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Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 127 records · Page 7Linked to original sources

Indications of stereotactic irradiation for brain lesions.

Stereotactic radiosurgery (SRS: single-fraction stereotactic irradiation) was originally developed to treat benign lesions in the brain, and has been adopted for the treatment of small primary or metastatic brain tumours. It has recently been recommended that stereotactic radiotherapy (SRT: fractionated stereotactic irradiation) be applied to the treatment of brain tumours; however, it requires much more time and work than SRS, and sufficient radiobiological evaluations of these techniques have never been carried out. Biologically effective doses were calculated to determine the indications for SRS and SRT, and to decide on an effective SRT schedule, incorporating the factors of 'repair' and 'cell proliferation'. The results suggest that SRS would be recommended for arteriovenous malformations and benign tumours that have distinct margins separating them from surrounding normal tissue and SRT would be recommended for benign or malignant brain tumours without clearly defined boundaries. The recommended SRT schedules would be 7 Gy x 7 fractions every other day for malignant tumours and 3.5 Gy x 12 fractions every other day for benign tumours. However, clinically, these schedules should be modified according to many other factors in individual cases.

Brain Neoplasms↗

Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease.

Cell bodies of neurons at risk of death in Alzheimer disease (AD) have increased lipid peroxidation, nitration, free carbonyls, and nucleic acid oxidation. These oxidative changes are uniform among neurons and are seen whether or not the neurons display neurofibrillary tangles and, in fact, are actually reduced in the latter case. In consideration of this localization of damage, in this review, we provide a summary of recent work demonstrating some key abnormalities that may initiate and promote neuronal oxidative damage. First, mitochondrial abnormalities might be the source of reactive oxygen species yielding perikaryal oxidative damage. The common 5-kb deletion mitochondrial (mt)DNA subtype was greatly increased in the AD cases, but only in neurons at risk. The importance of such mitochondrial abnormalities to oxidative stress was indicated by a high correlation coefficient between the extent of the mtDNA increase and RNA oxidative damage (r2 = 0.87). Nonetheless, because mitochondria in AD do not show striking oxidative damage, as one would expect if they were the direct producer of free radical species, we suspected that abnormal mitochondria supply a key reactant that, once in the cytoplasm, releases radicals. One such reactant, hydrogen peroxide, (H2O2), abundant in mitochondria, can react with iron via the Fenton reaction to produce.OH. To demonstrate this directly using a modified cytochemical technique that relies on the formation of mixed valence iron complexes, we found that redox-active iron is associated with vulnerable neurons. Interestingly, removal of iron was completely affected by using deferroxamine, after which iron could be rebound to re-establish lesion-dependent catalytic redox reactivity. Characterization of the iron-binding site suggests that binding is dependent on available histidine residues and on protein conformation. Taken together with our previous studies showing abnormalities in the iron homeostatic system including heme oxygenase, iron regulatory proteins 1 and 2, ceruloplasmin, and dimethylargininase, our results indicate that iron misregulation could play an important role in the pathogenesis of AD and therefore chelation therapy may be a useful therapeutic approach. Finally, we wanted to determine the proximal cause of mitochondrial abnormalities. One interesting mechanisms involves re-entry into the cell cycle, at which point organellokinesis and proliferation results in increased mitochondria. Supporting this, we have considerable in vivo and in vitro evidence for mitotic disturbances in AD and its relationship with the pathogenesis of AD.

Alzheimer Disease↗

Activation of p38 kinase links tau phosphorylation, oxidative stress, and cell cycle-related events in Alzheimer disease.

