Exercise programs have been shown to increase strength and endurance in patien ts with myopathic disorders. The authors investigated the effect of aerobic trai ning in patients with facioscapulohumeral dystrophy (FSHD...Exercise programs have been shown to increase strength and endurance in patien ts with myopathic disorders. The authors investigated the effect of aerobic trai ning in patients with facioscapulohumeral dystrophy (FSHD). Twelve weeks of lowi ntense aerobic exercise improved maximal oxygen uptake and workload with no sign s of muscle damage. The authors conclude that aerobic training is a safe method to increase exercise performance in patients with FSHD.展开更多
To identify genes responsible for cone dystrophies and determine the functiona l consequences of their underlying mutations. Case-control study. Two hundred f orty unrelated patients diagnosed with cone dystrophy, con...To identify genes responsible for cone dystrophies and determine the functiona l consequences of their underlying mutations. Case-control study. Two hundred f orty unrelated patients diagnosed with cone dystrophy, cone-rod dystrophy, macu lar dystrophy, macular degeneration, or Stargardt disease, 95 control individual s, and 2 unrelated families with a distinctive type of cone dystrophy. The DNAs of the 240 probands were screened for sequence variants in the PDE6H gene (that encodes the inhibitory γ-subunit of cone cyclic guanosine monophosphate [cGMP ] -phosphodiesterase [PDE]) by single-strand conformation polymorphism electro ph oresis. The effect of a nucleotide substitution in the DNA of a patient on gene expression efficiency was analyzed by in vitro transcrip-tion/translation. Cone -specific gene variants, fundus, visual field and electroretinogram (ERG) findi ngs, and protein synthesis efficiency. We found a heterozygous G to C substituti on in the 5′untranslated region (UTR) of the PDE6H gene in the DNA of a patient with a distinctive form of cone dystrophy, her sibling, and their father. This rare form of disease is very different in manifestation from other cone dystroph ies and has been described as “cone dystrophy with nyctalopia and supernormal r od responses,”“cone dystrophy with supernormal scotopic ERGs”and “supernorma l and delayed rod ERG syndrome.”Among the 240 patients that we studied, only 1 proband had the G to C variant. Furthermore, none of the 95 controls used in thi s study had this nucleotide change. We also determined that the PDE6H variant wa s not present in another family affected with this particular type of cone dystr ophy. Because the 5’UTR of mRNAs plays a critical role in the regulation of pro tein synthesis, we determined the effect of the G to C change in this process. B y use of in vitro transcription/translation experiments, we demonstrated that th is substitution could lead to an increase in PDE6H gene expression. Our results indicate that mutations in the PDE6H gene are not common, because only 1 of 240 patients with cone dystrophy showed a single nucleotide substitution in the 5′U TR of PDE6H mRNA that could be associated with the disease. If the effect of the G to C substitution we observed in vitro also occurs in vivo, it will lead to P DE6H overexpression in the photoreceptors. Excess of PDEγmay affect normal cone cGMP-PDE function by inhibiting the catalytic PDEα,βactivity and lead to pat hogenic elevation of cGMP and eventual degeneration of cone photoreceptors.展开更多
The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing an d muscle morphology before and after training. Patients in...The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing an d muscle morphology before and after training. Patients increased their maximal oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter incre ased significantly, and creatine kinase did not increase with training. The stud y indicates that aerobic training is safe and can improve fitness effectively in patients with myotonic dystrophy.展开更多
Background: To obtain a driver’s licence certain requirements for visual acui ty and visual field have to be fulfilled. Mesopic contrast and glare sensitivity are not regularly tested and are not crucial to passing t...Background: To obtain a driver’s licence certain requirements for visual acui ty and visual field have to be fulfilled. Mesopic contrast and glare sensitivity are not regularly tested and are not crucial to passing the driving test. Case report: We report a case of a 39-year-old professional bus driver whose only c omplaint was increased glare sensitivity. After he had been involved in four tra ffic accidents, ophthalmological investigations revealed binocular annular scoto mata and night blindness, leading to the diagnosis of rod-cone dystrophy. Discu ssion: Enhanced glare sensitivity is a common complaint in elderly people or peo ple with the beginnings of cataract but may also represent an initial symptom of a retinal disorder. It is therefore advisable for traf-fic safety if drivers w ith such complaints undergo a complete ophthalmological investigation including visual field testing.展开更多
