Vogt-Koyanagi-Harada disease masquerading anterior ischaemic optic neuropathy.
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Biomedical subjects
Publications and source records attributed to N Yoshimura.
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AIM: To determine whether mutations in the Stargardt's disease gene, ATP binding cassette transporter retina (ABCR) affect the occurrence of age related macular degeneration (AMD) in Japanese non-familial patients. METHODS: 80 unrelated Japanese patients with AMD (67 males and 13 females; mean age, 67.2 years) diagnosed by indocyanine green angiography and 100 age matched control subjects were studied. Among the AMD patients, 70 (87.5%) had choroidal neovascularisation of exudative type. Genomic DNA was purified from the total blood and 10 exons (exons 11, 23, 29, 32, 34, 37, 41, 43, 44, and 49) that have been reported to contain AMD associated mutations were amplified by polymerase chain reaction (PCR). The amplicons were analysed by the single strand conformation polymorphism (SSCP) method. The nucleotide sequencing of the amplicons was determined when necessary. RESULTS: Of the 10 exons, aberrant patterns of SSCP were detected in three exons-exons 29, 41, and 43. In exon 29, an aberrant pattern was found in seven of 80 patients (8.8%) and eight of 100 controls (8%). Sequencing of the PCR products revealed a heterozygous T1428M mutation which has been previously reported as one of the AMD associated mutations. Statistical analysis showed that there was no significant difference in the occurrence of this mutation between these AMD patients and the control groups (p = 0.86). In exons 23, 41, and 43, polymorphisms and sequence variations were found. CONCLUSION: No data to support the association between the ABCR gene mutations and AMD of Japanese patients, especially that of the exudative type, were obtained in this molecular genetic analysis.
To determine whether the nocturnal decrease in arginine vasopressin (AVP) secretion into the plasma, found in a patient with multiple system atrophy (MSA) reported previously, is a usual finding in MSA, the plasma AVP concentrations in 13 patients with MSA were measured every 4 hours during a 24 hour period. The plasma AVP concentrations in these patients showed significant daily variations and were the lowest during the night. This finding indicates that patients with MSA often exhibit nocturnal decrease in AVP secretion into the plasma. The results suggest the possibility that the system responsible for the daily variations in AVP secretion is involved in MSA.
The onset of reperfusion and the recovery of the ERG b-wave following retinal ischemia was examined among three groups of rats: group 1 (n = 12) and group 2 (n = 6) received pretreatment with NG-nitro-L-arginine (20 mg/kg, i.p., 2 h before ischemia) followed by intravenous injection of saline (group 1) or of 200 mg/kg L-arginine (group 2) 5 min before the end of ischemia; group 3 (n = 7) received saline pretreatment followed by intravenous injection of saline as a control. Group 1 showed delayed onset of reperfusion compared to the other two groups and a reduction in the rate of the b-wave recovery compared to the control on the 1st day after reperfusion (group 1 vs. group 3; p = 0.0357). The L-arginine posttreatment significantly increased the b-wave recovery (group 2 vs. group 1; p = 0.0005 on day 1 and p < 0.0006 on day 3). The rate of the b-wave recovery in group 1 was inversely proportional to the time to establish complete reperfusion. Inhibition of nitric oxide synthase during the initial phase of reperfusion may worsen the recovery of the b-wave following retinal ischemia, at least in part, by inhibiting establishment of reperfusion.
