Capsule plication as a protective measure against post-operative intracapsular haematoma formation following trans-sphenoidal removal of pituitary macroadenoma.

BACKGROUND: Post-operative haematoma and visual deterioration are rare but serious complications after trans-sphenoidal surgery. For more reliable decompression of the optic nerve, we introduce a new technique for volume reduction of the cavity remaining after trans-sphenoidal resection of macroadenomas. TECHNIQUE: After intracapsular removal of the adenoma, the suprasellar portion of the tumour 'capsule' spontaneously prolapsed into the sella turcica. The lowest part of the prolapsed capsule was sutured and/or clipped to reduce the volume of the residual cavity remaining after tumour resection. FINDINGS: A total of 23 patients with macroadenomas extending to suprasellar area had visual symptoms and were treated by trans-sphenoidal surgery. In seven (30%) patients, computerised tomography scans on the first post-operative day demonstrated haematoma formation in the residual cavity. The magnetic resonance imagings on the seventh post-operative day, however, showed approximately 80% reduction in the tumour size. Visual disturbance improved in 20 patients (87%). No patient had post-operative deterioration of visual function. The complications in this series included transient diabetes insipidus in three patients and panhypopituitarism in one patient. CONCLUSIONS: Capsule plication is a useful measure for volume reduction of the large residual cavity after trans-sphenoidal surgery for macroadenoma. It may prevent an acute post-operative complication due to intracapsular haematoma, and improve surgical outcome in well selected cases.

Metabolic activation of aflatoxin B1 and 2-amino-3-methylimidazo[4,5-f]-quinoline by human adult and fetal livers.

The mutagenic activation of promutagens by human adult and fetal livers was investigated using the umu test system. Among the promutagens studied, aflatoxin B1 (AFB1) and 2-amino-3-methyl-imidazo[4,5-f] quinoline (IQ) were efficiently activated to mutagens by both adult and fetal livers. 7,8-Benzoflavone inhibited the activation of IQ by fetal livers, but the inhibition observed in fetal livers was much less than that observed in adult livers. Antibodies to P450HM1 (P450111A4) and P450HFLa markedly inhibited the activation of AFB1 by adult and fetal livers, respectively. The formation of genotoxic product(s) from IQ in human adult livers was almost completely inhibited by anti-P448H (P4501A2) antibodies but not by anti-P450HM1 antibodies, whereas that in fetal livers was inhibited by both anti-P450HFLa and anti-P450IA2 antibodies. P450HFLa catalyzed the mutagenic activation of both AFB1 and IQ in a reconstituted system. On the contrary, P450HM1 catalyzed the mutagenic activation of AFB1 but not IQ. A preparation of cytochrome P450 partially purified from human fetal livers and cross-reactive with anti-P450IA2 antibodies was found to be active for mutagenic activation of IQ in a reconstituted system. These results indicate that P450HFLa and P450HM1 are mainly involved in the genotoxic product formation from AFB1 in fetal and adult livers, respectively, and that the metabolic activation of IQ in fetal livers is catalyzed by two forms of cytochrome P450, P450HFLa, and cytochrome P450 immunochemically related to P450IA2 but that in adult livers it is mainly catalyzed by cytochrome P450 related to P450IA2.

Expression of bone-related protein messenger RNA in human meningiomas: possible involvement of osteopontin in development of psammoma bodies.

Meningiomas often contain concentric calcified foci, referred to as psammoma bodies. Since calcium phosphate deposits in both psammoma bodies and bone tissues, we examined whether messenger (m) RNA of bone-related extracellular matrix proteins and bone morphogenetic proteins (BMP) were expressed in human meningioma tissues. Northern blotting demonstrated the expression of osteopontin (OPN), matrix Gla protein (MGP), osteonectin (ON) and BMP-4 mRNA but not bone sialoprotein, osteocalcin and BMP-2 mRNA. In situ hybridization revealed that most OPN mRNA-expressing cells were located around the psammoma bodies in meningothelial whorls. Moreover, combination of in situ hybridization and immunohistochemistry on serial sections showed that the OPN mRNA-expressing cells were CD68-positive, suggesting they were macrophages. Immunohistochemistry with anti-OPN antibody and von Kossa staining on the adjacent section showed that the deposition site of OPN protein was consistent with that of calcium phosphate. Neither MGP nor ON mRNA expression appeared to correlate with the calcification. The present result suggests that OPN produced by CD68-positive macrophages may play a significant role for development of psammoma bodies in meningiomas.

