RESUMO
Verbal trait disorders encompass a wide range of conditions and are marked by deficits in five domains that impair a person's ability to communicate: speech, language, reading, spelling, and writing. Nonword repetition is a robust endophenotype for verbal trait disorders that is sensitive to cognitive processes critical to verbal development, including auditory processing, phonological working memory, and motor planning and programming. In the present study, we present a six-generation extended pedigree with a history of verbal trait disorders. Using genome-wide multipoint variance component linkage analysis of nonword repetition, we identified a region spanning chromosome 13q14-q21 with LOD = 4.45 between 52 and 55 cM, spanning approximately 5.5 Mb on chromosome 13. This region overlaps with SLI3, a locus implicated in reading disability in families with a history of specific language impairment. Our study of a large multigenerational family with verbal trait disorders further implicates the SLI3 region in verbal trait disorders. Future studies will further refine the specific causal genetic factors in this locus on chromosome 13q that contribute to language traits.
Assuntos
Dislexia/genética , Transtornos da Linguagem/genética , Locos de Características Quantitativas/genética , Distúrbios da Fala/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Mapeamento Cromossômico , Cromossomos Humanos Par 13/genética , Proteínas de Drosophila , Dislexia/fisiopatologia , Feminino , Ligação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Transtornos da Linguagem/fisiopatologia , Escore Lod , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Proteínas Nucleares , Linhagem , Leitura , Distúrbios da Fala/fisiopatologia , RedaçãoRESUMO
Neuroendoscopy is an ever-evolving frontier in neurosurgery and its use has spanned decades with safe and efficacious treatment in a variety of cranial procedures. There are areas of technology that are broadening the cranial use of the endoscope. Here we discuss the foundations of cranial neuroendoscopy in the areas of cerebrospinal fluid diversion and tumor biopsy and discuss the recent advancements in the areas of craniosynostosis, endonasal surgery, ventriculo-cisternal approaches, brain parenchymal surgery and skull base surgery. We highlight the ongoing evolution of neuroendoscopic technology and consider the potential future applications that will help to revolutionize the current standards in endoscopy and its use inn neurosurgical practice.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/cirurgia , Neuroendoscopia/métodos , Neuroendoscopia/tendências , Cistos/diagnóstico , Cistos/cirurgia , Descompressão Cirúrgica/métodos , Descompressão Cirúrgica/tendências , HumanosRESUMO
The purpose of this study was to elucidate using transmission electron microscopy (TEM) the ultrastructural changes that occur within the cortical gray matter of a novel reproducible model of congenital hydrocephalus in mice created to overexpress the cytokine transforming growth factor-beta1 (TGF-beta1) in the central nervous system. Brain tissue was obtained from mice from a colony engineered to overexpress TGF-beta1 at two days postpartum and compared to a wild-type aged-matched control. This tissue was fixed using a solution containing 1.25% paraformaldehyde and 1.25% glutaraldehyde in phosphate buffer at least 3-4 h and then cut into 40-50 microm sections. Randomly selected thin sections were stained with uranyl acetate and lead citrate, and then analyzed using a JEOL-100CX or 1200EX transmission electron microscope at accelerating voltage 80 kV. Dramatic neuronal and glial pathology was observed throughout the cortical neuropil in TGF-beta1 mice. The most striking change in the hydrocephalic mice was severe edema with extracellular fluid, possibly due to cerebrospinal fluid (CSF) penetration into the cortex. In addition, severe disruption of the cytoplasmic matrix was seen throughout the cortex, with damage to cellular organelles and particularly severe damage to mitochondria. Our results suggest that congenital hydrocephalus may be associated with significant damage to cortical tissue.
