[Sumatriptan (Imigran) and migraine with aura--is the price still too high?].
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Biomedical subjects
Publications and source records attributed to T S Olsen.
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The view that "spreading oligemia" reflects spreading depression in the human brain during the migraine aura is based on a defective analysis of CBF data where the most important methodological source of error (scattered radiation) has been ignored. When scattered radiation is taken into account it appears that CBF in the low flow area during the migraine aura is reduced to the ischemic level. There is no reason to believe that "spreading" of the low flow area occurs. Most likely the blood flow decreases in an area of fixed size. All available CBF evidence in fact lends support to "the vascular theory" of migraine pathogenesis.
Fifteen consecutive patients with a diagnostic problem of ischaemia-induced migraine with aura (symptomatic migraine) or migraine-associated ischaemia (migrainous infarction) were studied in order to elucidate the mechanisms. Three had a 1 month flurry of daily attacks of migraine auras with or without headache. A severe internal carotid stenosis/occlusion and reduced regional cerebral blood flow (rCBF) was demonstrated. Borderline ischaemia may thus prime the brain for developing migrainous aura with or without migraine (symptomatic migraine). Four patients had a combination of permanent deficits after the very first migraine attack, severe atherosclerosis, risk factors for stroke, high age and no family history of migraine. In these cases the evidence indicates that thromboembolic ischaemia had triggered an attack of migraine with aura (likely symptomatic migraine). Three young females presented long-lasting typical and severe idiopathic migraine with aura. Attack-associated rCBF reduction was likely to have caused permanent, mild, visual or somatosensory deficits (migrainous infarction). In five patients the relationship between migraine and stroke remained unresolved. It seems that ischaemia-induced migraine attacks may be more frequent than migraine-induced ischaemic insults. Therefore, migraine is not as strong a risk factor for stroke as indicated by the mere coincidence of the two disorders.
BACKGROUND AND PURPOSE: In a feasibility and safety study of thrombolytic therapy in acute ischemic stroke, we explored the usefulness of measurements of regional cerebral blood flow. METHODS: Twenty-three patients with acute ischemic stroke were treated with 100 mg recombinant tissue plasminogen activator infused intravenously over 1 hour. Thrombolytic therapy was initiated 78 to 355 minutes after onset of symptoms. RESULTS: Angiography 16 to 24 hours after treatment in 17 patients showed patient intracranial arteries in 12, partial occlusion of the middle cerebral artery in 3, and total occlusion of the middle cerebral artery in 2. rCBF with 99mTc-hexamethylpropyleneamine oxime intravenously was measured 5 minutes before and within 24 hours after thrombolytic therapy in 12 patients. 10 of the 12 patients showed brain tissue reperfusion and 2, with angiographically documented middle cerebral artery occlusion, showed no reperfusion, thus documenting a relationship between reperfusion measured by regional cerebral blood flow and angiographic patency (P = .015). Three patients died. Patients who were reperfused within 24 hours (documented by repeated regional cerebral blood flow measurements) showed greater clinical improvement on the Scandinavian Stroke Scale the sooner their thrombolytic therapy was started and the more severe their neurological deficits. CONCLUSIONS: Acute cerebral ischemia can be documented by rCBF measurements without delay of thrombolytic therapy, and repeated rCBF measurements can reveal whether cerebral reperfusion has occurred. In our study, early reperfusion was associated with clinical improvement.
The diagnostic value of cerebrospinal fluid (CSF) ferritin was assessed in 30 patients with meningeal reaction (viral meningitis 10; bacterial meningitis 6; meningism 14) and in 37 patients with cerebrovascular disease (cerebral infarction 29; transient ischaemic attacks 4; cerebral haemorrhage 4). The control group comprised 13 subjects with minor neurological disorders. CSF-ferritin levels were not significantly different in the various subgroups, most patients having values within the normal reference interval (2-7 micrograms/l). A clearly elevated CSF-ferritin was seen in one patient with bacterial meningitis and in one patient with intraventricular bleeding. In patients with meningeal reaction, CSF-ferritin was significantly correlated to CSF-protein. Patients with cerebrovascular disease displayed significant correlations between CSF-albumin and CSF-IgG and between CSF-ferritin, CSF-albumin and CSF-IgG. The present study indicates that measurement of CSF-ferritin is of no practical clinical relevance in the evaluation of patients with meningeal reaction and cerebrovascular disease.
