronine (reverse T3, rT3), thyroxine-binding globulin capacity (TBGcap), chorionic gonadotrophin (hCG) and thyrotrophin (TSH) were carried out prospectively in eight women with uncomplicated pregnancies, in order to examine interrelationships between the thyroid gland and thyroid stimulating hormones during pregnancy. During pregnancy the levels of T4, free T4, T3, rT3 and TBGcap were significantly elevated, and TSH was decreased. It was noted that the elevation of T4 was maintained from the 8th to the 27th week of gestation while the level of TBGcap progressively increased. The levels of free T4 and rT3 in the first and third trimesters were significantly higher than those of age-matched, non-pregnant women. The levels of hCG showed a biphasic variation, with a peak in the 8th to 15th weeks, followed by a decline in the second trimester and a small, secondary elevation in the 32nd to 39th weeks. This later elevation was positively correlated with changes in free T4 and free T3 levels. The increase of serum T4 accompanied by an increase of free T4 in the first trimester appeared due to augmented secretion of T4, rather than being secondary to the elevated levels of TBGcap.     

1-溴丙烷对两种雄性大鼠肝脏毒性的研究

目的研究1-溴丙烷对两种雄性大鼠的肝脏毒性及谷胱甘肽S-转移酶(GST)在肝脏解毒代谢中的作用。方法将18只Fischer344大鼠和18只Wistar大鼠分别随机分为两组,一组给予新鲜空气,一组给予1000ppm1-溴丙烷,每天8h,连续暴露4周。通过血浆的生化指标和病理切片对肝脏的功能和形态进行了评价。利用化学比色法和实时定量PCR法对肝脏中的GST的活力和基因表达水平进行测量。结果1-溴丙烷暴露可引起两种大鼠体重的下降及肝脏重量的上升;病理发现肝脏中央静脉周围的肝细胞出现空泡样改变,血浆中CK、ALT和TBIL和DBIL等指标上升明显;两种大鼠肝脏细胞胞浆的GST活力增强,Fischer344大鼠微粒体GST的活力也增强;肝脏组织的GSTmRNA表达水平升高。结论1-溴丙烷暴露对两种雄性大鼠具有肝脏毒性,GST在1-溴丙烷的肝脏解毒代谢中可能起到较重要作用。     

Nation-wide Brain Tumor Registry-based Study of Intracranial Meningioma in Japan: Analysis of Surgery-related Risks

Although surgical resection is the most preferred treatment for intracranial meningiomas, a detailed analysis of the surgery-related risks based on large population data has not been conducted to date. In this study, we analyzed the nation-wide brain tumor registry to assess the surgical risk factors for intracranial meningiomas to provide information for an optimal treatment strategy. Data of 4081 meningioma patients who underwent initial resection between 2001 and 2008 were extracted from the Brain Tumor Registry of Japan (BTRJ) database and reviewed for postoperative mortality, aggravation of Karnofsky Performance Score (KPS), and complications. The total in-hospital mortality rate was 0.59%. Male sex and tumor size ≥30 mm were independent risk factors for mortality. Among 4081 cases, 4.4% of patients had KPS that were lowered by 20 or more points at the time of discharge after surgery. Age ≥65 years, higher WHO grading, tumor location at the skull base, tumor size ≥30 mm, and non-gross total resections were associated with lowering of KPS scores by 20 or more points. The overall incidence of surgical complications was 19.3%. The rate of occurrence of new postoperative seizure in patients with supratentorial meningioma was 10.9%. All complications except for vascular complications occurred with significantly lower frequencies in asymptomatic patients than in symptomatic patients. Our results provide useful information regarding the surgical risks when surgical intervention is being considered for intracranial meningiomas. Surgery is an important option for asymptomatic meningiomas as the mortality rate and complication rate in the current study were sufficiently low.     

Permeability of NS-3, a Thyrotropin-releasing Hormone Analogue,into the Brain After Its Systemic Administration in Rats: A Microdialysis Study

The concentration of NS-3 (montirelin hydrate, CG 3703), a thyrotropin-releasing hormone (TRH) analogue, in the cerebral cortex of urethane-anaesthetized rats was measured after its systemic administration (1 mgkg^?1, i.v.), using in-vivo microdialysis coupled with a radioimmunoassay. The concentration in microdialysates was highest (24nM) during the first 20 min after injection, and it fell below the detection limit (3.5 nM) 100 min after treatment. The maximal interstitial concentration was estimated to be 0.51 μM. From these results, it is suggested that NS-3 can readily penetrate into the brain.     

Detection of Philadelphia Chromosome in Chronic Neutrophilic Leukemia

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferativedisorder, differentiated from chronic myelogenous leukemia byseveral features. A case of CNL which was found by long-termculture to involve the Philadelphia chromosome is reported.