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Biomedical subjects

H Kasuya

Publications and source records attributed to H Kasuya.

At least 19 recordsLinked to original sources

Fatal intratumoral hemorrhage immediately after gamma knife radiosurgery for brain metastases: case report.

Radiosurgical treatment of brain tumors is sometimes considered to be free from significant acute complications or adverse effects. A rare case of fatal intratumoral hemorrhage immediately after gamma knife radiosurgery (GKR) for brain metastasis is reported. A 46-year-old woman with lung cancer complicated by systemic dissemination experienced an acute episode of headache, speech disturbances, and right-side hemiparesis. She had no history of arterial hypertension or coagulation disorders. CT and MRI disclosed multiple brain metastases. The largest tumor, which was located in the left frontal lobe and caused a significant mass effect, was removed microsurgically without any complications. GKR for nine residual metastases was done on the fourth postoperative day. The marginal dose, which corresponded to the 50% prescription isodose line, constituted 20 Gy. No complications were noticed during frame fixation, treatment itself, or frame removal. Fifteen minutes after the end of the GKR session the patient acutely fell into a deep coma. Urgent CT disclosed a massive hemorrhage in the left cerebellar hemisphere in the vicinity of the radiosurgically treated lesion. The patient died 4 days later and autopsy confirmed the presence of intratumoral hemorrhage. In conclusion, GKR for metastatic brain tumors should not be considered as a risk-free procedure and, while extremely rare, even fatal complications can occur after treatment.

Brain Neoplasms↗

Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11.

Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%-6%. Although IA has a substantial genetic component, little attention has been given to the genetic determinants. We report here a genomewide linkage study of IA in 104 Japanese affected sib pairs in which positive evidence of linkage on chromosomes 5q22-31 (maximum LOD score [MLS] 2.24), 7q11 (MLS 3.22), and 14q22 (MLS 2.31) were found. The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for IA. Fourteen distinct single-nucleotide polymorphisms (SNPs) were identified in ELN, and no obvious allelic association between IA and each SNP was observed. The haplotype between the intron-20/intron-23 polymorphism of ELN is strongly associated with IA (P=3.81x10-6), and homozygous patients are at high risk (P=.002), with an odds ratio of 4.39. These findings suggest that a genetic locus for IA lies within or close to the ELN locus on chromosome 7.

3' Untranslated Regions↗

Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The possible role of inflammatory reaction of the cerebral artery in the pathogenesis of cerebral vasospasm has been noted in recent studies. We quantitatively measured the levels of expression of genes related to inflammation in the spastic artery in a canine double-hemorrhage model. METHODS: Twenty dogs were assigned to 4 groups: group D0, control; group D2, dogs killed 2 days after cisternal injection of blood; group D7, dogs given double cisternal injections of blood and killed 7 days after the first injection; and group D14. Angiography was performed twice: on the first day and before the animals were killed. Total RNA was extracted from the basilar artery. The expressions of interleukin (IL)-1alpha, IL-6, IL-8, IL-10, tumor necrosis factor-alpha, E-secretin, fibronectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule-1, transforming growth factor-ss, basic fibroblast growth factor, and collagen types I, III, and IV were examined with TaqMan real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: Prolonged arterial narrowing peaking on 7 day was observed. There was a significant difference in vessel caliber between D0, D2, D7, and D14 groups (P:<0.0001). There were significant differences in mRNA expression in the basilar artery for IL-1alpha, IL-6, IL-8, ICAM-1, and collagen type I between D0, D2, D7, and D14 groups (P:=0.0079, 0. 0196, 0.0040, 0.0017, and <0.0001, respectively). The average level of mRNA was highest in D7 for IL-1alpha, IL-6, IL-8, and ICAM-1 (17-, 16-, 131-, and 1.7-fold compared with those of D0, respectively) and in D14 for collagen type I (10.9-fold). CONCLUSIONS: Increased expression of genes related to inflammation in the spastic artery suggests that inflammatory reaction of the cerebral artery is associated with sustained contraction.

