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1.
Retin Cases Brief Rep ; 17(3): 266-268, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37094297

ABSTRACT

PURPOSE: We describe a unique case of bilateral spontaneous vitreous base detachment in a female patient with neurofibromatosis Type 1 and no known history of ocular injury. This serves to add further to the medical literature. DISCUSSION: Vitreous base detachments usually occur after significant ocular trauma. There is only one other published case of this occurring spontaneously also in a female patient with neurofibromatosis Type 1. CONCLUSION: This suggests a rare association between neurofibromatosis Type 1 and spontaneous detachment of the vitreous base.


Subject(s)
Eye Injuries , Neurofibromatosis 1 , Retinal Detachment , Vitreous Detachment , Humans , Female
2.
AJNR Am J Neuroradiol ; 41(9): 1677-1682, 2020 09.
Article in English | MEDLINE | ID: mdl-32616585

ABSTRACT

Coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Inflammation affects atherosclerotic plaque vulnerability and promotes a thrombogenic environment. We report a series of 6 patients with COVID-19 with acute ischemic stroke due to intraluminal carotid artery thrombus presenting during an 8-day period. Six patients were included (5 men) with a mean age of 65.8 years (range, 55-78 years). COVID-19 was diagnosed by detection of Severe Acute Respiratory Syndrome coronavirus 2 in 5 patients and was presumed due to typical clinical and imaging findings in 1 patient. All patients had vascular risk factors including diabetes (83%), hyperlipidemia (100%), and smoking (17%). Four patients presented with large infarcts with initial NIHSS scores of 24-30. During their hospitalization, all patients had elevated D-dimer and C-reactive protein levels, 5 patients had elevated lactate dehydrogenase and ferritin levels, 3 had elevated interleukin-6 levels, and 2 had elevated troponin levels. Inflammation related to COVID-19 may result in rupture of vulnerable atherosclerotic plaques, resulting in thrombosis and acute ischemic stroke.


Subject(s)
Betacoronavirus , Brain Ischemia/etiology , Carotid Arteries/diagnostic imaging , Coronavirus Infections/complications , Cytokines/immunology , Pneumonia, Viral/complications , Stroke/etiology , Thrombosis/etiology , Aged , Brain Ischemia/diagnostic imaging , Brain Ischemia/immunology , COVID-19 , Computed Tomography Angiography , Coronavirus Infections/immunology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Risk Factors , SARS-CoV-2 , Stroke/diagnostic imaging , Stroke/immunology , Thrombosis/diagnostic imaging , Thrombosis/immunology
3.
AJNR Am J Neuroradiol ; 39(12): 2263-2269, 2018 12.
Article in English | MEDLINE | ID: mdl-30467216

ABSTRACT

Systemic lupus erythematosus is a chronic autoimmune disease characterized by the production of autoantibodies resulting in tissue injury across multiple organs; up to 50% of patients develop neurologic involvement, collectively referred to as neuropsychiatric systemic lupus erythematosus. The cases in this clinical report will highlight a subtype of neuropsychiatric systemic lupus erythematosus demonstrating imaging findings of striatal inflammation responsive to plasmapheresis similar to those in the subset of N-methyl-D-aspartate receptor autoimmune encephalitis that involves the striatum. Although the cause for this striking imaging appearance is not definitely known, literature will be presented supporting the hypothesis that it is due to peripheral anti-double-stranded DNA antibodies entering the central nervous system to cross-react with N-methyl-D-aspartate receptor antigens.


Subject(s)
Corpus Striatum/immunology , Encephalitis/immunology , Encephalitis/pathology , Lupus Vasculitis, Central Nervous System/immunology , Lupus Vasculitis, Central Nervous System/pathology , Adult , Aged , Antibodies, Antinuclear/immunology , Autoantibodies/immunology , Corpus Striatum/diagnostic imaging , Corpus Striatum/pathology , Cross Reactions , Encephalitis/therapy , Female , Humans , Lupus Vasculitis, Central Nervous System/therapy , Male , Plasmapheresis , Receptors, N-Methyl-D-Aspartate/immunology , Young Adult
4.
AJNR Am J Neuroradiol ; 39(6): 1185-1190, 2018 06.
Article in English | MEDLINE | ID: mdl-29724759

