RESUMO
DNA profiling and matching is one of the primary methods to identify missing persons in a disaster, as defined by the Interpol Disaster Victim Identification Guide. The process to identify a victim by DNA includes: the collection of the best possible ante-mortem (AM) samples, the choice of post-mortem (PM) samples, DNA-analysis, matching and statistical weighting of the genetic relationship or match. Each disaster has its own scenario, and each scenario defines its own methods for identification of the deceased.
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Impressões Digitais de DNA , Desastres , Autopsia , Comportamento Cooperativo , Impressões Digitais de DNA/normas , Guias como Assunto , Humanos , Comunicação Interdisciplinar , Incidentes com Feridos em Massa , Modelos Genéticos , Modelos Estatísticos , Controle de Qualidade , Software , Manejo de EspécimesRESUMO
In disaster situations it is not always possible to maintain an adequate supply of standard equipment and sterilizing solutions. We have compared bone samples from cadavers cleaned in commercial white alcohol to samples from the same individuals cleaned with 95% surgical spirit. We have found that it is possible to use a commercial, white spirit to clean specimens taken from human cadavers femoral diaphysis collected for DNA analysis.
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Depressores do Sistema Nervoso Central , Impressões Digitais de DNA , Etanol , Fêmur/patologia , Solventes , Esterilização/métodos , DNA/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase , Manejo de EspécimesAssuntos
Inibidores da Angiogênese/economia , Anticorpos Monoclonais Humanizados/economia , Edema Macular/tratamento farmacológico , Oclusão da Veia Retiniana/complicações , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Injeções Intraoculares , Edema Macular/etiologia , Ranibizumab , Suécia , Acuidade Visual/fisiologiaRESUMO
PURPOSE: This study describes the present legislation for visual requirements for driving in the Nordic countries in relation to the European Driving License Directive. METHODS: Information about the formal legislation was gathered from each countries legal text. Further information about the implementation and common practices were achieved from national authorities in vision and driving. RESULTS: Even though the Nordic countries use the same framework of legislation, the implementation varies widely. Sweden and Norway have more specified visual field requirements than the others. On the other hand, no periodic testing of visual acuity (VA) is performed in Sweden as in all other Nordic countries. Physicians on Iceland are not obliged to report a person no longer fulfilling the visual requirements, as in other Nordic countries. In Denmark, Finland and Norway a person may apply for dispensation from the requirements by performing a practical driving test. In Sweden, a person applying for dispensation can undergo a traffic simulator test. CONCLUSION: Because of the national legislation in the Nordic countries, a person with a visual impairment may be given different permissions depending on which country they live in. As the inhabitants in the Nordic countries frequently cross the regional borders, a harmonization of the legislation would be of value. More research in this field could provide future standards, combining the greatest autonomy with the highest possible safety.
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Acidentes de Trânsito/estatística & dados numéricos , Exame para Habilitação de Motoristas/legislação & jurisprudência , Condução de Veículo/legislação & jurisprudência , Oftalmologia , Visão Ocular , Humanos , Países Escandinavos e Nórdicos/epidemiologiaAssuntos
Neoplasias Hipofisárias/patologia , Complicações Neoplásicas na Gravidez/patologia , Prolactinoma/patologia , Testes de Campo Visual , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/tratamento farmacológico , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Prolactina/sangue , Prolactinoma/complicações , Prolactinoma/diagnóstico , Prolactinoma/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Transtornos da Visão/patologiaRESUMO
OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.
Assuntos
Adenoma , Neoplasias Hipofisárias , Substância Branca , Anisotropia , Imagem de Tensor de Difusão , Humanos , Vias VisuaisRESUMO
BACKGROUND: The human FUT2 gene encodes the alpha(1,2)fucosyltransferase that determines secretor status. Homozygous for the nonsense mutation are called non-secretors and are unable to express histo-blood group antigens in secretions and on mucosal surfaces. In this study we have investigated the importance of the FUT2 fucosyltransferase activity on the progress of HIV-1 infection. METHODS: Swedish blood donors (n = 276), 15 long-term non-progressors (LTNP) and 19 progressors were genotyped with respect to the nonsense mutation 428G-->A in the FUT2 gene. In addition 265/276 blood donors and 19 progressors with rapid or expected progression rate were Delta32 CCR5 genotyped. RESULTS: Of 276 blood donors 218 (79%) were found to be secretor positive (se+), either homozygous (se+/+) wild type (30%) or heterozygous (se+/-) (49%) and 58 (21%) were homozygous non-secretors (se-/-). Five LTNP (33%) were found to be secretor-positive (se+/+, se+/-) and 10 (67%) se-/-. Of the 19 individuals with normal HIV-1 progression 15 (79 %) were found to be secretor positive and four (21%) were non-secretors. No frequency differences were found in the Delta32 CCR5 allele among the groups studied. CONCLUSION: Strong association (P < 0.001) was observed between the nonsense mutation 428G-->A in the FUT2 gene and a slow disease progression of HIV-1 infection.
