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Biomedical subjects

R Ozaki

Publications and source records attributed to R Ozaki.

17 recordsLinked to original sources
PubMed2006

Assessment of glomerular filtration rate in addition to albuminuria is important in managing type II diabetes.

Although much emphasis has been placed on screening for albuminuria in type II diabetic patients, less attention has been focused on the role of glomerular filtration rate (GFR) in the assessment of risk. Herein, we examined the association between GFR and vascular complications in a consecutive cohort of 5174 type II diabetic patients between 1995 and 2000. Renal function was assessed by GFR (estimated by Modification of Diet in Renal Disease equation). The frequency of chronic kidney disease (CKD) as defined by GFR <60 ml/min/1.73 m(2), micro- and macrovascular complications, and their associations were analyzed. In this study cohort, 6% had serum creatinine > or =150 micromol/l and 15.8% had CKD. After adjustment for potential confounders, including urinary albumin excretion, odds ratios [95% confidence interval (CI)] across different stages of estimated GFR (> or =90, 60-89, 30-59, 15-29, <15 ml/min/1.73 m(2)) for macrovascular disease were 1.00, 1.42 [1.12-1.80], 1.80 [1.32-2.45], 2.74 [1.64-4.56], and 4.05 [1.77-9.26], respectively (P for trend <0.001); for retinopathy were 1.00, 1.23 [1.04-1.46], 1.80 [1.40-2.30], 2.05 [1.25-3.37], and 4.12 [1.56-10.90], respectively (P for trend <0.001); for sensory neuropathy were 1.00, 1.53[1.27-1.85], 2.09 [1.58-2.76], 4.32 [2.41-7.77], and 3.16 [1.25-8.02], respectively (P for trend <0.001); and for microalbumuria (with GFR <15 ml/min/1.73 m(2) excluded from the analysis) were 1.00, 1.51 [1.30-1.75], 5.80 [4.52-7.44], and 52.5 [16.4-168.2] respectively (P for trend <0.001). Measurement of serum creatinine alone without GFR may underestimate renal impairment in type II diabetic patients. Decreasing GFR was significantly associated with increasing frequency of micro- and macrovascular complications.

Adult↗
PubMed2006

Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients-- interaction with ACE insertion/deletion polymorphism.

Angiotensin-converting enzyme (ACE) insertion(I)/deletion (D) polymorphism may modify the effect of inhibition of the renin-angiotensin-aldosterone system (RAAS) on survival and cardiorenal outcomes in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (+/- standard deviation) age of 59.7 +/- 13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 (interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality (HR 0.34 (0.23, 0.50)) and renal end point (HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection (II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 (0.25, 0.72) vs 0.95 (0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers.

Aged↗
PubMed2006

Prediction of cardiovascular and total mortality in Chinese type 2 diabetic patients by the WHO definition for the metabolic syndrome.

AIM: The aim of this study is to investigate the prevalence of metabolic syndrome (MES) in type 2 diabetic patients and the predictive values of the World Health Organization (WHO) and National Cholesterol Education Programme (NCEP) definitions and the individual components of the MES on total and cardiovascular mortality. METHODS: A prospective analysis of a consecutive cohort of 5202 Chinese type 2 diabetic patients recruited between July 1994 and April 2001. RESULTS: The prevalence of the MES was 49.2-58.1% depending on the use of various criteria. There were 189 deaths (men: 100 and women: 89) in these 5205 patients during a median (interquartile range) follow-up period of 2.1 (0.3-3.6 years). Of these, 164 (87%) were classified as cardiovascular deaths. Using the NCEP criterion, patients with MES had a death rate similar to those without (3.51 vs. 3.85%). By contrast, based on the WHO criteria, patients with MES had a higher mortality rate than those without (4.3 vs. 2.4%, p = 0.002). Compared to patients with neither NCEP- nor WHO-defined MES, only the group with MES defined by the WHO, but not NCEP, criterion had significantly higher mortality rate (2.6 vs. 6.8%, p < 0.001). Using Cox regression analysis, only age, duration of diabetes and smoking were identified as independent factors for cardiovascular or total death. Among the various components of MES, hypertension, low BMI and albuminuria were the key predictors for these adverse events. CONCLUSIONS: In Chinese type 2 diabetic patients, the WHO criterion has a better discriminative power over the NCEP criterion for predicting death. Among the various components of the MES defined either by WHO or NCEP, hypertension, albuminuria and low BMI were the main predictors of cardiovascular and total mortality.

