[Clinical issues in gerontopsychiatry].
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Aged↗
Biomedical subjects
T Nishimura
Publications and source records attributed to T Nishimura.
[Interaction between Epstein-Barr virus (EBV) gene expression and antibodies to EBV in nasopharyngeal carcinomas].
In situ hybridization using EBERs and BHLF oligonucleotide probes and immunohistochemistry using monoclonal antibodies against LMP1, EBNA2, BZLF1 protein, p53 protein and bcl-2 protein were performed on 56 primary nasopharyngeal carcinomas. EBERs was detected in 46 cases (82%), and LMP in 17 cases (30%), but EBNA2 was not detected. While 30 of 32 cases (94%) in differentiated non-keratinizing carcinoma (NKC) and 16 of 17 cases (94%) in undifferentiated carcinoma (UNPC) showed EBERs, neither 5 cases of squamous cell carcinoma (SCC) nor 2 cases of adenocarcinoma showed EBERs. This finding confirms latent infection of EBV, especially phenotypical latency II, in NKC and UNPC but not in SCC. Bcl-2 protein was positive in 50 cases (89%), but its expression did not depend on expression of LMP1, which did not demonstrate induction of bcl-2 by LMP1 as seen in vitro. Cytoplasmic BZLF1 expression was detected in 18 cases (32%) whereas BHLF was positive only in 6 cases (11%). This suggests dysfunction of BZLF1, which disrupts viral latency despite its expression. p53 protein was positive in 31 cases (55%), and there was a distinct correlation between expression of BZLF1 and p53 protein (p < 0.001). This suggests that the interaction between BZLF1 protein and p53 protein, which inactivate each other, is one of the tumorigenic factors in NPC.
Adolescent↗
Cerebral hypoperfusion in orthostatic hypotension with globally denervated myocardium.
A 57-yr-old woman had frequent syncope when rising from a seated position. Her blood pressure fell from 140/80 mmHg to 60-70/40 mmHg while changing positions. Iodine-123-metaiodobenzylguanidine ([123I]MIBG) did not accumulate in the heart, whereas 201Tl-Cl (201Tl) did. Raise-up 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) brain SPECT revealed decreased activity in the bilateral frontal areas, and subsequent supine 99mTc-HMPAO brain SPECT revealed filling in these areas, indicating that the cerebral blood flow (CBF) was transiently decreased in the frontal areas more than others in a standing position. The plasma norepinephrine (NE) level of this patient was normal during supine rest, but when she stood up, failure to increase the plasma level of NE uncovered a sympathetic nervous dysfunction. The CBF abnormality in patients with orthostatic hypotension may be due to a "functional" hemodynamic mechanism that induces orthostatic stress. This patient had transient hypoperfusion in the frontal areas when standing, without organic cerebral arterial stenosis. Only CBF in the frontal areas revealed relative hypoperfusion. These regions might be highly susceptible to a change in blood flow. The causes of orthostatic hypotension of this patient were autonomic failure with a disturbance of the sympathetic nerve endings, which was revealed by 99mTc-HMPAO brain SPECT and cardiac [123l]MIBG imaging.
3-Iodobenzylguanidine↗
[A case report of a distal posterior cerebral artery (P3) aneurysm, not accessible through a subtemporal approach].
A case of a ruptured aneurysm located in the P3 portion of the posterior cerebral artery (PCA), which was not accessible through a subtemporal approach, was reported. In addition to the case presented here, alternative operative approaches to the distal P3 portion or higher ambient cistern were reviewed and discussed. A 64-year-old man was admitted because of sudden onset of headache. CT scan disclosed SAH which was recognized mainly in the left ambient cistern with intraventricular bleeding (Fisher Group 4, Hunt and Kosnik Grade 2). A left vertebral angiogram disclosed a small saccular aneurysm in the distal P3 portion of the left PCA, which was located as highly as the plexal point of the anterior choroidal artery. On day 4, neck clipping was tried via the left subtemporal approach. The distal P3 aneurysm, however, could not be reached by this approach, in spite of aspiration of the parahypocampal gyrus. On day 7, the patient died of massive bleeding from a Cushing ulcer. It was considered that an occipital interhemispheric approach might have been more suitable in the present case.
Aneurysm, Ruptured↗
[Indocyanine green angiography of choroidal neovascularization in age-related macular degeneration].
One hundred forty eyes with choroidal neovascularization (ChNV) in age-related macular degeneration were examined with fluorescein and indocyanine green (ICG) angiography. ChNVs covered with subretinal hemorrhage, and ChNVs with retinal pigment epithelial (RPE) detachment were demonstrated at a higher rate and more clearly with ICG angiography than with fluorescein angiography. On the other hand, ChNVs in serous retinal detachment, and in disciform lesions were demonstrated more clearly with fluorescein angiography than with ICG angiography. These results show that ICG angiography is valuable for delineating "occult ChNVs" with subretinal hemorrhage or RPE detachment in age-related macular degeneration.