Assuntos
Córtex Cerebral/ultraestrutura , Modelos Animais de Doenças , Hidrocefalia/patologia , Microscopia Eletrônica de Transmissão/métodos , Fator de Crescimento Transformador beta1/metabolismo , Animais , Animais Recém-Nascidos , Edema Encefálico/patologia , Hidrocefalia/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neuroglia/ultraestrutura , Neurônios/ultraestrutura , Fator de Crescimento Transformador beta1/genéticaRESUMO
The authors describe the use of a rigid endoscope lens to enhance microsurgical visualization of the corpus callosum. Using cadaver preparations, endoscopic dissection was carried out through a narrow corridor without significant retraction of the brain. The endoscope improves the operative exposure in corpus callosotomy and other transcallosal procedure.
Assuntos
Encefalopatias/patologia , Encefalopatias/cirurgia , Corpo Caloso/patologia , Corpo Caloso/cirurgia , Endoscopia/métodos , Microcirurgia/métodos , HumanosRESUMO
The far-lateral transcondylar approach was used in this cadaveric study in an attempt to evaluate the usefulness of endoscope-assisted microsurgery in this region of the skull base. The study was carried out using 4 latex-injected, formalin-fixed cadaver heads. After initial examination of intradural structures under an operating microscope, a zero degree 4 mm diameter solid-rod endoscope lens was introduced and guided into position under the direction of the operating microscope. Photographs of the regional anatomy were taken through this lens and through a 30 degree angled lens and compared to photographs of the anatomy taken through the microscope. Clear close-up views of the dural portals and intradural course of the cranial nerves were obtained using the endoscope. The endoscope was introduced through three corridors enclosed with cranial nerves, providing the surgeon with panoramic views of the vertebrobasilar arteries and anterior brainstem surface. The endoscope can be guided through narrow corridors and placed immediately adjacent to a region of interest at the skull base. It enables the surgeon to look around blind corners and work behind structures that are hidden from microscopic view.
Assuntos
Endoscopia , Procedimentos Neurocirúrgicos , Base do Crânio/cirurgia , HumanosRESUMO
The objective of the present study is to describe the diagnosis and treatment of intracranial complications of frontal sinusitis (Pott's puffy tumor) in a series of pediatric patients at our institution. A rare entity, Pott's puffy tumor has been reported in only 21 pediatric cases in the literature of the antibiotic era. The hospital records and radiographic files at Rainbow Babies and Childrens Hospital, Cleveland, Ohio, USA, over the previous 16 years were retrospectively reviewed in a search for patients with the diagnosis of Pott's puffy tumor, defined as scalp swelling and associated intracranial infection. There were 6 male patients and 1 female patient. Ages ranged from 11 to 18 years (median 14.5 years). Intracranial infections consisted of epidural abscess in 5 patients, subdural empyema in 4 and brain abscess in 1. Intraoperative cultures grew anaerobic organisms in 1 patient, microaerophilic streptococcus in 5 patients, Klebsiella species in 1 patient and Streptococcus pneumoniae in another. All patients presented with frontal scalp swelling, and other common symptoms included headache, fever, nasal drainage and frontal sinus tenderness. Five patients were treated with antibiotics prior to their presentation. Four patients presented with neurologic decompensation characterized by varying degrees of hemiparesis, obtundation, pupillary dilatation or aphasia. All patients underwent craniotomy and evacuation of the intracranial infection. Even severely impaired patients demonstrated full neurologic recovery. Despite the widespread use of antibiotics, neurosurgical complications of sinusitis continue to occur. A high degree of suspicion, along with prompt neurosurgical intervention and the use of appropriate antibiotics, can result in favorable outcomes in even the sickest patients.
