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OBJECTIVES: The aim of this study was to evaluate and compare the effect of acidic beverages on the hardness, elastic modulus, and wear resistance of four different resin-based restorative materials. METHODS AND MATERIALS: A total of 128 specimens (10 mm diameter, 4 mm thickness) were prepared from a conventional resin composite (Filtek Z250 [Z250]), a giomer bulk-fill (Beautifil Bulk Restorative [BBR]) and two nongiomer bulk-fill materials (Tetric N-Ceram Bulk Fill [TNC] and SonicFill 2 [SF2]). Each material group was divided into four subgroups (n=8) according to the storage media: artificial saliva (control), orange juice, regular Coke, and sports drink. The experimental specimens were immersed in the solutions for 30 minutes, five times a day for 5 days and kept in artificial saliva for an hour between the immersion periods. Control specimens were stored in artificial saliva for 5 days. The nanoindentation test with a Berkovich diamond tip was used to determine the hardness and elastic modulus before and after the 5-day storage periods. Following the nanoindentation tests, the specimens were subjected to a chewing simulator for 120,000 cycles. The specimens were then scanned with a three-dimensional scanner. The wear resistance was analyzed by measuring the volume and height loss. Specimens were observed by environmental scanning electron microscopy. The statistical analyses were performed by analysis of variance, Tukey HDS test, and paired samples t-test (α=0.05). RESULTS: Z250 showed significantly higher elastic modulus in all groups (p<0.05). After erosive cycles, the greatest decrease in hardness and elastic modulus was observed for BBR. TNC showed higher wear resistance than the other resin-based materials (p<0.05). The BBR specimens immersed in acidic solutions showed higher wear rates than the artificial saliva group (p<0.05). CONCLUSIONS: Conventional resin composite showed higher hardness and elastic modulus than bulk-fill materials when exposed to acidic beverages but comparable or lower wear resistance. Degradation due to acidic beverages most affected the mechanical properties of giomer bulk-fill.
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Resinas Compuestas , Materiales Dentales , Módulo de Elasticidad , Dureza , Saliva Artificial , Ensayo de Materiales , BebidasRESUMEN
BACKGROUND: Vertigo or dizziness is a common occurrence, but it remains a challenging symptom when encountered in the emergency department (ED). A diagnostic score for stroke with high accuracy is therefore required. METHODS: A single-center observational study (498 patients) was conducted. The predictor variables were derived from a multivariate logistic regression analysis with Akaike information criterion. The outcome was the occurrence of stroke. We evaluated the utility of a new diagnostic score (TriAGe+) and compared it with the ABCD2 score. RESULTS: The cohorts included 498 patients (147 with stroke [29.4%]). Eight variables were included: triggers, atrial fibrillation, male gender, blood pressure ≥140/90 mm Hg, brainstem or cerebellar dysfunction, focal weakness or speech impairment, dizziness, and no history of vertigo or dizziness or labyrinth or vestibular disease. We derived the TriAGe+ score from these variables. In the cohort, the prevalence of stroke increased significantly using the diagnostic score: 5.9% for a score of 0-4; 9.1% for 5-7; 24.7% for 8-9; and 57.3% for 10-17. At a cutoff value of 10 points, the sensitivity of the score was 77.5%, the specificity was 72.1%, and the positive likelihood ratio was 3.2. When the cutoff was defined as 5 points, the score obtained a high sensitivity (96.6%) with a good negative likelihood ratio (.15). The new score outperformed the ABCD2 score for the occurrence of stroke (C statistic, .818 versus .726; P < .001). CONCLUSIONS: The TriAGe+ score can identify the occurrence of stroke in patients with vertigo or dizziness presenting to the ED.
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Técnicas de Apoyo para la Decisión , Mareo/epidemiología , Servicio de Urgencia en Hospital , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Triaje/métodos , Vértigo/epidemiología , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype. AIM: To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype. METHODS: Twenty-eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty-four-hour intragastric pH monitoring was performed on day 7 on each regimen. RESULTS: In the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype-dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily. CONCLUSION: Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.
