Monocyte chemoattractant protein-1 is associated with silent cerebral infarction in patients on haemodialysis.

BACKGROUND: In patients with chronic renal failure undergoing haemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of monocyte chemoattractant protein-1 (MCP-1) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased MCP-1 concentration correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging (MRI) findings, 52 Japanese patients undergoing HD were divided into two groups: with SCI (61 ± 7 years, mean ± SD, n= 28) and without SCI (60 ± 6 years, n= 24). The gender, metabolic profiles and MCP-1 concentration were compared between the two groups. RESULTS: The level of MCP-1 was higher in the with-SCI group than in the without-SCI group (P < 0.0001). The proportion of smokers was higher in the with-SCI group (P < 0.05) than in the without-SCI group. Plasma level of high-density lipoprotein cholesterol was lower, while uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05 respectively) compared to the without-SCI group. Multiple logistic regression analysis identified MCP-1 level as being significantly associated with the presence of SCI (odds ratio 1.48, 95% confidence interval = 1.10-5.75, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI, and that MCP-1 is significantly associated with the presence of SCI in HD patients.

Interleukin-6 and silent cerebral infarction in hemodialysis patients: a cross-sectional study.

BACKGROUND: In patients with chronic renal failure undergoing hemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of interleukin-6 (IL-6) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased IL-6 levels correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging findings, we divided 50 Japanese patients undergoing HD into two groups: with SCI (60 ± 7 years, mean ± SD, n = 27) and without SCI (60 ± 6 years, n = 23). We compared the gender, body mass index, metabolic profiles, IL-6 levels, and smoking habits between the two groups. RESULTS: We made the following observations: (i) The prevalence of diabetes or hypertension did not differ between the two groups, (ii) the level of IL-6 was higher in the with-SCI group than in the without-SCI group (P < 0.0001), (iii) the proportion of smokers was higher in the with-SCI group (P < 0.05), (iv) plasma level of high-density lipoprotein cholesterol was lower, whilst uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05, respectively), and (v) multiple logistic regression analysis identified IL-6 levels as being significantly associated with the presence of SCI (odds ratio 3.13, 95% CI = 1.42-7.89, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI and that IL-6 is significantly associated with the presence of SCI in HD patients.

Correlations of HHV-6 viral load and plasma IL-6 concentration with HHV-6 encephalitis in allogeneic stem cell transplant recipients.

This study investigated factors associated with the development of human herpesvirus (HHV)-6 encephalitis. Among 111 enrolled subjects, 12 patients developed central nervous system (CNS) dysfunction. CNS dysfunction in four patients was found to have no association with HHV-6. The remaining eight patients displayed HHV-6 encephalitis (n=3), limbic encephalitis (HHV-6 DNA in cerebrospinal fluid was not examined; n=3) or CNS dysfunction because of an unidentified cause (n=2). Real-time PCR showed CNS dysfunction in the latter eight patients, which developed concomitant with the appearance of high plasma levels of HHV-6 DNA (> or =10(4) copies/ml). Overall, eight of the 24 patients with high-level HHV-6 DNA developed CNS dysfunction, whereas no patients developed CNS dysfunction potentially associated with HHV-6 infection if peak HHV-6 DNA was <10(4) copies/ml. We next analyzed plasma concentrations of IL-6, IL-10 and tumor necrosis factor-alpha among patients who displayed high-level plasma HHV-6 DNA and found elevated IL-6 concentrations preceding HHV-6 infection in patients who developed CNS dysfunction. (Mean+/-s.d.: 865.7+/-1036.3 pg/ml in patients with CNS dysfunction; 56.5+/-192.9 pg/ml in others; P=0.01). These results suggest that high-level HHV-6 load is necessary for the development of HHV-6 encephalitis, and systemic inflammatory conditions before HHV-6 infection form the preparatory conditions for progression to encephalopathy.

Induction of heat shock proteins prevents the arrhythmogenic substrate for atrial fibrillation.