The temporal association between oxidative stress and the hallmark pathologies of Alzheimer disease (AD) demonstrates that oxidative stress is among the earliest events in the disease. Nonetheless, neither the consequences of oxidative stress nor how oxidative stress relates to other pathological features of the disease are clear at this point. To begin to address these issues, we investigated p38 kinase, which is induced by oxidative stress, in the pathogenesis of AD. In hippocampal and cortical brain regions of individuals with AD, p38 is exclusively localized in association with neurofibrillar pathology. By marked contrast, these brain regions exhibit a low level of diffuse p38 staining in the neuronal cytoplasm in controls. We found a complete overlap of the immunostaining profiles of p38 and tau-positive neurofibrillary pathology and that the majority of p38 was activated in AD neurons, both of which support an association of p38 with the disease process. Moreover, the finding that PHF-tau co-immunoprecipitates with p38, and that p38 co-purifies with PHF-tau, strongly suggests that they are physically associated in vivo. Since p38 is also implicated in cell cycle regulation, our findings provide a link between the cell cycle re-entrant phenotype, cytoskeletal phosphorylation and oxidative stress in AD.

Aged↗

Course and distribution of facial corticobulbar tract fibres in the lower brain stem.

The course and distribution of the facial corticobulbar tract (CBT) was examined by correlating MRI of brain stem lesions with neurological symptoms and signs including central (C-FP) or peripheral facial paresis (P-FP) in 70 patients with localised infarction of the lower brain stem. C-FP occurred more often in patients with lesions of the lower pons or upper medulla of the ventromedial brain stem. Some patients with dorsolateral infarcts of the upper medulla to the lower pons showed C-FP, mostly on the lesion side. P-FP on the side of the lesion was also seen in patients with dorsolateral involvement of the lower pons. Patients with ventromedial infarction of the brain stem showed paresis of extremities contralateral to the lesion. Specific neurological symptoms and signs such as dysphagia, vertigo, nystagmus, Horner's syndrome, ipsilateral cerebellar ataxia, and contralateral superficial sensory impairment were seen in patients with dorsolateral infarcts of the brain stem. It is hypothesised that the facial CBT descends at the ventromedial lower pons, near the corticospinal tract, mainly to the level of the upper medulla, where the fibres then decussate and ascend in the dorsolateral medulla to synapse in the contralateral facial nucleus.

Adult↗

Anatomy of the right anterosuperior area (segment 8) of the liver: evaluation with helical CT during arterial portography.

PURPOSE: To evaluate the segmental anatomy of the right anterosuperior area (segment 8) of the liver by using helical computed tomography during arterial portography (CTAP). MATERIALS AND METHODS: Twenty-seven patients without lesions at segment 8 underwent helical CTAP. Three-dimensional portograms were reconstructed to verify the course of the portal veins. The number of subsegmental branches, in addition to the branching point and the distribution in segment 8, was assessed. RESULTS: In 25 (93%) patients, the dorsal branch of segment 8 gave rise to dorsally directed branches posterior to the right hepatic vein. In only four (25%) of 16 patients in whom the medial branch of segment 8 arose near the porta hepatis, the long paracaval portal branch of the caudate lobe extended upward above the interval between the middle and right hepatic veins. CONCLUSION: In most of the patients, the dorsal branches of segment 8 supplied the dorsocranial area of the right lobe posterior to the right hepatic vein. The paracaval portion of the caudate lobe was limited to below the interval between the middle and right hepatic veins in the majority of patients who showed medial branches of segment 8 arising near the porta hepatis. Recognition of this vascular anatomy is clinically important for preoperative evaluation of hepatic tumors in segment 8 because it may contribute to a safer surgical approach.

Adult↗

Early-stage rheumatoid arthritis: prospective study of the effectiveness of MR imaging for diagnosis.

PURPOSE: To assess the effectiveness of magnetic resonance (MR) imaging for the diagnosis of early-stage rheumatoid arthritis (RA). MATERIALS AND METHODS: Fifty subjects (nine men and 41 women) with polyarthralgia who were suspected of having early-stage RA on the basis of clinical and radiographic findings were selected to undergo gadolinium-enhanced MR imaging of the hands. The MR imaging criterion for the diagnosis of early RA was bilateral enhancement in both wrists and/or the metacarpophalangeal and/or proximal interphalangeal joints. Follow-up continued until a final diagnosis was determined. Two patients left the study before the end of follow-up. RESULTS: Final diagnoses were established after a mean follow-up of 776 days: rheumatoid arthritis in 26 patients and nonrheumatoid disease in 22. Use of the MR imaging criterion yielded the correct diagnosis in 25 patients with RA and three false-positive results in three patients without RA. As compared with the traditional format and classification tree criteria of the American Rheumatism Association, the MR imaging criterion allowed detection of seven and six additional patients with true RA, respectively. CONCLUSION: The introduction of MR imaging into the diagnostic criteria for early RA may contribute to more accurate diagnosis in patients suspected of having RA and thus allow an earlier decision to start proper medication.

