Onset signs, clinical course, prognosis, treatment and outcome of adult patients with Adamantiades-Behçet's disease in Greece.

OBJECTIVES: To examine the onset signs, clinical course, prognosis, treatment and outcome of Adamantiades-Behçet's disease in adult Greek patients during a 10-year follow-up period, and to compare the results with those of other series reported. METHODS: The studied population consisted of 82 adult patients (54 male and 28 female) of Greek origin. Patients filled out a standard questionnaire and were followed up regularly. The findings during the follow-up of these patients were compared with those of other series. RESULTS: The most frequent onset sign was oral aphthae, both in our patients and in those of other published series. Eye involvement, joint involvement, genital ulcers and skin lesions followed in frequency. During a 10-year follow-up differences were observed between men and women, with arthritis being more frequent in females compared to males and with an overall more severe course in males. Eye involvement occurred earlier than neurological and vascular manifestations. A few differences were found in the clinical parameters in comparison to previously reported ethnic series. HLA-B51 positive patients presented an odds ratio of 9.5, the activity index was 5.17 +/- 2.56 and the mean severity score 5.96 +/- 2.32. Early treatment led to improvement of the disease. CONCLUSION: The pattern of Adamantiades-Behçet's disease in adult Greek patients provides major similarities when compared to patterns in various other national groups.

Sequencing-based typing of HLA-B*51 alleles and the significant association of HLA-B*5101 and -B*5108 with Behçet's disease in Greek patients.

Behçet's disease (BD) is widely known to be strongly associated with human leukocyte antigen (HLA) B51 in many different ethnic groups.Recently, HLA-B51 allele typing of Greek BD patients was performed to study the distribution of B*5101-B*5107 alleles in this Greek population, the B51 antigen strongly associated with BD was found to be predominantly encoded by allele B*5101. As it is now known that the B51 antigen can be encoded by 21 alleles, B*5101-B*5121, we performed HLA-B*51 allele genotyping among 58 Greek patients with BD. After serological HLA typing, typing of HLA-B*51 alleles was performed using the polymerase chain reaction-sequencing-based typing (PCR-SBT) method. The frequency of the B51 antigen was found to be significantly higher in the patient group as compared with the control group (75.9% of patients vs 22.0% of controls. In the genotyping of B51 alleles, 34 out of 44 B51-positive patients possessed B*5101, 13 out of the 44 carried B*5108. In contrast, all of the 9 B51-positive normal controls carried B*5101. This study revealed a strong association between Greeks with BD, both B*5101, B*5108, provided important insights into the molecular mechanism underlying the association between HLA status, this disease.

Localization of the pathogenic gene of Behçet's disease by microsatellite analysis of three different populations.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS: The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, PC: = 0.000014; Greek, PC: = 0. 00047; Italian, PC: = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, PC: = 0.000000000017; Greek, PC: = 0.00000032; Italian, PC: = 0. 0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51. CONCLUSIONS: These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.

Association of MICA gene and HLA-B*5101 with Behçet's disease in Greece.

PURPOSE: Behçet's disease (BD) is known to be associated with HLA-B51 in many different ethnic groups. Recently MICA, a member of a novel family of the human major histocompatibility complex (MHC) class I genes termed MIC (MHC class I chain-related genes), was identified near the HLA-B gene, and a triplet repeat microsatellite polymorphism was found in the transmembrane (TM) region. Because a strong association with BD of one particular MICA-TM allele, A6, was shown in a Japanese population, the present study was conducted to investigate microsatellite polymorphism in Greek patients with BD to know whether this association is generally observed in BD occurring in other populations. METHODS: Thirty-eight Greek patients with BD and 40 ethnically matched control subjects were examined for MICA microsatellite polymorphism using polymerase chain reaction (PCR) and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Similar to the Japanese patients with BD, the phenotype frequency of the MICA-TM A6 allele was significantly increased in the Greek patients with BD (50.0% in control subjects versus 86.8% in BD cases), with an odds ratio (OR) of 6.60 (P = 0.0012). The MICA-A6 allele was found in a high frequency both in males and females (weighted OR = 6.68; P = 0.0017). No association was found between the A6 allele and several disease features. A strong association exists between the MICA-TM A6 allele and the B*5101 allele in both the control subjects and patients with BD (weighted OR = 44.39; P = 0.0000023). CONCLUSIONS: This study revealed in Greek patients a strong association of BD with a particular MICA-TM allele, MICA-A6, providing insight into the molecular mechanism underlying the development of BD.

