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1.
Eye (Lond) ; 36(10): 1966-1972, 2022 10.
Article in English | MEDLINE | ID: mdl-34611315

ABSTRACT

In 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th year, the Stickler Highly Specialised Service (HSS) has assessed 1673 patients from 785 families. Using a combination of accurate phenotyping and molecular genetic analysis it is possible to identify the underlying genetic mutation in over 95% of cases including those with deep intronic mutations likely to be missed by conventional exome panel analysis and which require whole gene sequencing and supplementary functional analysis to confirm pathogenicity. The vast majority that presents to ophthalmologists will be from one of three autosomal dominant sub-groups with a high associated risk of retinal detachment but the diagnosis is often overlooked, especially in adults. In contrast to many other blinding retinal conditions, blindness through giant retinal tear detachment particularly in children is largely preventable provided these high-risk groups are identified and appropriate evidence-based prophylaxis offered. This article summarises ten selected briefcase histories from the national dataset with key learning points from each.


Subject(s)
Arthritis , Connective Tissue Diseases , Craniofacial Abnormalities , Eye Diseases, Hereditary , Hearing Loss, Sensorineural , Retinal Detachment , Adult , Arthritis/epidemiology , Arthritis/genetics , Child , Connective Tissue Diseases/complications , Connective Tissue Diseases/genetics , Eye Diseases, Hereditary/diagnosis , Eye Diseases, Hereditary/epidemiology , Eye Diseases, Hereditary/genetics , Humans , Mutation , Pedigree , Retinal Detachment/diagnosis , Retinal Detachment/epidemiology
2.
Med Leg J ; 89(2): 102-105, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33691511

ABSTRACT

Recent reports suggest that the use of an outpatient-based procedure (pneumatic retinopexy, PR) for retinal detachment repair should be encouraged within the UK, especially in light of Covid-19 and possible restrictions/competing demands on access to operating theatres. It is therefore essential that patients receive comprehensive information about the risks and benefits of this approach compared with a formal surgical repair either by pars plana vitrectomy (PPV) and/or scleral buckling (SB). We report a retrospective case series of retinal detachments (RD) satisfying the strict selection criteria for PR but who were managed with formal surgery. Single-operation success rate for PPV/SB at six months follow-up was 93.8% in our study, higher than published primary success rates for PR (60-80%). When counselling patients for possible PR, the ease, speed and potentially reduced co-morbidity of an outpatient-based procedure needs to be balanced against its significantly higher failure rate in comparison with primary PPV/SB.


Subject(s)
Informed Consent/standards , Retina/surgery , Retinal Detachment/surgery , Scleral Buckling/standards , Vitrectomy/standards , Aged , COVID-19/prevention & control , COVID-19/transmission , Female , Humans , Informed Consent/legislation & jurisprudence , Male , Middle Aged , Retina/physiopathology , Retrospective Studies , Scleral Buckling/statistics & numerical data , Vitrectomy/statistics & numerical data
3.
Clin Radiol ; 73(7): 678.e13-678.e18, 2018 07.
Article in English | MEDLINE | ID: mdl-29661559

ABSTRACT

AIM: To review the radiological findings of the largest cohort to date of paediatric patients with Stickler syndrome, all with confirmed molecular genetic analysis and sub-typing. PATIENTS AND METHODS: It is understood that the National Health Service (NHS) commissioned service at Addenbrookes Hospital, Cambridge, UK has the largest cohort of Stickler syndrome patients in the paediatric age group worldwide with 240 registered children. Fifty-nine were assessed radiologically and for their genotypes. These radiographs were reviewed and 74 knee, 45 pelvic, and 47 spinal examinations were evaluated. RESULTS: Radiological features were noted in 45.9% of knee radiographs, 11.1% of pelvic radiographs, and 42.6% of spinal radiographs. The findings were reviewed in the light of each patient's specific genetic Stickler syndrome subtype. CONCLUSION: The prevalence of orthopaedic abnormalities overall in the present series is substantially below those published in previous smaller case series. This would support the more recent findings of an array of ocular only phenotypes of Stickler syndrome described in the literature.