Prostaglandin E1 induces c-Fos and Myc proteins and protects rat hippocampal cells against hypoxic injury.

We investigated the effects of prostaglandin (PG) E1 on the hypoxic injury of fetal rat hippocampal cells. Primary hippocampal cell cultures (embryonic day 18) were established and maintained. After 72 h in culture, PGE1 was added to the serum-free medium at a final concentration of 10(-5)-10(-9) M. Cultures were divided into two groups: The normoxia group was in culture for another 48 h, and the hypoxia group was exposed to 24 h of hypoxia followed by continuation of culture for another 24 h. As a quantitative measure of cell death, lactate dehydrogenase (LDH) activity was estimated in the culture medium. The LDH activity, released by the hypoxic insult, was significantly smaller with PGE1 treatment at 10(-6), 10(-7), and 10(-8) M (p < 0.01) and 10(-9) M (p < 0.05) compared with the control. No differences in the LDH activities were observed in the normoxia group. Glial culture was not affected by the hypoxia. Western blot analysis showed an increased induction of 62-kDa c-Fos and 58, 60, and 66 kDa Myc proteins in rat hippocampal cells with 10(-7) M PGE1 treatment. We conclude that PGE1 at concentrations of 10(-6)-10(-9) M protects rat hippocampal neurons against hypoxic insult.

Angiographic manifestations in postrecanalized cerebral infarction.

In 14 stroke patients showing angiographic recanalization of the occluded internal carotid artery or middle cerebral arterial axis, the postrecanalized angiograms demonstrated several findings that have been considered to be generally rare in cerebral infarction. These findings principally consisted of narrowing of arterial caliber in six cases (43 percent), mass effect in eight cases (57 percent) and capillary blush in five cases (36 percent).

Increased vascular permeability by a specific agonist of protease-activated receptor-2 in rat hindpaw.

The present study examined the effect of intraplantar (i.pl.) administration of a selective agonist of protease-activated receptor (PAR)-2, SLIGRL-NH2(PP6-NH2), on vascular permeability in rat hindpaw. PP6-NH2, administered i.pl. at 10-100 nmol per paw, enhanced vascular permeability and caused oedema formation in rat hindpaw. SLIGRL (PP6-OH) and trypsin, by i.pl. administration, also elicited an increase in vascular permeability, although i.pl. administration of the mixture of constituent amino acids of PP6-OH at an equivalent dose did not. The PP6-NH2-induced increase in vascular permeability was abolished by repeated pretreatment with compound 48/80 to deplete bioactive amines in mast cells. These findings suggest that the activation of PAR-2 induces acute inflammation, at least partially, via mast cell degranulation in rat hindpaw.

Enhancement of vascular permeability by specific activation of protease-activated receptor-1 in rat hindpaw: a protective role of endogenous and exogenous nitric oxide.

1. To clarify the role of the first thrombin receptor/protease-activated receptor (PAR)-1 in an inflammatory process, we tested and characterized the effect of intraplantar (i.pl.) administration of the highly specific PAR-1 agonist TFLLR-NH2 in rat hindpaw. 2. TFLLR-NH2 administered i.pl. at 0.01-0.03 micromol per paw enhanced vascular permeability in the hindpaw and produced paw oedema in a dose-dependent manner. This effect was almost completely abolished by repeated pretreatment with compound 48/80 to deplete inflammatory mediators in mast cells. 3. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester or N-iminoethyl-L-ornithine, preadministered i.pl., stereospecifically potentiated the i.pl. TFLLR-NH2-induced permeability increase, while the NO donor sodium nitroprusside or NOC-18, given i.pl., suppressed the effect of TFLLR-NH2. 4. These findings demonstrate that specific activation of PAR-1 produces increased vascular permeability accompanied by oedema formation in the rat hindpaw, predominantly via mast cell degranulation, and that endogenous and exogenous NO plays a protective role in the PAR-1-mediated inflammatory event.