Animals↗

Combined effects of adeno-associated virus vector and a herpes simplex virus mutant as neoplastic therapy.

BACKGROUND AND OBJECTIVES: Although surgical therapy for pancreatic cancer has not been successful, new gene therapies, such as adeno-associated virus (AAV) vectors hold promise for treating cancer. However, expression of AAV vectors alone is insufficient for adequate effects in vivo for cancer therapy. We describe a novel therapy using the combined herpes simplex virus-ICP6 deletion mutant (ICP6delta) and AAV vector. METHODS: We investigated ICP6delta and AAV regarding kinetics and dose-response relationships of LacZ expression in vitro. We studied the expression of LacZ in vivo using subcutaneous pancreatic cancer tumors (SW1990) in nude mice. RESULTS: In vitro, ICP6delta enhanced the expression of AAV; 24 hr following inoculation there was more expression with AAV plus ICP6delta than with AAV plus KOS, and a multiplicity of infection (MOI) of 0.5 was the optimal titer of ICP6delta to support maximal expression of AAV. In vivo, there was much higher expression of LacZ in mice injected with AAV-LacZ plus ICP6A than with AAV-LacZ alone. CONCLUSIONS: ICP6delta enhances expression of AAV-vector in vitro and in vivo. These results suggested that combined therapy have potential for human cancer.

Adenoviruses, Human↗

Molecular cloning of a novel brain-type Na(+)-dependent inorganic phosphate cotransporter.

We have isolated a human cDNA encoding a protein, designated DNPI, that shows 82% amino acid identity and 92% similarity to the human brain-specific Na(+)-dependent inorganic phosphate (Na(+)/P(i)) cotransporter (BNPI), which is localized exclusively to neuron-rich regions. Expression of DNPI mRNA in Xenopus oocytes resulted in a significant increase in Na(+)-dependent P(i) transport, indicating that DNPI is a novel Na(+)/P(i) cotransporter. Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels. In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels. No hybridizing signal for DNPI mRNA is observed in the glia-rich region of corpus callosum. In other regions examined, both mRNAs are moderately or highly expressed. These results indicate that BNPI and DNPI, which coordinate Na(+)-dependent P(i) transport in the neuron-rich regions of the brain, may form a new class within the Na(+)/P(i) cotransporter family.

Animals↗

Prevention of cerebral vasospasm by nicardipine prolonged-release implants in dogs.

The purpose of this study was to determine the efficacy of nicardipine prolonged-release implants for preventing vasospasm in a canine SAH model in a dose-escalating placebo-controlled blind fashion. Drug-release kinetics of copoly(lactic/glycolic acid) pellet containing nicardipine were evaluated in vitro. In vivo, 18 dogs were randomly assigned to one of three groups, i.e. placebo, low-dose (0.8 mg), or high-dose (8 mg) nicardipine. Angiography was performed, followed by right craniectomy, the induction of subarachnoid hemorrhage, and the placement of the pellets in the Sylvian fissure. On Day 7 and Day 14, the angiography was repeated. In the first four days, 61.9% of the actual nicardipine loaded was released and within 10 days, 96%. The average percent reductions of vessel diameters in the middle cerebral artery on Day 7 were 43%, 14% and 7% in the placebo, low-dose, and high-dose groups, respectively (p = 0.0319). The mean concentration of nicardipine in the clots on Day 14 was 9.7 x 10(-7) mol-1 l-1 and 5.1 x 10(-6) mol-1 l-1 in the low-dose and high-dose group, respectively. This drug delivery system prevented vasospasm in dogs significantly even at low dose, while maintaining an appropriate concentration of nicardipine in the clot adjacent to the arteries.

Animals↗

Clinical features of intracranial aneurysms in siblings.

