Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

Central serous chorioretinopathy after dacryocystorhinostomy operation on the same side.

A 43-year-old man developed central serous choroidoretinopathy in his left eye following dacryocystorhinostomy operation on the same side. He was using xylometazoline nasal drops in his left nostril. Action of xylometazoline or the stress related to the operation or the effect of both factors played the role in the causation of this ocular condition. Omission of nasal drops or relief from stress resulted in full recovery of vision and complete resolution of symptoms within one month.

Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India.

A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.

Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations.

In West Bengal, India more than 6 million people are exposed to high levels of arsenic through drinking water. Since, only 15-20% of the exposed individuals show arsenic-induced skin lesions, it is assumed that genetic variation might play an important role in arsenic toxicity and carcinogenicity. Arsenic exposure often leads to the development of hyperkeratosis, the precursor of arsenic-induced skin cancer. ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) is a nucleotide excision repair pathway gene, and its SNPs have been implicated in several types of epithelial cancers. We investigated the possible association of ERCC2 codon 751 A-->C polymorphism (lysine to glutamine) with arsenic-induced hyperkeratosis and correlated ERCC2 genotypes with increased frequencies of chromosomal aberration to ascertain whether any genotype leads to sub-optimal DNA repair. For this association study, 318 unrelated arsenic exposed subjects (165 with hyperkeratosis and 153 without any arsenic-induced skin lesions), drinking water contaminated with arsenic to a similar extent, were recruited. Genotyping was done through PCR-RFLP procedure. Lys/Lys genotype was significantly over-represented in the arsenic-induced hyperkeratosis-exhibiting group [odds ratio (OR) = 4.77, 95% confidence interval (CI) = 2.75-8.23]. A statistically significant increase in both CA/cell and percentage of aberrant cells was observed in the individuals with AA genotype compared to those with AC or CC genotype combined (P < 0.01) in each of the two study groups, as also, in the total study population. This study indicates that ERCC2 codon 751 Lys/Lys genotype is significantly associated with arsenic-induced premalignant hyperkeratosis and is possibly due to sub-optimal DNA repair capacity of the ERCC2 codon 751 Lys/Lys genotype.

Association of specific p53 polymorphisms with keratosis in individuals exposed to arsenic through drinking water in West Bengal, India.

Although, more than six million people are endemically exposed to inorganic arsenic in West Bengal, India by drinking heavily contaminated groundwater, only about 300,000 people show arsenic induced skin lesions. This suggests that genetic variability plays an important role in arsenic induced skin lesions and skin cancers. Arsenic induced keratosis is considered as a possible precancerous state of in situ carcinoma. Several reports have suggested the role of p53 polymorphisms as potential marker for risk assessment of different types of cancers. This prompted us to study the association of three p53 polymorphisms with arsenic induced keratosis in a population exposed to arsenic through drinking water. A total of 366 unrelated individuals (177 individuals with arsenic induced keratosis and 189 individuals with no arsenic induced skin lesions) were recruited from North 24 Parganas, Nadia and Murshidabad districts between January 2003 and February 2005 for the study of the genotypic distribution of three p53 polymorphisms (16bp duplication at intron 3, codon 72 Arg/Pro and G>A at intron 6 [nt 13,494]) by PCR-RFLP. The arginine homozygous genotype at codon 72, and homozygous genotype of no duplication polymorphism at intron 3 were over represented in the individuals with keratosis compared with individuals with no skin lesions (OR=2.086; 95% CI=1.318-3.299 and OR=2.086; 95% CI=1.257-3.457, respectively). This study indicates that individuals carrying the arginine homozygous genotype at codon 72, and/or no duplication homozygous genotype at intron 3 are at risk for the development of arsenic induced keratosis.

Persistent conjunctivitis associated with drinking arsenic-contaminated water.

PURPOSE: The aim of this study was to report on 2 cases of bilateral chronic conjunctivitis that were associated with the drinking of arsenic-contaminated underground water for a long time. DESIGN: Interventional case reports comprised the study. METHODS: This study was a review of clinical data and laboratory investigations. RESULTS: Papillary conjunctivitis developed in 2 members of a family who has been drinking underground water for 15 years. There were severe dermatological changes, including hyperkeratosis, on palms and soles, hypo- and hyperpigmented lesions (rain-drop) on the abdomen, chest, and back. Arsenic levels estimated in the nails and hair of both patients were very high. The arsenic level of the drinking water was above the permissible limit. Histopathological examination of conjunctival tissue confirmed the inflammatory response of a papillary type; however, an arsenic estimation in conjunctival tissue was not possible. There were no inclusions of bodies in conjunctival smears stained with hematoxylin and eosin (H&E) stain. There was no response to the usual treatment for papillary conjunctivitis, which only subsided, along with a regression of dermatological changes, when patients were treated with the chelating agent, dimercaprol, and multivitamin preparations, as well as no longer drinking the contaminated water. CONCLUSIONS: This is a rare association and, to the best of our knowledge, the first report of successful treatment with dimercarpol. The source of arsenic was contaminated underground drinking water (from a deep tube-well). The pathophysiology is thought to be the result of an inflammatory response caused by accumulated arsenic in local tissues. Papillary conjunctivitis and dermatological changes can be successfully managed with dimercaprol and multivitamins. Further studies are required to find out the possible link between the papillary response of conjunctiva and arsenic accumulation within the body.

Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water.

In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15-20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenic-induced genotoxicity.

Assessment of DNA damage in peripheral blood lymphocytes of individuals susceptible to arsenic induced toxicity in West Bengal, India.

Assessment of DNA damage was carried out using alkaline comet assay in lymphocytes of 30 individuals exposed to high levels of arsenic (247.12+/-18.93 microg/l) through contaminated groundwater in North 24 Parganas district, West Bengal, India. All of them exhibited high arsenic contents in nail (4.20+/-0.67 microg/g), hair (2.06+/-0.20 microg/g) and urine (259.75+/-33.89 microg/l) samples and manifested various arsenical skin lesions. Unexposed samples were collected from 30 residents of the unaffected East Midnapur district with very little or no exposure to arsenic (7.69+/-0.49 microg/l) in drinking water. The results were evaluated principally by manual analysis of comets and partly by computerized image analysis. Both the analytical methods exhibited a high degree of agreement in results. The exposed participants expressed significantly higher DNA damage (p < 0.01) in their lymphocytes than the unexposed participants. Alkaline comet assay was also combined with formamidopyrimidine-DNA glycosylase enzyme digestion to confirm that arsenic induced oxidative base damage in the lymphocytes. Significant positive trend effects of comet lengths in relation to arsenic levels in water prove that DNA damage can be used as a sensitive biomarker of arsenic exposure. This study demonstrates that arsenic induced significant DNA damage in the exposed participants, which could correspond to a higher susceptibility to arsenic induced toxicity and carcinogenicity.