ABSTRACT

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a complex neurologic disorder resulting from increased intracranial pressure. Our aim was to determine whether a correlation exists between the CSF pressure-volume relationship, specifically the craniospinal elastance and pressure-volume index, in patients with idiopathic intracranial hypertension and whether opening pressure affects this relationship. MATERIALS AND METHODS: Lumbar punctures performed for suspected idiopathic intracranial hypertension from 2006 to 2017 were identified. Opening and closing pressures, CSF volume removed, and clinical diagnosis of idiopathic intracranial hypertension were obtained from the medical records. The craniospinal elastance (pressure change per milliliter of CSF removed) and pressure-volume index were calculated, and the Pearson correlation coefficients between both the craniospinal elastance and pressure-volume index and opening pressure were determined. Linear regression models of craniospinal elastance and the pressure-volume index and interaction terms with opening pressure were assessed for covariate influence on this association. RESULTS: One hundred sixteen patients were included in the final analysis. The mean craniospinal elastance according to opening pressure group was 0.52 ± 0.18 for <20 cm H2O, 0.57 ± 0.20 for 20-29 cm H2O, 0.91 ± 0.28 for 30-39 cm H2O, and 1.20 ± 0.25 for ≥40 cm H2O. There was a positive linear association between opening pressure and craniospinal elastance with a 0.28 cm H2O/mL increase in craniospinal elastance (standard error = 0.03, P < .001) for every 10 cm H2O increase in opening pressure. Of the covariables analyzed, only age older than 50 years and total volume of CSF removed affected this association. CONCLUSIONS: As opening pressure increases, the craniospinal elastance increases in a linear fashion while the pressure-volume index decreases. Further studies are needed to determine whether these changes relate to the underlying pathophysiology of idiopathic intracranial hypertension or simply represent established CSF volume pressure dynamics.


Subject(s)
Cerebrospinal Fluid Pressure/physiology , Pseudotumor Cerebri/physiopathology , Adult , Female , Humans , Linear Models , Male , Middle Aged , Spinal Puncture
5.
AJNR Am J Neuroradiol ; 38(6): 1070-1078, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28183838

ABSTRACT

Autoimmune encephalitis is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with refractory seizure. Due to its diverse clinical features, which can mimic a variety of other pathologic processes, autoimmune encephalitis presents a diagnostic challenge to clinicians. Imaging findings in patients with these disorders can also be quite variable, but recognizing characteristic findings within limbic structures suggestive of autoimmune encephalitis can be a key step in alerting clinicians to the potential diagnosis and ensuring a prompt and appropriate clinical work-up. In this article, we review antibody-mediated encephalitis and its various subtypes with a specific emphasis on the role of neuroimaging in the diagnostic work-up.


Subject(s)
Encephalitis/diagnostic imaging , Encephalitis/physiopathology , Hashimoto Disease/diagnostic imaging , Hashimoto Disease/physiopathology , Neuroimaging/methods , Brain Diseases , Humans
6.
AJNR Am J Neuroradiol ; 36(12): 2373-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26359149

ABSTRACT

BACKGROUND AND PURPOSE: Minimally invasive parathyroidectomy requires accurate preoperative localization of suspected adenomas, and multiphase CT allows adenoma characterization while providing detailed anatomic information. The purpose of this study was to assess the feasibility of a protocol using only arterial and venous phases to localize pathologic glands in patients with primary hyperparathyroidism. MATERIALS AND METHODS: We identified 278 patients with primary hyperparathyroidism who had undergone 2-phase CT with surgical cure. All scans were read prospectively by board-certified neuroradiologists. A neuroradiology fellow retrospectively reviewed images and reports and classified suspected adenomas on the basis of anatomic location. Accuracy was determined by comparing imaging results with surgical findings. The ability of 2-phase CT to localize adenomas to 1 of 4 neck quadrants and lateralize them to the correct side was assessed. Accuracy of identifying multigland disease was also evaluated. RESULTS: In patients with single-gland disease, the sensitivity and specificity of 2-phase CT to correctly localize the quadrant were 55.4% and 85.9%, respectively. The sensitivity and specificity of correct lateralization were 78.8% and 67.8%, respectively. The sensitivity and specificity to identify multigland disease were 22.9% and 79.5%, respectively. CONCLUSIONS: While the 2-phase CT protocol in this study demonstrates lower accuracy compared with reports of other techniques, its lower radiation compared with 3- and 4-phase techniques may make it a feasible alternative for preoperative parathyroid localization. Further prospective studies are needed to identify patients for whom this technique is most suitable.


