FUT2 non-secretor status is associated with Type 1 diabetes susceptibility in Japanese children.

AIM: To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children. METHODS: We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined. RESULTS: The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075]. CONCLUSIONS: The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children.

Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21.

AIMS: The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes. METHODS: We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis. RESULTS: Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10-5 ; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years. CONCLUSIONS: The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood.

Meta-analysis of genome-wide association studies for panic disorder in the Japanese population.

Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10(-5), odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10(-4)). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD.

Comparison of methods for chemical-compound affinity prediction.

The selection of effective features from various descriptors of chemical compounds and the exploitation of the most appropriate classifier is a momentous issue in improving overall accuracies of virtual screening of chemical compounds. In this article, the performance of various feature-selection methods and various classifiers of chemical compound-protein binding affinities are compared by using six series of compounds: cytochrome P450 2C9 inhibitors, multi-drug-resistance reversal compounds, estrogen receptor ligands, inhibitors of human ether-a-go-go-related genes, and ligands of serotonin receptor 5HT1A and 5HT2A. As a result, it was found that the genetic algorithm was superior to the other feature-selection methods, and its combination with Random Forests and Adaboosts or Baggings gave almost the same performance as support-vector machines and was superior to the other classifiers. The precision and recall of these methods were almost the same or ascendant to those of previous work. The automatically selected descriptors for each protein-compound affinity prediction were plausible and would be informative to interpret the resulting model.

Cold-specific and light-stimulated expression of a wheat (Triticum aestivum L.) Cor gene Wcor15 encoding a chloroplast-targeted protein.

Wcor15, a member of the wheat cold-responsive (Cor) gene family, has been isolated and characterized. The deduced polypeptide WCOR15 (MW=14.7 kDa) showed high homology to the previously identified wheat and barley COR proteins. Southern blot analysis using diploid, tetraploid and hexaploid wheat and diploid Aegilops species showed that the wheat and related wild genomes possessed multiple copies of Wcor15 homologues. Five copies were assigned to the homologous group 2 chromosomes by nulli-tetrasomic analysis. Northern blot analysis showed that expression of Wcor15 was specifically induced by low-temperature. Homologous transcripts accumulated in leaves, and light markedly increased their steady-state levels. Bombardment-mediated transient expression analysis of a chimeric CaMV 35S::Wcor15-GFP construct showed protein-targeting to epidermal guard cell chloroplasts in excised spiderwort leaves. A promoter of Wcor15 contained at least three CRT/DRE-like sequence motifs found in Arabidopsis Cor genes and induced the reporter GUS gene expression in leaves of transgenic tobacco plants under low-temperature and light conditions. These results suggest that the functional Cor gene system involving the CRT/DRE cis-element is conserved in both monocotyledonous and dicotyledonous plants.

Efficacy of oral UFT as adjuvant chemotherapy to curative resection of colorectal cancer: multicenter prospective randomized trial.

BACKGROUND: The purpose of this study is to evaluate the efficacy of postoperative adjuvant chemotherapy using uracil and tegafur (UFT) for colorectal cancer. METHODS: In a multicenter trial among 43 institutions for patients who underwent curative resection of Dukes' B or C colorectal cancer, a surgery alone group (control group) and a treatment group (UFT group) to which UFT was administered at 400 mg/day for 2 years following surgery were compared. A total of 320 patients were registered between March 1991 and April 1994, and 289 of these patients were analyzed as a full-analysis set. RESULTS: The 5-year disease-free survival rate was 75.7% in the UFT group and 60.1% in the control group, respectively, and the stratified log-rank test showed the statistical significance ( P=0.0081). This difference was marked in rectal cancer ( P=0.0016) and, in particular, the local recurrence was reduced. No significant difference was observed in the 5-year survival rate. The incidence of adverse reactions on administration of UFT was low, and there was no serious adverse reaction. CONCLUSION: It is suggested that the consecutive administration of UFT at 400 mg/day was an effective and highly safe therapeutic method as postoperative adjuvant chemotherapy for rectal cancer.

Ethnic disparities in unmet need for alcoholism, drug abuse, and mental health care.

