Serum thrombomodulin as a marker of diabetic macroangiopathy.
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Biomedical subjects
Publications and source records attributed to M Kubota.
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OBJECTIVE: To evaluate the usefulness of plasma 1,5-anhydro-D-glucitol (1,5-AG) as a possible marker for daily glycemic excursion, we measured plasma 1,5-AG, HbA1c, fasting plasma glucose (FPG) level, and daily excursion of glycemia, from which the M-value (after Schlichtkrull) was calculated as an index of daily glycemic excursion. RESEARCH DESIGN AND METHODS: The subjects were 76 patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28), conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy (MIT, n = 15). RESULTS: HbA1c values were similar among all the groups (diet, 6.9 +/- 0.6; OHA, 7.2 +/- 0.5; CIT, 7.1 +/- 0.6; MIT, 7.2 +/- 0.5%). The MIT group showed a significantly higher 1,5-AG concentration (11.5 +/- 5.3 micrograms/ml), a significantly lower M-value (9.2 +/- 5.2), and little risk of hypoglycemia ( < 4 mmol/l) and hyperglycemia ( > 10 mmol/l) (1.3 +/- 1.1 times/24 h) compared with the CIT group (6.9 +/- 3.3 micrograms/ml, 15.7 +/- 8.9, 2.2 +/- 1.6 times/24 h, respectively). Insulin doses (22.4 +/- 4.5 vs. 22.0 +/- 8.9 U/day), FPG (6.6 +/- 2.2 vs. 7.4 +/- 2.4 mmol/l), and HbA1c concentrations were not significantly different between the CIT and MIT groups. M-values significantly correlated with 1,5-AG concentrations (r = 0.414, P < 0.05), but not with HbA1c concentrations. CONCLUSIONS: The findings suggest that the plasma 1,5-AG concentration can be a useful index of the daily excursion of blood glucose, especially in patients with well-controlled NIDDM.
We examined the relationship between alexithymia and psychosocial factors in 72 peritoneal dialysis patients. The 72 patients had significantly higher scores on alexithymia and anxiety than did 73 healthy volunteers. The alexithymia scores were significantly and positively correlated with anxiety scores, suggesting that alexithymia may be related to anxiety derived from the stress associated with dialysis therapy. After 3 yr. of follow-up consultations, patients were still showing higher scores on alexithymia and anxiety; however, alexithymia scores were not correlated with anxiety scores but rather were significantly associated with poor social support. Alexithymic characteristics may be related to psychosocial factors such as the availability of social support.
It is well known that IDDM cases can be complicated with osteopenia, but most of these results were reported using single photon absorptiometry. There have been few reports of diabetic osteopenia using dual energy X-ray absorptiometry (DXA), a method that is excellent for precise bone mineral measurement. Osteoarthritis and osteophytes of unknown origin in the lumbar vertebrae are often observed in elderly NIDDM patients. In this study, we examined the clinical characteristics of decreased bone mineral density (BMD) and whether anteroposterior (AP) scanning of the lumbar vertebrae (L2-L4) provides sufficient informations concerning osteopenia in elderly diabetic patients. The study was performed using DXA, which can quantify regional BMD throughout the body. The BMD in the total body and that in the lumbar vertebrae were measured by DXA (Lunar Co.) in 68 diabetics over age 60, 33 males and 35 females, mean age 68 +/- 8 yr, (mean +/- SD) and in 94 middle-aged diabetics (40 to 59), 56 males and 38 females, mean age 51 +/- 4 yr. The percentage of decrease in regional BMD in diabetic patients differed significantly by age and gender. The BMD in the head and spine especially decreased after menopause in women. However, the BMD of the leg and spine did not decrease with age in men. When the BMD of the lumbar vertebrae was plotted against the Y axis and the BMD in the total body against the X axis, the slope of the curve showed a greater increase in elderly diabetics than that in middle aged diabetics (1.8 vs 1.5) suggesting the BMD in the lumbar vertebrae has been overestimated.(ABSTRACT TRUNCATED AT 250 WORDS)