Subject(s)
Adenoma/diagnostic imaging , Hyperparathyroidism, Primary/etiology , Parathyroid Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Adenoma/complications , Aged , Female , Humans , Male , Middle Aged , Parathyroid Neoplasms/complications , Prospective Studies , Retrospective Studies , Sensitivity and Specificity
7.
AJNR Am J Neuroradiol ; 32(2): 388-94, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21071537

ABSTRACT

BACKGROUND AND PURPOSE: Tumor angiogenesis is very heterogeneous and in vivo correlation of perfusion imaging parameters with angiogenic markers can help in better understanding the role of perfusion imaging as an imaging biomarker. The purpose of this study was to correlate PCT parameters such as CBV and PS with histologic and molecular angiogenic markers in gliomas. MATERIALS AND METHODS: Thirty-six image-guided biopsy specimens in 23 patients with treatment-naive gliomas underwent PCT examinations. We correlated MVD, MVCP, VEGFR-2 expression, tumor cellularity, and WHO grade of the image-guided biopsy specimens with the PCT parameters. Histologic sections were stained with hematoxylin-eosin, CD34, and VEGFR-2 and examined under a light microscope. These histologic and molecular angiogenic markers were correlated with perfusion parameters of the region of interest corresponding to the biopsy specimen. Pearson correlation coefficients and multiple regression analyses by using clustering methods were performed to assess these correlations. RESULTS: CBV showed a significant positive correlation with MVD (r = 0.596, P < .001), whereas PS showed a significant positive correlation with MVCP (r = 0.546, P = .001). Both CBV (r = 0.373, P = .031) and PS (r = 0.452, P = .039) also showed a significant correlation with WHO grade. VEGFR-2 positive specimens showed higher PS and CBV; however, neither was statistically significant at the .05 level. CONCLUSIONS: CBV showed a significant positive correlation with MVD, whereas PS showed a significant positive correlation with MVCP, suggesting that these 2 perfusion parameters represent different aspects of tumor vessels; hence, in vivo evaluation of these could be important in a better understanding of tumor angiogenesis.


Subject(s)
Blood Volume/physiology , Brain Neoplasms , Glioma , Magnetic Resonance Imaging , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Adult , Aged , Biomarkers, Tumor/metabolism , Biopsy , Brain Neoplasms/blood supply , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Female , Glioma/blood supply , Glioma/metabolism , Glioma/pathology , Humans , Male , Microvessels/metabolism , Microvessels/pathology , Middle Aged , Permeability , Vascular Endothelial Growth Factor Receptor-2/metabolism , Young Adult
8.
Dentomaxillofac Radiol ; 37(2): 121-4, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18239041

ABSTRACT

Acute calcific retropharyngeal tendinitis or longus colli tendinitis is an uncommon benign condition presenting as acute neck pain. Clinically, it can be misdiagnosed as retropharyngeal abscess, traumatic injury, or infectious spondylitis. The diagnosis is made radiographically by calcification anterior to C1-C2 and prevertebral soft-tissue swelling. We present two cases of this uncommon condition to illustrate the classic findings on CT and MRI. In addition to the typical calcifications anterior to C1-C2, we detected a retropharyngeal effusion in both patients and effusions involving both lateral atlantoaxial joints in one patient, which to our knowledge has not been published in the literature. In both patients, the correct diagnosis was established by prospective review of the radiographic studies. Recognition of the pathognomonic imaging appearance allows for easy diagnosis preventing unnecessary tests and treatment.


Subject(s)
Calcinosis/diagnostic imaging , Calcinosis/pathology , Neck Muscles/diagnostic imaging , Tendinopathy/diagnostic imaging , Tendinopathy/pathology , Acute Disease , Adult , Atlanto-Axial Joint/pathology , Diagnosis, Differential , Edema/etiology , Female , Humans , Magnetic Resonance Imaging , Male , Neck Muscles/pathology , Neck Pain/etiology , Tendinopathy/complications , Tomography, X-Ray Computed
9.
AJNR Am J Neuroradiol ; 29(4): 694-700, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18202239