Atrial fibrillation (AF) is the commonest arrhythmia. Studies have shown that atrial tachypacing (artificial persistent AF) causes electrical remodelling. This is characterised by the shortening of the atrial effective refractory period (ERP), in which reduction in L-type Ca(2+) channel current plays an essential part. Atrial fibrosis, a feature of structural remodelling, is induced by continuous infusion of angiotensin II, and has been associated with conduction delay in atria, which promotes AF. Acute atrial ischaemia, frequently observed during development of acute coronary syndrome, has been associated with atrial conduction heterogeneity, which also promotes AF. Induction of heat shock proteins (Hsp72 and Hsp27) by hyperthermia and/or geranylgeranylacetone has demonstrated to protect the heart against such atrial remodelling. The potent protective role of Hsp72 and Hsp27 against clinical AF in patients who underwent open heart surgery has been shown. Taken together, interventions that induce heat shock responses (including induction of Hsp72 and Hsp27) may prevent newly developed AF and delay the progression of paroxysmal AF to persistent AF.

Visceral fat accumulation is a significant risk factor for white matter lesions in Japanese type 2 diabetic patients.

BACKGROUND: The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. The elevated visceral fat accumulation (VFA) has been reported to be closely related to the development of atherosclerosis. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with VFA and insulin resistance in type 2 diabetic patients not receiving insulin treatment. MATERIAL AND METHODS: Based on brain magnetic resonance imaging (MRI), 95 type 2 diabetic patients were divided into two groups: WML-positive group (aged 59 +/- 7 years, mean +/- SD n = 37) and WML-negative group (aged 58 +/- 5, years, n = 58). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin, homeostasis model assessment (HOMA) index, and haemoglobin A1c. The fat distribution was evaluated by measuring the visceral fat accumulation by abdominal computerized tomography at the umbilical level. RESULTS: The body mass index was higher in the WML-positive group than in the WML-negative group (P < 0.005). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < 0.05 and P < 0.01, respectively). FPG (P < 0.01), insulin concentrations (P < 0.0001), HOMA index (P < 0.0001) and VFA (<0.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high VFA and insulin resistance (P < 0.001, P < 0.0001, respectively). CONCLUSIONS: The results of this preliminary study indicate that the presence of WML was associated with the high VFA and insulin resistance in Japanese patients with type 2 diabetes mellitus. Further larger cohort studies are warranted to confirm these findings.

New squatting test indices are useful for assessing baroreflex sensitivity in diabetes mellitus.

AIMS: The heart rate (HR) responses after performance of the squatting and standing manoeuvre are thought to be a useful tool to assess autonomic neuropathy in diabetics. Our aim was to develop new simple squatting test indices and to analyse their applicability to the assessment of baroreflex sensitivity (BRS) in patients with diabetes. METHODS: Twenty healthy volunteers (mean age 23.2 +/- 3.8 years) and 51 patients with diabetes (mean age 55.9 +/- 10.6 years) were enrolled in study 1 and study 2, respectively. Each subject stood for 3 min (basal period), then squatted down for 1 min (Sq) and stood up again for 1 min (St). In study 1, the squatting test was performed before and after pharmacological autonomic blockade. In study 2, we measured HR in each period and calculated the difference between basal HR and HRSq (DeltaHRSq) and between HRSt and HRSq (DeltaHRSt). BRS was also measured using the phenylephrine method in diabetic patients. RESULTS: In healthy individuals during autonomic blockade, HR changes were mainly controlled by the vagal tone during squatting and by the sympathetic tone during standing. In diabetic patients, DeltaHRSq and DeltaHRSt positively correlated (r = 0.86, P < 0.0001) and both DeltaHRSq and DeltaHRSt significantly correlated with BRS (r = 0.66, P < 0.0001 and r = 0.61, P < 0.0001, respectively). CONCLUSIONS: The new squatting test indices provide useful information for assessing autonomic neuropathy and for identifying diabetic patients at high risk of cardiovascular events.

Hyperhomocysteinaemia is a significant risk factor for white matter lesions in Japanese type 2 diabetic patients.

