Three cases of corneal melting after instillation of a new nonsteroidal anti-inflammatory drug

PURPOSE: Three cases of corneal melting caused by a new nonsteroidal anti-inflammatory drug (NSAID), bromfenac sodium, are reported. CASE REPORTS: Case 1: A 58-year-old man with a history of bullous keratopathy caused by Fuchs' corneal dystrophy was treated for episcleritis with topical bromfenac sodium. After 15 days of treatment, melting (80% depth) was observed inferiorly in the paracentral cornea. Case 2: A 71-year-old man underwent uncomplicated pterygium surgery, followed by treatment with topical bromfenac sodium. After 40 days of treatment, a 60%-depth corneal melt occurred in the nasal limbus. Case 3: A 76-year-old woman had a suspected bacterial corneal ulcer that resolved with topical ofloxacin; however, after 5 days of treatment with topical bromfenac sodium, a perforation occurred in the inferonasal cornea. RESULTS: In all three cases, severe corneal melting was characterized by mild hyperemia, very faint infiltration, and mild pain. Conservative treatment, including the use of a bandage soft contact lens and/or antibiotics and lubrication, led to resolution in all cases. CONCLUSIONS: A new NSAID, bromfenac sodium, can lead to severe corneal melting. These findings, together with similar previous reports concerning diclofenac sodium and ketorolac, suggest that careful observation is required when using topical NSAIDs in the treatment of corneal disease.     

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.     

Prospective study of vegetable consumption and liver cancer in Japan

We examined the relationship between vegetable consumption and the risk of death from liver cancer in a cohort study in Japan. This analysis is based on data from 6,049 subjects aged 40 to 79 years enrolled in a cohort study conducted in Fukuoka Prefecture, Japan. The follow-up period was from 1986 to 1999. All liver cancer deaths were recorded. The vegetable consumption was classified into 3 groups: "once per week or less," "2-4 times per week" and "daily intake." The Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence interval (95% CI). A total of 51 male and 22 female liver cancer deaths were recorded during 62,343 person-years of follow-up. The "once per week or less" group was considered the referent group. In males, the multivariate HRs of liver cancer deaths were 0.61 (95% CI: 0.33-1.14) and 0.25 (95% CI: 0.11-0.59) in the "2-4 times per week" and "daily intake" groups, respectively. In females, the multivariate HRs were 0.44 (95% CI: 0.13-1.51) and 0.51 (95% CI: 0.16-1.69), respectively. The multivariate HRs were also reported by history of hepatitis and cirrhosis. In those without a history of these conditions, the multivariate HRs were 0.54 (95% CI: 0.27-1.09) and 0.36 (95% CI: 0.16-0.83). In those with a history of these conditions, the multivariate HRs were 0.58 (95% CI: 0.22-1.56) and 0.37 (95% CI: 0.13-1.06), respectively. Our study reveals an inverse association between vegetable consumption and the risk of death from liver cancer. These results provide further evidence of the protective effect of vegetables against liver cancer.     

Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population

Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene-alcohol interactions on HCC risk remain to be elucidated. We conducted a case-control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two-pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)]. Multiple logistic regression analyses revealed that heavy drinkers consuming >or=3 "go"s/day of sake (69 g of ethanol/day) showed an increased risk of HCC based on comparison of HCC cases with hospital controls [adjusted odds ratio (OR) = 13.5; 95% confidence interval (CI) 3.3-54.3] or CLD patients (adjusted OR = 7.0; 95% CI 2.5-19.2), whereas the overall risk was not elevated among light to moderate drinkers consuming <3 "go"s/day. Interestingly, light to moderate drinking was associated with an increased risk among those with ALDH2*1/*2 (adjusted OR = 4.5 or 2.0), but not among those with ALDH2*1/*1 (adjusted OR = 0.8 or 1.0; p interaction = 0.03 or 0.13). However, this gene-alcohol interaction was not observed for heavy drinking. Among light to moderate drinkers, people with the combination of ALDH2*1/*2 and ADH2*2/*2 revealed the highest risk of HCC. These findings indicate that the ALDH2 polymorphism may modify HCC risk among light to moderate drinkers.     

Overtime work, cigarette consumption, and addiction to cigarette among workers subject to mild smoking restrictions

The goal of the present study was to investigate the relation of hours of overtime work to cigarette consumption and addiction to cigarette, which was measured by the heaviness of smoking index. The subjects were 571 male daily smokers who responded to a cross-sectional survey of municipal employees of a Japanese city office, in which smoking was permitted in designated areas. Those who engaged in moderate overtime work (10-29 h per month) consumed less number of cigarettes per day and had lower levels of heaviness of smoking index, compared with those who worked either shorter or longer hours of overtime, although the differences were not statistically significant. In the workplace, men who worked 50 h or longer overtime last month consumed, on average, 4 cigarettes more than men who worked less than 30 h of overtime. Home cigarette consumption decreased as hours of overtime work increased. In stratified analysis, there was a significant difference in daily cigarette consumption according to hours of overtime work among smokers in staff position or under low psychological work stress; showing reduced consumption associated with medium levels of overtime work, compared to either no overtime work or extended overtime hours. The U-shaped relations of hours of overtime work to overall cigarette consumption and addiction to smoking deserve further investigations.