Exfoliative glaucoma and primary open-angle glaucoma: associations with death causes and comorbidity.

PURPOSE: To investigate whether type of glaucoma or use of acetazolamide are associated with main cause of death and comorbidity. MATERIAL AND METHODS: The survival data, including date and cause of death, for 1147 patients with capsular or simple glaucoma who were ultimately hospitalized at the Eye Department, National Hospital, Oslo, between 1961 and 1970, were analysed. Binary logistic regression was carried out to investigate the patterns of death causes and comorbidity in subgroup analyses. RESULTS: Patients with exfoliative glaucoma (XFG) and those with primary open-angle glaucoma (POAG) showed no significant differences in rates of death caused by acute cerebrovascular diseases, cardiac diseases and cancer. Interestingly, we found that chronic cerebral diseases such as senile dementia, cerebral atrophy and chronic cerebral ischaemia (n = 81) were more common in patients with XFG than in those with POAG (p = 0.01) and in the group of acetazolamide users (p = 0.03). Patients with XFG had a higher probability of developing an acute cerebrovascular disease than patients with POAG (n = 228, p = 0.03). CONCLUSION: In this retrospective study, we found that comorbidity with acute cerebrovascular disease and chronic cerebral diseases (senile dementia, cerebral atrophy and chronic cerebral ischaemia) were more common in patients with XFG than in patients with POAG. Prospective data are needed in order to conclude upon the associations found in this study.

Cytokine enhancement of endothelin ET(B) receptor-mediated contraction in human temporal artery.

Segments of human temporal artery were incubated in organ culture for 2 days in the absence or presence of cytokines. Thereafter, contractions were induced by the selective endothelin ET(B) receptor agonist sarafotoxin S6c, a peptide that does not induce contraction in fresh human temporal artery. Interleukin-1beta was most potent in increasing the sarafotoxin-induced contraction in cultured segments. Tumour necrosis factor (TNF)-alpha increased the magnitude of contraction to a similar degree, but at a higher dose. A significant increase was also induced by interferon-gamma, but not by interleukin-6 at the concentrations used. The results suggest that endothelin ET(B) receptor-mediated contraction can be enhanced by pro-inflammatory cytokines in a concentration-dependent manner, and this may have relevance for pathophysiological conditions where inflammation and vasoactivity are important.

Proton magnetic resonance spectroscopy of brain biopsies from patients with intractable epilepsy.

In the present study metabolite concentrations were determined by proton magnetic resonance spectroscopy (MRS) in biopsies obtained from patients suffering intractable epilepsy from several different causes. Seven patients had gliosis, four had mild cortical dysplasia, three had tuberous sclerosis, two had astrocytomas, and one had a cavernous angioma. No significant differences were found in gliotic tissue in comparison with controls except for an increase in lactate. However, in the subgroup with tuberous sclerosis an increase was found in GABA and a dramatic decrease in N-acetyl aspartate (NAA). The most marked changes were found in the group with mild cortical dysplasia. There was a considerable decrease in NAA as well as large increases in GABA, alanine, tyrosine, acetate, inositol, glucose and lactate. The GABA content did not appear to correlate with antiepileptic therapy. Moreover, since all these patients required surgery, an elevated GABA level does not necessarily provide protection from seizures. The results indicate that use of proton MRS could become a useful presurgical predictor of underlying pathology.

Cerebral haemodynamics during thoracic- and thoracoabdominal aortic aneurysm repair.

OBJECTIVE: To investigate cerebral haemodynamics during operations for thoracic and thoracoabdominal aortic aneurysms. DESIGN: Prospective clinical study. MATERIAL: 10 patients operated on consecutively with resection for thoracic (5) or thoracoabdominal aortic (5) aneurysms. METHODS: Blood flow velocity of the middle cerebral artery was measured through a temporal approach using a TC Doppler with a 2 MHz probe. Recordings were made during induction of anaesthesia and performed continuously before, during and after cross-clamping of the aorta. RESULTS: Following 10 min. of aortic cross-clamping blood flow velocity of the middle cerebral artery increased from 44 to 55 cm/s (p < 0.01). A further increase to 69 cm/s (p < 0.01) was observed 5 min after declamping. The pulsatility index averaged 0.74 increasing to 1.21 (p < 0.05) at clamping and 0.87 (p < 0.05) after declamping. CONCLUSION: There was an increased blood flow velocity of the middle cerebral artery during cross-clamping of the descending thoracic aorta in patients operated on for thoracic and thoracoabdominal aortic aneurysms. This increase in cerebral blood flow and blood volume could explain the acute increase in cerebrospinal fluid pressure observed during cross-clamping of the thoracic aorta.

Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid haemorrhage in man.

