Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Acta Odontol Scand ; 81(7): 555-561, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37171859

RESUMEN

OBJECTIVE: To clarify the occurrence and causes of non-infection-related surgical wound dehiscence (SWD) in intraorally treated mandibular fractures. MATERIAL AND METHODS: Patients with one or two fractures of the dentate part of the mandible treated surgically via an intraoral approach were included in this retrospective study. The primary outcome variable was SWD. Associations between patient-, fracture- and surgery-related variables and SWD were evaluated. RESULTS: Altogether 232 patients with 270 mandibular angle, body, symphysis and/or parasymphysis fractures were included in the analysis. In all, 22 SWDs were detected. These occurred in 9.5% of patients and in 8.1% of fractures. Surgery performed at night-time showed a significantly higher SWD rate than daytime surgeries (p = .012). Additionally, a significantly greater SWD rate was found among smokers (p = .041). Other studied variables remained statistically non-significant for SWD. In a multivariate analysis, night-time was the only significant independent variable with an odds ratio of 3.297 (95% CI 1.238 - 8.780, p = .017) for SWD. CONCLUSION: The approach or closure technique used and the fracture type had only a minor effect on non-infection-related SWD in patients with mandibular fractures. To avoid SWDs, mandibular fracture surgeries should be conducted during the daytime with adequate support from an experienced surgeon.

2.
Eur Arch Otorhinolaryngol ; 279(3): 1615-1620, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34596713

RESUMEN

OBJECTIVES: The study purpose was to evaluate the effects of the COVID-19 pandemic on the rate and disease profile of orofacial and respiratory infections in oral and maxillofacial surgery (OMFS) and ear, nose, and throat (ENT) emergency units. MATERIALS AND METHODS: Records of patients with orofacial or respiratory infection, or infectious symptoms, diagnosed in the OMFS or ENT Emergency Departments of the Helsinki University Hospital, Helsinki, Finland between 1st March and 30th October 2020 and the corresponding periods in 2018 and 2019 were reviewed. The main outcome variable was the occurrence of studied infections during the evaluated periods. Other study variables were age, gender, residence area, speciality, specific cause for the emergency department visit and admission to ward. RESULTS: There was a significant 37% decrease in the number of infection patients in 2020 compared to the years 2019 and 2018 (1894 vs. 2929 and 3077, respectively, p < .001). A mean decrease of 51% (from 1319 and 1249 patients in 2018 and 2019, respectively, to 592 patients in 2020) was seen in the "Other ENT respiratory infection" category. ENT patients were 51% less likely to be admitted to the ward in 2020 compared to 2019 and 2018 (p = .013). CONCLUSION: A significant decrease was observed in the volume of emergency department visits for orofacial and respiratory infections during the COVID-19-pandemic in 2020 compared to the non-COVID periods. CLINICAL RELEVANCE: It seems that social distancing, facial mask wearing, and other infection prevention precautions have changed the accustomed patient profile in orofacial and respiratory infections.


Asunto(s)
COVID-19 , Infecciones del Sistema Respiratorio , Cirugía Bucal , COVID-19/epidemiología , Servicio de Urgencia en Hospital , Humanos , Pandemias/prevención & control , Faringe , Estudios Retrospectivos , SARS-CoV-2
3.
Acta Odontol Scand ; 80(7): 494-500, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35130467

RESUMEN

OBJECTIVE: To evaluate the occurrence of surgical site infections and predisposing factors for these in simple mandibular fractures. MATERIAL AND METHODS: A retrospective study of patients with fractures of the dentate part of the mandible included patients with intraorally treated simple fractures of the mandibular body, symphysis, and parasymphysis. The primary outcome variable was postoperative surgical site infection. Use of antibiotics, injury mechanism, fracture and surgery-related explanatory variables, patient-related variables and level of oral hygiene according to the modified Total Dental Index were evaluated. RESULTS: Of 254 patients with mandibular fractures, 107 were included in the final analysis. The infection group consisted of 18 patients (16.8%). Despite the high infection occurrence, significant differences were not found between antibiotic use or other studied variables and infection occurrence. Infections occurred mainly in patients without any specific explanatory factor for infection. CONCLUSION: The notably high occurrence of surgical site infections despite antibiotic use after simple mandibular fracture surgery highlights the importance of perioperative tissue handling and local oral circumstances. It is also necessary to consider whether we generally accept the high risk of infection associated with the intraorally treated simple mandibular fractures.


