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Biomedical subjects

Y Kuwabara

Publications and source records attributed to Y Kuwabara.

At least 55 records · Page 3Linked to original sources

Dimeric inhibin A as a fourth marker for Down's syndrome maternal serum screening in native Japanese women.

OBJECTIVE: This study was conducted to assess the usefulness of dimeric inhibin A as a fourth marker for Down's syndrome screening in addition to AFP, hCG and uE3 markers for native Japanese women. METHODS: Serum specimens from 367 native Japanese women in the second trimester were assayed for dimeric inhibin A levels. Day specific dimeric inhibin A medians were established for gestational ages 15.0-21.9. Weekly median values for the native Japanese were compared with those of a U.S. population. Selected Japanese specimens from 15 diagnosed Down's syndrome and 3 trisomy 18 cases were also assayed for dimeric inhibin A. RESULTS: Dimeric inhibin A levels did not vary greatly over the gestational age range as expected. Median value comparison showed that native Japanese dimeric inhibin A medians are higher than the U.S. population medians by an average of 7.95%. Native Japanese dimeric inhibin A median values in this study are 1.77 times higher in Down's syndrome cases than in unaffected pregnancies. Trisomy 18 dimeric inhibin A levels show no significant difference from the unaffected pregnancies. CONCLUSIONS: This report shows for the first time that dimeric inhibin A can be informative as a fourth marker for Down's syndrome screening in native Japanese women. We expect the addition of dimeric inhibin A to a triple marker protocol will increase the accuracy of predicted risk for all pregnancies screened and increase the detection rate of Down's syndrome affected pregnancies.

Biomarkers↗

A clinicopathological study of postoperatively upgraded early squamous-cell carcinoma of the uterine cervix.

OBJECTIVE: To investigate the clinicopathological backgrounds and diagnostic problems of postoperatively upgraded early squamous-cell carcinomas of the uterine cervix. PATIENTS AND METHODS: A total of 23 patients with postoperatively upgraded early squamous-cell carcinomas who were treated at the Saitama Cancer Center during the period of January 1, 1976, through December 31, 1991, were analyzed clinicopathologically. We reexamined the Pap smears (ectocervix, endocervix), colposcopic findings, punch biopsies, and histological findings of the operative specimens. All patients were divided into one of 3 groups based on each patient's main location of the carcinoma of the cervix: Type A: ectocervical type; Type B: endocervical type; or Type C: combined (ectocervical and endocervical) type. Clinical staging of the uterine cervical carcinomas was done in accordance with the 1994 FIGO rules. RESULTS: The numbers of patients were: Type A, 2; Type B, 10; Type C, 11. Of the 23 patients, 21 (91.3%) had lesions in the endocervical portion at least. Fifteen patients (65.2%) complained of atypical vaginal bleeding. Colposcopic findings suggesting an invasive carcinoma appeared for only 6 patients (26.1%). A cytological reevaluation revealed that the endocervical findings were much stronger than the ectocervical ones in 10 (66.7%) of 15 patients whose smears of both sites could be rechecked. CONCLUSIONS: Even if the preoperative diagnosis was early cervical carcinoma, CIS or Stage Ia1, the signs of atypical vaginal bleeding suggested that the final clinical stage would be upgraded after an operation. Furthermore, when the endocervical cytological findings were much more exaggerated than the ectocervical ones, the possibility of deeply invaded endocervical lesions should be considered.

Adult↗

Close relationship of abnormal glucose tolerance with endothelial dysfunction in hypertension.