Assuntos
Abscesso Encefálico/etiologia , Sinusite Frontal/complicações , Adolescente , Adulto , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/patologia , Criança , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Sinusite Frontal/diagnóstico por imagem , Sinusite Frontal/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
Effective treatment of bleeding episodes in hemophilia with high titer inhibitors (HTI) remains a challenge, despite the fact that the therapeutic armamentarium has expanded considerably over the past few years. Treatment safety has improved with the availability of porcine factor VIII (FVIII) and bypassing products such as recombinant factor VIIa (rFVIIa), and plasma-derived activated Prothrombin Complex Concentrates (aPCCs) that are virally inactivated. The major drawbacks of rFVIIa and aPCCs are their unpredictable hemostatic effect, lack of laboratory assays to monitor efficacy and dosing frequency, and the risk of thrombosis. The proceedings of a one-day workshop of physicians who specialized in treating patients with hemophilia held in Vienna on May 13, 2000 have been summarized. In making a decision regarding the choice of product, physicians often consider the type of bleeding episode (life or limb threatening), age of the patient, volume of the reconstituted product, previous exposure to plasma derived products, cost, efficacy, and safety. For plasma naïve patients, to achieve rapid hemostasis a majority of the panelists used porcine FVIII (for patients who lack porcine inhibitory antibodies) or rFVIIa. For patients previously treated with plasma derived factors, in addition to the above concentrates, aPCCs were recommended. Although no data exists regarding safety and efficacy, switching products was routinely practiced either because of availability or cost. Furthermore, the panelists were uncertain about the efficacy of bypassing agents in the prevention of joint disease in inhibitor patients. The workshop participants felt that future research offers the best solution to resolve some of the dilemmas faced by clinicians and may help individualise treatment in a hemophilia patient with a high titer inhibitor.
Assuntos
Hemofilia A/imunologia , Hemofilia A/terapia , Animais , Fator VIIa/imunologia , Fator VIIa/uso terapêutico , Hemofilia A/complicações , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Isoanticorpos/sangue , Isoanticorpos/uso terapêutico , Guias de Prática Clínica como AssuntoRESUMO
Iron chelation therapy with deferoxamine enhances iron excretion and removes excessive tissue iron in regularly transfused patients with sickle cell disease. Long-term studies of deferoxamine in other hemoglobinopathies demonstrate that regular chelation therapy also reduces iron-related organ damage and mortality. Careful design of chelation regimens and attention to compliance are critical elements of successful therapy. The role of new chelators in sickle cell disease is currently under Investigation.
Assuntos
Anemia Falciforme/tratamento farmacológico , Terapia por Quelação/métodos , Quelantes de Ferro/administração & dosagem , Anemia Falciforme/sangue , Seguimentos , Humanos , Ferro/metabolismo , Quelantes de Ferro/normasRESUMO
OBJECT: The authors describe a series of children with Chiari I malformation who presented with fulminating symptoms of "cerebellar fits" characterized by drop attacks with or without deterioration of consciousness, opisthotonic posturing, and varying degrees of respiratory compromise. METHODS: A retrospective analysis was undertaken of the medical records of 47 consecutive patients undergoing surgery for symptomatic Chiari I malformations at Rainbow Babies and Children's Hospital. Thirteen (28%) of the 47 patients presented with complaints consistent with cerebellar fits. Before the correct diagnosis was made, nine (69%) of the 13 children had previously undergone evaluation with electroencephalography and/or electrocardicography and Holter monitoring because of suspected cortical epilepsy or cardiogenic syncope. In each of the 13 children magnetic resonance imaging demonstrated pegged cerebellar tonsils herniated below the foramen magnum. A deep indentation or blanched discoloration of the cerebellar tonsils was noted in five (38%) of these 13 patients at the time of surgery. Of patients with symptomatic Chiari I malformations, the mean degree of tonsillar herniation was significantly less for those in whom cerebellar fits occurred than those in whom they were absent (8.8 mm and 13.9 mm, respectively; p = 0.007). In only one of the patients with cerebellar fits was a syrinx present, and this was a small focal lower thoracic collection. Spells resolved after surgery in all patients who presented with cerebellar fits. CONCLUSIONS: Cerebellar fits may mimic other disorders such as cardiogenic syncope and epileptic seizures. The correct diagnosis may be delayed or the conditions may be misdiagnosed by those who fail to consider Chiari I malformation as a cause of drop attacks, abnormal extensor posturing, and apneic spells in children. The response to decompressive surgery in these patients is gratifying.