Subject(s)
Arthritis/diagnostic imaging , Connective Tissue Diseases/diagnostic imaging , Hearing Loss, Sensorineural/diagnostic imaging , Knee/diagnostic imaging , Pelvis/diagnostic imaging , Retinal Detachment/diagnostic imaging , Spine/diagnostic imaging , Child , Cohort Studies , Humans , Radiography , United Kingdom
4.
Eye (Lond) ; 32(2): 163, 2018 02.
Article in English | MEDLINE | ID: mdl-29417938
5.
J Dent Res ; 94(10): 1471-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26232387

ABSTRACT

Dental enamel formation is an intricate process tightly regulated by ameloblast cells. The correct spatiotemporal patterning of enamel matrix protein (EMP) expression is fundamental to orchestrate the formation of enamel crystals, which depend on a robust supply of Ca2+. In the extracellular milieu, Ca2+ -EMP interactions occur at different levels. Despite its recognized role in enamel development, the molecular machinery involved in Ca2+ homeostasis in ameloblasts remains poorly understood. A common mechanism for Ca2+ influx is store-operated Ca2+ entry (SOCE). We evaluated the possibility that Ca2+ influx in enamel cells might be mediated by SOCE and the Ca2+ release-activated Ca2+ (CRAC) channel, the prototypical SOCE channel. Using ameloblast-like LS8 cells, we demonstrate that these cells express Ca2+ -handling molecules and mediate Ca2+ influx through SOCE. As a rise in the cytosolic Ca2+ concentration is a versatile signal that can modulate gene expression, we assessed whether SOCE in enamel cells had any effect on the expression of EMPs. Our results demonstrate that stimulating LS8 cells or murine primary enamel organ cells with thapsigargin to activate SOCE leads to increased expression of Amelx, Ambn, Enam, Mmp20. This effect is reversed when cells are treated with a CRAC channel inhibitor. These data indicate that Ca2+ influx in LS8 cells and enamel organ cells is mediated by CRAC channels and that Ca2+ signals enhance the expression of EMPs. Ca2+ plays an important role not only in mineralizing dental enamel but also in regulating the expression of EMPs.


Subject(s)
Calcium/physiology , Dental Enamel/physiology , Gene Expression Regulation/physiology , Ameloblasts/physiology , Animals , Blotting, Western , Calcium Channels/physiology , Dental Enamel/cytology , Dental Enamel/metabolism , Dental Enamel Proteins/biosynthesis , Female , Fluorescent Antibody Technique , Homeostasis , Male , Mice , Mice, Inbred C57BL , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction
6.
Sex Transm Dis ; 42(4): 192-7, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25763671

ABSTRACT

BACKGROUND: Black teenagers have relatively high rates of sexually transmitted diseases (STDs), and recent research suggests the role of contextual factors, as well as risk behaviors. We explore the role of 4 categories of risk and protective factors on having a biologically confirmed STD among black, female teenagers. METHODS: Black teenage girls (14-19 years old) accessing services at a publicly funded family planning clinic provided a urine specimen for STD testing and completed an audio computer-assisted self-interview that assessed the following: risk behaviors, relationship characteristics, social factors, and psychosocial factors. We examined bivariate associations between each risk and protective factor and having gonorrhea and/or chlamydia, as well as multivariate logistic regression among 339 black female teenagers. RESULTS: More than one-fourth (26.5%) of participants had either gonorrhea and/or chlamydia. In multivariate analyses, having initiated sex before age 15 (adjusted odds ratio [aOR], 1.87) and having concurrent sex partners in the past 6 months (aOR, 1.55) were positively associated with having an STD. Living with her father (aOR, 0.44), believing that an STD is the worst thing that could happen (aOR, 0.50), and believing she would feel dirty and embarrassed about an STD (aOR, 0.44) were negatively associated with having an STD. CONCLUSIONS: Social factors and attitudes toward STDs and select risk behaviors were associated with the risk for STDs, suggesting the need for interventions that address more distal factors. Future studies should investigate how such factors influence safer sexual behaviors and the risk for STDs among black female teenagers.


Subject(s)
Adolescent Behavior/psychology , Black or African American , Sexual Partners , Sexually Transmitted Diseases/psychology , Unsafe Sex , Adolescent , Black or African American/psychology , Black or African American/statistics & numerical data , Cross-Sectional Studies , Female , Georgia/epidemiology , Health Knowledge, Attitudes, Practice , Health Surveys , Humans , Medical History Taking , Risk Factors , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Unsafe Sex/psychology , Unsafe Sex/statistics & numerical data
7.
Eye (Lond) ; 29(4): 475-82, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25592122