Hypertension is frequently accompanied by left ventricular hypertrophy, endothelial dysfunction, and abnormal glucose metabolism. However, no study has examined the relative pathological significance of left ventricular hypertrophy and abnormal glucose metabolism on endothelial dysfunction in hypertension. This study was conducted to evaluate whether abnormal glucose tolerance assessed by 75-g oral glucose tolerance test or left ventricular hypertrophy is more closely associated with endothelial dysfunction in never-treated hypertensive patients without elevated fasting blood glucose. We studied 107 unmedicated hypertensive patients (mean age, 54+/-10 years) whose fasting blood glucose was <7.0 mmol/L. Endothelial function was assessed by change in brachial artery diameter in response to reactive hyperemia, and left ventricular mass index was determined by ultrasonography. Simple linear regression analysis demonstrated that endothelial function significantly correlated with left ventricular mass index and 2-hour blood glucose in 75-g oral glucose tolerance test, but not with fasting blood glucose. Multiple linear regression analysis revealed that endothelial function significantly correlated with 2-hour blood glucose (beta=-2.68, P<0.05) after we controlled for other clinical variables. Patients were divided into 3 groups according to 2-hour blood glucose levels. Endothelial function was more impaired in patients with diabetes (n=12; 4.7+/-1.8%) and in those with impaired glucose tolerance (n=31; 6.3+/-2.9%) than in those with normal glucose tolerance (n=64; 8.4+/-4.5%) (P<0.05), but left ventricular mass index was similar in these 3 groups. Abnormal glucose tolerance assessed by 75-g oral glucose tolerance test, rather than left ventricular hypertrophy, may have direct pathophysiological relevance to endothelial dysfunction in borderline to moderate hypertensive patients.

Adult↗

[A pilot trial of high dose CEP (cyclophosphamide, epirubicin, cis-platinum) therapy in patients with advanced and recurrent ovarian cancer].

We evaluated the feasibility of high-dose CEP (cyclophosphamide 750 mg/m2, epirubicin 90 mg/m2, cis-platinum 70 mg/m2) therapy, with granulocyte colony-stimulating factor support every 21 days, in 18 patients with advanced and recurrent ovarian cancer. Ten patients (56%) received 6 cycles of this regimen as planned. Toxicities more than grade 3/4 on' the WHO scale of neutropenia and thrombocytopenia were observed in all cases. Nausea, vomiting, mucositis, malaise, alopecia, hepatotoxicity, and fever were common adverse effects. The average relative dose intensity of cyclophosphamide, epirubicin, cis-platinum was 0.77, 0.77, 0.79 respectively, and each RDI decreased in the last two cycles. These data suggest that this regimen could be performed safely with careful consideration on hepatotoxicity and thrombocytopenia.

Adult↗

[A case of amoxapine-induced tardive dystonia successfully treated with a low dose anti-cholinergic agent].

We report a 63-year-old man who presented with amoxapine-induced tardive dystonia. At 49 years of age, he developed depression and was administrated 50 mg amoxapine, 4 mg cloxazoram and 3 mg biperiden per day. The daily dose of amoxapine was gradually increased up to 150 mg at 58 years of age. At 61 years of age and after having been taking amoxapine for twelve years, he noticed a rotating left arm and muscle pain in his left shoulder and arm while walking. At 62 years of age, he stopped taking these three drugs. However, the dystonic movements and pain both continued to get worse. Neurological findings revealed no abnormality except for a dystonic posture and movements in the neck and bilateral arms while sitting, standing and walking. Positron emission tomography with C-11 raclopride revealed a mild decrease in the dopamine D 2 receptor numbers in the bilateral striatum. However, two dopamine agonists, pergolide and bromocriptine, worsened his dystonia. In contrast, the daily administration of 2 mg of trihexyphenidyl, an anti-cholinergic agent, markedly ameliorated the dystonia symptoms. As a result, the long-term co-administration of biperiden, an anti-cholinergic agent, may mask the toxicity of amoxapine, which may induce tardive dystonia.

Amoxapine↗

[Nuclear medicine for general radiologists: clinical application of brain SPECT].

Brain SPECT studies are used to evaluate the cerebral hemodynamic changes in cerebrovascular diseases and other neuro-psychiatric disorders. I-123 and Tc-99m labeled radiopharmaceuticals widely used for brain perfusion SPECT studies include I-123 IMP, Tc-99m HMPAO, and Tc-99m ECD. I-123 IMP is suitable for the quantitative evaluation of cerebral blood flow, while Tc-99m HMPAO and Tc-99m ECD have problems owing to the non-linearity between cerebral radioactivity and cerebral blood flow. In addition, Tc-99m ECD does not show cerebral blood flow in the subacute phase of cerebral infarct or other conditions. Thus, it is important to consider the characteristics of radiopharmaceuticals and the clinical aspect of brain lesions in the interpretation of brain perfusion SPECT images. In this review, some useful information on brain perfusion SPECT is presented mainly as it relates to the cerebrovascular diseases.