We identified a new point mutation in the CYP19 gene responsible for aromatase (P450arom) deficiency in a 46,XY male infant with unremarkable clinical findings at birth. This boy is homozygote for a 1-bp (C) deletion in exon 5 of the aromatase gene causing a frame-shift mutation. The frame-shift results in a prematurely terminated protein that is inactive due to the absence of the functional regions of the enzyme. Aromatase deficiency was suspected prenatally because of the severe virilization of the mother during the early pregnancy, and the diagnosis was confirmed shortly after birth. Four weeks after birth, the baby boy showed extremely low levels of serum estrogens, but had a normal level of serum free testosterone; in comparison with the high serum concentration of androstenedione at birth, a striking decrease occurred by 4 weeks postnatally. We previously reported elevated basal and stimulated FSH levels in a female infant with aromatase deficiency in the first year of life. In contrast, in the male infant, basal FSH and peak FSH levels after standard GnRH stimulation tests were normal. This finding suggests that the contribution of estrogen to the hypothalamic-pituitary gonadotropin-gonadal feedback mechanism is different in boys and girls during infancy and early childhood. In normal girls, serum estradiol concentrations strongly correlate with circulating inhibin levels, and thus, low inhibin levels may contribute to the striking elevation of FSH in young girls with aromatase deficiency. In contrast, estradiol levels are physiologically about a 7-fold lower in boys than in girls, and serum inhibin levels remain elevated even though levels of FSH, LH, and testosterone are decreased.
It is well known that cyclosporin, rapamycin and FK-506 (tacrolimus) are metabolized by the liver microsomal cytochrome P450 enzyme system. Although there have been reports of interaction between these drugs and the renal P450 enzyme system, differences among these immunosuppressants has not been comprehensively demonstrated. We have studied the individual capacities of these immunosuppressants to induce renal microsomal P450 enzymes similar to CYP2B4 and CYP4A2 by examining renal function in treated rats, and have correlated the results by means of biochemical, immunological and immunohistochemical assays of renal P450 enzymes. Cyclosporin caused impairment of renal function with an increase in renal-specific P450 content, but FK-506 and rapamycin did not. Laurate omega- and (omega-1)-hydroxylase activity increased in rats treated with rapamycin but decreased in those treated with FK-506. Prostaglandin A1 (PGA1) omega-hydroxylase activity increased in rats treated with FK-506 but was reduced by treatment with cyclosporin. Aminopyrine N-demethylase activity increased in rats treated with cyclosporin or FK-506, but not in those treated with rapamycin. Western-blot analysis revealed significant induction of P450, (similar to CYP2B4 of the rabbit P450 isozyme) in kidneys from rats treated with cyclosporin but not in those from rats receiving FK-506 or rapamycin. Histochemical studies clearly demonstrated a form of P450 such as CYP4A2 in the proximal tubules of rats treated with cyclosporin, but not in those of rats treated with FK-506 or rapamycin. These results show that although cyclosporin has a strong effect on renal P450 systems and induces such a system in kidney cortex (microsomal P450), FK-506 and rapamycin have no substantial effect on the induction of renal P450. These findings might clarify the nephrotoxicity induced by these immunosuppressive drugs.
A seven-year-old boy with tricuspid atresia successfully underwent a fenestrated total cavopulmonary connection and mitral valvuloplasty. Preoperative cardiac catheterization showed a mean pulmonary artery pressure of 16 mmHg. Pulmonary arteriography showed poor development of the branches (PA index: 180). Echocardiography revealed mild to moderate mitral valve incompetence due to prolapse of anterior leaflet. Mitral valve was exposed through the trans-septal approach. The excess chorda length was tucked into a longitudinal split in the top of the posterior papillary muscle. Then wedge resection of the redundant segment of the anterior leaflet and bilateral annuloplasty were performed. Finally, a total extracardiac cavopulmonary anastomosis with a 6 mm fenestration was completed. Postoperative clinical course was uneventful, and he is doing well with no recurrence of mitral incompetence 1 year after the operation.
A 23-year-old woman who was in the ninth month of pregnancy suffered a head injury by falling from the stairs. She regained consciousness in the ambulance car, however, could not recall anything about herself. The morning after, her neurological examination disclosed no abnormal findings. She was alert, spatially oriented, but unable to recall any personal information about herself, her work and family contexts. The results of WAIS-R and WMS were within normal range, and she showed a dissociation between a detailed knowledge of public events and famous people and a complete loss of autobiographic information. EEG and brain MRI were normal. Memory loss spontaneously recovered following several months, and 8 month later, the retrograde amnesia had almost resolved. Although it is well-known that autobiographic amnesia usually attributed to psychogenic etiology, the differential diagnosis of the similar selective retrograde amnesia by organic etiology is important.
