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A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.  相似文献   
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Direct measurement of intra-arterial blood pressure (BP) for 24-h provides approximately 100,000 values that vary enormously, but each (BPi) can be expressed by the equation BPi = BP0 + DeltaBPi (BP0, base BP; DeltaBPi, BP increment, i=1, 2, ..., 100 x 10(3)). About 20% of outpatients with hypertension exhibit white-coat hypertension (WCH). In such patients, DeltaBPc (i = c; c, time at the clinic) is surmised to be large. A method for explaining the physiological factors in DeltaBPc and the estimation of base BP in the outpatient clinic is important. This study addresses this issue. A total of 293 subjects were divided into four groups: 1) WCH group, 45 individuals (office BP > or = 140/90 mmHg and 24-h indirect BP < 125/80 mmHg); 2) normotensive (NT) group, 84 controls matched for age and sex; 3) WHO-I group, 95 hypertensive patients with WHO stage I (office BP > or = 140/90 mmHg and 24-h BP > or = 125/80 mmHg); and 4) WHO-II group, 69 hypertensive patients with WHO stage II. Their BPc and heart rate (HR; HRc, clinic HR) values were measured by a BP-ECG monitoring device in the outpatient clinic. Power-spectral analysis was used to obtain the ratio between the low-frequency component (LF) and high-frequency component (HF) of ECG-RR variability (LF/HF = LH). Twenty-four-hour indirect BP (and BP0) and base HR (HR0) were measured by a portable device (TM2425) at 30-min intervals. Then, DeltaBPc (= BPc - BP0) was estimated by performing linear multivariate analysis applying the model equation DeltaBPc = (BPc -alphaLH)(1-betaHR0/HRc) + epsilon to the above variables (alpha and beta, constant values; epsilon, error). This model equation made it possible to estimate BP0 (and DeltaBPc) with a high coefficient of correlation (r > or = 0.85, mean of error less than 0.82 +/- 5.9 mmHg). The predictive accuracy for discrimination between WCH and sustained hypertension (WHO-I and WHO-II groups) by this equation was 88%. The new DeltaBP-estimation device (BP-ECG monitor) enabled us to infer BP0 and is therefore useful in estimating WCH in the outpatient clinic.  相似文献   
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BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.  相似文献   
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The diuretic activity of a quinolinone oxime diuretic, M12285, was examined after renal arterial, i.v. and portal injection in rats. M12285 injected into the renal artery at a dose of 1 mg/kg caused no diuretic effect, whereas i.v. and portal injections induced marked diuresis dose dependently. The minimum effective dose with portal injection was lower (1 mg/kg) than that with i.v. injection (3 mg/kg) and the start of the effect was faster with portal injection. These results indicated that some metabolic modification in the liver is necessary for the diuretic activity to appear. Accordingly, we performed in situ rat liver perfusion with M12285 and obtained several metabolites. Renal arterial injection of each fractionated metabolite of M12285 revealed that all the diuretic activity derived from one of these metabolites. From IR and 1H-nuclear magnetic resonance (1HNMR) measurements, the chemical structure of this active metabolite was assumed to be a sulfate-conjugated form of M12285 at the oxime moiety. Based on this tentative chemical structure, we synthesized the oxime sulfate of M12285 (potassium salt, M17000) and confirmed the identity of IR and 1HNMR spectra. Administration of M17000 into the renal artery induced apparent diuresis in a dose-dependent manner in both rats and dogs. These results indicate that the oxime sulfate of M12285 is responsible for the diuretic activity of M12285. Therefore, we synthesized several derivatives of M17000 and confirmed their possible therapeutic value as a novel family of diuretics, namely quinolinone oxime sulfonic acids.  相似文献   
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Sodium valproate was administered to Jcl:ICR mice in order to evaluate teratogenicity in the cardiovascular system. A single dose of 600mg/kg of sodium valproate was injected intraperitoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized to observe incidence and type of cardiovascular abnormality in live fetuses. Cardiovascular abnormalities were found most frequently in the group treated on day 7, being recognized in 86% of litters (19/22) and in 29% of live fetuses (70/238). Among these, there were 28 cases of transposition of the great arteries, 13 of double outlet right ventricle, 11 of endocardial cushion defect, 9 of ventricular septal defect, 5 of tricuspid atresia, and 4 of hypoplastic left heart syndrome.  相似文献   
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Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.  相似文献   
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