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Biomedical subjects

C Nordborg

Publications and source records attributed to C Nordborg.

At least 55 records · Page 3Linked to original sources

Giant cell arteritis.

Whereas giant cell arteritis (GCA) was considered a rare disease 50 years ago, the generalized arteritis is now recognized as an important and significant cause of morbidity in elderly people; its cause and pathogenesis is poorly understood. Glucocorticosteroids are the drug of choice in all clinical types of GCA. In contrast to corticosteroids, nonsteroidal anti-inflammatory drugs have no proven effect on vascular complications to GCA, and cannot be recommended.

Adrenal Cortex Hormones↗

Effects of methylprednisolone on nucleus pulposus-induced nerve root injury.

STUDY DESIGN: The effects of intervention by intravenous injection of methylprednisolone to reduce the nerve root injury after epidural application of autologous nucleus pulposus was studied in an experimental model on the pig cauda equina in 20 animals. METHODS: Nucleus pulposus was harvested from a lumbar disc. After lowering the pH of the nucleus pulposus to 3.5 it was placed onto the sacrococcygeal cauda equina. Fifteen of the pigs received a single intravenous injection of 30 mg/kg methylprednisolone, 5 minutes, 24 hours, or 48 hours, respectively, after the application. After 7 days, the nerve conduction velocity was determined, and biopsies of the cauda equina was examined by lightmicroscopy. RESULTS: In the five pigs that did not receive any methylprednisolone treatment, nerve conduction velocity was reduced, whereas it was normal in the pigs treated 5 minutes and 24 hours after nucleus pulposus application. In pigs treated after 48 hours, nerve conduction velocity was reduced only slightly. At the light microscopic level, significant changes occurred in all series. CONCLUSIONS: This study indicates that the nucleus pulposus-induced effects on nerve function in an experimental pig model may be reduced dramatically by high-dose methylprednisolone administration within 24-48 hours after epidural application of autologous nucleus pulposus. The light microscopic changes were probably not significant for the nerve function. Instead, a morphologic explanation on a subcellular level should probably be sought.

Animals↗

The European Spine Society AcroMed Prize 1994. Acute thermal nerve root injury.

Bone cement is sometimes used for vertebral body reconstruction following tumor removal. During such procedures, the polymerization of the methyl-metacrylate in the bone cement generates heat. Such temperature increase might cause damage to the nerve roots within the spinal canal. In the present study, pig cauda equina nerve roots were subjected to controlled temperature increases by means of a heat-generating probe. A temperature of 40 degrees C applied for 5 min did not cause any changes in nerve root function. However, 70 degrees C resulted in a complete block of nerve root function within 5 min. Histological nerve fiber damage was seen after exposure to 60 degrees C and 70 degrees C. The present study provides basic knowledge of heat-resistance properties of spinal nerve roots that might be directly applicable as guidelines for safety margins during surgical spine reconstruction procedures using bone cement.

Action Potentials↗

Dendritic morphology in epileptogenic cortex from TRPE patients, revealed by intracellular Lucifer Yellow microinjection and confocal laser scanning microscopy.

Biopsy material was obtained from cortical epileptogenic zones (eight temporal, one occipital, one parietal and one frontal) of eleven patients aged 1.5-47 years with therapy-resistant partial epilepsy (TRPE) undergoing epilepsy surgery. Control autopsy material (two temporal, two occipital, one parietal and one frontal) was removed from six neurologically healthy cases within 6-10 hours postmortem delay. In each specimen, 100-300 pyramidal and non-pyramidal neurons were visualized by intracellular Lucifer Yellow microinjection. Single neurons were imaged using CLSM generated serial optical sections; 2-D reconstruction of each neuron was made using z-projection of serial optical images, and 3-D reconstructions and rotations were computerized. Neuronal maps from TRPE biopsies, compared to control autopsies, show markedly increased numbers of dendritic abnormalities of single pyramidal and non-pyramidal neurons in layers I, II-III, V-VII, and in the subcortical white matter. The abnormalities include: (1) increased number of non-pyramidal cells in layer I; (2) many pyramidal cells with two or three dendrites originating apically, rather than one single apical dendrite, in layers II-III; (3) atypical orientation of oblique apical and basal dendrites in pyramidal neurons of layers II-VII; (4) increased number of atypical 'dinosaur-like' and fusiform cells in layers V-VII; (5) numerous neurons in the white matter. These abnormalities may be etiological in cases with early onset, and predisposing in cases with late onset.