OBJECTIVE: Recent policy has focused on documenting and reducing ethnic disparities in availability and quality of health care. The authors examined differences by ethnic status in unmet need for alcoholism, drug abuse, and mental health treatment. METHOD: Data were from a follow-up survey of adult respondents to a 1996-1997 national survey. Non-Hispanic whites, African Americans, and Hispanics were compared in access to alcoholism and drug abuse treatment and mental health care (primary or specialty), unmet need for care, satisfaction with care, and use of active treatment for alcoholism, drug abuse, and mental health problems in the prior 12 months. RESULTS: A total of 31.9% of whites, 28.1% of African Americans, and 30.1% of Hispanics had some alcoholism, drug abuse, and mental health care, mostly in primary care. Among those with perceived need, compared to whites, African Americans were more likely to have no access to alcoholism, drug abuse, or mental health care (25.4% versus 12.5%), and Hispanics were more likely to have less care than needed or delayed care (22.7% versus 10.7%). Among those with need, whites were more likely than Hispanics or African Americans to be receiving active alcoholism, drug abuse, or mental health treatment (37.6% versus 22.4%-25.0%). CONCLUSIONS: The authors document greater unmet need for alcoholism and drug abuse treatment and mental health care among African American and Hispanics relative to whites. New policies are needed to improve access to and quality of alcoholism, drug abuse, and mental health treatment across diverse populations.

Comparative effects of dietary fat types on hepatic enzyme activities related to the synthesis and oxidation of fatty acid and to lipogenesis in rats.

The effects of different types of dietary fat on the activities of hepatic enzymes related to fatty acid synthesis [glucose-6-phosphate dehydrogenase (G6PDH) and acetyl-CoA carboxylase (ACC)], oxidation [acyl-CoA synthetase (AST), carnitine palmitoyl transferase (CPT), and peroxisomal beta-oxidation (PbetaOX)], and lipogenesis [phosphatidate phosphohydrolase (PAP), diacylglycerol acyltransferase (DGAT), and phosphocholine diacylglycerol transferase (PCDGT)], and plasma and liver lipid levels were investigated in male Wistar rats. The animals were 6 weeks old and about 120 g of body weight, and were fed on test diets containing 20% of a mixture of tripalmitin, tristearin and corn oil (SFA), olive oil (OLI), sunflower oil (SUN), linseed oil (LIS), and sardine oil (SAR) for 2 weeks. The concentrations of plasma total cholesterol (T-CHOL), high-density lipoprotein-cholesterol (HDL-CHOL), triacylglycerol (TG) and phospholipid (PL) were generally higher in the rats fed on SFA and OLI than in those given SUN, LIS and SAR. The rats fed on OLI had a higher level of liver T-CHOL than those fed on the other fats. The liver TG content was nearly higher from the intake of SFA and OLI than from SUN, LIS and SAR, although the liver PL level was not affected by the type of dietary fat. The SFA and OLI groups had the highest activities of hepatic G6PDH and ACC, and the SAR group, the lowest activities. The activities of AST and CPT, and peroxisomal PbetaOX in the liver were higher in the rats fed on the LIS and SAR diets than in those given the other diets. The hepatic PAP activity was higher from the intake of OLI and SUN, and tended to be higher from SFA than from LIS and SAR. The activity of liver DGAT was higher from SFA and inclined to be higher from OLI, SUN, and LIS than from SAR, while the PCDGT activity in the liver was not effected by the type of dietary fat. The concentrations of plasma and liver TG were generally positively correlated with the activities of liver enzymes related to the synthesis of fatty acids and lipids, and negatively with those involved in fatty acid oxidation. Based on these results, it is suggested that the levels of plasma and liver TG were controlled by different types of dietary fat through changes in the hepatic enzyme activities related to fatty acid synthesis, lipogenesis, and fatty acid oxidation.

Effects of dobutamine on critical capillary PO(2) and lactic acidosis threshold in patients with cardiovascular disease.

