Surgical removal of juxtafoveal and extrafoveal choroidal neovascularization in age-related macular degeneration

PURPOSE: In the treatment of age-related macular degeneration (AMD), the effect on the fovea of photocoagulation of juxtafoveal choroidal neovascularization(CNV) and extrafoveal CNV near the fovea has been of concern, and so usefulness of surgical excision of CNV was evaluated. SUBJECTS AND METHODS: Fifteen eyes with AMD that underwent removal of juxtafoveal CNV and extrafoveal CNV near the fovea and had been followed for over one year were included in this study. Eligibility criteria were preoperative visual acuity of 0.3 or less and evidence of CNV activity by fundus angiography. RESULTS: Visual acuity of 0.4 or more was obtained in 60% of the eyes with best visual acuity and 47% with final visual acuity. The mean best visual acuity was 0.51 in cases with Gass type 2, 0.51 in type 1 + 2 CNV, and 0.21 in type 1 CNV. Good post-operative visual acuity was obtained in type 2 and 1 + 2 cases with type 2 CNV at the foveal side accompanied by preoperative foveal retinal sensitivity of 25 dB or more. There was little improvement of visual acuity in type 1 CNV because the retinal pigmented epithelium defect occurred at the fovea. CONCLUSION: For juxtafoveal CNV and extrafoveal CNV near the fovea in AMD, type 2 and 1 + 2 cases with type 2 CNV at the foveal side are thought to be candidates for surgery. Especially, relatively good postoperative visual acuity was obtained in cases with preoperative foveal retinal sensitivity of 25 dB or above. Active surgical removal is thought to be indicated for these cases.     

Evaluation of oxidative stress during apoptosis and necrosis caused by D-galactosamine in rat liver

Eighteen and twenty-four hours after intraperitoneal administration of D-galactosamine (1g/kg body weight) to rats, the activity of caspase-3-like protease in the liver increased significantly compared with that in the control group given saline. Histological examinations including the in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method found apoptotic hepatocytes 18 hr after the administration of D-galactosamine. Caspase-3 activity was barely detectable in the plasma of control rats, but increased significantly 24 hr after drug administration along with a dramatic increase in glutamate-oxaloacetate transaminase (GOT). These results indicated that D-galactosamine causes apoptosis in the liver by activating caspase-3, which is released to the plasma by secondary necrosis. The concentration of lipid hydroperoxides in the liver increased significantly 24 hr after D-galactosamine administration. In contrast, the concentration of vitamin C in the liver decreased significantly 18 and 24 hr after D-galactosamine administration. These results suggest that D-galactosamine induces severe oxidative stress in the liver, leading to extensive necrosis.     

Postoperative recurrence of venous thromboembolism in patients with episodes of preoperative thromboembolism

BACKGROUND: Venous thromboembolism (VTE) has become a major health problem in Japan. METHODS: We examined, postoperative recurrence of VTE in patients with preoperative venous thromboembolic events and evaluated factors that are relevant to the occurrence of postoperative VTE. RESULTS: Forty-four cases out of 38500 had been diagnosed preoperatively as having VTE in the period of 1995-2001 at Kitasato University Hospital. Postoperative VTE was detected in four patients (9%) out of these 44 cases. Patients who had thrombophilia (antiphosholipid syndrome) or recent episode of VTE within 1 month were higher in the incidence of postoperative recurrence of VTE than the others. Temporary infra-vena cava filters were placed to prevent pulmonary thromboembolism in twelve patients. In 8 of the patients, thrombi were detected in or at the filter before explantation. Three patients (7%) had undergone thrombolysis therapy. Postoperative VTE was not found in patients who had already received anticoagulant therapy (warfarin) for 3 or more months. CONCLUSIONS: It is concluded that newly developed VTE occurred perioperatively in 9% of patients with preoperative VTE, and that thrombophilia and a recent episode of VTE were considered as risk factors of perioperative VTE. Temporary infra-vena cava filters are a valuable device for prevention of postoperative pulmonary thromboembolism.     

The effect of repeated sevoflurane anesthesia on hepatic function and immunological system

BACKGROUND: Sevoflurane is known as a useful and safe anesthetic because of its properties of fast uptake and elimination at the lungs and of no effects on hepatic function. In this study we examined the effect of repeated sevoflurane anesthesia on hepatic function and immunological system. METHODS: Eight patients (ASA, PS 2 or 3) received sevoflurane anesthesia three times in 6 months. Six patients had emergency operation for injuries. Aspirate transaminase (AST), alanine transaminase (ALT) and complements (CH50, C3, C4) were measured prior to anesthesia, and 1, 7 and 14 days after anesthesia. RESULTS: The values of AST and ALT were high prior to anesthesia at the first anesthesia. However, these were of no significant changes. CH50, C3, C4 increased significantly after the first anesthesia. However, there were no significant changes of these complements after the second and the third anesthesia. CONCLUSIONS: Our results suggest that sevoflurane is not likely to provide adverse effects on the liver and to suppress the production of complements accompanied by the surgical stress.     

Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular carcinoma

Although dendritic cells (DCs) play an important role in tumor immunity, there have been no reports on their role in cholangiocellular carcinoma (CCC). In 26 formalin-fixed, paraffin-embedded tissue sections from patients with CCC, cells positive for CD83 (a marker of mature DCs), CD1a (a marker of immature DCs), and CD8 and CD4 (T cell markers) were counted, and expression of glucose-regulated protein (grp) 94, which is considered to participate in the maturation of DCs, was evaluated by immunohistochemistry and Western blot analysis to study the relationship between their expression and patients' disease outcome. The number of CD83-positive DCs at the invasive margin of CCCs correlated significantly with the number of CD8-positive or CD4-positive T cells in the cancerous region and was significantly higher in grp94-positive cancer than in grp94-negative cancer (P = 0.0006). CD83-positive patients (positive cells in invasive margin > 12.4/field) had both a significantly lower incidence of lymph node metastasis (23.1% vs 69.2%; P = 0.0206) and a better outcome than CD83-negative patients (P <0.001). We conclude that mature DCs are distributed predominantly at the invasive margin of cancers, and a significantly higher number of mature DCs at the invasive margin are observed in patients with grp94-positive cancer cells. Mature DCs may enhance CD8- and CD4-positive cell infiltration into cancers and improve prognosis in patients with CCC, due in part to abatement of lymph node metastasis.     

Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization: its association with DNA methylation alteration and patient outcome

PURPOSE: The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. EXPERIMENTAL DESIGN: Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361 bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1, von Hippel-Lindau, and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51 clear cell renal cell carcinomas (RCC). RESULTS: By unsupervised hierarchical clustering analysis based on copy number alterations, clear cell RCCs were clustered into the two subclasses, clusters A (n=34) and B (n=17). Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of 1p, 4, 9, 13q, and 14q was frequent only in cluster B. The average number of methylated CpG islands in cluster B was significantly higher than those in cluster A. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B. The recurrence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. CONCLUSIONS: This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC.     

Delivery outcomes following loop electrosurgical excision procedure for microinvasive (FIGO stage IA1) cervical cancer

OBJECTIVE: The goal of this study was to report the delivery outcomes in women who had loop electrosurgical excision procedure (LEEP) for microinvasive cervical cancer (stage IA1 without lymphovascular invasion) and became pregnant and progressed beyond 24 weeks. METHODS: A case-control study was performed. Twenty-eight women who were managed exclusively with LEEP for microinvasive cervical carcinoma had at least one pregnancy beyond 24 weeks and were the cases. Each case was matched with one woman who delivered at the same department without prior treatment of her cervix (controls) and their delivery outcomes were compared with those of the cases. Known risk factors for preterm delivery were used as matching factors. RESULTS: There was no statistically significant difference (P > 0.05) between cases and controls in the duration of pregnancy (37.6-38.4 weeks respectively), birth weight (3212-3315 g), cesarean section rate (17.8-32.1%), neonatal unit admission rate (21.4-10.7%), and precipitate labor rate (13-10.5%). The duration of labor was significantly shorter in cases (5.5-7.1 h, P = 0.032). After LEEP the relative risk for preterm delivery is 3.67 (95% confidence interval, 0.97-20.27), for low birth weight infant 0.67 (0.06-5.8), for precipitate labor 1 (0.05-3.88), and for delivery by cesarean section 0.5 (0.17-4.46). CONCLUSIONS: Women treated for microinvasive cancer with LEEP did not have significantly more delivery complications compared with controls apart from shorter duration of labor. There was a possible non-statistically significant trend toward shorter duration of pregnancy in cases. While caution should be advised when selecting and treating women with microinvasive carcinoma by LEEP, the apparent safety of the management and the satisfactory delivery outcome seem to justify this approach in many cases.     

Gesashidine A, a beta-carboline alkaloid with an imidazole ring from a Thorectidae sponge

A new beta-carboline alkaloid with an imidazole ring, gesashidine A (1), has been isolated from an Okinawan marine sponge of the family Thorectidae (SS-1035), and the structure was elucidated from the spectroscopic data.