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Biomedical subjects

D H Verity

Publications and source records attributed to D H Verity.

14 recordsLinked to original sources
PubMed2006

Natural history of periocular capillary haemangiomas: changes in internal blood velocity and lesion volume.

AIM: Although the clinical characteristics of childhood periocular capillary haemangiomas are well known, serial measurements of blood velocity and lesion size are unknown. This investigation was designed to measure the changes in maximum blood velocity and estimated size of lesion in children with capillary haemangioma not requiring active intervention. STUDY DESIGN: Retrospective case-note review for a cohort of children with capillary haemangioma involving the eyelid and orbit. PATIENTS AND METHODS: Children with periocular capillary haemangioma, under the care of the Orbital unit at Moorfields Eye Hospital between 1996 and 2005, were monitored clinically and with repeated ultrasonographic examination. Volume estimates were calculated as an ovoid based on the three maximum orthogonal measurements for the haemangioma, and blood velocity was assessed by Colour Flow Mapping, Colour Doppler Energy Imaging, and Spectral Doppler techniques using a Sequoia 512 Acuson scanner. RESULTS: Twenty-four children (12 boys) had initial assessment by 18 months of age, and the haemangioma increased in size in 14/24 (58%), the increase being between 4 and 931% of initial volume estimate. The largest measured size for an individual haemangioma appears inversely related to the child's age at measurement, this mirroring a similar trend in measurements for the maximum blood velocity. Blood velocity measurements also tend to decrease with time, the peak velocity being before 1 year of age in the majority (15/24; 62%). In many children, both volume estimates and blood velocities show a cyclic variation-this occurring with increasing intervals between the maxima, before a final decay in both parameters. Although, for the whole group, there was no correlation (correlation coefficient=0.29) between estimated size and measured blood velocity, some individual children showed a significant correlation between the two parameters. The age at maximum blood velocity appeared to precede the age at maximum volume in most children, and in many there was an orbital anomaly detectable on ultrasonographic examination, even with complete clinical resolution of the haemangioma. CONCLUSIONS: Ultrasonographic examination of periocular capillary haemangiomas show that these lesions have a very high blood velocity in feeding vessels-about 2-3 orders of magnitude greater than normal capillary beds-and that the velocity and volume of such lesions undergo a cyclic variation during their natural history. Evidence suggests that both velocity and volume decrease with time, although often not returning to zero on ultrasonography (unlike the clinical resolution of the lesions). In most children, blood velocity peaks before volume estimates and this might suggest that decreasing perfusion leads to later tissue atrophy and involution of the haemangioma.

Blood Flow Velocity↗
PubMed2003

Behçet's disease in patients of west African and Afro-Caribbean origin.

AIM: To report the presence of Behçet's disease with ocular involvement in patients of west African or Afro-Caribbean origin. METHODS: Case series of eight patients reporting to a tertiary uveitis service. RESULTS: Eight patients with typical features of the disease are presented. Six of the eight patients were tested and found to be HLA-B51 negative. CONCLUSION: Behçet's disease has only been reported in sporadic case reports in the indigenous west African and Afro-Caribbean populations, in whom the incidence of HLA B51 is also very low. A series of patients from the London region presented with the typical symptoms and signs of disease, most of whom were also HLA B51 negative. The presence of disease in this population, when absent in the indigenous population, suggests either that ascertainment of disease is poor in the indigenous population or that acquired factors may be important in the aetiology of the disease.

Adult↗
PubMed2003

Behçet's disease: from Hippocrates to the third millennium.

Behçet's disease (BD) is characterised by recurrent episodes of orogenital aphthae, systemic vasculitis, and systemic and retinal venous thrombosis. An association between HLA-B51 and BD was first identified over 20 years ago, but recently identified gene associations implicate regions both within and without the MHC in the immunological events underlying the lesions in BD. These include allelic variants within the tumour necrosis factor gene region and within the MHC class I chain related gene region, the factor V Leiden mutation, which is associated with retinal vascular occlusion, and alleles of the intercellular adhesion molecule gene. No single causative gene for BD has emerged; the evidence indicates that the underlying immune events in BD are triggered by a microbial antigen and subsequently driven by genetic influences which control leucocyte behaviour and the coagulation pathways. Knowledge of these risk factors may permit a more accurate prognosis for a given patient, and identify new pathways for more targeted intervention than is currently available.