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Citocromo P-450 CYP2C19/genética , Esomeprazol/farmacología , Ácido Gástrico/metabolismo , Inhibidores de la Bomba de Protones/farmacología , Pirroles/farmacología , Sulfonamidas/farmacología , Adulto , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Esomeprazol/administración & dosificación , Esomeprazol/farmacocinética , Femenino , Genotipo , Humanos , Concentración de Iones de Hidrógeno , Japón , Masculino , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/farmacocinética , Pirroles/administración & dosificación , Pirroles/farmacocinética , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacocinéticaRESUMEN
PURPOSE: To evaluate the images created in a model eye during simulated cataract surgery. PATIENTS AND METHODS: This study was conducted as a laboratory investigation and interventional case series. An artificial opaque lens, a clear intraocular lens (IOL), or an irrigation/aspiration (I/A) tip was inserted into the 'anterior chamber' of a model eye with the frosted posterior surface corresponding to the retina. Video images were recorded of the posterior surface of the model eye from the rear during simulated cataract surgery. The video clips were shown to 20 patients before cataract surgery, and the similarity of their visual perceptions to these images was evaluated postoperatively. RESULTS: The images of the moving lens fragments and I/A tip and the insertion of the IOL were seen from the rear. The image through the opaque lens and the IOL without moving objects was the light of the surgical microscope from the rear. However, when the microscope light was turned off after IOL insertion, the images of the microscope and operating room were observed by the room illumination from the rear. Seventy percent of the patients answered that the visual perceptions of moving lens fragments were similar to the video clips and 55% reported similarity with the IOL insertion. Eighty percent of the patients recommended that patients watch the video clip before their scheduled cataract surgery. CONCLUSIONS: The patients' visual perceptions during cataract surgery can be reproduced in the model eye. Watching the video images preoperatively may help relax the patients during surgery.
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Catarata/patología , Modelos Biológicos , Facoemulsificación , Retina/fisiología , Grabación en Video , Visión Entóptica/fisiología , Percepción Visual/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Implantación de Lentes Intraoculares , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan. AIM: To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation to CYP2C19 genotype. METHODS: We performed 24-h pH monitoring studies on Day 7 of PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers (PMs)] using a randomised four-way crossover design: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg and rabeprazole 10 mg twice daily. RESULTS: Although median pH values with esomeprazole, omeprazole, lansoprazole and rabeprazole were 5.7 (3.5-7.2), 5.5 (2.4-7.2), 5.5 (3.7-7.3) and 5.2 (2.5-7.3), respectively (no statistically significant differences), CYP2C19 genotype-dependent differences were smaller for esomeprazole and rabeprazole compared with values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with esomeprazole [5.4 (3.5-6.8)] was significantly higher than those with omeprazole [5.0 (2.4-5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or rabeprazole [4.8 (2.5-6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0 independent of the PPI. CONCLUSIONS: In intermediate and rapid metabolisers of CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of the four PPIs. Therefore, esomeprazole may be effective in Japanese population when dosed twice daily.
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Hidrocarburo de Aril Hidroxilasas/genética , Esomeprazol/administración & dosificación , Ácido Gástrico/metabolismo , Inhibidores de la Bomba de Protones/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/metabolismo , Estudios Cruzados , Citocromo P-450 CYP2C19 , Esquema de Medicación , Esomeprazol/farmacología , Femenino , Genotipo , Humanos , Concentración de Iones de Hidrógeno , Japón , Lansoprazol/administración & dosificación , Lansoprazol/farmacología , Masculino , Omeprazol/administración & dosificación , Omeprazol/farmacología , Polimorfismo Genético/efectos de los fármacos , Inhibidores de la Bomba de Protones/farmacología , Rabeprazol/administración & dosificación , Rabeprazol/farmacología , Adulto JovenRESUMEN
We investigated the non-genomic effects of glucocorticoids (GCs) on inhibition of plasma membrane lipid raft formation in activated human basophils. Human basophils obtained from house dust mite (HDM)-sensitive volunteers were pretreated with hydrocortisone (CORT) or dexamethasone (Dex) for 30 min and then primed with phorbol 12-myristate 13-acetate (PMA, 10 ng/ml) or HDM (10 µg/ml). The expression of CD63, a basophil activation marker, was assessed by flow cytometry. Membrane-bound GC receptors (mGCRs) were analysed by flow cytometry and confocal laser microscopy. Lipid rafts were assessed using a GM1 ganglioside probe and visualization by confocal laser microscopy. Pretreatment of basophils with CORT (10(-4) M and 10(-5) M) and Dex (10(-7) M) significantly inhibited CD63 expression 20 min after addition of PMA or HDM. The inhibitory effects of GCs were not altered by the nuclear GC receptor (GCR) antagonist RU486 (10(-5) M) or the protein synthesis inhibitor cycloheximide (10(-4) M) (P < 0·05). CORT coupled to bovine serum albumin (BSA-CORT) mimicked the rapid inhibitory effects of CORT, suggesting the involvement of mGCRs. mGCRs were detectable on the plasma membrane of resting basophils and formed nanoclusters following treatment with PMA or HDM. Pretreatment of cells with BSA-CORT inhibited the expression of mGCRs and nanoclustering of ganglioside GM1 in lipid rafts. The study provides evidence that non-genomic mechanisms are involved in the rapid inhibitory effect of GCs on the formation of lipid raft nanoclusters, through binding to mGCRs on the plasma membrane of activated basophils.