Brain↗

Optimal hematocrit for the maximum oxygen delivery to the brain with recombinant human erythropoietin in hemodialysis patients.

AIM: Although hematocrit (Ht) around 33 to 36% has been recommended, Ht of 30% is usually achieved as a target level during recombinant human erythropoietin (rHuEPO) therapy in the majority of hemodialysis (HD) patients. The present study aimed at estimating an optimal hematocrit (Ht) for the maximum oxygen delivery to the brain with rHuEPO. PATIENTS AND METHODS: Oxygen delivery was defined as a product of cerebral blood flow and arterial oxygen content (CaO2). The regional cerebral blood flow (rCBF) in each region of interest was measured by positron emission tomography and CaO2 was calculated from hemoglobin concentration, arterial oxygen saturation, and arterial oxygen tension before and after rHuEPO therapy (1,500 units, 3 times a week) in 5 HD patients (the mean age of 52 +/- 2 (SEM) years old and the mean HD duration of 98 +/- 21 months). RESULTS: Ht rose significantly from 21 +/- 1 to 31 +/- 1% (p < 0.001) after the 3-month rHuEPO treatment in association with a significant increase in CaO2 from 7.7 +/- 0.4 to 11.6 +/- 0.3 ml O2/100 ml (p < 0.01). Hemispheric rCBF decreased significantly from 40 +/- 3 to 32 +/- 1 ml/100 g/min (p < 0.02). In all data both before and after rHuEPO treatment, Ht inversely correlated with the hemispheric rCBF (y = 55.7 - 0.76x, where y is rCBF and x is Ht, r = 0.80, p < 0.01), and positively with CaO2 (y = 0.85 + 0.34x, where y is CaO2 and x is Ht, r = 0.95, p < 0.01). By using these correlations, the hemispheric oxygen delivery was expressed as a function of Ht, being y = 47.3 + 18.3x - 0.3 x2, where y is cerebral oxygen delivery and x is Ht. From this curve, Ht at the highest cerebral oxygen delivery in the hemisphere, i.e. an optimal Ht was found to be 35.2%. Above this level of Ht, the hemispheric cerebral oxygen delivery would rather decline. CONCLUSION: The present study indicated that Ht of about 35% is required for a better oxygen delivery to the brain metabolism during anemia correction with rHuEPO.

Anemia↗

[The advantages and limitations of brain function analyses by PET].

PET has been proved to be a powerful tool for exploring the brain function. We discussed the advantages and limitations of PET for analyzing the brain function on the basis of our clinical and experimental experiences of functional imaging. A multimodality PET study measuring cerebral energy metabolism (CMRO2 and CMRglc), cerebral blood flow (CBF), oxygen extraction fraction (OEF) and neurotransmitter function (presynaptic and postsynaptic) opens up a closer insight into a precise pathophysiology of the brain dysfunction: In cerebral infarction, it reveals a state of "misery perfusion" in the acute stage, "luxury perfusion" in the intermediate stage, and proportionately decreased CBF and CMRO2 in the chronic stage. Neurotransmitter function may identify specifically a neuronal subgroup of dysfunction. Owing to the low temporal resolution of PET, a neuronal activity may propagate transsynaptically to remote areas during the period of scanning, resulting in an obscured primary site of the neuronal activity. Uncoupling between neuronal activities and cerebral energy metabolism/CBF may occur under a certain state of brain pathology, particularly after an acute destructive lesion, according to our experimental studies. Neurotransmitter function may reveal the effect of drugs on the brain function, and may be useful for developing a new method of drug therapy for brain diseases in the future.

Animals↗

Nutritional therapy of chronic hepatitis by whey protein (non-heated).