Behcet Syndrome↗
PubMed2002

Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations.

Natural killer (NK) and some T cells express killer cell immunoglobulin-like receptors (KIRs), which interact with HLA class I expressed by target cells and consequently regulate cytolytic activity. The number of KIR loci can vary and so a range of genetic profiles is observed. We have determined the KIR genetic profiles from one African (n = 62) and two South Asian (n = 108, n = 78) populations. Several of the KIRs are present at significantly different frequencies between the two major ethnic groups (eg KIR2DS4 gene frequency 0.82 African, 0.47 S Asian. Pc < 1 x 10(-6)) and this is due to uneven distribution of two KIR haplotype families 'A' and 'B'. All three populations described here displayed a greater degree of diversity of KIR genetic profiles than other populations investigated, which indicates further complexity of underlying haplotypes; in this respect we describe two individuals who appear homozygous for a large deletion including the previously ubiquitous 2DL4. We have also reanalysed three populations that we studied previously, for the presence of a KIR which is now known to be an indicator of the 'B' haplotype. South Asians had the highest overall frequencies of all KIR loci characteristic of 'B' haplotypes (Pc < 0.0001 to < 0.004). Furthermore, gene frequency independent deviances in the linkage disequilibrium were apparent between populations.

Africa, Western↗
PubMed2001

Distribution of natural killer cell immunoglobulin-like receptor sequences in three ethnic groups.

Killer cell immunoglobulin-like receptors (KIRs) are members of a group of molecules that specifically recognize HLA class I ligands and are found on subsets of human lymphopoetic cells. The number of KIR loci can vary between individuals, resulting in a heterogeneous array of possible KIR genes. The range of observed profiles has been explained by the occurrence of two haplotype families termed A and B which can be distinguished on the basis of certain KIR sequences. Here we attempted to determine whether the frequencies of putative KIR loci and the two haplotype groups vary in three ethnically defined, healthy, and unrelated control populations, namely UK Caucasoid (n=136), Palestinian (n=105) and Thai (n=119). We molecularly typed genomic DNA for the presence of 12 putative KIR loci, KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR3DL1, KIR3DL2, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1, using modified PCR sequence-specific primers. The patterns of KIR locus frequencies combined with the similar linkage disequilibrium values suggest that there was a distinction in the distribution of the two broad haplotype groups between the populations studied. The A haplotype was always the most prevalent, but the ratio of A to B varied between populations. The frequency of B haplotype was highest in the Palestinians and lowest in the Thais (Pc<0.0001).

Alleles↗
PubMed2000

Intercellular adhesion molecule-1 gene polymorphisms in Behçet's disease.

Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases, including multiple sclerosis and inflammatory bowel disease. The expression of both soluble and tissue ICAM-1 is increased in Behçet's disease (BD) but the contribution of ICAM-1 gene polymorphisms to this disease remains unknown. Associations with BD have been reported for genes within the MHC, including HLA-B51, TNF and MICA, but the role of non-MHC genes in BD remains largely unexplored. We have investigated the frequency of the R/G 241 and K/E 469 ICAM-1 gene polymorphisms in 83 patients with BD disease and 103 healthy controls, all of Palestinian and Jordanian descent, and demonstrated an association between BD and the ICAM-1 E469 allele (Pc = 0.046, OR = 2.1). Among patients, no association was found between the presence of ocular disease and ICAM-1 polymorphisms. While the functional correlate of this polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain, which is independent of the MHC, may contribute to disease.

Behcet Syndrome↗
PubMed2000

Hypopyon uveitis and iris nodules in non-Hodgkin's lymphoma: ocular relapse during systemic remission.

We report the case history of a patient with peripheral non-Hodgkin's lymphoma in systemic remission, who presented with a pseudohypopyon and iris nodules. Iris biopsy confirmed the presence of intraocular tumour, which subsequently responded to orbital radiation. Ocular remission, however, was soon followed by a systemic relapse, suggesting that the eye may act as a sanctuary site for tumour cells during chemotherapy, and that cells may metastasize from the eye back to the periphery during systemic remission.