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Basófilos/efectos de los fármacos , Glucocorticoides/farmacología , Microdominios de Membrana/efectos de los fármacos , Pyroglyphidae/metabolismo , Receptores de Glucocorticoides/metabolismo , Animales , Basófilos/inmunología , Basófilos/metabolismo , Bovinos , Membrana Celular/inmunología , Membrana Celular/metabolismo , Células Cultivadas , Cicloheximida/farmacología , Dexametasona/inmunología , Dexametasona/farmacología , Citometría de Flujo , Gangliósido G(M1)/metabolismo , Regulación de la Expresión Génica , Glucocorticoides/inmunología , Humanos , Hidrocortisona/inmunología , Hidrocortisona/farmacología , Leucocitos Mononucleares/citología , Microdominios de Membrana/inmunología , Microdominios de Membrana/metabolismo , Microscopía Confocal , Mifepristona/farmacología , Pyroglyphidae/inmunología , Receptores de Glucocorticoides/análisis , Receptores de Glucocorticoides/antagonistas & inhibidores , Albúmina Sérica Bovina/metabolismo , Acetato de Tetradecanoilforbol/inmunología , Acetato de Tetradecanoilforbol/farmacología , Tetraspanina 30/análisis , Tetraspanina 30/antagonistas & inhibidoresRESUMEN
BACKGROUND: Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid-related diseases. AIM: To evaluate acid inhibitory effects by different dosing times of a PPI at the same daily dosage, in a study involving 70 rounds of pH monitoring. METHODS: Using pH monitoring, we evaluated the efficacy of different divided treatment regimens with the same total daily dose of rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35 rounds) on day 7 or 8 of PPI dosing. RESULTS: In the study of divided treatment, the median pH (when administered once, twice or four times to achieve a daily dose of 40 mg) was 4.8 (3.6-6.4), 5.7 (4.1-7.4), 6.6 (4.9-8.4), respectively. When comparing the median pHs at the same CYP2C19 genotype among different dosing times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy: 95.5% (63.2-100.0%)], irrespective to CYP2C19 genotype. CONCLUSION: Four times daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including during the night-time, suggesting its potential usefulness as a regimen for patients who are refractory to standard once daily PPI treatment.
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2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/genética , Ácido Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Inhibidores de la Bomba de Protones/administración & dosificación , Administración Oral , Adolescente , Pueblo Asiatico , Citocromo P-450 CYP2C19 , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Determinación de la Acidez Gástrica , Mucosa Gástrica/metabolismo , Genotipo , Humanos , Concentración de Iones de Hidrógeno , Polimorfismo Genético/efectos de los fármacos , Rabeprazol , Factores de Tiempo , Adulto JovenRESUMEN
We observed a magnetic domain wall (DW) motion induced by the spin-polarized pulsed current in a nanoscale Fe(19)Ni(81) wire using a magnetic force microscope. High current density, which is of the order of 10(11) A m(-2), was required for the DW motion. A simple method to estimate the temperature of the wire was developed by comparing the wire resistance measured during the DW motion with the temperature dependence of the wire resistance. Using this method, we found the temperature of the wire was proportional to the square of the current density and became just beneath at the threshold Curie temperature. Our experimental data qualitatively support this analytical model that the temperature is proportional to the resistivity, thickness, width of the wire and the square of the current density, and also inversely proportional to the thermal conductivity.