Asunto(s)
Fracturas Mandibulares , Antibacterianos/uso terapéutico , Humanos , Mandíbula/cirugía , Fracturas Mandibulares/epidemiología , Fracturas Mandibulares/cirugía , Estudios Retrospectivos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control
4.
Acta Odontol Scand ; 80(2): 157-160, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34597251

RESUMEN

OBJECTIVES: To evaluate the effects of the COVID-19 pandemic on the occurrence of facial fractures in a tertiary trauma centre. MATERIALS AND METHODS: All facial fracture patients evaluated by an oral and maxillofacial surgeon during the first stage of the pandemic in spring 2020 were included in the study and compared to the corresponding periods in 2017 and 2018. Differences in age, sex, timespan from accident to diagnosis of facial fracture, injury mechanism, fracture type, treatment method, associated injuries (AIs), and alcohol consumption at the time of injury were analyzed between the forementioned time periods. RESULTS: The total number of patients (n = 107) during the COVID restriction period did not differ from the previous years (116 and 113 patients in 2017 and 2018, respectively, p=.368). Injury mechanism was less often assault during 2020 compared with previous years (14.0% in 2020 versus 31.8% in 2018 and 30.2% in 2017). Non-intracranial AIs were more common in the COVID period (28% in 2020 versus 14.2% in 2018 and 21.6%). The distribution was statistically significant (p=.041). Alcohol use prior to injury varied between years (p=.023). Alcohol was more often related to the injuries in 2020 compared to the previous years. CONCLUSIONS: COVID restrictions did not affect the overall facial fracture occurrence, but there was a significant decrease in assaults. The proportion of alcohol-related injuries did not decrease despite restrictions.


Asunto(s)
COVID-19 , Traumatismos Maxilofaciales , Finlandia/epidemiología , Humanos , Traumatismos Maxilofaciales/epidemiología , Pandemias , Distanciamiento Físico , Estudios Retrospectivos , SARS-CoV-2 , Centros Traumatológicos
5.
J Craniofac Surg ; 32(8): 2611-2614, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34727465

RESUMEN

ABSTRACT: The authors' aim was to evaluate the effect of perioperative systemic dexamethasone (DXM) administration on postoperative pain, edema, and trismus in mandibular fracture patients. The authors conducted a prospective randomized study of 45 patients with one or 2 noncomminuted fractures of the dentate part of the mandible. All patients underwent surgery for intraoral miniplate fixation. Patients in the study group were given a total of 30 mg DXM, while patients in the control group received neither DXM nor placebo. Only paracetamol and opioids were served as analgesics. Pain severity was assessed using the visual analog scale. The effect in facial swelling was measured in centimeters and analyzed as percentage change. Trismus was evaluated as the difference in maximal mouth opening by measuring interincisal distance in millimeters. The Mann-Whitney U test was applied to determine the statistical significance of differences between the groups. Thirty-four patients were included in the statistical analysis. The visual analog scale score was significantly lower in the study group than in the control group at 18 hours postoperatively (P = 0.033). Significant differences in edema or trismus were not found postoperatively between the DXM and control groups. In conclusion, perioperative DXM decreases postoperative pain in mandibular fracture patients when nonsteroidal anti-inflammatory drugs are not used, but it does not seem to be effective in reducing edema or trismus.


Asunto(s)
Fracturas Mandibulares , Diente Impactado , Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Edema/etiología , Edema/prevención & control , Humanos , Fracturas Mandibulares/cirugía , Tercer Molar , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Extracción Dental , Trismo/etiología , Trismo/prevención & control
6.
J Oral Maxillofac Surg ; 75(12): 2607-2612, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28886351

