Anti-inflammatory and analgesic effects of a novel pyrazole derivative, FR140423.

The pharmacological profile of a novel and newly discovered non-steroidal anti-inflammatory and analgesic compound, 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyraz ole (FR140423), was investigated. In recombinant human cyclooxygenase enzyme assays, the inhibition of prostaglandin E2 formation by FR140423 was 150 times more selective for cyclooxygenase-2 than cyclooxygenase-1. Oral administration of FR140423 dose dependently reduced carrageenin-induced paw edema and adjuvant arthritis. These effects were two- to three-fold more potent than those of indomethacin. Unlike indomethacin, FR140423 did not induce mucosal lesions in the stomach. FR140423 showed dose-dependent anti-hyperalgesic effects in the yeast-induced hyperalgesic model. This effect was five-fold more potent than that of indomethacin. Furthermore, FR140423 increased the pain threshold in non-inflamed paws and, unlike indomethacin, it produced an analgesic effect in the tail-flick test. These analgesic effects were blocked by the mu-opioid antagonist naloxone. These results suggest that FR140423, a selective cyclooxygenase-2 inhibitor, is a potent non-steroidal anti-inflammatory drug (NSAID) without gastrointestinal side effects and is a unique compound having morphine-like analgesic effects.

Thoracic flexion myelopathy. Case report.

A case of thoracic flexion myelopathy is reported in a 36-year-old man. The patient had a history of gradually progressing transverse thoracic myelopathy. Conventional myelography in the neutral position failed to reveal cord compression; however, a severe block of the dye column was evident on studies in the flexed position. Excellent recovery from this condition was obtained with posterolateral fusion of the thoracic spine in the neutral position.

Cystic meningioma in a 10-month-old infant: Case report.

The authors report a case of cystic meningioma in a 10-month-old boy diagnosed by metrizamide ventriculography and computerized tomography. Intracranial meningioma in infants under 1 year old is extremely rare. This case is only the 16th case reported in the world literature; the other 15 cases are reviewed.

[Combination of radiation and PVB chemotherapy for intracranial malignant germ cell tumor].

Intracranial malignant germ cell tumors such as embryonal carcinoma, endodermal sinus tumor, and choriocarcinoma are neoplasms of poor prognosis in the pediatric age group. Recently evidences of effectiveness of combination chemotherapy using cisplatin, vinblastine, and bleomycin (PVB therapy) have been reported. The authors experienced two cases with these tumors treated with radiation therapy and PVB therapy. PVB therapy was performed along with irradiation in hoping the effect of radiation sensitizer of cisplatin. Both patients showed no signs of tumor recurrence and no re-elevation of tumor makers even in the cerebrospinal fluid after more than ten months from the onset. Cisplatin has radiation sensitizing effect besides antitumor activity, but its permeability through the blood-CSF barrier is very poor. Also true is that germ cell tumors often disseminate in the cerebrospinal fluid. From these points, combination of irradiation and chemotherapy using cisplatin seems reasonable, though the superiority of this radiochemotherapy to simple PVB therapy can not be concluded from the present experience. Side effects of this combination therapy were the same as PVB therapy alone and tolerable.

[A case of the anterior choroidal artery aneurysm combined with the abnormal intracranial vascular network (author's transl)].

A case of the anterior choroidal artery aneurysm combined with the abnormal intracranial vascular net-work was reported. The patient was 43-year-old male who was attacked by subarachnoid hemorrhage in February 25th 1975. When he was admitted to our clinic 30 days after the ictus, his general status was good and the neurological examination showed no particular findings except only slightly accelerated deep tendon reflexes on the left side. Cerebrospinal fluid still remained xanthochromic although no nuchal rigidity was denoted. Based on the angiographic four vessel studies, the circulatory condition of the patient's brain was summarized as follows; the internal carotid arteries were stenosed or occluded between the C1 and C2 segment on both sides, and abundant collateral circulation was developed mainly around the circle of Willis making an angiographically peculiar vascular net-work in tha base of the brain. Another angiographic finding to be noticed was a berry aneurysm which originated from the distal part of the left anterior choirdal artery. No special treatment was performed on him. He was discharged without any neurological residuals. It would be difficult to find out any hemodynamic relationship between the occlusion of the internal carotid arteries and occurence of the aneurysm. But the abnormally dilated anterior choroidal artery might suggest that the vessel wall of this artery would be burdened in the abnormal distension stress due to the increased transaxial pressure in this artery. Unqder such a hemodynamically stressed state, it would be possible the aneurysm like outpouching of the vessel wall being developed in some fragile portion of the artery functioning as a prominent collateral circulation.

[Cerebral arterial occlusive disease in children -- clinical aspects and surgical treatment (author's transl)].