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BACKGROUND: Filamin myopathy is associated with mutations in the filamin C gene (FLNC) and is a myofibrillar myopathy characterized by focal myofibrillar destruction and cytoplasmic aggregates containing several Z-disk-related proteins. METHODS: This study investigated 6 Japanese patients with dominantly inherited myofibrillar myopathy manifested by adult-onset, slow and progressive muscle weakness and atrophy in the distal extremities. RESULTS: The abundantly expressed proteins in the affected muscles were identified as filamin C by nano liquid chromatography-tandem mass spectrometry. A genetic analysis of FLNC identified a heterozygous c.8107delG mutation that was localized to the dimerization domain of filamin C. A biochemical crosslinking analysis of bacterially expressed recombinant wild-type and mutant filamin C fragments demonstrated that the mutant monomer disturbed the proper dimerization of the wild-type filamin dimer, resulting in formation of a heterotrimer with the wild-type filamin dimer. The expression study in C2C12 myoblasts showed that the mutant filamin fragments formed cytoplasmic aggregates with endogenous wild-type filamin C. CONCLUSIONS: This study provides evidence for the dominant-negative effects of the FLNC mutation. These effects may be mutation-specific and likely result in the variation in the clinical phenotypes seen in patients with filamin myopathy.
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Proteínas Contráctiles/genética , Eliminación de Gen , Genes Dominantes/genética , Proteínas de Microfilamentos/genética , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/genética , Adulto , Anciano , Secuencia de Aminoácidos , Animales , Línea Celular , Femenino , Filaminas , Tamización de Portadores Genéticos , Humanos , Masculino , Ratones , Persona de Mediana Edad , Datos de Secuencia Molecular , Enfermedades Musculares/patología , Mioblastos/patología , Linaje , FenotipoRESUMEN
PURPOSE: To compare two ophthalmic viscosurgical devices (OVDs), DisCoVisc (viscous dispersive) and Healon5 (viscoadaptive), in terms of their overall clinical performance during phacoemulsification and intraocular lens (IOL) implantation. METHODS: In 323 patients (DisCoVisc; 157, Healon5; 166), the surgeons evaluated on a three-point scale, the maintenance of anterior chamber (AC) during continuous curvilinear capsulorhexis (CCC), maintenance of AC during IOL implantation, retention during phacoemulsification, ease of injection, facilitation of CCC, transparency during surgery, and ease of removal from the eye. The time needed to completely remove OVDs after IOL implantation was measured. Masked examiners measured intraocular pressure (IOP), corneal thickness, and corneal endothelial cell count up to 90 days postoperatively. RESULTS: DisCoVisc was assessed to be significantly better than Healon5 in maintenance of AC during CCC (P=0.0008, Cochran-Mantel-Haenszel test) and IOL implantation (P=0.0055), retention during phacoemulsification (P=0.0009), ease of injection (P<0.0001), facilitation of CCC (P<0.0001), transparency (P<0.0001), and ease of removal (P<0.0001). The washout time was 29.6+/-13.4 and 36.2+/-17.5 s in the DisCoVisc and Healon5 groups, respectively (P=0.0002, unpaired t-test). The mean endothelial cell loss was 1.8+/-8.7% in the DisCoVisc group and 3.8+/-8.3% in the Healon5 group (P=0.0358). There were no statistically significant between-group differences in IOP and corneal thickness. CONCLUSION: DisCoVisc was better retained in the eye during phacoemulsification and was easier to remove after IOL implantation. The corneal endothelial cell loss was significantly less with DisCoVisc than with Healon5. It was indicated that the whole surgical process can be efficiently covered by DisCoVisc alone.
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Implantación de Lentes Intraoculares/métodos , Facoemulsificación/instrumentación , Anciano , Cámara Anterior/patología , Femenino , Humanos , Ácido Hialurónico/administración & dosificación , Implantación de Lentes Intraoculares/instrumentación , Masculino , Facoemulsificación/métodos , Estudios Prospectivos , Sustancias Viscoelásticas/administración & dosificaciónAsunto(s)
Esclerosis Amiotrófica Lateral/genética , Pueblo Asiatico/genética , Factores de Intercambio de Guanina Nucleótido/genética , Heterocigoto , Mutación , Adulto , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/fisiopatología , Electromiografía , Humanos , Pierna , Masculino , Músculo Esquelético/fisiopatología , Hermanos , Lengua , Adulto JovenRESUMEN
This study investigated structural alterations and the immunohistochemical expression of androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) in the mammary glands from surgically postmenopausal cynomolgus monkeys (Macaca fascicularis). Fourteen animals were divided into 2 groups. Seven animals underwent an ovariectomy (OVX), and the other 7 animals underwent a sham operation (sham). The in-life phase of study was 78 weeks. Atrophy in the mammary glands of OVX monkeys was similar to early postmenopausal atrophy of the human breast. The proportion of AR-positive cells in the OVX group was significantly higher than in the sham group, but the proportion of ER and PgR-positive cells was significantly lower. These results suggest that use of a primate model for hormone receptor expression has potential applications in basic human endocrinology, particularly in research in hormone receptor expression in mammary glands (both normal and neoplastic).
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Regulación de la Expresión Génica/fisiología , Macaca fascicularis , Glándulas Mamarias Animales/metabolismo , Ovariectomía/veterinaria , Receptores Androgénicos/metabolismo , Animales , Femenino , Glándulas Mamarias Animales/patología , Receptores Androgénicos/genéticaRESUMEN
BACKGROUND: Acute hyperglycaemia has been associated with impaired microvascular function after acute myocardial infarction (AMI), whereas pre-infarction angina (PIA) occurring shortly before the onset of AMI has been shown to reduce microvascular injury after reperfusion. OBJECTIVE: To examine whether acute hyperglycaemia prevents the protective effect of PIA on microvascular function after AMI. METHODS: We studied 205 patients with a first anterior wall AMI who underwent primary angioplasty within 12 hours of onset. Coronary flow velocity parameters were assessed immediately after reperfusion using a Doppler guidewire. Severe microvascular injury was defined as the presence of systolic flow reversal and diastolic deceleration time <600 ms. Echocardiographic wall motion was analysed before revascularisation and 4 weeks later. RESULTS: Acute hyperglycaemia, defined as a blood glucose level of >or=198 mg/dl on admission, was found in 67 (33%) patients. In patients without acute hyperglycaemia, PIA was associated with a lower incidence of systolic flow reversal, a longer diastolic deceleration time and a higher coronary flow reserve. However, in patients with acute hyperglycaemia there was no significant difference in these same parameters between patients with and without PIA. In the presence of acute hyperglycaemia PIA did not improve the change in wall motion score. In a multivariate model, the absence of PIA was an independent determinant of severe microvascular injury in patients without acute hyperglycaemia (odds ratio 6.28, p = 0.001), but not in patients with acute hyperglycaemia. CONCLUSION: The protective effect of PIA on microvascular function was attenuated in patients with acute hyperglycaemia, resulting in unfavourable functional recovery.
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Angioplastia Coronaria con Balón , Hiperglucemia/fisiopatología , Microcirculación/fisiología , Angina Microvascular/fisiopatología , Infarto del Miocardio/terapia , Velocidad del Flujo Sanguíneo/fisiología , Angiografía Coronaria/métodos , Circulación Coronaria/fisiología , Ecocardiografía/métodos , Femenino , Humanos , Hiperglucemia/complicaciones , Masculino , Angina Microvascular/patología , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , PronósticoRESUMEN
BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) defines a group of genetic disorders characterized by brain iron deposition and associated with neuronal death. The known causes of NBIA include pantothenate kinase-associated neurodegeneration (PKAN), neuroferritinopathy, infantile neuroaxonal dystrophy (INAD), and aceruloplasminemia. OBJECTIVE: To define the radiologic features of each NBIA subtype. METHODS: Brain MRIs from patients with molecularly confirmed PKAN (26 cases), neuroferritinopathy (21 cases), INAD (four cases), and aceruloplasminemia (10 cases) were analyzed blindly to delineate patterns of iron deposition and neurodegeneration. RESULTS: In most cases of PKAN, abnormalities were restricted to globus pallidus and substantia nigra, with 100% having an eye of the tiger sign. In a minority of PKAN cases there was hypointensity of the dentate nuclei (1/5 on T2* sequences, 2/26 on fast spin echo [FSE]). In INAD, globus pallidus and substantia nigra were involved on T2* and FSE scans, with dentate involvement only seen on T2*. By contrast, neuroferritinopathy had consistent involvement of the dentate nuclei, globus pallidus, and putamen, with confluent areas of hyperintensity due to probable cavitation, involving the pallida and putamen in 52%, and a subset having lesions in caudate nuclei and thalami. More uniform involvement of all basal ganglia and the thalami was typical in aceruloplasminemia, but without cavitation. CONCLUSIONS: In the majority of cases, different subtypes of neurodegeneration associated with brain iron accumulation can be reliably distinguished with T2* and T2 fast spin echo brain MRI, leading to accurate clinical and subsequent molecular diagnosis.