Aged↗
Pharmacokinetics of radioiodinated fatty acid myocardial imaging agents in animal models and human studies.
Since the oxidation of long chain fatty acids is the major pathway for energy production for the normoxic myocardium, the use of radiolabeled fatty acids for myocardial imaging continues to be a major area of both basic and clinical research. This paper focuses on a discussion of the kinetics of myocardial uptake of radioiodinated fatty acids, including planar and SPECT imaging of various iodine-123-labeled analogues, and data from animal and isolated heart studies, and where possible, comparison with results of clinical studies. Key examples include iodoalkyl-substituted straight chain fatty acids such as 17-IHDA (17-iodoheptadecanoic acid). These analogues are rapidly metabolized in the myocardium, resulting in release of free radioiodide, and can only be practically used for planar imaging. Terminal iodophenyl-substituted fatty acids illustrate a successful approach of stabilizing radioiodine to overcome the release of free iodide encountered with the straight-chain analogues. These analogues, exemplified by p-IPPA [15-(p-iodophenyl)pentadecanoic acid], are widely used in clinical practice. Although washout can be delayed by increase in the arterial lactate levels by mild exercise, SPECT imaging must still be carefully timed. In contrast to these examples, the ortho iodide-substituted IPPA isomer (ortho- instead of para-phenyl substitution of radioiodide) is a unique example which shows rapid myocardial washout in laboratory animals but nearly irreversible retention in humans. Introduction of methyl-branching is a major important approach which has been successfully used to alter tracer kinetics of radioiodinated fatty acids by increasing myocardial retention. A key example in this class of compounds is 3-(R,S)-BMIPP [15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid], an analogue of p-IPPA in which methyl-branching has been introduced into the beta-position of the carbon chain. Although tracer washout is significantly delayed with this structural perturbation, a large number of clinical studies have shown that slow myocardial washout is still observed. Detailed biochemical studies with radioiodinated 3-BMIPP have demonstrated that initial alpha-oxidation produces a metabolite that can then be catabolized by alpha-oxidation. An unexpected and important observation with the (123I]-3-(R,S)-BMIPP agent has been the mis-match between perfusion tracer distribution and the regional BMIPP distribution which has been widely observed in jeopardized, but viable myocardial regions. Another example in the methyl-branched series is DMIPP [15-(p-iodophenyl)- 3,3-dimethylpentadecanoic acid], which has very prolonged myocardial retention and slow washout kinetics although only animal studies have been reported with this agent. Still another more recent approach has been the synthesis and laboratory animal and human evaluation of analogues containing a phenylene bridge in the fatty acid chain. One example is 3-10 [13-(4'-iodophenyl)]-3-(p-phenylene)tridecanoic acid (PHIPA 3-10), which has also proven successful in delaying myocardial tracer washout. This paper focuses on a discussion of the effects of molecular structure on the myocardial uptake and release of these various radioiodinated fatty acid analogues.
Animals↗
Ischemic and reperfused myocardium detected with technetium-99m-nitroimidazole.
UNLABELLED: To evaluate the utility of 99mTc-labeled nitroimidazole (BMS) in the detection of ischemic or reperfused myocardium, we performed dual-tracer autoradiography with BMS and [125I]iodoantipyrine (IAP). METHODS: In open-chest rats, the left coronary artery was ligated to produce 15- or 60-min ischemia followed by reperfusion or 60-min ischemia without reperfusion. BMS was injected just before ligation, 1 min before reperfusion or 15 min after reperfusion. RESULTS: In the area at risk, regional myocardial blood flow (rMBF) evaluated by IAP recovered to the level in the nonischemic septum in all hearts, except in 60-min occlusion without reperfusion. In myocardium reperfused after 15-min ischemia (stunned), normalized BMS uptake (%BMS) in the area at risk was significantly increased only when BMS was injected before ischemia. When BMS was injected before 60-min ischemia or just before reperfusion, %BMS was significantly higher at the marginal zone of infarction than in the infarcted area. In contrast, %BMS was significantly lower in the infarcted area when BMS was injected during reperfusion. After 60 min of occlusion without reperfusion (permanent occlusion), rMBF in the area at risk was significantly decreased as was %BMS. In the peripheral zone of the area at risk, rMBF was significantly reduced, but %BMS was significantly increased. CONCLUSION: BMS images stunned myocardium only when it is injected before ischemia, while it images the area at risk subjected to prolonged ischemia when it is injected up to the time of reperfusion. The infarcted area can be negatively visualized when BMS is injected after reperfusion.
Animals↗
Visualization of ischemic insult in caudate putamen with beta-CIT.