ABSTRACT

PURPOSE: To study the variability of the ophthalmic phenotype in Kniest dysplasia. Kniest dysplasia is an inherited disorder associated with defects in type II collagen and characterised by short-trunked dwarfism, kyphoscoliosis, and enlarged joints with restricted mobility. Other features include marked hand arthropathy, cleft palate, hearing loss, and ocular abnormalities (myopia, abnormal vitreous, and high risk of developing retinal detachment). METHODS: Data from eight unrelated individuals with a clinical and molecular diagnosis of Kniest dysplasia are reported. Clinical assessment included an audiogram and ophthalmological examination in all but one patient who died in the immediate postnatal period. Sanger sequencing of the COL2A1 gene was performed. RESULTS: Six of the seven patients tested were high myopes with one patient being an emmetrope. Bilateral quandratic cataracts and subluxed lenses were noted in one subject. Variable but abnormal vitreous architecture was observed in all seven individuals tested. Six of the seven patients had significant hearing impairment and five of the seven patients exhibited clefting abnormalities. One patient had bilateral retinal detachments in his twenties. Six dominant disease-causing COL2A1 variants were detected. In three cases, testing of parental samples revealed that the disease-causing variant was not present in either parent. CONCLUSION: The ophthalmic features in Kniest dysplasia are very similar to those in other disorders of type II collagen such as Stickler syndrome. It is likely that different type II collagenopathies have a similar level of ocular morbidity and regular ophthalmologic examination is recommended. Kniest dysplasia is associated with heterozygous COL2A1 mutations that are frequently de novo.


Subject(s)
Cleft Palate/genetics , Collagen Diseases/genetics , Collagen Type II/genetics , Dwarfism/genetics , Eye Diseases/pathology , Face/abnormalities , Hyaline Membrane Disease/genetics , Osteochondrodysplasias/genetics , Adolescent , Adult , Child , Child, Preschool , Cleft Palate/pathology , Collagen Diseases/pathology , Dwarfism/pathology , Eye Diseases/etiology , Eye Diseases/genetics , Face/pathology , Female , Hearing Disorders/etiology , Humans , Hyaline Membrane Disease/pathology , Male , Mutation , Osteochondrodysplasias/pathology , Phenotype , Young Adult
8.
AIDS Educ Prev ; 26(2): 95-108, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24694324

ABSTRACT

Mixed-method designs are increasingly used in sexually transmitted infection (STI) and HIV prevention research. The authors designed a mixedmethod approach and applied it to estimate and evaluate a predictor of continued female condom use (6+ uses, among those who used it at least once) in a 6-month prospective cohort study. The analysis included 402 women who received an intervention promoting use of female and male condoms for STI prevention and completed monthly quantitative surveys; 33 also completed a semistructured qualitative interview. The authors identified a qualitative theme (couples' female condom enjoyment [CFCE]), applied discriminant analysis techniques to estimate CFCE for all participants, and added CFCE to a multivariable logistic regression model of continued female condom use. CFCE related to comfort, naturalness, pleasure, feeling protected, playfulness, ease of use, intimacy, and feeling in control of protection. CFCE was associated with continued female condom use (adjusted odds ratio: 2.8, 95% confidence interval: 1.4-5.6) and significantly improved model fit (p < .001). CFCE predicted continued female condom use. Mixed-method approaches for "scaling up" qualitative findings from small samples to larger numbers of participants can benefit HIV and STI prevention research.


Subject(s)
Condoms/statistics & numerical data , HIV Infections/prevention & control , Sexual Behavior , Sexually Transmitted Diseases/prevention & control , Adult , Alabama , Condoms, Female/statistics & numerical data , Female , Health Knowledge, Attitudes, Practice , Health Promotion/methods , Health Surveys , Humans , Interviews as Topic , Logistic Models , Male , Prospective Studies , Qualitative Research , Sexual Partners , Socioeconomic Factors
9.
West Indian Med J ; 62(1): 56-61, 2013 Jan.
Article in English | MEDLINE | ID: mdl-24171329