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Química Encefálica , Hierro/análisis , Imagen por Resonancia Magnética/métodos , Enfermedades Neurodegenerativas/diagnóstico , Adolescente , Adulto , Anciano , Apoferritinas , Ceruloplasmina/deficiencia , Niño , Preescolar , Diagnóstico Diferencial , Europa (Continente) , Femenino , Ferritinas/genética , Fosfolipasas A2 Grupo VI/deficiencia , Fosfolipasas A2 Grupo VI/genética , Humanos , Masculino , Persona de Mediana Edad , Distrofias Neuroaxonales/diagnóstico , Distrofias Neuroaxonales/genética , Distrofias Neuroaxonales/metabolismo , Distrofias Neuroaxonales/patología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , América del Norte , Fosfotransferasas (Aceptor de Grupo Alcohol)/deficiencia , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Estudios RetrospectivosRESUMEN
Four-year-old monozygotic female twins with early onset Tay-Sachs disease are described. The sisters showed similar slowly progressive clinical symptoms and deterioration, however the younger sister also demonstrated intractable myoclonus in the right leg. The serial MR images and (1)H-MR spectroscopy of the brain were obtained in both twins. MR images showed high intensity on T (2)-weighted image in the bilateral white matter, however there were no signal changes in the basal ganglia and thalamus during any of the phases. The ratio of N-acetylaspartate (NAA)/creatine (Cr) was decreased in the both white matter lesions and the corpus striatum, and that of myoinositol (mI)/Cr was increased in the damaged white matter on MR spectroscopy. The elevation of the lactate peak was clearly demonstrated in the left basal ganglia of the younger sister; however it was not shown in cerebral lesions of the elder sister. Changes in metabolites on MR spectroscopy were closely linked to the respective clinical features of each twin. Follow-up examination by (1)H-MR spectroscopy is useful for the evaluation of neuronal changes in children with Tay-Sachs disease.
Asunto(s)
Encéfalo/fisiopatología , Enfermedades en Gemelos/diagnóstico , Metabolismo Energético/fisiología , Gangliosidosis GM2/diagnóstico , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Ganglios Basales/patología , Ganglios Basales/fisiopatología , Encéfalo/patología , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Preescolar , Colina/metabolismo , Cuerpo Calloso/patología , Cuerpo Calloso/fisiopatología , Creatina/metabolismo , Análisis Mutacional de ADN , Progresión de la Enfermedad , Enfermedades en Gemelos/genética , Enfermedades en Gemelos/fisiopatología , Dominancia Cerebral/fisiología , Epilepsias Mioclónicas/diagnóstico , Epilepsias Mioclónicas/genética , Epilepsias Mioclónicas/fisiopatología , Femenino , Gangliosidosis GM2/genética , Gangliosidosis GM2/fisiopatología , Hexosaminidasa A/genética , Humanos , Inositol/metabolismo , Fibras Nerviosas Mielínicas/patología , Fibras Nerviosas Mielínicas/fisiología , Examen Neurológico , Tálamo/patología , Tálamo/fisiopatología , Gemelos MonocigóticosRESUMEN
Aceruloplasminemia is an autosomal recessive and phenotypically primarily neurodegenerative disease caused by a homozygous mutation of the ceruloplasmin gene. The absence of ceruloplasmin and its ferroxidase activity leads to pathological iron overload in the brain and other organs. While heterozygous carriers of ceruloplasmin gene mutations have been believed to be asymptomatic, a number of cases with neurological deficits have recently been described. To date, an effective treatment has not been established for either aceruloplasminemia or symptomatic heterozygous aceruloplasminemia. The present report concerns the beneficial treatment of an 18-year-old girl with extrapyramidal and cerebellar-mediated movement disorder caused by a heterozygous mutation of the ceruloplasmin gene using oral zinc sulphate.