In the present study the pathology and treatment of occlusion of cerebral arteries in children were investigated in an attempt to find out an approach to the surgical treatment of cerebral arterial occlusive disease of childhood. We had a total of 55 children with cerebrovascular disorders seen at our Institute during the past 11 years. In this series there were 19 cases of cerebral arterial occlusive disease. The causes in 15 cases of cerebral arterial occlusive disease except for moyamoya disease were heart disease in 7 cases, trauma in 2 cases and unknown in 6 cases. The cerebral arterial occlusive disease had its onset at the age of less than 6 years in 12 of 15 cases. The disease began with hemiplegia of sudden onset. The disease onset was also attended frequently by a convulsive seizure, which distinguishes the condition from that in adults. In 10 of all 15 lesions the site of occlusion was in the distribution of the middle cerebral artery. One case in which there was occlusion of the basilar artery occurring in association with trauma was described in detail. In one instance the treatment consisted of STA-MCA anastomosis. Paroxysmal black out attacks, which had been of frequent occurrence in addition to hemiplegia were relieved postoperatively. In our opinion, STA-MCA anastomosis for cerebral arterial occlusive disease in children should be considered to be indicated only when 1) cerebral angiographic evidence of occlusion or stenosis of a trunk of cerebral artery is still present after the acute stage or 2) no extensive low density area is demonstrable on CT scan. Surgery is generally less indicated in those instances in which the occlusion is due to embolism. However since abscess may arise from such an arterial lesion, surgery should be considered, or at least its feasibility be evaluated, whenever 1) the underlying cardiac pathology well permits surgical intervention and 2) half a year has passed since an initial attack.

[Intracerebral granuloma with serum anti-human ascaris antibody: case report].

A 1.5-year-old girl with a convulsion attack due to intracerebral granuloma in the right frontal lobe is reported. Her serum was positive with anti-human ascaris antibody, although no ova of the parasites were detected in the feces. She had grown up intimately with several cats in the home. These findings suggested that the granuloma was due to larva migrans of toxocara, which cross-reacts immunologically with human ascaris. Histological examination of the granuloma revealed no eosinophilic infiltration. No systemic reactions such as eosinophilia and hepatomegaly were found except for elevation of protein in cerebrospinal fluid. These were similar to those of ocular type of toxocara larva migrans.

[Cerebral vasospasm following subarachnoid hemorrhage in arteriovenous malformation].

Cerebral vasospasm after SAH from AVMs is rare. Only few reports have been made. Vasospasm was confirmed in 4 out of 13 patients with SAH from AVMs at the Sagamihara National Hospital in the past 5 years. The incidence of vasospasm following rupture of AVM is higher than those in previous reports ranging between 8 and 12 percent. This high incidence (31%) might be attributable to the timing from the last SAH attack until angiography. The existence of massive subarachnoid blood clots around the arteries of the circle of Willis is the most important factor causing vasospasm after SAH from AVMs.

[Etiology of water and electrolyte metabolism imbalance following the rupture of cerebral aneurysms--with special reference to preoperative condition].

One hundred fourteen patients with ruptured cerebral aneurysms were reviewed in regard to the incidence and etiological factors of preoperative disturbances of water and electrolyte metabolism. Patients with inadequate salt intake, evidence of renal disease, cardiac failure or excessive diuretic therapy were excluded. Twenty-five (21.9%) patients developed water and electrolyte disturbances. Hyponatremia (less than 130 mEq/l) occurred in 18 (15.8%) of 114 patients. The majority of those patients with hyponatremia showed laboratory findings and/or clinical features suggesting the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The mean interval between the last subarachnoid hemorrhage (SAH) and the development of hyponatremia was 13.5 days (range 6 to 26 days). No patients developed hypernatremia (more than 155 mEq/l). Preoperative diabetes insipidus (DI) occurred in 7 (6.1%) of 114 patients. The mean interval between the last SAH and the onset of DI was 26.5 days (range 15 to 35 days). When compared with the onset of hyponatremia following SAH, the development of DI was significantly delayed. The present study showed that the following five types of patients significantly related to the development of preoperative water and electrolyte disturbances after SAH due to cerebral aneurysms. The patients with ruptured aneurysms of anterior communicating, anterior cerebral artery or internal carotid artery. The patients in grade III, IV according to Hunt & Hess. The patients with high density in the basal subarachnoid space on the CT scan. The patients with a small hematoma in the region of the basal frontal interhemispheric fissure in cases with aneurysms of the anterior communicating or anterior cerebral artery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Albumin therapy for patients with increased intracranial pressure: oncotic therapy].

Albumin plays an important role in maintaining an adequate plasma colloid osmotic pressure (COP). On the basis of the Starling's law, we postulated that elevation of plasma COP produced by infusion of serum albumin would result in the withdrawal of cerebral interstitial fluid. To test the hypothesis that an oncotic gradient would produce cerebral dehydration and result in reduction of intracranial pressure (ICP), we infused intravenously 25% solution of salt-poor human serum albumin, 2g/kg over 60 minutes for 10 patients with increased ICP. In these 10 patients, the degree of brain edema was not severe but mild to moderate by judging from CT scan findings. In addition to ICP, various parameters such as mean arterial blood pressure (MABP), central venous pressure (CVP), pulse rate, PaCO2 and urine volume were measured before, during and after albumin infusion. Hematological studies including COP, total protein, albumin-globulin ratio, protein fractions, hematocrit (Ht), blood urea nitrogen (BUN), creatinine and electrolytes were also performed before, during and after administration of albumin. The raised ICP (27.4 +/- S.E. 1.6 mmHg) decreased significantly down to 19.1 (+/- 1.9) mmHg and remained stable for at least 240 minutes without any changes of MABP, pulse rate and PaCO2. CVP elevated significantly and remained at higher levels in comparison with control despite increase of urine output after administration of albumin. This results suggested that an adequate circulatory volume was maintained. A significant increase of total protein, serum albumin concentrations and albumin-globulin ratio was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diabetes insipidus following the rupture of cerebral aneurysms--with special reference to preoperative cases].

