[2 cases of antiphospholipid syndrome with amaurosis fugax as the major symptom].
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Biomedical subjects
Publications and source records attributed to K Ota.
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We report on a trial of partial kidney transplantation performed on a low body weight child with impaired cardiac function due to mitral valve stenosis and uremic cardiomyopathy. The weight of the donated kidney was successfully reduced by one-third using bench surgery in order to obtain sufficient graft perfusion and function. Our procedure is justified when a graft is too large to be adequately perfused in a recipient suffering from cardiac failure.
Liblomycin (NK313) is a bleomycin analog that has proved to be associated with less pulmonary toxicity and with more potent antitumor activity than bleomycin in animal tumors. In a phase I study, pulmonary toxicity was not observed, whereas myelosuppression was the dose-limiting factor. The maximum tolerated dose was 140 mg/m2 given once a week for 4 weeks. In the present phase II study, patients with malignant lymphomas received liblomycin at 80 or 100 mg/m2 by intravenous infusion over 15 min once a week for 4 weeks. A total of 39 patients were entered, and 31 [4 with Hodgkin's disease (HD) and 27 with non-Hodgkin's lymphoma (NHL)] were evaluable. The median age of the patients was 52 years (range, 22-74 years), and their performance status ranged from 0 to 3. In all, 28 of the patients had a history of intensive anticancer chemotherapy. Responses were evaluated according to WHO criteria. We obtained 1 complete remission and 9 partial remissions (PRs), for an overall response rate of 37%, in the 27 patients with NHL, whereas 1 PR was achieved in the 4 patients with HD. In all, 9 PRs (32.1%) were obtained in patients who had been exposed to prior chemotherapy, including 4 PRs (33.3%) in 12 patients who had previously been treated with bleomycin. Myelosuppression and nausea and vomiting were the major toxicities, which occurred in about 50% of the patients, and myelosuppression was severe in two patients treated at a dose of 100 mg/m2. We concluded that liblomycin demonstrated significant antitumor activity against malignant lymphomas.
In order to assess the central effects of gamma-aminobutyric acid (GABA) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular function, the following two experiments (Exp) were carried out in conscious rats (n = 24). Experiment I: GABA (10 micrograms/kg.min) was intracerebroventricularly (i.c.v.) administered into conscious rats receiving an intravenous (i.v.) infusion of 2.5 M NaCl, and the vehicle alone was i.c.v. administered under i.v. 2.5 M NaCl in the control group. Experiment II: GABA (12 micrograms/kg.min) was infused i.c.v. in conscious rats during hemorrhage (1.6% of BW) and the vehicle alone was i.c.v. administered during hemorrhage in the control study. In Experiment I, plasma AVP and ANP and mean arterial blood pressure (MABP) increased in response to 2.5 M NaCl, but heart rate (HR) slightly decreased. I.C.V. GABA attenuated the AVP and ANP responses, but did not affect MABP and HR. In Experiment II, plasma AVP increased due to decreases in MABP induced by hemorrhage, but plasma ANP and HR never changed. I.C.V. GABA did not affect plasma AVP and ANP, MABP and HR. These results show that i.c.v. GABA has an inhibitory effect on AVP and ANP release in response to hypertonic NaCl, but not to hemorrhage, but never affected hypertonic NaCl-induced increases in blood pressure.
To determine whether hypotensive hemorrhage has an effect on arginine vasopressin (AVP) gene expression, 16 ml/kg of arterial blood was drawn over 10 min in conscious unrestrained rats. Mean arterial blood pressure (MABP) and heart rate (HR) were measured, and the rats were decapitated before and 10 min, 1, 3, 6, 9, 12, and 24 h after the initiation of hemorrhage. The hypothalamic or cerebro-hypothalamic tissue was used to measure AVP mRNA by Northern blot analysis, and the trunk blood to measure plasma AVP, osmolality and hematocrit. Hemorrhage brought about rapid and transient decreases in MABP and HR accompanied by transient increases in plasma osmolality and AVP. Hematocrit decreased after the bleeding and reached a stable level 6 h after hemorrhage and thereafter. AVP mRNA was detected in the hypothalamus and not in the extrahypothalamic cerebral brain tissue under basal and posthemorrhage conditions. AVP mRNA in the cerebro-hypothalamic tissue increased by 1.8-fold at 6 h and 2.1-fold at 9 h after hemorrhage. These results indicate that AVP mRNA in the brain increases 6 h after increased AVP release in response to hypotensive hemorrhage.