UNLABELLED: Dopamine (DA) has been considered to play an important role in the development of ischemic neuronal injury in the caudate putamen (CPu). The goal of this study was to examine the change in the dopamine transporter (DAT) after ischemic insult in CPu. METHODS: Male Mongolian gerbils (n = 10) were exposed to 10-min forebrain ischemia. Animals were decapitated 24 hr (n = 5) and 96 hr (n = 5) after ischemia. The change in the amount of DAT binding sites in CPu was evaluated by in vitro autoradiography with [125I]-beta-CIT (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester). In addition, the expression of DAT mRNA in CPu and the substantia nigra pars compacta (SNC) was examined. RESULTS: Iodine-125-beta-CIT specific binding was significantly increased in dorsolateral CPu with ischemic damage both 24 hr and 96 hr after ischemia, with greater increase at 96 hr. DAT mRNA in SNC was also significantly increased 96 hr after ischemia, which corresponded with the increase of [125I] beta-CIT binding. However, DAT mRNA in SNC was decreased 24 hr after ischemia. In the ischemic lesion in CPu, no expression of DAT mRNA could be detected both 24 hr and 96 hr after ischemia. CONCLUSION: The change in DAT after ischemic insult is clarified with [125I] beta-CIT. This increase of [125I] beta-CIT binding does not come from de novo expression of DAT in glial cells in the damaged area in CPu. This increase of beta-CIT binding reflects increase of DAT synthesis in DA neurons in SNC (96 hr) or other factors such as the impairment of the degradation of DAT in the damaged area in CPu.
Animals↗
[Computed tomographic findings in septic pulmonary emboli secondary to renal abscess].
A 73-year-old woman with diabetes mellitus and hypothyroidism had been well until 4 days before she presented with fever, productive coughing, and general malaise. Dyspnea gradually worsened, and she was admitted to Kobe City General Hospital. She appeared toxic and was in moderate respiratory distress on admission. There were scattered rales in both lung fields. The abdomen was soft with no tenderness. A chest roentgenogram showed peripheral infiltrates in both lung fields. Arterial blood gas analysis showed a Po2 of 48.6 Torr and Pco2 of 27.2 Torr. A blood culture on admission showed Escherichia coli. Computerized tomography of the chest showed multiple nodules of various sizes in the peripheral lung fields. Some nodules had necrotic centers and feeding vessels. Wedge-shaped lesions abutting the pleura were also seen. These findings strongly suggested septic pulmonary emboli. An abscess in the left kidney, which was considered to be the source of the septic pulmonary emboli, was found with Ga scintigraphy, ultrasonography, and computerized tomography of the abdomen. Treatment with antibacterial drugs was effective against the lung lesions but not the renal abscess. A left nephrectomy was done. In the proper clinical setting, characteristic CT features of septic emboli can contribute to early diagnosis of this disease.
Abscess↗
[Clinical evaluation of azithromycin in pediatric infections].
Azithromycin (AZM) was studied for its clinical efficacy in pediatric infections. The study on AZM was carried out in 43 patients whose diagnoses were given as follows: pharyngitis in five cases, tonsillitis in one, bronchitis in four, pneumonia in four, Mycoplasma pneumonia in 14, scarlet fever in nine, impetigo in four, pyodermia in one and Campylobacter enteritis in one. The patients received AZM once daily at 1.6 approximately 20.0 mg/kg body weight for three to five days. Effectiveness of AZM was evaluated in 39 cases and the drug was rated "excellent" in 15, "good" in 19, "fair" in one, "poor" in four, resulting in an efficacy rate of 87.2%. Twenty bacterial isolates were identified as causative isolates in 19 patients: Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Campylobacter jejuni and Mycoplasma pneumoniae. AZM eradicated 16 isolates but four persisted after therapy. One patient complained of loose stool, while two patients were found with decreases in white blood cell counts, and seven showed increases in eosinophils. However, no serious case of adverse event was reported.
Administration, Oral↗
[Muscular dystrophies].
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Cardiomyopathies↗
Tonsillar focal infection: clinical observations of low grade fever.
Thirty patients (above 18 years) who had complained of low grade fever were diagnosed as having tonsillar focal infection. We performed tonsillectomies on all the patients. A total of 24 were cured and 6 patients improved after the operation. These results indicate that tonsillectomy is often an effective treatment for tonsillar focal infection. However, the provocation test did not always give a good result.
Adult↗
Effect of surgery on obstructive sleep apnea.