Adolescent↗

Concentrations of amino acids in extracellular fluid after opening of the blood-brain barrier by intracarotid infusion of protamine sulfate.

This article evaluates the influence of an opening of the blood-brain barrier (BBB) on compounds in brain extracellular fluid. The concentrations of amino acids and some other primary amines were determined in dialysates sampled from the right parietal cortex of rats before and after an intracarotid infusion of protamine sulfate. Extravasated plasma proteins were visualized by Evans blue/albumin and immunohistochemistry. CSF albumin--an indicator of blood-CSF barrier opening--was quantified with immunoelectrophoresis. The brains were macroscopically edematous after 10 mg but not after 5 mg of protamine sulfate. The higher dose led to a 50% death rate. The concentrations of amino acids did not change 10 min after the BBB opening. No significant alterations in the amino acid concentrations were observed after the lower dose. The concentrations of glutamate, aspartate, GABA, glycine, taurine, and phosphoethanolamine increased significantly within 50-80 min after the infusion of 10 mg of protamine sulfate. CSF albumin levels were significantly increased 1 h after infusion. We conclude that a dysfunction of the BBB, of a degree known to induce brain edema (10 mg of protamine sulfate), significantly increases the extracellular concentration of excitatory amino acids, GABA, taurine, and phosphoethanolamine in the extracellular space.

Amino Acids↗

Oedema-related tissue damage after temporary and permanent occlusion of the middle cerebral artery.

Eleven adults spontaneously-hypertensive male rats (SHR) were studied 22 h or 7 days after a 2 h unilateral occlusion of the right middle cerebral artery (MCA). Another 11 SHR were studied after 24 h or 7 days of permanent MCA ligation. The brain infarcts were significantly larger (P < 0.05) after permanent occlusion than after a 2 h occlusion. More extensive and widespread vasogenic oedema, emanating from the infarcts, was visualized immunohistochemically in the temporarily-ligated animals and the relative number of astrocytes in their contralateral hemispheres was greater, thereby indicating that the vasogenic oedema influences the degree of gliosis. An immunopositivity for albumin but not for fibrinogen extended via the white matter into the ipsilateral thalamic nuclei, where cytolytic nerve cell damage, severely shrunken and karyorrhectic nerve cells as well as gliosis were found one week after permanent and temporary MCA ligation. The histological changes in the thalamus indicated a difference in timing between lateral and medial parts of the lesion as well as between temporarily- and permanently-ligated SHR. These findings together with the close spatial correlation with albumin immunoreactivity indicate that the spread of extravasated plasma constituents or degradation products with the oedema bulk flow from the infarct influences the timing, character and extent of thalamic lesions after cerebral infarction.

Animals↗

The nasal route of cerebrospinal fluid drainage in man. A light-microscope study.

The drainage routes from the subarachnoid space to the nasal mucosa were investigated in autopsy material. Indian ink, applied post-mortem to the olfactory groove, promptly filled the perineurial spaces around the olfactory nerve branches in the dura, the lamina cribrosa and the submucosal tissue in the nose. In a case of recent subarachnoid haemorrhage, the perineurial spaces even around the most distal olfactory nerve branches were congested with blood and there was an abundant accumulation of red corpuscles in the apical part of the nasal mucosa. Iron-containing pigment was found in the perineurial spaces of proximal and distal olfactory nerve branches as well as in the nasal mucosal stroma in cases with older haemorrhagic lesions. The findings show that the perineurial spaces provide an efficient drainage route from the subarachnoid space to the nasal mucosa in cases with haemorrhagic cerebral lesions. A complementary drainage route for the cerebrospinal fluid was indicated by the presence of indian ink, red corpuscles and iron pigment in arachnoid villi, which penetrated the lamina cribrosa and ended in the nasal submucosal tissue. Iron in the deep cervical lymph nodes should not be taken as evidence of transport from the CNS, since iron pigment was also found in cases without intracranial haemorrhage.