Assuntos
Códon sem Sentido , Fucosiltransferases/genética , Infecções por HIV/enzimologia , Infecções por HIV/imunologia , HIV-1 , Adulto , Antígenos de Grupos Sanguíneos , Progressão da Doença , Frequência do Gene , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Receptores CCR5/genética , Sobreviventes , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
OBJECTIVE: To study the prevalence of lens opacities in a well-defined Swedish population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Seven hundred inhabitants of the town of Skövde, Sweden were randomly selected and invited to an ophthalmologic examination. Invited persons were 70 to 84 years old and were assigned to 1 of 3 age groups: 70 to 74, 75 to 79, or 80 to 84. METHODS: All participants underwent visual acuity (VA) testing using the Early Treatment Diabetic Retinopathy Study acuity chart. Lens opacities were graded using the Lens Opacities Classification System III after pupil dilation. Causes of visual impairment, other than cataract, were identified by thorough ophthalmologic examination. MAIN OUTCOME MEASURE: Prevalence of lens opacities. RESULTS: Five hundred sixty-five persons underwent a complete examination (participation rate, 80.7%). As expected, the presence of lens opacities increased with age. Using a definition of cataract based on morphologic changes only, prevalences of cataract in one or both eyes were 23.5% for women and 14.0% for men in the entire cohort. If prevalence of previous cataract surgery was included, prevalence rose to 47.9% for women and 27.3% for men. In all age groups, lens opacities were denser and cataract prevalence was higher in women than in men. Consequently, VA was lower in females than in men, when other reasons for visual impairment were excluded. CONCLUSIONS: Lens opacities were common in the studied age groups and increased with age. In all studied age groups, lens opacities were denser in women than in men.
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Catarata/epidemiologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Catarata/classificação , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Distribuição por Sexo , Suécia/epidemiologia , Acuidade VisualRESUMO
A total of 708 men, with Swedish names, from different parts of Sweden have been typed for the Y-chromosome minimal haplotype STR markers DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393 and DYS385. Of these, 403 men were of geographically undefined Swedish origin and the rest, 305, from seven defined geographical regions. PCR-products were detected by ABI377 using sequenced allelic ladders. An evaluation of the 708 chromosomes revealed 423 different haplotypes. Only 100 of the haplotypes were found more than once. The over all haplotype diversity was 0.994. The haplotype 14, 12, 28, 23, 10, 11, 13, 14-14 has the highest frequency of 5.79% and is significantly Swedish, when compared to other European populations.
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Cromossomos Humanos Y , Genética Populacional , Haplótipos , Sequências de Repetição em Tandem , Impressões Digitais de DNA , Humanos , Masculino , Reação em Cadeia da Polimerase , SuéciaRESUMO
PURPOSE: The purpose of this study was to describe clinical characteristics and prevalence of carotid stenosis in patients with amaurosis fugax (AF). METHOD: Patients diagnosed with AF and subjected to carotid ultrasound in 2004-2010 in Sahlgrenska University Hospital, Gothenburg (n=302), were included, and data were retrospectively collected from medical records. RESULTS: The prevalence of significant carotid stenosis was 18.9%, and 14.2% of the subjects were subjected to carotid endarterectomy. Significant associations with risk of having ≥70% stenosis were male sex (adjusted odds ratio [aOR]: 2.62; 95% confidence interval [CI]: 1.26-5.46), current smoking (aOR: 6.26; 95% CI: 2.62-14.93), diabetes (aOR: 3.68; 95% CI: 1.37-9.90) and previous vasculitis (aOR: 10.78; 95% CI: 1.36-85.5). A majority of the patients (81.4%) was seen by an ophthalmologist prior to the first ultrasound. Only 1.7% of the patients exhibited retinal artery emboli at examination. CONCLUSION: The prevalence of carotid stenosis among patients with AF is higher than has previously been demonstrated in stroke patients. An association with previously reported vascular risk factors and with vasculitis is seen in this patient group. Ocular findings are scarce.