BACKGROUND: Muscle capillary PO(2) has been found to reach a minimal value, ie, a critical capillary PO(2), in the midrange of work capacity in patients with cardiovascular disease. However, it is not known if the critical capillary PO(2) can be influenced by a change in blood flow response to exercise. This study was carried out to determine the effect of changing the blood flow response to exercise, using low-dose infusion of dobutamine, on muscle end-capillary PO(2) (as approximated by femoral vein PO(2)), lactate concentration, oxygen uptake (O(2)), and the relation among these variables. METHODS: Eleven male patients with coronary artery disease performed an incremental exercise test on a cycle ergometer with and without continuous infusion of dobutamine, 6 microg/kg/min. Respiratory gas analysis was performed on a breath-by-breath basis; femoral vein blood was sampled every minute through a percutaneous catheter. RESULTS: Dobutamine increased resting O(2) and O(2) at the lactic acidosis threshold (LAT) but not peak O(2). The femoral vein PO(2) rapidly decreased toward a minimal value with increasing work rate (O(2)) irrespective of the infusion of dobutamine. After reaching its nadir (critical PO(2)), femoral vein lactate began to increase without further decrease in PO(2). Infusion of dobutamine significantly increased femoral vein resting PO(2) (27.4 +/- 4.9 mm Hg vs 32.5 +/- 3.8 mm Hg) and critical PO(2) (20.5 +/- 1.5 mm Hg vs 21.9 +/- 1.7 mm Hg), but not the PO(2) at peak O(2) (22.1 +/- 3.3 mm Hg vs 22.0 +/- 2.9 mm Hg). CONCLUSIONS: Infusion of dobutamine was found to raise the critical PO(2) and LAT but not peak O(2). These findings suggest that some of the acute increase in blood flow induced by dobutamine infusion benefits exercising muscle by increasing capillary PO(2), thereby delaying the onset of lactic acidosis.

Expression and chromosome location of hamster Ku70 and Ku80.

Ku proteins play an important role in DNA double-strand break (DSB) repair, chromosome maintenance, and growth regulation. To understand the fundamental characteristics of Ku proteins, we examined the electrophoretic mobility and expression of hamster Ku70 and Ku80 and determined the chromosome locations of their genes. The electrophoretic mobility of hamster Ku proteins are different from that of human Ku proteins. No significant changes in the quantity of Ku proteins were observed in CHO-K1 cells treated with 10 Gy of ionizing radiation, suggesting that both proteins are expressed constitutively in amounts adequate to repair DNA DSBs. The chromosome locations of the Ku genes were determined by direct R-banding fluorescence in situ hybridization. The Ku70 gene was localized to Syrian hamster chromosome 4qa4.1--> qa4.2 and Chinese hamster chromosome 2p3.1, and the Ku80 gene was localized to Syrian hamster chromosome 4qb5--> qb6.1 and Chinese hamster chromosome 2p3.5-->p3.6. These results provide clues to the biological functions of Ku, as well as useful information for constructing comparative chromosome maps between hamsters and other mammalian species, including human, mouse, and rat.

Collaborative interventions for physically injured trauma survivors: a pilot randomized effectiveness trial.

Posttraumatic behavioral and emotional disturbances occur frequently among physically injured hospitalized trauma survivors. This investigation was a pilot randomized effectiveness trial of a 4-month collaborative care intervention for injured motor vehicle crash and assault victims. As surgical inpatients, intervention subjects (N=16) were assigned to a trauma support specialist who provided counseling, consulted with surgical and primary care providers, and attempted postdischarge care coordination. Control subjects (N=18) received usual posttraumatic care. For all participants, posttraumatic stress disorder (PTSD) and depressive symptoms, episodic alcohol intoxication, and functional limitations were evaluated during the hospitalization and 1 and 4 months postinjury. Study logs and field notes revealed that over 75% of intervention activity occurred in the first month after the trauma. One-month post-trauma intervention subjects when compared to controls demonstrated statistically significant decreases in PTSD symptoms as well as a reduction in depressive symptoms. However, at the 4-month assessment, intervention subjects evidenced no significant improvements in PTSD and depressive symptoms, episodic alcohol intoxication, or functional limitations. Future larger scale trials of stepped collaborative care interventions for physically injured trauma survivors are recommended.

Dimerization and nuclear localization of ku proteins.

Ku, a heterodimer of Ku70 and Ku80, plays a key role in multiple nuclear processes, e.g. DNA repair, chromosome maintenance, and transcription regulation. Heterodimerization is essential for Ku-dependent DNA repair in vivo, although its role is poorly understood. Some lines of evidence suggest that heterodimerization is required for the stabilization of Ku70 and Ku80. Here we show that the heterodimerization of these Ku subunits is important for their nuclear entry. When transfected into Ku-deficient xrs-6 cells, exogenous Ku70 and Ku80 tagged with green fluorescent protein accumulated into the nucleus, whereas each nuclear localization signal (NLS)-dysfunctional mutant was undetectable in the nucleus, supporting the idea that each Ku can translocate to the nucleus through its own NLS. On the other hand, the nuclear accumulation of each NLS-dysfunctional mutant was markedly enhanced by the presence of an exogenous wild-type counterpart. In Ku-expressing HeLa cells, each NLS-dysfunctional mutant, as well as wild-type Ku70 and Ku80, was still detectable in the nucleus, whereas the double mutant of each Ku subunit with decreased functions of both nuclear targeting and dimerization was undetectable in the nucleus. Our results indicate that each Ku subunit can translocate to the nucleus not only through its own NLS but also through heterodimerization with each other.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Effects of physical training on the recovery of the autonomic nervous activity during exercise after coronary artery bypass grafting: effects of physical training after CABG.