PURPOSE: The aim of this study was to identify a method to determine whether segmental artery reconstruction was indicated during aortic clamping. METHOD: Spinal cord evoked potential (SCEP) and regional spinal blood flow were studied in 24 adult dogs. Using the left heart bypass technique, aortic clamping divided the aorta into thoracic, abdominal, and terminal segments. After the occlusion of the descending aorta and discontinuation of the perfusion to the abdominal segment, animals were assigned to four groups: no treatment with perfusion to the terminal aorta (group IA), no treatment with cessation of bypass (group IB), 5% lidocaine administration (5 mg/kg) into the abdominal segment with perfusion to the terminal aorta (group IIA), and lidocaine administration with cessation of bypass (group IIB). RESULTS: Cessation of bypass reduced spinal blood flow and SCEP amplitude. Lidocaine injection allowed for a significant rapid decrease in SCEP amplitude in group IIB compared with group IB (24.2% +/- 13.4% versus 92.3% +/- 33.2%; p = 0.0039). The degree of spinal blood supply was reflected immediately in the magnitude of SCEP amplitude change by the direct lidocaine injection. (group IB versus group IIB; p = 0.023). CONCLUSION: The direct injection of lidocaine into the clamped aorta results in a rapidly change in SCEP in the threat of ischemia and can be used to make an early detection of the segmental arteries perfusing to the spinal cord.
BACKGROUND: The choice of palliative procedure for neonates with congenital cyanotic heart defects remains controversial. Several reports have questioned whether the classic Blalock-Taussig shunt is adequate in neonates, because it shows a high rate of mortality and early shunt failure. The purpose of this study is to evaluate the early and late results of classic Blalock-Taussig shunt in neonates. METHODS: From December 1981 to December 1996, 31 neonates underwent a classic Blalock-Taussig shunt. Mean age at operation was 15.9 days (range, 2 to 28 days), and mean body weight was 3214 g (range, 2229 to 4468 g). The major diagnoses were pulmonary atresia with intact ventricular septum (6 patients) and with ventricular septal defect (4), univentricular heart (6), tricuspid atresia (5), tetralogy of Fallot (4), transposition of the great arteries (3), and double outlet right ventricle (3). RESULTS: There were no early deaths. There was one early shunt failure. The patient underwent a replacement of Blalock-Taussig shunt by vascular graft on the 1st postoperative day. Two patients with non-confluent central pulmonary artery underwent a contralateral modified Blalock-Taussig shunt on the 22nd and 42nd postoperative day, respectively. There were two late deaths before the definitive repair was performed. Twelve patients required an additional shunt operation. The mean interval between the initial and the second shunt procedure was 27.7 months (range, 6 to 67 months). Ten patients underwent definitive operation and the mean interval to that procedure was 55.5 months (range, 14 to 121 months). Shunt patency was 94.7+/-5.1% at 3 years. The freedom from cardiac event (cardiac deaths or repeat shunting procedure) was 80.5+/-7.1% at 1 year and 54.9+/-9.4% at 3 years. CONCLUSIONS: The classic Blalock-Taussig shunt has a low operative mortality and has provided excellent long-term palliation in the neonate. We conclude that a classic Blalock-Taussig shunt should be considered a reasonable choice in neonates requiring a palliative procedure for congenital cyanotic heart defects.