Adult↗

A morphometric study of the effect of bilateral cervical sympathetic ganglionectomy on the architecture of pial arteries in spontaneously hypertensive and normotensive rats.

The influence of the cranial sympathetic nerves on the architecture of pial arteries in normo- and hypertension was examined. For this purpose the effect of bilateral superior cervical ganglionectomy was evaluated in normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). The operations were performed at the age of 1 wk, which is just prior to the onset of ganglionic transmission. The length of the inner media contour was measured and the media cross-sectional area was determined planimetrically, with computerized digitalization of projected photographic images of transversely sectioned pial arteries. Four wk after sympathectomy there was a 20% reduction in media cross-sectional area and a consequent reduction in the ratio between media area and calculated luminal radius in the major pial arteries at the base of the brain in WKY but not in SHRSP. Conversely, in small pial arteries linear regression analysis showed that in WKY subjected to ganglionectomy the relationship between media cross-sectional area and luminal radius was significantly larger in arteries with a radius less than 21 microns compared to untreated WKY. No such effect was seen in the corresponding SHRSP vessels. In addition, the cross-sectional area of the internal elastic membrane (IEM) in the basilar arteries of WKY was measured by means of a computerized image-analysing system. Mean cross-sectional area of the IEM was approximately 45% larger following SE than in control animals. The present findings propose a 'trophic' role for the sympathetic perivascular nerves in large pial arteries of the rat. The increased media-radius ratio in the small pial arteries of the WKY following sympathectomy might reflect a compensatory hypertrophy due to reduced protection from the larger arteries against the pressure load. The inability to detect any morphometrically measurable effect of the sympathectomy in the cerebral arteries of SHRSP is probably explained by a marked growth-stimulating effect of the high pressure load in these animals.

Animals↗

Hormone conference at Sahlgren's University Hospital: polycythemia and inappropriately high serum erythropoietin concentration in a 62-year-old man.

A 62-year-old man with a history of coronary insufficiency complained at his scheduled visit to the outpatient clinic of symptoms suggestive of gastritis. His blood hemoglobin concentration, however, was markedly increased. Results of a hematological work-up suggested an erythropoietin-producing tumor. Signs of increased intracranial pressure then led to the finding of a cerebellar tumor, which could explain his vertigo and abdominal symptoms. This cystic capillary hemangioblastoma probably was responsible for the erythropoietin production and also seemed to produce basic fibroblast growth factor. The clinical evaluation of polycythemia as well as erythropoietin biochemistry and clinical application are reviewed.

Capillaries↗

Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots.

Epidural application of autologous nucleus pulposus in pigs, without mechanical nerve root compression, induced a pronounced reduction in nerve conduction velocity in the cauda equina nerve roots after 1-7 days, compared to epidural application of retroperitoneal fat in control experiments. Histologically, the nerve fiber injury was more pronounced after application of nucleus pulposus than after control tissue application. The results demonstrate that nucleus pulposus may induce nerve tissue injury by mechanisms other than mechanical compression. Such mechanisms may be based on direct biochemical effects of nucleus pulposus components on nerve fiber structure and function and microvascular changes including inflammatory reactions in the nerve roots.

Animals↗

Glutamate enhances brain damage and albumin content in cerebrospinal fluid after intracarotid protamine infusion.

The blood-brain barrier was opened by intracarotid infusion of 5 mg protamine sulfate in 100 microliters 0.9% NaCl over a period of 30 s either alone or followed by infusion of 10 mg L-glutamate in 0.9% NaCl. Glutamate alone was infused in four control rats. Cisternal cerebrospinal fluid (CSF) was withdrawn before protamine administration and before the brains were fixed in situ 1, 24 or 72 h later. The albumin extravasation and glial reactivity was evaluated by immunohistochemistry on paraffin sections. The CSF albumin was significantly increased in both the protamine and protamine/glutamate groups but remained high at 24 and 72 h in the protamine/glutamate group only. Spongiotic lesions with shrunken nerve cells were observed 1 and 24 h after infusion of protamine alone or in combination with glutamate. Whereas such changes were not seen 72 h after protamine infusion, they remained and had progressed at 72 h in the protamine/glutamate group, indicating that glutamate induces delayed cellular damage when given access to the brain through an altered blood-brain barrier.

