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Introduction: Parkinson's disease (PD) is typically diagnosed when motor symptoms first occur. However, PD-related non-motor symptoms may appear several years before diagnosis. REM sleep behaviour disorder (RBD) and olfactory deficits (hyposmia) are risk factors, but they are not specific for predicting progression towards PD. Other PD-related markers, for example brain imaging markers, may help to identify preclinical PD in hyposmic RBD patients. Studies have reported abnormal structural characteristics in the corticospinal tract (CST) of PD patients, but it is unclear whether hyposmic RBD patients have similar abnormalities that may help to predict PD in these individuals. This study examined whether CST abnormalities may be a potential marker of PD risk by using diffusion tensor imaging (DTI) measures. Methods: Twenty hyposmic RBD patients, 31 PD patients, and 29 healthy controls (HCs) were studied. DTI data were collected on a 1.5 T MRI scanner and CST characteristics (FA, MD, AD, and RD) were evaluated using probabilistic tractography (with seed regions in the bilateral primary motor cortex and mediolateral cerebral peduncles). Olfactory function was assessed with the University of Pennsylvania Smell Identification Test (UPSIT). Results: Hyposmic RBD patients showed significantly higher mean diffusivity (MD) values of the right CST compared to HCs but did not differ from PD patients. PD patients showed a trend of higher MD values compared to HCs. Conclusions: Altered diffusivity in the CST seems to be associated with RBD. The combination of RBD, hyposmia, and CST alterations may be related to later development of PD with comorbid RBD.
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Parkinson's disease (PD) is a neurodegenerative disorder that is typified by motor signs and symptoms but can also lead to significant cognitive impairment and dementia Parkinson's Disease Dementia (PDD). While dementia is considered a nonmotor feature of PD that typically occurs later, individuals with PD may experience mild cognitive impairment (PD-MCI) earlier in the disease course. Olfactory deficit (OD) is considered another nonmotor symptom of PD and often presents even before the motor signs and diagnosis of PD. We examined potential links among cognitive impairment, olfactory functioning, and white matter integrity of olfactory brain regions in persons with early-stage PD. Cognitive tests were used to establish groups with PD-MCI and with normal cognition (PD-NC). Olfactory functioning was examined using the University of Pennsylvania Smell Identification Test (UPSIT) while the white matter integrity of the anterior olfactory structures (AOS) was examined using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) analysis. Those with PD-MCI demonstrated poorer olfactory functioning and abnormalities based on all DTI parameters in the AOS, relative to PD-NC individuals. OD and microstructural changes in the AOS of individuals with PD may serve as additional biological markers of PD-MCI.
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Disfunção Cognitiva , Demência , Doença de Parkinson , Humanos , Imagem de Tensor de Difusão , Eletroencefalografia , Disfunção Cognitiva/diagnóstico , BiomarcadoresRESUMO
PURPOSE: The purpose of this study was to evaluate the sensitivity, specificity, and positive and negative predictive values of the diffusion-weighted periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique in the detection of cholesteatoma at our institution with surgical confirmation in all cases. METHODS: A retrospective review of 21 consecutive patients who underwent diffusion-weighted PROPELLER magnetic resonance imaging (MRI) on a 1.5T MRI scanner prior to primary or revision/second-look surgery for suspected cholesteatoma from 2009-2012 was performed. RESULTS: Diffusion-weighted PROPELLER had a sensitivity of 75%, specificity of 60%, positive predictive value of 86%, and negative predictive value of 43%. In the 15 patients for whom the presence or absence of cholesteatoma was correctly predicted, there were 2 cases where the reported locations of diffusion restriction did not correspond to the location of the cholesteatoma observed at surgery. CONCLUSION: On the basis of our retrospective study, we conclude that diffusion-weighted PROPELLER MRI is not sufficiently accurate to replace second look surgery at our institution.