OBJECTIVE: Among the family members of patients with aneurysmal subarachnoid hemorrhage (SAH), siblings have been documented to be at high risk of SAH and to have a high prevalence of unruptured aneurysms. We studied the distinctive features of aneurysms in siblings and attempted to determine the risk of rupture. METHODS: We analyzed detailed data on 159 patients with siblings who had ruptured and unruptured aneurysms in 77 families from throughout Japan. RESULTS: Seventy-three percent of the patients were female, and the mean age at the time of rupture was 55.6 years. In 39 families, two or more siblings had SAH. Eighty of 107 patients with ruptured aneurysms and 28 of 52 with unruptured aneurysms had a family history of SAH in siblings (P = 0.0082). Multiple and mirror-image aneurysms were found in 42 and 21 patients, respectively. Among 218 aneurysms, middle cerebral artery aneurysms were the most common type (43%). Anterior communicating artery aneurysms were underrepresented (15%). There were significantly more ruptured than unruptured anterior communicating artery aneurysms, compared with other aneurysms (P = 0.01). CONCLUSION: The clinical features of aneurysms in siblings in this population agreed well with those reported for familial intracranial aneurysms and SAH, except for the age at the time of rupture. It is suggested that the risk of rupture is greater when patients with unruptured aneurysms have siblings with aneurysmal SAH and/or anterior communicating artery aneurysms.

Aneurysm, Ruptured↗

Change in circulating blood volume following craniotomy.

OBJECT: The importance of monitoring circulating blood volume (CBV) during perioperative management is widely recognized in critically ill patients. The purpose of this study was to investigate the change in CBV following craniotomy by using indocyanine-green pulse spectrophotometry. METHODS: Circulating blood volume and plasma hormones related to stress and fluid regulation were measured five times: preoperatively, immediately postoperatively, and 1, 2, and 7 days after craniotomy was performed in 17 patients with a brain tumor or an unruptured aneurysm. The mean value of CBV preoperatively was 82 ml/kg, which decreased to 64 ml/kg (78%) immediately postoperatively and gradually recovered to 82 ml/kg on Day 7 postsurgery (p = 0.0069). The mean values of adrenaline, noradrenaline, arginine vasopressin, renin, and aldosterone were highest immediately postoperatively. The mean intraoperative balances of water and sodium were 1,090 ml and 113 mEq, respectively. Partial correlation coefficients of CBV to noradrenaline and serum sodium during the entire study were -0.430 (p = 0.0036) and 0.418 (p = 0.0048), respectively. CONCLUSIONS: Attention should be paid to decreased CBV following craniotomy, which is caused by the shift of fluid to interstitial spaces due to surgical stress. Hypovolemia can be suspected from a postoperative decrease in serum sodium.

Adult↗

[Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy].

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).

Adult↗

[Left Sylvian fissure meningioma in a one-year-eight-month old child].

We report a case of a Sylvian fissure meningioma in a one-year-eight-month old child who experienced the onset of a convulsive seizure. He had no neurological deficit and no developmental disorders. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large left temporal tumor which was well enhanced and without dural attachment. Angiography revealed a slight tumor stain in the left Sylvian fissure supplied by branches of the internal carotid artery. Total removal of the tumor was performed, and we found that the tumor had no dural attachment, but was strongly attached to the M2 segment of the left middle cerebral artery. Pathological examinations revealed it to be a fibrous meningioma without malignancy. This is the youngest case among the reported five pediatric deep Sylvian meningiomas. Introducing this case, we discuss the clinical features of pediatric meningiomas.

Brain Neoplasms↗

[The efficacy and safety of the nicardipine prolonged-release implant in a canine double hemorrhage model].

