Ultrasound biomicroscopic examination of acute hydrops in patients with keratoconus

PURPOSE: To investigate the possible factors involved in the development of acute hydrops in patients with keratoconus. DESIGN: Prospective interventional case series. METHODS: Thirteen consecutive keratoconic eyes of 13 patients with acute hydrops were examined by ultrasound biomicroscopy (UBM). RESULTS: Ultrasound biomicroscopy (UBM) examinations revealed a rupture of Descemet membrane and intrastromal clefts in all eyes. In 11 of 13 eyes, the intrastromal clefts were connected to the anterior chamber. CONCLUSIONS: Formation of intrastromal clefts may be an important factor in the development of acute hydrops in keratoconic eyes. The clefts may cause severe corneal edema and delay the closure of Descemet membrane during the resolution of corneal edema.     

Influence of pupil diameter on the relation between ocular higher-order aberration and contrast sensitivity after laser in situ keratomileusis

PURPOSE: To investigate the influence of pupil diameter on the relation between induced changes in ocular higher-order wavefront aberrations and changes in contrast sensitivity by conventional laser in situ keratomileusis (LASIK) for myopia. METHODS: In 215 eyes of 117 patients (age, 33.2 +/- 8.3 years) undergoing LASIK for myopia of -1.25 to -13.5 D (-5.28 +/- 2.55 D), ocular wavefront aberrations and contrast sensitivity function were determined before and 1 month after surgery. Preoperative photopic pupil diameter was measured with a digital camera. Ocular higher-order aberrations were measured for a 4-mm pupil with a Hartmann-Shack wavefront analyzer. The root-mean-square (RMS) of the third- and fourth-order Zernike coefficients was used to represent coma- and spherical-like aberration, respectively. From the contrast-sensitivity data, the area under the log contrast sensitivity function (AULCSF) was calculated. RESULTS: One hundred five eyes had a photopic pupil diameter of 4 mm or larger, and the remaining 110 had a photopic pupil diameter smaller than 4 mm. There were no statistically significant differences in the background clinical data between these two groups. In the eyes with a photopic pupil diameter of 4 mm or larger, the changes in third-order comalike aberrations did not correlate with the changes in AULCSF (Pearson correlation coefficient, r = -0.037, P = 0.723) and 10% low-contrast visual acuity (r = 0.125, P = 0.224), but fourth-order spherical-like aberrations correlated significantly with the changes in AULCSF (r = -0.229, P = 0.024) and 10% low-contrast visual acuity (r = 0.221, P = 0.038). In the eyes with photopic pupil size smaller than 4 mm, there were significant correlations between the changes in comalike aberrations and the changes in AULCSF (r = -0.487, P < 0.001) and 10% low-contrast visual acuity (r = 0.310, P = 0.003), but spherical-like aberrations showed no correlation with the changes in AULCSF (r = -0.078, P = 0.485) and 10% low-contrast visual acuity (r = 0.208, P = 0.158). CONCLUSIONS: In eyes with larger photopic pupil diameter, increases in spherical-like aberration dominantly affect contrast sensitivity, whereas in eyes with smaller pupil size, changes in coma-like aberration exert greater influence on visual performance.     

p53 mutation spectra for squamous cell carcinomas at different levels of human bronchial branches

The question of whether squamous cell carcinomas (SCCs) arising in different sites of lung are caused by different etiological factors is of obvious importance for prevention, early detection and effective treatment. We here subclassified a large series of resected SCCs (74 cases) into 3 tumor-sites, central (main to segmental bronchi), intermediate (subsegmental to sub-subsegmental) and peripheral (distal to sub-subsegmental bronchi), and examined relationships with p53 mutational spectra and smoking history to provide clues to etiological factors. The rate for G-->A transitions at CpG sites considered to be caused by endogenous mechanism was higher in central (40%) than in intermediate (0%) and peripheral (14%) lesions, in spite of highest percentage of heavy smokers. In contrast, G-->T transversions associated with tobacco smoke carcinogens were most frequent (50%) in the intermediate location, although proportions of heavy smoker's ratio were the same among the locations when confined to p53 mutation cases. In the periphery, other mutations were highest (67%) compared with 33 and 50% in the central and intermediate regions, respectively. Thus, different etiological factors may be playing causal roles in the development of SCCs in different locations of bronchial tree. Furthermore, the results suggest that more extensive study of the influence of tobacco smoke carcinogens on endogenous mechanisms is warranted.     

2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing tumors by suppressing matrix metalloproteinase-9

Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor. 2-Deoxy-D-ribose (D-dRib), the degradation product of thymidine generated by TP activity, has been suggested to be a downstream mediator of TP function. 2-Deoxy-L-ribose (L-dRib), a stereoisomer of D-dRib, inhibited the promotion of angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that nude mice inoculated with TP-overexpressing KB/TP cells had shorter survival times than those injected with control KB/CV cells. KB/TP tumors were also more highly invasive than KB/CV tumors in mice. The expression levels of matrix metalloproteinase (MMP)-9 in KB/TP tumors were significantly higher than those in KB/CV tumors. L-dRib and a TP inhibitior, TPI, extended the survival period of KB/TP tumor-bearing mice. L-dRib also reduced MMP-9 mRNA levels in KB/TP tumors. Furthermore, L-dRib suppressed the mRNA level of MMP-9 in cultured KB/TP cells, and the invasive activity of the cells. L-dRib may be useful for the suppression of invasion of TP-expressing tumor cells.     

