Analysis of Renal Transplant Protocol Biopsies in ABO-Incompatible Kidney Transplantation

Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6–12 months, respectively. At 6–12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.     

Comparison of effects of olmesartan and telmisartan on blood pressure and metabolic parameters in Japanese early-stage type-2 diabetics with hypertension.

Angiotensin II type-1 receptor blockers (ARBs) are regarded as first-line treatments for type-2 diabetes with hypertension. Despite the availability of various types of ARBs, there are no comparative studies of their effects on patients with diabetes. In this open-label prospective crossover study, we compared the effects of olmesartan (20 mg/day) and telmisartan (40 mg/day). Twenty Japanese early-stage type-2 diabetes patients with hypertension treated with valsartan (80 mg/day) for at least 8 weeks were recruited to this study. At study entry, valsartan was changed to olmesartan (20 mg/day) or telmisartan (40 mg/day) and administered for 8 weeks. The drugs were then switched and treatment was continued for another 8 weeks. We analyzed the blood pressure lowering effects of each drug by 24-h ambulatory blood pressure monitoring at 0, 8, and 16 weeks. Simultaneously, we measured metabolic parameters and inflammation markers. Olmesartan lowered mean systolic and diastolic blood pressure more significantly than did telmisartan. While there were no differences between the groups in metabolic parameters, including HbA1c and adiponectin, the decreases in serum interleukin-6 and highly sensitive C-reactive protein were more significant by olmesartan treatment. Our results indicate that olmesartan has more potent arterial blood pressure lowering and anti-inflammatory effects than telmisartan.     

Correlations between blood pressure, left ventricular hypertrophy, and left ventricular diastolic function in hypertensive patients]

We examined the relationship of hypertension to left ventricular hypertrophy (LVH) and left ventricular diastolic function by ambulatory blood pressure monitoring device and echocardiography. We studied 36 untreated hypertensive non-diabetic patients (16 males and 20 females) whose casual systolic blood pressure (CSBP) and/or diastolic blood pressure (CDBP) were higher than 140 mmHg and 90 mmHg, respectively. All patients were less than 65 years of age without organic heart disease. Resting systolic and diastolic blood pressures (RSBP, RDBP) were measured after lying in a supine position for 30 min by the auscultatory method. Ambulatory blood pressure was measured every 30 or 60 min for 24 hours by Colin ABPM 630, and the mean 24-hour ambulatory systolic and diastolic blood pressures (ASBP, ADBP) and the systolic and diastolic hyperbaric indices (SHI, DHI) were obtained. The left ventricular mass index (LVMI) was obtained as an indicator of LVH by M-mode echocardiography. The ratio of peak velocity of mitral inflow caused by atrial contraction to that of rapid inflow (A/R) was obtained as an indicator of the LV diastolic function by Doppler echocardiography. The coefficients of correlation between BP and the LVMI, and the A/R were determined. There were significant positive correlations between the LVMI and ASBP (r = 0.51, p < 0.005), the SHI (r = 0.49, p < 0.005), CSBP (r = 0.47, p < 0.01) and RSBP (r = 0.41, p < 0.05), however, there were no significant correlations between the LVMI and ADBP, the DHI, CDBP, RDBP and age. There were significant positive correlations between the A/R and ADBP (r = 0.44, p < 0.01), age (r = 0.40, p < 0.02), CSBP (r = 0.38, p < 0.05) and RDBP (r = 0.38, p < 0.05), however, no significant correlations between the A/R and ASBP, the SHI, DHI, RSBP and CDBP. Only a weak correlation was observed in all subjects between the LVMI and A/R, which was slightly improved by use of > 90 mmHg CSBP readings (r = 0.32). It was concluded that LVH is related mainly to continuous systolic hypertension, and that LV diastolic dysfunction is related mainly to continuous diastolic hypertension. Therefore, it was suggested that LVH and LV diastolic dysfunction in hypertensive patients are caused by different mechanisms.     

Cephalosporin antibiotics. I. Synthesis and structure-activity relationships of 3-thiazoliomethyl derivatives

The synthesis and the structure-activity relationships of 3-thiazoliomethyl cephalosporins are described. In a series of these parenteral compounds, 2-(2-aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido group was found to be a favorable substituent for the C-7 position of the cephem nucleus. They showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species.     

Effects of essential oils on erythrocytes and hepatocytes from rats and dipalmitoyl phosphatidylcholine-liposomes

