Stephen Charles - Academia.edu (original) (raw)
Papers by Stephen Charles
Postgraduate Medical Journal, 1999
Cytomegalovirus (CMV) retinitis is the most common intra-ocular infection in patients with acquir... more Cytomegalovirus (CMV) retinitis is the most common intra-ocular infection in patients with acquired immune deficiency syndrome (AIDS), and a leading cause of AIDS-related morbidity. Untreated CMV retinitis in AIDS patients is a progressive and potentially blinding disorder. The diagnosis of CMV retinitis is a clinical one and it is important for physicians to be familiar with the clinical features of the disease. Ophthalmic screening of AIDS suVerers should be undertaken at regular intervals, and this is dictated, in part, by the patient's CD4+ T-lymphocyte (CD4) counts. CMV retinitis may be treated with systemic ganciclovir, foscarnet or cidofovir, or with local (intravitreal) therapy. CMVrelated retinal detachment is treated surgically. In some patients with quiescent CMV retinitis receiving highly active antiretroviral therapy, anti-CMV maintenance therapy may be discontinued in favour of close ophthalmologic observation and CD4 count monitoring.
Singapore medical journal, 2000
There have been profound changes in the pattern of cytomegalovirus (CMV) retinitis over the last ... more There have been profound changes in the pattern of cytomegalovirus (CMV) retinitis over the last two decades. The epidemiology and behaviour of CMV retinitis has been significantly altered by Acquired Immune Deficiency Syndrome (AIDS). It was uncommon prior to the AIDS epidemic, but soon became the most common retinal infection in AIDS patients. In the past several years, highly active anti-retroviral treatment (HAART) has achieved a dramatic improvement in the prognosis for patients infected with human immunodeficiency virus (HIV). As a result, HIV patients are living longer and have a reduced risk of CMV retinitis. Some patients with CMV retinitis who respond to HAART develop a transient symptomatic vitritis while others undergo no reactivation of their retinitis despite having no specific anti-CMV therapy. This pattern is likely to undergo further change as the treatment of HIV and CMV disease continues to improve.
Postgraduate Medical Journal, 2001
A 16 year old boy awaiting a defunctioning colostomy for Crohn's disease complained of reduced vi... more A 16 year old boy awaiting a defunctioning colostomy for Crohn's disease complained of reduced vision in his left eye. Four weeks previously candida had been isolated from his central line used for parenteral feeds. Fundal examination of the left eye revealed a macular abscess with a classic "string of pearls" appearance of multiple vitreous abscesses. This was treated with pars plana vitrectomy and intravitreal antifungal therapy. Microbiological studies confirmed a diagnosis of candida endophthalmitis.
Journal of Medical Genetics, 1990
We report a case of Alstrom's syndrome with hypothyroidism in addition to the cardinal features o... more We report a case of Alstrom's syndrome with hypothyroidism in addition to the cardinal features of blindness, deafness, obesity, and insulin dependent diabetes meflitus. The parents were first cousins once removed which strengthens the case for autosomal recessive inheritance. Alstrom's syndrome was first described in 1959 as a combination of atypical retinal pigmentary degeneration, obesity, diabetes mellitus, sensorineural deafness, and normal intelligence.1 Further cases have been described and the constellation of signs now recognised as part of the syndrome includes acanthosis nigricans, male hypogenitalism, hyperuricaemia, hypertriglyceridaemia, baldness, kyphosis, and renal dysfunction.2A Renal disease is a late manifestation and renal failure is a cause of death in some patients. Hypothyroidism has not previously been described in Alstrom's syndrome. Case report The patient was the youngest in a sibship of three girls. Her parents were first cousins once removed (fig 1). The common ancestors were not known to be of Scandinavian extraction. She was noted to have poor
Journal of Medical Genetics, 1993
The X linked form of Kallmann syndrome (KAL) and X linked ocular albinism (OA1) have both been ma... more The X linked form of Kallmann syndrome (KAL) and X linked ocular albinism (OA1) have both been mapped to Xp22.3. We have used a dinucleotide repeat polymorphism at the Kallmann locus to type 17 X linked ocular albinism families which had previously been typed for the Xg blood group (XG) and the DNA markers DXS237 (GMGX9), DXS143 (dic56), and DXS85 (782). Close linkage was found between KAL and OAI with a maximum lod score (Zmax) of 30-14 at a recombination fraction (Omax) of 0-06 (confidence interval for 0: 0'03-010). KAL was also closely linked to DXS237 (Zmax= 15-32; Omax=0-05; CI 0-02-0-12) and DXS143 (Zmax = 14-57; Omax = 0 05; CI 0-02-0 13). There was looser linkage to the Xg blood group (XG) and to DXS85 (782). Multipoint linkage analysis gave the map: Xpter-XG-0 13-DXS237-0-025-KAL-0025-DXS143-0015-OA1 0-09-DXS85-Xcen. Placement of OA1 proximal to DXS143 was supported by odds of 2300:1 compared to other orders. This confirms our previous localisation of OAl and improves the genetic mapping of both disease loci.