107 hemodialysis patients at high risk for intradialytic bleeding due to previous surgery or active bleeding from other sites were treated with nafamostat mesilate (FUT-175; FUT) as hemodialysis anticoagulant for 2 weeks. In contrast to heparin. FUT prolonged clotting times only in the extracorporeal circuit. Clotting times were not prolonged even at the conclusion of the treatment, and bleeding from the puncture site after removal of the needle was shorter than with heparin. The exacerbation of bleeding by hemodialysis was noted in only 21 out of 573 hemodialysis procedures (3.7%), and 134 of 145 hemodialysis procedures (92.4%) with active bleeding were successfully completed without increasing the bleeding. Adverse effects of FUT were noted in only 6 cases (5.6%) or 1.2% of HD procedures. These results indicate that FUT is a very useful anticoagulant for HD, especially in patients with high risk of bleeding.
According to the authors' clinical analysis, about half of the patients who suffer from arteriosclerotic obstruction (ASO) in the lower extremity(-ies) with clinical manifestation are dyslipidemic (total cholesterol > or = 220 mg/dL or LDL cholesterol > or = 140 mg/dL). As suggested by clinical success in regression of ASO in the coronary arteries as a result of aggressive removal of LDL, LDL adsorption utilizing an extracorporeal circulation technique with a dextran sulfate/cellulose adsorbent column was applied in 33 patients (22 men and 11 women) with ASO. Clinical results obtained after a series of 10 LDL adsorption procedures as a standard showed encouraging success. Improvement in subjective symptoms was achieved as follows: 88.5% for cold lower extremity, 87.1% for intermittent claudication, 53.8% for leg/toe pain at rest, and 60% for disappearance/size diminution of ulcer/necrosis. Improvements in objective examination findings supported subjective ones: 85.7% by plethysmography, 81% by thermography and 70% by ankle pressure index. No serious complications or untoward effects were observed during or after the adsorption procedures. In conclusion, LDL adsorption appears to be a useful and safe tool in treatment of ASO patients with dyslipidemia.
To assess whether increases in circulating atrial natriuretic hormone (ANH) in response to the plasma volume expansion, besides the volume receptor-mediated mechanisms, attenuate the arginine vasopressin (AVP) response to increased plasma osmolality and whether changes in plasma AVP and ANH affect renal solute excretion under hypertonic plasma volume expansion, hypertonic saline (0.95 mol/l saline) alone, hypertonic saline with 6% dextran (6D-HS) and hypertonic saline with 9% dextran (9D-HS) were administered into anesthetized dogs. In the control study, 0.15 mol/l NaCl alone was administered. Plasma AVP and ANH and cardiovascular and renal functions were determined. Hypertonic saline and 9D-HS also were administered into the vagotomized and sham operated dogs, and the same parameters were determined. Mean blood pressure and heart rate never changed in all the groups, but central venous pressure and plasma volume increased markedly in 6D-HS and 9D-HS groups. In the control and hypertonic saline groups, central venous pressure increased slightly but plasma volume never changed. Plasma AVP increased in the order of hypertonic saline, 6D-HS and 9D-HS, but plasma ANH increased in reverse order. Vagotomy restored the AVP response to 9D-HS to 75% of its response to hypertonic saline, with a marked rise in plasma ANH. Urine sodium and potassium excretion and urine flow increased in hypertonic saline, 6D-HS and 9D-HS groups, but these increases were comparable among the groups. In the control group, these parameters never changed. These results suggest that the volume receptor-mediated vagal neural and ANH responses to the plasma volume expansion may have an effect on the suppression of the AVP response to osmotic stimuli, and increased plasma ANH release never potentiated the natriuresis under the hypertonic plasma volume expansion.
