Cyclin E mRNA overexpression in epithelial ovarian cancers: inverse correlation with p53 protein accumulation.

OBJECTIVE: We investigated the relationship between cyclin E mRNA overexpression and p53 protein accumulation in epithelial ovarian cancers. METHODS: mRNA was isolated and cDNA was prepared from 36 epithelial ovarian tumors (three adenomas, three low malignant potential tumors, and 30 carcinomas), and six normal ovaries. The cyclin E mRNA expression levels relative to an internal control, beta-tubulin, were determined by semiquantitative polymerase chain reaction (PCR). Cyclin E and p53 protein expression in ovarian cancer tissues were examined by immunohistochemistry using the same series of samples. Fisher exact test of significance and an unpaired t test were used for statistical analysis. RESULTS: Considerable levels of cyclin E mRNA were detected in all normal ovaries and ovarian tumor samples examined by semiquantitative PCR amplification. mRNA levels of cyclin E were significantly higher in nine of 30 (30%) ovarian cancers compared with those in normal ovaries. The immunohistochemical expression of cyclin E protein was confirmed in the nuclei of tumor cells in 13 of 30 (43%) ovarian cancers. p53 protein accumulation was detected in 12 of 30 (40%) ovarian cancers examined. There was a significant inverse correlation between cyclin E mRNA overexpression and p53 protein accumulation (P <.01, Fisher exact test). CONCLUSIONS: Cyclin E mRNA overexpression frequently occurs in ovarian cancers without p53 protein accumulation. Cyclin E might have an important effect on the development of a limited number of ovarian cancers.

Underexpression of cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in serous ovarian carcinomas.

Reduced expression of a cyclin-dependent kinase inhibitor, p27, has been reported to be associated with poor prognosis in several human cancers. The aim of this study was to investigate the potential role of p27 in ovarian cancer development and progression. Immunohistochemical expression of p27 was determined using 117 epithelial ovarian tumor tissues and 8 normal ovaries. p27 mRNA expression was examined by semi-quantitative PCR amplification using 26 ovarian cancer samples. Nuclear staining of p27 was commonly observed in the normal ovarian surface epithelium and the epithelial cells of germinal inclusion cysts. Positive p27 staining rates were significantly higher in serous adenomas (p=0.006) and in serous LMP tumors (p=0.013) than that in serous carcinomas (Fisher's exact test). In serous ovarian cancers, positive p27 staining rate was significantly higher in early stage (stage1/2) than that in advanced stage (stage 3/4) diseases (p=0.030, Fisher's exact test). Log-rank testing showed that negative p27 expression significantly correlates with poor survival in serous ovarian cancer patients (p=0.041). Considerable levels of p27 mRNA were detected in all ovarian cancer samples examined. These results suggest that the underexpression of p27 caused by post-translational mechanism may contribute to the development and progression and result in poor prognosis of serous ovarian cancers.

Effects of sevoflurane and isoflurane on the ratio of cerebral blood flow/metabolic rate for oxygen in neurosurgery.

PURPOSE: To examine the changes in cerebral blood flow (CBF) equivalent (CBF divided by cerebral metabolic rate for oxygen) during craniotomy under isoflurane and sevoflurane anesthesia in patients with intracranial disorders. METHODS: In 16 neurosurgical patients (8 anesthetized with isoflurane and 8 with sevolflurane), the CBF equivalent was measured while the end-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 minimum alveolar concentration (MAC) before surgery, and then 1.0 MAC during surgery, which lasted more than 4 hr. RESULTS: There was no significant difference in CBF equivalent at 0.5 MAC between isoflurane (20 +/- 4ml blood.ml oxygen) groups. With increasing anesthetic depth from 0.5 to 1.0 MAC, the CBF equivalent significantly (P<0.5) increased in both groups (22 +/- 7 and 21 +/- 5, respectively). At 1.0 MAC during operation, the CBF equivalent with both anesthetics was maintained with minimal fluctuation for 4h. There were no significant differences in the average value of the CBF equivalent during a 4-h period at 1.0 MAC between the isoflurane (23 +/- 5) and the sevoflurane (20 +/- 4) groups. CONCLUSION: Deepening anesthesia from 0.5 to 1.0 MAC was maintained with no difference between the two agents during 4h of neurosurgery.

[Motor cortex stimulation therapy in patients with thalamic pain].

Seven patients with thalamic pain were treated by electrical stimulation of the motor cortex. Patients ranged from 55 to 71 years of age. There were six men and one woman. Causes of thalamic pain were thalamic infarction in 2 patients and thalamic hemorrhage in five. Six patients had intractable pain associated with dysesthesia in the upper and lower limb (upper limb dominant). One patient had intractable pain in the face contralateral to the lesion. Magnetic resonance images (MRI) were performed in 5 patients and showed the deposit of hemosiderin in the internal capsule, posterolateral nucleus and pulvinar. Electrodes were placed on the motor cortex epidurally in seven patients. Electrodes were implanted permanently in six patients and removed in one patient after an unsatisfactory result of test stimulation. Motor cortex stimulation provided satisfactory pain relief in all six patients for a month after the beginning of stimulation, however, by the time three months had passed, pain relief had become gradually unsatisfactory in five patients. We compared pain relief between 10 Hz and 100 Hz of stimulus rate in four patients and observed that all patients complained of fatigue in the upper extremity at the 100 Hz of stimulus rate, though no differences in pain relief was obtained according to which of these two stimulus rates were used. We concluded that motor cortex stimulation brought about pain inhibition in patients with thalamic pain, but pain control tended to become less gradual within several months after the beginning of stimulation.

[Multi-drug antiemetic treatment and effect of treatment duration of concurrent steroids--for complete control of chemotherapy-induced nausea/vomiting in gynecological cancer].

Antiemetic effect and safety of concurrent administration of ondansetron and other antiemetics (dexamethasone, domperidone and ethyl loflazepate), given for complete suppression of nausea/vomiting, were examined in 46 patients (109 courses) with gynecological cancer receiving single high-dose of cisplatin or carboplatin. As for the delayed emesis, antiemetic effect depending on the steroid treatment duration, given concurrently to ondansetron, was compared. The results were as follows; 1. In 78 courses, anticancer drugs were given concurrently to cisplatin or carboplatin only on Day 1. In the remaining 31 courses, those drugs were concurrently administered up to Day 6 at the longest. 2. Complete suppression (i.e., no onsets) rate of acute emesis was 64.2% (70/109 courses) for nausea, and 84.4% (92/109 courses) for vomiting. 3. When the complete suppression depending on duration of concomitant steroid was examined mainly in patients receiving CAP (cyclophosphamide, adriamycin and cisplatin), higher antiemetic effect, especially in nausea, was observed in those on concomitant steroids for 3 days compared to that for 1 day. 4. The food intake rate improved along with nausea symptoms. 5. No adverse event or laboratory abnormality due to the multi-antiemetic treatment was observed. Based on the above, the efficacy of the antiemetic treatment in this study was confirmed. In delayed emesis, concurrent steroids given for 3 days after chemotherapy were considered effective and were also regarded to improve food intake.

Comparison of Xe-CT/CBF and quantitative ECD-SPECT.

We compared stable xenon enhanced X-ray computed tomography (Xe-CT) with Technetium-99m ethylsteinate dimer single-photon emission computed tomography (ECD-SPECT) in 12 patients. We evaluated the cerebral blood flow (CBF) values in the territory of the anterior, middle and posterior cerebral artery, and in the thalamus. The CBF values were higher in ECD-SPECT than in Xe-CT except for the values of the thalamus. The posterior cerebral artery territory showed a lower correlation and the thalamus had no correlation between two methods. We discussed causes of these differences.

Apnea associated with Chiari malformation: medullary hemorrhage revealed by MRI.

Medullary hemorrhage in the medulla oblongata of an infant with Chiari malformation, hydrocephalus, meningomyelocele and hypogenesis of the corpus callosum is reported. Four days after placement of a ventriculoperitoneal shunt, spontaneous respiration diminished. Magnetic resonance imaging (MRI) successfully revealed a small medullary hemorrhage.

Sequential changes in plasma fibronectin in patients with subarachnoid hemorrhage.

Sequential changes in plasma fibronectin level in 17 patients with subarachnoid hemorrhage (SAH), with 16 due to ruptured cerebral aneurysms, were compared for patients with good and poor outcomes, and patients with and without vasospasm. Plasma fibronectin concentrations were measured by an immune diffusion method. The clinical outcome was evaluated 3 months after SAH according to the Glasgow Outcome Scale. Plasma fibronectin concentrations were significantly lower on days 3 (p < 0.02) and 9 (p < 0.05) after ictus in patients with poor outcomes (moderately disabled or worse) than in those with good outcomes (good recovery). Patients with vasospasm had lower fibronectin concentrations during the 4 weeks after ictus. Decreased levels of plasma fibronectin were correlated with poor outcomes, most related to vasospasm. Plasma fibronectin levels reflect the overall severity in patients with SAH and are a useful marker for prediction of the final clinical outcome.

Balloon occlusion of a spontaneous carotid-cavernous fistula in Ehlers-Danlos syndrome type IV.

A case of spontaneous carotid-cavernous fistula associated with Ehlers-Danlos syndrome Type IV was treated successfully by transarterial balloon embolization. To minimize the stress to the arterial wall, we detached three silastic balloons with low-attachment force in the cavernous sinus with the aid of a proximal balloon to control the high flow of the fistula. To achieve complete obliteration, we had to inflate the third balloon to dimensions that occluded the cavernous portion of the internal carotid artery. Patients with Ehlers-Danlos syndrome Type IV carry a high risk when undergoing any diagnostic or therapeutic endovascular procedure due to the fragility of their blood vessels. Recognition of this entity is important and special attention should be paid to its pathophysiology for a successful treatment.

Paraplegia due to a ruptured aneurysm of the distal posterior inferior cerebellar artery.

A case of paraplegia was due to a ruptured aneurysm of the distal posterior inferior cerebellar artery. The paraplegia was caused by a unilateral lesion located between the cervicomedullary junction and the C2 level, where it involved both crossed and uncrossed pyramidal fibres projecting to the lower extremities. Since a vascular lesion near the cervicomedullary junction is likely to be missed, special attention should be paid to this region when investigating subarachnoid haemorrhage with paraplegia.

[A study of ionized calcium in the whole blood of patients with subarachnoid hemorrhage].

In 14 normal volunteers and 22 consecutive patients with subarachnoid hemorrhage (SAH) due to a ruptured cerebral aneurysm, ionized calcium (Ca2+) concentrations in whole blood were measured using an automatic calcium analyzer. The values were corrected against pH 7.4. The relationships between the Ca2+ concentration and the following aspects were studied: neurological grading by Hunt and Kosnik, grade of SAH on computed tomography scan by Fisher's definition, and the presence of vasospasm. Clinical vasospasm was recognized in eight cases. The averaged Ca2+ value of the control group was 1.23 +/- 0.02 mmol/l. In patients with a poor neurological grade or severe SAH, the Ca2+ level was apt to be lower than that of the control group. In patients with vasospasm, the values of Ca2+ were significantly decreased, especially between 8 and 14 days after SAH, compared with those patients without vasospasm and the control group (p less than 0.05). These results indicate that measurement of Ca2+ concentration in whole blood may give a useful clue to treatment of vasospasm by calcium antagonist and that it may also provide a possible indicator as to the time of vasospasm in patients with severe SAH. However, it is very difficult to conclude whether decreased level of Ca2+ in patients with vasospasm is caused by the vasospasm itself.

[The effect of glycerol on local cerebral blood flow in patients with chronic ischemic cerebrovascular lesions].

The effect of glycerol on local cerebral blood flow was examined in patients with chronic ischemic cerebrovascular diseases (CVD). Twelve patients with minor completed stroke (10 cases) or transient ischemic attacks (2 cases) were subjected to the study (8 males, 4 females, the age ranging 27 to 70 with average of 56 +/- 15 years). Cerebral blood flow (CBF) was measured with stable xenon computerized tomography (Xe-CT). Each patient had 3 sequential Xe-CTs; resting, with intravenous administration of 200 ml of glycerol (group A) or lactated Ringer's solution (group B), and with intravenous administration of 1 g of acetazolamide. The resting CBF, CBF with glycerol, and CBF with acetazolamide were 30.4 +/- 1.6 ml/100 g/min (ml), 35.1 +/- 2.6 ml, 44.2 +/- 2.2 ml in group A, and 29.9 +/- 2.0 ml, 28.5 +/- 1.9 ml, 45.0 +/- 3.2 ml in group B, respectively. Glycerol increased CBF significantly in patients with chronic CVD, and seemed to be effective in ameliorating chronic low perfusion state in these patients.

The relationship of cloverleaf skull syndrome to hydrocephalus.

In 1960, Holtermüller and Wiedemann described chondrodystrophic hydrocephalus as Kleeblattschädel syndrome. In the present paper, we review 23 cases of this syndrome associated with hydrocephalus, including 2 cases of our own. Of these 23 cases, 8 involved communicating hydrocephalus and 15 non-communicating hydrocephalus. It has been speculated that the associated hydrocephalus results from basilar impression, compression of infratentorial structures, aqueductal stenosis in non-communicating hydrocephalus, and impairment of venous drainage and cerebral spinal fluid flow at the level of the constrictive cranial ring in communicating hydrocephalus. Our present cases also showed this cranial ring, as demonstrated by skull X-rays and computed tomography scans. Since cloverleaf skull syndrome often has other general anomalies, we consider the hydrocephalus in this syndrome to have causes associated with the osteocartilaginous system.

Changes in brain stem blood flow under various grades of brain stem ischemia.

This report describes a study of brain stem blood flow (BBF) change under various grades of brain stem ischemia in a new experimental rat model. The main damage was caused by occlusion of the median and paramedian perforating arteries of the basilar artery. In this model, hyperperfusion was generally observed in cases of mild or moderate ischemia within 1 hr after recirculation and lasted for approximately 1 hr. During hyperperfusion, BBF increased to over 60 ml/100 g brain/min and was significantly greater than basal values (p less than 0.01). The fact that hyperperfusion was unobserved in some cases might be due to the degree of damage to the medulla oblongata. Hypoperfusion or lack of reflow phenomena was also followed by severe ischemia with remarkable hypotension. It is fairly clear from our results that the pattern of postischemic hyperperfusion is responsible for decreased oxygen availability in the brain stem and dysfunction of autoregulation. Acetazolamide reactivity was disturbed and had an inverse response during hyperperfusion. Such phenomena can be explained by paralytically dilated vessels due to ischemia. If BBF falls below a critical level, as we have seen, postischemic hyperperfusion may be induced with dysfunction of autoregulation and inverse acetazolamide reactivity due to vasoparalysis in the brain stem.

[An examination of change in blood flow in the brainstem of rats under various grades of ischemia].

UNLABELLED: A study was made of changes in brainstem blood flow (BBF) under various grades of ischemia in a rat recirculation model. MATERIALS AND METHODS: Adult male Wistar rats were anesthetized with pentobarbital sodium (40mg/kg i.p.). After exposure of the cervical vertebra (C2 portion), embolic threads of various sizes prepared were inserted into the vertebral artery. By the hydrogen clearance technique, changes in BBF were measured in 30 rats before, during and after brainstem ischemia. RESULTS AND DISCUSSION: The mean arterial blood pressure (MABP) was 113 +/- 5.8mmHg, and the mean BBF was 35.5 +/- 2.4ml/100g/min before ischemia. The alteration of BBF during and after ischemia was classified into three groups. The mildly ischemic group showed no significant changes in MABP; BBF was above 15ml/100g/min during ischemia, with slight reactivity revealed by acetazolamide after recirculation. In the moderately ischemic group, MABP dropped significantly to 62.0 +/- 12.4mmHg. After recirculation, it increased gradually to almost the control level. BBF decreased to below 15ml/100g/min immediately after ischemia, followed by a gradual increase to hyperperfusion after recirculation. After 1hr of recirculation, BBF increased to more than 60ml/100g/min with inverse acetazolamide reactivity. In the severely ischemic group, both BBF and MABP decreased irreversibly even after recirculation. These data indicate that the changes in MABP and BBF could be classified according to the degree of ischemic damage in the brainstem, where the vasomotor center is located. Acetazolamide reactivity was disturbed during hyperperfusion. Such phenomena could be explained by the presence of paralytically dilated vessels. If BBF falls below the critical level, as we showed here, it may induce postischemic hyperperfusion associated with dysfunction of autoregulation and vasoparalysis in the brainstem.

The effect of EC-IC bypass surgery on resting cerebral blood flow and cerebrovascular reserve capacity studied with stable XE-CT and acetazolamide test.

Cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) were measured by stable xenon computerized tomography (Xe-CT) and acetazolamide test in 15 patients with cerebrovascular disease before and after extracranial-intracranial (EC-IC) bypass surgery for minor stroke, reversible ischemic neurological deficit or transient ischemic attack. All had angiographically shown occlusive lesions of the major arterial trunk. In the present series, global analysis showed that the bypass did not increase the resting rCBF, but did increase the rCRC. We divided the patients into four groups according to the preoperative resting rCBF and rCRC. All 3 patients with normal resting rCBF and reduced rCRC showed postoperative improvement of rCRC. Of 6 patients with reduced CBF and reduced CRC, three had postoperative increase in resting CBF and four had increased CRC. One of two patients with reduced CBF and normal CRC showed only an increase in CRC. We propose that reduced CRC or reduced CBF with reduced CRC are criteria for selection of candidates for bypass surgery. We conclude that Xe-CT with the Diamox test is a useful and simple method for evaluating cerebral hemodynamics. Preoperative grouping with a combination of preoperative resting rCBF and preoperative rCRC is useful for predicting the effect of EC-IC bypass surgery.

[Intracerebral hemorrhage immediately following the operation of chronic subdural hematoma].

Complications following the operations for chronic subdural hematoma include recurrence of the hematoma, infection, seizure, and failure of the brain to expand due to cerebro-cranial disproportion. This report presents cases with intracerebral hemorrhage which is relatively rare complication. In case 1, a 35-year-old man developed status epilepticus immediately after the operation for chronic subdural hematoma. An emergency CT scan revealed acute brain swelling, and still, after the external decompressive craniotomy, CT scan showed severe brain swelling with subcortical diapedetic hemorrhage. In case 2, a 78-year-old woman whose CT scan had shown bilateral CSH and brain herniation, demonstrated intracerebral hemorrhage in the medial occipital lobe when examined post-operatively by CT scan. It is possible that the mechanisms of intracerebral bleeding following the operation for CSH are 1) diapedesis through increased permeability of parenchymal blood vessels due to the sudden increase in cerebral blood flow following the existence of longstanding extracerebral mass, and 2) hemorrhagic infarction due to recanalization of posterior cerebral artery compressed by the herniating medial temporal lobe. We should therefore avoid sudden decompression in the management of the cases which showed pre-operative consciousness disturbance or abnormal low or high density on CT scan, because these findings may be preoperative indications of brain fragility.

[Intracranial neurinomas of the jugular foramen and hypoglossal canal].

Intracranial neurinomas of the jugular foramen and the hypoglossal canal are relatively rare. Most reports have been of either single cases or of only two or three patients, and few large series exist in the literature. Although some of these tumors present palsies of the ninth, tenth, and eleventh cranial nerves as a jugular foramen syndrome, this is not always present. Unexpectedly, symptoms involving the eighth nerve are more frequently than those of ninth, tenth and eleventh nerves. This variability of clinical symptoms frequently leads to an initial misdiagnosis of glomus jugulare, acoustic or hypoglossal neurinoma. We report 2 cases of jugular foramen neurinomas and 2 cases of hypoglossal neurinomas. Our review of literature has tabulated 92 jugular foramen neurinomas and 34 hypoglossal neurinomas. These neurinomas had become considerably large in size by the time they were detected. So, we should endeavor, by clinical or neuroradiological finding to detect them at the early stage when they exert less influence on the brain. In this series we discuss clinical pictures of these neurinomas.