PubMed Health⌕ Search

Biomedical subjects

T Inamura

Publications and source records attributed to T Inamura.

At least 73 records · Page 4Linked to original sources

Radiation-induced brain tumours: potential late complications of radiation therapy for brain tumours.

The development of neoplasms subsequent to therapeutic cranial irradiation is a rare but serious and potentially fatal complication. In this study, we retrospectively reviewed the clinical and pathological aspects of 11 patients who underwent cranial irradiation (range, 24-110 cGy) to treat their primary disease and thereafter developed secondary tumours within a span of 13 years. All tumours arose within the previous radiation fields, and satisfied the widely used criteria for the definition of radiation-induced neoplasms. There was no sex predominance (M: 5, F: 6) and the patients tended to be young at irradiation (1.3-42 years; median age: 22 years). The median latency period before the detection of the secondary tumour was 14.5 years (range: 6.5-24 years). Meningiomas developed in 5 patients, sarcomas in 4, and malignant gliomas in 2. A pre-operative diagnosis of a secondary tumour was correctly obtained in 10 patients based on the neuro-imaging as well as nuclear medicine findings. All patients underwent a surgical removal of the secondary tumour, 3 underwent additional chemotherapy, and one received stereotactic secondary irradiation therapy. During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). Based on these data, the clinicopathological characteristics and possible role of treatment for secondary tumours are briefly discussed.

Adolescent↗

Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated lymphoproliferative disorder of the brain.

EBV-associated lymphoproliferative disorder (LPD) is a rare but serious complication in marrow transplant recipients. A 31-year-old Japanese woman in the second chronic phase of CML received an allogeneic BMT from her HLA 2-locus-incompatible 62-year-old father. Around day +200, she developed EBV-LPD of the right parieto-temporal lobe which caused slowly progressive left hemiparesis. Two courses of donor lymphocyte transfusions (DLT) of 10(6)CD3+ T cells/kg of body weight failed to suppress her central nervous system (CNS) EBV-LPD. The patient died of recurrent blastic crisis of CML. This case suggests that DLT may be ineffective for the treatment of CNS EBV-LPD.

Adult↗

Decreased hydration state of the stratum corneum and reduced amino acid content of the skin surface in patients with seasonal allergic rhinitis.

Recent studies of the stratum corneum (SC) in patients with atopic dermatitis (AD) have disclosed various functional impairments even in clinically unaffected skin. However, it has not been clear whether the presence of atopic background itself has any influence on the function of the SC. In this study, we conducted functional studies of the SC in the mid-portion of the flexor surface of the forearm of 49 skin lesion-free patients with allergic rhinitis to Japanese cedar pollen (atopic respiratory disease; ARD) in early spring, their disease-active season, by comparing the findings obtained with those in 28 patients with AD and 57 age-matched healthy control subjects. The results showed that the patients with ARD had significantly lower skin surface hydration levels assessed by high-frequency conductometry than those of the healthy control subjects. These levels were, however, not as low as those noted in moderately or severely affected patients with AD. Moreover, by measuring the amounts of water-soluble amino acids contained in the superficial portions of the SC, we found that these are also decreased at a marginal level (P = 0.051) in patients with ARD compared with levels in healthy control subjects. In contrast, the water barrier function of the SC evaluated by measurements of transepidermal water loss in patients with ARD was not different from that of the healthy control subjects. These results suggest that, although their skin appears normal clinically, the SC of the patients with ARD has functional deficiency in water-holding capacity.

Adult↗

Surgery of angiomas in the brainstem with a stress on the presence of telangiectasia.