Adolescent↗
PubMed2006

The efficacy and tolerability of fosinopril in Chinese type 2 diabetic patients with moderate renal insufficiency.

BACKGROUND: The renoprotective effect of angiotensin II antagonists has been demonstrated in type 2 diabetic patients with nephropathy but similar data on angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and renal clearance, in 38 type 2 diabetic patients with moderate renal impairment (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled trial comparing fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive treatment over a 2-year period. The primary endpoints were the rate of change and the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range 47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For similar blood pressure control, the percentage change of UAE in patients with microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/- 28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In the fosinopril group, the rate of change of endogenous CrCl was slower than the placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The incidence of adverse events was similar between the two groups. CONCLUSIONS: Fosinopril treatment reduced albuminuria and rate of decline in renal function in type 2 diabetic patients with moderate renal insufficiency and did not increase the incidence of adverse events.

Aged↗
PubMed2003

Triglyceride, albuminuria and blood pressure are the major associations of non-fatal cardiovascular disease in Chinese type 2 diabetes.

Diabetes is associated with an increased risk of cardiovascular disease (CVD). We studied risk factors for CVD in a cohort of Chinese type 2 diabetic patients recruited between July 1994 and August 1998. Ischemic heart disease (IHD) was defined as a history of: (i) confirmed coronary artery disease (with typical electrocardiographic changes or a positive exercise tolerance test) in patients under care of a cardiologist; (ii) documented myocardial infarction; or (iii) coronary interventions such as angioplasty or coronary artery bypass graft. Cerebrovascular accident (CVA) was defined as any definite cerebral vascular event with or without residual neurological deficit. CVD was defined as a history of IHD or CVA. The study enrolled 3333 patients, including 1370 men (41.1%) and 1963 women (58.9%) of mean age 55.9+/-13.3 years (range, 16-91 years; median, 57 years). A total of 279 patients (8.4%) had CVD (including 4.1% with CVA, 4.9% with IHD, and 0.6% with both CVA and IHD). Men had an overall higher rate of CVD than women (10.1% vs. 7.1%, p=0.002). All cardiovascular diseases showed a progressive increase in prevalence with increasing age with the peak among those aged </=60 years. Logistic regression analysis was used to examine the predictive value of age, body mass index, waist-to-hip ratio, blood pressure, fasting plasma glucose, glycated hemoglobin, lipid profiles, albuminuria, smoking and family history of diabetes on the risk of CVD. In women, age, systolic blood pressure and triglyceride level and in men, age and albuminuria, were predictive for CVD. In conclusion, 8.4% of Hong Kong Chinese type 2 diabetic patients being followed in a hospital out-patient setting have a history of established and confirmed cardiovascular disease. Age, systolic blood pressure, triglyceride and albuminuria were the major independent risk factors for non-fatal cardiovascular diseases.

Adolescent↗
PubMed1995

Effects of vamicamide on urinary bladder functions in conscious dog and rat models of urinary frequency.