Delayed hemispheric neuronal loss in severely head-injured patients.

Recent experimental studies have revealed that traumatic brain injury as well as ischemic brain injury can cause chronic progressive neuronal damage. In the present study, we demonstrate previously unreported delayed cerebral atrophy on computerized tomography (CT) scans in severely head-injured patients. Seventeen severely head-injured patients who required mild hypothermia to control intracranial hypertension after the failure of conventional therapies were retrospectively analyzed. All 17 patients survived more than 1 year. Delayed neuronal loss (DNL) was observed in only eight of the 17 patients. Eight patients with DNL required longer durations of mild hypothermia to control intracranial hypertension than nine patients without DNL. Six of these eight patients with DNL achieved functional recovery despite progressive atrophic changes demonstrated on CT scans. On CT scans, DNL was characterized by (1) the sudden appearance at several months postinjury of a low-density area in the hemisphere ipsilateral to the injury; (2) the preservation of essential cortical structure although related white matter structures showed severe atrophic changes; and (3) no spread of the low-density area to the contiguous territory of the other main cerebral artery. It is concluded that focal primary injury to underlying brain, if severe enough, can result in delayed hemispheric atrophy.

Expression of basic fibroblast growth factor receptor messenger RNA in the periinfarcted brain tissue.

The present study examined whether expression of basic fibroblast growth factor receptor (bFGFR) messenger ribonucleic acid (mRNA) was upregulated by focal ischemia. We have studied the in situ hybridization autoradiography for bFGFR mRNA in the rat model of middle cerebral artery (MCA) occlusion. Male Wistar rats were used for occlusion of the left MCA, and were sacrificed 1, 3, 7 and 14 days after MCA occlusion. In situ hybridization was performed on the brain sections of these animals and sham controls by using 35S-labeled antisense and sense (control) RNA probes for rat bFGFR. Expression of bFGFR mRNA was observed in the periinfarcted area of the rats within 1-14 days after MCA occlusion. Expression was evident in the whole hemisphere of the infarcted side, especially at 1 and 3 days after ischemia, but no expression was detected in the contralateral side. On microautoradiograms, the signals of bFGFR mRNA were detected in both neurons and non-neural cells located in the periinfarcted area. Upregulation of bFGFR mRNA detected in the periinfarcted brain tissue suggests that receptor-mediated action of bFGF may be related to preservation of neurons injured by ischemia.

Electrophysiological changes in substantia nigra after striatal infarction.

The GABAergic efferent pathway from the striatum exerts inhibitory control on the substantia nigra pars reticulata (SNR) neurones. We studied sequential changes in spontaneous single-unit activities in the ipsilateral SNR 1 h, 1 day, 7 days and 14 days after striatal infarction induced by middle cerebral artery occlusion (MCAO) in rats. Compared with a sham-operated group, there was no change in the firing rate 1 h after MCAO, and one day after MCAO the mean firing rate decreased. The firing rate of SNR neurones at 7 and 14 days after MCAO was significantly reduced compared with the sham-operated group. Only two neurones (sham-operated group and 1 h after MCAO group) fired with high frequency. Histological examination revealed degeneration of the ipsilateral SNR 7 and 14 days after MCAO. Our results indicated that SNR neuronal degeneration accompanied by striatal ischaemia does not simply depend on hyperexcitation due to the activation of a disinhibition mechanism.

Asymmetrical regulation of blood pressure in the rat medulla.

The effects of microinjection of serotonin-1 (5-HT1) antagonist methiothepin and 5-HT1 agonist buspirone into the nucleus reticularis parvocellularis were investigated in the anaesthetized rats. Methiothepin produced an increase in arterial blood pressure when injected into the left side, but it did a decrease when injected into the right side. On the contrary, buspirone produced a decrease in arterial blood pressure when injected into the left side, but it did an increase when injected into the right side. These findings provide the clue to clarify that there is a reciprocal regulation of arterial blood pressure between the left and right sides in the rat medulla.