The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Plasma total homocysteine (tHcy), which increases with diabetes, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of WML correlates with tHcy and insulin resistance in type 2 diabetic patients not receiving insulin treatment. Based on brain magnetic resonance imaging findings, 81 type 2 diabetic patients were divided into two groups, with-WML group (57 +/- 8 years, mean +/- standard deviation, n = 31) and without-WML group (57 +/- 6 years, n = 50). The blood glucose level was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin, Homeostasis Model Assessment (HOMA) Index and hemoglobin A1c. The body mass index was higher in the with-WML group than in the without-WML group (P < 0.05). Plasma levels of triglyceride were higher whilst high-density lipoprotein cholesterol was lower in the with-WML group than in the without-WML group (P < 0.05 and P < 0.0001 respectively). FPG (P < 0.005), insulin concentrations (P < 0.0001), HOMA Index (P < 0.0001) and tHcy (<0.0001) levels were higher in the with-WML group than in the without-WML group. Multivariate logistic analysis revealed that WML was independently predicted by the high tHcy and insulin resistance. Our findings indicate that the presence of WML was associated with the high tHcy and insulin resistance in these Japanese patients with type 2 diabetes mellitus.

Plasma HHV-6 viral load-guided preemptive therapy against HHV-6 encephalopathy after allogeneic stem cell transplantation: a prospective evaluation.

Human herpesvirus 6 (HHV-6) causes life-threatening encephalopathy in recipients of allogeneic SCT, but no consensus has been reached regarding appropriate preventive methods. This study evaluated a plasma HHV-6 viral load-guided preemptive approach against HHV-6-associated encephalopathy. Plasma real-time PCR assay was performed once a week. Among 29 patients, 19 developed positive plasma HHV-6 DNA. Median maximum plasma HHV-6 DNA was 4593.5 copies/ml plasma (range, 150.0-127 891.0 copies/ml plasma). In one of eight events with low-level HHV-6 DNA (defined as <1000 copies/ml plasma) and four of seven events with mid-level HHV-6 DNA (1000-9999.5 copies/ml plasma), HHV-6 loads in plasma subsequently continued increasing. Ganciclovir was administered against six of nine patients with high-level HHV-6 DNA (> or =10,000 copies/ml plasma). High-level HHV-6 DNA resolved similarly in both groups with or without ganciclovir therapy. Among the nine patients with high-level HHV-6 DNA two developed encephalopathy. As encephalopathy developed before the detection of high-level HHV-6 DNA in plasma, these two patients had not received preemptive ganciclovir therapy. In conclusion, our preemptive approach against HHV-6-associated encephalopathy cannot prevent all cases of HHV-6 encephalopathy in SCT recipients due to the dynamic kinetics of plasma HHV-6 viral load.

Pioglitazone shift circadian rhythm of blood pressure from non-dipper to dipper type in type 2 diabetes mellitus.

BACKGROUND: Insulin resistance significantly correlated with a non-dipper type of essential hypertension. Thiazolidinediones (TZD), oral hypoglycaemic agents that act as insulin sensitizers, have been demonstrated in multiple in vivo and in vitro studies to possess antihypertensive properties. This study examined the efficacy of TZD therapy with pioglitazone at transforming the circadian rhythms of blood pressure from a non-dipper to a dipper type. MATERIALS: We examined 31 patients with type 2 diabetes mellitus during both a baseline period and a period of treatment with pioglitazone. Patients received 15 mg day(-1) pioglitazone for four weeks and 30 mg day(-1) for 12 weeks. Twenty-four hour ambulatory blood pressure monitoring (ABPM) and laboratory data (blood tests for cardiovascular risk factors) were obtained at the beginning and end of the study. RESULTS: In non-dippers (n = 16), but not dippers (n = 15), we observed a significant interaction between pioglitazone therapy and nocturnal falls in systolic and diastolic blood pressure. This examination indicated that the magnitude of the nocturnal blood pressure fall was affected by pioglitazone therapy. In non-dippers, but not dippers, a significant correlation was observed between the percent decrease in nocturnal BP and the homeostasis model assessment (HOMA) index (r = 0.774, P = 0.0007). CONCLUSIONS: The present study demonstrated that pioglitazone can restore the nocturnal BP declines in parallel to reductions in the HOMA index, suggesting that insulin resistance may play an important role in the genesis of circadian BP rhythms. TZD-based treatment may thus have the additional therapeutic advantage of reducing the risk of cardiovascular complications by transforming the circadian rhythm of BP.