Analysis of heart rate variability (HRV) can identify patients at risk of sudden cardiac death after myocardial infarction. The present study examined the effect of 2 weeks of supervised aerobic exercise training on the recovery of the autonomic nervous activity, exercise capacity, and cardiac output (CO) after coronary artery bypass grafting (CABG). Twenty-eight patients were randomly divided into the training group or the control group and performed exercise tests at 1 week, 3 weeks, 3 months, 6 months and 1 year after CABG. The HRV was measured, and the high-frequency component of HRV was used as an index of parasympathetic nerve activity (PNA); the plasma norepinephrine concentration (NE) was used as an index of sympathetic nervous activity. Cardiac output was also measured. In the training group, peak VO2, peak CO and PNA during exercise had improved at 3 weeks, but there was no improvement in these indices in the control group. NE decreased 1 week after CABG in both groups. These results indicate that physical training soon after CABG improves not only the exercise capacity, but also PNA.

Impaired heart rate response during incremental exercise in patients with acute myocardial infarction and after coronary artery bypass grafting: evaluation of coefficients with Karvonen's formula.

Heart rate (HR) response during exercise in patients with ischemic heart disease was evaluated, and the appropriateness of Karvonen's method for determining rehabilitation exercise target HR was investigated. The study group comprised 24 patients with acute myocardial infarction (AMI) and 37 patients who had undergone coronary artery bypass grafting (CABG). Cardiopulmonary exercise testing (CPX) was performed with a cycle ergometer and changes in HR (deltaHR)/changes in work rate (deltaWR) and interval changes of the coefficient of Karvonen's formula were evaluated. In the AMI group and the CABG group, deltaHR/deltaWR were significantly lower than those of age-matched control subjects (p<0.01). Karvonen's coefficients ranged from 0.37 to 0.54 when calculated from actual peak HR and 0.21 to 0.32 calculated from the predicted peak HR. An impaired HR response was found in patients with AMI and those who had had CABG up to 6 months previously. Because the Karvonen's coefficient values, which ranged from 0.6 to 0.8, were elevated for these patients, and considering the data from the CPX, increased exercise is recommended for such cases.

Accuracy and repeatability of blood volume measurement by pulse dye densitometry compared to the conventional method using 51Cr-labeled red blood cells.

OBJECTIVE: To determine the accuracy and repeatability of pulse dye densitometry (PDD) in measuring blood volume (BV) by comparing it with the conventional method using 51Cr-labeled red blood cells (RI method) and by assessing sequential measurements. DESIGN: Prospective clinical study. SETTING: University hospital. PATIENTS AND PARTICIPANTS: Eleven adult ICU patients who received cardiac surgery (1st ICU day). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: After injecting indocyanine green (10 or 20 mg) into the right atrium, its arterial concentration was continuously monitored at the nose and finger by PDD, and BV was calculated by back extrapolating the logarithmic dye concentration on the dye elimination curve between 2.5 and 5.5 min after mean transit time to each mean transit time with the least squares method. These measurements were repeated in eight patients and performed only once in the other three, and the BV was measured concurrently by the RI method one time. The Bland-Altman method was used for evaluating differences between methods and within methods. The (percentage) biases and standard deviations between the PDD and RI methods and between the successive measurements by PDD at the finger and nose were 0.26 +/- 0.491 (8.8 +/- 15.3%) and 0.004 +/- 0.251 (0.06 +/- 5.9%) with the probe on a nostril, and 0.16 +/- 0.561 (2.5 +/- 14.4%) and 0.19 +/- 0.311 (4.7 +/- 7.3%) using the finger probe. The bias between methods was less than 10%, and the repeatability of PDD was better. CONCLUSIONS: As PDD can measure BV with good repeatability and with a small bias compared to the RI method, serial changes in BV can be evaluated at the bedside of critically ill patients noninvasively and repeatedly.

Ku70 can translocate to the nucleus independent of Ku80 translocation and DNA-PK autophosphorylation.