RESUMO
PURPOSE: To describe the time course of management of patients with amaurosis fugax and analyze differences in management by different specialties. METHODS: Patients diagnosed with amaurosis fugax and subjected to carotid ultrasound in 2004-2010 at the Sahlgrenska University Hospital, Gothenburg, Sweden (n=302) were included in this retrospective cohort study, and data were collected from medical records. RESULTS: The prevalence of significant carotid stenosis was 18.9%, and 14.2% were subjected to carotid endarterectomy. A trend of longer delay for surgery was noted for patients first consulting a general practitioner (P=0.069) as compared to hospital-based specialties. For 46.3% of the patients, an ophthalmologist was their first medical contact. No significant difference in time interval to endarterectomy was seen between ophthalmologists and neurologists/internists. Only 31.8% of the patients with significant carotid stenosis had carotid endarterectomy within 2 weeks from the debut of symptoms, and this proportion was smaller for patients residing outside the Gothenburg city area (P=0.038). CONCLUSION: Initially consulting an ophthalmologist does not delay the time to ultrasound or carotid endarterectomy. The overall time from symptoms to surgery is longer than recommended for a majority of the patients, especially for patients from rural areas and for patients initially consulting a general practitioner.
RESUMO
Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (+/- standard deviation) S/R ratio for citalopram was 0.67 +/- 0.25 and for desmethylcitalopram, 0.68 +/- 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Citalopram/sangue , Citocromo P-450 CYP2D6/genética , Oxigenases de Função Mista/genética , Inibidores Seletivos de Recaptação de Serotonina/sangue , Detecção do Abuso de Substâncias/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Hidrocarboneto de Aril Hidroxilases/sangue , Causas de Morte , Cromatografia Líquida de Alta Pressão , Citalopram/análogos & derivados , Citalopram/farmacocinética , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2D6/sangue , DNA/análise , Feminino , Medicina Legal/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/sangue , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Estereoisomerismo , Fatores de TempoRESUMO
X-chromosomal markers in forensic genetics have become more widely used during recent years, particularly for relationship testing. Linkage and linkage disequilibrium (LD) must typically be accounted for when using close X-chromosomal markers. Thus, when producing the weight-of-evidence, given by a DNA-analysis with markers that are linked, the normally used product rule is invalid. Here we present an implementation of an efficient model for calculating likelihood ratios (LRs) with markers on the X-chromosome which are linked and in LD. Furthermore, the model was applied on several cases based on data from the eight X-chromosomal loci included in the Mentype(®) Argus X-8 (Biotype). Using a simulation approach we showed that the use of X-chromosome data can offer valuable information for choosing between the alternatives in each of the cases we studied, and that the LR can be high in several cases. We demonstrated that when linkage and LD were disregarded, as opposed to taken into account, the difference in calculated LRs could be considerable. When these differences were large, the estimated haplotype frequencies often had a strong impact and we present a method to estimate haplotype frequencies. Our conclusion is that linkage and LD should be accounted for when using the tested set of markers, and the used model is an efficient way of doing so.
Assuntos
Cromossomos Humanos X , Família , Ligação Genética , Marcadores Genéticos , Funções Verossimilhança , Feminino , Haplótipos , Humanos , Masculino , LinhagemRESUMO
PURPOSE: To analyse retinal nerve fibre layer (RNFL) thickness in eyes with compression of the optic chiasm by a pituitary adenoma. RNFL thickness was analysed with optical coherence tomography (OCT) and compared to visual field measurements using high-pass resolution perimetry (HRP). METHODS: Sixteen eyes from eight patients with pituitary adenoma were studied. All had bitemporal visual field depression caused by compression of the optic chiasm. Patients were submitted to an ophthalmic examination more than 14 months after surgery (seven patients had undergone trans-sphenoidal and one trans-cranial adenomectomy). The examination included HRP, fundus photography and measurement of the peripapillar RNFL thickness using OCT. RESULTS: In spite of temporal visual field depression, not all eyes showed reduced RNFL thickness by OCT. This was also true for some eyes in which RNFL was judged to be reduced on fundus photographs. Contrary to our expectations, RNFL thickness in the nasal quadrant was normal in nine of the 16 eyes. Corresponding figures for the superior, inferior and temporal quadrants were eight, six and five, respectively. The overall RNFL thickness, as measured by OCT, did not correlate well with neural capacity, which is an index of remaining retino-cortical neural channels in HRP. CONCLUSION: RNFL thickness as measured with OCT was reduced in most, but not all, eyes with temporal field depression caused by chiasmal compression. The pattern of RNFL loss did not correlate well with the visual field defect. Sensitivity of RNFL thickness measurement in OCT was low. The method has limited value in the diagnosis of pituitary tumour compression.