Assuntos
Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/cirurgia , Doenças Cerebelares/etiologia , Doenças Cerebelares/cirurgia , Descompressão Cirúrgica/métodos , Procedimentos Neurocirúrgicos/métodos , Adolescente , Cerebelo/patologia , Cerebelo/fisiopatologia , Cerebelo/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/cirurgia , Síncope/etiologia , Síncope/cirurgia , Resultado do TratamentoRESUMO
We have maintained a transgenic mouse model of hydrocephalus created to overproduce the cytokine, transforming growth factor-beta1 (TGF-beta1) in the central nervous system (CNS). The aim of the present study was to estimate the embryonic period when the transgenic mice would develop hydrocephalus, by investigating the chronological developmental changes of the cerebral ventricles. Qualitative analysis of ventricular size was performed on sections cut in the coronal plane of embryos at the 15th (E15) and 18th (E18) embryonic days, and postnatal mice aged 4 days (P4). The presence of the TGF-beta1 transgene was determined by performing polymerase chain reaction (PCR) analysis. We have examined 24 embryos and 14 postnatal mice. By performing PCR analysis, the TGF-beta1 transgene was determined to be present in 16 (42.1%). Five of 16 embryos at E15 carried the transgene, and showed a slight enlargement of the lateral ventricles. Three of 8 embryos at E18 carried the transgene, and had remarkable enlargement of the lateral ventricles. Eight of 14 pups at P4 carried the transgene, and 7 of 8 pups with the transgene developed hydrocephalus. In pups that were positive for the transgene, massive enlargement of the lateral ventricles was observed and there was an associated thinning of the overlying cerebral cortex. These results suggest that congenital hydrocephalus may develop at an important embryonic time period, which coincides with the stage of neural stem cell proliferation and differentiation in the CNS.
Assuntos
Encéfalo/patologia , Ventrículos Cerebrais/patologia , Hidrocefalia/genética , Hidrocefalia/patologia , Fator de Crescimento Transformador beta/genética , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Ventrículos Cerebrais/embriologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hidrocefalia/embriologia , Masculino , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase , Fatores de Tempo , Fator de Crescimento Transformador beta1RESUMO
OBJECTIVE: Lhermitte-Duclos disease, or dysplastic gangliocytoma of the cerebellum, is an unusual hamartomatous lesion that can cause progressive mass effects in the posterior fossa. Cowden disease, or multiple hamartoma-neoplasia syndrome, is a rare autosomal dominant disorder characterized by mucocutaneous hamartomas and high incidences of systemic malignancies. We recently treated a patient with manifestations of both Lhermitte-Duclos disease and Cowden disease, and we were intrigued by the occurrence of these two rare disorders in the same patient. The purpose of the present study was to examine the nature of the association between Lhermitte-Duclos disease and Cowden disease. METHODS: The records for all patients who had been diagnosed at our institution as having Lhermitte-Duclos disease were reviewed, to determine whether these patients also exhibited manifestations of Cowden disease. Data were obtained from multiple sources, including patient interviews, correspondence with treating physicians, and chart reviews. RESULTS: During the past 40 years, five patients were diagnosed at Case Western Reserve University as having Lhermitte-Duclos disease. All five patients exhibited manifestations of Cowden disease. Before this review, Cowden disease had not been diagnosed for three of the patients. In our most recent case, the diagnoses of both disorders were established preoperatively. That patient was observed to have a deletion in the critical portion of Exon 5 of the PTEN gene, the gene associated with Cowden disease. CONCLUSION: Inclusion of Lhermitte-Duclos disease in the Cowden disease spectrum suggests that Cowden disease is a true phakomatosis, with hamartomas arising from cutaneous and neural ectoderm. Recent advances in molecular genetics may help to refine the current descriptive classification of the phakomatoses. The association between Lhermitte-Duclos disease and Cowden disease has been under-recognized and under-reported. Recognition of this association has direct clinical relevance, because diligent long-term follow-up monitoring of individuals with Lhermitte-Duclos disease and Cowden disease may lead to the early detection of malignancy.
