[Psychological care of opiate dependent patients].
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Biomedical subjects
Publications and source records attributed to H M Liu.
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We examined 23 patients with pituitary dwarfism by dynamic MRI; with a repetition time of 150 or 50 ms. The time-enhancement difference curves of selected regions in the anterior lobes were plotted. Another 48 patients with no definite clinical pituitary disfunction were examined with the same technique. We found that the intensity of maximum enhancement in both groups was similar, but the time to achieve maximum enhancement was delayed in pituitary dwarfism with or without stalk transection; the time seemed longest with stalk transection. There was little difference in enhancement between patients with multiple hormone deficiency or isolated growth hormone deficiency. Dynamic MRI of the anterior lobes may be an important functional imaging study, and our results imply that poor perfusion is a useful finding in pituitary dwarfism, especially in patients without stalk transection and normal pituitary height.
Retrospectively, the dura in 18 adult patients with acute leukemia were evaluated by gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI). Abnormal dural enhancements were detected in three of four patients with positive cerebrospinal fluid (CSF) cytology, in one of five with suspicious central nervous system (CNS) disease, and in two of nine asymptomatic patients. Computed tomography failed to demonstrate any dural abnormality in these six patients. The abnormal dural enhancement was found in either (a) the brain and the spine, (b) the thoracolumbar spine, or (c) the area adjacent to the parenchymal lesions. Three of the patients were in hematological remission stage; disappearance of the abnormal dural enhancement was observed 1-2 months after radiotherapy and high-dose systemic chemotherapy. The results suggest that MRI is a sensitive and noninvasive imaging modality and superior to CT in detecting dural disease in leukemic patients.
When a silicone tube is implanted in transected rat sciatic nerve, there is plasma accumulation and formation of a fibrin cable followed by proliferation and migration of neural and nonneural cells from the nerve stumps into the cable. The wound fluid exhibited neurotrophic activity of unknown origin and nature. In this study, we analyzed the NGF level in wound fluid by a sensitive enzyme immunoassay and correlated the NGF level with the cytological localization of NGF, low affinity NGF receptor (p75NGFR), and Trk receptor in the axotomized nerve by immunohistochemistry. We demonstrated a rising NGF level in wound fluid from 490 pg/ml on Day 1 to 950 pg/ml on Day 7; the serum NGF level was 1/20 of that in the wound fluid. The infiltrating leukocytes expressed strong NGF but no p75NGFR. The proliferative fibroblasts and vascular cells exhibited a short period of NGF but no p75NGFR staining. Schwann cells in the distal segment showed a prolonged period of NGF and p75NGFR expression. No Trk receptor was demonstrated on leukocytes or non-neural cells. These findings suggest that locally synthesized NGF is mainly responsible for the neurotrophic activity in the wound chamber fluid. The NGF produced by the nonneural cells may be bound and stored in the p75NGFR in Schwann cells in the distal segment prior to the arrival of the regenerating axons.
Four patients with the classic form and 1 patient with the connatal form of Pelizaeus-Merzbacher disease were studied with magnetic resonance imaging, electroencephalography, and multimodal evoked potentials, including brainstem auditory evoked potentials, somatosensory evoked potentials, and visual evoked potentials. Comparisons between these findings were made. It was determined that the neurophysiologic studies, particularly brainstem auditory evoked potentials, are of value in early diagnosis of Pelizaeus-Merzbacher disease; brainstem auditory evoked potentials with only normal wave I may be a relatively reliable clue suggesting the classic form of Pelizaeus-Merzbacher disease in patients with nystagmus and chronic progressive encephalopathy. Magnetic resonance imaging allows an accurate assessment of the degree of hypomyelination; however, the clinical severity of various forms of Pelizaeus-Merzbacher disease seemed to be independent of the age of onset and the amount of residual myelin. The following may be distinguishing features between the connatal and classic forms of Pelizaeus-Merzbacher disease: hypoplasia of the cerebellum and brainstem, and diffuse brain atrophy on magnetic resonance imaging; optic atrophy with abnormal visual evoked potential; seizure disorder with abnormal electroencephalography, and/or auditory nerve impairment with abnormal wave I of brainstem auditory evoked potentials in the early stage of the disease.