A possible involvement of perivascular vasodilatory neuropeptides in subarachnoid haemorrhage (SAH) has been evaluated in man by measuring the levels of calcitonin gene related peptide (CGRP)-, substance P (SP)- and vasoactive intestinal peptide (VIP)-like immunoreactivity (LI) in the cranial venous outflow and in CSF in 34 patients admitted to the hospital after an acute SAH. After operation with aneurysm clipping and nimodipine treatment, blood samples were taken from the external jugular vein (EJV) or cerebrospinal fluid (CSF) and analysed for neuropeptide levels with specific radioimmuno assays (RIA) during the postoperative course. The degree of vasoconstriction in the patients was monitored with Doppler ultrasound recordings bilaterally from the middle cerebral (MCA) and internal carotid arteries (ICA) following the EJV blood sampling every second day. The mean value of all CGRP-LI measurements in EJV during the entire course of SAH (n = 20) revealed a significantly higher level as compared to controls. The highest CGRP-LI levels were found in patients with the highest velocity index values (vasospasm). The relationship Vmean MCA/Vmean ICA was used as an index of vasoconstriction. In patients with MCA aneurysms (n = 10), a significant correlation (r = 0.65, p < 0.05) was found between the vasospasm index and CGRP-LI levels. There were no changes observed in the SP- and VIP-LI levels. Alterations in cerebrovascular tone induced by changing arterial CO2 tension or lowering of blood pressure (ketanserin infusion test) did not alter the levels of the perivascular peptides in the EJV. In addition, CGRP-, SP-, VIP- and neuropeptide Y (NPY)-LI were analysed in CSF in the post-operative course after subarachnoid haemorrhage (SAH) in 14 patients. The CSF VIP-LI was lower in SAH than in control (p < 0.05). The CGRP-LI level was measurable in SAH CSF but not in CSF of controls. In individual patients with marked vasoconstriction increased levels of CGRP-LI (up to 14 pmol/L) and NPY-LI (up to 232 pmol/L) were observed. The results of this study are in support of our hypothesis that there is an involvement of the sensory peptide CGRP in a dynamic reflex aimed at counterbalancing vasoconstriction in SAH.

Perivascular neuropeptides (NPY, VIP, CGRP and SP) in human brain vessels after subarachnoid haemorrhage.

INTRODUCTION--Cerebral blood vessels are innervated by sympathetic nerve fibres storing neuropeptide Y (NPY), parasympathetic nerves storing acetylcholine, vasoactive intestinal peptide (VIP) and sensory afferent fibres containing calcitonin gene-related peptide (CGRP), substance P (SP) and neurokinin A. In experimental studies on subarachnoid haemorrhage (SAH) there are indications that perivascular peptides are involved. In the present study we have in man measured the levels of NPY, VIP, SP and CGRP in brain vessels of patients that have suffered a fatal SAH and compared this with the levels encountered in subjects that died of an extracerebral cause. MATERIAL AND METHODS--Vessels from patients who have died from SAH or nonSAH were obtained during autopsy performed within 24 hrs after death. The peptides were extracted and fractionated with reversed phase liquid chromatography (HPLC). The levels of NPY, VIP, SP, and CGRP were measured with radioimmunoassay. Vasomotor responses of human cerebral arteries were performed using a sensitive in vitro system. RESULTS--Human cerebral vessels contained NPY, VIP, CGRP and SP which eluted at the same positions as the authentic peptides. The level of CGRP was significantly lower (p < 0.01) in arteries removed from SAH patients as compared to control subjects. The level of SP was not changed, if anything it tended to be increased after SAH. The levels of NPY and VIP were not significantly altered after SAH. In isolated brain vessels alpha-CGRP was a potent vasodilator of arteries precontracted with whole blood, prostaglandin F2 alpha or endothelin. It had a poor effect on vessels precontracted with 60 mM potassium. CONCLUSION--The evidence suggest that the trigemino-cerebrovascular system, storing CGRP and SP, is to a differential degree involved in the pathophysiology of SAH in man and supports the hypothesis of an exhaustion of CGRP as one important factor in the development of late spasm occurring after SAH.

Cerebral haemodynamics during proximal aortic cross-clamping.

This study was carried out to examine cerebral blood flow, including the microcirculation and intracranial pressure during cross-clamping (XC) of the thoracic aorta in pigs. Blood flow in the internal carotid artery was measured by electromagnetic flowmetry. Cerebral microcirculation was studied by the laser Doppler technique, and intracranial pressure measured by applying a fibre optic pressure monitoring catheter in the same craniotomy. Maximal and mean blood flow velocity of the middle cerebral artery was recorded using a transcranial Doppler and cardiac output measured by thermodilution. The thoracic aorta was cross-clamped distal to the left subclavian artery for 30 min. During aortic XC the internal carotid artery blood flow increased 191% (p less than 0.05). Simultaneously mean and maximal blood flow velocity of the middle cerebral artery both increased 125% (p less than 0.01). Intracranial pressure increased 163% (p less than 0.05), and there was an increase in cerebral flux of 23% (p less than 0.05). Within the first minutes following the release of XC, all values decreased to preocclusive values. In conclusion, we observed a significant increase in cerebral blood flow during XC of the thoracic aorta. This is in accordance with the finding of a simultaneous increase in cardiac output. These haemodynamic changes support the theory that an increased blood flow via the proximal feeding system to the anterior spinal artery might be important in avoiding neurological sequelae following proximal aortic XC.