From 1989, 4 patients underwent bilateral enlargement of the aortic valve ring for valve replacement. Age at the operation ranged from 2 to 8 (mean 6) years; body weight ranged from 14.9 to 25.4 (mean 19.0) kg. This procedure enabled us to implant a prosthesis 3 to 4 sizes larger (19 to 23 mm) than that measured with the native aortic annulus (13 to 17 mm). There was no late death and no cardiac event over a mean follow-up period of 6.2 years. Pressure gradient across the prosthesis measured by echocardiography was 40 mmHg in 1 patient who underwent aortic valve replacement with the use of 19 mm St. Jude Medical valve at 2 years of age. There was no significant pressure gradient in other 3 patients. All patients showed normal left ventricular function. We conclude that bilateral enlargement of the aortic valve ring for valve replacement has provided good midterm results with no mortality and no cardiac event.
We report a 10-year-old girl with a right coronary artery-right atrial fistula and aneurysm formation. The proximal orifice was closed from the inside of the aneurysm, and the distal orifice through the right atrium under cardiopulmonary bypass. On the 9th postoperative day, myocardial infarction developed due to thrombosis in the fistula stump and the dilated coronary artery. Thrombosis may have been induced by postoperative dehydration and inadequate anticoagulant therapy. It is important to minimize a fistula stump and to strictly administer postoperative anticoagulant therapy.
A 70-year-old male with renal cell carcinoma extending into the retrohepatic inferior vena cava was scheduled for radical nephrectomy with vena caval resection under general anesthesia. He had received partial gastrectomy for gastric cancer twelve years before. Computed tomography and inferior vena cavography confirmed that the vena cava was almost completely occluded and that a collateral venous network was well established. It was considered that the surgical approach to the retrohepatic cavals area was technically very difficult, and that there was a high possibility of a pulmonary embolus during the surgical manipulation. To prevent a pulmonary embolus and get good control of the vena cava above the tumor and below the hepatic vein, we decided to use a partial cardiopulmonary bypass (CPB) until the vena cava was clamping above the tumor. Anesthesia was induced with propofol and fentanyl, and maintained with fentanyl and isoflurane-N2O-O2. In the partial CPB blood from the hepatic vein was drained from the inferior vena cava cannula through right atrium, oxygenated by microporus membrane oxygenator, and returned to the left femoral artery. Cannulation to drain the venous circulation entering the vena cava below the tumor was abandoned because the extensive collateral venous network ultimately drains into the superior vena cava. The partial CPB time was 90 min, and the bladder temperature during the CPB was 35-36 degrees C. During the 7.3 hr procedure, the pulmonary embolus did not occur and the total blood loss was 5515 ml. The patient made an uncomplicated recovery and was discharged 30 days after the operation. This newly reported partial-CPB method may be safe and effective for the management under anesthesia of other patients.
PURPOSE: To determine whether an angiogenic inhibitor, TNP- 470 (TNP), an analogue of fumagillin, inhibits choroidal neovascularization (CNV) induced by diode laser photocoagulation in a rat experimental model. METHODS: Fundus laser photocoagulation was performed on Brown Norway rats to induce CNV. In the treatment group, TNP was administered intraperitoneally at the time of laser photocoagulation and on day 7 (50 mg/kg at each time). The incidence of CNV formation was evaluated by fluorescein angiography. The retina was collected from the rats on days 1, 3, 7, and 14 after laser photocoagulation, and semiquantitative polymerase chain reaction (PCR) analyses for the expression of mRNA of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were carried out. Localization of bFGF mRNA was studied by in situ reverse transcription-PCR (RT-PCR). The numbers of positively labeled cells for bFGF mRNA were compared between the TNP treatment and control groups. RESULTS: The incidence of CNV formation was 22.7% in the TNP-treated rats and that in the control rats was 61.4% (P < 0.001). The semiquantitative PCR analyses showed that bFGF mRNA was upregulated on days 3 and 7 in the control rats, but no significant changes were found in TNP-treated rats. There was no detectable difference in VEGF gene expression between the control and TNP-treated rats. bFGF mRNA was detected by in situ RT-PCR in the regenerated retinal pigment epithelial cells and cells of the outer and inner nuclear layers of the control rats. The number of positive cells for bFGF mRNA in the TNP treatment group was significantly smaller than that of the control group (P < 0.05) on days 3 and 14. CONCLUSIONS: TNP- 470 treatment reduced the incidence of laser-induced CNV formation in this experimental model. The expression of bFGF associated with CNV formation was also significantly reduced by the TNP treatment.