Dietary fatty acids and serum lipids were evaluated in 68 middle-aged women living in the northern, rural area of Okayama Prefecture, and were compared with the values obtained from 65 urban women from the southern part of this prefecture. A higher level in HDL cholesterol and a lower atherogenic index were observed in the rural women. The percent of energy intake as fat was lower (20.4 +/- 0.8% vs. 23.2 +/- 0.7%) and that of carbohydrate was greater in the rural group. Eicosapentaenoic (EPA, 0.41 +/- 0.04 g/day) and docosahexaenoic acid (DHA, 0.70 +/- 0.08 g/day) intakes were significantly higher in the rural subjects than in the urban group. Significantly higher DHA levels and n-3/n-6 fatty acid ratios in serum total phospholipids were found in rural women in their fifties and the sixties compared to urban women. Dietary linoleic acid (LA) amounts were positively correlated with LA (p < 0.05), and negatively with the EPA (p < 0.05) and DHA (p < 0.01) contents of serum total phospholipids. These results suggest that the traditional Japanese diet, containing little fat but enriched in complex carbohydrates and n-3 fatty acids of marine origin, may be related to the low atherogenic index in this rural area.
BACKGROUND: We studied the clinical efficacy of sclerotherapy with injection of 3% polidocanol for hydrocele testis. METHODS: From July, 1992 to March, 1995 sclerotherapy with single injection of polidocanol was performed for 11 patients with 12 hydrocele testis on an outpatient basis. We instilled 3 or 5ml of 3% polidocanol after complete removal of fluid in the hydrocele testis. RESULTS: Complete disappearance on ultrasonography was observed in 75% of the hydrocele testis 6 months after this sclerotherapy. There was neither pain during instillation of 3% polidocanol nor any other complication. Two patients with fluid reaccumulation underwent hydrocelectomy 16 and 6 months after sclerotherapy, respectively. CONCLUSION: This procedure seems to be a safe and useful technique as primary treatment for hydrocele testis.
Levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by middle cerebral artery occlusion. Ceramide began to increase at 6 hours of ischemia and increased to 4.5 folds at 96 hours. Amino-linked fatty acids in increased ceramide were composed solely of non-hydroxy fatty acids, and stearic acid was the most prominent. Sphingomyelin, whose amino-linked fatty acids were mostly stearic acid, decreased in a time-dependent manner and became about a half of controls at 96 hours. Hydroxy fatty acid linked cerebroside decreased at and after 6 hours of ischemia, whereas significant decrease of non-hydroxy fatty acid linked cerebroside occurred only at 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. The results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during ischemia.
MELAS is a type of the mitochondrial myopathy characterized by elevation of pyruvate and lactate levels in both the blood and cerebrospinal fluid. This syndrome frequently accompanies cerebral infarction like symptoms. Recently, we experienced two patients for anesthesia with MELAS (both 11-year-old girls). V-P shunt construction and IVH reservoir implantation were conducted, respectively. Anesthesia was induced with fentanyl and midazolam, and vecuronium was used to facilitate tracheal intubation. Volatile anesthetic was avoided, and anesthesia was maintained with fentanyl, midazolam, and nitrous oxide. Arterial blood gases and pH were frequently checked, and acetated electrolyte solution was infused mainly during surgery. No complications occurred during anesthesia in both patients. In the anesthetic management for MELAS, measures to prevent malignant hyperthermia must also be considered.