This report deals with the surgery of angiomas other than arteriovenous malformation in the brainstem. The surgical cases were three cavernomas, two telangiectasias, and two venous malformations. We performed surgery when an angioma bled and the resulting hematoma was situated near the surface of the brainstem or the fourth ventricle. The cases were operated on at the subacute or chronic stages after hemorrhage. Although a magnetic resonance (MR) image showed a subacute or chronic localized hematoma with a low intensity rim, the case was not always a cavernoma, but a telangiectasia. Cavernomas could be totally removed, but telangiectasia could not. In the cases of medullary venous malformation the diagnosis was obtained radiologically, and when the hematoma was large, only hematoma evacuation was performed. In all cases the postoperative Karnofsky scores were improved or unchanged. Postoperative rebleeding in the hematoma cavity continued insidiously in a case of telangiectasia. The abnormal vessels of telangiectasia in the brainstem were preoperatively not visualized by cerebral angiography or MR imaging, but became visualized by enhanced MR imaging after evacuation of hematoma in two cases. It is stressed that an angioma with a hematoma intensity core surrounded by a low intensity rim on MR images is not always a cavernoma, but possibly is a telangiectasia.

Adolescent↗

Thiamine-deficient lactic acidosis with brain tumor treatment. Report of three cases.

Lactic acidosis due to thiamine deficiency is known to complicate chemotherapy and radiotherapy treatment of malignant extracranial tumors, but to the authors' knowledge, this complication has not been reported in patients treated for malignant brain tumors. They report three such cases, demonstrating that this complication can occur during treatment of brain tumors. In all patients, consciousness levels deteriorated within 1 to 2 days. Serum lactic acid levels increased to concentrations between 62 and 96.7 mg/dl, resulting in severe metabolic acidosis. A low blood thiamine level (9 ng/ml) was demonstrated at the onset in one case, and high-dose thiamine infusions dramatically improved lactic acidemia as well as impairment of consciousness in two cases. In the other case, hydrocephalus was suspected initially, resulting in a delay in thiamine supplementation. Clinical differentiation of this form of lactic acidosis from hydrocephalus or tumor progression can be very difficult in a patient undergoing treatment for a malignant brain tumor. Demand for thiamine is thought to be increased in patients with malignant brain tumors, and supplemental thiamine during treatment is necessary to prevent lactic acidosis. When this complication occurs, immediate treatment with sufficient thiamine is essential, together with normalization of pH by using sodium bicarbonate. With timely intervention, the level of consciousness can recover to the preacidotic state with no new neurological deficits.

Acidosis, Lactic↗

[Epstein-Barr virus-associated malignant lymphoma in an immuno-deficiency patient: a case report].

Human infection with Epstein-Barr (EB) virus occurs commonly, and EB virus exists in the B cell as a cryptic infection. Infected B cells become immortal by expressing both the EBNA2 and the LMP1 genes derived from the EB virus. Under normal condition of cellular immunity, the T cells recognize the EBNA2 and LMP1 as foreign proteins and attack the immortal B cells. However, under the condition of immunodeficiency, the immortal B cells can proliferate and form a tumor. We report a case of malignant lymphoma associated with immuno-deficiency which may correspond to this mechanism. A 33-year-old woman, who had an immuno-deficiency due to treatment for leukemia, had a progressing hemiparesis on her left extremities. Magnetic resonance imagings revealed a ring enhanced tumor with massive brain edema in the right fronto-parietal lobe. Stereotactic biopsy was performed and histological examination showed it to be a malignant lymphoma. The tumor cells were positive for L26 (B cell marker), CD79a LMP1, and EBNA2. They were negative for UCHL-1 and CD3 (T cell marker). According to these results, this lymphoma was caused by EB virus infection under the condition of immuno-deficiency.

Adult↗

Apparent diffusion coefficient (ADC) and magnetization transfer contrast (MTC) mapping of experimental brain tumor.

Brain tumor tissue contains different pathological areas, such as tumor cell rich parts, necrotic tissues, and cyst. Furthermore, both neovascularization and edema formation progress along with the tumor progression. In this study we employed diffusion weighted (DW) and magnetization transfer contrast (MTC) imaging to chronologically investigate the biological characteristics of a rat glioma. RG-2 glioma cells were implanted stereotactically into the right hemisphere of male Wistar rats. MR images were taken 1, 2 and 3 weeks after inoculation. Apparent diffusion coefficient (ADC) and MTC values were calculated as follows; ADC = -ln (SI-DW/SI-T2)/1096, MTC = 1-SI-MTon/SI-MToff. Each mapping image was made based on the calculated average values of four pixels. The spatial signal changes and the real values were compared to the histological findings. The apparent increase of ADC was noted in the parenchyma adjacent to tumor suggesting the progression of edema. The tumor itself had similar or slightly increased ADC. Cystic and necrotic components appeared 2 weeks after implantation and they showed significantly higher ADC than those calculated in the contralateral putamen. On the other hand, MTC was slightly decreased in the parenchyma adjacent to the tumor, markedly within the tumor, and maximally in the cystic and necrotic area suggesting accumulation of macromolecules such as growth factors, cytokines, and serum albumin.