Smoking is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients.

BACKGROUND: Smoking and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This study tested the hypothesis that smoking is associated with insulin resistance/hyperinsulinaemia and cardiovascular autonomic dysfunction in type 2 diabetic patients who are not treated with insulin. MATERIALS AND METHODS: The study patients were 22 current smokers with type 2 diabetes mellitus (age: 57 +/- 5 years, mean +/- SD) and 30 age-matched never-smoked patients with type 2 diabetes mellitus (control group, 57 +/- 8 years). The quality of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index and haemoglobin A1c (HbA1c). The severity of smoking status was expressed by the Brinkman index, which is calculated as number of cigarettes per day multiplied by years of smoking. Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart-rate variability, plasma norepinephrine concentration and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the current smokers group than in the never-smoked group (P < 0.05). Early and delayed (123)I-MIBG myocardial uptake values were lower (P < 0.05, and P < 0.01, respectively) and the percentage washout-rate of (123)I-MIBG was higher (P < 0.0001) in the current smokers group than in the never-smoked group. Fasting immunoreactive insulin (F-IRI) concentration (P < 0.0001) and the homeostasis model assessment (HOMA) index (P < 0.0001) were higher in the current smokers group than the never-smoked group. Multiple logistic regression analysis revealed that smoking was independently predicted by F-IRI and the percentage washout-rate of (123)I-MIBG. CONCLUSIONS: The results of the study suggested that smoking was associated with cardiovascular autonomic dysfunction and hyperinsulinaemia and that F-IRI and the percentage washout-rate of (123)I-MIBG were independent predictors of smoking in these Japanese patients with type 2 diabetes mellitus.

Development of a new method for assessing the cardiac baroreflex: response to downward tilting in patients with diabetes mellitus.

OBJECTIVE: To investigate the clinical value of a new non-invasive method for assessing baroreflex sensitivity using downward tilting. PATIENTS: 34 patients with diabetes mellitus, mean (SD) age, 53.6 (11.8) years. DESIGN: Arterial blood pressure and ECG were recorded simultaneously while the patients were on a tilt table. After 20 minutes at a 70 degrees upright tilt, the patients were returned to the supine position at a speed of 3.2 degrees /s (downward tilting baroreflex sensitivity test, DT-BRS). A beat to beat systolic blood pressure increase associated with a corresponding lengthening of the RR interval was noted during downward tilting. Baroreflex sensitivity was also assessed using the conventional method of an intravenous injection of phenylephrine (Phe-BRS). Heart rate variability was analysed during rest and tilting. RESULTS: The slope of the regression line for systolic blood pressure v RR interval during downward tilting was highly correlated with Phe-BRS (r = 0.83, p < 0.0001). Both DT-BRS and Phe-BRS were correlated with the high frequency (HF) component of resting heart rate variability (p < 0.005) and with the ratio of the low frequency to the high frequency component (LF/HF) during upright tilting (p < 0.005). DT-BRS and Phe-BRS were also correlated with the difference between rest and tilting values of HF and LF/HF (p < 0.005). CONCLUSIONS: DT-BRS provides a physiological, non-invasive method for determining baroreflex sensitivity and may be a useful index of reflex cardiac vagal and sympathetic function in patients with diabetes mellitus.

Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart.

BACKGROUND: Induction of heat-shock proteins (HSPs) results in cardioprotection against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer agent, reportedly induces HSP72 in the gastric mucosa and small intestine of rats. The present study tested the hypothesis that oral GGA would induce HSP72 in the heart and thus render cardioprotection against ischemia/reperfusion injury in rats. METHODS AND RESULTS: Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. Ten minutes of whole-body hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after administration. Therefore, isolated perfused heart experiments using a Langendorff apparatus were performed 24 hours after administration of 200 mg/kg GGA (GGA group) or vehicle (control group). After a 5-minute stabilization period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by 30 minutes of reperfusion. During reperfusion, the functional recovery was greater and the released creatine kinase was less in the GGA group than in the control group. Electron microscopy findings revealed that the ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA-treated myocytes. CONCLUSIONS: The results suggest that oral GGA is cardioprotective against ischemic insult through its induction of HSP72.