ABSTRACT

OBJECTIVES: Although common worldwide, intravaginal cleansing is associated with poor health outcomes. We sought to describe intravaginal cleansing among women attending a sexually transmitted infection (STI) clinic in Jamaica. METHODS: We examined intravaginal cleansing ("washing up inside the vagina", douching, and products or materials used) among 293 participants in a randomized trial of counselling messages at an STI clinic in Kingston. We focussed on information on intravaginal cleansing performed in the 30 days and three days preceding their baseline study visit. We describe reported cleansing behaviours and used logistic regression to identify correlates of intravaginal cleansing. RESULTS: Fifty-eight per cent of participants reported intravaginal cleansing in the previous 30 days, and 46% did so in the three days before baseline. Among those who cleansed in the previous 30 days, 88% reported doing so for hygiene unrelated to sex, and three-fourths reported generally doing so more than once per day. Soap (usually with water) and water alone were the most common products used for washing; commercial douches or detergents were reported infrequently. Intravaginal cleansing in the three days before the baseline visit was positively associated with having more than one sex partner in the previous three months (adjusted odds ratio [AOR], 1.9; 95% CI, 1.1, 3.2), and negatively associated with experiencing itching in the genital area at baseline (AOR, 0.6; 95% CI, 0.4, 1.0). CONCLUSIONS: A large proportion of women attending STI clinics in Jamaica engage in frequent intravaginal cleansing, indicating a need for clinicians to discuss this topic with them accordingly.


Subject(s)
Health Behavior , Sexual Behavior , Sexually Transmitted Diseases/prevention & control , Vaginal Douching , Adult , Ambulatory Care Facilities/statistics & numerical data , Female , Humans , Jamaica , Logistic Models , Sexual Partners , Sexually Transmitted Diseases/physiopathology , Sexually Transmitted Diseases/psychology , Soaps/therapeutic use , Time Factors , Treatment Outcome , Vaginal Douching/instrumentation , Vaginal Douching/methods
10.
Public Health Rep ; 128 Suppl 1: 5-22, 2013.
Article in English | MEDLINE | ID: mdl-23450881

ABSTRACT

OBJECTIVES: We reviewed the literature focused on socioeconomic influences on teen childbearing and suggested directions for future research and practice related to this important indicator of teen sexual health. METHODS: We conducted an electronic search of Medline, ERIC, PsychLit, and Sociological Abstracts databases for articles published from January 1995 to November 2011. Selected articles from peer-reviewed journals included original quantitative analyses addressing socioeconomic influences on first birth among teen women in the U.S. Articles were abstracted for key information, ranked for quality according to the U.S. Preventive Services Task Force guidelines, assessed for bias, and synthesized. RESULTS: We selected articles with a range of observational study designs. Risk for bias varied across studies. All 12 studies that considered socioeconomic factors as influences on teen childbearing (vs. moderators or mediators of other effects) reported at least one statistically significant association relating low socioeconomic status, underemployment, low income, low education levels, neighborhood disadvantage, neighborhood physical disorder, or neighborhood-level income inequality to teen birth. Few reports included any associations contradicting this pattern. CONCLUSIONS: This review suggests that unfavorable socioeconomic conditions experienced at the community and family levels contribute to the high teen birth rate in the U.S. Future research into social determinants of sexual health should include multiple levels of measurement whenever possible. Root causes of teen childbearing should be evaluated in various populations and contexts. Interventions that address socioeconomic influences at multiple levels could positively affect large numbers of teens and help eliminate disparities in teen childbearing.


Subject(s)
Poverty , Pregnancy in Adolescence/statistics & numerical data , Social Environment , Adolescent , Databases, Bibliographic , Educational Status , Family Characteristics , Female , Humans , Pregnancy , Pregnancy in Adolescence/psychology , Residence Characteristics , Risk Factors , Socioeconomic Factors , United States/epidemiology , Young Adult
11.
Biomaterials ; 34(13): 3303-14, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23398885

ABSTRACT

Enamel formation involves highly orchestrated intracellular and extracellular events; following development, the tissue is unable to regenerate, making it a challenging target for tissue engineering. We previously demonstrated the ability to trigger enamel differentiation and regeneration in the embryonic mouse incisor using a self-assembling matrix that displayed the integrin-binding epitope RGDS (Arg-Gly-Asp-Ser). To further elucidate the intracellular signaling pathways responsible for this phenomenon, we explore here the coupling response of integrin receptors to the biomaterial and subsequent downstream gene expression profiles. We demonstrate that the artificial matrix activates focal adhesion kinase (FAK) to increase phosphorylation of both c-Jun N-terminal kinase (JNK) and its downstream transcription factor c-Jun (c-Jun). Inhibition of FAK blocked activation of the identified matrix-mediated pathways, while independent inhibition of JNK nearly abolished phosphorylated-c-Jun (p-c-Jun) and attenuated the pathways identified to promote enamel regeneration. Cognate binding sites in the amelogenin promoter were identified to be transcriptionally up-regulated in response to p-c-Jun. Furthermore, the artificial matrix induced gene expression as evidenced by an increased abundance of amelogenin, the main protein expressed during enamel formation, and the CCAAT enhancer binding protein alpha (C/EBPα), which is the known activator of amelogenin expression. Elucidating these cues not only provides guidelines for the design of synthetic regenerative strategies and opportunities to manipulate pathways to regulate enamel regeneration, but can provide insight into the molecular mechanisms involved in tissue formation.