Assuntos
Neoplasias Cerebelares/diagnóstico , Ganglioneuroma/diagnóstico , Síndrome do Hamartoma Múltiplo/diagnóstico , Síndromes Neurocutâneas/diagnóstico , Proteínas Supressoras de Tumor , Adolescente , Adulto , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Cerebelo/patologia , Cerebelo/cirurgia , Criança , Deleção Cromossômica , Diagnóstico Diferencial , Éxons , Feminino , Ganglioneuroma/genética , Ganglioneuroma/patologia , Ganglioneuroma/cirurgia , Síndrome do Hamartoma Múltiplo/genética , Síndrome do Hamartoma Múltiplo/patologia , Síndrome do Hamartoma Múltiplo/cirurgia , Humanos , Imageamento por Ressonância Magnética , Síndromes Neurocutâneas/genética , Síndromes Neurocutâneas/patologia , Síndromes Neurocutâneas/cirurgia , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
In previous trials, the orally active iron chelator deferiprone (L1) has been associated with sporadic agranulocytosis, milder forms of neutropenia and other side-effects. To determine the incidence of these events, we performed a multicentre prospective study of the chelator. Blood counts were performed weekly, and confirmed neutropenia mandated discontinuation of therapy. Among 187 patients with thalassaemia major, the incidence of agranulocytosis (neutrophils < 0.5 x 109/l) was 0.6/100 patient-years, and the incidence of milder forms of neutropenia (neutrophils 0.5-1.5 x 109/l) was 5.4/100 patient-years. All cases of neutropenia resolved after interruption of therapy. Neutropenia occurred predominantly in non-splenectomized patients. Nausea and/or vomiting occurred early in therapy, was usually transient and caused discontinuation of deferiprone in three patients. Mild to moderate joint pain and/or swelling did not require permanent cessation of deferiprone and occurred more commonly in patients with higher ferritin levels. Mean alanine transaminase (ALT) levels rose during therapy. Increased ALT levels were generally transient and occurred more commonly in patients with hepatitis C. Persistent changes in immunological studies were infrequent, although sporadic abnormalities occurred commonly. Mean zinc levels decreased during therapy. Ferritin levels did not change in the overall group but decreased in those patients with baseline levels > 2500 microgram/l. This study characterized the safety profile of deferiprone, and, under the specific conditions of monitoring, demonstrated that agranulocytosis is less common than previously predicted.
Assuntos
Quelantes de Ferro/efeitos adversos , Piridonas/efeitos adversos , Talassemia beta/tratamento farmacológico , Agranulocitose/induzido quimicamente , Alanina Transaminase/metabolismo , Deferiprona , Gastroenteropatias/induzido quimicamente , Humanos , Artropatias/induzido quimicamente , Neutropenia/induzido quimicamente , Dor/induzido quimicamente , Estudos Prospectivos , Resultado do Tratamento , Zinco/metabolismo , Talassemia beta/urinaRESUMO
The authors describe an endoscopic approach to the anterior aspect of the third ventricle and demonstrate its use in the cadaver. This technique consists of a small supraorbital craniotomy and a subfrontal trans-lamina terminalis approach to the third ventricle. It may be helpful in the management of refractory third ventricular lesions that cannot be easily accessed endoscopically through the foramina of Monro.
Assuntos
Endoscopia/métodos , Microcirurgia/métodos , Terceiro Ventrículo/cirurgia , Ventriculostomia/métodos , Craniotomia/métodos , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Basketball is played by millions of athletes throughout the world and is the most popular team sport in American high schools. Basketball is the leading cause of sports-related injury in the United States. Acute basketball injuries most often involve the extremities, especially the hands, wrists, ankles, and knees. This article reviews the history, epidemiology, and common injury patterns that occur in this sport. We include several case reports to emphasize diagnostic dilemmas frequently encountered by emergency physicians.