Journal of Medical Genetics, 1993
A population based clinical and molecular genetic study of familial adenomatous polyposis coli (F... more A population based clinical and molecular genetic study of familial adenomatous polyposis coli (FAPC) was perpriate restriction enzyme according to the
Human Genetics, 2001
Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus... more Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G proteincoupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis
Eye, 1992
A prospective study was performed over a 4-year period of 56 infants presenting with infantile es... more A prospective study was performed over a 4-year period of 56 infants presenting with infantile esotropia to assess development of binocularity after surgical alignment before 2 years of age. In 50% of cases infantile esotropia was associated with neurological problems or prematur ity. Forty-three cases have undergone surgery (mean age 15.7 months ±3.46); 86% were aligned (±10 dioptres) at 2 years. Eighty-seven per cent of normal children and 74% of children with neurological problems or prematurity were aligned at last follow-up (mean 27.2 months since surgery). Tests of fusion and stereopsis have to date been possible upon 21 'successfully' aligned infants and although most have evidence of peripheral sensory fusion none showed stereopsis to more than one test. Although early surgery achieves a good cosmetic result in normal children and those with neurological problems, our findings question its ability to promote the development of even gross stereopsis in most children.
British Journal of Ophthalmology, 2001
British Journal of Ophthalmology, 1994
Sixty two females at 50% carrier risk were assessed from 19 families affected by X linked ocular ... more Sixty two females at 50% carrier risk were assessed from 19 families affected by X linked ocular albinism (OA1). Twenty nine (47%) had definite fundus changes ofthe carrier state with a mud splattered fundus appearance and 23 (37%) had a normal ophthalmic examination. Ten (16%) had mild peripheral retinal pigmentary changes so that it was difficult to exclude the carrier state; six of these females were shown to be at low risk and only one at high risk of being a carrier by DNA analysis using linked DNA polymorphisms, including a highly informative dinucleotide repeat at the Kallmann locus. Mild peripheral retinal pigmentary changes are not a definite indication of carrier status and in 45 age matched female controls five (11%) had similar changes. No female with a clinically normal fundus was found to be at high risk by DNA analysis. Molecular genetic analysis improves the accuracy of carrier detection in OA1 families and should be considered if the clinical findings are equivocal.
British Journal of Ophthalmology, 1991
We report the case of a mentally retarded male with a ring 17 chromosome who had subretinal druse... more We report the case of a mentally retarded male with a ring 17 chromosome who had subretinal drusen-like deposits in each eye. This is the second report offlecked retina in a patient with ring 17 chromosome, suggesting that there may be a causal relationship between abnormalities of chromosome 17 and retinal pigment epithelial or photoreceptor dysfunction. the ring chromosome, rather than loss of chromatin.4 We describe a patient with ring 17 chromosome with a flecked retina, seizures, and cafe au lait spots in addition to mental retardation and short stature.
British Journal of Ophthalmology, 1993
Seventy four males affected by X linked ocular albinism (XLOA) from 19 pedigrees were examined to... more Seventy four males affected by X linked ocular albinism (XLOA) from 19 pedigrees were examined to assess phenotypic variation and visual prognosis. Nystagmus was present in all cases except one. Best visual acuity ranged from 6/9 to 6/60; 79.7% could see 6/36 or better; most could read N5. Marked iris translucency and foveal hypoplasia were present in all cases. Posterior embryotoxon was present in 30% and dysplastic optic discs were often seen. Pigmentation of the posterior pole was associated with better visual acuity. XLOA is underdiagnosed: almost 20% of cases had been previously diagnosed as having congenital nystagmus until reviewed in this study.