ABSTRACT

BACKGROUND AND PURPOSE: Glioma angiogenesis and its different hemodynamic features, which can be evaluated by using perfusion CT (PCT) imaging of the brain, have been correlated with the grade and the aggressiveness of gliomas. Our hypothesis was that quantitative estimation of permeability surface area product (PS), cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in astroglial brain tumors by using PCT will correlate with glioma grade. High-grade gliomas will show higher PS and CBV as compared with low-grade gliomas. MATERIALS AND METHODS: PCT was performed in 32 patients with previously untreated astroglial tumors (24 high-grade gliomas and 8 low-grade gliomas) by using a total acquisition time of 170 seconds. World Health Organization (WHO) glioma grades were compared with PCT parameter absolute values by using Student or nonparametric Wilcoxon 2-sample tests. Receiver operating characteristic (ROC) analyses were also done for each of the parameters. RESULTS: The differences in PS, CBV, and CBF between the low- and high-grade tumor groups were statistically significant, with the low-grade group showing lower mean values than the high-grade group. ROC analyses showed that both CBV (C-statistic 0.930) and PS (C-statistic 0.927) were very similar to each other in differentiating low- and high-grade gliomas and had higher predictability compared with CBF and MTT. Within the high-grade group, differentiation of WHO grade III and IV gliomas was also possible by using PCT parameters, and PS showed the highest C-statistic value (0.926) for the ROC analyses in this regard. CONCLUSIONS: Both PS and CBV showed strong association with glioma grading, high-grade gliomas showing higher PS and CBV as compared with low-grade gliomas. Perfusion parameters, especially PS, can also be used to differentiate WHO grade III from grade IV in the high-grade tumor group.


Subject(s)
Astrocytoma/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Capillary Permeability , Cerebrovascular Circulation , Tomography, X-Ray Computed , Adult , Aged , Astrocytoma/blood supply , Astrocytoma/pathology , Blood Flow Velocity , Blood Volume , Brain Neoplasms/blood supply , Brain Neoplasms/pathology , Contrast Media , Female , Humans , Male , Middle Aged
10.
J Orthop Surg (Hong Kong) ; 16(3): 378-80, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19126911

ABSTRACT

We report a case of isolated rupture of the lateral collateral ligament (LCL) of the knee while attempting to place the left foot behind the head during yoga practice. The 34-year-old man had discomfort of the lateral aspect of the knee particularly with varus strain. A magnetic resonance image revealed rupture of the LCL at the insertion onto the fibula. The patient had grade-II laxity of the LCL and was treated non-operatively. At the 12-month follow-up, grade-I laxity of the LCL remained clinically evident, but function was not impaired.


Subject(s)
Collateral Ligaments/injuries , Knee Injuries/diagnosis , Knee Injuries/etiology , Yoga , Adult , Humans , Knee Injuries/therapy , Male , Rupture/diagnosis , Rupture/etiology , Rupture/therapy
11.
AJNR Am J Neuroradiol ; 28(10): 1981-7, 2007.
Article in English | MEDLINE | ID: mdl-17893216

ABSTRACT

BACKGROUND AND PURPOSE: Perfusion imaging using CT can provide additional information about tumor vascularity and angiogenesis for characterizing gliomas. The purpose of our study was to demonstrate the usefulness of various perfusion CT (PCT) parameters in assessing the grade of treatment-naïve gliomas and also to compare it with conventional MR imaging features. MATERIALS AND METHODS: PCT was performed in 19 patients with glioma (14 high-grade gliomas and 5 low-grade gliomas). Normalized ratios of the PCT parameters (normalized cerebral blood volume [nCBV], normalized cerebral blood flow [nCBF], normalized mean transit time [nMTT]) were used for final analysis. Conventional MR imaging features of these tumors were assessed separately and compared with PCT parameters. Low- and high-grade gliomas were compared by using the nonparametric Wilcoxon 2-sample tests. RESULTS: Mean nCBV in the high- and low-grade gliomas was 3.06 +/- 1.35 and 1.44 +/- 0.42, respectively, with a statistically significant difference between the 2 groups (P = .005). Mean nCBF for the high- and low-grade gliomas was 3.03 +/- 2.16 and 1.16 +/- 0.36, respectively, with a statistically significant difference between the 2 groups (P = .045). Cut points of >1.92 for nCBV (85.7% sensitivity and 100% specificity), >1.48 for nCBF (71.4% sensitivity and 100% specificity), and <1.94 for nMTT (92.9% sensitivity and 40% specificity) were found to identify the high-grade gliomas. nCBV was the single best parameter; however, using either nCBV of >1.92 or nCBF of >1.48 improved the sensitivity and specificity to 92.9% and 100%, respectively. The sensitivity and specificity for diagnosing a high-grade glioma with conventional MR imaging were 85.7% and 60%, respectively. CONCLUSIONS: PCT can be used for preoperative grading of gliomas and can provide valuable complementary information about tumor hemodynamics, not available with conventional imaging techniques. nCBV was the single best parameter correlating with glioma grades, though using nCBF when nCBV was <1.92 improved the sensitivity. An nCBV threshold of >1.92 was found to identify the high-grade gliomas.


