ABSTRACT
OBJECTIVES: To describe the importance of craniofacial approach in extensive tumours of the nose and paranasal sinuses with intracranial extension. MATERIALS AND METHODS: This is a retrospective study and descriptive analysis of craniofacial approaches to extensive tumors of the nose and paranasal sinuses that were carried at Usmanu Danfodiyo university teaching Hospital Sokoto Nigeria over a nine year period (July 1999 to June 2008). RESULTS: Out of 111 patients seen with tumours of the nose and paranasal sinuses during the period, 29(26.1%) were radiologically reported through computerised tomographic scan to have intracranial extension. Twenty-four (82.8%) were males while 5 (17.2%) were females. Twenty five (86.2%) patients underwent transfacial approach ( modified lateral rhinotomy). Intraoperative findings in these cases only warranted the repair of dural tear in 6 cases through the transfacial approach who had anterior skull base invovlement while 4 had combined transcranial and transfacial approaches (anterior craniofacial resection). Therefore only 10 (34.5%) patients of all the radiologically reported cases of intracranial extension were confirmed intraoperatively to have intracranial extension (5 males, 5 females) with an age range of 1 1/2 to 60 years and mean age of 34.1 years. One patient had orbital exenteration also carried out. Four out of 10 patients are alive after a minimum period of 2 years follow up due to extensive intracranial spread and late presentation of the patient. CONCLUSION: Extensive tumours of the nose and paranasal sinuses with suspected intracranial extension requires not only computerized tomographic scans to assess the extent of the tumour but also a combined transfacial and transcranial approach to successfully resect the tumour.
Subject(s)
Nose Neoplasms/surgery , Paranasal Sinus Neoplasms/surgery , Skull Neoplasms/surgery , Adolescent , Adult , Child , Child, Preschool , Craniotomy , Female , Follow-Up Studies , Hospitals, Teaching , Humans , Infant , Male , Middle Aged , Neoplasm Invasiveness , Nigeria/epidemiology , Nose Neoplasms/diagnostic imaging , Nose Neoplasms/epidemiology , Otorhinolaryngologic Surgical Procedures/methods , Paranasal Sinus Neoplasms/diagnostic imaging , Paranasal Sinus Neoplasms/epidemiology , Retrospective Studies , Sex Distribution , Skull Neoplasms/diagnostic imaging , Skull Neoplasms/epidemiology , Survival Rate , Tomography, X-Ray Computed , Treatment Outcome , Young AdultABSTRACT
OBJECTIVES: To describe the importance of craniofacial approach in extensive tumours of the nose and paranasal sinuses with intracranial extension. MATERIALS AND METHODS: This is a retrospective study and descriptive analysis of craniofacial approaches to extensive tumors of the nose and paranasal sinuses that were carried at Usmanu Danfodiyo University Teaching Hospital, Sokoto Nigeria over a nine year period (July 1999 to June 2008). RESULTS: Out of 111 patients seen with tumours of the nose and paranasal sinuses during the period, 29(26.1%) were radiologically reported through computerised tomographic scan to have intracranial extension. Twenty-four (82.8%) were males while 5 (17.2%) were females. Twenty-five (86.2%) patients underwent transfacial approach (modified lateral rhinotomy). Intraoperative findings in these cases only warranted the repair of dural tear in 6 cases through the transfacial approach who had anterior skull base invovlement while 4 had combined transcranial and transfacial approaches (anterior craniofacial resection). Therefore only 10 (34.5%) patients of all the radiologically reported cases of intracranial extension were confirmed intraoperatively to have intracranial extension (5 males, 5 females) with an age range of 1 1/2 to 60 years and mean age of 34.1 years. One patient had orbital exenteration also carried out. Four out of 10 patients are alive after a minimum period of 2 years follow up due to extensive intracranial spread and late presentation of the patient. CONCLUSION: Extensive tumours of the nose and paranasal sinuses with suspected intracranial extension requires not only computerized tomographic scans to assess the extent of the tumour but also a combined transfacial and transcranial approach to successfully resect the tumour.