RESUMEN

PURPOSE: This study sought to clarify the rate of neurosensory disturbance (NSD) after zygomatic complex fractures in general, as well as the effect of perioperatively administered dexamethasone on neurosensory recovery. PATIENTS AND METHODS: This was a single-blinded randomized study aiming to clarify the benefits of perioperative dexamethasone after surgery. The patients were randomly assigned either to receive dexamethasone (up to a total dose of 10 or 30 mg) or to act as control patients (no glucocorticoid treatment). The outcome variable was NSD, the presence of which was established when patients had any sensory disturbance of the infraorbital nerve. Other predictor variables included in the analysis were age, gender, time span from accident to surgery, surgical approach to the fracture line, and relation of the fracture to the infraorbital foramen. The statistical significance of associations was evaluated with χ2 tests. RESULTS: We included 64 patients in the analyses. Of the patients in the dexamethasone group (either 10 or 30 mg), 58.3% had NSD at 6 months postoperatively, whereas in the control group, 66.7% of the patients had NSD. This finding was not statistically significant (P = .565). At the 1-month interval, the patients without a fracture through the infraorbital foramen had less NSD (P = .009); this finding was not significant at 3 and 6 months postoperatively. Age, gender, injury mechanism, surgical approach, and time span from accident to surgery were not significant predictors of NSD. In total, 64.4% of the patients still had NSD at 6 months postoperatively. CONCLUSIONS: This study showed no benefits of short-term, high-dose dexamethasone administration in the neurosensory recovery of patients with zygomatic complex fractures. The type of primary trauma is the main cause of NSD, but the precise predictors remain unknown.


Asunto(s)
Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Nervio Maxilar/lesiones , Atención Perioperativa/métodos , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Trastornos Somatosensoriales/tratamiento farmacológico , Fracturas Cigomáticas/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Traumatismos de los Nervios Periféricos/etiología , Método Simple Ciego , Trastornos Somatosensoriales/etiología , Resultado del Tratamiento , Fracturas Cigomáticas/cirugía
7.
Oral Maxillofac Surg ; 28(2): 839-847, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38286958

RESUMEN

PURPOSE: To clarify reasons for infections, surgical techniques, and occurrence of postoperative surgical site complications in infected mandibular fractures. METHODS: Patients with clinically infected mandibular fracture of the dentate part without preceding surgery were studied retrospectively. Clinical infection was defined to occur if pus, abscess, or a fistula in the fracture area was present. Patient-, fracture-, and surgery-related variables were evaluated, and predictors for postoperative complications were analysed. RESULTS: Of 908 patients with surgically treated fracture in the dentate part of the mandible, 41 had infected fracture at the time of surgery (4.5%). Of these patients, 46.3% were alcohol or drug abusers. Median delay from injury to surgery was 9 days. Patient-related factors were the most common cause for delayed surgery (n = 30, 73.2%), followed by missed diagnosis by a health care professional (n = 8, 19.5%). Twenty-two fractures were treated via extraoral approach (53.7%) and the remaining 19 intraorally (46.3%). Postoperative surgical site complications were found in 13 patients (31.7%), with recurrent surgical site infections predominating. Notable differences between total complication rates between intraoral and extraoral approaches were not detected. Secondary osteosynthesis for non-union was conducted for one patient treated intraorally. CONCLUSIONS: Postoperative surgical site complications are common after treatment of infected mandibular fractures, and these occur despite the chosen surgical approach. Infected mandibular fractures heal mainly without bone grafting, and non-union is a rare complication. Due to the high complication rate, careful perioperative and postoperative care is required for these patients.


Asunto(s)
Fracturas Mandibulares , Infección de la Herida Quirúrgica , Humanos , Fracturas Mandibulares/cirugía , Adulto , Masculino , Femenino , Infección de la Herida Quirúrgica/etiología , Persona de Mediana Edad , Estudios Retrospectivos , Adolescente , Anciano , Adulto Joven , Fijación Interna de Fracturas , Complicaciones Posoperatorias/etiología , Tiempo de Tratamiento , Trastornos Relacionados con Sustancias/complicaciones , Diagnóstico Tardío
8.
J Pers Med ; 14(5)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38793092

RESUMEN

(1)The study aimed to measure the depth, volume, and surface area of the intact human orbit by applying an automated method of CT segmentation and to evaluate correlations among depth, volume, and surface area. Additionally, the relative increases in volume and surface area in proportion to the diagonal of the orbit were assessed. (2) CT data from 174 patients were analyzed. A ball-shaped mesh consisting of tetrahedral elements was inserted inside orbits until it encountered the bony boundaries. Orbital volume, area depth, and their correlations were measured. For the validation, an ICC was used. (3) The differences between genders were significant (p < 10-7) but there were no differences between sides. When comparing orbit from larger to smaller, a paired sample t-test indicated a significant difference in groups (p < 10-10). A simple linear model (Volume~1 + Gender + Depth + Gender:Depth) revealed that only depth had a significant effect on volume (p < 10-19). The ICCs were 1.0. (4) Orbital volume, depth, and surface area measurements based on an automated CT segmentation algorithm demonstrated high repeatability and reliability. Male orbits were always larger on average by 14%. There were no differences between the sides. The volume and surface area ratio did not differ between genders and was approximately 0.75.