OBJECTIVES: We studied the effects of nipradilol, which has both a nonselective beta-blocker action and a vasodilating action similar to nitroglycerin, on portal hypertension. METHODS: We measured hepatic venous pressure gradient and splanchnic and systemic hemodynamics before beginning therapy, 2 h after an oral dose of 6 mg, and after either 6 months of nipradilol 6 mg twice a day (n = 14) or of a placebo (n = 6) in 20 cirrhotic patients. RESULTS: No significant changes were observed after the administration of the placebo. Oral nipradilol induced a significant reduction in the hepatic venous pressure gradient (base line: 14.8 +/- 3.2 mm Hg vs 2 h: 12.3 +/- 3.4 mm Hg, p < 0.01; 6 mo: 12.5 +/- 3.2 mm Hg, p < 0.05) without a significant change in the free hepatic venous pressure. The hepatic vascular resistance decreased significantly (base line: 1811 +/- 778 dyn.sec.cm-5 vs 2 h: 1540 +/- 701 dyn.sec.cm-5, p < 0.05; 6 mo: 1564 +/- 693 dyn.sec.cm-5, p < 0.05) without a significant change in hepatic blood flow. A decrease in the hepatic venous pressure gradient greater than 10% was observed in nine patients (64%), defined as "responders," at 2 h and in 10 patients (71%) at 6 months. The reduction of mean heart rate and hepatic venous pressure gradient in these responders was 16.2% and 28.3% at 2 h and 15.1% and 27.1% at 6 months, respectively. CONCLUSIONS: We found that in some cirrhotic patients, at the doses used in this study, long term oral nipradilol administration produces a reduction in the hepatic venous pressure gradient with both a beta-blocking and a nitrovasodilating action.
Chemotherapy plays a major indispensable role in treating patients with recurrent breast cancer. Although standard regimens such as CAF, FAC or CMF yield approximately a 50% response rate, the response usually lasts only for 6 months or so on average. For those who have an unfavorable response to chemotherapy, significant portions of their remaining time are to be consequently lost with only identifying damaging effects of treatment, depressed quality of life. Because of this dismal outcome, many of the patients are deeply discouraged about the future, and there is a desperate need for better treatment. Autologous stem cell support, originally practiced in the form of autologous bone marrow transplantation, has been found instrumental in treating breast cancer, and our pilot study started some fifteen years ago showed a higher response rate and survival rate compared to conventional chemotherapy. Moreover, there have been some long-term disease-free survivors with probable cures among complete responders. This is because quality of life is not a mere rating of health status, and is something perceived by each patient individually, reflecting the way in which individual patients feel about their health status. Although high-dose chemotherapy with autologous stem cell support will cause quite a lower quality of life for a significant period of time, it has been fairly well accepted and tolerated by many patients who would be able to maintain some degree of hope. The need to incorporate patients' values, preferences and hopes is what distinguishes quality of life from all other health measures, and physicians' values ought to play no major role in the decision making process when the outcome is often palliation and treatments may be unpleasant.
We presented a case of intracranial vascular malformations associated with pregnancy. A 32 year-old woman who was at 36 weeks of gestation had been experiencing loss of consciousness and convulsions for 3 years. MRI revealed an intracerebral AVM measuring 3.5 x 3.0cm in the left temporal lobe. Cesarean section was carried out under general anesthesia and epidural anesthesia to prevent the rise of blood pressure and intracranial pressure owing to stress of delivery and labor pain. Intermittent injection of nicardipine was quite effective to control the hypertension during anesthesia.
Three hundred fifty-nine freshmen and freshwomen of Tokai University and Tamagawa University were examined for alcohol habituelle using questionnaires on life style and club activity as well as the established questionnaires of the Adolescent Alcohol Involvement scale (AAIS). The scores of AAIS of the male and female students were 30.6 and 27.7, respectively. About 10% of the subjects were revealed to be alcohol misusers. In both sexes, the drinking patterns remarkably changed after the entrance of university. Even in females, the drinking pattern markedly changed. The grade of club activity is one of factors influencing the drinking pattern of students. Especially big changes were observed in the students of cultural clubs.
