RESUMEN
BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain. RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-ß levels contralateral (râ =â 0.86, Pâ <â 0.0001; râ =â 0.96, Pâ =â 0.0008) and ipsilateral (râ =â 0.82, Pâ =â 0.0002; râ =â 0.87, Pâ =â 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (râ =â 0.97, Pâ =â 0.0003). CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-ß in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-ß pathology, both in patients with possible NPH and among the wider population.
Asunto(s)
Péptidos beta-Amiloides/metabolismo , Compuestos de Anilina , Benzotiazoles , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Hidrocéfalo Normotenso/metabolismo , Hidrocéfalo Normotenso/patología , Tiazoles , Anciano , Compuestos de Anilina/efectos adversos , Benzotiazoles/efectos adversos , Biopsia , Corteza Cerebral/diagnóstico por imagen , Femenino , Neuroimagen Funcional , Humanos , Hidrocéfalo Normotenso/diagnóstico por imagen , Masculino , Placa Amiloide/patología , Cintigrafía , Sensibilidad y EspecificidadRESUMEN
Since the introduction of Guglielmi detachable coils to treat intracranial aneurysms in 1991, the number of patients undergoing endovascular coiling has continuously risen as well as the number of those residual and recurrent previously coiled aneurysms that necessitate a microsurgical occlusion. Between July 1995 and August 2009 we retrospectively analyzed 81 patients with 82 previously coiled aneurysms treated microsurgically at two Finnish Neurosurgical University Hospitals, Helsinki and Kuopio. Fifty-eight aneurysms (71%) were located at anterior circulation and 24 (29%) at posterior circulation. Fifteen patients were operated on within the first month (early surgery) after coiling, whereas 66 were treated later (late surgery). Complete or partial removal of coils during surgery may facilitate clipping, but is significantly (P<0.001) more difficult to accomplish in late surgery. Removal of coils may also increase the chance for poor outcome. Chance of poor outcome increased also with intraoperative aneurysm rupture, size of the aneurysm and posterior circulation location. Good clinical outcome, three months after surgery, was achieved in 71 patients (88%); four patients were severely disabled, and six patients died (three of them due to poor clinical condition). Complete microsurgical occlusion of the residual previously coiled aneurysm is a high-risk procedure in large and giant aneurysms, and these patients should be referred to a dedicated neurovascular center to minimize surgical complications. Bypass procedures may be the best option for demanding growing lesions, especially those in posterior circulation.
Asunto(s)
Revascularización Cerebral/métodos , Aneurisma Intracraneal/cirugía , Microcirugia/métodos , Procedimientos Neuroquirúrgicos/métodos , Hemorragia Subaracnoidea/cirugía , Adolescente , Adulto , Anciano , Niño , Remoción de Dispositivos , Embolización Terapéutica , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Intracraneal/terapia , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Hemorragia Subaracnoidea/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND AIMS: To compare six Finnish hospitals for the quality of treatment of hip fractures and to obtain information for the development of care. MATERIAL AND METHODS: Data of 1179 consecutive hip fracture patients (about 200 patients per hospital) was collected prospectively, using similar standardized forms and focusing on background factors and the four-month functional outcome. RESULTS: There were significant differences between the hospitals in patient characteristics (age, place of residence, walking ability, use of walking aids, morbidity and type of fracture) and in the unadjusted outcome variables at four months' follow-up (place of residence, mobility, use of walking aids and pain in injured hip). After adjustment for baseline characteristics, there was a significant difference in the post-fracture walking ability between the centres but no significant differences in post-fracture place of residence. Unadjusted mortality did not vary between the centres, but adjustment resulted in significant differences. The most marked difference in surgical methods between the hospitals was seen in the use of either sliding hip screw or Gamma Nail for trochanteric fractures, but this difference was not reflected in the results of multivariate analysis. CONCLUSIONS: We found minor differences in mobility and mortality between the participating hospitals, and these might serve them as a stimulus for improving their standard of good practice. Continuous quality improvement by repeating the audit cycle is recommended in order to reach and then improve the prevalent standards in the care of hip fracture patients. Confounding factors should be adjusted when comparing the medical centres treating hip fractures, and the evaluation of the results should be multidimensional.