Purpose:To correlate the functional results of maculartranslocation(MT )in a patient suffering from an adult-onset foveomacular vitellif orm dystrophy(AFVD)with the microscopic findings of the surgically removed subfo...Purpose:To correlate the functional results of maculartranslocation(MT )in a patient suffering from an adult-onset foveomacular vitellif orm dystrophy(AFVD)with the microscopic findings of the surgically removed subfoveal retinal pigment epithelium(RPE).Methods:A78-year-old woman with AFVD underwe nt MT with 360°retinotomy 3-4months after loss of r eading ability.Most of the vitelliform material was lost during surgery;the subfoveal tissue was excised,fixed in aldehydes,postfixed in reduced OSO4and embedded in epoxy resin.Semithin sections were stained with toluidin e blue for light mi-croscopy(LM)and thin sections with uranyl acetate and lead citrate for transmission electron microscopy(TEM).Results:Postoperatively,the pati ent developed a retinal detachment complicated by proliferative vitreoretinopathy(PVR)requiring two additional vitreoretinal procedures before finally the silicone oil coul d be removed.Twen-ty-two months after MT the distance v isual acuity was un-changed at 0.2;the near visual acuit y had improved from less than 0.1before MT to 0.4.The retina was completely attached.LM and TEM revealed seriou s alterations in-dicative of a breakdown of the outer l ayer of the retina.Conclusion:Through the present sin gle case it is not possible to determine whether MT cou ld be a therapeutic approach in patients with AFVD.The m ost important cause for the limited postoperative visual improvement seems to be a primary injury of the foveal function due to the AFVD.This is supported by the extensive subfoveal degeneration and necrosis affectin g not only the RPE cells but also their basement membrane and the interposed basal laminar deposits.展开更多
Purpose Fundus autofluorescence is due to accumulation of lipofuscin in the retinal pigment ep ithelium(RPE)resulting from incomplete digestion of N-retinylidene-phosphatidyl-ethanolamine from shed photorecep tor oute...Purpose Fundus autofluorescence is due to accumulation of lipofuscin in the retinal pigment ep ithelium(RPE)resulting from incomplete digestion of N-retinylidene-phosphatidyl-ethanolamine from shed photorecep tor outer segment discs.Alteration in autofluorescence reflects changes in lipofuscin content of the RPE.Mutations on both alleles of RPE65result in absent or largely decrease d formation of rhodopsin,due to a defect in alltrans retinol is omerization in the RPE.Autofluorescence could therefore b e altered.This study was conducted to evaluate fundus autofl uorescence in patients with early-onset severe retinal dystrophy(EOSRD,or ear-ly-onset rod-cone dystrophy)associated with mutations on both alleles of RPE65.Design Case se ries.Participants and controls Ten 10-to 55-year-old p atients with EOSRD and compound heterozygous or homozy gous mutations in RPE65.For comparison,6heterozygous parents and 2patients with other forms of EOSRD we re examined.Methods Participants underwent,in addition to standard clinical and electrophysiological examination,autofluores-cence imaging using a confocal scanning laser ophthalmo-scope.Three of the patients were als o examined by optical coherence tomography(OCT)to evaluate the status of retinal degeneration.Mutations in7patients have been reported previously;the other pati ents were investigated by polymerase chain reaction-single-strand conformation poly-morphism and direct sequencing for mutations in RPE65and lecithin retinol acyltransfera se(LRAT).Main outcome measures Fundus autofluorescence a nd OCT.Results Ab-sent or minimal autofluorescence wa s found in all patients with compound heterozygous or homozygous RPE65muta-tions.Autofluorescence was normal in the heterozygous parents.Autofluorescence was present in 2children with EOSRD not associated with mutations in RPE65or LRAT,another gene involved in retinol recycling.Optical coher-ence tomography in younger patients revealed an intraretinal appearance similar to that of their h ealthy,heterozygous parents.Conclusions Lack of autofl uorescence in patients with EOSRD associated with mutation s in RPE65is in ac-cordance with the biochemical defect and can be used as a clinical marker of this genotype.Optical coherence tomog-raphy results in younger patients wo uld indicate still viable photoreceptors despite the absence of autofluorescence.展开更多
文摘Exercise programs have been shown to increase strength and endurance in patien ts with myopathic disorders. The authors investigated the effect of aerobic trai ning in patients with facioscapulohumeral dystrophy (FSHD). Twelve weeks of lowi ntense aerobic exercise improved maximal oxygen uptake and workload with no sign s of muscle damage. The authors conclude that aerobic training is a safe method to increase exercise performance in patients with FSHD.