In an open study the clinical efficacy of milk serum (whey) protein (Immunocal; cysteine content: 7.6-fold higher than that of casein) isolated from fresh milk and purified without heating was evaluated in 25 patients with chronic hepatitis B or C. Immunocal (12 g as protein) food (mousse) was given twice a day, in the morning and evening, for 12 weeks (test period). Casein (12 g as protein) food (mousse) was similarly given for two weeks prior to the start of the supplement with Immunocal food (induction period) and for four weeks after the end of the supplement with Immunocal food (follow-up period). Serum alanine aminotransferase (ALT) activity was reduced, and plasma glutathione (GSH) levels increased in six and five of eight patients with chronic hepatitis B, respectively, 12 weeks after the start of the supplement with Immunocal food. Serum lipid peroxide levels significantly decreased, and interleukin (IL)-2 levels and natural killer (NK) activity significantly increased. However, there were no significant Immunocal-related changes in 17 patients with chronic hepatitis C. These findings suggest that the long-term supplement with Immunocal alone may be effective for improving liver dysfunctions in patients with chronic hepatitis B.

Adult↗

Prognostic utility of myocardial blood flow assessed by N-13 ammonia positron emission tomography in patients with idiopathic dilated cardiomyopathy.

Previous studies in patients with idiopathic dilated cardiomyopathy (IDC) have suggested that myocardial perfusion is impaired and spatially heterogeneous in such cases. Our objective was to identify any association between an abnormality in myocardial perfusion and the prognosis of patients with IDC. We collected data on N-13 ammonia positron emission tomography (PET) studies performed in 26 patients with IDC (9 nonsurvivors, 17 survivors) and in 8 normal control subjects. Regional myocardial blood flow (rMBF) was quantified using N-13 ammonia positron emission tomography and the Simple flow model. The spatial heterogeneity of myocardial perfusion was assessed by calculating the coefficient of variance of rMBF. Mean rMBF of the survivors was significantly lower (0.54 +/- 0.13 ml/min/g) than that of control subjects (0.66 +/- 0.06 ml/min/g) (p = 0.03 vs control), but did not differ significantly between nonsurvivors (0.58 +/- 0.15 ml/min/g) and control subjects. The coefficient of variance of rMBF was significantly higher in nonsurvivors than in either survivors or control subjects (0.24 +/- 0.08 vs 0.15 +/- 0.08, p = 0.007, and 0.16 +/- 0.05, p = 0.03, respectively). The probability of 3-year survival (Kaplan-Meier method) was 33.0% in subjects whose coefficient of variance of rMBF was above the median compared with 90.0% in subjects whose coefficient of variance of rMBF was below the median (p = 0.01). The probability of 3-year survival did not differ among subjects whose mean rMBF was above versus below the median (61.5% vs 62.9%, respectively). The results suggest that the prognosis of patients with IDC is associated with the spatial heterogeneity of myocardial perfusion, not with initial absolute rMBF.

Adult↗

Idiopathic cortical myoclonus restricted to the lower limbs: correlation between MEPs and 99mTc-ECD single photon emission computed tomography activation study.

We report a 63-year-old woman with cortical reflex myoclonus restricted to the bilateral lower limbs. Somatosensory evoked cortical potentials to posterior tibial nerve stimulation were enlarged with C-responses. Jerk-locked back averaging of the EEG identified a cortical spike related to myoclonic jerks. Motor evoked potentials recorded from the abductor hallucis muscle showed an exaggerated late response. These findings suggest hyperexcitability of the sensorimotor cortex. 99mTc-ECD single photon emission computed tomography (SPECT) after stimulation of the posterior tibial nerve showed increased perfusion in the contralateral peri-Rolandic area which corresponded to the hyperexcitable region. A SPECT activation study as well as MEPs therefore can be employed to determine the hyperexcitable region in cortical myoclonus.

Brain↗

Intestinal energy metabolism during ischemia and reperfusion.