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Adenoma/diagnóstico , Fibras Nervosas/patologia , Disco Óptico/patologia , Neoplasias Hipofisárias/diagnóstico , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/diagnóstico , Quiasma Óptico/patologia , Testes de Campo Visual , Campos Visuais , Adulto JovemRESUMO
X-chromosomal short tandem repeats (X-STR) have proven to be informative and useful in complex relationship testing. The main feature of X-STR markers, compared to autosomal forensic markers, is that all loci are located on the same chromosome. Thus, linkage and linkage disequilibrium may occur. The aim of this work was to study population genetic parameters of eight X-STR markers, located in four linkage groups. We present haplotype frequencies, based on 718 Swedish males, for the four linkage groups included in the Argus X-8 kit. Forensic efficiency parameters have been calculated as well as the allelic association between the tested markers for detection of linkage disequilibrium. To study the occurrences of recombination between the loci, both Swedish and Somali families were typed. A mathematical model for the estimation of recombination frequencies is presented and applied on the family samples. Our study showed that the tested markers all have highly informative forensic values and that there is a significant degree of linkage disequilibrium between the STR markers within the four linkage groups. Furthermore, based on the tested families, we also demonstrated that two of the linkage groups are partially linked. A consequence of these findings is that both linkage and linkage disequilibrium should be accounted for when producing likelihood ratios in relationship testing with X-STR markers.
Assuntos
Mapeamento Cromossômico , Genética Forense/métodos , Desequilíbrio de Ligação , Repetições de Microssatélites/genética , Cromossomos Humanos X/genética , Feminino , Amplificação de Genes/genética , Frequência do Gene , Haplótipos , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Recombinação GenéticaRESUMO
PURPOSE: To study the presence of relative afferent pupillary defect (RAPD) in patients with glaucoma with the help of a custom-built pupillometer. METHODS: Sixty-five participants were recruited (32 with open-angle glaucoma and 33 healthy subjects). All underwent standard clinical examination including perimetry and optic disc photography. Pupillary light reflexes were examined with a custom-built pupillometer. Three video sequences were recorded for each subject. Alternating light stimulation with a duration of 0.5 seconds was used, followed by a 1 second pause. Mean values of pupil area ratio (PAR), pupil contraction velocity ratio (PCVR), and pupil dilation velocity ratio (PDVR) were calculated. Receiver operating characteristic (ROC) curves were constructed for each of the three parameters. Intra-individual variability was estimated. RESULTS: PAR and PDVR differed significantly between the group with glaucoma and the control group (P < 0.0001). PAR was more sensitive for glaucoma detection than the other pupillometric parameters (PCVR and PDVR). The area under the receiver operating characteristic curve was largest for PAR. At a fixed specificity of 90%, sensitivity for PAR was 86.7%. CONCLUSION: Measuring RAPD with infrared computerized pupillometry can detect optic neuropathy in glaucoma with high sensitivity and specificity. The method is fast and objective. Pupil area amplitude measurements were superior to pupil velocity measurements for the detection of RAPD in glaucoma.