文摘To identify genes responsible for cone dystrophies and determine the functiona l consequences of their underlying mutations. Case-control study. Two hundred f orty unrelated patients diagnosed with cone dystrophy, cone-rod dystrophy, macu lar dystrophy, macular degeneration, or Stargardt disease, 95 control individual s, and 2 unrelated families with a distinctive type of cone dystrophy. The DNAs of the 240 probands were screened for sequence variants in the PDE6H gene (that encodes the inhibitory γ-subunit of cone cyclic guanosine monophosphate [cGMP ] -phosphodiesterase [PDE]) by single-strand conformation polymorphism electro ph oresis. The effect of a nucleotide substitution in the DNA of a patient on gene expression efficiency was analyzed by in vitro transcrip-tion/translation. Cone -specific gene variants, fundus, visual field and electroretinogram (ERG) findi ngs, and protein synthesis efficiency. We found a heterozygous G to C substituti on in the 5′untranslated region (UTR) of the PDE6H gene in the DNA of a patient with a distinctive form of cone dystrophy, her sibling, and their father. This rare form of disease is very different in manifestation from other cone dystroph ies and has been described as “cone dystrophy with nyctalopia and supernormal r od responses,”“cone dystrophy with supernormal scotopic ERGs”and “supernorma l and delayed rod ERG syndrome.”Among the 240 patients that we studied, only 1 proband had the G to C variant. Furthermore, none of the 95 controls used in thi s study had this nucleotide change. We also determined that the PDE6H variant wa s not present in another family affected with this particular type of cone dystr ophy. Because the 5’UTR of mRNAs plays a critical role in the regulation of pro tein synthesis, we determined the effect of the G to C change in this process. B y use of in vitro transcription/translation experiments, we demonstrated that th is substitution could lead to an increase in PDE6H gene expression. Our results indicate that mutations in the PDE6H gene are not common, because only 1 of 240 patients with cone dystrophy showed a single nucleotide substitution in the 5′U TR of PDE6H mRNA that could be associated with the disease. If the effect of the G to C substitution we observed in vitro also occurs in vivo, it will lead to P DE6H overexpression in the photoreceptors. Excess of PDEγmay affect normal cone cGMP-PDE function by inhibiting the catalytic PDEα,βactivity and lead to pat hogenic elevation of cGMP and eventual degeneration of cone photoreceptors.
文摘The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing an d muscle morphology before and after training. Patients increased their maximal oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter incre ased significantly, and creatine kinase did not increase with training. The stud y indicates that aerobic training is safe and can improve fitness effectively in patients with myotonic dystrophy.
文摘Background: To obtain a driver’s licence certain requirements for visual acui ty and visual field have to be fulfilled. Mesopic contrast and glare sensitivity are not regularly tested and are not crucial to passing the driving test. Case report: We report a case of a 39-year-old professional bus driver whose only c omplaint was increased glare sensitivity. After he had been involved in four tra ffic accidents, ophthalmological investigations revealed binocular annular scoto mata and night blindness, leading to the diagnosis of rod-cone dystrophy. Discu ssion: Enhanced glare sensitivity is a common complaint in elderly people or peo ple with the beginnings of cataract but may also represent an initial symptom of a retinal disorder. It is therefore advisable for traf-fic safety if drivers w ith such complaints undergo a complete ophthalmological investigation including visual field testing.