Subject(s)
Biocompatible Materials/pharmacology , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Dental Enamel/physiology , Integrins/metabolism , Nanofibers/chemistry , Proto-Oncogene Proteins c-jun/metabolism , Regeneration/drug effects , Amelogenin/genetics , Amelogenin/metabolism , Animals , Base Sequence , Cell Line , Cells, Cultured , Dental Enamel/drug effects , Dental Enamel/enzymology , Enzyme Activation/drug effects , Epithelial Cells/drug effects , Epithelial Cells/enzymology , Female , Focal Adhesion Protein-Tyrosine Kinases/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Mice , Molecular Sequence Data , Oligopeptides/pharmacology , Peptides/pharmacology , Phosphorylation/drug effects , Signal Transduction/drug effects , Surface-Active Agents/pharmacology , Up-Regulation/drug effects
12.
Acta Biomater ; 9(2): 5341-52, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23159566

ABSTRACT

Titanium (Ti) and its alloys are among the most successful implantable materials for dental and orthopedic applications. The combination of excellent mechanical and corrosion resistance properties makes them highly desirable as endosseous implants that can withstand a demanding biomechanical environment. Yet, the success of the implant depends on its osteointegration, which is modulated by the biological reactions occurring at the interface of the implant. A recent development for improving biological responses on the Ti-implant surface has been the realization that bifunctional peptides can impart material binding specificity not only because of their molecular recognition of the inorganic material surface, but also through their self-assembly and ease of biological conjugation properties. To assess peptide-based functionalization on bioactivity, the present authors generated a set of peptides for implant-grade Ti, using cell surface display methods. Out of 60 unique peptides selected by this method, two of the strongest titanium binding peptides, TiBP1 and TiBP2, were further characterized for molecular structure and adsorption properties. These two peptides demonstrated unique, but similar molecular conformations different from that of a weak binder peptide, TiBP60. Adsorption measurements on a Ti surface revealed that their disassociation constants were 15-fold less than TiBP60. Their flexible and modular use in biological surface functionalization were demonstrated by conjugating them with an integrin recognizing peptide motif, RGDS. The functionalization of the Ti surface by the selected peptides significantly enhanced the bioactivity of osteoblast and fibroblast cells on implant-grade materials.


Subject(s)
Implants, Experimental , Peptides/pharmacology , Titanium/pharmacology , Adsorption , Amino Acid Sequence , Animals , Cell Adhesion/drug effects , Cell Death/drug effects , Cell Line , Circular Dichroism , Fibroblasts/cytology , Fibroblasts/drug effects , Mice , Microscopy, Atomic Force , Molecular Sequence Data , Osteoblasts/cytology , Osteoblasts/drug effects , Peptides/chemistry , Peptides/metabolism , Protein Binding/drug effects , Surface Properties
13.
Eye (Lond) ; 25(11): 1389-400, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21921955

ABSTRACT

The entity described by Gunnar Stickler, which included hereditary arthro-ophthalmopathy associated with retinal detachment, has recently been recognised to consist of a number of subgroups, which might now more correctly be referred to as the Stickler syndromes. They are the most common clinical manifestation of the type II/XI collagenopathies and are the most common cause of inherited rhegmatogenous retinal detachment. This review article is intended to provide the ophthalmologist with an update on current research, subgroups, and their diagnosis together with a brief overview of allied conditions to be considered in the clinical differential diagnosis. We highlight the recently identified subgroups with a high risk of retinal detachment but with minimal or absent systemic involvement--a particularly important group for the ophthalmologist to identify.