Assuntos
Traumatismos em Atletas/epidemiologia , Basquetebol/lesões , Adolescente , Traumatismos do Tornozelo/diagnóstico por imagem , Traumatismos do Tornozelo/etiologia , Feminino , Humanos , Incidência , Masculino , Radiografia , Estados Unidos/epidemiologia , Traumatismos do Punho/diagnóstico por imagem , Traumatismos do Punho/etiologiaRESUMO
Severe pediatric head injury has negative consequences for children of all ages. Even mild and moderate head injury results in residual impairment for school-age children and adolescents. Data are needed on the effects of these less severe insults, especially for preschoolers. Although research on the impact of the child's head injury on the parent-child relationship and family functioning is limited, the experience is likely to be very stressful for the parent and the family. Indeed, family integrity may be at risk. Research is needed that examines the effects of a child's head injury for the parent and the family over time and identifies factors related to these outcomes.
Assuntos
Cuidadores/psicologia , Traumatismos Craniocerebrais/psicologia , Traumatismos Craniocerebrais/reabilitação , Saúde da Família , Adulto , Criança , Efeitos Psicossociais da Doença , Traumatismos Craniocerebrais/enfermagem , Humanos , Pais/psicologia , Relações Profissional-FamíliaRESUMO
We describe our experience with the use of a polymeric biodegradable system for the correction of congenital pediatric craniofacial malformations. These fixation methods present several advantages over conventional metallic fixation systems. Our series consists of 51 patients that underwent craniofacial surgery, 46 for craniosynostosis, and 5 for encephalocele. The mean age of the patients was 3 years (median age 9 months). Patients with coronal or metopic craniosynostosis underwent a bifrontal craniotomy and anterior cranial vault and orbital reconstruction. Three patients with late sagittal synostosis underwent cranial vault reconstruction in two stages. Encephalocele defects were repaired with osteotomies, and/or onlay bone graft. Lactosorb (Lorenz Biomet, Warsaw, Ind.) plates (cut from a prefabricated mesh) and screws were employed using established fixation techniques. Cranial bone was the source of all bone graft when required. Pre- and postoperative clinical, radiographic and photographic examinations were performed on all patients. At 2 years follow-up, no evidence of infection, erythema, extrusion, instability of the bony fragments or relapse has been noted. The plates themselves were universally impalpable by the one year follow-up examination. The results in this series support the use of resorbable fixation systems in the correction of congenital craniofacial deformities.
Assuntos
Implantes Absorvíveis , Placas Ósseas , Craniossinostoses/cirurgia , Craniotomia , Implantes Absorvíveis/efeitos adversos , Placas Ósseas/efeitos adversos , Criança , Pré-Escolar , Encefalocele/cirurgia , Ossos Faciais/cirurgia , Seguimentos , Humanos , Lactente , Recém-Nascido , Órbita/cirurgiaRESUMO
OBJECT: The purpose of this study was to elucidate the pathophysiological characteristics of hydrocephalus in a new transgenic model of mice created to overproduce the cytokine transforming growth factor-beta1 (TGFbeta1) in the central nervous system (CNS). METHODS: Galbreath and colleagues generated transgenic mice that overexpressed TGFbeta1 in the CNS in an effort to examine the role of this cytokine in the response of astrocytes to injury. Unexpectedly, the animals developed severe hydrocephalus and died. The authors have perpetuated this transgenic colony to serve as a model of congenital hydrocephalus, breeding asymptomatic carrier males that are heterozygous for the transgene with wild-type females. One hundred twelve (49.6%) of 226 mice developed clinical manifestations of hydrocephalus, characterized by dorsal doming of the calvaria, spasticity, limb tremors, ataxia, and, ultimately, death. The presence of the TGFbeta1 transgene was determined by performing polymerase chain reaction (PCR) analysis of sample tail slices. Animals with the hydrocephalic phenotype consistently carried the transgene, although some animals with the transgene did not develop hydrocephalus. Animals without the transgene did not develop hydrocephalus. Alterations in brain structure were characterized using magnetic resonance (MR) imaging, gross and light microscopic analysis, and immunocytochemical studies. Magnetic resonance imaging readily distinguished hydrocephalic