British Journal of Ophthalmology, 2009
ABSTRACT
Eye, 1992
Forty-nine obligate heterozygotes and 64 at risk females were assessed from 17 families affected ... more Forty-nine obligate heterozygotes and 64 at risk females were assessed from 17 families affected by X-linked ocular albinism to determine the relative values of clinical examination and skin biopsy in carrier detection. 92 % of obligate heterozygotes had a mud-splattered appearance of the fundus with hyperpigmented streaks and in 74% this was associated with marked iris translucency. Skin histology showed macromelanosomes in 84%. 27 of 64 (42%) at risk females had definite features of the carrier state and 19 (30%) were unequivocally normal but a further 18 (28%) had mild RPE abnormalities, often with iris transillumination defects, of uncertain significance. Fundus examination will detect most carrier females but will not allow reliable genetic counselling for all at risk females, even when supplemented by skin biopsy. Albinism is a cause of poor visual acuity and nystagmus and can be broadly divided into two groups: 1 oculo cutaneous albinism, of which there are several types,
Journal of Medical Genetics, 1995
We have found abnormal fibrillin microfibrils isolated from tissues and cell cultures from two co... more We have found abnormal fibrillin microfibrils isolated from tissues and cell cultures from two cousins with Marfan syndrome whose major clinical abnormality is bilateral ectopia lentis, but who
British journal of ophthalmology, 1991
The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented wit... more The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented with corneoscleral inflammatory disease are described. Marginal corneal infiltrates were seen in all patients with anterior scleritis and were a valuable sign of disease activity. Nine out ...
British Journal of Ophthalmology, 2000
European Journal of Ophthalmology
Postgraduate Medical Journal, 1999
Cytomegalovirus (CMV) retinitis is the most common intra-ocular infection in patients with acquir... more Cytomegalovirus (CMV) retinitis is the most common intra-ocular infection in patients with acquired immune deficiency syndrome (AIDS), and a leading cause of AIDS-related morbidity. Untreated CMV retinitis in AIDS patients is a progressive and potentially blinding disorder. The diagnosis of CMV retinitis is a clinical one and it is important for physicians to be familiar with the clinical features of the disease. Ophthalmic screening of AIDS suVerers should be undertaken at regular intervals, and this is dictated, in part, by the patient's CD4+ T-lymphocyte (CD4) counts. CMV retinitis may be treated with systemic ganciclovir, foscarnet or cidofovir, or with local (intravitreal) therapy. CMVrelated retinal detachment is treated surgically. In some patients with quiescent CMV retinitis receiving highly active antiretroviral therapy, anti-CMV maintenance therapy may be discontinued in favour of close ophthalmologic observation and CD4 count monitoring.
Singapore medical journal, 2000
There have been profound changes in the pattern of cytomegalovirus (CMV) retinitis over the last ... more There have been profound changes in the pattern of cytomegalovirus (CMV) retinitis over the last two decades. The epidemiology and behaviour of CMV retinitis has been significantly altered by Acquired Immune Deficiency Syndrome (AIDS). It was uncommon prior to the AIDS epidemic, but soon became the most common retinal infection in AIDS patients. In the past several years, highly active anti-retroviral treatment (HAART) has achieved a dramatic improvement in the prognosis for patients infected with human immunodeficiency virus (HIV). As a result, HIV patients are living longer and have a reduced risk of CMV retinitis. Some patients with CMV retinitis who respond to HAART develop a transient symptomatic vitritis while others undergo no reactivation of their retinitis despite having no specific anti-CMV therapy. This pattern is likely to undergo further change as the treatment of HIV and CMV disease continues to improve.
Postgraduate Medical Journal, 2001
A 16 year old boy awaiting a defunctioning colostomy for Crohn's disease complained of reduced vi... more A 16 year old boy awaiting a defunctioning colostomy for Crohn's disease complained of reduced vision in his left eye. Four weeks previously candida had been isolated from his central line used for parenteral feeds. Fundal examination of the left eye revealed a macular abscess with a classic "string of pearls" appearance of multiple vitreous abscesses. This was treated with pars plana vitrectomy and intravitreal antifungal therapy. Microbiological studies confirmed a diagnosis of candida endophthalmitis.