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Colesteatoma da Orelha Média/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Processamento de Imagem Assistida por Computador , Adulto , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
Pediatric intracranial calcification may be caused by inherited or acquired factors. We describe the identification of a novel rearrangement in which a downstream pseudogene translocates into exon 9 of OCLN, resulting in band-like brain calcification and advanced chronic kidney disease in early childhood. SNP genotyping and read-depth variation from whole exome sequencing initially pointed to a mutation in the OCLN gene. The high degree of identity between OCLN and two pseudogenes required a combination of multiplex ligation-dependent probe amplification, PCR, and Sanger sequencing to identify the genomic rearrangement that was the underlying genetic cause of the disease. Mutations in exon 3, or at the 5-6 intron splice site, of OCLN have been reported to cause brain calcification and polymicrogyria with no evidence of extra-cranial phenotypes. Of the OCLN splice variants described, all make use of exon 9, while OCLN variants that use exons 3, 5, and 6 are tissue specific. The genetic rearrangement we identified in exon 9 provides a plausible explanation for the expanded clinical phenotype observed in our individuals. Furthermore, the lack of polymicrogyria associated with the rearrangement of OCLN in our patients extends the range of cranial defects that can be observed due to OCLN mutations.
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Encéfalo/fisiopatologia , Calcinose/fisiopatologia , Rearranjo Gênico , Rim/fisiopatologia , Ocludina/genética , Canadá , Pré-Escolar , Mapeamento Cromossômico , Variações do Número de Cópias de DNA , Exoma , Éxons , Feminino , Deleção de Genes , Genótipo , Homozigoto , Humanos , Íntrons , Malformações do Desenvolvimento Cortical/genética , Reação em Cadeia da Polimerase Multiplex , Mutação , Ocludina/metabolismo , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Splicing de RNA , Análise de Sequência de DNARESUMO
A sensitive and accurate spectrofluorimetric method has been developed for the determination of sulpiride in pharmaceutical preparations and human plasma. The developed method is based on the derivatization reaction of 2-cyanoacetamide with sulpiride in 30% ammonical solution. The fluorescent derivatized reaction product exhibited maximum fluorescence intensity at 379 nm after excitation at 330 nm. The optimum conditions for derivatization reactions were studied and the fluorescence intensity versus concentration plot was found to be linear over the concentration range 0.2-20.0 µg/mL with a correlation coefficient of 0.9985. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.82 and 2.73 ng/mL, respectively. The proposed method was validated according to ICH guidelines. The effects of common excipients and co-administered drugs were also studied. The accuracy of the method was checked using the standard addition method and percent recoveries were found to be in the range of 99.00-101.25% for pharmaceutical preparations and 97.00-97.80% for spiked human plasma. The method was successfully applied to commercial formulations and the results obtained for the proposed method were compared with a high-performance liquid chromatography reference method and statistically evaluated using the Student's t-test for accuracy and the variance ratio F-test for precision. A reaction pathway was also proposed.
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Nitrilas/química , Preparações Farmacêuticas/química , Sulpirida/análise , Amônia/química , Humanos , Estrutura Molecular , Espectrometria de Fluorescência , Temperatura , Fatores de TempoRESUMO
BACKGROUND: The lupus anticoagulant (LA) belongs to family of immunoglobulins, most commonly an IgG isotype. These antibodies have been identified most frequently in association with thromboembolic events, recurrent fetal loss and thrombocytopenia. The aim of the present study was to evaluate the presenting clinical and pathological features in patients LA positive presenting at AFIP Rawalpindi over the period of Jan 1993 to Nov 2000. MATERIAL/METHODS: Retrospective analysis of patients presenting with positive LA was carried out. RESULTS: 1583 suspected cases were screened for LA including 1370 females and 213 males. 1024 cases presented with history of recurrent abortions, 292 with thrombosis, 152 with thrombotic strokes before the age of 45 years, 52 with thrombocytopenia and 63 with miscellaneous disorders. Out of 1024 patients tested for recurrent abortions, 130 (13%) females were positive for lupus anticoagulant. Ten (6.5%) of 152 patients presenting with strokes were found positive. Out of 292 cases presenting with thrombosis 17 (5.9%) were found positive. CONCLUSIONS: The lupus anticoagulant prevalence in Pakistani patients with recurrent fetal loss, stroke and thrombosis is statistically significant. Clinicians should be made aware of association of LA with various diseases. The successful management of these patients depends upon close liaison with obstetricians, physicians and haematologists.
