Renoprotective effects of telmisartan in patients with advanced chronic kidney disease.

BACKGROUND: Angiotensin II receptor blockers (ARBs) provide renoprotective effects in patients with mild-to-moderate chronic kidney disease (CKD). However, there have been few reports regarding whether ARBs show clinical efficacy and safety in patients with advanced CKD. METHODS: Seventy-two hypertensive patients with Stages 3 - 4 CKD receiving no ARBs were enrolled in this study and observed up to 48 months. Telmisartan was added to conventional antihypertensive agents (n = 36, mean estimated glomerular filtration ratio [eGFR] 19.7 ml/min/1.73 m2) whilst the remaining control patients were not treated with ARBs (n = 36, mean eGFR 19.2 ml/min/1.73 m2). Urinary protein excretion, kidney function, and the occurrence of end-stage renal disease requiring renal replacement therapy, hyperkalemia, and death were analyzed. RESULTS: Baseline characteristics of each group were similar. During the observation period, the blood pressures of each group decreased at similar rates. In the telmisartan group, 17 patients (47.2%) were introduced to renal replacement therapy, as compared with 31 patients (86.1%) in the control group (relative risk 0.55, 95% confidence interval 0.19 - 0.92, p < 0.05). Telmisartan significantly reduced proteinuria levels (from 3.47 +/- 3.00 to 2.41 +/- 2.46 g/g . creatinine, p < 0.05) and was associated with a reduction of 49.6% in the decline rate of eGFR. The incidence of major adverse events in both groups was similar. CONCLUSIONS: The addition of telmisartan to conventional antihypertensive therapy is associated with significant improvement in kidney outcome without increased incidence of adverse effects, even in patients with advanced CKD.

[Hansen's disease and nephropathy as its sequence].

Nephropathy as the sequences of Hansen's disease before and after the introduction of chemotherapy was compared referring to the report by Hayashi in 1943 and the summary of the autopsy reports from 1978 to 1981 at National Hansen's disease hospital Zenseien. Unlike the high rates of tuberculosis as the cause of death before the introduction of chemotherapy (41.3%) those thereafter decreased to be negligible. On the other hand the comparison of the rates of nephropathy with the same way as that of tuberculosis was impossible since the description about nephropathy by Hayashi was not sufficient to characterize each nephropathy since he included arteriolitis, glomerulonephritis and interstitial nephritis together in the term of nephritis. Death rate due to nephritis among Hansen's disease patients according to Hayashi at that time was 21.2% which was twice as many comparing to that in the other cases. According to the report about the cases of Zenseien those reported to have glomerulonephritis was 37.3% though those were not necessarily listed as the cause of death. Also the nephropathy including fibrinoid angitis with occasional microaneurysmal dilatation of afferent arteries, glomerulitis, sclerosis and stricture of efferent arteries likewise ischemic acute tubular necrosis possibly as the result of these angiopathy seemed to be present. These vascular changes partially resemble to that of microscopic periarteritis nodosa but seems to be common in the smaller arteries. In conclusion, unlike the case of tuberculosis the rate of nephritis including glomerulitis, arteriolitis and interstitial nephritis as Hayashi used as his criteria does not seem to have decreased. Therefore, the critical analysis of the nephropathy especially of that relating to the arteriolitis should be done to obtain the knowledge to suppress its occurrence.

[On the lesions caused by a leproma-derived and cultivated Mycobacterium HI-75 produced in ddY mice. With special reference to a factor influencing the lesions and the differences from those by BCG].

Not only in the experimental leprosy, primary aim to make every experimental model crucial for the medical research has been the simulation of the aspect of disease encountered in human case by the simplest possible way. The present study was conducted to do so making some variations in addition to the experimental lepromata, produced in nude mice by Sasaki et al. and by Hamit, utilizing a leproma-derived and cultivated Mycobacterium HI-75 (HI-75). In this study HI-75, Mycobacterium bovip BCG (BCG) and female SPF ddY(ddY) were utilized to make experimental models. In addition to these combinations, the effect of the immunization of beta-glucuronidase binding protein (BGBP) to the lesion was also examined. The BGBP extracted from pisum sativum and utilized in this study shows cross-immunoreactivity with those of HI-75 and M. leprae. As the results, the lesions caused by HI-75 and BCG were somewhat resembling though HI-75 caused a little more extensive lesions especially in lymphocytic and monocytic infiltration. Also HI-75 caused distinct nerve lesions(NL) in which the bacilli were often encountered in the endoneurium but not in those by BCG. Contrarily in mice immunized with BGBP, the lesions were only a little milder and the affected tissue was a little fibrosed. However, in NL the solid form HI-75 were more often observed in the endoneurium. The results indicated that the effect of BGBP immunization on the HI-75 induced lesion was not very clear by the present study alone, however, the proposed models itself should be and will become very useful, for experimental leprology with only slight modifications.

