Nitric oxide synthase expression and enzymatic activity in human brain tumors.

Nitric oxide (NO) is synthesized by NO synthases (NOS), existing in 3 isoforms. NO influences a great variety of vital functions including vascular tone and neurotransmission. Under conditions of excessive formation, NO emerges as an important mediator of neurotoxicity in a variety of disorders of the central nervous system (CNS). Inhibitors of NOS are available that may modify the activity of all isoforms, which may be of clinical relevance. The expression of the 3 NOS isoforms nNOS, iNOS and eNOS and NOS enzymatic activity was examined in 40 patients with primary CNS tumors (gliomas WHO grades I - IV and meningeomas WHO grades I - III) and in 13 patients with metastases from adenocarcinomas or malignant melanomas. A polyclonal antibody directed against nNOS and monoclonal antibodies directed against iNOS and eNOS were used for immunohistochemical staining. NOS enzymatic activity, measured by labeled arginine to citrulline conversion, was assessed in tissue specimens obtained from the same tumors. NOS data were compared with clinical variables and the degree of edema as judged from MR scanning. nNOS expression was increased in tumor cells of glial neoplasms and most pronounced in high-grade tumors, WHO grades III and IV, and in the carcinoma and melanoma metastases. Low-grade gliomas, WHO grades I and II and meningeomas expressed no or only little nNOS. iNOS was only expressed in a few tumors. eNOS was expressed sporadically in the tumor cells while the expression was increased in vascular endothelial cells in both the tumor itself and the peritumoral area of glial neoplasms, and in metastases. eNOS expression was sporadic in endothelial cells of meningeomas. NOS enzymatic activities were heterogeneous among tumor types (0 - 13.8 pmol/min/mg of protein) without correlation to the NOS expression found by immunohistochemical techniques. Likewise, NOS activity and expression was not correlated to the clinical scores or brain edema. In conclusion, nNOS expression may be a putative useful indicator of brain tumor differentiation and malignancy. The enhanced expression of eNOS in vascular endothelial cells of glial neoplasms and metastases raises the possibility that NO production in tumor endothelial cells may contribute to tumor blood flow regulation and possibly brain edema.

[CT scanning in the diagnosis of internal carotid artery dissection]. / CT-scanning til påvisning af dissektion i a. carotis interna.

Dissection of the internal carotid artery is becoming more frequently recognized as a cause of neurological deficits or stoke in younger adults. A dissection is diagnosed in relation to minor often primarily unrecognized trauma to the neck and the typical clinical features seen with dissection are headache, Horner's syndrome and symptoms of focal brain ischaemia. Treatment, i.e. anti-coagulant therapy, is initiated to avoid thrombosis or recurrent embolism from the damaged arterial wall. The prognosis is generally good. The diagnosis of carotid dissection can be confirmed with ultrasound-duplex-scanning, conventional angiography or magnetic resonance imaging/angiography. In this paper two cases are reported in which computed tomography (CT-scanning) with intravenous contrast enhancement has been a valuable diagnostic tool in the diagnosis of this entity.

[Clinical value of SPECT scanning in children with neurological disorders]. / Den kliniske vaerdi af SPECT-scanning hos børn med neurologiske sygdomme.

We retrospectively evaluated the clinical value of Tc-99-HMPAO brain single photon emission tomography (SPECT) in 21 children with neurological disorders of varied aetiology. All 21 patients were examined with electroencephalograms (EEGs), 17 with computed tomography (CT) and ten with magnetic resonance imaging (MR). New relevant information was obtained from SPECT in all 21 cases and in four of these cases the investigation directly led to a change in diagnosis and better assessment of the prognosis. It is concluded that SPECT is an important investigational method in children with neurological symptoms of partly or completely unknown aetiology.

[CT of primary cerebral lymphoma in non-immunosuppressed patients]. / CT af primaert cerebralt lymfom hos ikkeimmunsupprimerede patienter.