Methylation status of genes upregulated by demethylating agent 5-aza-2'-deoxycytidine in hepatocellular carcinoma

BACKGROUND/AIMS: To determine the clinical significance of gene promoter methylation in hepatocellular carcinoma (HCC), we examined in clinical samples the methylation status of those promoters that showed elevated activity in hepatoma cell lines after 5-aza-2'-deoxycytidine treatment. METHODS: Regarding the genes with promoter hypermethylation in the cell lines, their expression levels and methylation status in HCC and non-HCC tissues were assessed by semiquantitive RT-PCR and methylation-specific PCR. To confirm the result, the expression levels and methylation status in 16 additional HCC and non-HCC tissues were assessed. RESULTS: The promoter regions of caveolin 1 (CAV1), cysteine and glycine-rich protein 1 (CSRP1), Kruppel-like factor 6 (KLF6), myosin (light polypeptide 9) (MYL9), and transgelin (TAGLN) were highly methylated in the cell lines. CAV1 and CSRP1 were methylated in HCC more frequently than in non-HCC. KLF6, MYL9, and TAGLN were fully methylated in both HCC and non-HCC. Using additional clinical samples, downregulation of CAV1 and CSRP1 was observed in 38 and 56%, respectively, of the 16 HCC samples and aberrant methylation of CAV1 and CSRP1 was observed in 56% of HCC in both cases. CONCLUSION: CAV1 and CSRP1 were inactivated in HCC by aberrant methylation and they may serve as important biomarkers of malignancy.     

Novel heteroduplex method using small cytology specimens with a remarkably high success rate for analysing EGFR gene mutations with a significant correlation to gefitinib efficacy in non-small-cell lung cancer

We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.     

Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) trial

BACKGROUND: The Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) study was a randomized, multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large, operable (T2/3, N0-2, M0), or potentially operable (T4b, N0-2, M0) breast cancer. The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated. METHODS: Patients with hormone receptor-positive breast cancer received anastrozole (n = 228) or tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary surgery. RESULTS: Objective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0% and 46.2% of patients, respectively (caliper measurements). In hormonal therapy-only patients (n = 314), feasible surgery at baseline improved after 3 months in 43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04). In the intent-to-treat population, improvement in feasible surgery at baseline to actual surgery at 3 months was found to be numerically higher in the anastrozole group compared with the tamoxifen group, although this difference did not reach significance. Drug-related adverse events were reported in 20.2% and 18.1% of patients, respectively, in the anastrozole and tamoxifen groups. CONCLUSIONS: Anastrozole is an effective and well-tolerated preoperative therapy, producing clinically beneficial tumor downstaging and reductions in tumor volume. These effects enable more minimal surgical interventions in patients scheduled for mastectomy, and mastectomy in patients with previously inoperable tumors. Anastrozole appears to be at least as effective as tamoxifen in this setting, and more effective than tamoxifen in certain clinically relevant subgroups. Cancer 2006. (c) 2006 American Cancer Society.     

Risk factors contributing to hepatic artery thrombosis following living-donor liver transplantation

Background/Purpose This study was carried out to investigate the risk factors contributing to hepatic artery thrombosis in living-donor liver transplantation. Methods Two hundred and twenty-two recipients (113 adults and 109 children) of living-donor liver transplantation were the subjects of this study. The diagnosis of hepatic artery thrombosis was made by color-Doppler ultrasonography and/or hepatic angiography. Parameters for this study were: (1) donor sex, age, and body weight; (2) recipient sex, age, body weight, liver disease, preoperative prothrombin time, and type of arterial reconstruction; and (3) previous liver transplantation. Results Hepatic artery thrombosis occurred in 12 patients (5.4%) at 3 to 15 days posttransplant. Recipient female sex and metabolic disorder as the original disease were found to be significantly associated with hepatic artery thrombosis. The 5-year patient survival rate in recipients with hepatic artery thrombosis (58.3%) was significantly lower than that in recipients without this complication (84.4%). Conclusions Female sex and metabolic disease may be factors contributing to hepatic artery thrombosis after living-donor liver transplantation. More intensive anticoagulation therapy for this patient population might decrease the incidence of hepatic artery thrombosis and, thus, posttransplant recipient mortality.     

Questionnaire on Perioperative Antibiotic Therapy in 2003: Postoperative Prophylaxis

We distributed a questionnaire to institutions accredited by the Japan Surgical Society asking about the use of antibiotics in digestive tract surgery in Japan in 2003, and compared the results with those of a similar questionnaire distributed in 1993. The period of antibiotic administration for esophageal resection was at least 6 days in 64.9% of the 1993 questionnaire responses, but less than 4 days in 60.4% of the present questionnaire responses. For distal gastrectomy, antibiotics were given for 5 days postoperatively at 53.0% of the responding institutions in the 1993 survey, but for only 3 days, at 72.4%, in the present survey. An oral antibiotic was given as part of antibacterial colon preparation before colon resection at 70% or more of the institutions in the 1993 survey, while no antibiotic colon preparation was given at 80% of the institutions in the present survey. The period of antibiotic administration for laparoscopic cholecystectomy was at least 4 days in 72% of the institutions in the 1993 survey, but this decreased remarkably to fewer than 2 days at 80.8% of the institutions in the current survey. There were no differences in the selection of antibiotics between the two surveys. The period of antibiotic administration has decreased remarkably in the last decade.