Adult↗

Chronic unilateral ureteral obstruction represented as renin-dependent hypertension.

A 50-year-old woman developed renin-dependent hypertension immediately after accidental unilateral ureteral ligation during hysterectomy, and the hypertension lasted for 5 months. Surgical release of the obstruction was carried out 157 days after the ligation. Then, her blood pressure was normalized. However, the obstructed kidney showed intensive tubulointerstitial fibrosis and functional recovery was not obtained. This case suggests that the renin-angiotensin system may be upregulated in human kidney during unilateral ureteral obstruction for a long duration.

Atrophy↗

Clinical and pathophysiological features of amaurosis fugax in Japanese stroke patients.

OBJECTIVE: It has been emphasized that amaurosis fugax (AmF) is caused by thromboembolism due to atheromatous lesions of the extracranial carotid artery (EC-CA) in Caucasian populations. However, there have been few studies of AmF in Japan. We analyzed the clinical and pathophysiologic features of AmF in 43 Japanese AmF patients. SUBJECTS AND METHODS: Forty-three patients presented with AmF from a group of 2,056 Japanese patients with acute ischemic stroke. We investigated angiographic and transcranial Doppler findings, precipitating factors, medical treatment and prognosis, to elucidate the pathogenetic mechanism of AmF. RESULTS: Angiographic findings revealed an intracranial lesion in 22 patients (51%), extracranial lesion in 16 (37%), and no abnormality in 5 (12%). Blood flow in the ophthalmic artery (OA) examined by the transcranial Doppler ultrasonography (TCD) showed normal antegrade flow in 24 patients and reversed flow in 7. Precipitating factors for AmF were seen in 7 out of 43 patients. Regarding the pathogenesis of AmF, the micro-thromboembolism originated from the internal carotid artery (ICA) in 25 patients, the thromboembolism was via the external carotid artery (ECA) in 7, the hemodynamic retinal vascular insufficiency in 6 patients showed various atheromatous changes in the intracranial carotid artery (IC-CA) or EC-CA, and the cause was unknown in 5. CONCLUSION: In this series of patients, AmF was mainly caused by thromboembolism from IC-CA atheromatous lesions. Micro-thromboemboli from the ECA or hemodynamic retinal vascular insufficiency, although less frequent, should also be considered as possible etiologies for AmF.

Adolescent↗

[Three patients with systemic sclerosis complicated by microangiopathic hemolytic anemia and thrombocytopenia].

Clinical profiles and the treatment process of three female patients with systemic sclerosis (cases 1, 2, and 3) complicated by thrombotic microangiopathic hemolytic anemia (TMHA) were described. Thrombocytopenia preceded renal damage and hypertension in cases 1 and 2, although the chronological relationship between these parameters were unknown in case 3. Plasma exchange therapy using fresh frozen plasma was beneficial in cases 1 and 2. Cases land 3 presented with delirium and fluctuating psychosis, respectively. Early detection of thrombocytopenia and insidious hemolysis might be essential for starting effective plasmapheresis treatment in a part of patients with scleroderma kidney who present with thrombotic thrombocytopenic purpura (TTP) like disorder.

Aged↗

[mRNA expression of chemokines in rat kidneys with ureteral obstruction].