Ischemia/hypoxia rapidly induce ischemic changes in vulnerable neurons: cortical neurons in layers II-III and V, hippocampal neurons, cerebellar Purkinje cells and certain basal ganglia and brainstem neurons. The ischemic changes are manifested histologically by nuclear pyknosis, cytoplasmic shrinkage and basophilia. These neurons exhibit strong and persistent expression of immediate early genes (IEGs): c-fos and c-jun. The onset of IEG expression is followed within a day by enhanced bFGF expression in non-ischemic neurons in the same general regions. The appearance of bFGF is followed within another day by proliferation of blood vessels, macrophages and glial cells around the infarct. The newly-formed blood vessels and macrophages migrate into the necrotic infarct aiming at disposal of the necrotic debris. The gliosis although concentrated around the infarct spreads to involve remote regions of both hemispheres. Based on the spatiotemporal correlation between cell proliferation and bFGF and the known mitogenic properties of bFGF, we believe that this molecule may be responsible for the late response in brain infarct including angiogenesis, gliosis and macrophage proliferation. The physiological roles of IEGs in the chain of adaptive response following brain infarction and its relationship with bFGF are subjects pending future investigations.
OBJECTIVES: Based on the findings in computed tomography scans, we defined a grading system that is well correlated to the changes of the brainstem and its perimesencephalic cistern during intracranial hypertension. MATERIALS AND METHODS: The grades are defined as follows: Grade 0 is normal, grade 1 represents widening of the perimesencephalic cistern without brainstem change, grade 2 represents obliteration of the cistern without brainstem change, grade 3 represents a deformed brainstem; grade 4 represents brainstem density change, and grade 5 represents any combination of grades 3 and 4. As a comparison to the Glasgow Coma Scale (GCS) system, we examined this new system in 334 cases, in which 138 cases were classified as severe head injuries. RESULTS: In cases of mild head injury (GCS score > 8), this new system was correlated to the GCS system well in grades 0 to 2. In cases of severe head injury, the prediction of outcome is better in our system because it is well correlated to dynamic change of intracranial hypertension, especially in cases with nonsurgical masses of grades 3 and 5. CONCLUSIONS: Our grading system is easy to use, and is well correlated to give an accurate prediction of outcome in cases with severe head injury based primarily on the results of an initial computed tomography scan, even without clinical information, and it should play a role in the classification of head injury.
Spinal intradural arteriovenous fistula is a rare type of spinal vascular malformation. It is usually fed by the anterior spinal artery and causes episodic myelopathy in young adults. We present a pediatric patient with such a vascular malformation which was fed directly by a medullary artery. The clinical course, complete radiological study and the excellent outcome will be described in detail. This rare subtype of spinal vascular malformation will be discussed.
The role of Schwann cells (SC) during Wallerian degeneration has been controversial. The consensus opinion is that monocytes/macrophages are mainly responsible for myelin removal although SC were shown to phagocytose myelin in vitro and in vivo. In the present study, we correlate proto-oncogene expression with phenotypic changes in SC during Wallerian degeneration using immunohistochemistry and electron microscopy. The proliferative cells are labeled with proliferative cell nuclear antigen (PCNA), and macrophages are labeled with ED1 macrophage marker. We demonstrate c-fos expression in SC at the onset of axon disintegration 12 hours post-axotomy followed by expression of ED1, basic fibroblast growth factor (bFGF) and PCNA after 1 day. The myelin sheath fragments at the nodal region and forms ellipsoids. Schwann cells move to internodes and undergo nuclear and cytoplasmic hypertrophy; they phagocytose myelin ellipsoids with thick vimentin-rich processes and undergo mitosis. Resident macrophages express c-fos and phagocytose myelin debris sequestered into endoneurium by SC after 3 days, but they do not enter the tube until the fifth day. We believe that SC are induced by signals from injured axons to express c-fos which activates downstream genes that lead to the acquisition of phagocytic and proliferative activities. Myelin debris processed by SC may act as an inducer and a chemoattractant for resident macrophages. Cytokines produced by macrophages may stimulate SC proliferation and production of neurotrophic factors.