文摘Purpose:To correlate the functional results of maculartranslocation(MT )in a patient suffering from an adult-onset foveomacular vitellif orm dystrophy(AFVD)with the microscopic findings of the surgically removed subfoveal retinal pigment epithelium(RPE).Methods:A78-year-old woman with AFVD underwe nt MT with 360°retinotomy 3-4months after loss of r eading ability.Most of the vitelliform material was lost during surgery;the subfoveal tissue was excised,fixed in aldehydes,postfixed in reduced OSO4and embedded in epoxy resin.Semithin sections were stained with toluidin e blue for light mi-croscopy(LM)and thin sections with uranyl acetate and lead citrate for transmission electron microscopy(TEM).Results:Postoperatively,the pati ent developed a retinal detachment complicated by proliferative vitreoretinopathy(PVR)requiring two additional vitreoretinal procedures before finally the silicone oil coul d be removed.Twen-ty-two months after MT the distance v isual acuity was un-changed at 0.2;the near visual acuit y had improved from less than 0.1before MT to 0.4.The retina was completely attached.LM and TEM revealed seriou s alterations in-dicative of a breakdown of the outer l ayer of the retina.Conclusion:Through the present sin gle case it is not possible to determine whether MT cou ld be a therapeutic approach in patients with AFVD.The m ost important cause for the limited postoperative visual improvement seems to be a primary injury of the foveal function due to the AFVD.This is supported by the extensive subfoveal degeneration and necrosis affectin g not only the RPE cells but also their basement membrane and the interposed basal laminar deposits.
文摘Purpose Fundus autofluorescence is due to accumulation of lipofuscin in the retinal pigment ep ithelium(RPE)resulting from incomplete digestion of N-retinylidene-phosphatidyl-ethanolamine from shed photorecep tor outer segment discs.Alteration in autofluorescence reflects changes in lipofuscin content of the RPE.Mutations on both alleles of RPE65result in absent or largely decrease d formation of rhodopsin,due to a defect in alltrans retinol is omerization in the RPE.Autofluorescence could therefore b e altered.This study was conducted to evaluate fundus autofl uorescence in patients with early-onset severe retinal dystrophy(EOSRD,or ear-ly-onset rod-cone dystrophy)associated with mutations on both alleles of RPE65.Design Case se ries.Participants and controls Ten 10-to 55-year-old p atients with EOSRD and compound heterozygous or homozy gous mutations in RPE65.For comparison,6heterozygous parents and 2patients with other forms of EOSRD we re examined.Methods Participants underwent,in addition to standard clinical and electrophysiological examination,autofluores-cence imaging using a confocal scanning laser ophthalmo-scope.Three of the patients were als o examined by optical coherence tomography(OCT)to evaluate the status of retinal degeneration.Mutations in7patients have been reported previously;the other pati ents were investigated by polymerase chain reaction-single-strand conformation poly-morphism and direct sequencing for mutations in RPE65and lecithin retinol acyltransfera se(LRAT).Main outcome measures Fundus autofluorescence a nd OCT.Results Ab-sent or minimal autofluorescence wa s found in all patients with compound heterozygous or homozygous RPE65muta-tions.Autofluorescence was normal in the heterozygous parents.Autofluorescence was present in 2children with EOSRD not associated with mutations in RPE65or LRAT,another gene involved in retinol recycling.Optical coher-ence tomography in younger patients revealed an intraretinal appearance similar to that of their h ealthy,heterozygous parents.Conclusions Lack of autofl uorescence in patients with EOSRD associated with mutation s in RPE65is in ac-cordance with the biochemical defect and can be used as a clinical marker of this genotype.Optical coherence tomog-raphy results in younger patients wo uld indicate still viable photoreceptors despite the absence of autofluorescence.