BACKGROUND: It has been demonstrated that leukocyte infiltration, mainly of macrophages and lymphocytes, into obstructed kidneys (OBK) of rats during unilateral ureteral obstruction (UUO). Chemokines (C-C subfamily) may be involved in this mechanisms. Thus, we accessed the gene expression of chemokines in renal cortex of rats with UUO. MATERIALS AND METHODS: Female SD rats were sacrificed at various time points after UUO. mRNA expression of MCP-1, RANTES and MIP-1 alpha was determined by semi-quantitative RT-PCR. RESULTS: Control kidneys (CNK) showed a weak mRNA expression of MCP-1, RANTES and MIP-1 alpha. OBKs showed an increase in MCP-1 at 2 hours of UUO and a significant increase at 4 hours of UUO as compared with CNKs or contralateral unobstructed kidneys (CLK). The mRNA levels of RANTES and MIP-1 alpha were not increased until 72 hours of UUO in CLKs or OBKs. There were slight, but significant, differences of RANTES and MIP-1 alpha expression between OBKs and CNKs at 120 hours of UUO. CONCLUSIONS: We suggest that the early increase in MCP-1 contributes to the leukocyte infiltration and that RANTES and MIP-1 alpha plays a partial role in a late increases.

Animals↗

[A case of Wernicke-Korsakoff syndrome with dramatic improvement in consciousness immediately after intravenous infusion of thiamine].

A 68-year-old man was hospitalized on March 4, 1998 for disturbances in consciousness. In 1995, he had received proximal subtotal gastrectomy and reconstructive surgery of the jejunal interposition for gastric cancer. Thereafter he had been taking enough food without the habit of taking liquor. In October 1997, his short term memory was becoming gradually worse. On February 12, 1998, he suffered from numbness in the feet, and then dysphagia, unsteady gait, and diplopia developed gradually. On February 26, brain MRI showed no abnormalities. On March 3, he had a fever of 38.5 degrees C and his consciousness became unclear. Neurological examination revealed semi-coma, total ophthalmoplegia, and absence of doll's eye movement. Deep tendon reflexes were absent. The serum thiamine level was 9 ng/ml (normal range: 20-50). Brain MRI demonstrated symmetrical high intensity lesions in the periaqueductal area of the midbrain, dorsomedial nuclei of bilateral thalami, and vestibular nuclei. About 30 seconds after intravenous infusion of thiamine, his consciousness improved dramatically, but returned to semi-coma after about two minutes. Wernicke-Korsakoff syndrome usually occurs acutely. In the present case, however, the disease showed slow onset, chronic progression, and then rapid worsening after fever. Reconstructive surgery of the jejunal interposition might have caused the slow onset of Wernicke-Korsakoff syndrome, and fever might have facilitated the rapid progression of the disease. An immediate high concentration of thiamine modifies the kinetics of acetylcholine receptor ion channels, thereby maintaining wakefulness, and the level of consciousness may change dramatically.

Aged↗

A case of aortoduodenal fistula occurring after surgery and radiation for pancreatic cancer.

The patient was a 58-year-old woman given curative treatment (pancreatectomy (body and tail) + intraoperative irradiation (25 Gy)) on the basis of a diagnosis of pancreatic carcinoma. Having a favorable postoperative course, she was discharged 24 days after surgery. A week after discharge, she was readmitted for a hemorrhagic gastric ulcer. She was later discharged again on conservative treatment, and followed up at the outpatient clinic, but nine months postoperatively, was readmitted complaining of loss of appetite and abdominal pain. Subsequent tests revealed stricture of the horizontal portion of the duodenum with distension oral to the stricture. Around the celiac artery, the paraaortic lymph nodes were swollen, and a diagnosis of stricture due to recurrent pancreatic carcinoma was made. On the day before bypass surgery was scheduled, the patient vomited blood, so the operation was postponed, conservative treatment such as blood transfusion was administered, and emergency angiography was performed simultaneously. The findings were an aortic pseudoaneurym 1 cm in diameter immediately below the origin of the superior mesenteric artery and between the left and right renal arteries, and a hemorrhage, caused by an aortoduodenal fistula, issuing from the horizontal portion of the duodenum. Hemostasis via a laparotomy was judged difficult, and so an indwelling stent-graft in the aorta was tried to stanch the blood, but without success. Another stent then had to be inserted within the first, thus stopping the flow, but the blood supply to the celiac artery, the superior mesenteric arteries and the renal arteries was impaired, and the patient died about six hours later. Postmortem examination revealed aortoduodenal fistula without recurrence of the carcinoma. The duodenal wall around the fistulous tract showed delayed radiation changes with deep ulceration. The intraoperative radiation may have played an important part in the formation of the fistula.