PURPOSE: To investigate the usefulness of vamicamide, (+/-)-(2R*, 4R*)-4-dimethylamino-2-phenyl-2-(2-pyridyl)valeramide, as a novel drug for the treatment of urinary frequency and incontinence. MATERIALS AND METHODS: Urinary frequency was evaluated in specially devised conscious dog and rat models by investigating the effects of the drug on urinary bladder function of these animals by cystometrography. RESULTS: In the dog model with transected hypogastric nerves, the bladder volume at micturition (bladder capacity) was less than 50% that of the sham-operated dog, and in the rat model with bilateral lesioning of nuclei basalis, a part of the brain, by ibotenic acid injection, bladder capacity was about 50% that of the sham-operated rat. Other bladder functions in both models were unchanged. In the dog model, orally administered vamicamide at 0.32 and 1.0 mg./kg. significantly increased bladder capacity and did not change residual urine volume or micturition pressure. Oxybutynin 0.10 mg./kg., one of the most popular drugs for the treatment of urinary frequency and incontinence, or atropine 0.10 mg./kg. induced significant increases in bladder capacity similarly to vamicamide at 0.32 mg./kg. In the rat model, oral vamicamide 0.32 mg./kg. also significantly increased bladder capacity and did not change micturition pressure or threshold pressure. Again, oxybutynin 0.10 mg./kg. or atropine 0.32 mg./kg. had almost the same effects as vamicamide 0.32 mg./kg. CONCLUSIONS: These findings suggest that vamicamide should be useful for the treatment of urinary frequency.

Animals↗
PubMed1994

Tolerance to the vascular effect of a novel nitric oxide-donating vasodilator, FK409.

We investigated whether tolerance develops to the vasorelaxant effects of a new vasodilator, (+-)-(E)-4-ethyl-2-[(E)-hydroxy-imino]-5-nitro-3-hexenamide (FK409), in isolated canine coronary artery strips and to its hypotensive effect in rats, and whether FK409 activates soluble guanylate cyclase isolated from vascular tissues in the absence of L-cysteine. No tolerance to FK409 (0.46 nM to 0.46 microM or 1-1000 micrograms/kg, i.v.) or cross-tolerance between FK409 and glyceryl trinitrate was demonstrated in in vitro and in vivo experiments, whereas the tolerance to glyceryl trinitrate (0.44 nM to 4.4 microM or 1-1000 micrograms/kg, i.v.) was marked in both conditions. In addition, FK409 (0.1-10 microM) activated soluble guanylate cyclase without L-cysteine, but glyceryl trinitrate (1-100 microM) required the addition of L-cysteine (5 mM) for the activation of the enzyme. The results suggest that FK409 may be advantageous compared to tolerance-producing nitrates currently in clinical use, and that this property of FK409 is probably due to its independence of a sulfhydryl group donor.

Animals↗
PubMed1994

Antianginal effects of FK409, a new spontaneous NO releaser.

1. The aim of this study was to compare antianginal effects of (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), a new spontaneous nitric oxide releaser, with those of isosorbide dinitrate (ISDN). We used two types of rat angina model; methacholine- and arginine vasopressin (AVP)-induced coronary vasospasm models. 2. In the in vitro study, FK409 showed 80 times more potent vasorelaxant effect in dog isolated coronary artery than ISDN (EC50 = 16.7 +/- 4.8 and 1340 +/- 320 nM, respectively). 3. In the rat methacholine-induced coronary vasospasm model, FK409 suppressed the elevation of ST segment dose-dependently and significantly at 0.1 mg kg-1, i.d. On the other hand, ISDN suppressed it significantly at 3.2 mg kg-1, i.d. In addition, the efficacy of 3.2 mg kg-1 ISDN in the model was almost the same as that of 0.1 mg kg-1 FK409. 4. In the above experiments, FK409 and ISDN decreased mean blood pressure significantly at the maximum dose tested (1.0 mg kg-1, i.d. and 3.2 mg kg-1, i.d., respectively) but did not change heart rate at these doses. Therefore, the hypotensive effect of FK409 was 10 times weaker than the antianginal effect of the compound, while those of ISDN were almost the same. 5. In the rat AVP-induced coronary vasospasm model, 32 mg kg-1 FK409 significantly inhibited the depression of ST segment 60 min after oral administration. On the other hand, 32 mg kg-1 ISDN did not inhibit it at 60 and 120 min after oral administration. 6. In conclusion, FK409 inhibits coronary vasospasm more potently in two types of rat angina models than ISDN. In addition, FK409 shows an antianginal effect more selectively that a hypotensive effect,compared with ISDN.