BACKGROUND: In order to evaluate acute ischemic damage in the small intestine induced by superior mesenteric artery occlusion (SMAO) and subsequent reperfusion, changes in ATP, ADP, and AMP were measured by high-performance liquid chromatography, and changes in tissue blood flow were measured (from the serosal surface) by the laser doppler flow meter in a rat model. MATERIALS AND METHODS: The superior mesenteric artery of the rat was occluded for 30, 60, 90, and 120 min and then reopened. Core temperature was maintained carefully at 37 +/- 0.3 degrees C. RESULTS: All rats that underwent 90 and 120 min of SMAO died within 2 days, but those with 30 and 60 min of SMAO survived. ATP (10.39 +/- 0.90 micromol/g dry weight), ADP (3.34 +/- 0.33), and total adenine nucleotides (TAN; 14.08 +/- 0. 86) decreased with longer SMAO times. After 30 and 60 min of SMAO followed by reperfusion, recoveries of ATP and TAN were relatively good and ADP levels remained fairly steady, but little or no recovery of these levels was observed after 90 and 120 min of SMAO followed by reperfusion. There were linear correlations between the levels of ATP and TAN after 30 min of reperfusion and the time of SMAO. Tissue blood flow levels were constant during SMAO. After reperfusion, those levels were recovered along with the SMAO periods. But recovery rates compared with control values were not related with those of ATP. CONCLUSIONs. ATP and TAN levels, particularly at 30 min after reperfusion, seemed to be in good agreement with the tissue damage and the viability of the small intestine. We propose that the measurement of these levels may be useful for the evaluation of intestinal damage and viability.

Adenosine Diphosphate↗

Functional evaluation of myocardial viability by 99mTc tetrofosmin gated SPECT--a quantitative comparison with 18F fluorodeoxyglucose positron emission CT (18F FDG PET).

UNLABELLED: To validate functional analysis of gated SPECT in detecting myocardial viability, seventeen patients (male 15, female 2, mean age 58) with angiographically proven chronic ischemic heart disease (RCA 6, LAD 10, LCX 1) and eight normal volunteers (all male) were studied. All patients underwent 18F FDG PET and 99mTc tetrofosmin (TF) gated SPECT within a week. After being displayed in a polar map, myocardial perfusion was regionally determined by the mean count in 9 segments at end diastole (ED) and end systole (ES) in gated SPECT. Systolic function was determined by the count increase ratio from ED to ES (WTI: ES - ED/ED). Glucose metabolism was assessed by 18F FDG PET in the segments correspondent to those defined for SPECT. TF %uptake of < 60% was defined as hypoperfusion, and FDG %uptake of < 50% was defined as reduced glucose metabolism. RESULTS: The myocardial segments were classified into 3 categories: "normal" perfusion (n = 85), "mismatch" (reduced perfusion with reserved FDG uptake, n = 25) and "matched" reduced perfusion and metabolic reduction (n = 26). Mean WTI in "mismatch" segment was 0.38 +/- 0.21, and was significantly greater than that in "matched reduced" segments, 0.15 +/- 0.20 (p < 0.001). It was also greater than that in "normal" segments, 0.27 +/- 0.16. Regression analysis showed that association between WTI and FDG %uptake was significant (r = 0.57, p < 0.0005) for the ischemic segments ("mismatch" + "matched", n = 51), but the association was weak for the entire segments although it was statistically significant (r = 0.26, p = 0.02, n = 136). CONCLUSION: For the segments determined as infarct by perfusion image, systolic functional analysis by gated SPECT is helpful in differentiation of a viable myocardial region or artifact from a scar. Nevertheless, further clinical and technical assessment is required for ECG gating to eliminate overestimation of viability and to warrant clinical use.

Adult↗

Structural identification and characterization of arteries and veins in the placental stem villi.

The vascular wall structure in the human full-term placental villi of normal pregnancy was studied by means of light and electron microscopy with an improved technique of perfusion fixation and tissue preparation. We observed 81 sections of stem villi that showed cross-sectional profiles of paired vessels in their center. Both vascular walls contained a large amount of extracellular matrix and no elastic lamina between smooth muscle cells of the media, making identification of the artery and the vein quite difficult at first sight. We then noted that the density of the smooth muscle cell population was always considerably higher in one than the other, and identified the former as artery and the latter as vein on the basis of their connection with larger arteries and veins running on the chorionic plate. Between the paired vessels, the artery had a smaller caliber than the vein, and the ratio of venous to arterial caliber was distributed from 1.0 to 2.5. The thickness of media was usually thicker in the vein than in the artery. Clusters of elastic fibers were found occasionally in the media of arteries and veins, and basement membrane-like materials were associated frequently with the elastic fibers and were distributed widely in the media as well as in the adventitia. In the veins, the smooth muscle cells of the most superficial part of the media contained well-developed rough endoplasmic reticulum and Golgi apparatus, indicating differentiation to secrete extracellular matrices. The present study revealed the difference of wall structure between arteries and veins in the placental stem villi for the first time at the ultrastructural level, and suggested differentiation of venous smooth muscle cells, possibly by some influence from the luminal side.