Aortic Diseases↗

[Therapeutic effect and clinical findings in patients with MPO-ANCA associated vasculitis syndrome].

We investigated to clarify the clinical findings, course and therapeutic effect in the patients with MPO (myeloperoxidase)-ANCA (anti-neutrophil cytoplasmic antibody) associated vasculitis syndrome. We analyzed clinical findings and data of 19 cases of MPO-ANCA associated vasculitis. These patients were diagnosed with clinical symptoms (fever, arthralgia, body weight loss, etc.), laboratory data (high titer of CRP, leukocytosis, thrombocytosis, and high titer of MPO-ANCA) and pathologic findings of necrotizing vasculitis. They were 14 male and 5 female aged 18 to 84 years (mean 65 years) and were treated with prednisolone and immunosuppressive agents, and additional therapy included pulse therapy and plasma exchange. Seven cases were dead within 3 months. Post-mortum examination showed that these cases died of pneumonitis, cerebral events and gastric bleeding. There was no mortal case induced by over-immunosuppression. In survival cases, the MPO-ANCA levels decreased rapidly after these therapies and these antibodies were maintained low levels (360 to 25 EU/l). Comparison of fatal cases and survival cases, there were difference in the initial dose of prednisolone (27 mg/day vs. 56 mg/day), the ratio of double filtration plasmapheresis (14% vs. 42%), and the ratio of immunosuppressive therapy (14% vs. 83%). The measurement of MPO-ANCA is useful makers of the diagnosis and effectiveness of the therapy in patients with MPO-ANCA associated vasculitis. We recommend the aggressive therapy, including prednisolone, immunosuppressive agents and plasma exchange for MPO-ANCA associated vasculitis. We believe that the aggressive therapy improve the survival rate of the patients with MPO-ANCA associated vasculitis.

Adolescent↗

[Pulmonary infection caused by Mycobacterium gordonae in immunocompetent patient].

We report a case of 67-year-old female immunocompetent patient admitted to our hospital because of hemoptysis. Computed tomography (CT) of the lung showed bronchiectasis in the right S5 and small nodules in the right S6 and left S5. The cultures of sputum and bronchial washing specimen repeatedly revealed acid-fast bacilli identified as Mycobacterium gordonae (M. gordonae) by DNA-DNA hybridization (DDH) method. Thus, she was diagnosed to be infected with M. gordonae. She was treated with isoniazid, rifampicin, ethambutol and streptomycin. After treatment, the cultures of sputum and bronchial washing specimen converted to negative, and the chest CT showed improvement of small nodules. M. gordonae is a nontuberculous mycobacterium of very low pathogenic potency. Recently there have been a few reports of infection by M. gordonae not only in immunocompromised patients but also in immunocompetent patients. These cases were considered to be sensitive to initial standard antimycobacterial therapy, therefore, it is important to examine for M. gordonae in cases suspected of nontuberculous mycobacterial infection.

Aged↗

[Clinical significance of serum p53 antibody detection in a chemosensitivity assay in cases of human colorectal cancer].