animals from nonhydrocephalic controls and demonstrated an obstruction at the outlets of the fourth ventricle. Gross and light microscopic examination confirmed the MR findings. The results of immunofluorescent staining of brain tissue slices revealed the presence of the TGFbeta1 cytokine and its receptor preferentially in the meninges and subarachnoid space in both hydrocephalic and control mice. Reverse transcriptase-PCR analysis demonstrated tissue-specific expression of the TGFbeta1, gene in the brains of transgenic mice, and enzyme-linked immunosorbent assay confirmed overexpression of the TGFbeta1 cytokine in brain, cerebrospinal fluid, and plasma. CONCLUSIONS: The transgenic murine model provides a reproducible representation of congenital hydrocephalus. The authors hypothesize that overexpression of TGFbeta1 in the CNS causes hydrocephalus by altering the environment of the extracellular matrix and interfering with the circulation of cerebrospinal fluid. A model of hydrocephalus in which the genetic basis is known should be useful for evaluating hypotheses regarding the pathogenesis of this disorder and should also help in the search for new treatment strategies.
Assuntos
Modelos Animais de Doenças , Hidrocefalia/genética , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Cruzamentos Genéticos , Feminino , Expressão Gênica/fisiologia , Triagem de Portadores Genéticos , Humanos , Hidrocefalia/patologia , Hidrocefalia/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Genéticos , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/fisiologiaRESUMO
We describe a simple midline approach to posterior fossa lesions in children that involves removal and replacement of a bone flap. This approach offers several advantages over conventional suboccipital craniectomy. Elevation of the bone flap is facilitated by the relatively small size of the midline bony keel in children. This method is simple, safe and expeditious, and restores normal anatomical planes and improved protection to the contents of the posterior fossa. While this approach has been described previously for individual cases, the authors employ craniotomy as the standard method of access to the posterior fossa in pediatric patients, and suggest a straightforward technique for removing and replacing the bone flap.
Assuntos
Craniotomia/métodos , Neoplasias Infratentoriais/cirurgia , Astrocitoma/cirurgia , Criança , Craniotomia/instrumentação , Cistos/cirurgia , Ependimoma/cirurgia , Humanos , Meduloblastoma/cirurgia , Retalhos Cirúrgicos , Resultado do TratamentoRESUMO
OBJECTIVE: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-delta32/delta32 homozygous genotype has phenotypic expressions other than those related to HIV-1. DESIGN: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-delta32/delta32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-delta32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. RESULTS: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-delta32/delta32 study subjects. Based on blood pressure measurement and treatment history, CCR5-delta32/delta32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were approximately 20% higher in CCR5-delta32/delta32 study subjects than in CCR5-+/+ study subjects (p < .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-delta32/delta32 homozygotes (p < .05), but serum HCV levels did not differ by CCR5-delta32 genotype. CCR5-delta32/delta32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. CONCLUSIONS: CCR5-delta32/delta32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-delta32/delta32 homozygosity does not provide broad protection against viral infections.
Assuntos
Homozigoto , Receptores CCR5/genética , População Branca/genética , Adulto , Anticorpos Antivirais/sangue , Estudos de Coortes , Genótipo , Infecções por HIV/genética , HIV-1 , Hemofilia A/complicações , Hemofilia A/genética , Hepatite C/complicações , Hepatite C/enzimologia , Hepatite C/genética , Homossexualidade/genética , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Fígado/enzimologia , Contagem de Linfócitos , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Prevalência , Estudos ProspectivosRESUMO
We retrospectively characterized clinical features of 55 patients with severe nutritional iron deficiency anemia. Anemia was commonly discovered in the absence of related complaints. Forty percent of patients were of Southeast Asian ancestry. Most were treated successfully with iron therapy alone; 8 required transfusion.