9.
Head Face Med ; 19(1): 45, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37872614

RESUMEN

BACKGROUND: This retrospective study clarified patients´ psychiatric morbidity in IPV-related facial fractures; in particular, their additional psychiatric care. We hypothesized that patients in need of additional support can be identified, allowing overall care processes to be improved. METHODS: Patients' age, sex, anamnestic psychiatric disorders, history of substance abuse, and psychiatric interventions were recorded, as well as the perpetrator, location, time of day, assault mechanism, fracture type, treatment, and associated injuries. RESULTS: In all, 807 adult patients were included in the study. Of these, 205 patients (25.4%) had anamnestic psychiatric disorders that were associated independently with female sex (OR 1.95, 95% CI 1.12, 3.41; p = 0.019) or history of substance abuse (OR 5.82, 95% CI 4.01, 8.46; p < 0.001). Patients with anamnestic psychiatric disorder were more likely to be subjected to severe violence, with an increased risk for combination fractures (OR 2.51, 95% CI 1.30, 4.83; p = 0.006). Of all patients, 61 (7.6%) received a psychiatric intervention within the first 12 months. The most common reasons for intervention were anxiety/fear and psychotic symptoms, surfacing within one month in 57% of patients. Anamnestic psychiatric disorders (OR 2.00, 95% CI 1.04, 3.82; p = 0.036), severe mental illnesses (OR 2.45, 95% CI 1.04, 5.77; p = 0.040), and use of an offensive weapon (OR 2.11, 95% CI 1.11, 4.02; p = 0.023) were the strongest independent predictors of psychiatric intervention. CONCLUSIONS: Our results emphasize the need for more structured treatment protocols for patients sustaining IPV injury. Special attention is recommended for patients with anamnestic psychiatric disorders, severe mental illnesses, and those assaulted with an offensive weapon.


Asunto(s)
Trastornos Mentales , Trastornos Relacionados con Sustancias , Adulto , Humanos , Femenino , Estudios Retrospectivos , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Violencia
10.
Stomatologija ; 24(2): 35-42, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-37140236

RESUMEN

OBJECTIVE: To clarify antibiotic use by oral and maxillofacial surgeons in mandibular fracture patients and evaluate practices based on scientific evidence. MATERIAL AND METHODS: We assessed antibiotic use in simple symphysis and angle mandibular fractures among oral and maxillofacial surgeons in the Nordic countries through an e-survey. In addition, we performed a literature review of antibiotic administration in mandibular fracture surgery. RESULTS: A total of 41 oral and maxillofacial surgeons who treat mandibular fractures responded to the questionnaire. Timing and duration of antibiotic use varied. The duration of postoperative antibiotic treatment ranged from 1 to 7 days (mean 5.6 days). Respondents' practices were not in concordance with scientific evidence. According to previous studies, restricting antibiotic exposure to a maximum of 24 hours postoperatively was not related to a higher risk of surgical site infections. No articles described a benefit of prolonged postoperative antibiotic therapy. CONCLUSIONS: Antibiotic use in connection with mandibular fracture treatment varied in the Nordic countries and antibiotic practices are not in concordance with the current literature. Restricting antibiotic exposure to a maximum of 24 hours postoperatively should be considered. Clear guidelines for antibiotic prophylaxis as part of the surgical management of mandibular fractures are required.