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Aborto Habitual/diagnóstico , Síndrome Antifosfolipídica/diagnóstico , Inibidor de Coagulação do Lúpus/análise , Acidente Vascular Cerebral/diagnóstico , Tromboembolia/diagnóstico , Aborto Habitual/imunologia , Adulto , Feminino , Humanos , Masculino , Gravidez , Acidente Vascular Cerebral/imunologia , Tromboembolia/imunologiaRESUMO
BACKGROUND: Deferiprone (DFP,L1) is a bidentate oral iron chelator which binds to iron in a 3:1 ratio. It has the potential advantage of reduced cost and increased compliance. We conducted a study in order to determine the efficacy and adverse effects of DFP in Pakistani thalassaemic patients. METHODS: A group of 26 thalassaemic patients entered the study during the period Jan 1999 to Aug 2002. DFP supplied by Lipomed, Switzerland was given at a daily dose of 75 mg/kg/day (range 50-75 mg/kg/day). After giving informed written consent all the patients were subjected to clinical examination and investigations for monitoring the response. Blood complete picture, liver function tests, blood urea & creatinine, antinuclear factor antibodies (ANF) were tested in all cases before starting DFP treatment. RESULTS: The patients ages ranged from 11 to 27 years, 16 were male and 10 were female. Initial serum ferritin level ranged from 3100-8800 microg/l, mean serum ferritin level was 7129 +/- 1467 microg/l (95% CI 6536 - 7721 microg/l). ECG and Echocardiography was performed in all cases and in 11 cases Cardiac Multigated acquisition (MUGA) Scan was also performed and six patients with impaired left ventricular function were identified. Four patients were lost to follow up and one patient died due to cardiomyopathy. Among the remaining 21 patients serum ferritin levels dropped to 1900 microg/l to 5600 microg/l with mean level of 4288 microg/l (95%CI 3874 - 4702 microg/l), SD 911 microg/l. Significance of difference was (p < 0.001) by Paired samples 't' test. Six patients had gastrointestinal symptoms along with two having arthropathy. ANF positivity was not detected in any patient while on DFP treatment. Similarly, agranulocytosis was not detected in any patient. CONCLUSION: Mean serum ferritin level estimated at the start of trial was 7129 microg/l. This shows that Pakistani thalassaemic patients are quite iron overloaded due to socioeconomic reasons that are peculiar to our setup. In this study DFP was well tolerated and caused fewer side effects. It had much better patient compliance and was effective in lowering serum ferritin level in previously most poorly chelated patients.
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Ferritinas/sangue , Quelantes de Ferro/uso terapêutico , Piridonas/uso terapêutico , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Criança , Deferiprona , Demografia , Feminino , Ferritinas/efeitos dos fármacos , Humanos , Quelantes de Ferro/efeitos adversos , Masculino , Paquistão , Estudos Prospectivos , Piridonas/efeitos adversos , Resultado do Tratamento , Talassemia beta/genéticaRESUMO
Conjoined twinning is a rare occurrence, and ischiopagus variety is even more rare. So far, only 20 cases have been reported. The incidence is 1 in 500,000. Because of its rarity and variable anatomy, no definite line of treatment can be adapted. Time of operation and mode of treatment have to be tailored according to the local circumstances and organ sharing in each individual pair. The twins in this report were xi phi-omphalo-ischiopagus tetrapus conjoined twins. Although several internal organs were fused and shared, they were complete mirror image sets for each twin. In this case report, details of anatomy and more importantly, preoperative investigations, preparations, and organizational aspects that were designed to suit local conditions are described. Operative details, postoperative care, and short and long-term progress also has been highlighted.