Animals↗

Epidemiological survey of moyamoya disease in Korea.

To both clarify the current clinico-epidemiological features of Moyamoya disease in Korea as well as compare these cases with Japanese patients, 451 cases were collected from 26 Korean major neurosurgical institutes and 296 definite cases were analyzed statistically. Although the Korean age distribution patterns of Moyamoya disease showed two peaks, similar to Japanese patients, the Korean pattern was shifted to the right thus indicating Korean adult population to be 20% higher than that of Japanese patients. The female/male ratio was 1:3, which was slightly less than that for Japanese. The family occurrence rate in Koreans was 1.8%. The incidence of cerebral infarction and bleeding in Koreans was higher while transient ischemic attack (TIA) and seizure were less than that of Japanese. The incidence of infarction in children and of hemorrhage in children and adults were also statistically higher in Koreans. The incidence of hemorrhage was higher in females than in males. Both the age at onset and sex affected the disease type. Single encephalo-duro-arterio-synangiosis (EDAS) was performed on 87.6% of all surgical cases. Although the incidence of bleeding was higher in Korea, the outcomes of the patients were similar to that of the Japanese patients. Although Korean Moyamoya disease showed a relatively higher incidence of hemorrhage and adult onset, the overall clinical background was similar to that of Japanese patients.

Adolescent↗

Clinical features of probable moyamoya disease in Japan.

To clarify the current clinical features of probable Moyamoya disease in Japan, 180 cases were analyzed based on the cases collected by the Research Committee on Spontaneous Occlusion of the Circle of Willis of the Ministry of Health and Welfare, Japan. Although the age distribution patterns of probable Moyamoya disease showed two peaks similar to that of definite cases, the pattern shifted to the right thus indicating a reversed children versus adult ratio. The female/male ratio was 1.65, which was not significantly different from that observed in definite cases. The family occurrence rate was 6.7%. The incidence of cerebral infarction and bleeding in probable cases was higher than that in definite cases. The incidence of hemorrhage was higher in females than in males. Angiographically probable cases were at earlier stages in comparison to definite cases. The rebuild-up phenomenon in electroencephalograms was less detectable than in definite cases. Surgical procedures were performed in 63.3% of all cases and approximately 81% of them underwent bypass surgery. Single encephalo-duro-arterio-synangiosis, direct bypass and combined bypass procedures were performed in 35, 40 and 25% of all surgical cases, respectively. Although the incidence of bleeding was higher in the probable cases, the outcomes of the patients were similar to that of the definite cases except for mortality. Approximately 7% of the probable cases developed into definite type within an average 6.6 year follow-up period. The majority of probable Moyamoya disease cases thus seems to have somewhat different clinical characteristics from the definite disease cases.

Adolescent↗

The current status of the treatment for hemorrhagic type moyamoya disease based on a 1995 nationwide survey in Japan.