Subject(s)
Carcinoma/surgery , Nose Neoplasms/surgery , Paranasal Sinus Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Carcinoma/pathology , Child , Child, Preschool , Craniotomy , Female , Follow-Up Studies , Hospitals, Teaching , Humans , Infant , Male , Middle Aged , Nigeria , Nose Neoplasms/pathology , Otologic Surgical Procedures , Paranasal Sinus Neoplasms/pathology , Retrospective Studies , Sex Distribution , Tomography, X-Ray Computed , Young AdultABSTRACT
INTRODUCTION: signalling through dopamine receptors is of critical importance in the brain and is implicated in schizophrenia and bipolar disorder, but its underlying molecular mechanisms remain poorly understood. MATERIALS AND METHODS: using a yeast two-hybrid approach, we previously identified 11 novel dopamine receptor-interacting proteins. Here we compare gene expression levels for 17 genes [including all 11 dopamine receptor interacting proteins, all 5 dopamine receptors (DRD1-DRD5) and DARPP-32] by real-time polymerase chain reaction, using prefrontal cortex post mortem brain samples from 33 schizophrenic, 32 bipolar disorder and 34 control subjects. RESULTS: the expression of C14ORF28, GNB2L1, MLLT3, DRD2 and DARPP-32 genes was altered in schizophrenia and/or bipolar disorder samples relative to controls (P < 0.05). Hierarchical clustering analysis revealed the expression of these five genes (C14ORF28, GNB2L1, MLLT3, DARPP-32, DRD2) is closely correlated in patients. However, in controls, DRD2 expression in relation to the other genes appears to be very different, suggesting abnormal DRD2 activity is an important trigger in the pathophysiology of schizophrenia and bipolar disorder. CONCLUSIONS: our data suggest: (i) C14ORF28, GNB2L1, MLLT3, DRD2 and DARPP-32 are important in the pathogenesis of schizophrenia and bipolar disorder; (ii) these two disorders share common disease-related mechanisms linked to dopamine signalling; (iii) the expression of these genes is closely correlated; and (iv) DRD2 provides the initial trigger in the pathogenesis of these disorders.
Subject(s)
Bipolar Disorder/genetics , Gene Expression , Receptors, Dopamine/metabolism , Schizophrenia/genetics , Bipolar Disorder/metabolism , Cluster Analysis , Dopamine/metabolism , Dopamine and cAMP-Regulated Phosphoprotein 32/biosynthesis , Dopamine and cAMP-Regulated Phosphoprotein 32/genetics , Female , GTP-Binding Proteins/biosynthesis , GTP-Binding Proteins/genetics , Humans , Male , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Nuclear Proteins/biosynthesis , Nuclear Proteins/genetics , Receptors for Activated C Kinase , Receptors, Cell Surface/biosynthesis , Receptors, Cell Surface/genetics , Receptors, Dopamine D2/biosynthesis , Receptors, Dopamine D2/genetics , Reverse Transcriptase Polymerase Chain Reaction , Schizophrenia/metabolism , Signal Transduction/physiology , Two-Hybrid System TechniquesABSTRACT
We report a case of hypothalamic hamartoma in an adult female who presented with gelastic seizures, generalized convulsions, and ictal aggressive psychotic behavior. Anticonvulsant treatment was ineffective in controlling the epileptic seizures. Surgical excision after accurate imaging diagnosis 3 decades after the onset of symptoms markedly ameliorated her condition. Delayed and erroneous diagnosis had unnecessarily prolonged the suffering of our patient.
Subject(s)
Epilepsies, Partial/etiology , Epilepsy, Generalized/etiology , Hamartoma/complications , Hypothalamic Diseases/complications , Psychotic Disorders/etiology , Adult , Female , Hamartoma/pathology , Humans , Hypothalamic Diseases/pathology , Magnetic Resonance Imaging/methodsABSTRACT
We report a case of hypothalamic hamartoma in an adult female who presented with gelastic seizures, generalized convulsions, and ictal aggressive psychotic behavior. Anticonvulsant treatment was ineffective in controlling the epileptic seizures. Surgical excision after accurate imaging diagnosis 3 decades after the onset of symptoms markedly ameliorated her condition. Delayed(AU)
Subject(s)
Humans , Female , Adult , Hamartoma/complications , Hypothalamic Diseases/complications , Epilepsy/drug therapy , Seizures/drug therapy , Epilepsy/etiology , Anticonvulsants/therapeutic use , Psychotic Disorders/etiologyABSTRACT
Pakistan is seriously confronted by many complex and difficult environmental challenges related to air, water, soil, forests and food including issues such as climate change. The close link between environment and health is neither well understood nor appreciated. The annual cost of environmental degradation in Pakistan has been estimated to be around US $4.0 billion orat least 6% of the country's GDP. Up to 35% of the burden of disease is attributable to environmental hazards and risk factors and most of this burden is preventable. A systematic process for identifying environmental health needs and issues as well as the efforts made by the government of Pakistan and the World Health Organization in establishing and launching an environmental health protection unit are described. Also presented are the mission, functions, structure (operational and logistical) and technical requirements as well as sustainability aspects of the environmental health protection unit.