Ku plays an important role in multiple nuclear processes, e.g., DNA repair, chromosome maintenance, and transcriptional regulation. Although some evidence suggests that the nuclear translocation of Ku plays a key role in regulating the function of Ku, the mechanism is poorly understood. Using the site-directed mutagenesis technique, we demonstrate here that Ku70 can translocate to the nucleus without heterodimerization with Ku80. The nuclear accumulation of Ku70 mutants of the nuclear localization signal, which retained their binding ability with Ku80, was diminished. On the other hand, Ku70 mutants which lacked the ability to bind with Ku80 could translocate to the nuclei. Human Ku70, when transfected, accumulated within the nuclei of hamster xrs-6 cells which had undetectable DNA-PK activity and Ku80. Ku70 and Ku80 mutants of DNA-PK phosphorylation sites showed normal heterodimerization and nuclear translocation. These findings also support the idea that Ku70 can translocate to the nucleus independent of DNA-PK autophosphorylation.

Lack of a relation between serum potassium concentration and exercise hyperpnea in patients with chronic heart disease.

Exertional dyspnea, a major symptom of patients with chronic heart failure, mainly stems from an abnormally high ventilatory response to exercise. However, there has been considerable controversy surrounding the mechanisms of respiratory control during exercise, especially regarding the role of serum potassium. We investigated the relation between serum potassium concentration [K+] and ventilation (VE) during exercise before and after oral supplements of potassium chloride in cardiac patients. Thirteen patients with chronic heart disease performed a 6-min constant-work-rate exercise (65.8+/-11.1 W) with respiratory gas measurements before initiating oral supplements of potassium chloride, 4 weeks after continued supplements, and 4 weeks after discontinuing supplements. Blood was sampled from a forearm vein at rest before exercise and at the end of exercise for measurement of [K+] and blood gases. The [K+] at rest was 3.66+/-0.30 mmol/L before oral supplements of potassium and significantly increased to 4.08+/-0.31 mmol/L (p<0.01) after supplements. In spite of the significant increases in the [K+], resting VE was not changed. While serum [K+] during exercise was significantly higher after potassium supplements than before, exercise VE was not influenced by the changes in [K+] throughout the study period. The findings of the present study strongly suggest that the chronic increase in the serum [K+] has no influence on the resting or exercise VE in patients with heart disease.

Percutaneous transluminal coronary angioplasty improves oxygen uptake kinetics during the onset of exercise in patients with coronary artery disease.

STUDY OBJECTIVES: Although percutaneous transluminal coronary angioplasty (PTCA) is known to have beneficial effects on exercise capacity, its effects on the cardiovascular response during the onset of exercise have not been clarified. The present study was undertaken to determine the effects of PTCA on the kinetics of oxygen uptake (VO(2)) during constant-work-rate exercise in patients with coronary artery disease, as well as on their indexes of maximal work capacity. METHODS: Seventeen patients with coronary artery disease who received successful PTCAs performed a 50-W constant-work-rate exercise test for 6 min and a symptom-limited incremental exercise test both before and 4 months after the PTCA procedure. VO(2) was calculated from breath-by-breath analysis of respired gases. The time constant of VO(2) kinetics during the onset of 50-W exercise was determined by fitting a single exponential function to the VO(2) response. RESULTS: In 14 patients without coronary restenosis, the time constant of VO(2) kinetics was significantly shortened from (mean +/- SD) 57.4 +/- 12.6 before PTCA to 48.2 +/- 9.5 s after PTCA (p = 0. 0035), indicating improved kinetics of the VO(2) response. In these subjects, the peak VO(2) obtained during maximal exercise testing also increased from 23.1 +/- 3.5 to 26.5 +/- 3.2 mL/min/kg, respectively (p = 0.0005). However, there was no improvement in these indexes in the patients who had restenosis after undergoing PTCA (n = 3). CONCLUSION: Indexes of cardiopulmonary exercise testing, which reflect an efficiency of oxygen flow to the exercising muscle, can be used as an objective, noninvasive, and cost-effective guide for understanding which patients will not have coronary restenosis following PTCA.

A phase III randomized study comparing doxifluridine and 5-fluorouracil as supportive chemotherapy in advanced and recurrent gastric cancer.

We conducted a phase III randomized study to investigate effects of supportive chemotherapy with oral doxifluridine (group A, 75 patients) or 5-fluorouracil (group B, 75 patients) in advanced gastric cancer when intensive chemotherapy was not an option. Although there were no significant differences between the groups with regard to survival, hospital-free survival and time to progression, median values of 3 endpoints were superior in group A. Secondary analysis showed that group A patients with prior chemotherapy tended to have longer survival and hospital-free survival and significantly longer time to progression.