PURPOSE: To study the role of caspase-like proteases, especially roles of more extensively characterized caspase-1 and caspase-2, in apoptotic photoreceptor cell degeneration in Royal College of Surgeons (RCS) rats. METHODS: Both RCS and Sprague-Dawley rats were used. Cryosections of the retinas at various postnatal times were immunostained with antibodies against caspase-1 (interleukin-1beta-converting enzyme, ICE) and caspase-2 (Nedd2/Ich-1). Double staining with TdT-dUTP terminal nick-end labeling (TUNEL), propidium iodide, and the antibodies was also performed. To evaluate the time course of protein expression, western blot analysis was carried out. The temporal profile of caspase-like protease activity was studied using a fluorogenic tetrapeptide substrate, acetyl-tyrosyl-valyl-alanyl-aspartic acid alpha (4-methyl-coumaryl-7-amide) (Ac-YVAD-MCA). Intravitreal injection of a caspase-1 inhibitor, acetyl-tyrosyl-valyl-alanyl-aspartic-aldehyde (Ac-YVAD-CHO), at postnatal days 21 (P21) and P26 was performed to see if this caused a decrease in apoptotic cell number at P28. RESULTS: TUNEL-positive photoreceptors of RCS rats stained strongly with antibodies against caspase-1 and caspase-2. Double staining studies revealed that caspase-1 and caspase-2 were coexpressed in apoptotic cells. Western blot analysis showed that active forms of caspase-1-like and caspase-2-like proteases were upregulated at P28, concurrent with the peak in TUNEL-positive cells. The enzymatic activity of caspase-1-like protease was elevated in RCS rat retinas at P28, and the inhibitor of caspase-1 transiently reduced the number of the apoptotic photoreceptors. CONCLUSIONS: Activation of caspase-like proteases plays an important role in photoreceptor apoptosis of RCS rats.
We report a case of drug-induced pneumonitis associated with the herbal medications Sho-saiko-to and Ouren-gedoku-to. A 62-year-old man experienced fever and dry cough after using Ouren-gedoku-to for 2 months. He was admitted to our hospital because a subsequent 5-day course of Sho-saiko-to for suspected bronchitis aggravated these symptoms and caused exertional dyspnea. Chest X-ray films revealed a ground-glass appearance in both lower lung fields. Cessation of these medications improved the patient's clinical and X-ray findings. Bronchoalveolar lavage showed an increase in lymphocytes with a decreased CD 4/CD 8 ratio. While drug-induced lymphocyte stimulation tests gave negative results, challenge tests for Ouren-gedoku-to and Sho-saiko-to were both positive. A diagnosis of drug-induced pneumonitis was made. Our findings suggested the involvement of Ougon, the only common ingredient in the two medications.
A 68-year-old man was admitted to our hospital with complaints of fever, cough, and shortness of breath. He had several erythematous maculae on the trunk and experienced hypesthesia in his lower extremities. Laboratory data showed marked eosinophilia (20,235/mm3) and enhanced hepatobiliary enzymes. Chest X-ray films and computed tomographic scans revealed diffuse patchy infiltrative changes in the lungs. Histologic findings confirmed eosinophilic infiltration of the skin, liver, and lungs. A diagnosis of hypereosinophilic syndrome (HES) was made in accordance with clinical criteria proposed by Chusid et al. The patient was positive for antineutrophil cytoplasmic antibodies (a marker for vasculitis). This suggested a clinical picture resembling Churg-Strauss syndrome (CSS) despite the lack of bronchial asthma. The findings in this report could contribute to a better understanding of the diversity of HES cases, several of which are considered to represent a continuum of pathologies sharing an etiology similar to that of CSS.