We correlated the histopathological findings of six human brain abscesses with the expression of basic fibroblast growth factor (bFGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF beta). The clinical courses ranged from 1 month to 1 year and viridans streptococcus was the major pathogen. In early abscesses, we demonstrated strong bFGF and moderate NGF and PDGF immunoreactivities in neutrophils and monocytes/macrophages infiltrating the abscess wall and in the fibrin layer lining the abscess center. In the subacute cases, growth of capillaries and fibroblasts into the fibrin layer and deposition of collagen resulted in the formation of a mesodermal layer between the abscess center and the outer gliotic layer. The proliferative non-neural cells (endothelial cells, fibroblasts and glial cells) expressed mild to strong bFGF, NGF and PDGF immunoreactivities, while strong TGF beta staining was seen in the extracellular matrix. A loss of growth factor expression and increased fibrosis was seen in the chronic case. These findings suggest that bFGF, NGF, PDGF and TGF beta produced by the continued influx of leukocytes and by the proliferating non-neural cells may mediate various steps of defense mechanisms and wound healing such as angiogenesis, fibrogenesis and gliosis.
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Astrogliosis, angiogenesis and macrophage activity are classical responses of brain to injury. The factors that induce these changes and the dynamic interaction among cells in the environs of the injured brain remain unclear. In the present rat brain infarct model, we studied the spatiotemporal relationship between basic fibroblast growth factor (bFGF) expression and cell proliferation using proliferating cell nuclear antigen (PCNA) as an S-phase marker. We demonstrated an early astrocytic and neuronal activation with enhanced expression of bFGF in areas adjacent to the infarct. This was followed by a period from 3-5 days of intense cell proliferation. Proliferating cell nuclear antigen-labeled nuclei were demonstrated in perineuronal satellite cells, endothelial cells, vascular pericytes, macrophages and glial cells. These cells appeared to respond to the same mitogen(s) and they produced bFGF during the proliferative phase. There was a simultaneous spreading of neuronal activation and glial proliferation from the infarct to the entire ipsilateral hemisphere and through the coronal radiations to the contralateral hemisphere. This spreading follows the pattern of spreading of edema fluid. Our findings suggest that cell proliferation in the brain infarct may be induced by bFGF released by neurons and sustained by bFGF and other growth factors produced by non-neural cells on an autocrine basis.
Injuries to the brain induce rapid expression of c-fos and c-jun proto-oncogenes in neurons. The protein products (Fos and Jun) of these cellular immediate early genes are thought to regulate target genes that participate in fundamental biological responses. In recent studies of rat brain infarct we demonstrated that gliosis and angiogenesis, two of the fundamental biological responses, are related to neuronal expression of basic fibroblast growth factor (bFGF). In the present study, we explore the linkage between c-fos and bFGF genes by comparing the temporal and spatial domains of Fos and bFGF immunoreactivities (IR) in brain infarct and in transient global ischemia. We demonstrate colocalization of Fos-IR and ischemic changes in neurons at infarct periphery and in regions of "selective vulnerability" beginning 3 hours post-infarction and lasting up to 1-2 weeks. These are: cortical neurons in layers II-III and V, interneurons in hippocampal formation, cerebellar Purkinje cells, and many subcortical nuclei and brainstem nuclei. bFGF-IR appears 12-24 hours later than Fos-IR in the same region but in non-ischemic neurons and the expression persists beyond 2 weeks. Persistent and not transient c-fos expression appears to be associated with ischemic neuronal death, although some of these neurons may survive beyond 2 weeks postinfarction.