Journal of Medical Genetics, 1990
We report a case of Alstrom's syndrome with hypothyroidism in addition to the cardinal features o... more We report a case of Alstrom's syndrome with hypothyroidism in addition to the cardinal features of blindness, deafness, obesity, and insulin dependent diabetes meflitus. The parents were first cousins once removed which strengthens the case for autosomal recessive inheritance. Alstrom's syndrome was first described in 1959 as a combination of atypical retinal pigmentary degeneration, obesity, diabetes mellitus, sensorineural deafness, and normal intelligence.1 Further cases have been described and the constellation of signs now recognised as part of the syndrome includes acanthosis nigricans, male hypogenitalism, hyperuricaemia, hypertriglyceridaemia, baldness, kyphosis, and renal dysfunction.2A Renal disease is a late manifestation and renal failure is a cause of death in some patients. Hypothyroidism has not previously been described in Alstrom's syndrome. Case report The patient was the youngest in a sibship of three girls. Her parents were first cousins once removed (fig 1). The common ancestors were not known to be of Scandinavian extraction. She was noted to have poor
Journal of Medical Genetics, 1993
The X linked form of Kallmann syndrome (KAL) and X linked ocular albinism (OA1) have both been ma... more The X linked form of Kallmann syndrome (KAL) and X linked ocular albinism (OA1) have both been mapped to Xp22.3. We have used a dinucleotide repeat polymorphism at the Kallmann locus to type 17 X linked ocular albinism families which had previously been typed for the Xg blood group (XG) and the DNA markers DXS237 (GMGX9), DXS143 (dic56), and DXS85 (782). Close linkage was found between KAL and OAI with a maximum lod score (Zmax) of 30-14 at a recombination fraction (Omax) of 0-06 (confidence interval for 0: 0'03-010). KAL was also closely linked to DXS237 (Zmax= 15-32; Omax=0-05; CI 0-02-0-12) and DXS143 (Zmax = 14-57; Omax = 0 05; CI 0-02-0 13). There was looser linkage to the Xg blood group (XG) and to DXS85 (782). Multipoint linkage analysis gave the map: Xpter-XG-0 13-DXS237-0-025-KAL-0025-DXS143-0015-OA1 0-09-DXS85-Xcen. Placement of OA1 proximal to DXS143 was supported by odds of 2300:1 compared to other orders. This confirms our previous localisation of OAl and improves the genetic mapping of both disease loci.
Journal of Medical Genetics, 1993
A population based clinical and molecular genetic study of familial adenomatous polyposis coli (F... more A population based clinical and molecular genetic study of familial adenomatous polyposis coli (FAPC) was perpriate restriction enzyme according to the
Human Genetics, 2001
Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus... more Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes. We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G proteincoupled receptors. We and others have identified mutations of various types within the OA1 gene in patients with this disorder, including deletions and splice site, frameshift, nonsense, and missense mutations. However, different prevalences of large intragenic deletions have been reported, ranging from 10% to 50% in independent studies. To determine whether these differences might be related to the geographic origin of the OA1 families tested, we performed a further extensive mutation analysis study leading to the identification of pathogenic mutations in 30 unrelated OA1 patients mainly from Europe and North America. These results, together with our earlier mutation reports on OA1, allow us to resolve the apparent discrepancies between previous studies and point to a substantial difference in the frequency of large intragenic deletions in European (<10%) compared with North American (>50%) OA1 families. These observations and our overall refinement of point mutation distribution within the OA1 gene have important implications for the molecular diagnosis
Eye, 1992
A prospective study was performed over a 4-year period of 56 infants presenting with infantile es... more A prospective study was performed over a 4-year period of 56 infants presenting with infantile esotropia to assess development of binocularity after surgical alignment before 2 years of age. In 50% of cases infantile esotropia was associated with neurological problems or prematur ity. Forty-three cases have undergone surgery (mean age 15.7 months ±3.46); 86% were aligned (±10 dioptres) at 2 years. Eighty-seven per cent of normal children and 74% of children with neurological problems or prematurity were aligned at last follow-up (mean 27.2 months since surgery). Tests of fusion and stereopsis have to date been possible upon 21 'successfully' aligned infants and although most have evidence of peripheral sensory fusion none showed stereopsis to more than one test. Although early surgery achieves a good cosmetic result in normal children and those with neurological problems, our findings question its ability to promote the development of even gross stereopsis in most children.