Subject(s)
Brain Neoplasms/physiopathology , Cerebrovascular Circulation , Glioma/physiopathology , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Blood Flow Velocity , Blood Volume , Brain Neoplasms/diagnosis , Brain Neoplasms/pathology , Contrast Media , Female , Glioma/diagnosis , Glioma/pathology , Humans , Male , Middle Aged , Sensitivity and Specificity
13.
Neurology ; 65(4): 612-5, 2005 Aug 23.
Article in English | MEDLINE | ID: mdl-16116128

ABSTRACT

The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) > or = 4 (11.1 +/- 5.9), treated within 3 to 24 (13.6 +/- 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 +/- 3.2 and the 24-hour lesion growth on DWI was +23% (-50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Anticoagulants/administration & dosage , Brain Ischemia/drug therapy , Brain/drug effects , Immunoglobulin Fab Fragments/administration & dosage , Stroke/drug therapy , Abciximab , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Anticoagulants/adverse effects , Brain/pathology , Brain/physiopathology , Brain Ischemia/diagnosis , Brain Ischemia/physiopathology , Cerebral Arteries/drug effects , Cerebral Arteries/pathology , Cerebral Arteries/physiopathology , Female , Humans , Immunoglobulin Fab Fragments/adverse effects , Infusions, Intravenous , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/pathology , Intracranial Hemorrhages/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Patient Selection , Stroke/diagnosis , Stroke/physiopathology , Time Factors , Treatment Outcome
14.
Neuroscience ; 128(3): 561-70, 2004.
Article in English | MEDLINE | ID: mdl-15381285

ABSTRACT

Niemann-Pick disease type C (NP-C) is an inherited disorder that is characterized biochemically by cellular cholesterol and glycolipid storage, and clinically by progressive neurodegeneration. Most cases of NP-C are caused by inactivating mutations of the npc1 gene, but about 5% are linked to npc2, which encodes a soluble cholesterol binding protein, previously identified as epididymal secretory glycoprotein 1 (HE1). The present study was carried out to investigate the immunocytochemical localization of HE1/NPC2 protein in the mouse brain. Using an antibody against recombinant HE1/NPC2, we found HE1/NPC2 to be localized predominantly in neurons in the brain. Immunoreactivity for HE1/NPC2 was observed in pyramidal or projection neurons in the cerebral cortex and amygdala, and Purkinje neurons in the cerebellum. Neurons in the thalamus, hypothalamus, and globus pallidus were lightly labeled, or unlabeled. This regional pattern of expression of HE1/NPC2 is similar to our previous findings with NPC1, with a low level of expression of both NPC1 and HE1/NPC2 proteins in regions derived from the diencephalon, such as the thalamus and hypothalamus. In contrast to NPC1, however, which is predominantly in astrocytes, HE1/NPC2 was observed mainly in neurons. Electron microscopic immunocytochemistry showed that HE1/NPC2 is present in the cytosol of dendrites and on post-synaptic densities (PSD). The occurrence of HE1/NPC2 in the PSD was confirmed by Western blots of PSD-enriched brain subcellular fractions that showed the presence of HE1/NPC2 together with the PSD-associated protein, PSD-95. These results suggest that NPC1 and HE1/NPC2 are differentially enriched in astrocytes and neurons, respectively, and that HE1/NPC2 may function in supporting the integrity of the PSD of neurons.