This review concerns the acute phase of stroke. It describes incidence, prevalence, etiology, diagnosis and treatment together with the possibilities for prevention. The incidence of stroke in the Danish population is about 2/1000 person years and has been largely unchanged during the last 20 years. About 85 per cent of strokes are caused by cerebral infarcts, ten percent by intracerebral haemorrhages and about five per cent by subarachnoid bleeding. The incidence increases with age. Up till age 65 years the ratio between men and women is two to one, while the ratio in the oldest age group approaches one to one. The most important risk factors for stroke are smoking, arterial hypertension, previous cerebrovascular disease, heart disease and diabetes mellitus. Till now, no treatment has been documented as effective in reducing the cerebral damage caused by acute stroke. Ongoing controlled clinical trials in the acute state of ischaemic stroke are testing the effect of thrombolytic therapy, treatment with calcium antagonists, glutamate receptor antagonists, aspirin and heparin. The general medical treatment including nursing and physiotherapy in the acute phase is described. Within recent years benefit of various strategies of stroke prevention has been documented.
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In acute interstitial nephritis (AIN), mononuclear cells invade the tubules (tubulitis). The segmental localization of tubulitis is not precisely known. To clarify this question, formalin-fixed kidney biopsy specimens from 13 patients with AIN were studied stereologically by identifying cortical tubules with segment-specific markers. The periodic acid-Schiff reaction, peanut lectin, and antibodies against Tamm-Horsfall protein and epidermal cytokeratins all applied to the same section were used to identify the proximal tubules (PTs), distal convoluted tubules, distal straight tubules, and the cortical collecting system (connecting tubules and cortical collecting ducts), respectively. Morphometrically, an estimate of the relative volume of the inflammatory cell infiltrates within each category of tubular segments was obtained. Inflammatory cells were infrequently found in PTs (1.2%) but were frequently localized in distal tubules and the cortical collecting system (7.6%). There was no difference in the amount of the inflammatory cell infiltrate within these segments. Re-examination of an electron microscopic study of AIN carried out in this laboratory revealed that mononuclear cells were rarely seen in convoluted PTs but were frequently observed in straight PTs and all segments distal to them. The observations indicate that it is the distal nephron which is primarily affected by inflammatory cell infiltration in AIN.
BACKGROUND AND PURPOSE: The early time course after acute stroke of cerebral N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline was studied in vivo by means of localized water-suppressed proton magnetic resonance spectroscopy. METHODS: Eight patients with acute stroke were studied serially in the acute phase, 1 week after, and 2-4 weeks after the onset of clinical symptoms. Ten healthy volunteers served as controls. A stimulated echo (STEAM) sequence was used for measurement of the brain metabolites in a volume of interest located within the infarcted area as visualized by magnetic resonance imaging. For quantification, the unsaturated water signal was used as the internal standard. Regional cerebral blood flow in the infarcted area was measured relative to a symmetrically located unaffected area by means of single-photon emission computed tomographic scanning, using 99mTc-labeled d,l-hexamethylenepropyleneamine oxime as the flow tracer. RESULTS: Relative regional cerebral blood flow was considerably reduced in the infarcted area in the acute phase. After 1 week, hyperemia was seen in all but one patient. The N-acetylaspartate content was significantly reduced, with the loss appearing to occur between 6 and 24 hours after the stroke incident. The reduction in N-acetylaspartate content was greater in the central part than in the peripheral part of the infarcted area. Creatine and phosphocreatine were also reduced in the infarcted area, whereas no significant change was seen in the choline content. CONCLUSIONS: Assuming that N-acetylaspartate content reflects neuronal survival or loss, our results may suggest that treatment procedures with restoration of blood flow to severely ischemic areas should be initiated within the first 6 hours after stroke onset.