Alteration of the p53 gene product occurs frequently during the progression of colorectal cancer. Recently, mutated p53 protein was found to induce the production of anti-p53 antibodies in the serum of patients. The purpose of this study was to evaluate the relationship between p53 status in serum and chemosensitivity in resectable colorectal cancer patients. A total of 35 patients with primary colorectal cancer who underwent surgical treatment were examined by chemosensitivity test with the viable tumor samples using Histoculture Drug Response Assay (HDRA). Serum samples of these patients to test for p53 antibodies were obtained before tumor resection, and assayed in duplicate by using an enzyme-linked immunosorbent assay (ELISA) kit. The inhibition index of 5-FU and CDDP, determined by the HDRA method, in the sero-positive group was significantly lower than that of the sero-negative group (p < 0.01). Furthermore, significant statistical differences in chemosensitivity to 5-FU and CDDP were revealed depending on the presence of serum p53 antibodies. There was no relationship between chemosensitivity assay and tumor marker positivity or clinicopathological features in these patients. Detection of serum p53 antibodies, which reflects p53 mutations in tumor tissue, is a simple method which correlates with chemosensitivity, and may contribute to the selection of favorable chemotherapeutic strategies of colorectal cancer.

Antineoplastic Agents↗

[Clinical effects of trandolapril in chronic glomerulonephritis patients with renal insufficiency].

Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI) whose characteristic is that it undergoes hepatic excretion. ACEI appears to have a specific reno-protective and antiproteinuric role in patients with chronic glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and cause side-effects in patients with renal dysfunction, the pharmacokinetics of trandolapril were not affected by renal dysfunction. We compared the effect of other renally excreted ACEI with those of trandolapril on serum creatinine (s-Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients who switched from another ACEI to trandolapril. Twelve hypertensive patients with chronic renal failure(nine males and three females, ranging from 30 to 72 years of age) who were treated by other renally excreted ACEIs for long periods(2 to 8 years) with some effects on proteinuria and renal function, were enrolled in the present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p < 0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral dose of 1 mg of trandolapril was administered to these patients regardless of their blood pressure status and renal functions. After change to trandolapril therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34 g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to 7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction except for coughing, were observed in these patients. Furthermore, none of the 12 patients treated with trandolapril required discontinuation of the compound. In conclusion, it was shown from this study that trandolapril is effective for the treatment of hypertensive patients with renal insufficiency irrespective of the original diseases. Thus, it can be envisaged that trandolapril is one of the most appropriate agents compared to other renally excreted ACEI for these patients with renal insufficiency. We recommend the change from other ACEIs to trandolapril, when renal dysfunction might be due to ACEI accumulation.

Adult↗

[A case of pulmonary tuberculosis complicated with multiple bone and joint tuberculosis].

A 29-year-old male complaining of fever and general fatigue was admitted to our hospital. On admission chest X-ray showed infiltrative shadows with cavities in the bilateral lung apical areas, and sputum examination for acid fast bacilli was smear positive, Gaffky 1. He was treated as pulmonary tuberculosis (TB), and chest X-ray findings and sputum examination improved after a few months of treatment with antituberculous chemotherapy (INH, RFP, EB, PZA). However, tuberculous cold abscess appeared in retropharyngeal area, subcutaneous tissue of thoracic cage and retroperitoneal space, and shortly later, bone and joint TB were recognized in shoulder and wrist joints and vertebrae. The findings of vertebral foci were not recognized by a simple X-ray picture of vertebrae. at that time, but MRI of vertebrae showed low intensity areas with ring enhancement in the cervical, thoracic and lumbar vertebrae. Despite treatment with antituberculous agents, new bone and joint TB had developed in many tissues and had accompanied with cold abscess in adjacent tissue, whereas pulmonary TB had improved after the initial transient worsening. The appearance of bone and joint TB was most probably caused by the initial transient worsening of hidden bone and joint TB as a part of the initial systemic transient worsening of tuberculosis. After treatment for 4 months, pulmonary TB as well as bone and joints TB had improved. Tuberculous cold abscess in retropharyngeal may be secondary to cervical vertebral TB but is now rarely seen. In this case, involvement in many tissues such as retropharyngeal area, subcutaneous tissue of thoracic cage and retroperitoneal space were seen, and these findings are now uncommon and usually represents involvement secondary to contiguous infection.

Adult↗