A drug delivery system using copoly (lactic/glycol acid) was tested to determine its efficacy and safety in preventing cerebral vasospasm following subarachnoid hemorrhage in dogs. Rod shaped implants (1 mm diameter, 10 mm length, and approximately 10% of nicardipine) was prepared by a heat compression method. Ten dogs were assigned to two groups: double hemorrhage group and double hemorrhage group treated with implants. Vertebral angiography and arterial blood injection into the cisterna magna were performed, followed by midline suboccipital craniectomy and laminectomy of the atlas and placement of nicardipine implants in the cisterna magna. On day 2, arterial blood injection into the cisterna magna was repeated (double hemorrhage model). On day 7, vertebral angiography was repeated. The animals were then sacrificed and the brain and blood clot were taken out. All the animals involved in both groups had been clinically well. Though 5 animals of the control group showed severe vasospasm, no vasospasm was observed in 3 animals and only very mild vasospasm in 2 of the nicardipine-treated group. There was a statistically significant difference in diameter between the two groups (0.5 mm vs 1.1 mm, p = 0.009). Histological examination showed no specific changes related to implants. Furthermore, left frontotemporal craniotomy and placement of nicardipine implants in the carotid-optico cistern were preformed in 3 dogs. Neither clinical symptoms related to implants nor specific histological changes were observed (e.g. hypotension, seizure). These results suggested that nicardipine-prolonged release preparation is safe as well as effective for cerebral vasospasm.

Animals↗

Intraperitoneal delivery of hrR3 and ganciclovir prolongs survival in mice with disseminated pancreatic cancer.

UNLABELLED: BACKGROUND AND OBJECTIVES; Intraperitoneal dissemination of pancreatic cancer is associated with a poor prognosis. Surgical resection does not prolong survival. Here we describe a novel approach to this difficult clinical problem consisting of intraperitoneal delivery of the herpes simplex virus (HSV) vector (hrR3) to mice with peritoneal dissemination of the pancreatic cancer cells. METHODS: The human pancreatic cancer cell line (SW1990) was implanted into the abdominal cavity of nude mice. Fifteen days later, the abdominal neoplasm was treated by intraperitoneal injection of the replication-conditional HSV vector (hrR3). The mutant lacks the ribonucleotide reductase gene, but contains an intact HSV-tk gene. Beginning 5 days after vector injection, mice were treated with a 14-day course of ganciclovir. RESULTS: Long-term survival (150 days) was seen in 70% of mice receiving hrR3 and ganciclovir, 40% of mice receiving hrR3 alone, and 0% of untreated mice. No vector-related mortality was observed. X-Gal tissue staining revealed blue-stained cells only in tumor nodules, not in normal organs. CONCLUSIONS: Intraperitoneal delivery of hrR3 and ganciclovir improves survival in this murine model of peritoneal dissemination of pancreatic cancer. The ability of hrR3 to replicate only in rapidly dividing cells makes this virus an attractive vector for gene therapy of cancer.

Animals↗

Phenytoin as a liquid material for embolisation of tumours.

We carried out embolisation with phenytoin in seven patients with meningiomas; in three by cannulation of the middle meningeal artery during surgery and in four by microcatheter introduced into the middle meningeal artery. Phenytoin (125-500 mg) diluted with saline (25 mg/ml) was injected slowly as a bolus. There was no evidence of devascularisation in two meningiomas treated with 125 mg and 150 mg of phenytoin. Large areas of ischaemic and haemorrhagic necrosis were found in five meningiomas treated with 250-500 mg. After embolisation, the tumour blush disappeared, with preservation of the feeding arteries. Total resection of the tumour was performed with minimum blood loss. Caution and proper use are emphasised to avoid increase in tumour volume and reflux. Phenytoin could be a suitable material for superselective embolisation.

Adult↗

Aneurysmal bone cyst of the coronoid process of the mandible.

A rare case of an aneurysmal bone cyst (ABC) involving the right coronoid process of the mandible in a 12-year-old girl is presented. The characteristic features with fluid-fluid levels within the lesion observed on Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) was helpful in the preoperative diagnosis.

Bone Cysts, Aneurysmal↗