HLA-B*5101 in Greek patients with Behçet's disease.

Behçet's disease (BD) is a recurrent systemic vasculitis of unknown etiology. Genetic factors and infectious agents seem to be related to the etiology and pathogenesis of the disease. BD is strongly associated with HLA-B51 antigen in many ethnic groups. As there are differences in HLA profile in different ethnic groups, we designed this case-control study to examine the association of HLA-B51 alleles and BD as well as to investigate the influence of sex, age at development of the International Study Group (ISG) for Behçet's Disease criteria and certain features of disease severity on the strength of this association. The study includes 62 Greek BD patients who fulfill the ISG criteria for Behçet's disease and 87 controls. Serological HLA Class-I typing was performed by standard microlymphocytotoxicity technique. HLA-DNA typing for the B5 group was performed in all B51 subjects and controls by PCR-SSO. Allele B*5101 was found in 80% of BD patients and in 26% of controls (odds ratio (OR) 10.48, p < 10[-6]). Males who carry this allele have a higher risk than females for BD (OR 16.97 and 5.74 respectively). B*5101 predisposes to BD at a younger age in both sexes and to the development of erythema nodosum (OR = 11, p = 0.004). This was confirmed by multiple logistic regression analysis. A weak but not significant association was found between B*5101 and uveitis (OR = 2). No association was found between B*5101 and vasculitis or skin lesions in either sex. It was concluded that in the Greek population allele B*5101 is a predisposing marker for BD, as in most ethnic groups, and that this allele predisposes to the development of the disease at a younger age in both sexes and to the development of erythema nodosum.

A strong association between HLA-B*5101 and Behçet's disease in Greek patients.

Behçet's disease is known to be associated with HLA-B51, one of the split antigens of HLA-B5, among many different ethnic groups. In a Greek population, an increased incidence of HLA-B5 in the patient group has also been reported. Because the B51 antigen has been recently identified to comprise seven alleles, B*5101-B*5107, we performed HLA-B51 allele genotyping by the PCR-SSP method as well as serological HLA-A and -B typing among 31 Greek patients with Behçet's disease to investigate whether there is any correlation between one particular B51-associated allele and Behçet's disease. The frequency of B51 was remarkably high (80.6%) in the patient group as compared to the ethnically matched control group (26.7%). In addition, HLA-A26 was also increased in the patients (29.0%) as compared with the healthy controls (3.3%). B51 allele genotyping revealed that all these B51-positive patients carried B*5101. This study revealed a strong association of Behçet's disease in Greeks with one of the B51 subantigens, providing insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I chain-related gene A): allele frequency data in the nine population groups Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian.

We recently identified a trinucleotide repeat polymorphism, (GCT)n, within the transmembrane (TM) segment of the human MHC class I MICA gene (MHC class I chain-related gene A). Five distinct alleles (A4, A5, A5.1, A6, A9) corresponding to 4, 5, 5 with one nucleotide insertion, 6 and 9 repetitions, respectively, have been detected in various HLA-homozygous B cell lines. Here we present allele frequencies for this trimeric short tandem repeat (STR) in 604 unrelated individuals collected from nine human populations (Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian) determined using the polymerase chain reaction (PCR) combined with fluorescent-based automated fragment detection technology. All alleles were present in each population, but allelic distributions varied from one population to another. No new alleles (such as A7 or A8) were identified. The evolutionary and structural significance of these data as well as the potential application to forensic medicine is discussed.

Intermediate uveitis: what is the natural course of the disease and its relationship with other systemic diseases?