The optimal treatment regimen for hemorrhagic type Moyamoya disease has yet to be clearly established. Furthermore, it remains unclear as to whether or not bypass surgery can help prevent future intracranial hemorrhaging in Moyamoya patients. In Japan, several treatment options, such as conservative, medical, and surgical intervention, have been employed for the treatment of hemorrhagic type of Moyamoya disease. In this study, 282 hemispheres with hemorrhagic onset were analyzed based on a 1995 nationwide survey by the Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare Japan to clarify the current status of treatment for hemorrhagic type Moyamoya disease. Questionnaires were distributed to the departments of neurology, neurosurgery, and pediatrics all over Japan asking about both treatment and rebleeding. As a result, 12.5% of the affected hemispheres were treated conservatively while 32.3% were medically treated. Ventricular drainage and/or hematoma removal was performed in 15.8%, and revascularization surgery in 38.3% of all hemorrhagic sides. Among the revascularization procedures used, 45.7% of the hemispheres underwent single indirect bypass surgery, such as EDAS while 22.2% of them received a direct (superficial temporal artery--middle cerebral artery: STA-MCA) bypass surgery. A combination of direct and indirect bypass surgery or a combination of different kinds of indirect procedures comprised 32.1%. Forty-nine out of 282 hemorrhagic hemispheres demonstrated rebleeding. An intracranial hemorrhage occurred in 15 hemispheres with ischemic onset even though nine of them had undergone bypass surgery prior to hemorrhaging. Nearly 18% of the patients with hemorrhagic type disease experienced rebleeding regardless of the treatment modalities. Based on these findings, there remains no clearly superior treatment plan for hemorrhagic Moyamoya disease to prevent rebleeding at this time. However, the selection of patients, treatment modalities, and the timing of the surgery might all play an important role in controlling rebleeding. The final outcome of the patients are therefore mainly considered to correlate with the initial severity of the clinical features.

Cerebral Hemorrhage↗

[Radiation-induced leiomyosarcoma of the dura mater: a case report].

A 31-year-old man underwent total resection for a fibrillary astrocytoma in the right frontal lobe followed by 6MV x-ray radiotherapy. The portal field size was a square of 8 cm x 7 cm, and the total dose of irradiation was 50Gy, with single fractions of 2Gy. For the next 6.5 years there was no recurrence of the astrocytoma. At 38 years of age, the patient noticed a subcutaneous mass in the scar of the previous operation and developed generalized convulsive seizures. MRI revealed a dural tumor within the previous radiation field, and the tumor was partially removed. Histologically, it was diagnosed as a leiomyosarcoma. This dural sarcoma satisfies the widely used criteria for definition of radiation-induced malignancies first described by Cahan et al. Both the clinical features and the possible histogenesis of this secondary tumor are briefly discussed.

Adult↗

Increased delivery of a new cisplatin analogue (254-S) in a rat brain tumor by an intracarotid infusion of bradykinin.

The intracarotid infusion of bradykinin has been shown to selectively increase capillary permeability in a brain tumor without affecting either normal brain capillary permeability or the systemic blood pressure. We examined whether the intracarotid infusion of bradykinin could selectively increase the delivery of a new watersoluble antitumor agent, cis-diammine glycolato-platinum (254-S, 303.2 mol. wt.), to transplanted RG2 glioma in rats. The platinum contents in the brain, tumor tissues and plasma were measured using an atomic absorption spectrophotometer. The transfer ratio of 254-S from plasma to the tissues was calculated and expressed as the volume of plasma containing platinum per g tissue (Dp, microliter g-1). Intracarotid bradykinin infusion at a rate of 20 micrograms kg-1 min-1 increased the delivery of 254-S in the tumor tissue by 1.3-fold when compared with intracarotid infusion of 0.9% saline (48.78 +/- 18.11 vs. 37.12 +/- 12.53; p < 0.05). In normal brain tissue including the ipsilateral cortex, the contralateral basal ganglia and the contralateral cortex, bradykinin did not significantly increase the delivery of 254-S in comparison with 0.9% saline (12.28 +/- 9.53 vs. 10.70 +/- 5.05, 4.96 +/- 3.54 vs 4.96 +/- 4.80, 7.64 +/- 4.10 vs. 13.07 +/- 11.38, respectively). These results indicate that the intracarotid infusion of bradykinin selectively increases the delivery of 254-S to the brain tumor without affecting the normal brain. This method may, therefore, enhance the antitumor effect of 254-S for the treatment of brain tumors and also reduce neurotoxicity in the normal brain.

Animals↗

Enhanced tumor uptake of carboplatin and survival in glioma-bearing rats by intracarotid infusion of bradykinin analog, RMP-7.