The case is presented of a 48-year-old female suffering from diffuse cutaneous systemic sclerosis (diffuse scleroderma) since 8 years, who went into renal failure as part of hemolytic uremic syndrome following 3 weeks' treatment with 3.8 mg/kg cyclosporin A. Hemolytic uremic syndrome has previously been described in transplant patients receiving cyclosporin A. There are also four cases reported in the literature of renal failure developing in middle aged females with diffuse cutaneous systemic sclerosis after short-term use of low dosage cyclosporin A treatment. It is suggested, that it may be wise not to use cyclosporin A to this category of patients, in which it can not be ruled out, that even a low dose therapy may trigger the rapid onset of scleroderma renal crisis or as in our case provoke hemolytic uremic syndrome.
To describe ultrastructural changes in renal peritubular capillaries during acute allograft rejection, biopsy specimens from five allografts with acute rejection were studied electron microscopically and compared with control specimens. The thickness, cross-sectional area, and luminal circumference of capillary endothelium were estimated morphometrically. Thickening of endothelial cells, loss of fenestration, increase in endothelial cell organelles, increased adherence and passage of lymphocytes and monocytes, and defects in the endothelial lining were demonstrated. The luminal circumference representing the size of the capillary was not changed. A balloonlike fragmentation of endothelial cells was sometimes observed around lymphocytes, suggesting cytotoxic injury to capillaries. The observations indicate that during rejection-induced endothelial activation, peritubular capillaries exhibit postcapillary venule-like transformation that enhances the influx of inflammatory cells into the kidney allograft.
A close relationship exists between the severity of a stroke and the functional level that can be obtained after rehabilitation. The goal of rehabilitation, therefore, should be based on the severity of the stroke. Remission mainly takes place (more than 80%) within the first three months post stroke. Remission after six months is very rare. Age and side of hemiparesis do not seem to influence the effect of rehabilitation significantly. It is not elucidated whether the severity of the stroke influence the effect of rehabilitation. Most of the controlled and the randomized studies indicate that rehabilitation of stroke patients, especially in rehabilitation units, accelerate remission, reduces length of stay and gives rise to a lasting improvement of function.
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In six patients, we observed remarkably unsteady blood flow and indications of vasospasms on the arteriolar level in connection with episodes of focal cerebral ischemia. The patients originated from a prospective consecutive study of 53 patients with stroke and transient ischemic attack who had been examined by cerebral angiography and rapidly repeated regional cerebral blood flow measurements using the intracarotid xenon 133 method. In 47 patients, regional cerebral blood flow values, flow patterns, and clinical condition were stable during the repeated regional cerebral blood flow measurements. In six patients, pronounced regional hypoperfusion and hyperperfusion developed during the course of examination. In the hypoperfused regions, flow was transiently reduced to values consistent with ischemia, and in four of these patients this was accompanied by transient neurological deficits. The arteriogram and isotope angiograms ruled out spasms of large arteries or thromboembolism. A condition of cerebrovascular instability on the arteriolar level probably was induced by the examination procedure. These patients were hypersensitive to the provoking stimuli either habitually or as a consequence of previous ischemic accidents. It is suggested that in some patients with focal cerebral ischemia, the primary cause might be spasms of the smallest resistance vessels rather than thromboembolism.