Assuntos
Glaucoma de Ângulo Aberto/complicações , Doenças do Nervo Óptico/complicações , Distúrbios Pupilares/complicações , Idoso , Técnicas de Diagnóstico Oftalmológico , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Luz , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Distúrbios Pupilares/diagnóstico , Reflexo Pupilar , Sensibilidade e Especificidade , Campos VisuaisRESUMO
BACKGROUND: The Heidelberg Retina Tomograph (HRT) is a commercially available instrument for the detection of glaucomatous damage by analysis of optic nerve head topography. The main purpose of the study was to investigate the ability of HRT to detect changes in optic disc topography indicating progression of optic neuropathy in eyes with open-angle glaucoma or, in eyes with ocular hypertension, conversion to open-angle glaucoma. METHODS: Fifty-nine subjects (34 with ocular hypertension, 25 with glaucoma) from the glaucoma service at Sahlgrenska University Hospital were included in this study. One eye of each patient was selected. All participants underwent thorough clinical examination, including HRT, high-pass resolution perimetry (HRP), and optic disk photography. After a mean follow-up time of 50 months, patients were re-examined. Based on analyses of optic disc photographs and HRP, eyes were classified into one of two groups: progressive or stable. The differences between baseline and follow-up HRT parameters in the two groups were analysed. The topographic HRT change images were also compared after digital image processing. A pixel ratio was calculated defined as the ratio between the area of pixels representing deepening of the disc surface and the total disc area. Receiver operating characteristic (ROC) curves for HRT parameters and pixel ratio were compared. RESULTS: In the group judged to have progressive optic neuropathy, a statistically significant change between baseline and follow-up examination was found for the following HRT parameters: cup shape measurement, classification index, the third moment in contour, cup/disc ratio, cup area, rim area, and area below reference). In the stable group no HRT parameters had changed significantly. A well-defined distinction between the two groups was found by comparing digitally processed HRT change images. The area under the ROC curve was larger for pixel ratio than for any of the HRT parameters. CONCLUSIONS: The HRT is a useful tool for long-term follow-up of glaucomatous optic neuropathy. Digital image processing of HRT change images could facilitate the detection of progressive change.
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Glaucoma de Ângulo Aberto/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Idoso , Técnicas de Diagnóstico Oftalmológico/instrumentação , Progressão da Doença , Feminino , Seguimentos , Humanos , Pressão Intraocular , Masculino , Hipertensão Ocular/diagnóstico , Fotografação , Estudos Retrospectivos , Tomografia/métodos , Transtornos da Visão/diagnóstico , Campos VisuaisRESUMO
PURPOSE: To assess resource utilization and costs associated with glaucoma management in France and Sweden. METHODS: A total of 267 patient records (121 in France, 146 in Sweden) with diagnoses of primary open-angle glaucoma (POAG) and ocular hypertension (OH), treated medically, were reviewed for a 2-year period (beginning during 1997-99) for relevant clinical and resource utilization data. Economic data were applied to estimate treatment costs. RESULTS: The annual cost of treating glaucoma was estimated at SEK5305 (531 euro )/patient in Sweden and 390 euro/patient in France. In both countries, medication costs comprised about half of the total costs. Surgical procedures and hospitalizations represented greater proportions of total cost in France (7.0% and 9.6%, respectively) than in Sweden (3.7% and 0.6%, respectively). CONCLUSION: Medication costs represent a high proportion of total treatment costs. These findings highlight the relative importance of medical therapy and of assessing the cost-effectiveness of medications in glaucoma.
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Glaucoma de Ângulo Aberto/economia , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Idoso , Anti-Hipertensivos/economia , Análise Custo-Benefício , Custos de Medicamentos , Feminino , França , Glaucoma de Ângulo Aberto/terapia , Humanos , Pressão Intraocular , Masculino , Hipertensão Ocular/economia , Hipertensão Ocular/terapia , Procedimentos Cirúrgicos Oftalmológicos/economia , Estudos Retrospectivos , SuéciaRESUMO
BACKGROUND: Identification of CYP2D6 alleles *5 (deletion of the whole CYP2D6 gene) and *2xN (gene duplication) is very important because they are associated with decreased or increased metabolism of many drugs. The most commonly used method for analysis of these alleles is, however, considered to be laborious and unreliable. METHODS: We developed a method to determine the copy number of the CYP2D6*5 and CYP2D6*2xN alleles by use of Pyrosequencing technology. A single set of PCR and sequencing primers was used to coamplify and sequence a region in the CYP2D6 gene and the equivalent region in the CYP2D8P pseudogene, and relative quantification between these fragments was performed. The CYP2D8P-specific Pyrosequencing peak heights were used as references for the CYP2D6-specific peak heights. RESULTS: Analysis of 200 pregenotyped samples showed that this approach reliably resolved 0-4 genome copies of the CYP2D6 gene. In 15 of these samples, the peak pattern from one analyzed position was unexpected but could be solved by conclusive results from a second position. The method was verified on 270 other samples, of which 267 gave results that corresponded to the expected genotype. One of the samples could not be interpreted. The reproducibility of the method was high. CONCLUSIONS: CYP2D6 gene copy determination by Pyrosequencing is a reliable and rapid alternative to other methods. The use of an internal CYP2D8P control as well as generation of a sequence context ensures a robust method and hence facilitates method validation.