OBJECTIVE: Intracarotid infusion of the bradykinin analog, RMP-7, can increase permeability in brain tumor capillaries. This study sought to determine the following: 1) the unidirectional transport, Ki, of radiolabeled [14C]carboplatin into brain tumors with either intravenous or intracarotid RMP-7 infusions; 2) the duration and extent of increased permeability in tumor capillaries during continuous RMP-7 infusions; and 3) the effect on survival of carboplatin combined with RMP-7 treatment in rats with gliomas. METHODS: Wistar rats with RG2 gliomas were used, and a unidirectional transfer constant, Ki, was determined using quantitative autoradiography. In the survival study, the rats were treated with intra-arterial carboplatin and RMP-7 at Days 5 and 7 after tumor implantation. RESULTS: Intracarotid infusion of RMP-7 for 15 minutes increased the transport of [14C]carboplatin to tumors by 2.7-fold, as compared with saline infusion alone (P < 0.001). The transports of [14C]dextran and [14C]carboplatin into tumors were significantly higher with 15 minutes of intracarotid infusion of RMP-7 (0.1 microgram/kg/min), compared to those with 10-, 30-, or 60-minute infusions (P < 0.01). Rats treated at Days 5 and 7 after tumor implantation with carboplatin alone (10 mg/kg) exhibited a modest increase in survival at 31 days (37%, compared to < 10% of controls), while those given the combination of carboplatin with RMP-7 exhibited a significantly higher survival rate (74%). CONCLUSION: Intracarotid infusion of RMP-7 can selectively increase transport of carboplatin into brain tumors and results in higher survival in rats with gliomas. These findings support the use of intracarotid infusion of RMP-7 to enhance the delivery of carboplatin to patients with malignant brain tumors.

Animals↗

VEGF and flt. Expression time kinetics in rat brain infarct.

BACKGROUND AND PURPOSE: Vascular endothelial growth/vascular permeability factor (VEGF) is a candidate for an angiogenic and hyperpermeability inducing factor in an infarct because it is a secretable mitogen specific for endothelial cells and is upregulated by hypoxia. Our study attempts to clarify the chronological expression of VEGF and its receptor (flt) system in experimental cerebral infarction. METHODS: With the use of a reproducible middle cerebral artery occlusion model in rats, VEGF expression was identified by Western blotting with anti-VEGF antibody. The chronological expression of the VEGF/flt system was analyzed semiquantitatively by immunohistochemical means in infarcts with different time courses from 3 hours to 3 weeks. RESULTS: VEGF and flt were expressed exclusively in the ischemic brain. The bands obtained on the immunoblot at 38 and 45 kD are related to those of VEGF121 and VEGF165 isoforms. Macrophages, neurons, and glial cells chronologically expressed VEGF immunoreactivity in a different fashion. Both VEGF (bound) and flt were detected in endothelial cells along with the development of angiogenesis. CONCLUSIONS: In the ischemic brain the macrophages, neurons, and glial cells appear to contain VEGF. The VEGF receptor flt was induced in endothelial cells along with the progression of angiogenesis in infarct. The VEGF/flt system is thus considered to be involved in the healing process of brain infarct.

Animals↗

Chemotherapy for progressive pilocytic astrocytomas in the chiasmo-hypothalamic regions.

Over the past 25 years, we have treated 17 patients with chiasmo-hypothalamic astrocytomas. Before 1988, the initial treatments consisted of surgery and/or radiotherapy, while since 1989, 4 children (1 male, 3 females, aged 3-8 years) were treated primarily with chemotherapy. None of them was associated with neurofibromatosis. After a biopsy of the tumor, the intravenous administration of ranimustine (MCNU; 30-86 mg/m2) and/or nimustine (ACNU; 30.3-64.1 mg/m2) was given without radiation therapy. Chemotherapy was usually given as an out-patient, with a total of 5-13 courses. The total doses of MCNU and ACNU administered ranged from 150 to 570 mg and from 64.8 mg to 100 mg, respectively. After chemotherapy 2 patients showed clinical improvement and tumor regression on neuro-imaging, while one patient showed clinical improvement and tumor size stabilization on neuro-imaging. The remaining one child, however, showed a clinical worsening and tumor progression on neuro-imaging studies. He was thus treated with a second chemotherapy regimen with carboplatin and etoposide, which brought about tumor regression. The acute and subacute toxicity of chemotherapy was mild. All patients are now leading almost normal lives with a median of 43 months after diagnosis. Although a longer and more careful clinical observation is required, the authors conclude that chemotherapy with MCNU and/or ACNU may benefit patients with unresectable pilocytic astrocytoma requiring treatment. The advantages of this therapy include its mild side effects and the lack of any hospitalization in most patients. It may also delay the need for radiation therapy, which can have a deleterious effect on the young developing brain.