Subject(s)
Brain/metabolism , Carrier Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Niemann-Pick Diseases/metabolism , Synaptic Membranes/metabolism , Animals , Astrocytes/metabolism , Brain/physiopathology , Cells, Cultured , Cytosol/metabolism , Dendrites/metabolism , Dendrites/ultrastructure , Disks Large Homolog 4 Protein , Fibroblasts , Glycoproteins/metabolism , Guanylate Kinases , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins , Membrane Proteins , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Microscopy, Electron, Transmission , Niemann-Pick Diseases/physiopathology , Synaptic Membranes/ultrastructure , Vesicular Transport Proteins
15.
East Afr Med J ; 80(9): 447-51, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14640164

ABSTRACT

OBJECTIVE: To evaluate our experience of laparoscopic appendicectomy at the Aga Khan Hospital, Nairobi over a six year period from the inception of the technique and to assess its advantages and disadvantages. DESIGN: Case series study. SETTING: The Aga Khan Hospital, Nairobi. PATIENTS: One hundred and six cases operated on from May 1996 to June 2002. MAIN OUTCOME MEASURES: Clinical presentation, age and sex demographics, average hospital stay, operating time, intra-operative and post-operative complications and outcome. RESULTS: There was a female preponderance with a female to male ratio of 2:3:1. Mean age was 30.6 years. There was a slightly more number of patients with recurrent appendicitis as opposed to the acute form. Totally laparoscopic procedure was in 39.6% of the cases, laparoscopic assisted in 45.3%. The conversion rate to an open procedure was 15.1%. Post operative port-site infection was 8.5%. No mortality was reported in these series. However there was one case which required re-operation following significant port site haemorrhage. Mean post-operative hospital stay was 2.2 days. CONCLUSION: Laparoscopic appendicectomy is a safe procedure in well trained hands. The major advantages are less morbidity and excellent cosmesis. Discovery of other intraabdominal pathologies is possible through laparoscopy as opposed to classical appendicectomy.


Subject(s)
Appendectomy/methods , Appendectomy/statistics & numerical data , Laparoscopy/statistics & numerical data , Adolescent , Adult , Appendectomy/adverse effects , Appendicitis/surgery , Child , Female , Humans , Kenya/epidemiology , Laparoscopy/adverse effects , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Hemorrhage/epidemiology , Surgical Wound Infection/epidemiology
16.
Acta Paediatr Suppl ; 92(443): 63-73; discussion 45, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14989468

ABSTRACT

UNLABELLED: The cellular location of Niemann-Pick C2 protein (NPC2) in cultured human fibroblasts and Chinese hamster ovary cells was examined immunocytochemically and in living cells by expression of a functional red fluorescent protein chimeric analogue. RESULTS: NPC2 is present in the lysosomes of both cholesterol-depleted and -replenished cells, unlike Niemann-Pick C1 protein (NPC1) which is recruited to late endosomes only upon uptake of low-density lipoprotein. With mobilization of cholesterol from lysosomes, immunocytochemical detection of NPC2 in lysosomes is greatly diminished, whereas NPC1 remains in the late endosomal compartment. We found a partial overlap in the trafficking and organellar sites of accumulation of NPC2 and NPC1. In living cells, NPC2 traffics with NPC1 in late endosomal tubules. However, in contrast to NPC1, which remains either in late endosomal vesicles and tubules or at the peripheries of cholesterol-laden lysosomes, NPC2 moves into the central core of lysosomes. Glycolipid analysis reveals that, in contrast to null mutant NPC1 cells, which accumulate GM2 ganglioside only at the plasma membrane, with no endocytic storage, absence of NPC2 protein in null mutant NPC2 cells does not block internalization of GM2 into endocytic vesicles. This difference in the cellular distribution of GM2 in NPC1 and NPC2 null mutants is the first report of a variation in the phenotypic expression of these genotypically distinct lesions. CONCLUSION: We speculate that while NPC1 may play a major role in the sorting of glycolipids as well as cholesterol within the late endosomes, NPC2 primarily plays a role in the egress of cholesterol and, potentially, glycolipids from lysosomes. These proteins appear not to be integrated into a tightly bound biological complex, but rather represent separate functional entities that complement each other.