Asunto(s)
Antibacterianos , Fracturas Mandibulares , Humanos , Antibacterianos/uso terapéutico , Fracturas Mandibulares/cirugía , Fracturas Mandibulares/tratamiento farmacológico , Profilaxis Antibiótica , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & control , Encuestas y Cuestionarios
11.
Proc Natl Acad Sci U S A ; 105(1): 311-6, 2008 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-18165320

RESUMEN

Members of the SLC4 bicarbonate transporter family are involved in solute transport and pH homeostasis. Here we report that disrupting the Slc4a10 gene, which encodes the Na(+)-coupled Cl(-)-HCO(3)(-) exchanger Slc4a10 (NCBE), drastically reduces brain ventricle volume and protects against fatal epileptic seizures in mice. In choroid plexus epithelial cells, Slc4a10 localizes to the basolateral membrane. These cells displayed a diminished recovery from an acid load in KO mice. Slc4a10 also was expressed in neurons. Within the hippocampus, the Slc4a10 protein was abundant in CA3 pyramidal cells. In the CA3 area, propionate-induced intracellular acidification and attenuation of 4-aminopyridine-induced network activity were prolonged in KO mice. Our data indicate that Slc4a10 is involved in the control of neuronal pH and excitability and may contribute to the secretion of cerebrospinal fluid. Hence, Slc4a10 is a promising pharmacological target for the therapy of epilepsy or elevated intracranial pressure.


Asunto(s)
Encéfalo/metabolismo , Encéfalo/patología , Líquido Cefalorraquídeo/metabolismo , Antiportadores de Cloruro-Bicarbonato/líquido cefalorraquídeo , Antiportadores de Cloruro-Bicarbonato/fisiología , Regulación de la Expresión Génica , Mutación , Neuronas/metabolismo , Simportadores de Sodio-Bicarbonato/líquido cefalorraquídeo , Simportadores de Sodio-Bicarbonato/fisiología , Animales , Conducta Animal , Transporte Biológico , Antiportadores de Cloruro-Bicarbonato/genética , Eliminación de Gen , Concentración de Iones de Hidrógeno , Iones , Aprendizaje , Ratones , Ratones Noqueados , Modelos Genéticos , Simportadores de Sodio-Bicarbonato/genética
12.
J Neurochem ; 112(1): 193-203, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19845830

RESUMEN

Cathepsin D (CTSD) deficiencies are fatal neurological diseases that in human infants and in sheep are characterized by extreme loss of neurons and myelin. To date, similar morphological evidence for myelin disruption in CTSD knockout mice has not been reported. Here, we show that CTSD deficiency leads to pronounced myelin changes in the murine brain: myelin-related proteolipid protein and myelin basic protein were both markedly reduced at postnatal day 24, and the amount of lipids characteristically high in myelin (e.g. plasmalogen-derived alkenyl chains and glycosphingolipid-derived 20- and 24-carbon acyl chains) were significantly lowered compared with controls. These changes were accompanied by ultrastructural alterations of myelin, including significant thinning of myelin sheaths. Furthermore, in CTSD knockout brains there was a pronounced accumulation of cholesteryl esters and abnormal levels of proteins related to cholesterol transport, with an increased content of apolipoprotein E and a reduced content of ATP-binding cassette transporter A1. These results provide evidence for dysmyelination and altered trafficking of cholesterol in brains of CTSD knockout mice, and warrant further studies on the role of lipid metabolism in the pathogenesis of CTSD deficiencies.


Asunto(s)
Encéfalo/metabolismo , Catepsina D/deficiencia , Ésteres del Colesterol/metabolismo , Enfermedades Desmielinizantes/metabolismo , Vaina de Mielina/metabolismo , Animales , Transporte Biológico Activo/genética , Encéfalo/patología , Catepsina D/genética , Enfermedades Desmielinizantes/genética , Enfermedades Desmielinizantes/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Vaina de Mielina/genética , Vaina de Mielina/patología
13.
J Neuropathol Exp Neurol ; 67(1): 16-29, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18091563

RESUMEN

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.