BACKGROUND AND PURPOSE: Cerebral endothelial cells are quiescent under normal conditions; they are stimulated to proliferate around an infarct, although the mechanism is unclear. In the present study we explored the relation between angiogenesis and the expression of basic fibroblast growth factor (bFGF) by participating cells in brain infarct. METHODS: Brain infarct was created in rats by ligation of a branch of the left middle cerebral artery followed by permanent occlusion of the left common carotid artery and temporary occlusion of the right common carotid artery. The brains were removed after 1 to 14 days and studied with histological and immunohistochemical methods. Bromodeoxyuridine (BRdU) was used as an S-phase marker for the proliferative cells. RESULTS: Enhanced bFGF immunoreactivity was observed in neurons adjacent to the infarct after 1 day, and the change subsequently spread to distant neurons in the ipsilateral hemisphere. After 2 days blood vessels and glial cells around the infarct began to incorporate BRdU. During the first week new capillaries accompanied by macrophages extended into the infarct. The macrophages, endothelial cells, and reactive astrocytes expressed mild to moderate bFGF immunoreactivity. CONCLUSIONS: The spatial and temporal correlation between bFGF expression and angiogenesis in conjunction with the well-known biological properties of bFGF suggest that bFGF produced by neurons, macrophages, and glial cells may participate in angiogenesis in brain infarct.
The hemodynamic classification of the CCF has important implications for prognosis and therapy, but satisfactory criteria for such a differentiation are still lacking. We studied the application of extracranial duplex sonography in 14 cases of CCF with emphasis on the hemodynamic parameters of the RI and flow volume and made a correlation with the angiographic findings. We conclude with proposed duplex sonographic criteria for hemodynamic classification: (1) small RI with increased flow volume in the ICA: direct ICA-cavernous sinus fistulas (type A); (2) normal RI and flow volume in the ICA and ECA: dural branch of ICA-cavernous sinus fistulas (type B); (3) small RI with or without increased flow volume in the ECA: dural branch of ECA-cavernous sinus fistulas (type C) or dural branches of ICA- and ECA-cavernous sinus fistulas (type D). Application for assessment of the therapeutic effectiveness was also demonstrated.
We describe a Chinese male patient with clinicopathologically definite Churg-Strauss syndrome. He had a clinical pattern of mononeuropathy multiplex and unusual optic neuritis, the latter probably being due to vasculitis related demyelination of the optic nerve. Magnetic resonance imaging of the brain revealed many clinically silent central nervous system lesions. He initially received steroid therapy, but an early cessation of treatment resulted in acute exacerbation. Later on, he was treated with combined prednisolone-cyclophosphamide therapy for 1 year. His ophthalmological and neurological symptoms responded well to such a regimen and disappeared within 6 months.
A 23-year-old female developed progressive cerebellar ataxia as the only presentation of multiple sclerosis for 6 years. Abnormal evoked potentials, an increased oligoclonal band of IgG-K in the cerebrospinal fluid and disseminated white matter lesions in magnetic resonance images (MRI) were compatible with a diagnosis of clinically definite multiple sclerosis. After cyclosporine treatment, the ataxia became stable without further deterioration. A follow-up MRI six months later did not reveal any active lesions. The importance of MRI in the confirmation of the clinical diagnosis and the evaluation of therapeutic effects in patients with atypical multiple sclerosis is emphasized.
This study represents a preliminary retrospective assessment of the value of spin-echo magnetic resonance imaging (MRI) in detecting and describing total or partial anomalous pulmonary venous return (APVR). MRI was performed in 21 cases of APVR; orthogonal planes were used in all. Of the 21 cases, 19 were classified as total APVR (TAPVR) and two were partial APVR (PAPVR). Of the 19 cases of TAPVR, seven supracardiac, nine cardiac, one infracardiac and two mixed type were noted. The detection rate of each pulmonary vein combined in all three planes was 57% in the right superior pulmonary vein (RSPV), 62% in the left superior pulmonary vein (LSPV), 76% in the right inferior pulmonary vein (RIPV), and 86% in the left inferior pulmonary vein (LIPV). The axial plane was most effective (RSPV: 38%; LSPV: 52%; RIPV: 71%; LIPV: 81%). The coronal plane offered a better detection rate than the axial plane in RSPV (43%) and additional information of bronchial and visceral situs. Imaging of the combined axial and coronal planes was sufficient to evaluate each individual pulmonary vein. The sagittal plane gave no additional information in this respect. Accurate identification of pulmonary venous confluence and anomalous pulmonary venous channel was 95% (20/21). Limitation of echocardiography and and angiocardiography makes cardiac MRI important in assessing pulmonary vein and pulmonary venous confluence. It obviates the need for invasive angiocardiography and is an important supplement to an inadequate echo.