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method.

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left ventricular ejection dynamics, and that (3) the basket catheter is useful because it allows these assessments in the same heart with a nearly fixed left ventricular contractility, at least in our animal model.

On the beta-glucuronidase binding protein (BGBP) of microorganisms. Its purification, the antiserum preparation against that and its localization in leproma and the other infectious lesions shown by immunohistologic method.

Our previous studies suggested that M. leprae (ML) grow in peripheral nerves and lepra cells because ML metabolize hyaluronic acid (HA), and use its component for their growth by the aid of host enzyme combined to the bacilli derived beta-glucuronidase binding protein (BGBP). In this study, therefore, we examined the method to purify BGBP from a mycobacterium HI-75 originally separated from a leproma and cultured by modified Ogawa's medium containing split products of HA (glucuronic acid and N-acetylglucosamine). The distribution of BGBP in leproma and the other lesions consisting of hepatitis B virus infected liver and M. avium-intracellulare infected lung tissue were also immunohistologically examined. As the result, the best method to get BGBP was preparatory electrophoresis in the final step of the purification and not the molecular sieving. The BGBP was actually proven in leproma and the other infected tissues as described, indicating the abilities of these microorganisms to utilize the metabolic machinery of the host with the similar ways to that of ML.

Synthesis of (+)- and (-)-nojirimycin and their 1-deoxy derivatives from myo-inositol.

The conversion of the naturally abundant cyclitol, myo-inositol (4), into (+)-nojirimycin (1a), its enantiomer (1b), and their 1-deoxy analogues (2a and 2b) is described. Biological assay of 2a, 2b, and the bisulfite adducts of 1a and 1b (3a and 3b) showed that the compounds having the unnatural L-gluco configuration (2b and 3b) possess moderate-to-high inhibitory activity against almond beta-D-glucosidase and bovine liver beta-D-galactosidase.

Myocardial blood flow, alternans of ST segment elevation, conduction delay and ventricular arrhythmia during acute myocardial ischemia with and without retrograde blood flow in canine hearts.

The technique of retrograde blood flow has been shown to decrease collateral flow into the ischemic myocardium, and to cause severe myocardial ischemia in dogs. Ischemia with retrograde blood flow in dogs is similar to ischemia in human hearts. Therefore, we examined the effect of retrograde blood flow on myocardial blood flow, ST segment elevation, alternans of ST segment elevation, conduction delay and ventricular arrhythmia in dogs. Sixty dogs were divided into two groups. In group A (N = 32), the left anterior descending coronary artery was occluded for 10 min. In group B (n = 28), ischemia was induced by the technique of retrograde blood flow for 10 min. During ischemia, the myocardial blood flow at the ischemic zone measured by a H2 gas clearance method was 11.2 +/- 1.6 in group A and 5.7 +/- 0.7 ml/min/100 g in group B (p less than 0.01). The maximal ST segment elevation was 13.6 +/- 1.9 in group A and 27.2 +/- 2.1 mV in group B (p less than 0.001); the maximal alternans of ST segment elevation was 5.3 +/- 1.1 in group A and 10.1 +/- 1.4 mV in group B (p less than 0.01); the maximal conduction delay was 51.6 +/- 8.4 in group A and 111.1 +/- 6.2 msec in group B (p less than 0.001); and the incidences of ventricular premature beats (greater than 5/min), ventricular tachycardia and fibrillation were 34%, 41% and 22% in group A, and 68%, 79% and 25% in group B (p less than 0.01, p less than 0.01 and not significant, respectively). It is concluded that ischemia with retrograde blood flow can be used to examine occlusive and reperfusion ventricular arrhythmia in dogs, because the incidences of ventricular premature beats and ventricular tachycardia were high, but that of ventricular fibrillation was not high despite the severe ischemia.

Reflection as a cause of mid-systolic deceleration of pulmonary flow wave in dogs with acute pulmonary hypertension: comparison of pulmonary artery constriction with pulmonary embolisation.