Subject(s)
Conservation of Natural Resources/methods , Environmental Health/organization & administration , Health Services Needs and Demand , PakistanABSTRACT
Pakistan is seriously confronted by many complex and difficult environmental challenges related to air, water, soil, forests and food including issues such as climate change. The close link between environment and health is neither well understood nor appreciated. The annual cost of environmental degradation in Pakistan has been estimated to be around US $ 4.0 billion orat least 6% of the country's GDP. Up to 35% of the burden of disease is attributable to environmental hazards and risk factors and most of this burden is preventable. A systematic process for identifying environmental health needs and issues as well as the efforts made by the government of Pakistan and the World Health Organization in establishing and launching an environmental health protection unit are described. Also presented are the mission, functions, structure [operational and logistical] and technical requirements as well as sustainability aspects of the environmental health protection unit
Subject(s)
Environment and Public Health , Needs Assessment , World Health Organization , Climate Change , Risk Factors , Environmental HealthABSTRACT
Programmed cell death (pcd) may take the form of apoptotic or nonapoptotic pcd. Whereas cysteine aspartyl-specific proteases (caspases) mediate apoptosis, the mediators of nonapoptotic cell death programs are much less well characterized. Here, we report that paraptosis, an alternative, nonapoptotic cell death program that may be induced by the insulin-like growth factor I receptor (among other inducers), is mediated by mitogen-activated protein kinases (MAPKs) and inhibited by AIP-1/Alix. The inhibition by AIP-1/Alix is specific for paraptosis since apoptosis was not inhibited. Caspases were not activated in this paradigm, nor were caspase inhibitors effective in blocking cell death. However, insulin-like growth factor I receptor (IGFIR)-induced paraptosis was inhibited by MEK-2-specific inhibitors and by antisense oligonucleotides directed against c-jun N-terminal kinase-1 (JNK-1). These results suggest that IGFIR-induced paraptosis is mediated by MAPKs, and inhibited by AIP-1/Alix.
Subject(s)
Calcium-Binding Proteins/metabolism , Carrier Proteins/metabolism , Cell Cycle Proteins/metabolism , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Caspase Inhibitors , Caspases/metabolism , Cell Death/drug effects , Cell Line , Endosomal Sorting Complexes Required for Transport , Humans , Kinetics , Receptors, Somatomedin/genetics , Receptors, Somatomedin/metabolism , Signal TransductionABSTRACT
To identify risk factors likely to cause developmental disabilities and to generate hypotheses for a further study of risk factors predisposing to disability and slow mental and physical development. Mothers and children attending/visiting the Sandy Gall's Afghanistan Appeal (SGAA) clinics in the East Zone of Afghanistan. The main outcome measures, developmental disabilities, cerebral palsy (CP), club foot, CDH and polio. Results, 37.5% of the disabilities were present at birth, 46% of the disabled children were born from parents who are 1st cousin which was confirmed by computing chi2 value, which is 10.87 with one degree of freedom. 58.3% of the disabled children were born from parents who lack antenatal care. 22.4% of the pregnant women in the defined population had antenatal checkups, and 97% of the mothers in the defined population are illiterate, 52% of the children found with CP specific and mental retardation. 25% were with delayed physical and mental development. 13% were with CP specific and 10% were club foot. 2% of the children were visually handicapped, 9% with hearing impairment. 61% of children were from Nangarhar, 25% from Laghman and 14% from Kunar.