Angina Pectoris, Variant↗
PubMed1994

Urinary bladder-selective action of the new antimuscarinic compound vamicamide.

1. The inhibitory action of vamicamide (FK176, (+/-)-(2R*,4R*)-4-dimethylamino-2-phenyl-2-(2-pyridyl)valeramide, CAS 132373-81-0) on the responses of various tissues to the cholinergic agonists, carbachol and McN-A-343 (4-[m-chlorophenylcarbamoyloxy]-2-butynyl-trimethylammonium chloride, CAS 55-45-8), was investigated in isolated tissue preparations. Vamicamide showed competitive antagonistic actions against all the preparations tested and its pA2 value for the urinary bladder was 6.82, which was higher than that for the atria (5.94) and almost the same as that for the vas deferens (6.90) and for the stomach (6.81). The pA2 values of oxybutynin hydrochloride (oxybutynin) and atropine sulfate monohydrate (atropine) were nearly the same in all the tissues tested. 2. Oral administration of vamicamide 0.1-1.0 mg/kg inhibited dose-dependently spontaneous bladder contractions caused by raising the intravesical volume in conscious rats. Inhibitory actions were also obtained with 0.32-3.2 mg/kg of oxybutynin or 0.0032-0.032 mg/kg of atropine, but the duration of action of oxybutynin was shorter than that of vamicamide or atropine. Vamicamide further inhibited bladder contractions in rats following intravesical administration of 0.05-0.5 mg/ml solution. 3. Vamicamide had no effect or only slightly inhibited spontaneous motility of the stomach and distal colon in conscious rats, as well as heart rate and salivary secretion in conscious dogs, after oral dosing with 3.2 mg/kg of the compound. Similar results were obtained with oxybutynin, excepting the occurrence of tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of FK409, a novel nitric oxide donor, on acute experimental myocardial ischemia.

The anti-ischemic heart effect of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]- 5-nitro-3-hexenamide (FK409), a novel nitric oxide donor, was studied in dog and rat preparations in vivo and in vitro. In anesthetized dogs with partially occluded coronary artery that were subjected to atrial pacing at a constant blood pressure, FK409 (1-100 micrograms/kg, i.v.) suppressed the ST-segment elevation on epicardial electrocardiograms. Glyceryl trinitrate (GTN; 10, 32 micrograms/kg) or dipyridamole (1000 micrograms/kg) failed to suppress the ST-segment elevation, although continuous i.v. infusion of GTN (32, 100 micrograms/kg/min) was effective. FK409 also suppressed the ST-segment elevation induced by methacholine in anesthetized rats by both i.v. (10, 100 micrograms/kg) and intraduodenal (i.d., 100, 1000 micrograms/kg) injections, while GTN (100 micrograms/kg, i.v.; 1000 micrograms/kg, i.d.) was effective only by the i.v. route. FK409 (0.32 microgram/kg/min, i.v.) and GTN (10 micrograms/kg/min) increased the blood flows of the endomyocardium (ENDO) and the epicardium (EPI) and the flow ratio of ENDO/EPI in the ischemic zone in anesthetized dogs with occluded coronary artery. Furthermore, in isolated dog vascular preparations, FK409 (4.6 x 10(-10)-4.6 x 10(-7) M) had a greater vasorelaxing effect on the large coronary artery [2.0-2.5-mm outer diameter (od)] than on the small coronary artery (0.3-0.5-mm od) or the saphenous artery. The results suggest that FK409 protects against acute experimental myocardial ischemia through relaxation of the large conductive coronary artery, and may be a useful oral drug for the treatment of angina pectoris.

Animals↗
PubMed1991

Incidence and mortality patterns of malignancy and factors affecting the risk of malignancy in dialysis patients.