Subject(s)
Arthritis/diagnosis , Connective Tissue Diseases/diagnosis , Hearing Loss, Sensorineural/diagnosis , Retinal Detachment/etiology , Arthritis/complications , Arthritis/genetics , Collagen Type II/genetics , Collagen Type XI/genetics , Connective Tissue Diseases/complications , Connective Tissue Diseases/genetics , Diagnosis, Differential , Hearing Disorders/etiology , Hearing Loss, Sensorineural/complications , Hearing Loss, Sensorineural/genetics , Humans , Jaw Abnormalities/etiology , Phenotype , Retinal Detachment/complications , Retinal Detachment/diagnosis , Retinal Detachment/genetics , Vitreous Body/chemistry
14.
Orthod Craniofac Res ; 12(3): 243-53, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19627527

ABSTRACT

Emdogain (enamel matrix derivative, EMD) is well recognized in periodontology, where it is used as a local adjunct to periodontal surgery to stimulate regeneration of periodontal tissues lost to periodontal disease. The biological effect of EMD is through stimulation of local growth factor secretion and cytokine expression in the treated tissues, inducing a regenerative process that mimics odontogenesis. The major (>95%) component of EMD is Amelogenins (Amel). No other active components have so far been isolated from EMD, and several studies have shown that purified amelogenins can induce the same effect as the complete EMD. Amelogenins comprise a family of highly conserved extracellular matrix proteins derived from one gene. Amelogenin structure and function is evolutionary well conserved, suggesting a profound role in biomineralization and hard tissue formation. A special feature of amelogenins is that under physiological conditions the proteins self-assembles into nanospheres that constitute an extracellular matrix. In the body, this matrix is slowly digested by specific extracellular proteolytic enzymes (matrix metalloproteinase) in a controlled process, releasing bioactive peptides to the surrounding tissues for weeks after application. Based on clinical and experimental observations in periodontology indicating that amelogenins can have a significant positive influence on wound healing, bone formation and root resorption, several new applications for amelogenins have been suggested. New experiments now confirm that amelogenins have potential for being used also in the fields of endodontics, bone regeneration, implantology, traumatology, and wound care.


Subject(s)
Amelogenin/therapeutic use , Dental Enamel Proteins/therapeutic use , Periodontal Diseases/surgery , Amelogenin/physiology , Calcification, Physiologic/physiology , Conserved Sequence , Dental Enamel Proteins/physiology , Extracellular Matrix Proteins/physiology , Humans , Matrix Metalloproteinases/physiology , Osteogenesis/physiology , Regeneration/drug effects , Root Resorption/physiopathology , Wound Healing/physiology
15.
Eye (Lond) ; 22(10): 1257-62, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18425061

ABSTRACT

Separation of the vitreous and posterior hyaloid membrane (PHM) or posterior vitreous detachment (PVD) typically occurs between the ages of 45 and 65 years in the general population, but may occur earlier in myopic or otherwise predisposed individuals. Age-related synergetic changes occurring within the cortical and central gel must be distinguished from the PHM, which envelopes it. This study reports on the correlation between 'true' PVD seen clinically by the physician using dynamic examination, high-power slit-lamp biomicroscopy, and oblique illumination with some of its histological, immunohistochemical, and ultrastructural features post-mortem. The presence of the Weiss ring does not necessarily indicate total clean separation of PHM, nor does its absence confirm that the PHM remains attached, since it may be destroyed during the process of separation. Immediately prior to PVD with the vitreous gel attached, the PHM must, by definition, form part of the inner limiting membrane. The detached PHM frequently exhibits basement membrane (BM) and its indigenous laminocytes stain focally for GFAP and type IV collagen. The PHM is distinct from and much thicker than the BM of Müller cells alone and the factors that initiate or limit separation of the PHM require greater study, particularly the role of laminocyte proliferation and migration.


Subject(s)
Vitreous Detachment/pathology , Aged , Humans , Middle Aged , Vitrectomy , Vitreous Detachment/complications
16.
Eye (Lond) ; 22(10): 1310-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18344963

