PURPOSE:Keratoconus (KC) is a bilateral, noninflammatory, and progressive corneal ectasia that occurs mostly as a sporadic disorder, but it has long been recognized that a significant minority of ...patients also exhibit a family history. In recent years, several candidate genes, including VSX1 and SOD1, have been proposed and some disease-causing mutations have been identified.
METHODS:To investigate the role of the 2 genes in 113 Slovenian patients with sporadic and familial KC, the complete coding region with corresponding intronic sequences was analyzed. The same regions of both genes were also checked in 100 healthy blood donors. We also checked the relation of 627+23G>A polymorphism in the VSX1 gene with the hereditary form of the disease.
RESULTS:No disease-causing mutations were identified in either gene. We did discover a significant association of 627+23G>A polymorphism distribution (VSX1) with unrelated patients diagnosed with the hereditary form of KC.
CONCLUSION:The absence of pathogenic mutations in our large number of unrelated patients with KC indicates that other genetic factors are involved in the development of this disorder.
Serum cystatin C, a cysteine protease inhibitor, has been suggested as a new marker of glomerular filtration rate (GFR). This study explored the possibility of replacing the creatinine clearance ...(CrCl) estimation of GFR with cystatin C in early detection of renal impairment in cancer patients on chemotherapy.
Serum creatinine and cystatin C concentrations as well as 24-h CrCl were determined simultaneously in 72 cancer patients. Among them, 60 were treated with combined chemotherapy with cisplatin (CDDP). Creatinine was determined enzymatically with a spectrophotometric method. Serum cystatin C was determined by a particle-enhanced turbidimetric immunoassay.
Cystatin C and creatinine correlated significantly (P = 0.001) with CrCl. The correlation was significantly better for cystatin C than creatinine (r = 0.84 vs 0.74; P = 0.01). Stepwise regression analysis identified no differences for the correlations between cystatin C and CrCl in patients with or without metastases (r = 0.82 and 0.84, respectively) as well as before treatment and before the fourth cycle of chemotherapy (r = 0.70 and 0.75, respectively). A cystatin C cutoff concentration of 1.33 mg/L had 87% sensitivity and 100% specificity for detecting CrCl <78 mL/min. ROC analysis indicated that cystatin C was superior to serum creatinine for predicting CrCl <78 mL/min (P <0.04).
Serum cystatin C is superior to serum creatinine for detection of decreased CrCl and potentially for the estimation of GFR in cancer patients independent of the presence of metastases or chemotherapy.
Alterations in collagen type IV, alpha-3 (COL4A3) and collagen type IV, alpha-4 (COL4A4) genes may be responsible for a decrease in collagen types I and III, a feature often detected in keratoconus ...(KC). To evaluate the significance of alterations in COL4A3 and COL4A4 genes in KC patients, we screened both genes and estimated the significance of polymorphisms in Slovenian patients with KC.
The study included 104 unrelated patients with KC and 157 healthy blood donors. Diagnosis was established by clinical examination, electronic refractometry, and keratometry. DNA was extracted from blood, and gene exons were amplified by PCR. Non-isotopic high-resolution single-stranded conformation analysis (SSCA) was used to screen COL4A3 and COL4A4 genes, and migration shifts detected by SSCA were subsequently sequenced. For statistical evaluation, control blood donors were chosen according to age, sex, and not having blood relationship. Neither patients nor control blood donors chosen for statistical analysis were in blood relationship. We used Fisher's exact test for statistical evaluation, with p<0.05 considered significant.
We detected eight polymorphisms in the COL4A3 gene and six in the COL4A4 gene. Allele differences in D326Y in COL4A3 and M1237V and F1644F in COL4A4 are significantly distinctive of KC patients (Fisher's exact test, p<0.05). When analyzing different genotypes under three models (dominant, recessive, and additive), we established that P141L, D326Y, and G895G in COL4A3 and P482S, M1327V, V1516V, and F1644F in COL4A4 have significant differences in genotype distribution between KC patients and the control group.
This is the first mutational screening of COL4A3 and COL4A4 genes in KC patients to establish the status of these genes and compare them to a control population. Analysis of COL4A3 and COL4A4 revealed no mutations related to KC patients, but specific genotypes of seven previously described polymorphisms are significantly associated with KC under dominant, recessive, or additive models. Differences in the expression of type IV collagen in previously published data about chromosomal instabilities in the regions in which the analyzed genes were mapped and our data indicate a probability that some of the polymorphisms we detected could be related to KC.
Corneal collagen cross-linking increases the stability of the cornea through the use of the photosensitive materialriboavin (vitamin B2) and ultraviolet A radiation. Progressive keratoconus is the ...most common indication and the frequency of these procedures is increasing worldwide. As cross-links in the cornea are a physiological principle of all connective tissues, additional indications were proposed. These include post-refractive surgery ectasia, bullous keratopathy, and, infectious keratitis. Without proper antimicrobial therapy, infectious keratitis can lead to blindness. But even prompt initial management with appropriate antimicrobial treatment depends on microorganism sensitivity and resistance. This article presents current data regarding the use of corneal collagen cross-linking in the treatment of corneal infections. This treatment modality may become important, but unanswered questions remain. Larger, prospective comparative studies should provide the answers.
Genetics and clinical characteristics of keratoconus Stabuc-Silih, Mirna; Strazisar, Mojca; Ravnik-Glavac, Metka ...