We had a 20-year-old male patient of secondary aldosteronism similar to Bartter's syndrome, which had proved to be evident after the remission of nephrotic syndrome. In the patient, hypokalemic alkalosis and hyperreninemic hyperaldosteronemia were observed, although the blood pressure was normal. Hyperplasia of juxtaglomerular cells was observed and no abnormalities indicating either glomerulonephritis or renal artery stenosis were found; the pressor response to intravenously infused angiotensin (ang) II was markedly decreased; urinary prostaglandin (PG) E2, kallikrein and kinin excretion were elevated. The inhibition of PG synthesis with indomethacin decreased renal PG production and partially corrected both hypokalemia and pressor responsiveness to ang II. Thus, this case is considered to be a case of Bartter's syndrome. Contrary to the previously reported observations, the effective fractional chloride reabsorption rate in the renal distal tubules was normal (> 80%) and not changed by PG inhibition. Plasma atrial natriuretic peptide level was normal. An interaction between renin-angiotensin and PG systems appears to play a prior role in this case. To explain the pathophysiology, we have hypothesized an abnormal function of ang II receptor signal transduction which excessively stimulates PLA2, resulting in overproduction of PG synthesis in tissues.
In order to clarify the mechanism of proteinuria in diabetic nephropathy, ultrastructural changes of the glomerular basement membrane (GBM) in patients with diabetic nephropathy were examined by electron microscopy using our newly devised "tissue negative staining method". The normal human GBM showed a fine meshwork structure consisting of fibrils forming the small pores. The diameter of these pores was slightly smaller than that of human albumin molecules. The GBM in patients with diabetic nephropathy showed irregular thickening. At higher magnification, hitherto unknown cavities and tunnel structures, which were not seen in normal controls, were observed in the thickened GBM. In some portions, these cavities presented a honeycomb-like appearance. The diameters of the cavities and tunnels were far larger than the dimensions of albumin molecules. These enlarged structures are believed to allow serum protein molecules to pass through the GBM from the capillary lumen to the urinary space. These results suggest that the cause of massive proteinuria in diabetic nephropathy is the disruption of the size barrier of the GBM.
In Japan, the major transfusion-associated disease is non-A, non-B hepatitis. We studied the relationship between transfusion history and blood donor antibodies to hepatitis C virus (HCV). The positive rate of antibodies to the HCV nonstructural protein (c100-3) depended on age and the time elapsed since transfusion. The anti-c100-3 ratio for subjects with transfusions made prior to 20 years ago was high. One quarter century ago, a change occurred in national blood policy from paid to non-paid voluntary donations. We also have studied the anti-HCV positive rate among donors with prior transfusion using a second generation HCV test kit which includes anti-HCV core antibody detection. The anti-HCV positive rate for the second generation test was higher than that for the anti-c100-3 test. Introduction of the second generation test is therefore more useful in screening than the anti-c100-3 test for blood programs.
The presence of T lymphocytes bearing the gamma delta T cell receptor (gamma delta T cells) has been studied in peripheral blood from 21 patients with multiple sclerosis (MS) and 13 normal controls. The amount of gamma delta T cells of CD3 positive T cells in MS was (mean +/- SEM; 7.7 +/- 1.3%) higher than in normal controls (5.5 +/- 1.0%), but not significantly. However, in MS group, 6 patients had definitely a higher frequency of gamma delta T cells, exceeding the mean +/- 2SD of normal control (22.3, 18.5, 17.7, 14.8, 12.0, 10.3%). Furthermore, there is no correlation between the presence of gamma delta T cells and disease type, clinical course, disease duration and disability score. But some patients with short disease duration tend to have higher proportion of gamma delta T cells than in other patients. It is suggested that gamma delta T cells might be related to causes of the disease of some MS patients in early phase.
Simultaneous measurements of zinc (Zn) and iron (Fe) concentrations were determined using neutron activation analysis in gray and white matter of the frontal and occipital regions obtained from four patients with parkinsonism-dementia (PD), eight with amyotrophic lateral sclerosis (ALS), and four neurologically normal controls from Guam. Zn content in gray matter from the frontal cortex in ALS and PD cases was significantly decreased, compared with that of controls (p < 0.05). No significant differences were found in the Zn content of white matter from the frontal cortex, and/or gray and white matter from the occipital cortex between the groups. The Zn content in gray matter from both frontal and occipital regions was less in ALS and PD patients than in controls. Fe content in gray matter from the frontal cortex of ALS and PD increased significantly compared with that of controls (p < 0.05). Fe content in white matter from the frontal cortex in PD patients was greater than in controls (p < 0.05), with an overall difference: controls < ALS < PD. These data indicate that an increase in Fe in gray and white matter, and a decrease concentration of Zn in gray matter, combined with an excess and deficiency of bioavailable aluminum and calcium, respectively, may be involved in the pathogenic process of these disorders.