In the last 10-15 years primary lymphoma of the brain has tripled in frequency in the non-immunosuppressed population. The correct diagnosis by CT-examination is difficult as primary lymphoma imitates different pathological conditions. Five examples from a series of 13 patients are presented.

Does nimodipine influence sex difference in outcome after aneurysmal subarachnoid haemorrhage?

Before nimodipine was introduced as a standard treatment in patients with aneurysmal subarachnoid haemorrhage (SAH) females had a significantly poorer outcome which might be due to a higher frequency of delayed cerebral ischaemia (DCI). We evaluated the overall outcome with regard to gender in 188 consecutive patients with a verified ruptured intracranial aneurysm treated with nimodipine. The only significant differences concerning prognostic factors between the sexes were a higher frequency of SAH at the primary CT in female (p < 0.05) and a higher frequency of middle cerebral artery aneurysms in females (p < 0.01). These factors affect the outcome in females unfavourably. However, contrary to previous studies, we found no difference in overall outcome after three months between the sexes in this clinical material. Our observation can be explained by a positive effect of nimodipine on DCI.

[Iatrogenic rhinolithiasis?]. / Iatrogen rinolit?

A case of rhinolithiasis in a young man is presented. The radiological (CT-scan) and clinical findings of a rhinolith may be similar to other benign or malignant nasal lesion such as inverted papilloma. This similarity and the possibility that a rhinolith may have iatrogen origin is presented in this article.

CT demonstration of prostatic zonal anatomy during dynamic contrast infusion.

CT of the pelvis was made after i.v. administration of 100 ml Omnipaque (300 mg I/ml) in 8 patients. The 1st series postcontrast was obtained dynamically and the 2nd 5 to 15 min after injection. Postcontrast enhancement of the prostate was shown in all patients. Dynamic contrast-enhanced CT was better than delayed postcontrast CT in showing the zonal anatomy in 6 patients. The method might be useful in patients where transrectal ultrasound is not applicable and when MR is not available.

[Cerebral toxoplasmosis primarily diagnosed as a tumor]. / Cerebral toksoplasmose primaert diagnosticeret som tumor.

Three cases of cerebral toxoplasmosis as the presenting manifestation of AIDS are reported. The initial diagnoses were brain tumors because of the cerebral mass lesions which resembled glioblastoma. In the light of the increasing occurrence of AIDS, attention is drawn to cerebral toxoplasmosis as a differential diagnosis from glioblastoma multiforme.

Comparison of precontrast, postcontrast, and delayed CT scanning for the staging of rectal carcinoma.

An attempt is made to establish the most appropriate examination procedure for staging rectal carcinoma by computed tomography (CT). Twenty-two patients with rectal carcinoma had CT performed preoperatively. The following three CT sequences were performed in all patients: a precontrast scan with 10-mm slices; a rapid sequence scan with 5-mm slices during bolus injection of contrast medium; and a postcontrast scan after a 10-min delay. Tumor extension and the presence of perirectal lymph nodes were evaluated separately and independently in all three CT sequences according to the TNM classification. All patients had surgical follow-up and the CT scans were compared to the surgical and histopathological findings. There was no significant difference in diagnostic outcome in the three CT procedures. Information obtained by frontal and lateral scout views were compared, and the lateral scout view proved more informative than the frontal scout view. For staging rectal carcinoma, narrow slice scanning and intravenous contrast media are superfluous and should be reserved for special cases. We recommend the use of lateral scout views.

Radiologic manifestations of focal cerebral hyperemia in acute stroke.