Subject(s)
Cerebral Palsy/etiology , Congenital Abnormalities/etiology , Developmental Disabilities/etiology , Disabled Children/statistics & numerical data , Adolescent , Afghanistan/epidemiology , Cerebral Palsy/congenital , Cerebral Palsy/epidemiology , Child , Child, Preschool , Congenital Abnormalities/epidemiology , Consanguinity , Developmental Disabilities/epidemiology , Female , Genetic Predisposition to Disease/epidemiology , Health Services Needs and Demand , Humans , Infant , Infant, Newborn , Male , Obstetric Labor Complications/epidemiology , Pregnancy , Risk Factors , Surveys and QuestionnairesABSTRACT
Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of juvenile ALS and has been mapped to human chromosome 2q33. Here we report the identification of two independent deletion mutations linked to ALS2 in the coding exons of the new gene ALS2. These deletion mutations result in frameshifts that generate premature stop codons. ALS2 is expressed in various tissues and cells, including neurons throughout the brain and spinal cord, and encodes a protein containing multiple domains that have homology to RanGEF as well as RhoGEF. Deletion mutations are predicted to cause a loss of protein function, providing strong evidence that ALS2 is the causative gene underlying this form of ALS.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , GTP Phosphohydrolases/metabolism , Guanine Nucleotide Exchange Factors/genetics , Mutation , Amino Acid Sequence , Animals , Chromosome Mapping , Chromosomes, Human, Pair 2 , Female , Guanine Nucleotide Exchange Factors/chemistry , Humans , Male , Mice , Molecular Sequence Data , Polymorphism, Genetic , Sequence Homology, Amino AcidSubject(s)
Arabidopsis/genetics , Paranoid Disorders/genetics , Arabidopsis/enzymology , Arabidopsis/microbiology , Gene Expression Regulation, Plant , Humans , Mitogen-Activated Protein Kinases/genetics , Mutation , Paranoid Disorders/enzymology , Plant Diseases/genetics , Plant Diseases/microbiologyABSTRACT
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that manifests as selective upper and lower motor neuron degeneration. The autosomal recessive form of juvenile amyotrophic lateral sclerosis (ALS2) has previously been mapped to the 1.7-cM interval flanked by D2S116 and D2S2237 on human chromosome 2q33-q34. We identified three novel full-length transcripts encoded by three distinct genes (HGMW-approved symbols ALS2CR1, ALS2CR2, and ALS2CR3) within the ALS2 critical region. The intron-exon organizations of these genes as well as those of CFLAR, CASP10, and CASP8, which were previously mapped to this region, were defined. These genes were evaluated for mutations in ALS2 patients, and no disease-associated sequence alterations in either exons or intron-exon boundaries were observed. Sequence analysis of overlapping RT-PCR products covering the whole coding sequence for each transcript revealed no aberrant mRNA sequences. These data strongly indicate that ALS2CR1, ALS2CR2, ALS2CR3, CFLAR, CASP10, and CASP8 are not causative genes for ALS2.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Chromosomes, Human, Pair 2/genetics , Intracellular Signaling Peptides and Proteins , Physical Chromosome Mapping , Proteins , Adaptor Proteins, Signal Transducing , Base Sequence , Brain/metabolism , CASP8 and FADD-Like Apoptosis Regulating Protein , Carrier Proteins , Caspase 10 , Caspase 8 , Caspase 9 , Caspases/genetics , Cloning, Molecular , Co-Repressor Proteins , Consensus Sequence , DNA Mutational Analysis , Gene Library , Humans , Molecular Sequence Data , Nerve Tissue Proteins/genetics , RNA, Messenger/geneticsSubject(s)
Genetic Linkage , Language Development Disorders/genetics , Quantitative Trait, Heritable , Adolescent , Adult , Child, Preschool , Cloning, Molecular , Female , Humans , Language Development Disorders/diagnosis , Language Development Disorders/etiology , Male , Nuclear Family , Pedigree , Psychometrics , ScotlandABSTRACT
The huntingtin-associated protein (HAP-1) interacts with the Huntington disease gene product, huntingtin. It is predominantly expressed in the brain and shows an increased affinity for mutant huntingtin. We have sequenced an 18,656bp genomic region encompassing the entire human HAP-1 gene and determined its genomic organisation, with 11 exons spanning 12.1kb. We have also found an intragenic polymorphism within intron 6 of HAP-1. We have recently shown that HAP-1 maps to a region of the genome which has been implicated in a variety of neurological conditions, including progressive supranuclear palsy (PSP), a late-onset atypical parkinsonian disorder. The detailed characterisation of the genomic organisation of HAP-1 and the presence of an intragenic polymorphism will be helpful in evaluating its role in different disorders, using candidate gene approaches.
Subject(s)
Genes/genetics , Nerve Tissue Proteins/genetics , Alleles , Amino Acid Sequence , Base Sequence , DNA/chemistry , DNA/genetics , DNA, Intergenic/genetics , Exons , Humans , Introns , Molecular Sequence Data , Polymorphism, Genetic , Repetitive Sequences, Nucleic Acid , Sequence Analysis, DNAABSTRACT
We have produced yeast artificial chromosome (YAC) transgenic mice expressing normal (YAC18) and mutant (YAC46 and YAC72) huntingtin (htt) in a developmental and tissue-specific manner identical to that observed in Huntington's disease (HD). YAC46 and YAC72 mice show early electrophysiological abnormalities, indicating cytoplasmic dysfunction prior to observed nuclear inclusions or neurodegeneration. By 12 months of age, YAC72 mice have a selective degeneration of medium spiny neurons in the lateral striatum associated with the translocation of N-terminal htt fragments to the nucleus. Neurodegeneration can be present in the absence of macro- or microaggregates, clearly showing that aggregates are not essential to initiation of neuronal death. These mice demonstrate that initial neuronal cytoplasmic toxicity is followed by cleavage of htt, nuclear translocation of htt N-terminal fragments, and selective neurodegeneration.