To identify the renal cortical tubular segments involved in tubulo-interstitial disease in formalin-fixed, paraffin-embedded percutaneous kidney biopsies, we developed multiple immunolabeling protocols using segment-specific tubular markers. The present study of biopsies from patients with minimal change or thin basement membrane nephropathy provides a baseline for interpretation of histopathology. Proximal tubules were stained either by the PAS reaction or by the biotinylated Phaseolus vulgaris erythroagglutinin (PHA-E)-streptavidin-gold-silver system (brush borders black). The anti-Tamm-Horsfall (THP) antibody-immunoperoxidase (aminoethylcarbazole, AEC-IPO), and anti-epidermal cytokeratins (ECK) antibodies-immunoalkaline-Fast Blue BB methods marked the distal straight tubules and the cortical collecting system red-brown and blue, respectively. When these immunolabelings were combined, the coapplication of AEC-PO-labeled peanut agglutinin (PNA) or anti-epithelial membrane antigen antibody-AEC-IPO technique (both are markers for distal nephron) visualized the apical membranes of distal convoluted tubules. In the protocol PHA-E + PNA + THP + ECK, the tubular basement membranes were outlined by the anti-laminin antibody-AEC-IPO staining, carried out simultaneously. The protocol PNA + THP + ECK + PAS was found to be quite appropriate multiple immunolabeling method for the tubules, and is recommended for use as a tool in the study of tubulo-interstitial diseases.
Outcome was studied prospectively in 28 consecutive patients with occlusion of the middle cerebral artery (MCA). They comprise a subgroup of 101 consecutive patients with TIA or stroke less than or equal to 75 years of age, admitted within 72 h after the stroke. Cerebral angiography and CT-scan were performed within 1-2 days of admission. CT-scan was repeated 6 months later. Functional status on admission, 3 and 6 months after the stroke was evaluated using the Rankin disability scale (score 1-2: independent of others care, score 3-5: dependent on others care). The degree of hemiparesis was measured using the Medical Research Council's score. Thirteen had infarcts with a diameter less than or equal to 3 cm (mean 2.5 +/- 0.9 cm); 15 had infarcts greater than 3 cm (mean 6.3 +/- 1.4 cm); 10 had trunk occlusions; 18 had branch occlusions. MCA occlusions with large infarcts and severe hemiparesis on admission carried a poor outcome. Eleven (85%) of 13 patients with the case in only 1 (7%) of the 15 with infarcts greater than 3 cm, the remaining 14 (93%) had either died (40%) or were dependent (53%) (p less than 0.00005). Eleven (85%) of 13 patients with mild hemiparesis on admission were independent, while 13 (87%) of 15 with moderate or severe hemiparesis on admission had either died (40%) or were dependent on others' care (47%) 6 months after the stroke (p less than 0.0004). Type of occlusion (branch trunk) was a poor predictor of outcome.
A close relationship exists between the severity of a stroke and the functional level that can be obtained after rehabilitation. The goal of rehabilitation, therefore, should be based on the severity of the stroke. Remission mainly takes place (more than 80 per cent) within the first three months post stroke. Remission after six months is very rare. Age and side of hemiparesis do not seem to influence the effect of rehabilitation significantly. It is not elucidated whether the severity of the stroke influence the effect of rehabilitation. Most of the controlled and the randomized studies indicate that rehabilitation of stroke patients, especially in rehabilitation units, accelerate remission, reduces length of stay and gives rise to a lasting improvement of function.
A rare syndrome of portal hypertension with esophageal varices but without evidence of cirrhosis in the liver biopsy was seen in 3 patients in a series of 1000 renal allotransplant recipients immunosuppressed with azathioprine and prednisone. The liver disease began 3-6 years after transplantation with abnormal liver function tests and esophageal varices with bleeding episodes. One patient had also ascites. Liver biopsy at the beginning of liver disease showed in one patient normal structure which eventually developed to slight diffuse fibrosis and nodular hyperplasia. One patient had diffuse fibrosis, and the third patient had strong sinusoidal engorgement with nodular hyperplasia, later on developing to cirrhosis. One patient is still alive and well, the two others died from liver insufficiency. 39 cases of non-cirrhotic portal hypertension in renal transplant recipients and histologic evidence of peliosis, sinusoidal dilatation, nodular hyperplasia or hepatic veno-occlusive disease have been identified in the literature. The cause of this disease is presumably azathioprine, but its rarity shows that it must depend also on other factors.