In 16 acute stroke patients with focal cerebral hyperemia angiography and regional cerebral blood flow (rCBF) were studied 1 to 4 days post stroke. CT was performed twice with and without contrast enhancement 3 +/- 1 days and 16 +/- 4 days post stroke. Angiographic evidence of focal cerebral hyperemia was seen in 8 patients in the form of early filling veins. In 5 of these the hyperemic areas were located within infarcted areas and in 3 patients in areas which appeared normal on CT. In the remaining 8 patients the hyperemias were located perifocally around ischemic infarcts. Early filling veins were not seen in this type of hyperemia. The blood flow was higher and the transit time of the contrast medium was faster in the former type of hyperemia probably because of arteriovenous shunting. Contrast enhancement was not observed on the early CT but was typically seen in the infarcts on the late CT at a time when the hyperemic state is known to have vanished. It is concluded that focal cerebral hyperemia is not responsible for contrast enhancement on CT.

Mass effect and atrophy after stroke.

Cerebral edema, resolution of edema, and subsequent development of cerebral atrophy were studied prospectively in 83 patients with ischemic stroke with CT 3 days, 2 weeks, and 6 months post-stroke. Nineteen patients had large (diameter greater than 3 cm), 25 medium sized (diameter greater than or equal to 1.5 less than or equal to 3 cm), and 15 lacunar infarcts (diameter less than 1.5 cm). In 24 patients no infarcts were seen. Changes of Evans' ratio (ER), septum-caudate distance (S/C), and width of widest cortical sulci (SuW) were taken as markers of mass effect/atrophy. These parameters were within normal limits in most cases. However, when all CT scans performed in each patient were compared, changes of ER, S/C, and SuW became apparent as evidence of mass effect and subsequent atrophy development. Mass effect occurred in 81 percent and atrophy in 58 percent of patients with large infarcts. In patients with medium sized infarcts, mass effect occurred in 38 percent and atrophy in 45 percent.

Repeated computed tomography in lacunar infarcts of the brain.

This prospective and consecutive study of 74 patients with completed stroke elucidates occurrence, localization and evolution of lacunar infarcts on repeated CT examinations. Twenty patients had large infarcts (diameter greater than 3 cm), 25 medium-sized infarcts (diameter greater than or equal to 1.5 cm - less than or equal to 3 cm), and 16 had lacunar infarcts (diameter less than 1.5 cm). In 13 patients no infarct was seen. The lacunar infarcts were characterized by delayed appearance on CT, low incidence of fog effect, and infrequent presence of contrast enhancement. In 9 of the 16 patients (56%) the lacunar infarct could be identified on the first CT, performed approximately 3 days after the stroke. In 2 patients the infarct was first revealed on the second (2 weeks post stroke) and in 5 on the third CT (6 months post stroke). The delayed appearance might be due to a partial volume effect. Early development of fog effect may also be considered. As contrast enhancement was observed in only 8 per cent of the patients with lacunar infarcts on CT, and in 70 per cent of the entire group of patients in our series with ischemic infarcts, contrast enhancement seemed to be a function of lesion size.

Percutaneous introduction of double-J ureteral stents.

Insertion of percutaneous indwelling ureteral stents was performed or attempted in 10 patients with ureteral obstruction or postoperative urinary extravasation. All patients had previously sustained an unsuccessful endoscopic retrograde attempt. The percutaneous double-J stent was inserted anatomically correctly in 8 (73%) cases and was functionally successful in 7 (64%). No significant complications occurred. As the percutaneous indwelling ureteral stent offers many advantages, i.e. little discomfort to the patient and none or insignificant complications, we want to advocate for the use of this method whenever the endoscopic technique fails.

Tissue damage at computed tomography following resolution of intracerebral hematomas.

Tissue damage as sequelae after spontaneous intracerebral hemorrhage in eight consecutive patients was investigated with computed tomography performed 3 days, 2 weeks and 6 months after the stroke. The presence of contrast enhancement after 2 weeks, hypodense areas after 6 months, and atrophy of adjacent structures were considered to be markers of irreversible tissue damage. Except for a narrow zone in the periphery of the hematoma (ring blush) contrast enhancement was not observed, neither in the hematoma nor in areas where resolution had taken place. After 6 months the site of the hematomas was not identifiable in 3 patients, and 4 patients had small 'lacunar' hypodense lesions. Only one patient had a more extensive hypodense area 6 months after the hemorrhage. The most prominent sequelae after intracerebral hematoma were atrophy of adjacent structures (i.e. atrophy of basal ganglia, thalamus and ventricular enlargement) which were seen in all patients even though irreversible de loco damage in the hematoma area was sparse or absent.