Animals↗

Biochemical correlates to cortical dysplasia, gliosis, and astrocytoma infiltration in human epileptogenic cortex.

The study provides detailed biochemical correlates to the common histopathological diagnoses in epilepsy. A dot immunobinding procedure was used for quantification of NSE, GFA, S-100, NCAM, NF 68 and NF 200. The material consisted of samples from 48 patients either selected for surgical treatment of partial epilepsy or for disorders not related to epilepsy. The histopathological diagnosis of the epileptic cases was: MCD (mild cortical dysplasia, microdysgenesis), gliosis, astrocytoma, ganglioglioma, oligodendroglioma and single cases. The concentration in non-epileptic white matter, in per cent of that in grey matter was: NSE, 85; GFA, 175; S-100, 117; NCAM, 43; NF 68,227 and NF 200, 173. The concentration of NSE as well as of GFA was close to normal in the specimens of the MCD and gliosis groups and of one subgroup of the astrocytomas. There was a striking inverse relationship of the GFA vs the NSE concentrations in the whole material. The concentrations of S-100 showed no such inverse relationship to NSE levels. In all the epileptic groups, total NCAM was lower than 50% of that of the non-epileptic group. The mean NF 68 and NF 200 concentration in the gliosis and astrocytoma groups was 75% of that of the non-epileptic group while the corresponding value for the MCD group was 50%. There was a positive correlation of immunochemically determined GFA and the histopathological gliosis score in the samples of epileptogenic cortex. There was no correlation between the concentration of GFA in the samples and the duration of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Brain capillary density and cerebral blood flow after occlusion of the middle cerebral artery in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats.

OBJECTIVE: In order to elucidate why spontaneously hypertensive rats (SHR) develop larger brain infarcts distal to an arterial occlusion than normotensive Wistar-Kyoto (WKY) rats, we determined the surface and volume densities of cerebral capillaries, and the regional cerebral blood flow distal to an arterial occlusion in SHR and WKY rats. DESIGN: Occlusion of the middle cerebral artery was chosen because the middle cerebral artery territory is most commonly affected by cerebral infarcts in man. METHODS: Surface and volume densities of capillaries in the neocortex of the middle cerebral artery territory were measured by stereological techniques on histological sections. Fifteen minutes after ligation of the right middle cerebral artery, regional cerebral blood flow was measured autoradiographically by the [14C]-iodoantipyrine method. RESULTS: The capillary density of the neocortex did not differ between the SHR and WKY rats. The blood flow was significantly lower within the middle cerebral artery territory in the SHR than in the WKY rats. CONCLUSIONS: The reduced blood flow distal to the occlusion in SHR is probably a consequence of structural adaptation of arterial resistance vessels, rather than being caused by reduced capillary density.

Animals↗

Comparison of dietary casein and soybean protein effects on plasma lipid and gastrin levels, hepatic delta 6-desaturase activity and coronary arteriosclerosis in male Sprague-Dawley rats. A 9-month study.

An increased concentration of gastrin was observed in plasma of male Sprague-Dawley strain rats fed on soybean protein diet for a 9-month period, compared with rats fed on casein diet. Both diets contained 0.5% (w/w) cholesterol. Protein-dependent differences were also observed in the fatty acid pattern of hepatic phospholipids, hepatic delta 6-desaturase activity, and plasma cholesterol. No signs of arteriosclerosis were observed in the aortas. Sixty percent of the hearts showed various degrees of lipid staining in coronary arterial branches of different sizes. Despite a large difference in plasma cholesterol level, there was no quantitative or qualitative difference between groups in the occurrence of coronary lipid staining.

Animals↗

Neurovascular microdysgenesis in a case of Unverricht-Lundborg's disease.