Subject(s)
Carrier Proteins/metabolism , Endosomes/metabolism , Glycoproteins/metabolism , Membrane Glycoproteins/metabolism , Niemann-Pick Diseases/metabolism , Animals , CHO Cells , Cells, Cultured , Cricetinae , Histocytochemistry , Intracellular Signaling Peptides and Proteins , Luminescent Proteins , Lysosomes , Microscopy, Confocal , Niemann-Pick C1 Protein , Polymerase Chain Reaction , Protein Transport/physiology , Transfection , Vesicular Transport Proteins , Red Fluorescent Protein
17.
Neurology ; 59(1): 72-8, 2002 Jul 09.
Article in English | MEDLINE | ID: mdl-12105310

ABSTRACT

BACKGROUND: Previously, hyperoxia and blood volume increase were reported in the red nucleus and substantia nigra during spontaneous migraine with aura. OBJECTIVE: To further understand the pathophysiologic role of these centers, activation of brainstem structures was investigated in patients with visually triggered migraine. METHODS: Twenty-six patients with migraine (23 with aura and 3 without aura), and 10 normal control subjects were studied with blood oxygen level-dependent (BOLD) fMRI during repeated checkerboard visual stimulation. Three axial image sections, which covered the occipital cortex and brainstem, were acquired 224 times with a temporal resolution of 3.5 seconds. RESULTS: Repetitive visual stimulation triggered symptoms in 12 patients; four who had migraine with aura developed both visual symptoms and headaches, and six who had migraine with aura and two who had migraine without aura had headaches only. Four patients who had migraine with aura experienced the onset of their usual aura or onset of their typical headache either during the experiment or immediately after. In the remaining 10 patients with migraine, and all control subjects, visual stimulation failed to trigger symptoms at any time. In 75% of the patients who developed symptoms during stimulation, baseline T2*-weighted MR signal intensities increased in the red nucleus and substantia nigra before occipital cortex signal elevation or the onset of visually triggered symptoms. CONCLUSION: Activation (hyperoxia and blood volume increase) of the red nucleus and substantia nigra in association with visually triggered symptoms of migraine suggest that these brainstem structures are a part of a neuronal network activated during an attack.


Subject(s)
Magnetic Resonance Imaging , Migraine with Aura/physiopathology , Migraine without Aura/physiopathology , Red Nucleus/physiopathology , Substantia Nigra/physiopathology , Adult , Female , Humans , Male , Middle Aged , Migraine with Aura/etiology , Migraine without Aura/etiology , Occipital Lobe/physiopathology , Photic Stimulation/adverse effects
18.
JAMA ; 286(22): 2830-8, 2001 Dec 12.
Article in English | MEDLINE | ID: mdl-11735758

ABSTRACT

CONTEXT: The prevalence and clinical significance of early ischemic changes (EICs) on baseline computed tomography (CT) scan of the head obtained within 3 hours of ischemic stroke are not established. OBJECTIVE: To determine the frequency and significance of EIC on baseline head CT scans in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA (recombinant tissue plasminogen activator) Stroke Trial. DESIGN AND SETTING: The original study, a randomized controlled trial, took place from January 1991 through October 1994 at 43 sites, during which CT images were obtained within 3 hours of symptom onset and prior to the initiation of rt-PA or placebo. For the current analysis, detailed reevaluation was undertaken after October 1994 of all baseline head CT scans with clinical data available pretreatment (blinded to treatment arm). PATIENTS: Of 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%). MAIN OUTCOME MEASURES: Frequency of EICs on baseline CT scans; association of EIC with other baseline variables; effect of EICs on deterioration at 24 hours (>/=4 points increase from the baseline National Institutes of Health Stroke Scale [NIHSS] score); clinical outcome (measured by 4 clinical scales) at 3 months, CT lesion volume at 3 months, death at 90 days; and symptomatic intracranial hemorrhage (ICH) within 36 hours of treatment. RESULTS: The prevalence of EIC on baseline CT in the combined rt-PA and placebo groups was 31% (n = 194). The EIC was significantly associated with baseline NIHSS score (rho = 0.23; P<.001) and time from stroke onset to baseline CT scan (rho = 0.11; P =.007). After adjusting for baseline variables, there was no EIC x treatment interaction detected for any clinical outcome, including deterioration at 24 hours, 4 clinical scales, lesion volume, and death at 90 days (P>/=.25), implying that EIC is unlikely to affect response to rt-PA treatment. After adjusting for NIHSS score (an independent predictor of ICH), no EIC association with symptomatic ICH at 36 hours was detected in the group treated with rt-PA (P>/=.22). CONCLUSIONS: Our analysis suggests that EICs are prevalent within 3 hours of stroke onset and correlate with stroke severity. However, EICs are not independently associated with increased risk of adverse outcome after rt-PA treatment. Patients treated with rt-PA did better whether or not they had EICs, suggesting that EICs on CT scan are not critical to the decision to treat otherwise eligible patients with rt-PA within 3 hours of stroke onset.