We report a case of chronic progressive external ophthalmoplegia with pituitary hypothyroidism. This patient had complained of hearing-loss at the age of fourteen and loss of body weight at fifteen. She was examined by otorhinolaryngologists at large hospitals yearly over a period of 5-6 years, but hearing-loss remained unknown. As her ophthalmoplegia progressed (as is evident from family photographs from the age of sixteen onward), with hindsight it should have been recognized. When examined on October 11, 1991, she complained of ptosis, speech disturbance and dysphagia at the age of thirty-four. Neurological examination revealed limitation of ocular movement, bilateral ophthalmoplegia, facial muscle atrophy, and weak gag reflex. She showed muscle atrophy in her neck including both sternocleidomastoid, major and minor rhomboid, girdle and distal parts of upper and lower extremities. Muscle biopsy of her biceps demonstrated ragged-red fibers, cytochrome c oxidase (CCO) deficient fibers and deletion of mitochondrial DNA. A plain CT scan revealed bilateral periventricular lucency, and a brain MR image showed a normal sized pituitary gland but diffuse high-signal intensities in the both periventricular white matter with proton density weighted and T2-weighted axial MR image. And also her electroencephalogram showed diffuse 7 Hz slow waves in all areas and increased slow waves by hyperventilation, and all waves from I to V of the auditory brain stem response disappeared. The effect of TRH on serum TSH secretion was not evident in this patient. This case was ascertained to be chronic progressive external ophthalmoplegia with pituitary hypothyroid function.
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The pathogenesis oriented diagnoses and therapies of epilepsy and myoclonus was tended to describe, but their pathogeneses were partially elucidated. The pathogenesis of both diseases was firstly demonstrated to have genuine or hereditary factors to be discharged abnormal electrical potentials which were provoked varieties of symptoms of both epilepsy and myoclonus. The careful observation of clinical symptoms, the introduction of monitoring EEG, computed tomogram, spike voltage topography, magnetoencephalography, somatosensory evoked potential (SEP) and MRI were comparatively easily provided the diagnoses of both diseases and topographical foci of abnormal discharge. The diagnosis of myoclonus was more difficult than those of epilepsy, because the clarification of pathogenesis and definition of diagnosis was lacked. The therapies of both epilepsy and myoclonus were surgically removed the topographically abnormal discharged focus to be congenital or secondary, and their conventional discharge, monitoring the findings of EEG, and checking out the clinical symptoms and side effects of drugs. We suggest that the clear-cut description on diagnoses and therapies of both disease are required to be further investigated.
A 53-year-old man was hospitalized for the development of watery diarrhea associated with decreased appetite and progressive weight loss and was found to have leukocytosis. The white blood cell count was 14,600/microliters with 66 percent abnormal lymphocytes. Serum anti-HTLV-I was positive and monoclonal insertion of HTLV-I provirus into the atypical cell genome was confirmed with the southern blotting hybridization technique. A diagnosis of ATL was made. Examination of fresh stool specimens revealed Isospora belli (I. belli) oocysts. Initial treatment for I. belli consisted of oral trimethoprim 160mg and sulfamethoxazole 400mg given twice daily for nine days. Diarrhea ceased within 2 days of the start of treatment, but I. belli oocysts were again detected after 20 days. Trimethoprim 160mg and sulfamethoxazole 400mg were reinstituted four times daily for 10 days, and then twice daily for 21 days. The clinical response was again dramatic, with rapid clearance of oocysts from the stool. There has been no recurrence of diarrhea. The patient's leukemia was refractory to chemotherapy; the white blood cell count continued to rise, pneumonia developed, and the patient died. I. belli is a previously unrecognized opportunistic pathogen that must be considered in the clinical setting of chronic diarrhea in patients with ATL.