[Electrophysiological tests in clinical laboratory].

We briefly described recently developed methods for testing cardiac electrophysiological phenomena such as 24-hour Ambulatory ECG, high resolution ECG, body surface mapping ECG, heart rate variability, QT and QT dispersion, and T wave alternans. Of these methods ambulatory ECG monitoring is important and useful for detecting malignant arrhythmias and ischemia attacks, especially in cases of vasospastic angina. Using this method, it is possible to quantitatively analyze arrhythmia and elucidate the pathophysiology of vasospastic angina. The monitoring system is useful not only for diagnosis, but also for assessing treatment efficacy. Heart rate variability is currently used for analyzing the autonomic nervous system; however, the exact meaning of each index still remains to be confirmed. The concept of QT dispersion was recently introduced as an index for detecting dispersion of ventricular repolarization and QT dispersion is still controversial. T wave alternans monitoring has been recently introduced as a new method of assessing the microvolt level of T wave alternans, which has been hypothesized to correlate with the occurrence of arrhythmic events in myocardial infarction. The possible roles of these methods and their applications for clinical practice are discussed.

Effect of essential hypertension on cardiac autonomic function in type 2 diabetic patients.

OBJECTIVES: The aim of this study was to examine the effects of essential hypertension on cardiac autonomic function in type 2 diabetic patients. BACKGROUND: Hypertension is common in type 2 diabetic patients and is associated with a high mortality. However, the combined effects of type 2 diabetes and essential hypertension on cardiac autonomic function have not been fully elucidated. METHODS: Thirty-three patients with type 2 diabetes were assigned to a hypertensive diabetic group (n = 15; age: 56 +/- 8 years, mean +/- SD) or an age-matched normotensive diabetic group (n = 18, 56 +/- 6 years). Cardiac autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability (HRV), plasma norepinephrine concentration and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.05). The early and delayed myocardial uptake of 123I-MIBG was lower (p < 0.01 and p < 0.05, respectively), and the percent washout rate of 123I-MIBG was higher (p < 0.05) in the hypertensive diabetic group. However, the high frequency (HF) power and the ratio of low frequency (LF) power to HF power (LF/HF) of HRV and plasma norepinephrine concentration were not significantly different. The homeostasis model assessment index was higher in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.01). CONCLUSIONS: Our results indicate that essential hypertension acts synergistically with type 2 diabetes to depress cardiac reflex vagal and sympathetic function, and the results also suggest that insulin resistance may play a pathogenic role in these processes.

[An approach for the quality control in clinical microbiology laboratory by antibiotic susceptibility].

It is important to develop a system for the prevention of various errors and the maintenance of the high quality level in the department of laboratory medicine. We developed a computer program to infer the species of microorganisms by assessing the minimal inhibitory concentration of respective microorganisms to various antibiotics, antibiotic susceptibility patterns(ASP). Retrospective analysis of 3,405 strains from 39 species using this program resulted in a sensitivity of 91.4% and specificity of 98.9%. Furthermore, in 1,660 strains isolated from September 1999 to August 2000, the efficacy of this program was evaluated using both this program and conventional identifying method such as VITEK, api and ATB. The discrepancy between this inferring method and conventional method was noted in 179 strains, revealing errors in 12 strains. We conclude that this ASP inferring program is useful for preventing errors and the maintenance of high quality examination by combining with conventional methods in the laboratory.

The effect of propafenone on premature ventricular contractions (PVC): an analysis based on heart rate dependency of PVCs.