Asunto(s)
Catepsina D/deficiencia , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/patología , Corteza Somatosensorial/patología , Sinapsis/fisiología , Tálamo/patología , Animales , Antígenos de Diferenciación/metabolismo , Atrofia/etiología , Encéfalo/patología , Muerte Celular , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/genética , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/metabolismo , Vías Nerviosas/patología , Lipofuscinosis Ceroideas Neuronales/complicaciones , Neuronas/metabolismo , Sinapsis/patología , Sinapsis/ultraestructura
14.
Brain ; 129(Pt 6): 1438-45, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16670177

RESUMEN

Congenital neuronal ceroid-lipofuscinosis (NCL) is a devastating inherited neurodegenerative disorder of unknown metabolic basis. Eight patients with this rare disorder, all with similar clinical and neuropathological findings, have been reported, and here we describe two further patients. Previously, we showed that a mutation in the cathepsin D gene causes congenital NCL in sheep. On the basis of the neuropathological and ultrastructural similarities between the sheep and patients affected with congenital NCL, we screened the cathepsin D gene for mutations in a patient of Pakistani origin. We identified a nucleotide duplication, c.764dupA, in the cathepsin D gene in homozygous form in the patient, and in heterozygous form in his father. This duplication is likely to be disease-causing, as it creates a premature stop codon, predicting a truncation of the protein. When transiently expressed in cell cultures, the mutant protein was enzymatically inactive, but stable. In paraffin-embedded brain tissue samples of two affected siblings of the Pakistani patient, cathepsin D was absent, suggesting rapid degradation of the c.764dupA mutant cathepsin D at mRNA or protein level in vivo. Further, we were able to confirm lack of cathepsin D in the brain tissue of yet another, unrelated, patient of English origin with congenital NCL. On the basis of the present data, and the nearly identical clinical and/or pathological phenotype of the other reported cases of congenital NCL, it is reasonable to suggest that cathepsin D deficiency caused by mutations in the corresponding gene may underlie all cases of congenital NCL. The present observations also suggest that cathepsin D deficiency should be considered as a possible diagnosis in microcephalic neonates, who present with seizures at or before birth.


Asunto(s)
Catepsina D/deficiencia , Mutación/genética , Lipofuscinosis Ceroideas Neuronales/genética , Animales , Secuencia de Bases , Encéfalo/metabolismo , Encéfalo/patología , Catepsina D/genética , Catepsina D/metabolismo , Células Cultivadas , Cricetinae , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Recién Nacido , Masculino , Mutagénesis Sitio-Dirigida/métodos , Lipofuscinosis Ceroideas Neuronales/congénito , Lipofuscinosis Ceroideas Neuronales/metabolismo , Lipofuscinosis Ceroideas Neuronales/patología , Fenotipo , Transfección
15.
Magn Reson Imaging ; 25(7): 1024-31, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17451907

RESUMEN

Cathepsin D (CTSD; EC 3.4.23.5) is essential for normal development and/or maintenance of neurons in the central nervous system: its deficiency causes a devastating neurological disorder with severely shortened life span in man, sheep and mouse. Neuropathologically, the CTSD deficiencies are characterized by selective neuronal degeneration, gliosis and accumulation of autofluorescent proteinaceous storage material in neurons. Our aim was to study the dynamics behind the pathological alterations occurring in the brains of CTSD-deficient (CTSD-/-) mice by using in vivo magnetic resonance imaging (MRI) and histology. In order to do this, we measured T(2) signal intensity (SI), apparent diffusion coefficient, area and volume of multiple brain structures from MR images acquired using T(2)-, T(1)- and diffusion-weighted sequences at three time points during disease progression. MRI revealed no differences in the brains between CTSD-/- and control mice at postnatal day 15+/-1 (P15+/-1), representing an initial stage of the disease. In the intermediate stage of the disease, P19(+/-1), SI alterations in the thalami of the affected mice became evident in both T(1)- and T(2)-weighted images. The terminal stage of the disease, P25, was characterized by marked alterations in the T(2) SI, apparent diffusion coefficient and volume of multiple brain structures in CTSD-/- mice. In addition, manganese enhanced high-resolution T(1)-weighted 3D sequences (MEMRI) and histological stainings revealed that the hyperintense signal areas in MEMRI matched perfectly with areas of microglial activation in the brains of CTSD-/- mice at the terminal disease stage. In conclusion, the SI alterations in the thalami of CTSD-/- mice preceded other changes, and the degenerative process was greatly enhanced at the age P19(+/-1), leading to severely reduced brain volume in just 6 days.


Asunto(s)
Encéfalo/patología , Catepsinas/deficiencia , Imagen por Resonancia Magnética/métodos , Manganeso , Microglía/patología , Animales , Procesamiento de Imagen Asistido por Computador , Técnicas para Inmunoenzimas , Ratones
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA