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During skull base surgery, reconstruction of the dura is a very important procedure. Here, the use of a temporofrontal pedicled fascia flap tunnelled between temporal muscle fibres is described. This technique is easily performed and has a low postoperative morbidity, including skin and temporal muscle complications.

Liver cirrhosis (LC) is often complicated by hyperinsulinemia due to insulin resistance (IR), which is considered to be closely related to shunt formation and impaired liver function. This study evaluates whether balloon-occluded retrograde transvenous obliteration (B-RTO) can affect glucose and insulin metabolism in patients with LC. Twenty-five cirrhotic patients (mean age = 69.6 years; female/male = 12/13; hepatitis C virus/alcohol/nonalcoholic steatohepatitis = 14/6/5; Child-Pugh’s class A/B = 10/15) with gastric varices and/or hepatic encephalopathy caused by portosystemic shunts (PSS) due to portal hypertension (PH) underwent B-RTO at our hospital. Testing was performed before and at 1 month after the procedure. Shunt occlusion resulted in a decrease in extrahepatic collateral blood flow and an increase in portal venous flow, as well as a dramatic improvement in hepatic function markers. In addition, B-RTO significantly decreased homeostasis model assessment (HOMA) of IR without a statistical decline of HOMA of β-cell function. The 75-g oral glucose tolerance test (75-OGTT) revealed that occlusion of PSS reduced both fasting immunoreactive insulin (IRI) levels and the area under the curve for IRI. However, no significant change in preprandial or postprandial plasma glucose levels was observed. Furthermore, according to the criteria of the American Diabetes Association, B-RTO led to an improved 75-OGTT profile in 58.3 % of patients who had impaired glucose tolerance or diabetes mellitus before the procedure. Shunt occlusion improves IR-related hyperinsulinemia through increased portal venous flow, ameliorated liver function, and consequent augmented hepatic insulin clearance in cirrhotic patients with PH.

Aim Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)-related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV-related chronic liver disease. Methods We retrospectively examined 71 patients with HCV-related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment – Insulin Resistance (HOMA-IR). Amino acids were assayed by examining branched-chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR). Results HOMA-IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = −0.46, P = 0.0001) and tyrosine (r = 0.55, P

Aim We recently reported that the iron chelator deferoxamine (DFO) is efficacious in advanced hepatocellular carcinoma (HCC) patients. Iron regulation may thus have an important impact in HCC therapy. Because transferrin is a native chelator that regulates iron homeostasis, it may act as an anticancer agent in a similar manner as DFO. The objective of this study was to evaluate serum transferrin as a prognostic predictor in advanced HCC patients undergoing hepatic arterial infusion chemotherapy (HAIC). Methods We retrospectively studied 44 patients receiving HAIC and analyzed various parameters for their possible use as prognostic predictors. Results The 1-, 2- and 3-year cumulative survival rates were 36.4%, 18.2% and 8.5%, respectively, and the median survival time (MST) was 7.0 months. The survival rates of patients who had serum transferrin of 190 mg/dL or more (MST, 12.0 months) were significantly better than those of patients who had serum transferrin of less than 190 mg/dL (MST, 4.9 months). Multivariate analysis identified serum transferrin of 190 mg/dL or more (hazard ratio [HR], 0.282; 95% confidence interval [CI], 0.132–0.603; P = 0.001) and Child–Pugh score B (HR, 1.956; 95% CI, 1.034–3.700; P = 0.039) as independent prognostic predictors. There was a significant correlation between serum transferrin level and therapeutic effect (P

57歳の男性．B型肝硬変・肝細胞癌に対して外来経過観察中，下血に対する精査加療目的で当科に緊急入院した．上部消化管内視鏡検査（EGD）で十二指腸下行脚に静脈瘤が認められたものの活動性出血および血液貯留の所見はなく，下部消化管内視鏡検査・カプセル内視鏡検査・経肛門的ダブルバルーン内視鏡検査においても回腸～結腸内に凝血塊の貯留が認められたのみで出血源の同定には至らなかった．腹部血管造影検査では十二指腸周辺に著明な門脈系-大循環系短絡路の発達が認められ，血管造影下CTで十二指腸下行脚付近に造影剤の血管外漏出が疑われた．直後の緊急EGDにより十二指腸静脈瘤破裂と診断し，内視鏡的静脈瘤結紮術（EVL）にて一次止血に成功した．しかしその２日後に出血性ショックに陥ったため，EVLで止血した上で引き続きバルーン閉塞下逆行性経静脈的塞栓術（B-RTO）を施行して完全止血を得た．十二指腸静脈瘤破裂は非常に稀な難治性消化管出血であるが，今回我々はEVL・B-RTO併用療法で止血し救命し得た症例を経験したので報告する．

左脈絡膜悪性黒色腫に対する手術歴（2004年4月，左眼球摘出術）を有する79歳の男性患者が2009年10月に右季肋部痛を主訴に当院外来を受診した．血液検査にて軽度の肝機能障害と高度の凝固系異常が認められたため精査加療目的で同日当科に緊急入院となった．HBs抗原・抗HBs抗体・抗HBc-IgG抗体・抗HCV抗体はいずれも陰性であり，腹部超音波検査・CT検査・MRI検査・血管造影検査で肝両葉に多血性腫瘤が多数認められた．悪性黒色腫に特異的な腫瘍マーカーである5-S-cysteinyldopaが異常高値を呈したがPIVKA IIも著明に上昇していたため画像・血液検査所見からは悪性黒色腫肝転移と肝細胞癌の鑑別には至らなかった．超音波下肝腫瘍生検にて悪性黒色腫の確定診断を得た上で同病変に対してシスプラチンを用いた肝動脈化学塞栓療法を施行した．今回我々は「脈絡膜悪性黒色腫肝転移」という非常に稀な一例を経験したので報告する．

AIM A late evening snack (LES) is recommended for protein-energy malnutrition in patients with liver cirrhosis. However, many cases of liver cirrhosis have accompanying impaired glucose tolerance and there are concerns that LESs might aggravate glucose intolerance. In this study, we concomitantly used an alpha-glucosidase inhibitor with a LES and examined the effects on glucose tolerance. In addition, we examined whether or not there was an improvement in energy metabolism by slowing glucose absorption with the concomitant use of the alpha-glucosidase inhibitor. METHODS The subjects were 11 patients with liver cirrhosis. From before the study, all the patients had been taking a LES supplementation with a branched-chain amino acid (BCAA)-enriched nutrient mixture. The patients were started on the concomitant use of alpha-glucosidase inhibitor (0.2 mg) taken just prior to the LES. The change of glucose tolerance and energy metabolism were examined using a 75-g oral glucose tolerance test and indirect calorimetry. RESULTS One week and three months after the start of the concomitant use of the alpha-glucosidase inhibitor, the area under the concentration curve for plasma glucose was significantly decreased. Three months after the concomitant use, the non-protein respiratory quotient was significantly improved. There were no serious side effects during the follow-ups. CONCLUSION The concomitant use of the alpha-glucosidase inhibitor use with LES showed the possibility of improving glucose tolerance and energy metabolism. In patients with impaired glucose tolerance, the concomitant use of an alpha-glucosidase inhibitor with LES might be a useful measure for nutritional management.

Aim: We investigated the effect of supplementation with branched-chain amino acids (BCAA) in patients with liver cirrhosis on the change of energy metabolism as well as glucose tolerance. Methods: Thirty liver cirrhosis patients underwent nutrient supervision by a dietician for one week. They were then prescribed oral supplementation with three packs of a BCAA nutrient (Livact 4.15 g/pack; Ajinomoto Pharma, Tokyo, Japan), taken three times a day: after breakfast, dinner and before sleep. The change in energy metabolism and glucose tolerance was examined using an indirect calorimeter and 75 g oral glucose tolerance test (75 g OGTT). Results: Non-protein respiratory quotient (npRQ) as well as branched-chain amino acid/tyrosine ratio (BTR) showed significant improvement, especially in patients with a creatinine height index (CHI) greater than 80. There was also a significant correlation between npRQ after one week of BCAA supplementation and the CHI. The patients with CHI greater than 80 and those with borderline pattern assessed by 75 g OGTT showed significant improvement in impaired glucose tolerance. Conclusion: Liver cirrhosis patients with CHI greater than 80 are the first candidates for BCAA supplementation. These patients showed improvement not only in energy metabolism and BTR, but also glucose tolerance.

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

Background & Aims Hepatic arterial infusion chemotherapy (HAIC) is an option for treating advanced hepatocellular carcinoma (HCC). Because of the poor prognosis in HAIC non-responders, it is important to identify patients who may benefit from continuous HAIC treatment; however, there are currently no therapeutic assessment scores for this identification. Therefore, we aimed to establish a new therapeutic assessment score for such patients. Methods We retrospectively analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP) and/or des-gamma-carboxy prothrombin (DCP) levels and analyzed various parameters for their possible use as predictors of response and survival. AFP and DCP responses were assessed after half a course of HAIC (2 weeks); a positive-response was defined as a reduction of ≥ 20% from baseline. Results Multivariate analysis identified DCP response (odds ratio 16.03, p < 0.001) as an independent predictor of treatment response. In multivariate analysis, Child-Pugh class A (hazard ratio [HR] 1.99, p = 0.018), AFP response (HR 2.17, p = 0.007), and DCP response (HR 1.90, p = 0.030) were independent prognostic predictors. We developed an Assessment for Continuous Treatment with HAIC (ACTH) score, including the above 3 factors, which ranged from 0 to 3. Patients stratified into two groups according to this score showed significantly different prognoses (≤1 vs. ≥2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003). Conclusions The ACTH score may be useful in the therapeutic assessment of HCC patients receiving HAIC.

Leptin is now recognized as a proinflammatory cytokine and thought to be a progressive factor for non-alcoholic steatohepatitis (NASH). Here we showed the effects of leptin on the production of TNF-alpha (tumor necrosis factor-alpha) by Kupffer cells (KCs) with signal transduction. Leptin enhanced TNF-alpha production accompanied by a dose-dependent increase of MAPK activity in lipopolysaccharide (LPS)-stimulated KCs. SB203580 and JNK inhibitor I, specific inhibitors of P38 and JNK, inhibited TNF-alpha production in KCs but PD98059, an inhibitor of the ERK pathway, did not affect TNF-alpha production by KCs. Recombinant constitutively active adenovirus (Ad)-MKK6 and-MKK7 increased TNF-alpha production in KCs with activation of P38 and JNK without any change by Ad-MEK1 delivery. On the other hand, KCs isolated from the Zucker rat (fa/fa), a leptin receptor-deficient rat, showed reduced production of TNF-alpha on stimulation with LPS. The delivery of Ad-MKK6 and-MKK7, but not Ad-MEK1, increased TNF-alpha production in KCs of Zucker rats with activation of P38 and JNK. Addition of leptin to normal rats increased LPS-induced hepatic TNF-alpha production in vivo and leptin receptor-deficient Zucker rats showed reduced hepatic TNF-alpha production on addition of LPS in vivo. These findings indicate that P38 and JNK pathways are involved in the signal transduction of leptin enhancement of LPS-induced TNF-alpha production.

Background Temporal bone chondroblastoma is a rare primary bone tumor that affects the floor of the middle cranial fossa. This tumor is known to have high recurrence rate after curettage, and wide resection is therefore recommended. However, the literature provides little information regarding long-term results after wide resection of temporal bone chondroblastoma. Methods Four cases of surgically treated temporal bone chondroblastoma underwent long-term follow-up. Results Four patients, 3 males and 1 female, with mean age of 34, were surgically treated at the neurosurgery department of Keio University Hospital. Two patients were treated for recurrent tumor and the other two for new disease. In all cases the tumor mainly involved the mandibular fossa with variable degree of infiltration into tympanic and petrous parts. The tumor was totally removed via zygomatic approach in all patients. In 3 patients, the mandibular condyle was removed to expose the tumor. These patients had temporary malocclusion and restricted motion postoperatively, which resolved within 3 to 12 months with conservative treatment. All patients have no recurrence to date with a mean follow-up period of 9 years. Conclusion Temporal bone chondroblastoma was removed totally with skull base surgical technique and no recurrence has occurred for 6 to 13 years postoperatively. We found that removal of the mandibular head does not cause permanent problems of mastication in patients with normal dentures.

Jugular foramen meningioma is very rare. Papillary meningioma, the histological aspects and clinical behavior of which are highly malignant, is also very rare. Only 55 cases of jugular foramen meningioma have been reported in the literature. To our knowledge, this is the first report of a jugular foramen papillary meningioma. A 25-year-old woman presented with hoarseness and right hearing disturbance. Neurological examination showed deficits of the right hypoglossal and vagus nerves with palsy. Magnetic resonance imaging (MRI) revealed a mass on the right jugular foramen extending intracranially and extracranially, with weak contrast enhancement. The intracranial tumor was removed via the right lateral suboccipital approach. Histopathological examination confirmed the diagnosis of papillary meningioma. We report here the first case of jugular foramen papillary meningioma. No completely effective treatment for papillary meningiomas exists at present, with the exception of surgery.

BACKGROUND Only 2 cases of abducens nerve schwannoma solely inside the cavernous sinus have been reported. In both cases, abducens nerve palsy remained after operation. We report the first case of abducens nerve schwannoma inside the cavernous sinus proper with postoperative recovery from abducens nerve palsy. CASE DESCRIPTION The patient was a 47-year-old female who developed left abducens and trigeminal nerve palsies. Neuroradiological examination revealed left intra-cavernous sinus tumor. Total removal of the tumor was performed. The location of the tumor was confirmed intraoperatively inside the cavernous sinus itself, with no relation to the trigeminal nerve. Further, the relation of the tumor to one particular nerve fiber within the abducens nerve bundle was confirmed inside the cavernous sinus. After surgery, the patient had transient abducens nerve palsy. It had totally disappeared by 6 months. CONCLUSION When the tumor origin is just within the spacious cavernous sinus rather than more posterior in the narrow dural tunnel of Dorello's canal, successful preservation of the nerve function is possible postoperatively through a thorough knowledge of the membranous anatomy and careful preoperative study of the radiographic findings.

The goal of this study was to determine the membranous protection of the abducens nerve in the petroclival region. The petroclival portion of the abducens nerve was studied in ten dissections from five cadaveric head specimens. One of the heads was used for histological sections. Four heads were injected with colored latex for microsurgical dissections. The histological sections were prepared from petroclival dura mater, embedded in paraffin blocks, stained, sectioned in the axial, coronal, and sagittal planes, and evaluated by light microscopy. The abducens nerve was covered by a dural sleeve and arachnoidal membrane during its course within the petroclival area. Following the petrous apex, the abducens nerve was fixed by a sympathetic plexus and connective tissue extensions to the lateral wall of the cavernous segment of the internal carotid artery and to the medial wall of Meckel's cave. Fibrous trabeculations inside the venous space were attached to the dural sleeve. The lateral clival artery accompanied the dural sleeve of the abducens nerve and supplied the petroclival dura mater. The arterioles accompanying the abducens nerve through the subarachnoid space supplied the nerve within the dural sleeve. The arachnoid membrane covered the abducens nerve within the dural sleeve to the petrous apex, and arachnoid granulations found on the dural sleeve protruded into the venous space. The extension of the arachnoid membrane to the petrous apex and the presence of arachnoid granulations on the dural sleeve suggest that the subarachnoid space continues in the dural sleeve.

Cerebral infarction results in impairment of motor and cognitive functions. We performed intracranial transplantation of multipotential neuro-epithelial stem cells with mesenchyme into experimentally large ischemic lesions to study their potential to relieve deficits.Wistar albino rats were subjected to transient middle cerebral artery occlusion for 60 minutes, producing an extensive ischemic lesion in the ipsilateral striatum and adjacent cerebral cortex. The rat mesencephalic neural plate at the early somite stage (embryonic day 10.5) together with adjacent ventral mesenchyme was used as donor material. We performed histological and immunohistochemical studies, with antibodies against tyrosine hydroxylase, and dopamine- and adenosine 3': 5'-monophosphate-regulated phosphoprotein 32 (DARPP-32; a striatal marker). Micro-angiograms were made by using Microfil silicone rubber. Morris Water-maze learning and treadmill task were employed to evaluate motor and cognitive functions.A viable non-tumoral mass was recognized in the rat striatum, up to as long as 156 days after transplantation. There were many cells positive for tyrosine hydroxylase or DARPP-32 in the graft. Some of the DARPP-32 positive cells within the graft had extended their dendrites into host tissues. In the micro-angiograms, many fine vessels were observed within the graft and dilated vessels meandered around the graft. Transplanted animals recovered significantly better in motor and cognitive functions than animals injected with only culture medium.Neuro-epithelial stem cells may follow several lines of differentiation; along the naturally genetically programmed line of differentiation, or along other cell lines depending on different environments. Grafting of neuro-epithelial stem cells with mesenchyme may merit a further study as a treatment for cerebral infarction.

The petroclival or prepontine tumors originating medial to the trigeminal nerve include meningiomas, trigeminal neurinomas, laterally extended chordomas and prepontine epidermoids. They frequently show middle fossa or parasellar extension and have been one of the difficult tumors requiring a combined large craniotomy or multiple step surgery. Here, we will present a surgical method of tumor removal through a keyhole, epidurally created in a petrous apex. The technical points presented are based on my experience of 95 cases. This approach has the following advantages: (1) One-stage epidural surgery to the petroclival and dumbbell parasellar–clival lesions through a small craniotomy; (2) Minimal venous complications compared to the presigmoid approach; (3) Minimal facial and lower cranial nerves injury by jumping into the petroclival area medial to the internal auditory meatus; (4) Bloodless tumor removal being possible by detachment of the tentorial artery; (5) Hearing preservation by limited petrous resection.

Tumor necrosis factor-alpha (TNF-alpha), may be involved in the pathogenesis of inflammatory bowel diseases (IBDs). The aim of this study was to evaluate the effect of TNF-alpha on the inflammatory activity of IBD.TNF-alpha mRNA expression in intestinal mucosal biopsy specimens from IBD patients [ulcerative colitis (UC), n = 54; and Crohn's disease (CD), n = 11] was analyzed using a competitive polymerase chain reaction. The degree of macrophage infiltration was analyzed by immunohistochemistry, using an antihuman CD68 antibody.TNF-alpha mRNA expression was increased in UC patients, corresponding to the inflammatory activity. However, in CD, TNF-alpha mRNA expression was not correlated with the endoscopic findings.We clarified that TNF-alpha mRNA expression was responsible for the inflammatory activity in UC. However, TNF-alpha mRNA expression was not correlated with the mucosal injury in CD.

OBJECTIVE: The goals of this investigation were to perform a detailed analysis of petroclival microanatomic features, to investigate the course of the abducens nerve in the petroclival region, and to identify potential causes of injury to neurovascular structures when anterior transpetrosal or transvenous endovascular approaches are used to treat pathological lesions in the petroclival region. METHODS: Petroclival microanatomic features were studied bilaterally in seven cadaveric head specimens, which were injected with colored silicone before microdissection. Another cadaveric head was used for histological section analyses. RESULTS: A lateral or medial location of the abducens nerve dural entrance porus, relative to the midline, was correlated with the course and angulation of the abducens nerve in the petroclival region. The angulation of the abducens nerve was greater and the nerve was closer to the petrous ridge in the lateral type, compared with the medial type. The abducens nerve exhibited three changes in direction, which represented the angulations in the petroclival region, at the dural entrance porus, the petrous apex, and the lateral wall of the internal carotid artery. The abducens nerve was covered by the dural sleeve and the arachnoid membrane, which became attenuated between the second and third angulation points. The abducens nerve was anastomosed with the sympathetic plexus and fixed by connective tissue extensions to the lateral wall of the internal carotid artery and the medial wall of Meckel's cave at the third angulation point. There were two types of trabeculations inside the sinuses around the petroclival region (tough and delicate). CONCLUSION: The petroclival part of the abducens nerve was protected in a dural sleeve accompanied by the arachnoid membrane. Therefore, the risk of abducens nerve injury during petrous apex resection via the anterior transpetrosal approach, with the use of the transvenous route through the inferior petrosal sinus to the cavernous sinus, should be lower than expected. The presence of two anatomic variations in the course of the abducens nerve, in addition to findings regarding nerve angulation and tethering points, may explain the relationships between adjacent structures and the susceptibility to nerve injury with either surgical or endovascular approaches. Venous anatomic variations may account for previously reported cases of subarachnoid hemorrhage with the endovascular approach.

A 40-year-old female was admitted to the hospital with complaints of headache worsening gradually over a 1-month duration. Her past history included surgery to treat a left cerebellar cystic lesion 3 years before, and an untreated small solid right supracerebellar lesion of 1 cm diameter. On admission, magnetic resonance imaging showed that the right cerebellar lesion had grown to approximately 4 cm diameter abutting the tentorium and causing obstructive hydrocephalus. She also had two more small lesions, a right supratentorial solid lesion with cystic component near the splenium and an intramedullary cystic lesion at the C-2 level. Right suboccipital craniectomy was done. The vascular attachments between the superior aspect of the tumor and the tentorium were coagulated and the tumor was totally removed. C1-2 laminectomy was also performed to drain the intramedullary cyst. The patient deteriorated and lost consciousness with respiratory arrest 6 hours postoperatively and was reoperated for intracerebellar hematoma due to oozing from the tentorial vessels. Histological investigation revealed hemangioblastoma. Dural tentorial vascular attachments in solid hemangioblastomas located subjacent to the tentorium may cause early postoperative complications of hematoma at the site of vascular attachment following the resection. Computed tomography study in the early postoperative period is helpful to identify this problem.

A 17-year-old male presented with a wound on the right temporal region, oozing hemorrhagic necrotic brain tissue and cerebrospinal fluid, following a fall. Computed tomography showed temporoparietal and petrous apex fractures on the right. Neurological examination revealed abducens nerve paresis, ptosis, and myosis on the right side. The patient was treated surgically for the removal of the free bony fragments at the fracture site and to close the dural tear. The abducens nerve paresis, ptosis, and myosis persisted at the 3rd monthly postoperative follow-up examination. The anatomy of the abducens nerve at the petroclival region was studied in four cadaveric heads. Two silicone-injected heads were used for microsurgical dissections and two for histological sections. The abducens nerve has three different angulations in the petroclival region, located at the dural entrance porus, the petrous apex, and the lateral wall of the cavernous segment of the internal carotid artery. The abducens nerve had fine anastomoses with the trigeminal nerve and the periarterial sympathetic plexus. There were fibrous connections extending inside the venous space of the petroclival area. The abducens nerve seems to be vulnerable to damage in the petroclival region, either directly by trauma to its dural porus and petrous apex or indirectly by stretching of the nerve through the nervous and/or fibrous connections. Concurrent functional loss of the abducens nerve and the periarterial sympathetic plexus clinically manifested as incomplete Horner's syndrome in our patient.

A 39-year-old woman was admitted with complaints of headache and nasal discharge on the left for 3 months which was later on proved to be cerebrospinal fluid (CSF). Neurological examination found no abnormalities except bilateral papilledema. Neuroimaging demonstrated enlargement of the lamina cribrosa foramina through which the olfactory nerves pass, as well as empty sella and cerebral cortical atrophy. Bone mineral densitometry showed osteopenia. CSF Ca++ and blood parathyroid hormone levels were elevated. CSF pressure was 280 mmH2O. Bilateral frontal craniotomy was performed to expose the anterior fossa. Foraminal enlargement at the lamina cribrosa was confirmed, and islands of extra-osseous calcifications on the arachnoid membrane were identified. The base of the anterior fossa was repaired intradurally with fascial graft and fibrin glue on both sides. No CSF leakage was noted at 1-year follow up. Spontaneous CSF leakage probably resulted from enlargement of the foramina at the lamina cribrosa due to Ca++ mobilization from bones and pseudotumor cerebri not to the extent of hydrocephalus caused by poor CSF absorption at the arachnoid granulations obliterated by extra-osseous calcareous accumulation.

The aim of the study was to investigate the effect of the immunosuppressant FK 506 (tacrolimus hydrate) on acute liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS). Acute liver injury was induced in male Wistar rats by injecting the animals with P. acnes (10 mg/rat), and administering LPS (10 μg/rat) seven days later. One group was given FK 506 (1 mg/kg) 24 and 2 hr before administration of LPS, and the other group was given the same dose of saline. The 24-hr survival rate, serum alanine aminotransferase (ALT) concentration, and tumor necrosis factor (TNF) -α mRNA and protein concentrations in the liver and spleen were then compared. Hepatic macrophages were also isolated from rats seven days after P. acnes injection, LPS, and FK 506 or saline were added to the culture supernatant, and TNF-α production was studied. The 24-hr survival rate was 100% in the FK 506-treated group, in contrast with 16.6% in the saline group. Four hours after LPS injection, the serum ALT concentration was 755 ± 401 in the saline group versus 119 ± 42 units/ml (P < 0.01) in the FK 506-treated group. The serum TNF-α concentration was lower in the FK 506-treated group (1419 ± 957 pg/ml) than in the saline group (9205 ± 2215) (P < 0.01). The mRNA and protein concentrations in the liver and spleen in the two groups did not differ significantly 1 hr after LPS injection but were significantly lower in the FK 506-treated group after 4 hr. FK 506 did not directly inhibit TNF-α production by isolated cultured hepatic macrophages. FK 506 is unable to inhibit initial TNF-α production by hepatic macrophages (or probably that by splenic macrophages either) stimulated by injection of LPS in P. acnes + LPS-induced acute liver injury. However, the immunosuppressant does limit hepatic damage by inhibiting subsequent aggravation of inflammation by the cytokine network.

The proliferation and differentiation of stellate (Ito, or fat-storing) cells into myofibroblast-like cells is responsible for the development of liver fibrosis. Using computer image analysis, we evaluated the changes of alpha smooth muscle actin-positive stellate cells and liver fibrosis after interferon-alpha or -beta (IFN-alpha, beta) therapy in patients with chronic hepatitis C.Patients with chronic hepatitis C were treated with IFN-alpha or -beta and were divided into three groups on the basis of clinical criteria; a complete responder group (CR, 18 of 51), a partial responder group (PR, 17 to 51), and a nonresponder group (NR, 16 of 51). Liver fibrosis was assessed from specimens stained with Sirius red and was quantitated by computer image analysis. We also evaluated alpha-smooth muscle actin expression in the liver before and after IFN therapy by a semiquantitative scoring method (the alpha-smooth muscle actin index).Before IFN therapy, a large number of stellate cells expressing a-smooth muscle actin were present in the liver biopsy specimens. There was a significant correlation (r = 0.699, p0.05) between the change in the percent area of fibrosis and the alpha-smooth muscle actin index before and after IFN therapy in all groups. The complete responder group also showed a significant reduction of a-smooth muscle actin-expressing cells that was correlated with the reduction of serum ALT (r = 0.686, p0.05).These results suggest a-smooth muscle actin-expressing cells are responsible for liver fibrosis, and the elimination of factors stimulating matrix synthesis (e.g., hepatitis virus) may decrease liver fibrosis.

We have recently had many opportunities to operate on patients who presented with no neurologic deficits and were incidentally detected to have unruptured cerebral aneurysms. Therefore, it is very important to know how craniotomy affects the normal brain when making decisions regarding surgery for asymptomatic cerebral diseases.Thirty patients with unruptured cerebral aneurysms were evaluated. Aneurysm sites were as follows: internal carotid artery (ICA) (eight cases), anterior communicating artery (ACoA) (seven), middle cerebral artery (MCA) (five), basilar artery-superior cerebellar artery (BA-SCA) (two), and multiple aneurysms (three) [bilateral MCA: (two), ICA + Basilar top: (one)]. These patients underwent neuropsychological examinations [the Mini-Mental State (MMS) test, the "Kana-hiroi" test, and the "Maze" test] and single photon emission computed tomography (SPECT) before and after surgery.The details of the 17 cases whose Kana-hiroi tests deteriorated 1 month after surgery are as follows: ACoA: seven, MCA: five, ICA: three, BA: two. SPECT showed a decrease in CBF in nine cases (ACoA: six, ICA: two, MCA: one). There was a statistically significant difference (p0.05) between patients with ACoA aneurysms and ICA aneurysms. Three months after operation, all of the patients with neuropsychological deterioration and four of the six low CBF patients recovered to preoperative levels.These results indicated that the operation for unruptured cerebral aneurysms is moderately safe and meaningful; such a study should be required to determine when those patients could return to normal life.

The aim of this study was to investigate wheThe ran iron chelator, deferoxamine (DFO) can prevent lipidperoxidation, resulting in reduced liver injury as wellas reducing preneoplastic lesions induced by a choline-deficient L-amino acid-defined(CDAA) diet. CDAA diet administration resulted in anincreased serum ALT level (367 ± 58) after twoweeks, but simultaneous DFO treatment for two weeksreduced this elevation of ALT as well asmalondialdehyde (MDA) production in the liver. Feedingrats a CDAA diet for 12 weeks led to the development ofsevere liver fibrosis and preneoplastic lesions detectedas enzymealtered lesions. DFO treatment preventedthe expression of activated stellate cells, resulting inThe reduction of liver fibrosis as well as reducing thedevelopment of preneoplastic lesions. These results indicate that iron chelation can reducethe development of preneoplastic lesions in a CDAA dietmodel.

It is of extreme importance to prevent liver fibrosis and subsequent progression to liver cirrhosis. The aim of our study was to elucidate in vitro whether Sho-saiko-to exerted inhibitory effects on hepatic stellate cells.Hepatic stellate cells were isolated from male Wistar rats. Water-soluble ingredients of Sho-saiko-to were obtained at concentrations of 10, 100, 250, 500 and 1000 microg/ml. Morphological transformation was observed under a phase-contrast microscope. Flow cytometric analysis was performed on day 4 after culture to evaluate the potential to proliferate of the stellate cells by analyzing cell cycles. Northern blot analysis was carried out on day 3 after culture to determine the expressions of type I and type III procollagen mRNAs.(i) Sho-saiko-to 500 and 1000 microg/ml inhibited morphological transformation of the stellate cells to myofibroblast-like cells. (ii) Sho-saiko-to 500 and 1000 microg/ml significantly (p0.0001) accumulated the cells in the G0/G1 phase (118.8+/-0.7%, 119.2+/-0.5%, respectively as compared with control) and significantly (p0.0001) decreased cell numbers subsequently in G2/M phase (47.5+/-8.1%, 48.9+/-2.0%, respectively). (iii) Sho-saiko-to 500 and 1000 microg/ml also significantly (p0.05 or p0.0001) suppressed procollagen mRNA expression of type I to 51.5+/-6.4%, 34.9+/-3.7%, respectively, and type III to 51.3+/-12.3%, 46.7+/-11.4%, respectively.We have clarified the inhibitory effects of Sho-saiko-to on hepatic stellate cells in vitro. Sho-saiko-to could be a potent inhibitor in the pathogenesis of liver fibrosis.

Recent advances in technology have not substantially changed the high mortality rate associated with acute renal failure (ARF). To obtain a simple, valid prognostic index, we retrospectively evaluated the relative importance of demographic data, causes (acute insults) of renal failure, and comorbid clinical conditions for the outcome in 102 ARF patients who received renal replacement therapy with an overall mortality rate of 65% (66 of 102). There were no significant differences between survivors and nonsurvivors in age and gender. Mortality according to acute insults was similar to that of the whole population studied. Of the 10 clinical conditions at the time of the first renal replacement therapy, mechanical ventilation (p = 0.0002), cardiac failure (p = 0.0006), hepatic failure (p = 0.003), central nervous system dysfunction (p = 0.005), and oliguria (p = 0.04) were found to be significantly related to mortality by univariate analysis. Furthermore, multivariate analysis demonstrated that only mechanical ventilation, cardiac failure, and hepatic failure were significant risk factors. Survival was directly related to the number of significant variables in univariate analysis: zero, 89% (8 of 9); one, 62% (21 of 34); two, 19% (5 of 27); three, 10% (2 of 20); four, 0% (0 of 8); five, 0% (0 of 4). This simple and early prognostic index, derived from the assessment of clinical conditions which were easily determined at the patient's bedside, could be useful for outcome prediction in ARF patients requiring renal replacement therapy.

維持透析患者における二重エネルギーX線吸収法 (DXA) を用いた栄養学的評価について検討した. 対象は男性維持透析患者34例で, 年齢は平均55.2±12.3歳, 透析歴は119.6±71.2か月であり, 基礎疾患は, 糸球体腎炎28例, 腎硬化症5例, 嚢胞腎1例であった. 身体学的計測によるbody mass index (BMI) および上腕筋囲 (AMC) とDXAにより得られた%Fat, lean body mass (LBM), bone mineral content (BMC) の各項目について比較検討したところ, BMIと%Fat (r=0.773, p

We previously described the effectiveness of autologous bone marrow cell infusion (ABM i) therapy for patients with liver cirrhosis (LC). We analyzed chronological changes in 19 serum cytokines as well as levels of specific cytokines in patients after ABM i therapy and in a mouse model of cirrhosis generated using green fluorescent protein (GFP)/carbon tetrachloride (CCl4). We measured expression profiles of cytokines in serum samples collected from 13 patients before and at 1 day and 1 week after ABM i. Child–Pugh scores significantly improved in all of these patients. To analyze the meaning of early cytokine change, we infused GFP-positive bone marrow cells (BMCs) into mice with CCl4-induced LC and obtained serum and tissue samples at 1 day and as well as at 1, 2, 3, and 4 weeks later. We compared chronological changes in serum cytokine expression in humans and in the model mice at 1 day and 1 week after BMC infusion. Among 19 cytokine, both granulocyte colony-stimulating factor (G-CSF) and interleukin-1β (IL-1β) in serum was found to show the same chronological change pattern between human and mice model. Next, we examined changes in cytokine expression in cirrhosis liver before and at 1, 2, 3, and 4 weeks after BMC infusion. Both G-CSF and IL-1β were undetectable in the liver tissues before and at 1 week after BMC infusion but increased at 2 weeks and continued until 4 weeks after infusion. The infused BMCs induced an early decrease of both G-CSF and IL-1β in serum and an increase in the model mice with LC. These dynamic cytokine changes might be important to repair liver cirrhosis after BMC infusion.

AIM To evaluate the inhibitory effects of deferasirox (DFX) against hepatocellular carcinoma (HCC) through basic and clinical studies. METHODS In the basic study, the effect of DFX was investigated in three hepatoma cell lines (HepG2, Hep3B, and Huh7), as well as in an N-nitrosodiethylamine-induced murine HCC model. In the clinical study, six advanced HCC patients refractory to chemotherapy were enrolled. The initial dose of DFX was 10 mg/kg per day and was increased by 10 mg/kg per day every week, until the maximum dose of 30 mg/kg per day. The duration of a single course of DFX therapy was 28 consecutive days. In the event of dose-limiting toxicity (according to the Common Terminology Criteria for Adverse Events v.4.0), DFX dose was reduced. RESULTS Administration of DFX inhibited the proliferation of hepatoma cell lines and induced the activation of caspase-3 in a dose-dependent manner in vitro. In the murine model, DFX treatment significantly suppressed the development of liver tumors (P < 0.01), and significantly upregulated the mRNA expression levels of hepcidin (P < 0.05), transferrin receptor 1 (P < 0.05), and hypoxia inducible factor-1α (P < 0.05) in both tumor and non-tumor tissues, compared with control mice. In the clinical study, anorexia and elevated serum creatinine were observed in four and all six patients, respectively. However, reduction in DFX dose led to decrease in serum creatinine levels in all patients. After the first course of DFX, one patient discontinued the therapy. We assessed the tumor response in the remaining five patients; one patient exhibited stable disease, while four patients exhibited progressive disease. The one-year survival rate of the six patients was 17%. CONCLUSION We demonstrated that DFX inhibited HCC in the basic study, but not in the clinical study due to dose-limiting toxicities.

Liver cirrhosis patients generally progress to liver failure. To cure this progressive disease, we developed a novel cell therapy using bone marrow cells; autologous bone marrow cell infusion (ABMi) therapy. We previously described the possible action mechanism of ABMi therapy in the cirrhotic liver, and showed the timeline and results of clinical studies of ABMi therapy. We have also carried out other clinical studies using bone marrow cells and granulocyte colony-stimulating factor. Here, we report a new randomized clinical trial to evaluate the effects of ABMi therapy. However, ABMi therapy may not be possible in patients who are unable to undergo general anesthesia; therefore, we have started to develop a next-generation stem cell therapy using cultured mesenchymal stem cells.

Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs.A total of 50 HCC patients [Child-Pugh A/B, 34/16 patients; maximum tumor size 2.9 cm (mean); tumor number5/≥5 = 29/21 patients] were administered a mixture of cisplatin and lipiodol, followed by the injection of DSMs.According to the criteria of the Liver Cancer Study Group of Japan, the response [complete response (CR) + partial response (PR)] rate and CR rate were 72 and 38%, respectively [CR, 19 patients; PR, 17; stable disease, 9; progressive disease, 5]. The 1-, 2-, 3-, and 4-year cumulative survival rates were 85, 67, 41, and 35%, respectively, and the median survival time was 32.6 months. Multivariate analysis identified tumor number5 nodules [odds ratio 10.651, 95% confidence interval (CI) 2.168-52.317; P = 0.004] as an independent predictor of response and des-γ-carboxyprothrombin level100 mAU/mL [hazard ratio (HR), 0.268, 95% CI 0.091-0.786, P = 0.017] and therapeutic effect CR or PR (HR 0.255, 95% CI 0.099-0.659; P = 0.005) as independent predictors of survival.Transcatheter arterial infusion chemotherapy using lipiodol and DSMs might be considered as a potential intervention in HCC patients, especially those with tumors of5 nodules.

In 2003, we initiated a clinical trial to examine autologous bone marrow cell infusion (ABMi) therapy for cirrhotic patients and reported the clinical effect of the therapy. To analyze how splenectomy may potentiate the effects of bone marrow cell infusion on cirrhosis, we performed a mouse study and a clinical trial on patients with cirrhosis.In mice, we analyzed the effect of splenectomy on bone marrow cell infusion in four experimental groups (group A, splenectomy + bone marrow cell infusion + CCl(4); group B, sham operation + bone marrow cell infusion + CCl(4); group C, splenectomy + CCl(4); group D, sham operation + CCl(4)). In clinical, we compared the effect of splenectomy on ABMi therapy.We observed significantly increased average serum albumin levels and higher expression of green fluorescent protein (GFP), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen in the livers of group A. We observed MMP9/GFP double-positive cells in the cirrhotic livers. A significant decrease in the liver fibrosis areas was observed in group A. Splenectomy enhanced the repopulation of bone marrow cells into the cirrhotic liver and improved the liver microenvironment via expression of MMP9 secreted from repopulating GFP-positive cells. Next, we performed a clinical trial to compare the effect of splenectomy on the efficacy of ABMi therapy. Cirrhotic patients who underwent splenectomy before ABMi therapy tended to have a greater improvement in liver function.ABMi therapy with splenectomy may be an effective therapeutic modality for cirrhosis.

We designed a novel transcatheter arterial infusion chemotherapy (TAI) using iodized oil (lipiodol) and degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) patients. In this study, we investigated the efficacy of TAI using lipiodol and DSM in a prospective randomized trial.We randomly divided 45 patients with HCC into 3 groups: TAI using lipiodol (lipiodol group, n = 15), TAI using DSM (DSM group, n = 15), and TAI using lipiodol and DSM (lipiodol + DSM group, n = 15). In the lipiodol group, a mixture of cisplatin and lipiodol was administered. In the DSM group, a mixture of cisplatin and DSM was administered. In the lipiodol + DSM group, a mixture of cisplatin and lipiodol was administered, followed by DSM.The response rates were 40% in the lipiodol group, 53.4% in the DSM group, and 80% in the lipiodol + DSM group, respectively. The response rate tended to improve in the lipiodol + DSM group (lipiodol group vs. lipiodol + DSM group, P = 0.07). The median progression-free survival time was 177 days in the lipiodol group, 287 days in the DSM group, and 377 days in the lipiodol + DSM group. The progression-free survival in the lipiodol + DSM group was significantly better than those in the DSM group (P = 0.020) and the lipiodol group (P = 0.035). There were no serious adverse effects among the 3 groups.TAI using lipiodol and DSM was superior to TAI using lipiodol only and TAI using DSM only because of improvements in therapeutic effects and progression-free survival.

Background There are few blood tests for an efficient detection of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection. Methods The abilities of quantitative analyses of 7 genes hypermethylation in serum DNA, α-fetoprotein (AFP) and prothrombin-induced vitamin K absence II (PIVKA-II), and various combinations to detect HCC were evaluated in a training cohort of 164 HCV-infected patients (108 HCCs; 56 non-HCCs). An optimal hybrid detector, built using data for 2 methylated genes (SPINT2 and SRD5A2), AFP, and PIVKA-II, achieved the most satisfactory ability to detect HCC in the training cohort. We evaluated the ability of the optimal hybrid detector to detect HCC in an independent validation cohort of 258 consecutive HCV-infected patients (112 HCCs; 146 non-HCCs) who were newly enrolled in 4 distinct institutes. Results In the validation cohort of 258 patients, accuracy, sensitivity, and specificity of the hybrid detector for detection of HCC were 81.4%, 73.2%, and 87.7%, respectively. Notably, even when detecting HCC ≤ 2 cm in diameter, the hybrid detector maintained markedly high abilities (84.6% accuracy, 72.2% sensitivity, 87.7% specificity). Youden's index (sensitivity + specificity − 1) for HCC ≤ 2 cm was 0.60, vastly much superior to the 0.39 for AFP at a cut-off value of 20 ng/ml and the 0.28 for PIVKA-II at a cut-off value of 40 mAU/ml. Conclusions These results show that the optimal hybrid blood detector can detect HCV-related HCC more accurately.

Cis-dlamminedichloroplatinum (II) (シスプラチン) は臨床各領域の悪性腫瘍に対し広く用いられているが, 腎毒性を始めとする副作用により投与量が規定される. 本剤の抗腫瘍効果および副作用の発現には透析性を有する蛋白非結合型シスプラチンの血中濃度が重要である. そこで, 今回, 婦人科領域の悪性腫瘍患者を対象とし, 抗腫瘍作用を弱めることなく副作用を軽減する目的で, 血液透析 (HD) 併用下にシスプラチン動注療法を行い, その有効性につき検討した. その結果, 100mg投与では, HDにより同一時間内の腎排泄量の約3倍の蛋白非結合型シスプラチン除去が得られ, 動注後5時間までの総シスプラチンのarea under the time-concentration curveは46%減少した. HD併用200mgおよび250mg投与においても最高血中濃度をHD非併用100mg単独投与とほぼ同程度まで抑制し得た. また, HD併用により100mg投与では明らかに副作用の発現頻度が減少し, 尿中N-acetyl-β-D-glucosaminidaseおよびβ2-microgloblinを指標とした腎毒性の程度も軽減した. HD併用200mgおよび250mg投与でも重篤な副作用は認めなかった. 一方, 抗腫瘍効果は良好に認められ, 特に子宮頸部癌において顕著であった. これらの成績は, HD併用局所シスプラチン動注化学療法が, 全身の副作用を軽減させると共に, 腫瘍局所への投与量を増加させ得ること, さらに腎機能低下例に対しても応用し得る治療法であることを示しており, 今後の臨床応用が期待される.

OBJECTIVE We have reported that radiofrequency (RF) ablation with balloon occlusion of the hepatic artery (balloon-occluded RF ablation) increases the coagulation area compared with standard RF ablation. In this study, we evaluated the efficacy and safety of combination therapy with transcatheter arterial infusion chemotherapy (TAI) using iodized oil and balloon-occluded RF ablation in patients with hepatocellular carcinoma. PATIENTS AND METHODS We studied 12 patients with 12 HCC nodules (mean tumor diameter, 27.3 mm). All patients were classified as Child-Pugh Class A. Immediately after TAI using iodized oil, we performed balloon-occluded RF ablation. RESULTS One treatment session of the combination therapy was done for 10 of 12 nodules (83%). The greatest long-axis and short-axis dimensions of the area coagulated after the combination therapy were 48.8+/- 5.5 mm and 41.9 +/- 4.1 mm, respectively. During follow-up (mean, 33.4 months), there was no local recurrence. The 1, 2, and 3-year survival rates were 100%, 92%, and 83%, respectively. No fatal complications were observed. CONCLUSIONS The combination therapy is an effective and safe treatment under favorable liver reserve capacity. Using the combination therapy, it is possible to finish one treatment session for patients with HCC nodules measuring less than 3 cm in greatest dimension.