Subject(s)
Brain Ischemia/diagnostic imaging , Plasminogen Activators/therapeutic use , Stroke/diagnostic imaging , Stroke/drug therapy , Tissue Plasminogen Activator/therapeutic use , Aged , Humans , Intracranial Hemorrhages/diagnostic imaging , Logistic Models , Middle Aged , Poisson Distribution , Recombinant Proteins , Risk , Severity of Illness Index , Stroke/physiopathology , Survival Analysis , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
19.
Exp Brain Res ; 141(2): 218-31, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11713633

ABSTRACT

Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disorder associated with intracellular cholesterol and glycolipid trafficking defects. Two separate genes, NPC1 and NPC2, have been linked to NP-C. NPC1 encodes a polytopic membrane-bound protein with a putative sterol-sensing domain. NPC2 has been recently identified as epididymal secretory glycoprotein 1. The NPC1 protein functions in the vesicular redistribution of endocytosed lysosomal cargo, but how its inactivation leads to neurodegeneration is not known. The neurological symptoms of NP-C typically appear after a period of normal early development and reflect progressive degeneration of widespread brain regions. Here we have delineated the pattern of neurodegeneration in NP-C mice, whose genetic defect has been shown to be an inactivating mutation of the mouse NPC1 gene. The results reveal a spatially and temporally specific pattern of degeneration of nerve fibers followed by degeneration of neuronal cell bodies beginning as early as day 9 and continuing throughout life. We have recently showed that in the primate brain, the NPC1 protein is localized predominantly within perisynaptic astrocytic processes. The present observations suggest that a functional disturbance in NPC1 could disrupt vesicular transport of cholesterol, glycolipids and possibly other endocytic cargo in glia, which is critical for maintaining the integrity of neurons.


Subject(s)
Brain/pathology , Nerve Degeneration/pathology , Neurons/pathology , Niemann-Pick Diseases/pathology , Proteins/metabolism , Aging/genetics , Aging/metabolism , Aging/pathology , Animals , Brain/metabolism , Brain/physiopathology , Cholesterol/genetics , Cholesterol/metabolism , Glycolipids/genetics , Glycolipids/metabolism , Image Processing, Computer-Assisted , Intracellular Signaling Peptides and Proteins , Mice , Mice, Mutant Strains , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Neurons/metabolism , Niemann-Pick C1 Protein , Niemann-Pick Diseases/genetics , Niemann-Pick Diseases/physiopathology , Proteins/genetics , Silver Staining
20.
J Neurocytol ; 30(3): 209-18, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11709627

ABSTRACT

Apolipoprotein D, a lipocalin transporter of small hydrophobic molecules including sterols, steroid hormones and arachidonic acid, is a widely expressed protein in peripheral and neural tissues. It has been shown to be upregulated in the context of neural injury, and with neuronal degeneration and regeneration. Here we have used light and electron microscopic immunocytochemistry with immunogold labeling to delineate the pattern of expression of apoD in the human brain. Our results confirm previous observations that apoD is a predominantly glial protein in the nervous system. In addition we have found that apoD is present in the cytosol and outer membrane of the nuclear envelope of glial cells in the neuropil. The labeled glial cells were putatively identified as a population of oligodendrocyte precursor cells. Immunoreactivity was also associated with the cytosol of perivascular cells, and lysosomes of pericytes, in the walls of blood vessels. These observations suggest a potential role for glial cells and apoD, in the transport of sterols and small hydrophobic molecules to, or from, blood vessels in the cortex.


Subject(s)
Apolipoproteins/metabolism , Blood Vessels/metabolism , Cerebral Cortex/metabolism , Oligodendroglia/metabolism , Pericytes/metabolism , Stem Cells/metabolism , Adult , Apolipoproteins D , Blood Vessels/ultrastructure , Carrier Proteins/metabolism , Cerebral Cortex/ultrastructure , Female , Humans , Immunohistochemistry , Male , Microscopy, Electron , Middle Aged , Neurons/metabolism , Neurons/ultrastructure , Neuropil/metabolism , Neuropil/ultrastructure , Oligodendroglia/ultrastructure , Pericytes/ultrastructure , Stem Cells/ultrastructure , Sterols/metabolism
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