STUDY OBJECTIVE: The aim was to examine whether mid-systolic deceleration of the pulmonary flow wave occurred in acute pulmonary hypertension due to pulmonary artery constriction and pulmonary embolisation, and if so whether it was related to reflection. DESIGN: Various degrees of pulmonary hypertension were induced by both pulmonary artery constriction and pulmonary embolisation in dogs. During control periods and during pulmonary artery constriction and pulmonary embolisation, pulmonary flow and pulmonary artery pressure were recorded, and the forward and backward (reflected) flow waves were separated from the measured pulmonary flow wave by the method of Westerhof et al. MATERIALS: 20 adult mongrel dogs were used and 10 dogs qualified for analysis. The other 10 dogs, which died before both interventions were completed, were excluded. MEASUREMENTS AND MAIN RESULTS: During pulmonary artery constriction, a distinct mid-systolic deceleration of the pulmonary flow wave was observed in five of the 10 dogs, while during pulmonary embolisation, no mid-systolic deceleration was found in these five dogs. The distinct deceleration of the pulmonary flow wave was related to a steep fall and early negative peak in the backward flow wave. CONCLUSION: Mid-systolic deceleration of pulmonary flow wave is likely to be related to reflection.

Effects of captopril on the hypertrophied heart of essential hypertensive patients.

Changes in blood pressure and heart rate after exercise, left ventricular wall thickness, ejection fraction and left ventricular mass were examined by echocardiography before and at the 8th week administration of captopril (37.5-75.0 mg/day) in 11 patients with essential hypertension. The blood pressure showed a gradual and significant decrease from the second week of captopril administration, but the heart rate remained unchanged. No changes were observed in the blood pressure or heart rate after exercise, nor before, during and after the administration of captopril. In the echocardiographic examinations, the wall thickness decreased significantly from 12.1 +/- 2.1 mm before administration to 10.6 +/- 1.5 mm at the 8th week of administration in the interventricular septum, from 11.2 +/- 1.8 mm to 10.1 +/- 1.5 mm in the left ventricular posterior wall, and the left ventricular mass in parallel decreased from 266 g to 218 g. In 7 patients, whose wall thickness was 12 mm or more, the thickness of the septum decreased significantly from 13.9 +/- 1.2 mm to 11.7 +/- 2.1 mm and that of the left ventricular posterior wall from 12.6 +/- 1.5 mm to 10.6 +/- 1.8 mm. Captopril administration produced regression of cardiac hypertrophy in patients with essential hypertension within a period of only 8 weeks.

Effect of pre-existing four hour coronary stenosis on ventricular arrhythmias during a subsequent 10 minute occlusion in dogs.

STUDY OBJECTIVES: The aim was to assess the effect of pre-existing coronary stenosis on ventricular arrhythmia during subsequent acute coronary occlusion. DESIGN: Dogs with a 4 h intact interval followed by a 10 min occlusion of left anterior descending coronary artery (group A) were compared for ventricular arrhythmias with dogs with a 4 h stenosis of the same artery followed by a 10 min occlusion (group B). Myocardial blood flow was measured in the ischaemic myocardium using the H2 gas clearance method to exclude dogs with good collateral flow (myocardial blood flow greater than 11.0 ml.min-1.100g-1). EXPERIMENTAL ANIMALS: 35 mongrel dogs of either sex, weight range 11-26 kg, were used in the experiments (group A, n = 17; group B, n = 18). After exclusion of dogs with good collateral circulation there were 11 dogs in group A (subgroup A1) and 12 dogs in group B (subgroup B1). MEASUREMENTS AND MAIN RESULTS: The incidence of ventricular fibrillation was lower in group B (pre-existing stenosis) than in group A during the 10 min occlusion, though there was no difference in numbers of ventricular premature beats. Maximum ST segment elevation and maximum conduction delay were less in group B than in group A, but myocardial blood flow did not differ during the 10 min occlusion. In the subgroups the incidence of both types of ventricular arrhythmia was lower in subgroup B1 during the 10 min occlusion, while the maximum ST segment elevation and maximum conduction delay were less, and myocardial blood flow was greater. CONCLUSIONS: Pre-existing 4 h coronary stenosis causes the development of collateral flow and reduces the incidence of ventricular arrhythmias during subsequent occlusion.

Left ventricular outflow tract obstruction due to mitral annulus calcification in patient with mild concentric left ventricular hypertrophy.

The combination of the systolic anterior motion of the anterior leaflet of the mitral valve and/or the mitral annular calcification in the case of asymmetrical septal hypertrophy has been fully recognized. However, in concentric left ventricular hypertrophy the systolic anterior motion of the anterior mitral valve and the massive posterior submitral calcification have not been commonly reported. We present a case with mild concentric left ventricular hypertrophy and massive posterior submitral calcification which displace the entire mitral ring anteriorly, namely, toward the left ventricular outflow tract. In this case, typical left ventricular outflow obstruction with systolic anterior motion of the anterior mitral valve was seen. Thus, we considered that this rare condition may have contributed to the formation of the systolic anterior motion of the anterior mitral leaflet in this case. We have provided additional information regarding the possible causes of systolic outflow obstruction in hypertrophic obstructive cardiomyopathy.