Antineoplastic Agents↗

Intracarotid infusion of bradykinin selectively increases blood-tumor permeability in 9L and C6 brain tumors.

This study investigated the effects of bradykinin on blood-tumor barrier (BTB) permeability in transplanted 9L gliosarcomas (9L) and C6 gliomas (C6) in rats. Permeability, expressed as the unidirectional transfer constant, Ki (microliter/g/min), was measured by quantitative autoradiography. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid ([14C]AIB), sucrose ([14C]sucrose) and dextran ([14C]dextran). Intracarotid infusion of bradykinin (10 mg/kg/min) significantly increased the BTB permeability in both 9L and C6 tumors to [14C]AIB and [14C]sucrose, but did not increase permeability to [14C]dextran. Blood-brain barrier (BBB) permeability in normal (non-tumor) brain was not significantly increased to any of the tracers by intracarotid bradykinin infusion. Ki values for [14C]AIB, [14C]sucrose and [14C]dextran of 9L tumors in the bradykinin group versus control group were 41.6 +/- 12.6 vs. 24.8 +/- 6.30 (P < 0.02), 17.5 +/- 9.34 vs. 9.05 +/- 4.36 (P < 0.05), and 3.90 +/- 2.59 vs. 2.42 +/- 1.76, respectively (mean +/- S.D.). Ki values to [14C]AIB, [14C]sucrose and [14C]dextran of C6 tumors in the bradykinin group versus control group were 41.4 +/- 19.0 vs. 19.5 +/- 11.4 (P < 0.01), 18.0 +/- 8.88 vs. 7.06 +/- 3.05 (P < 0.01), and 4.07 +/- 1.45 vs. 2.27 +/- 1.26, respectively (mean +/- S.D.). Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. Intracarotid infusion of bradykinin may be a useful technique for selective delivery of compounds to brain tumors.

Aminoisobutyric Acids↗

Differential tissue expression of immunoreactive dehydropeptidase I, a peptidyl leukotriene metabolizing enzyme.

We previously reported that intracarotid infusion of leukotriene C4 (LTC4) causes a selective increase in vascular permeability within brain tumor capillaries in experimental rat brain tumor. Normal brain capillaries are rich in gamma-glutamyl transpeptidase (gamma-GTP), an enzyme which converts LTC4 to leukotriene D4 (LTD4), and acts as an 'enzymatic barrier' to the vasoactive effects of LTC4. Metabolism of LTD4 in brain capillaries is, however, not known. In this study, rat renal dipeptidase (dehydropeptidase-I, microsomal dipeptidase; EC 3.4.13.11), which converts LTD4 to leukotriene E4 (LTE4) in kidney, was purified from rat kidney and the distribution of immunoreactive dipeptidase in multiple rat organs was determined. Immunocytochemical multi-organ analysis in the rat, which included brain, lung, heart, liver, spleen, small intestine, and testis, was performed. The antigen corresponding to renal dipeptidase was recognized in lung, liver, and testis. There was no antigen in the brain, heart, spleen, and small intestine. In order to confirm the absence of dipeptidase activity in brain capillaries, the metabolism of LTD4 by isolated brain capillaries were examined by reversed phase high performance liquid chromatography. When LTD4 was incubated with the isolated rat brain capillary, no measurable conversion of [3H] LTD4 to LTE4 and leukotriene F4 (LTF4) by brain capillaries was observed with 30 min of incubation. These findings suggest that although gamma-GTP acts as an enzymatic barrier and inactivates LTC4, brain capillaries do not have metabolic activity against LTD4.

Animals↗