A questionnaire study was performed among 23,209 dialysis patients in 589 institutions together with a retrospective study at Keio University Hospital to determine the risk of malignancy and factors affecting the risk ratio in dialysis patients. The incidence and mortality were 1.4-fold and 1.9-fold higher in dialysis patients than the expected rates in the general population. Incidence and mortality were 1.9-fold and 2.6-fold higher in males than in females. The risk ratios were remarkably high in university hospitals, followed by public hospitals. However, there was no significant difference between those in private hospitals and in the general population. The incidence was very high during the first 6 months of dialysis treatment and rather low in the 7th-10th year. The risk ratio of malignancy was higher in younger patients. Beyond the age of 60, the influence of age was greater than that of renal failure. Malignancies of the digestive organs were frequent and constituted 56% of all malignancies. Frequencies of malignancy in the liver, colon, rectum, bladder and kidney were higher than expected, whereas in the pancreas the frequency was lower than expected. Metastasis of malignancy was observed in 30% of the cases. Our study demonstrated a slight to moderate overall increase in the risk of malignancy and a widely differing risk ratio of malignancy by organ involved, sex, age, hospital group, epidemiological index and length of dialysis treatment in a large single racial population of maintenance dialysis patients.

Adult↗
PubMed1983

High risk ratio on mortality and characteristics of malignancies in dialysis patients.

A questionnaire study was done in order to clarify the risk ratios on the mortality of malignancy and the characteristics of malignancies in dialysis patients. The risk ratios were 4.2 times in males and 7.5 times in females greater than those among the age adjusted general population respectively. The average interval from the first dialysis to the clinical onset of malignant disease was 12 months. About a half of the patients died within 3 months. Frequencies of death in colon cancer, especially rectum, uterus and liver were higher in dialysis patients. Dialysis patients died of malignancies belonged to the older group of the dialysis patient population, however they were younger comparing with those died of malignancies in the general population.

Adolescent↗
PubMedDate not supplied

Phenotypic and genetic clustering of diabetes and metabolic syndrome in Chinese families with type 2 diabetes mellitus.

BACKGROUND: The aim of this study was to investigate the familiality and clustering of type 2 diabetes (T2DM) and metabolic syndrome (MES) predominantly in families with young-onset diabetes from the Hong Kong Family Diabetes Study. METHODS: One hundred and seventy-nine families (913 subjects) were ascertained through a diabetic proband. Anthropometry, glucose homeostasis, blood pressure and lipid levels were examined. Familial aggregation and inter-relationships of these traits were examined by recurrence risk ratio, heritability, genetic and environmental correlations. RESULTS: One hundred and forty families (78%) had at least one subject with early-onset T2DM (age-at-diagnosis </=40 years). MES was highly prevalent in probands (53%) and siblings (25%). Recurrence risk ratios in siblings were high for T2DM (4.3), hypertension (2.9) and central obesity (2.0). Body mass index, waist circumference, blood pressure, plasma insulin, triglyceride, HDL-cholesterol levels, insulin resistance and beta-cell function had high estimates of heritability (0.45-0.63). Bivariate quantitative analyses revealed differential contribution of genetic and environmental factors to the phenotypic correlation between metabolic trait pairs. Obesity indices showed the strongest phenotypic correlation with other traits, and were significantly influenced by genetic factors (genetic correlation = 0.29-0.60). CONCLUSION: There was significant familial aggregation of T2DM and related phenotypes including obesity, hypertension and dyslipidaemia. The clustering of metabolic traits is likely due to genetic effects, interacting with shared and unique lifestyle/environmental factors. The high familiality suggests that screening for MES is important, especially in families with young-onset diabetes, and that the families in HKFDS are valuable subjects for genetic studies of these metabolic diseases.

Adult↗
PubMedDate not supplied

Seizure recurrence in temporal lobe epilepsy.

We report on a patient with clinical, electroencephalographic and radiological features of temporal lobe epilepsy, whose seizures were initially controlled with antiepileptic treatment. Five years after the onset of seizures, he developed more frequent and prolonged episodes of confusion, which were misinterpreted as secondary to temporal lobe epilepsy. Further investigation revealed the presence of hypoglycaemia and the eventual diagnosis of metastatic insulinoma.

Adult↗