The effect of 450 mg/day propafenone for two weeks on premature ventricular contractions (PVCs) was studied in combination with an assessment of heart rate (HR) dependency of PVCs using Holter ECG monitoring in patients with more than 720 PVCs per day. The PVC-HR correlation was classified into positive (P), bidirectional (B), and flat and negative (FN) correlation groups. The positive group included only patients in whom PVC frequency increased with a heart rate increase, while the bidirectional group included patients with PVCs whose frequency increased at low heart rates and decreased at high heart rates. The FN group contained both flat (PVC frequency was almost fixed regardless of heart rate changes) and negative (PVC frequency decreased as heart rate increased) correlations. The effectiveness of propafenone was 70% in the positive group and 50% in the nonpositive group which included both bidirectional (67%) and FN (0%) groups, using a > 70% PVC reduction as a criterion of efficacy. From this, we concluded that propafenone is effective in patients showing either positive or bidirectional PVC-HR correlation. The coupling interval (CI) of PVCs was also prolonged by propafenone as a whole. The present study suggests that there are differences in the mechanism of PVC development in patients with flat or negative correlation and those with a positive or bidirectional correlation. Thus, this type of analysis contributes to an understanding of the action of antiarrhythmic agents, and may allow the prediction of their efficacy on PVCs.

[Present and future of cardiac function tests: electrophysiologic tests].

Various electrocardiographic and physiologic tests have been developing for almost 100 years since Einthoven established the standard 12 lead electrocardiogram(ECG) system. Recently, interest has focused on the new developing parameters associated with cardiac ventricular repolarization, such as transmural dispersion of repolarization, T wave alternans and QT dispersion. QT dispersion, measured as interlead difference of QT interval, has been suggested to reflect regional variation of ventricular repolarization. However, still unsolved basic problems give difficulties for clinical acceptance of this parameter. On the other hand, it is generally accepted that heart rate variability obtained from Holter ECG is useful tool to assess the autonomic tone. Head-up tilt test is a valuable diagnostic tool to identify patients with neurally mediated syncope and also useful for assessment of reflex cardiac autonomic function, such as baroreflex sensitivity. The number of electrophysiologic study(EPS) dramatically increased together with increase of radiofrequency catheter ablation. A new three-dimensional nonfluoroscopic electroanatomical mapping system(CARTO) is an exciting development in catheter ablation treatment. Transtelephonic ECG and its computer-assisted answering system are also useful for diagnose and treatment in the patients of paroxysmal cardiac symptoms.

[Respiratory function tests--current and future perspective].

The apparatus for the respiratory function test have recently made a great progress and become very easy to handle owing to the development of computer technology and medical ordering system. However, the respiratory function tests depend its result on the cooperation of patients. Thus, it is important for the medical technician to obtain the maximum efforts and cooperation of the patients in the testing. In the sense, the standardization of the testing should be done urgently regarding procedures, softwares, hardwares and maintenance of apparatus. In the future perspectives, we would like to emphasize following 3 points. First, more noninvasive and sophisticated testing methods and instruments should be developed, since the patients' age will become more and more old and vigorous active cooperation may not be possible for the assessment of respiratory function. The testing for the transplantation of lung should also be developed. Second, the development of screening test and its performance for the routine medical check for the local inhabitants have been important for the early detection, treatment, and follow up of respiratory diseases. Finally, the medical technician should be prepared so that the testing is available when it is needed.

[Clinical characterization of blaIMP positive gram-negative rods isolated cases].

We detected the metallo-beta-lactamase gene blaIMP positive strains of the gram-negative rods (GNR) isolated in Oita Medical University Hospital between 1993 and 1999 and studied the clinical characteristics of patients infected or colonized with blaIMP positive GNR. 25 strains (20 Pseudomonas aeruginosa and 5 Serratia marcescens) were detected and most of them were isolated from urinary samples after 1997. In the studies of antimicrobial susceptibility, some strains had sensitivity to aztreonum or imipenem although most of the strains showed multidrug resistance. When blaIMP positive GNR were isolated from patients, these strains were thought to have caused infection in 88% of the patients. About half of the patients were over 65 years old and had malignant diseases. Most of the patients had inserted urinary tract catheters, intratracheal tube or intravernous catheters. It was suggested that the insertion of the catheters were related to infection of blaIMP positive GNRs. Two patients were not treated with any antibiotics before the isolation of blaIMP positive GNRs although more than half of the patients were administered carbapenems and cephems. Most of strains were isolated in the same department and showed the same genotype by pulsed field gel electrophoresis.