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Sixteen cases of fibroadenomas with epithelial proliferative lesions (EP lesions) with histologic features resembling those of epithelial hyperplasia, sclerosing adenosis, and microglandular adenosis, and four cases of carcinomas in fibroadenomas (CA lesions) were studied histopathologically and immunohistochemically. The CA lesions included one intraductal carcinoma, two invasive ductal carcinomas, and one lobular carcinoma in situ. The histologic features of the EP lesions and CA lesions were fundamentally the same as those of carcinomas commonly observed in the mammary gland. Immunohistochemically, smooth muscle actin was useful in the detection of myoepithelial cells, particularly in EP lesions of the adenosis type (sclerosing adenosis or microglandular adenosis), and in distinguishing carcinoma. The differences between EP lesions and CA lesions of sites of immunoreactivity to CA15-3, CEA, and EMA were also helpful for differential diagnosis.
The vitamin D receptor (VDR) is a nuclear transcription factor which binds to the vitamin D response element (VDRE) of the human osteocalcin gene and regulates its expression. Humans with VDR gene mutations, ever among those with the same point mutation in their VDR gene, demonstrate clinical heterogeneity. In addition, in some patients with these mutations, rickets has not recurred following cessation of therapy during follow-up ranging from 6 to 24 years. While important, it is likely that the VDR protein is not the sole factor in the development of rickets. To try to understand these clinical findings, the complex formed between the VDRE and one or more proteins in the nuclear extracts of cultured skin fibroblasts treated with 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3), retinoic acid (RA), and/or triiodothyronine (T3) was investigated since such complexes are likely to precede the transcription of the VDR gene. Complex formation in the control cells with an intact VDR was increased by treatment with either 0.1 nM, 1 nM, 10 nM 1,25(OH)2D3, 100 nM RA, or 100 nM T3; however, combinations of these compounds did not produce an additive effect. In cells of affected patients, 1,25(OH)2D3, RA, or T3 increased complex formation, while no combination had an additive effect. These results indicate that 1,25(OH)2D3, RA, and T3 play a role in the regulation of bone remodeling through modulating the formation of protein complexes on the VDRE. Therefore, the clinical observations in patients with a VDR mutation might be explained at least in part by the overlapping control of osteocalcin expression by 1,25(OH)2D3, RA and T3.
We examined the effect of pyrrolidine dithiocarbamate (PDTC), which potently blocks the activation of nuclear factor kappa B (NF-kappa B), on the induction of apoptosis by a variety of agents. Treatment of a human promyelocytic leukemia cell line, HL-60, with 10 micrograms/mL etoposide or 2 microM 1-beta-D-arabinofuranosylcytosine induced NF-kappa B activation within 1 hr and subsequently caused apoptosis within 3-4 hr. The simultaneous addition of 50-500 microM PDTC with these agents blocked NF-kappa B activation and completely abrogated both morphologically apoptotic changes and internucleosomal DNA fragmentation for up to 6 hr. However, PDTC failed to inhibit the endonuclease activity contained in the whole cell lysates. The inhibitory effect of PDTC was also observed in etoposide- and dexamethasone-induced apoptosis in human thymocytes at a concentration of 1-10 microM. Since PDTC has both antioxidant and metal-ion chelating activities, we tested the effects of N-acetyl-L-cysteine (NAC) (antioxidant) or o-phenanthroline (OP) (metal-ion chelator) on the induction of apoptosis. Pretreatment of HL-60 cells or thymocytes with 100-500 microM OP for 2 hr, but not 10-60 mM NAC, suppressed subsequent occurrence of apoptosis induced by etoposide. These results suggest that the activation of NF-kappa B plays an important role in the apoptotic process of human hematopoietic cells.
Male F344 rats were treated with lead nitrate, nickel chloride, cobalt chloride or cadmium chloride, and changes in the expression of cytochrome P450IA2 (CYP1A2) in the livers were assessed by enzymatical, immunochemical, and molecular biological methods. All ionic metals used significantly decreased total CYP amount in the liver microsomes. However, among ionic metals used only lead showed inhibitory effects on the microsomal activity for CYP1A2-dependent mutagenesis of aromatic amines and on the expression of mRNA and protein of the enzyme, indicating that ionic lead is a unique inhibitor for the expression of CYP1A2 enzyme in the rat liver.