Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Antitumor effects of oral administration of an interferon-inducing pyrimidinone,Bropirimine, on murine renal-cell carcinoma

Bropirimine [2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone] is a low-molecular-weight compound that acts as an inducer of interferon in several animal species. Experiments were designed to explore the possibility of using this drug for the treatment of renal-cell carcinoma (RCC). Euthymic BALB/c mice were inoculated with murine RCC (Renca) cells and given graded doses of Bropirimine p.o. for 5 consecutive days beginning on day 1 following tumor inoculation. These mice were killed and tumors were excised on day 21. Bropirimine significantly (P<0.01) inhibited the tumor growth at a daily dose of 1,000 or 2,000 mg/kg. No adverse effect or toxicity was noted at 1,000 mg/kg, and at 2,000 mg/kg there was only a marginal body-weight reduction without any other appreciable side effect. In addition to the inhibition of tumor growth, there was a small yet significant (P<0.05) increase in the duration of survival (in days) in the Bropirimine-treated animals. When the treatment was delayed to begin on day 6 following tumor inoculation, Bropirimine did not suppress tumor growth in euthymic mice, pointing to the importance of the timing of the treatment. In athymic nude BALB/c mice lacking T-cells or T-cell function, Bropirimine also inhibited tumor growth (P<0.01). The antitumor effect of this drug was abolished by pretreatment with anti-asialo GM1 serum, which eliminated natural killer (NK) activity in euthymic mice. In vivo treatment with Bropirimine augmented the cytotoxicity of lymphocytes isolated from the spleens or lungs of the tumor-bearing mice, which were active against Renca and YAC-1 cells in vitro. This activity was NK-cell-dependent as judged on the basis of the results of the in vitro complement-dependent cytotoxicity assay. Since Bropirimine induced interferon (IFN)-/ production, significantly (P<0.05) elevating its serum concentration, and since this drug mimics the effects of IFN-/, it seemed likely that the Bropirimine-induced NK cell augmentation we found was mediated by IFN-/. These results suggest that Bropirimine, a booster of NK activity, may have potential as an adjunct to other therapeutic modalities in the treatment of human RCC.     

Simultaneous assessment of right ventricular function and hypertrophy by Tc-99m MIBI

PURPOSE: Tc-99m MIBI allows the simultaneous performance of cardiac blood pool scintigraphy and myocardial SPECT. The authors performed studies to determine whether right ventricular function and hypertrophy can be evaluated simultaneously using Tc-99m MIBI in patients with right heart disease. METHODS: Using right heart catheterization, several parameters of pulmonary circulation were measured, including right ventricular ejection fraction, in 23 patients with chronic pulmonary disease and pulmonary vascular disease. Within 1 week, right heart blood pool scintigraphy was performed using the first-pass method using Tc-99m MIBI. The right ventricular ejection fraction calculated from right heart blood pool scintigraphy was compared with that measured using right heart catheterization. Myocardial SPECT was performed 1 hour after right heart blood pool scintigraphy. On the short axis images, which allowed optimal visualization of the right ventricle, the right and left ventricular free walls were established as regions of interest. Myocardial wall counts were determined. The right ventricular uptake: left ventricular uptake ratio was calculated to study the relation of that ratio to mean pulmonary artery pressure and total pulmonary resistance. RESULTS: A significant correlation was observed between the right ventricular ejection fraction calculated on right heart catheterization and that calculated on right heart blood pool scintigraphy. The right ventricular uptake:left ventricular uptake ratio correlated positively with pulmonary artery pressure and total pulmonary resistance. CONCLUSION: These results suggest that Tc-99m MIBI allows simultaneous noninvasive evaluation of cardiac function and structure, which previously was considered impossible in patients with right heart disease.     

Diaphragm reconstruction with autologous fascia lata: Report of a case

When the diaphragm is excised so wiely that the defect cannot be closed directly during an operation on either thoracic or epigastric tumors, a reconstruction of the defect is necessary. We used harvested autologous fascia lata to reconstruct the diaphragm in a patient undergoing a pleuropneumonectomy with a partial diaphragmatic resection for malignant mesothelioma.     

Bright light treatment for night-time insomnia and daytime sleepiness in elderly people: comparison with a short-acting hypnotic

Night-time bright light (BL) treatment and triazolam (0.125 mg/day) were given to three healthy elderly people in a cross-over design. They kept a daytime sleepiness test and a sleep log, and their wrist-activity was monitored simultaneously. Subjectively, BL increased daytime sleepiness and naps, and decreased night-time sleep. Triazolam decreased daytime sleepiness and naps, and increased night-time sleep. Actigraphic night-time sleep and naps on the first day were similar to these results. However, on the fourth day night-time insomnia induced by BL had recovered, and naps were shorter than the baseline. Triazolam increased actigraphic naps as the days passed.     

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.     

Factors influencing joint-preserving operations in the treatment of the late stages of osteoarthritis of the hip

Between November 1983 and December 1992, 136 hips (119 patients) with coxarthritis were operated on using joint-preserving techniques based on the rationale of Pauwels' osteotomy. The criterion for selection was a patient in whom the height of the joint space in the weight-bearing area of the hip was less than 1 mm. The mean age at operation was 48 years and the mean follow-up 109 months (60 to 171). Hips were categorised using Bombelli's classification of osteoarthritis, into atrophic and non-atrophic types. The endpoint was defined as that at which the height of the joint space became less than 1 mm again. The Kaplan-Meier curve showed that the rate of survival of the non-atrophic group was significantly better than that of the atrophic group. Cox's proportional hazard model indicated that the factors influencing the results of joint-preserving operations included Bombelli's classification, postoperative incongruence of the joint and the height of the joint space.     

A clinical study of posttraumatic hydrocephalus

From 1989 to 1998, 721 patients with head injury were admitted to our department and 22 (3.1%) of them developed posttraumatic hydrocephalus. These patients included 16 males and 6 females, ranging in age from 17 to 86 years (mean age, 66 yrs) with peak incidence in the eighth decade. CT scan on admission immediately after head injury showed subarachnoid hemorrhage (SAH) in 18 cases. The other 4 cases without SAH had once suffered head injuries severe enough to give rise to consciousness disturbance. The typical clinical symptoms of hydrocephalus were observed in only 5 (23%) patients, and in the other 17 cases prolonged or deteriorated of consciousness disturbance were the main symptoms. Hydrocephalus was diagnosed between 1 and 3 months in 15 cases and in 7 cases after 4 months. Clinical improvement has been seen in 17 (77%) cases and marked recovery of consciousness was achieved in 12 cases after V-P shunt, but 5 cases with severe disturbance of consciousness revealed no improvement of clinical signs even after decrease of ventricular size. These results indicate that elderly patients with traumatic SAH should be followed up for at least 4 to 5 months, paying attention to development of hydrocephalus, and V-P shunt would be effective to improve consciousness disturbance in most of the cases.