Adult↗
PubMed1999

MIC-A allele profiles and HLA class I associations in Behçet's disease.

Recently a new family of non-classical MHC molecules, the MHC class I chain-related protein (MIC), encoded by genes located in the major histocompatability complex have been identified. On the basis of the location of MIC genes and the structure and expression of MIC molecules it has been postulated that MIC may be a susceptibility factor in Behçet's disease (BD). We investigated the association of the 16 described external domain alleles and the transmembrane triplet repeats of MIC-A with BD in a Middle Eastern population. DNA from ninety-five patients and 102 age- and sex-matched controls were analyzed by polymerase chain reaction using allele specific primers. Our results show an increase of MIC-A*009 in the BD patient group 44/95 (46%) compared with controls 24/102 (24%) (chi2=11.3, OR=2.8, P=0.00078). MIC-A*009 was also found to be strongly associated with HLA-B51 in the patients 39/44 (88%) when compared with controls 10/24 (42%) (chi2=4, P=0.04). MIC-A*009 was also found in linkage disequilibrium with HLA-B52, but only in controls. The A6 form of a MIC-A transmembrane triplet repeat was found to be significantly raised in the patients (80/95; 84%;) compared with controls (58/102, 57%) (chi2=17.5, OR=4, P=0.000028). Although the MIC-A associations described are highly significant, the association with HLA-B51 independently remains the most significant factor (chi2=56.8, P<10(-6)). The data suggests that as both MIC-A*009 and A6 are in strong linkage disequilibrium with HLA-B51, they are unlikely to be the susceptibility gene for BD but may be markers for additional risk factors.

Adolescent↗
PubMed1999

Factor V Leiden mutation is associated with ocular involvement in Behçet disease.

PURPOSE: Behçet disease is a systemic disease of young adults characterized by venous occlusion in both the deep venous and retinal circulations. In severe ocular disease, blindness may occur despite immunosuppressive treatment. The most common inherited risk factor for the development of idiopathic venous thrombosis is the presence of the Factor V (FV Leiden) mutation, which confers resistance to activated protein C. The association of FV Leiden with Behçet disease has been reported, but its influence on ocular disease is not known. We therefore investigated the prevalence of this mutation in patients with Behçet disease to determine its contribution to the presence and severity of ocular disease. METHODS: One hundred and six Middle Eastern patients satisfying international criteria, and 120 healthy control subjects without a history of venous thrombosis were included in the study, and patients underwent standard examination by two ophthalmologists with an interest in Behçet disease. Genomic DNA was extracted from peripheral blood leukocytes and screened for the FV Leiden mutation with the polymerase chain reaction method with sequence-specific primers (PCR-SSP). RESULTS: FV Leiden was detected in 19% (23/120) of the control population compared with 27% (29/106) of all patients with Behçet disease (P = .13). However, among patients with Behçet disease who had ocular disease (75/106), the prevalence of FV Leiden was significantly higher (32%) than it was in control subjects (P = .04). Furthermore, ocular patients with Behçet disease in whom retinal occlusive disease was observed (25/75) had the highest expression of FV Leiden (44%). CONCLUSIONS: These data suggest that FV Leiden may be an additional risk factor for the development of ocular disease and, in particular, retinal vaso-occlusion, and it may contribute to the poor visual outcome in these patients.

Adolescent↗
PubMed1999

Behçet's disease, the Silk Road and HLA-B51: historical and geographical perspectives.