ABSTRACT

PURPOSE/BACKGROUND: Epiretinal membrane (ERM) formation is a common change resulting in disturbance of macular vision and predisposing to rhegmatogenous retinal detachment. Current treatment strategies rely chiefly on surgical removal of the membranes from the surface of the retina, allowing the retina to remodel and reattach. Improved knowledge of the pathological process behind the formation of these membranes, particularly knowledge of the cell types involved in their formation, is likely to increase our understanding of the way this group of diseases behave and to improve treatment. METHODS: We reviewed the histological findings of 109 surgically removed specimens and correlated these to age-related changes seen in a 32 cadaver eyes studied after corneal harvesting. The samples were studied using light microscopy and immunocytochemistry. RESULTS: In all cases of idiopathic ERMs, including cellophane maculopathy, macular hole, and vitreomacular traction syndrome, laminocytes were the exclusive cell type present. In cases of macular pucker associated with retinal tears, the membranes contain variable cohesive groups of retinal pigment epithelial (RPE) cells in addition to laminocytes. In cases of proliferative diabetic retinopathy, membranes consist almost entirely of capillaries and hyaline stromal tissue, with or without haemosiderin pigment and RPE cells and in which laminocytes and ILM were not identified. In cadaver eyes PVD was seen in 17/32 (53%) of cases, and the vitreous was attached in 14/32 (43.7%) and in one case no vitreous was present. Isolated laminocytes were present on the retinal surface in 12/18 cases with detached vitreous and in 1/14 cases with attached vitreous. In all cases laminocytes were scanty and confined to the optic nerve head, macular or subjacent macular retina. Immunohistochemistry findings indicate that laminocytes are positive for glial fibrillary acidic protein (GFAP), cytokeratin marker AE1/AE3, type II collagen, and type IV collagen. In some cases novel basement membrane formation was seen. There was a tendency for increased positivity of GFAP and AE1/AE3 with increased cellularity, and where novel basement membrane formation was present. CONCLUSION: Laminocytes are the fundamental cell type in idiopathic ERMs. These cells are frequently found in small and dispersed numbers in eyes containing a PVD. The presence of retinal pigment cells invariable indicates proliferative retinopathy and is only seen in association with a retinal detachment or tear. Diabetic membranes are composed of neovascular stromal tissue, which is most likely to be a response to retinal hypoxia.


Subject(s)
Diabetic Retinopathy/pathology , Epiretinal Membrane/pathology , Retinal Detachment/pathology , Vitreoretinopathy, Proliferative/pathology , Adult , Aged , Aged, 80 and over , Cadaver , Epiretinal Membrane/etiology , Humans , Immunohistochemistry , Middle Aged , Retrospective Studies
17.
J Dent Res ; 87(4): 391-5, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18362326

ABSTRACT

The H(+)/base transport processes that control the pH of the microenvironment adjacent to ameloblasts are not currently well-understood. Mice null for the AE2 anion exchanger have abnormal enamel. In addition, persons with mutations in the electrogenic sodium bicarbonate co-transporter NBCe1 and mice lacking NBCe1 have enamel abnormalities. These observations suggest that AE2 and NBCe1 play important roles in amelogenesis. In the present study, we aimed to understand the roles of AE2 and NBCe1 in ameloblasts. Analysis of the data showed that NBCe1 is expressed at the basolateral membrane of secretory ameloblasts, whereas AE2 is expressed at the apical membrane. Transcripts for AE2a and NBCe1-B were detected in RNA isolated from cultured ameloblast-like LS8 cells. Our data are the first evidence that AE2 and NBCe1 are expressed in ameloblasts in vivo in a polarized fashion, thereby providing a mechanism for ameloblast transcellular bicarbonate secretion in the process of enamel formation and maturation.


Subject(s)
Ameloblasts/metabolism , Anion Transport Proteins/genetics , Antiporters/genetics , Nerve Tissue Proteins/genetics , Sodium-Bicarbonate Symporters/genetics , Amelogenesis/genetics , Animals , Cell Membrane/metabolism , Cells, Cultured , Incisor/cytology , Mice , Molar/cytology , Reverse Transcriptase Polymerase Chain Reaction , SLC4A Proteins , Transcription, Genetic/genetics
18.
Eye (Lond) ; 22(10): 1243-50, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18309338

ABSTRACT

PURPOSE: This paper will illustrate how variation in the processing of mutant pre-mRNA can affect the phenotypic outcome of inherited disorders of type II collagen. METHODS: Type 1 Stickler's syndrome is one of the different phenotypes resulting from mutations in COL2A1 (the type II collagenopathies). It is also the commonest, but often goes undiagnosed due to the variability of phenotypic features, which in some cases may consist of only abnormal vitreous development. Most cases of type 1 Stickler's syndrome are due to premature termination codons in the mRNA, resulting in haploinsufficiency. This leaves a conundrum as to why the disease is so variable. Using RT-PCR of illegitimate transcript and also minigenes, we have investigated how certain mutations can variably affect mRNA processing. RESULTS: Here, we demonstrate and discuss how apparently similar mutations can have a dramatically different effect on splicing of the pre-mRNA, switching transcripts from ones which would be degraded by nonsense-mediated decay into messages that will be translated into mutant proteins that can exert a dominant-negative effect and ultimately modify the resulting phenotype. CONCLUSION: Variability of Stickler's syndrome can, in part, be due to the variable effect that mutations have on the processing of the COL2A1 transcript.