This study examined the natural course of intermediate uveitis, to find a possible correlation with systemic diseases and to identify the ocular complications. Patients were classified according to follow-up time in three groups: A (1-5 years) 12 pts, B (6-10 years) 10 pts, C (11-15 years or more) 6 pts for a total of 28 patients (52 eyes). We studied the recurrences, the complications of the disease and the overall prognosis. Eight patients were found to be suffering from systemic diseases: sarcoidosis 2, Adamantiades-Behcet 2, multiple sclerosis 3 and Lyme disease 1. Cataract was found in 21 eyes (40.5%) and macular changes in 20 eyes (38.4%) but chronic cystoid macular edema persisted in only six cases (12.5%). Group C presented more complications than group B. Group A had the fewest. The frequency of recurrences was 1-5 for group A. 1-3 for group B and 1-2 for group C. Four patients received no therapy, 15 received steroids and nine received cyclosporine and steroids. In this series intermediate uveitis was bilateral in 85.8% of patients and related with systemic diseases in 28.5%. Recurrences appeared mainly during the first five years. The longer the presence of the disease the more frequent were complications and the final visual acuity depended mostly on the severity of the initial attack and the number of exacerbations.

[The macula in Adamantiades-Behçet disease]. / La macula dans le syndrome d'Adamantiades-Behçet.

Adamantiades-Behçet disease is a well known clinical entity in the Mediterranean area. Signs and complications in these patients, arising from the macular area, are often overlooked for a prolonged period of time, because they are masked by the inflammatory signs of the anterior segment and/or the vitreous. Although blindness, in most cases, is the result of the optic disc atrophy, the macular alterations--as a sequelae of inflammation--are responsible for the low visual acuity. The authors in a retrospective clinical study of the last 100 consecutive cases of A-B disease, studied these macular alterations in detail. Their findings are also described in detail. Therapeutic modalities center around treatment with steroids, Cyclosporine A, and argon laser application. The results obtained from a long follow-up period are discussed.

Glycose tolerance curve, HbA1 determination and cataract.

In a series of patients with advanced cataract and in another one of patients with incipient cataract, aged under 55 years, with no history of trauma or diabetes and a normal fasting blood sugar, the standard glycose tolerance test, as well as the HbA1 determination were performed. About 34% of the patients of the first group and 10% of the second group showed abnormalities of the tests. Asymptomatic diabetes was diagnosed in these patients and it is concluded that glycose intolerance is common in patients with advanced or incipient cataract, under 55 years of age, who show no glycosuria and have a normal fasting blood sugar on routine examination.

Some observations on the treatment of ischemic optic neuropathy.

We examined the efficacy of the treatment with steroids, vasodilators, and vitamins B1, B6, and B12 in 23 cases of anterior ischemic optic neuropathy treated at the Athens University Eye Clinic. We stress the necessity of an extended medication for 2 to 3 months, depending upon the improvement of visual acuity. Good results were achieved in 14 of the 23 patients.

[Intravitreal injection of gentamicin--experimental findings (author's transl)]. / Intravitreale Injektion von Gentamicin--eigene Versuchsergebnisse.

In this experimental investigation the authors studied the electro-retinographic alterations and the histological lesions of the retina of rabbits following the intravitreal injection of different doses of gentamicin.

Retinoblastoma: some aspects concerning diagnosis, heredity, and treatment.

The authors set forth their views on the early diagnosis, heredity, and therapeutic problems of retinoblastoma. They regard as imperative the frequent ophthalmological check-up of familial tumors and of tumors of sporadic occurence, notably when they are bilateral. The further problems posed by the surviving patients are discussed in detail in the light of follow-up examinations extended up to 15 years.

On the management of congenital cataract with Dardenne's equipment.

After a short review of the operative techniques applied for the extraction of congenital cataract the authors describe the method of irrigation-aspiration of the lens material by means of the Dardenne equipment. Following an analysis of the results obtained with this procedure in a number of patients operated on at the Eye Clinic at Athens University, they discuss the advantages and shortcomings of the method, insisting in particular on: the importance of a complete removal of the lens debris; the careful scraping of the posterior lens capsule, and the necessity of an intensive postoperative anti-inflammatory therapy, especially in cases of congenital cataract due to rubella.

The necessary resection of the levator muscle of the upper eyelid in the operation for congenital blepharoptosis.

The authors comment on the excellent postoperative results obtained in 22 eyes operated on according to the Blaskovics method for congenital blepharoptosis. They discuss the length of the resected part of the levator muscle of the upper lid, the length depending in each case on the degree of the ptosis and on the functional ability of the levator muscle. They arrive at the conclusion that the shortening of the levator muscle must be considerably greater than heretofore advocated by the classical view.