An 18 year old female presented with a characteristic clinical course of Unverricht-Lundborg's disease. She was treated with several antiepileptic drugs but never with phenytoin. This patient died quietly during sleep. Coronal sectioning of the fixed brain revealed a 10 mm large red-brown solid cortical-subcortical lesion in the mesial part of the right frontal lobe and a similar alteration measuring 4 mm in the centromedian nucleus of the left thalamus. Histologically the lesions displayed supernumerary irregularly oriented vessels, mainly capillaries, and, in the cortex, a markedly disturbed neuronal orientation and lamination. Numerous heterotopic nerve cells were found in the subcortical white matter, especially under the calcarine cortex. A similar vascular malformation was found in the pons. The neuropathological changes in Unverricht-Lundborg's disease have been described as non-specific atrophy of various neuronal populations, especially medial thalamic nuclei and Purkinje cells. The present case shows that the same clinical picture may be associated with multiple cerebral microvascular malformations and a disturbance in neuronal migration and organization which may be more generalized than appears in light microscopical sections.

Adolescent↗

Neuropathologic findings after long-term intrathecal infusion of morphine and bupivacaine for pain treatment in cancer patients.

Epidural or intrathecal infusions of morphine and bupivacaine mixtures are presently used for the treatment of "refractory" cancer pain even though the neurotoxic potential of such mixtures is unknown. The pathologic findings of the spinal column, the meninges, the nerve roots, and the spinal cord, and the clinical neurologic deficits were recorded in 15 patients (5 men and 10 women), aged 26-83 (median 68) yr, treated for 4-274 (median 81) days with intrathecal infusions of morphine (with preservatives [sodium metabisulfite and sodium edetate]) and bupivacaine mixtures, given through open, subcutaneously tunneled nylon catheters. Six patients had been subjected to radiation therapy (20-96 Gy), applied over the spinal column, and four had been treated with antineoplastics believed to be neurotoxic. Ten patients had various neurologic deficits before the intrathecal treatment. The cumulative doses (ranges) given intrathecally were: morphine 33-11,900 mg, sodium metabisulfite 3.3-1,050 mg, sodium edetate 0.33-105 mg, and bupivacaine 10-41,400 mg; cumulative volumes were 16-9,400 ml. The concentrations of the drugs in the mixtures were: morphine 0.25-4.0 mg/ml, sodium metabisulfite 0.025-0.40 mg/ml, sodium edetate 0.0025-0.04 mg/ml, and bupivacaine 3.0-4.75 mg/ml. The osmolality of the mixtures in vitro ranged from 282 to 286 mOsm/kg and the pH from 4.1 to 4.6. The pathologic findings consisted of vertebral metastases (n = 6), epidural and/or intrathecal tumor masses (n = 8), focal subdural fibrosis (n = 6), infiltration of mononuclear cells in the subarachnoid space (n = 10), and discrete injuries (nerve fiber degeneration or fibrosis) to the anterior (five patients) and posterior (seven) nerve roots, and spinal cord (tumor compression [one], slight thickening of the leptomeninges [one], and thrombosis of a spinal artery and medullary infarction [one]). In none of the cases was any reaction against the nylon catheter within its subarachnoid course recorded. The neuropathologic findings were not related to the duration or cumulative doses of the intrathecal treatment. No new neurologic deficits that could be attributed to the intrathecal administration of the opiate-bupivacaine mixtures were recorded. The neuropathologic and clinical neurologic findings in cancer patients treated with intrathecal morphine-bupivacaine mixtures appeared similar to those in animals and humans reported with either intrathecal morphine or bupivacaine alone.

Adult↗

Atypical pyramidal cells in epileptic human cortex: CFLS and 3-D reconstructions.

Epileptic temporal cortices, removed from 3 patients with intractable partial epilepsy (IPE) during neurosurgery, were studied. Pyramidal neurons (40-50 per slice) in laminae III, V and white matter, were injected with lucifer yellow. Samples were examined in a confocal laser scanning microscope (Biorad 600) and individual cells scanned at 0.1-1 microns incremental levels. 2-D maximal linear projection was used for overview. Frames (50-60) of scanned neurons were transformed into 3-D volumes, using VoxelView software on a Silicone Graphics workstation and rotated. All samples contained neurons with duplicated apical dendrites, additional basal dendrites or were misplaced in a horizontal position in the white matter. The relation between these preliminary observations and the disease is discussed.

Epilepsies, Partial↗

Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats.

Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25% and left ventricular weight (LVW/BW) increased by 18% compared to Wistar-Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine-therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B12 and normalized for organ weight. PSCr-EDTA, PSB12 and the ratio PSCr-EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated.

Animals↗