Acta dermatovenerologica Alpina, Panonica, et Adriatica,
01/2010, Letnik:
19, Številka:
2
Journal Article
Recenzirano
Keratoconus (KC) is a bilateral, non-inflammatory, and progredient corneal ectasia that mostly occurs as a sporadic disorder, but it has long been recognized that a significant minority of patients ...also exhibit a family history. In recent years several candidate genes such as VSX1 and SOD1 have been proposed, and some disease-causing mutations have been identified. Lately research has also focused on collagen genes, especially those that are differentially expressed in KC cornea. Alterations in COL4A3 and COL4A4 genes may be responsible for decreases in collagen types I and III, a feature often detected in KC. To investigate the role of all four genes in 113 Slovenian patients with sporadic or familial keratoconus, DNA extraction, polymerase chain reaction amplification, and sequencing of both genes were performed. No disease-causing mutations were found, but two previously identified single nucleotide polymorphisms were identified (A128A and 627+23G>A) in the VSX1 gene. D326Y in COL4A3 and M1237V and F1644F in COL4A4 were also found to be significantly associated with KC patients. The absence of pathogenic mutations in VSX1, SOD1, COL4A3, and COL4A4 genes in our large number of unrelated keratoconus patients indicates that other genetic factors are involved in the development of this disorder; nevertheless, a significant correlation of a few polymorphisms indicates that there could be a link between specific polymorphisms and KC disease.
Corneal collagen cross-linking increases the stability of the cornea through the use of the photosensitive material - riboflavin (vitamin B2) and ultraviolet A radiation. Progressive keratoconus is ...the most common indication and the frequency of these procedures is increasing worldwide. As cross-links in the cornea are a physiological principle of all connective tissue, additional indications were proposed. These include postrefractive surgery ectasia, bullous keratopathy, and, infectious keratitis.Infectious keratitis can lead to blindness without proper antimicrobial therapy. But even prompt initial management, with appropriate antimicrobial treatment, can be subjected to microorganism sensitivity and resistance.This article presents current data regarding the use of corneal collagen cross-linking in the treatment of corneal infections. This treatment modality may become important, but unanswered questions remain. Larger, prospective comparative studies should give the answers.
Corneal collagen cross-linking increases the stability of the cornea through the use of the photosensitive material - riboflavin (vitamin B2) and ultraviolet A radiation. Progressive keratoconus is ...the most common indication and the frequency of these procedures is increasing worldwide. As cross-links in the cornea are a physiological principle of all connective tissue, additional indications were proposed. These include postrefractive surgery ectasia, bullous keratopathy, and, infectious keratitis.Infectious keratitis can lead to blindness without proper antimicrobial therapy. But even prompt initial management, with appropriate antimicrobial treatment, can be subjected to microorganism sensitivity and resistance.This article presents current data regarding the use of corneal collagen cross-linking in the treatment of corneal infections. This treatment modality may become important, but unanswered questions remain. Larger, prospective comparative studies should give the answers.
Contact lenses are freely available without professional examination and fitting, as well as without adequate introduction and instructions on handling, disinfection and storage. Contact lenses may ...have physiological, metabolic and anatomic effect on the eyes, which is manifested both on the eyelids, lacrimal film, conjunctiva and in all layers of the cornea - the epithelium, stroma and the endothelium. We can see these complications too often at our everyday work. The purpose of this paper is to draw attention to the potential complications due to inappropriate use of contact lenses.Contact lenses are otherwise a safe and effective method of correcting visual acuity; they are also useful for therapeutic purposes. Complications related to contact lenses wear could be largely avoided with an appropriate professional approach and the compliance of contact lens wearers. It is important to discuss with patients their medical history, their desires and expectations, their working and living environment; followed by professional examination of patients and appropriate fitting of contact lenses. Patients should receive detailed oral and written instructions and be subscribed to regular checks. But unfortunately, all this is not enough, if patients do not comply every day with given instructions.
Contact lenses are freely available without professional examination and fitting, as well as without adequate introduction and instructions on handling, disinfection and storage. Contact lenses may ...have physiological, metabolic and anatomic effect on the eyes, which is manifested both on the eyelids, lacrimal film, conjunctiva and in all layers of the cornea - the epithelium, stroma and the endothelium. We can see these complications too often at our everyday work. The purpose of this paper is to draw attention to the potential complications due to inappropriate use of contact lenses.Contact lenses are otherwise a safe and effective method of correcting visual acuity; they are also useful for therapeutic purposes. Complications related to contact lenses wear could be largely avoided with an appropriate professional approach and the compliance of contact lens wearers. It is important to discuss with patients their medical history, their desires and expectations, their working and living environment; followed by professional examination of patients and appropriate fitting of contact lenses. Patients should receive detailed oral and written instructions and be subscribed to regular checks. But unfortunately, all this is not enough, if patients do not comply every day with given instructions.
Contact lenses are freely available without ophthalmic examination and fitting, as well as without adequate introduction and instructions on handling, disinfection and storage. Contact lenses may ...have physiological, metabolic and anatomic effect on the eyes, which is manifested both on the eyelids, lacrimal lm, conjunctiva and in all layers of the corneathe epithelium, stroma and the endothelium. We can see these complications too often at our everyday work. The purpose of this paper is to draw attention to the potential complications due to inappropriate use of contact lenses.
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