Asunto(s)
Fracturas de Cadera/cirugía , Artroplastia , Factores de Confusión Epidemiológicos , Femenino , Finlandia , Fijación Interna de Fracturas , Humanos , Modelos Logísticos , Masculino , Estudios Prospectivos , Calidad de la Atención de Salud , Reoperación , Resultado del TratamientoRESUMEN
BACKGROUND: Variegate porphyria (VP) is an inherited disorder of heme biosynthesis that results from a partial deficiency of protoporphyrinogen oxidase (PPOX). Patients with VP may experience acute neurovisceral attacks and cutaneous photosensitivity. To date we have characterized 109 VP patients representing 19 VP families in the Finnish population of 5 million, both biochemically and clinically. MATERIALS AND METHODS: Mutations were identified by direct sequencing of the patients' genomic DNA. The effect of the mutations was determined by sequencing the reverse transcriptase polymerase chain reaction (RT-PCR) product amplified from total RNA extracted from the patients' lymphoblast cell lines and expressing the mutations in E. coli and COS-1 cells. RESULTS: Of the six mutations identified in the PPOX gene, three mutations (IVS2-2a-->c, 338G-->C, and 470A-->4C) caused splicing defects, one produced a frameshift (78insC) and two mutations (R152C and L401F) caused amino acid substitutions. In RT-PCR, the IVS2-2a-->c mutation caused a retention of a 36-bp fragment in the 3' end of intron 2, the 338G-->C mutation caused an exon 4 deletion, and the 470A-->C mutation caused an exon 5 deletion with retention of a 19-bp fragment of the 3' end of intron 5. In both prokaryotic and eukaryotic expression systems, the PPOX activities of five mutants were decreased to 0-5% of the normal activity. CONCLUSIONS: This study describes five novel mutations and one earlier described major mutation among Finnish VP patients. All mutations produced detectable transcripts, but resulted in decreased PPOX activity confirming the causality of the mutations and the biochemical defects in these patients.
Asunto(s)
Mutación , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Oxidorreductasas/genética , Porfirias Hepáticas/genética , Animales , Células COS , Análisis Mutacional de ADN , Escherichia coli , Proteínas de Escherichia coli , Exones , Femenino , Finlandia , Flavoproteínas , Mutación del Sistema de Lectura , Tamización de Portadores Genéticos , Heterocigoto , Humanos , Masculino , Proteínas Mitocondriales , Mutación Missense , Oxidorreductasas/deficiencia , Linaje , Mutación Puntual , Porfirias Hepáticas/diagnóstico , Protoporfirinógeno-Oxidasa , Mapeo Restrictivo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Transcripción GenéticaRESUMEN
The long-term follow-up of a homozygous variegate porphyria patient revealed severe photosensitivity accompanied by mild sensory neuropathy and IgA nephropathy. A 35T to C transition in exon 2 (I12T) and a 767C to G transversion in exon 7 (P256R) of the protoporphyrinogen oxidase gene were identified from both alleles of the patient's cDNA and genomic DNA samples. Both prokaryotic and eukaryotic expression studies showed that the first mutation in the evolutionary conserved region resulted in a decrease in the protoporphyrinogen oxidase activity in contrast to the polymorphic substitution in exon 7, which affected the function of the enzyme assayed in Escherichia coli but not COS-1 cells.
Asunto(s)
Variación Genética , Homocigoto , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Porfirias/genética , Secuencia de Bases/genética , Flavoproteínas , Estudios de Seguimiento , Humanos , Masculino , Proteínas Mitocondriales , Datos de Secuencia Molecular , Oxidorreductasas/genética , Linaje , Porfirias/patología , Porfirias/fisiopatología , Protoporfirinógeno-OxidasaRESUMEN
Variegate porphyria (VP) is an inherited metabolic disease that results from the partial deficiency of protoporphyrinogen oxidase. In this communication we have used DNA technology in the diagnosis of VP and compared the results with the biochemical and clinical data. To date, we have diagnosed 107 VP patients using either biochemical or DNA techniques or both. In addition, in 106 family members the diagnosis of VP could be excluded. The sensitivity and specificity of the biochemical screening for VP were studied among 38 family members. These individuals were either asymptomatic (n = 19) or had experienced occasional skin symptoms (n = 13), acute attacks (n = 5) or both (n = 1). The sensitivity of urinary and fecal coproporphyrin analysis was 48% and 52%, respectively. The sensitivity of urinary uroporphyrin analysis was 71% and for fecal protoporphyrin 77%. Plasma fluorescence was sensitive in symptomatic patients even in remission, but resulted in false negatives in four asymptomatic patients with normal excretion of porphyrins in the urine. In our series of mutation screening, many new asymptomatic patients were identified, and this demonstrated that DNA analysis is the only reliable way to screen (a)symptomatic patients facilitating correct treatment and proper genetic counselling of family members at risk. Biochemical analyses (e.g. plasma fluorescence, fecal protoporphyrins, urinary copro- and uroporphyrins, porphobilinogen and delta-aminolevulinic acid) are essential when the diagnosis of VP is confirmed at the symptomatic phase.