Asunto(s)
Ceruloplasmina/deficiencia , Sobrecarga de Hierro/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/fisiopatología , Sulfato de Zinc/administración & dosificación , Administración Oral , Adolescente , Encéfalo/efectos de los fármacos , Encéfalo/patología , Ceruloplasmina/análisis , Ceruloplasmina/genética , Femenino , Humanos , Sobrecarga de Hierro/genética , Sobrecarga de Hierro/fisiopatología , Mutación , Enfermedades Neurodegenerativas/genética , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Aceruloplasminaemia is an autosomal recessive disorder caused by specific mutations in the ceruloplasmin gene. Aceruloplasminaemia is clinically characterized by diabetes mellitus, pigment degeneration of the retina, and neurological abnormalities, such as cerebellar ataxia, extrapyramidal signs, and dementia. We present a patient with aceruloplasminaemia who, until progressive neurological abnormalities were noticed, had been treated for more than 30 years as having Type 1 diabetes mellitus requiring multiple insulin injection therapy. CASE REPORT: The patient was a 58-year-old man. At the age of 23 years, he developed diabetes that required multiple insulin injection therapy. At the age of 39 years, he was commenced on continuous subcutaneous insulin infusion (CSII) therapy. Despite CSII therapy, the patient's blood glucose levels were poorly controlled (HbA(1c), approximately 9.5%). He was diagnosed as having aceruloplasminaemia at 58 years of age when he presented with progressive cerebellar ataxia, extrapyramidal signs of recent onset and pigment degeneration of the retina. CONCLUSIONS: It is possible that some diabetic patients with aceruloplasminaemia are mistakenly diagnosed as having Type 1 diabetes mellitus, as they have reduced insulin secretion and develop diabetes at a younger age, before neurological abnormalities associated with aceruloplasminaemia are apparent. Therefore, aceruloplasminaemia should be considered in patients with insulin-dependent diabetes mellitus who develop progressive neurological abnormalities of unknown aetiology along with a microcytic hypochromic anaemia and retinal degeneration.
Asunto(s)
Trastornos de las Proteínas Sanguíneas/tratamiento farmacológico , Ceruloplasmina/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/genética , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Trastornos de las Proteínas Sanguíneas/genética , Ceruloplasmina/genética , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The authors performed PINK1 mutation analysis of 51 families with autosomal recessive Parkinson disease (ARPD). They found two novel PINK1 mutations: one was a homozygous deletion (13516-18118del) and the other a homozygous missense mutation (C388R). Clinically, the patients with the deletion had dementia. Thus, early-onset PD with dementia may be considered PINK1-linked parkinsonism. Furthermore, patients with PINK1 mutations form 8.9% of parkin- and DJ-1-negative ARPD families.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Mutación/genética , Trastornos Parkinsonianos/genética , Proteínas Quinasas/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Niño , Análisis Mutacional de ADN , Etnicidad/genética , Femenino , Pruebas Genéticas , Geografía , Homocigoto , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Persona de Mediana Edad , Mutación Missense/genética , Proteínas Oncogénicas/genética , Trastornos Parkinsonianos/etnología , Trastornos Parkinsonianos/metabolismo , Linaje , Proteína Desglicasa DJ-1 , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
The Bisurface knee prosthesis (BP) has a posterior stabilising cam (ball-and-socket joint) in the mid-posterior region of the femorotibial joint in an attempt to improve the range of movement. Based on an in vitro weight-bearing study contact areas of the Insall/Burstein 2 (IB2) and the BP knee were compared using pressure-sensitive films. The stability afforded by the cam was evaluated by means of dislocation distances in the vertical and horizontal planes. Significant adverse anterior translation in mid-flexion was not observed with the BP knee since the cam was effective above 60 degrees of flexion. At flexion of 60 degrees or more, the total contact areas were larger, as the cam represented a weight-bearing surface. The dislocation distances for the BP knee compared favourably with those for the IB2 knee. We conclude that the cam of the BP knee allows good movement, stability and wear.