Adult↗

Mesenteric venous thrombosis associated with protein C deficiency.

An 83-year-old man had gradually worsening abdominal pain and vomiting. Laparotomy revealed segmental intestinal infarction resulting from thrombosis in the superior mesenteric vein. Necrosed intestine was resected and anastomosis was performed successfully. The patient was anticoagulated with intravenous heparin and nafamostat mesilate followed by oral aspirin. He recovered rapidly. Blood chemistry revealed protein C deficiency, while protein S and antithrombin III levels were normal. Laboratory evaluation of these proteins may help define the cause of mesenteric venous thrombosis.

Abdominal Pain↗

Functional imaging in periventricular nodular heterotopia with the use of FDG-PET and HMPAO-SPECT.

We analyzed the interictal [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FGD-PET) and single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime (HMPAO-SPECT) in two epileptic patients with periventricular nodular heterotopia (PNH). In both cases, we found both the glucose metabolism and the perfusion of PNH to be almost identical to those of the normal cerebral cortex. The metabolic activity and perfusion in the heterotopic gray matter in a subependymal white matter area probably represent the glucose metabolism and perfusion of the abnormally located gray matter rather than a subclinical ictal phenomenon. FDG-PET and HMPAO-SPECT were thus found to be a useful complement to magnetic resonance imaging in the evaluation of PNH.

Adult↗

Functional imaging in schizencephaly using [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime (HMPAO-SPECT).

We analyzed interictal [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FGD-PET) and single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime (HMPAO-SPECT) in a 23-year-old female with schizencephaly. She had epilepsy and mild left hemiparesis, but was otherwise developmentally normal. We found the glucose metabolism and perfusion of the wall of the schizencephalic cleft to be identical to those of normal cerebral cortex. The wall of the transcerebral clefts, which were observed to be lined by abnormally organized gray matter as a result of a migration disorder, demonstrated gray matter metabolic activity and perfusion. FDG-PET and HMPAO-SPECT were thus found to be a useful complement to magnetic resonance imaging for evaluating schizencephaly.

Adult↗

Effects of intensive lipid lowering by low-density lipoprotein apheresis on regression of coronary atherosclerosis in patients with familial hypercholesterolemia: Japan Low-density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS).

Twenty-five heterozygous familial hypercholesterolemic patients treated with LDL-apheresis and drugs and 11 patients treated with drugs underwent follow-up angiography 2.3 years later. One-hundred thirteen lesions were measured by quantitative angiography. Mean LDL-cholesterol levels during the trial were 140 +/- 34 mg/dl in the apheresis group and 170 +/- 58 mg/dl (P < 0.05) in the control group. The mean changes in minimal lumen diameter of lesions were +0.19 +/- 0.30 mm (improved) in the apheresis group (n = 76) and -0.44 +/- 0.40 mm (worsened) in the control group (n = 37) (P < 0.0001). When progression and regression were defined as a change in minimal lumen diameter of +/- 0.67 mm, in the apheresis group, two (8%) patients had progression, 19 (76%) stayed unchanged and four (16%) had regression, but in the control group seven (64%) patients had progression and four (36%) stayed unchanged. The frequency of regression or no change was significantly higher in the apheresis group than in the control group (P < 0.004). Intensive cholesterol lowering therapy with LDL-apheresis and lipid lowering drugs can achieve a substantial decrease in LDL-cholesterol levels to induce regression of coronary lesions in familial hypercholesterolemic patients with advanced coronary artery disease.

Adult↗