The authors reported 4 cases with preoperative diabetes insipidus (DI) following the rupture of cerebral aneurysms. In addition, the incidence of preoperative DI and the mechanisms as the cause of DI in cases with the ruptured cerebral aneurysms were also discussed. In the 114 cases underwent clipping of the ruptured cerebral aneurysms more than 14 days after the bleed, only 4 cases (3.5%) developed DI preoperatively. The time period between last subarachnoid hemorrhage and the onset of DI ranged from 23 to 35 days. This delayed onset of DI after subarachnoid hemorrhage was different from previous reports. A few of mechanisms had been suggested through which DI could be brought about in cases with cerebral aneurysm. That is; direct compression to the hypothalamo-hypophysial system by a giant aneurysm. compression and destruction of the hypothalamus by a hematoma or hemorrhage, ischemic changes in the hypothalamo-hypophysial system caused by vasospasm. In the present 4 cases, no had giant aneurysms. Although CT scan revealed subarachnoid clot in all cases, it did not show apparent hypothalamic lesion except case 1 who had small hematoma in the region of the basal frontal interhemispheric fissure. Symptomatic vasospasm was recognized in 3 cases. However, one of them had mild vasospasm restricting in M1 portion and case 3 was free of any vasospasm. Furthermore, the time period from the identification of vasospasm until the onset of DI ranged from 2 to 3 weeks. These results suggest that another mechanism in addition to a hemorrhage, hematoma and/or vasospasm may exist.(ABSTRACT TRUNCATED AT 250 WORDS)

[Case of calcified prolactinoma combined with Rathke's cleft cysts].

A case of chromophobe adenoma with capsular calcification combined with Rathke's cleft cysts is presented. A 28-year-old woman presented with a seven-year history of amenorrhea. Several months before admission to our department of neurosurgery on November 6, 1982, she developed galactorrhea and difficulty in reading because of visual failure. Neurological examination on admission revealed bitemporal hemianopsia, visual disturbance, left optic atrophy. Plain skull films and CT scan showed suprasellar capsular calcification. The patients hormonal status was assessed pre- and postoperatively. The basal serum prolactin (PRL) level was elevated at 790ng/ml, but other hormone basal plasma levels were within normal limits despite decrease in FSH, LH, The LH, FSH and PRL demonstrated a blunted response to LH-RH (100 micrograms). Both TSH and PRL demonstrated a blunted response to TRH (500 micrograms). The GH showed no response to insulin tolerance test (0.1 U/kg). On November 24, right frontal craniotomy was performed. A grayish bulging mass was noted surrounded by a calcified layer(2-3 mm) in the suprasellar region. When incised this calcified hard layer, showed multi-small cysts with yellow fluid. Under the cyst layer, there was a soft mass which was curetted easily. Histologically, under the ossified layer, there were multi-small cysts, lined by a single layer of ciliated columnar epithelium. The central soft mass was regarded as a chromophobe adenoma with no calcified body. Following partial removal of the tumor, there was prompt improvement in clinical signs and plasma PRL level.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of dural sarcoidosis].

A 26 year-old man, who was treated for meningitis in our hospital previously, was rehospitalized 1 year later because he developed disturbance of consciousness, gait disturbance and urinary incontinence. Blood examination revealed accelerated ESR, elevated GPT, slight elevation of serum Ca, strong positive CRP, and a decrease in PHA and Con A. ACE was within normal range and tuberculin reaction was negative. Lumbar puncture revealed that the initial pressure was 310 mmH2O, cells were 152/3, and protein was 343 mg/dl. Bilateral hilar lymphadenopathy was absent in chest X ray film. Head CT revealed enlarged lateral ventricles and irregularly enhancing nodular lesions in the anterior half of the falx cerebri, and abnormally strong enhancement of the choroid plexus. Ventriculoperitoneal shunt was performed. As a diagnosis was difficult to obtain from the clinical data, biopsy of the nodular lesions was performed. The histopathologic diagnosis was sarcoidosis. Steroid hormone was administered thereafter, and the nodular lesions of the falx disappeared in the follow-up. In the literature, only 8 cases of sarcoidosis of the dura mater have been reported. Since intracranial sarcoidosis is a part of systemic sarcoidosis, its diagnosis is not difficult in most cases. However, in cases difficult to diagnose as in our case, biopsy may be necessary. When nodular lesion occurs in the dura mater, sarcoidosis must be included as a possibility in the differential diagnosis in addition to the usual meningioma, lymphoma, and metastatic brain tumor.