The statistical analysis of data obtained by monitoring pre- and post-operative conditions of patients treated for sleep apnea syndrome is reported. In the past 3 years, surgery was performed on 149 patients (55 children and 94 adults), who complained of snoring and symptoms related to the sleep apnea syndrome at Fujita Health University, The Second Hospital. Treatment for children was adeno-tonsillectomy. Treatment for adults was uvulo-palato-pharyngoplasty (UPPP), midline laser glossectomy (MLG) and/or nasal surgery. Apnea hypopnea index was defined as frequency of apnea hypopnea per hour. Pathological apnea (sleep apnea syndrome) was defined as apnea hypopnea (AHI) 10 in adults and AHI 5 in children. Marked improvement was defined as 75% reduction in AHI or a postoperative AHI below 10 in adults and 5 in children. Improvement was defined as 50-74% reduction of AHI. Slight improvement was defined as 25-49% reduction of AHI. No improvement was defined as less than 25% reduction of AHI. Of these 55 children, the AHI of 35 of them was above 5. Thirty cases (86%) showed marked improvement after treatment; 3 cases (8%) showed improvement; 1 case (3%) slight improvement and 1 case (3%) no improvement. Of these 94 adults, 40 cases (48%) showed marked improvement after treatment; 12 cases (14%) showed improvement; 14 cases (17%) slight improvement and 18 cases (21%) no improvement at all.
Adenoidectomy↗
Diagnosis by dynamic MRI in sleep disordered breathing.
According to the obstructive site, different types of obstructive type sleep disordered breathing are classified as the soft palate type, palatine tonsil type, soft palate and depressed lingual root type, depression of the lingual root type, and epiglottis type. In this study, we conducted dynamic MRI examinations of the oral and pharyngeal and lingual root sites in patients with obstructive sleep disordered breathing, and studied MRI's usefulness as a diagnostic tool in the examination of such obstructive sites. In this paper, we present mainly the adult cases of patients with obstructive sleep disordered breathing which appeared to be caused by an enlarged palatine tonsil.
Humans↗
Immunohistochemical staining for glutathione S-transferase predicts response to platinum-based chemotherapy in head and neck cancer.
The glutathione S-transferases (GSTs) play an important role in the cell's defense against toxic substances. The GSTs are a family of enzymes produced by several genes that interact with distinct but overlapping substrates and that may play a role in resistance of tumor cells to several chemotherapeutic agents. We examined the correlation between expression of GSTs determined by immunohistochemistry and clinical response to platinum-based chemotherapy in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (complete response + partial response) for patients with low GST scores was 88% (21 of 24), whereas among the patients with high GST scores, the overall response rate was 19% (6 of 32; P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 23 patients treated with neoadjuvant chemotherapy, the overall response rate for patients with low GST scores was 100% (14 of 14), whereas among the patients with high GST scores, the overall response rate was 44% (4 of 9; P = 0.002). Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST scores was 70% (7 of 10), whereas among the patients with high GST scores, the overall response rate was 8.6% (2 of 23; P < 0.001). We conclude that GST expression correlates well with response to platinum-based chemotherapy in head and neck cancer.
Antineoplastic Agents↗
Immunohistochemical investigation of tau-positive structures in the cerebral cortex of patients with progressive supranuclear palsy.
We have investigated tau-positive structures immunohistochemically in the cerebral cortex of patients with progressive supranuclear palsy (PSP). In addition to neurofibrillary tangles, a variety of tau-positive structures occur. They are particularly abundant in the precentral gyrus and other frontal cortices. Double immunostaining has demonstrated that coil-like structures (coiled bodies) are located in the oligodendroglial cell bodies. Three forms of tau-positive astrocytic inclusions are discerned: those with tuft-like profiles, thorn-like structures, and concentric clusters of short stubby fibers. The concentric clusters of tau-positive fibers are present in some, but not all, PSP brains. They appear to be identical to 'astrocytic plaques' previously reported in patients with corticobasal degeneration (CBD). PSP and CBD might share a common pathological background which causes abnormal accumulation of tau protein in neurons and glial cells of neuroectodermal origin.
Aged↗
Fas antigen expression in brains of patients with Alzheimer-type dementia.
Fas antigen (CD95) is a cell surface protein that mediates apoptosis. We have investigated the immunohistochemical localization of Fas antigen in postmortem brain tissue from control subjects, patients with Alzheimer-type dementia (ATD), and from a few patients with diffuse Lewy body disease, progressive supranuclear palsy and adrenoleukodystrophy. In all brains, including controls, vascular endothelial cells and residual blood plasma were weakly stained. In ATD brains, senile plaques and a small number of star-like cells were brains of patients with neurological diseases other than ATD. In double immunostaining for Fas and glial fibrillary acidic protein (GFAP), a small number of cells were positive for both antigens. The majority of Fas-positive astrocytes were, however, negative for GFAP. This implies the downregulation of GFAP production in these cells. Doubly labeled astrocytes were also found around senile plaques, suggesting that the Fas immunoreactivity in senile plaques was derived from astrocytic membranes. The results of this study indicate that Fas antigen is expressed by a subset of reactive astrocytes in degenerative neurological diseases. Such astrocytes may undergo the Fas-mediated apoptotic process.
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