Edema and atrophy following cerebral stroke. A prospective and consecutive study.

Ninety-six consecutive stroke patients were examined by sequential CT scans. Edema in the acute/subacute state and atrophy in the chronic state were evaluated by measuring a frontal horn index, septum-caudate distance and width of cortical sulci. In the acute state the degree of edema increased with increasing size of the infarct. Cerebral swelling was more marked and persisted for a longer period in patients having intracerebral hematomas than in patients with ischemic infarcts. Surprisingly, edema was present in the unaffected hemisphere as well. Development of atrophy was seen in the affected hemisphere in patients having large infarcts and intracerebral hematomas. Atrophy did not develop in the unaffected hemisphere.

Cause of cerebral infarction in the carotid territory. Its relation to the size and the location of the infarct and to the underlying vascular lesion.

Seventy-three patients with acute nonhemorrhagic stroke in the carotid territory were investigated for the cause of the stroke: middle cerebral artery (MCA) occlusion/stenosis or internal carotid artery (ICA) occlusion/stenosis; embolus from the heart and extra-cranial arteries or thrombosis. The study is prospective and consecutive comprising stroke patients below the age of 75 years, admitted in the acute state i.e. within 3 days after stroke onset. Excluded were patients with intracerebral hematoma, subarachnoid hemorrhage, vertebrobasilar stroke and patients in whom another severe disease was present. Cerebral angiography and CT-scan were performed in all patients within one and two days after admission. CT-scan was repeated 2 weeks and 6 months later. Forty percent had MCA occlusion, none had MCA stenosis, 12% had ICA occlusion, 14% had severe ICA stenosis (half of these were associated with MCA occlusion) and 41% were without significant MCA/ICA lesions. Twenty-seven percent had large infarcts with a diameter greater than 3 cm; 34% had medium-sized infarcts with a diameter between 3 and 1.5 cm; 21% had small infarcts with a diameter less than 1.5 cm; 18% had no identifiable infarct on CT-scan. MCA occlusion was responsible for 62% of the large or medium-sized infarcts. ICA occlusion or severe ICA stenosis were responsible for only 27% of the large or medium-sized infarcts. Only 11% of the patients with small or no infarct on CT-scan had significant MCA/ICA lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke.

In a group of 48 patients with completed stroke, 8 patients had viable collaterally perfused brain tissue which was accessible for rCBF recordings with a two dimensional technique. All 8 had deep subcortical infarcts on CT-scan, and angiographic occlusion of the arteries normally supplying the infarcted territory. The brain tissue overlying the deep infarcts appeared normal on CT-scan and was supplied by collateral circulation. rCBF was measured in all within 72 hours after the stroke. The intra-carotid Xe-133 injection method and a 254 multidetector camera were used to study rCBF. Relatively ischemic low flow areas were a constant finding in the collaterally perfused tissue. In 6 of the patients, the collaterally perfused part of the brain had low flow values comparable to those of an "ischemic penumbra" (viable, but functionally depressed brain tissue due to inadequate perfusion). Autoregulation was impaired in all of the collaterally perfused areas while the CO2-response always was preserved. Steal phenomena were not seen. In the surrounding brain tissue, autoregulation was normal in 5 patients and impaired in 3 while the CO2-response seemed to be normal. The results confirm the experimental finding of an ischemic penumbra associated with acute cerebral infarcts and suggest that early restoration of the blood flow in acute stroke patients might improve recovery and prognosis in selected patients.