Subject(s)
Collagen Diseases/genetics , Collagen Type II/genetics , RNA Precursors/genetics , RNA Splicing/genetics , Base Sequence/genetics , Collagen Diseases/pathology , Exons/genetics , Humans , Mutation, Missense/genetics , Phenotype , RNA Precursors/metabolism , Syndrome , Vitreous Body/abnormalities
19.
Eye (Lond) ; 22(6): 815-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-17277751

ABSTRACT

AIMS: For rhegmatogenous retinal detachment, reattachment with a single procedure is associated with better visual outcomes. In the past, silicone oil has been used mostly as a last resort following failed primary surgery. This study evaluates a novel approach to patients at high risk of primary failure, using silicone tamponade as the primary stage of a planned two-stage procedure. METHODS: We report a series of 140 eyes that underwent primary surgery for rhegmatogenous retinal detachment. Patients at higher risk of surgical failure (eg giant retinal tear, inability to posture, poor view, uncertainty of location of primary break, primary proliferative vitreoretinopathy (PVR), multiple tears with rolled posterior edges, retinoschisis/detachment, staphyloma with macular hole) were managed by a planned staged procedure using primary silicone oil tamponade. This was followed by silicone removal at a later date. RESULTS: Fifty-four eyes underwent scleral buckling alone, with primary success in 52/54 (96%). Fifty-three eyes underwent vitrectomy and gas, achieving primary success in 50/53 (94%). Thirty-three eyes were classified high risk and managed with primary silicone. Silicone was safely removed in 22/25. In eight eyes, silicone was retained without attempt at removal. In total, primary retinal reattachment was achieved in 128 of 140 eyes (91.4%). Of these, 124 (97%) did not require long-term tamponade. Only four eyes (2.9%) developed PVR. DISCUSSION: A planned two-stage approach to highrisk cases of retinal detachment using primary silicone oil tamponade followed by silicone removal can achieve a high primary reattachment rate with less than 3% incidence of PVR.


Subject(s)
Retinal Detachment/surgery , Scleral Buckling/methods , Silicone Oils/administration & dosage , Vitrectomy/methods , Vitreoretinopathy, Proliferative/prevention & control , Control Groups , Female , Follow-Up Studies , Humans , Male , Retina/surgery , Retinal Detachment/complications , Risk Assessment , Silicone Oils/adverse effects , Treatment Outcome , Visual Acuity/physiology , Vitreoretinopathy, Proliferative/complications , Vitreoretinopathy, Proliferative/surgery , Vitreous Body/surgery
20.
Eye (Lond) ; 22(2): 200-3, 2008 Feb.
Article in English | MEDLINE | ID: mdl-16946755

ABSTRACT

AIM: The use of adjunctive scleral buckling during vitrectomy for retinal detachment associated with inferior breaks has been the recent focus of some debate. It has been suggested that any benefit might be outweighed by potential complications associated with buckling surgery. The purpose of this study was to compare the success rate of vitrectomy, gas, and supplementary scleral buckling with the results of two recently published case series suggesting that acceptable results in inferior break detachments can be achieved with vitrectomy and gas alone. METHODS: A retrospective analysis of 60 consecutive patients with inferior break retinal detachments was conducted. All patients underwent vitrectomy, gas, and scleral buckling. In all cases, fellow eyes were examined under anaesthesia for retinal breaks if posterior vitreous detachment (PVD) had occurred at the time of presentation. Demographics, preoperative, and postoperative complications and outcome were recorded. RESULTS: Primary retinal attachment at 3 months was achieved in 95% of patients. This exceeds success rates of published data of patients who underwent vitrectomy and gas without buckling (81-89%). In patients with PVD in the fellow eye, 53% had horseshoe tears and all were treated with cryopexy. No sight-threatening complications occurred, but five patients developed minor buckle-related complications postoperatively. CONCLUSION: Supplementary scleral buckling is a safe procedure that improves and enhances primary success rates in inferior break detachments over vitrectomy and gas without buckling. There is a high rate of PVD-related breaks requiring treatment in the fellow eyes.


Subject(s)
Retinal Detachment/surgery , Retinal Perforations/surgery , Scleral Buckling , Vitrectomy , Female , Gases , Humans , Male , Middle Aged , Retinal Detachment/complications , Retinal Perforations/complications , Retrospective Studies , Scleral Buckling/adverse effects , Treatment Outcome
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