Roles of urokinase type plasminogen activator in a brain stab wound.

Urokinase type plasminogen activator (uPA) may influence brain pathophysiology after injury. We studied disruption of the blood-brain barrier (BBB) and changes in the vasculature after a brain stab wound in uPA-deficient, uPA receptor-deficient, and PA inhibitor-1 (PAI-1) deficient mice. The extravasation of immunoglobulin was greater in PAI-1 deficient mice; less pronounced in uPA-deficient mice; similar to controls in uPA receptor-deficient mice. Vasculatures in the wound proliferated in PAI-1 deficient mice. Our study shows that uPA affects BBB disruption. PA enhances angiogenesis after brain injury.

A new animal model of cerebral infarction: magnetic embolization with carbonyl iron particles.

A new animal model of cerebral infarction was developed by magnetic embolization with carbonyl iron particles. An electromagnet was placed upon the lateral portion outside the orbit of Mongolian gerbils and charged with a current intensity of 2 A, 3 V (400 G) for 10 min. By intracardiac injection of iron particles at the beginning of the electric charge, infarction was selectively produced in the cerebral cortex. Two days after the operation, microhemorrhaging was seen in the necrotic region. Multiple scattered infarctions accompanied with microhemorrhagic signs closely resembled embolic infarction encountered in the human brain.

Nigral degeneration following striato-pallidal lesion in tissue type plasminogen activator deficient mice.

Tissue type plasminogen activator (tPA) has been suggested as a key factor in excitotoxic neuronal death in the hippocampus. Transneuronal degeneration of the substantia nigra pars reticulata (SNR) neurons after striato-pallidal lesions is attributable to excess excitatory glutamatergic inputs into the SNR following inhibitory GABAergic deafferentation and tPA may contribute to the mechanism of transneuronal degeneration of the SNR. To examine this possibility, we studied pathological changes in the SNR following striato-pallidal lesions produced by electrocoagulation in tPA-deficient mice. There was no difference in the degree of SNR degeneration, or in microglial activation and proliferation in the degenerating SNR of tPA-deficient and control mice. Our results indicate that tPA does not contribute to transneuronal degeneration in the SNR following striato-pallidal lesions in mice.

Lipopolysaccharide-induced subsensitivity of protease-activated receptor-2 in the mouse salivary glands in vivo.

Protease-activated receptor-2 (PAR-2) acts as a modulator of multiple physiological/pathophysiological functions including salivary exocrine secretion. Given the supersensitivity of endothelial PAR-2 under endotoxaemia, we investigated if endotoxin/lipopolysaccharide (LPS) could alter the sensitivity of PAR-2 in the salivary glands. The in vivo salivation in response to i.v. administration of the PAR-2-activating peptide SLIGRL-NH2, but not of carbachol, gradually decreased 6-20 h after LPS administration in the mice. The LPS-induced hyporeactivity to the PAR-2 agonist was partially reversed by repeated administration of aprotinin, a non-specific protease inhibitor. PAR-2 mRNA levels in the salivary glands, as assessed by the semi-quantitative RT-PCR analysis, remained unchanged following LPS challenge. Our findings indicate that in contrast to the supersensitivity of endothelial PAR-2 as described previously, subsensitivity of PAR-2 in the salivary glands develops during the LPS-induced systemic inflammation, which might involve desensitisation of PAR-2 by endogenous proteases.

Effect of early operation for ruptured aneurysms on prevention of delayed ischemic symptoms.

The effect of removal of subarachnoid blood clots on the prevention of delayed ischemic deficit was evaluated in 239 consecutive patients with ruptured supratentorial non-giant aneurysms. All patients were hospitalized within 24 hours after subarachnoid hemorrhage (SAH) and were classified in Grades 1 to 4 according to the system of Hunt and Hess; classification was made immediately preoperatively in patients operated on within 48 hours after SAH, or 48 hours after SAH in patients for whom delayed operation was planned. Delayed ischemic deficit causing permanent disability or death occurred in 11 (25%) of 44 patients in whom surgery was planned to be delayed for 10 days or more, in 26 (27.7%) of 94 patients in whom the aneurysms were obliterated and blood clots adjacent to them were removed within 48 hours of SAH, and in 11 (10.9%) of 101 patients in whom the aneurysms were obliterated and extensive and aggressive removal of thick subarachnoid clots lying along the arteries (identified on computerized tomographic scan) was performed within 48 hours of SAH. Accordingly, early operation is an effective and reliable method to reduce the occurrence of severe delayed ischemic deficit only when subarachnoid blood clots are removed extensively and aggressively along the arteries within 48 hours of SAH.