The aim of this study was to evaluate the effect of scatter and attenuation correction in region of interest (ROI) analysis in brain perfusion single-photon emission tomography (SPECT) and to assess the influence of selecting the reference area on semi-quantification. Ten normal subjects were enrolled and injected with123I-iodoamphetamine to undergo simultaneous emission and transmission scanning for scatter and attenuation correction. We reconstructed three SPECT images from common projection data of each subject: with scatter correction and non-uniform attenuation correction, with scatter correction and uniform attenuation correction, and with uniform attenuation correction applied to data without scatter correction. A program for automated ROI drawing was used to set ROIs on various regions in brain images. Regional count ratios were compared in images with different correction procedures by using three different reference areas. The effect of the combination of scatter and attenuation correction was marked in the precentral, temporal, posterior, hippocampus and especially in the cerebellum. In contrast, it was not appreciable in the central and parietal areas. When using the cerebellar ROI as the reference, the count ratio varied widely depending on the correction procedures. On the other hand, the whole brain reference offered the least variation in the count ratio. The influence of photon scattering and attenuation was dependent on regions. Since the count in the cerebellar ROI is greatly affected by photon scattering and attenuation, nonuniform attenuation correction combined with scatter correction deserves consideration when using the cerebellar ROI as the reference.

Background Physiologic saline is routinely used as an irrigant in neurosurgery especially in Japan. Cerebrospinal fluid (CSF) differs from physiologic saline in its concentration of inorganic salts, osmolality, and pH and is completely different insofar as it contains glucose, protein, cholesterol, and other lipids. The present study was designed to compare the possible functional and morphologic deleterious influence of these differences on cultured rat neural cells using saline (S), Ringer's solution with glucose (Lactec G, LG; Otsuka Pharmaceutical Co.; Tokyo, Japan) and without glucose (Lactec, L; Otsuka Pharmaceutical Co.), and an artificial CSF (ACSF). Methods Primary cultured rat neurons and astrocytes were divided into five groups according to the medium used, the four experimental groups (ACSF, L, LG, and S) and one control group (C). At various time points up to 24 hours, the rhodamine 123 uptake by neuronal or astrocytic cellular mitochondria was evaluated as cell function assessment. Morphologic assessment for both neuron and astrocyte culture was carried out with scanning electron microscopy (SEM) at the 24-hour time point. Results SEM showed little difference between the C and ACSF groups, whereas morphologic deterioration was particularly severe in the S group for both neurons and astrocytes. In the case of neuronal mitochondrial activity, the L and S groups demonstrated respectively severe and some deterioration, particularly in the mitochondria of the neuronal processes. The deleterious effects in mitochondrial activity of the S group were even more apparent in the astrocytic cells. Conclusion These results suggest that physiologic saline, when used as an irrigant in neurologic surgery, might in some circumstances cause damage to exposed and compromised neural cells.

Postoperative changes in higher cortical function and cerebral blood flow (CBF) were investigated in patients with unruptured cerebral aneurysms to assess the effect of habitual smoking on the known transient changes after aneurysm surgery. Fifty-six adults with unruptured cerebral aneurysms, including 11 heavy smokers (smoking indexor = 600) and 45 non-smokers, were evaluated using three neuropsychological examinations, the Mini-Mental State Examination, the Maze test, and the Kana-hiroi test, and single photon emission computed tomography to measure CBF before and after surgery. Neuropsychological changes were assessed by reliable change indices to take into account the practice effects. The scores of at least one examination decreased in 15 of 56 patients 1 month after surgery. On the Maze test, five of 11 heavy smokers and five of 45 non-smokers deteriorated after surgery, showing a significant difference (p = 0.018). The CBF in heavy smokers often decreased after surgery, but there was no statistically significant difference in logistic regression. Three months after surgery, the neuropsychological scores of 13 of the 15 deteriorated patients recovered to the preoperative level. Higher cortical function in heavy smokers with unruptured cerebral aneurysms often decreases transiently after operation, compared to non-smokers. Therefore, surgery planning for heavy smokers with unruptured cerebral aneurysms should consider this outcome.

A rare case of brain stem infarction caused by mucormycotic emboli, preceded by acute hydrocephalus, is reported. The patient, who had suffered from leukemia and had undergone bone marrow transplantation several months before, presented initially with seizure and persistent disturbance of consciousness. A head CT scan revealed marked ventricular dilation and diagnosed as acute hydrocephalus. The patient received emergent ventricular drainage. Despite the aggressive treatment, the patient did not survive. Autopsy revealed systemic mucormycosis occluding and invading various arteries including basilar artery and its branches, causing fatal brainstem infarction. Although early diagnosis remains difficult in the cases of systemic mucormycosis, prompt initiation of treatment is mandatory; one must have in mind the possibility of presence of fungal infection when treating patients with acute neurological deterioration who have underlying debilitating diseases, even though fungi themselves are hard to detect in most cases.

Cutaneous vasculitis is an uncommon complication of propylthiouracil therapy. Although its pathogenesis remains to be established, detection of antineutrophil cytoplasmic antibodies (ANCA) in association with this type of vasculitis has recently been described. We report here 2 patients who developed ANCA-associated crescentic glomerulonephritis without evidence of cutaneous vasculitis during propylthiouracil treatment of hyperthyroidism. Improvement of the renal function and the disappearance of ANCA were correlately found after discontinuation of propylthiouracil and by corticosteroid therapy in both patients.

The present study was undertaken to investigate whether the development of proteinuria in the borderline hypertensive rat (BHR) is influenced by the Y chromosome and to determine if the onset of proteinuria in the BHR is delayed when blood pressure is lowered with enalapril, an angiotensin I converting enzyme inhibitor. Male F1, rats were the first-generation offspring of the mating of spontaneously hypertensive (SHR) females and Wistar-Kyoto (WKY) males and the mating of SHR males and WKY females. At 20 weeks of age, enalapril (125 mg/l) was added to the drinking water. Untreated BHR and enalapril-treated BHR (BHRE) were followed to 90-100 weeks of age. Urine was collected every 10-20 weeks for determination of protein, albumin, and nitric oxide (NO2/NO3) metabolite excretion. Indirect blood pressure in BHR from both crosses was approximately 175 mm Hg from 20 to 90-100 weeks of age. Enalapril lowered blood pressure by about 30 mm Hg, but was ineffective in reducing urinary protein or albumin excretion rates at any age. Urinary excretion of nitric oxide metabolites was similar in all groups at all time periods. There were significant differences in the percent of glomerulosclerosis between the two matings. Based on these results, renal injury in the BHR is not associated with the Y chromosome and can be dissociated from hypertension. Further studies using congenic and transgenic technology will be necessary to identify functions of genes and associations with hypertension in order to understand the kidney disease in this model of hypertension.