British Journal of Ophthalmology, 2001
British Journal of Ophthalmology, 1994
Sixty two females at 50% carrier risk were assessed from 19 families affected by X linked ocular ... more Sixty two females at 50% carrier risk were assessed from 19 families affected by X linked ocular albinism (OA1). Twenty nine (47%) had definite fundus changes ofthe carrier state with a mud splattered fundus appearance and 23 (37%) had a normal ophthalmic examination. Ten (16%) had mild peripheral retinal pigmentary changes so that it was difficult to exclude the carrier state; six of these females were shown to be at low risk and only one at high risk of being a carrier by DNA analysis using linked DNA polymorphisms, including a highly informative dinucleotide repeat at the Kallmann locus. Mild peripheral retinal pigmentary changes are not a definite indication of carrier status and in 45 age matched female controls five (11%) had similar changes. No female with a clinically normal fundus was found to be at high risk by DNA analysis. Molecular genetic analysis improves the accuracy of carrier detection in OA1 families and should be considered if the clinical findings are equivocal.
British Journal of Ophthalmology, 1991
We report the case of a mentally retarded male with a ring 17 chromosome who had subretinal druse... more We report the case of a mentally retarded male with a ring 17 chromosome who had subretinal drusen-like deposits in each eye. This is the second report offlecked retina in a patient with ring 17 chromosome, suggesting that there may be a causal relationship between abnormalities of chromosome 17 and retinal pigment epithelial or photoreceptor dysfunction. the ring chromosome, rather than loss of chromatin.4 We describe a patient with ring 17 chromosome with a flecked retina, seizures, and cafe au lait spots in addition to mental retardation and short stature.
British Journal of Ophthalmology, 1993
Seventy four males affected by X linked ocular albinism (XLOA) from 19 pedigrees were examined to... more Seventy four males affected by X linked ocular albinism (XLOA) from 19 pedigrees were examined to assess phenotypic variation and visual prognosis. Nystagmus was present in all cases except one. Best visual acuity ranged from 6/9 to 6/60; 79.7% could see 6/36 or better; most could read N5. Marked iris translucency and foveal hypoplasia were present in all cases. Posterior embryotoxon was present in 30% and dysplastic optic discs were often seen. Pigmentation of the posterior pole was associated with better visual acuity. XLOA is underdiagnosed: almost 20% of cases had been previously diagnosed as having congenital nystagmus until reviewed in this study.
British Journal of Ophthalmology, 2009
ABSTRACT
Eye, 1992
Forty-nine obligate heterozygotes and 64 at risk females were assessed from 17 families affected ... more Forty-nine obligate heterozygotes and 64 at risk females were assessed from 17 families affected by X-linked ocular albinism to determine the relative values of clinical examination and skin biopsy in carrier detection. 92 % of obligate heterozygotes had a mud-splattered appearance of the fundus with hyperpigmented streaks and in 74% this was associated with marked iris translucency. Skin histology showed macromelanosomes in 84%. 27 of 64 (42%) at risk females had definite features of the carrier state and 19 (30%) were unequivocally normal but a further 18 (28%) had mild RPE abnormalities, often with iris transillumination defects, of uncertain significance. Fundus examination will detect most carrier females but will not allow reliable genetic counselling for all at risk females, even when supplemented by skin biopsy. Albinism is a cause of poor visual acuity and nystagmus and can be broadly divided into two groups: 1 oculo cutaneous albinism, of which there are several types,
Journal of Medical Genetics, 1995
We have found abnormal fibrillin microfibrils isolated from tissues and cell cultures from two co... more We have found abnormal fibrillin microfibrils isolated from tissues and cell cultures from two cousins with Marfan syndrome whose major clinical abnormality is bilateral ectopia lentis, but who
British journal of ophthalmology, 1991
The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented wit... more The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented with corneoscleral inflammatory disease are described. Marginal corneal infiltrates were seen in all patients with anterior scleritis and were a valuable sign of disease activity. Nine out ...
British Journal of Ophthalmology, 2000
European Journal of Ophthalmology