Behçet's disease (BD), also known as the Silk Road disease, is a blinding inflammatory disorder of young adults found predominantly between the Mediterranean basin and the Orient, and is strongly associated with the major histocompatibility complex (MHC) antigen HLA-B51. In this article we review the history of Behçet's disease since its first description by Hippocrates, the development of the trading routes collectively known as the Silk Road and the effect of population movement on the distribution of HLA-B51. The global distribution of this antigen among healthy control populations bears a striking similarity both to the ancient trading routes and the distribution of Behçet's disease, suggesting a genetic risk that migrated in parallel with population movement between the Mediterranean and Asia. However, certain indigenous Amerindian peoples have a high prevalence of HLA-B51 but no reported cases of BD. Furthermore, a clear genealogical relationship exists between eastern, but not central, Siberian populations with the Amerindians. Since a high level of recombination within the MHC is known to have occurred in these eastern populations before their migration into Beringia, we suggest that disruption of genetic loci in linkage disequilibria with HLA-B51 may be one reason for the absence of disease in these high HLA-B51-bearing populations. However, a contributory influence of environmental factors is not excluded by this data, and the wide variation that exists in relative risk of HLA-B51 even within Europe would support other non-genetic risk factors on the Silk Road which may be absent, or non-contributory to disease, in the Americas.

Arabia↗
PubMed1999

HLA and tumour necrosis factor (TNF) polymorphisms in ocular Behçet's disease.

The role of HLA-B*51 and other major histocompatibility complex (MHC) genes in Behçet's disease (BD) remains unknown. We have performed HLA and tumour necrosis factor (TNF) polymorphism analysis in BD and evaluated their contribution to ocular disease. In this study, 102 patients and 115 controls of Middle Eastern descent were investigated by HLA and B*51 subtyping using novel primers, and by LT alpha NCo 1 and TNF 308 promoter polymorphism analysis. The frequency of the HLA-B*51 family of alleles was raised in patients compared to controls (66% vs. 15%, Pc=2.5x10(-12), OR=10.9). The odds ratio (OR) of this group of alleles for subgroups of patients was as follows: non-ocular patients 7.8, all ocular patients 12.6, blind patients >22. HLA-B*51 subtyping detected B*5101, 07, 08 and 09 alleles, with a similar frequency among patients and controls. HLA-Cw*1602 was associated with B*5108, but was not an independent risk factor for disease. The LT alpha (TNFB*2) allele was associated with HLA-B*51 among patients and the frequency of this allele was significantly higher among completely blind patients compared to both non-ocular patients (P=0.048, OR >3.6) and to healthy controls (P=0.022, OR >4.3). The rare TNF-2 polymorphism at the TNF -308 promoter position was associated with HLA-B*50 (not B*51), and was not associated with BD. Thus, in this population the HLA*B51 family of alleles is a strong risk factor for BD, and in particular the development of ocular disease. HLA-B*51 subtyping did not define new markers for BD. A primary role for TNF gne polymorphisms in BD was not identified, but co-expression of the TNFB*2 allele with HLA-B*51 may contribute to severity of ocular disease.

Adolescent↗
PubMed1998

Soluble adhesion molecules in Behçet's disease.

BACKGROUND: Behçet's disease (BD) may lead to blindness in up to 25% of eyes. Soluble (s)ICAM-1 but not sVCAM-1 is associated with relapse in idiopathic uveoretinitis and is reported to be raised in BD patients. We have investigated the levels of sICAM-1 and sVCAM-1 in Palestinian patients with BD and related them to both ocular and systemic disease activity and to immunosuppressive treatment. METHODS: A total of 51 patients (43 male, 8 female; mean ages 29.8 & 31.9 yr) were examined at the St John Ophthalmic Hospital during a one year period (135 consultations). Disease activity was determined from history and standard ocular examination. Anterior uveitis, vitritis and retinal vasculitis acted as markers of ocular inflammation. Peripheral venous sICAM-1 and sVCAM-1 levels were determined by standard ELISA. A total of 53 healthy age- and sex-matched clinic staff members acted as controls. RESULTS: sICAM-1 and sVCAM-1 were both significantly lower in patients on systemic immunosuppression than in those off treatment (p < 0.001). Among patients off systemic treatment, sICAM was higher in the group with active systemic disease but quiet eyes (p = 0.003), but not in those with active ocular disease (p = 0.09), compared to controls. sVCAM was not raised in either group. CONCLUSION: Systemic immunosuppression was associated with reduced sICAM-1 and sVCAM-1, supporting a role for adhesion molecules in the pathogenesis of BD. sICAM-1 levels were raised in association with inflammatory features implicating endothelial activation in active BD. The mean sICAM-1 was higher in active ocular patients than controls.

Adolescent↗