Extended transsphenoidal approach with submucosal posterior ethmoidectomy for parasellar tumors. Technical note.

The authors have developed an extended transsphenoidal approach with submucosal posterior ethmoidectomy for resection of tumors located in the cavernous sinus or the suprasellar region that are difficult to remove via the conventional transsphenoidal approach. Surgery was performed using this approach in 14 patients with large pituitary adenomas, three patients with craniopharyngiomas, and one patient with a meningioma of the tuberculum sellae. The submucosal dissection of the nasal septum used in the conventional transsphenoidal approach was extended to the superior lateral wall of the nasal cavity to expose the bony surface of the superior turbinate lying under the nasal mucosa. Submucosal posterior ethmoidectomy widened the area visualized through the conventional transsphenoidal approach both superiorly and laterally. This provided a safer and less invasive access to lesions in the cavernous sinus or the suprasellar region through the sphenoid sinus. Using this approach the authors encountered no postoperative complications, such as olfactory disturbance, cranial nerve palsy, or arterial injury. In this article the authors present the surgical methods used in this approach.

Direct approach to a traumatic giant internal carotid artery aneurysm associated with a carotid-cavernous fistula. Case report.

The case is reported of a giant intracranial internal carotid artery aneurysm associated with a carotid-cavernous fistula following a closed head injury. The aneurysm and the fistula disappeared after only the neck of the aneurysm was clipped. This is the first case in which a direct surgical approach was successful in sparing the internal carotid flow. Reports of similar cases are reviewed.

Angiographic disappearance of multiple dural arteriovenous malformations. Case report.

Angiographic disappearance of two dural arteriovenous malformations (AVM's) in different locations in one case is reported. One of the AVM's involved the right transverse sinus, and the other involved the superior sagittal sinus. The patient's presenting symptoms were due to obstructive hydrocephalus resulting from a small intraventricular hemorrhage that was diagnosed by computerized tomography on admission. The symptoms cleared 25 hours after the ictus in conjunction with improvement of hydrocephalus. The AVM involving the right transverse sinus was supplied by the occipital artery, but ligation of that artery was not successful in eliminating the anomaly. One year later, follow-up angiography revealed disappearance of both dural AVM's.

Primary cerebellar hemorrhage. Quadrigeminal cistern obliteration on CT scans as a predictor of outcome.

The authors studied a consecutive series of 75 patients with cerebellar hemorrhage diagnosed by computerized tomography (CT) scanning, and assessed the relationship of outcome to the CT appearance of the quadrigeminal cistern, which in some cases was obliterated by rostral displacement of the vermis resulting from the cerebellar mass. Obliteration of the quadrigeminal cisterns was classified on the CT scans into three grades: normal (Grade I), compressed (Grade II), or absent (Grade III). There were 43 patients with Grade I, 16 with Grade II, and 16 with Grade III cisterns. Of the 75 patients, 38 (88.4%) of those with Grade I, 11 (68.8%) of those with Grade II, and none of those with Grade III cisterns returned to their previous activities at 6 months or more after onset. A Grade I cistern predicted a good outcome whether the hematoma was evacuated or not, as long as obstructive hydrocephalus, if present, was relieved early. However, a Grade II cistern was not predictive of a good outcome unless the hematoma was evacuated within 48 hours after onset of the hemorrhage. A Grade III cistern invariably predicted an unfavorable outcome. It is concluded that the CT grade of quadrigeminal cistern obliteration is an accurate indicator of outcome and is highly useful in selecting appropriate treatment for patients with cerebellar hemorrhage.