The effect of essential oils, eugenol, thymol and menthol, on erythrocytes, hepatocytes, dipalmitoyl phosphatidylcholine (DPPC)-liposomes and surface tension were studied at various concentrations. Maximal inhibition of eugenol, thymol and menthol on the hypotonic hemolysis in rat erythrocytes were observed at a concentration of 2 mM, 1 mM and 1 mM, respectively. Eugenol at 4 mM and thymol at 2 mM caused an acceleration of hypotonic hemolysis. In isolated rat hepatocytes, thymol caused an increase in GOT leakage, but eugenol at 4 mM and menthol at 0.1 and 0.4 mM inhibited the GOT leakage. The leakage of GPT from hepatocytes was inhibited by eugenol at 0.1 mM and 0.4 to 4 mM and menthol at 0.1 to 0.6 mM. The inhibition of eugenol and menthol on the LDH leakage in hepatocytes were observed at a concentration of 0.001 to 4 mM and 0.1, 0.4 and 0.6 mM, respectively. Thymol caused no change in GPT and LDH leakage. Eugenol, thymol and menthol indicated a depression of surface tension at a concentration of 0.1 mM. The rank by order of surface activity was eugenol greater than thymol. Eugenol, thymol and menthol depressed the phase-transition temperature of DPPC-liposomes. The depression of phase-transition temperature by thymol was greater than that by eugenol and menthol. These results suggest the periapical tissue damage produced by essential oils may be related to membrane lysis and surface activity and that their tissue penetration may be related to membrane affinity and lipid solubility.     

Pulmonary complication after resection of lung cancer--difficulty in expectoration and cough dynamics

From January 1975 to December 1986, 415 patients were operated for primary lung cancer. Postoperative pulmonary complications were observed in 83 patients and among them 48 patients (57.8%) suffered from difficulty in expectoration. Postoperative expectoration mostly depends on the ability of coughing. To evaluate cough dynamics, expiratory flow-rate and volume at voluntary maximal cough were measured. The more expiratory flow rate and volume a cough has, the more effective it is for expectoration. In those patients with decreased FEV1.0, or respiratory muscle weakness because of emaciation and aging, or severe pain in the wound, the cough dynamics was decreased. By cleaning retained secretions in the respiratory tract, postoperative pulmonary complications would be prevented. However in cases where the decrease in postoperative cough dynamics is predictable, application of limited resection should be considered as well.     

Polarographic method for rapid microdetermination of cholesterol with cholesterol esterase and cholesterol oxidase.

Cholesterol concentrations in serum are enzymatically determined rapidly by use of a polarographic oxygen analyzer with a circuit modified to record simultaneously the amount and rate of oxygen consumption. The final assay system, assessed from the oxygen consumption value that we found to be optimum, consists of 1 ml of sodium phosphate buffer (0.6 mol/liter, pH 7.0) containing NaN3 (10 mg/liter), Triton X-100 surfactant (10 ml/liter), 0.4 U of cholesterol ester hydrolase, and 0.6 U of cholesterol oxidase. Oxygen consumption and cholesterol concentration are linearly related to 8.0 g/liter, and only 10 mul of serum is required. Replicate analyses of pooled serum by the present method demonstrated the following inter-run precision: mean = 1731 mg/liter, SD = 22.3 mg/liter, CV = 1.3%. Bilirubin and ascorbic acid were without effect on the present method, unlike the enzymatic colorimetric methods.     

In vitro and in vivo activities of sparfloxacin and reference drugs againstChlamydia pneumoniae

The activities of sparfloxacin and reference drugs againstChlamydia pneumoniae were compared by using in vitro and in vivo methods. The minimum inhibitory concentration (MIC) (μg/ml) ranges of sparfloxacin, levofloxacin, tosufloxacin, grepafloxacin, AM-1155, DU-6859a, clarithromycin, azithromycin, and minocycline for sixC. pneumoniae strains (two standard and four clinical strains) were 0.031 to 0.063, 0.25 to 0.5, 0.063 to 0.125, 0.063 to 0.125, 0.063 to 0.125, 0.031 to 0.063, 0.016 to 0.031, 0.125 to 0.25, and 0.016 to 0.031, respectively. The in vitro potency of sparfloxacin againstC. pneumoniae was similar to that of clarithromycin, minocycline, and DU-6859a, and higher than that of the other fluoroquinolones and azithromycin. Fatal pneumonia was induced in cyclophosphamide-treated leukopenic mice by intranasal inoculation withC. pneumoniae KKpn-2. Infiltration of the lung by neutrophils and lymphocytes was confirmed by histopathologic examination. Oral treatment with the various antichlamydial agents was given for seven days; sparfloxacin and minocycline had the lowest ED₅₀ (effective treatment dose in 50% of the mice; given as mg/kg per dose) (1.11 each), followed by DU-6859a (1.92), tosufloxacin (2.09), grepafloxacin (2.41), clarithromycin and azithromycin (2.48 each), AM-1155 (2.77), and levofloxacin (>10). These results suggest that sparfloxacin may be an effective agent forC. pneumoniae infection in humans.     

A comparison of bolus versus continuous cardiac output in an experimental model of heart failure

OBJECTIVE: The majority of studies examining cardiac output measurement have been done in physiologically stable models with low thermal background noise. Research comparing continuous cardiac output (CCO) with bolus thermodilution cardiac output (COTD) measures in human and animal models have reported high correlations, negligible bias, but large limits of agreement. The purpose of this project was to compare CCO with COTD measures in an experimental model of heart failure where the cardiac output values were low and the range was narrow. DESIGN: A one-group experimental design with preintervention control measures and repeated CCO and COTD measures across nine time points. SETTING: Cardiovascular research laboratory. SUBJECTS: Thirty dogs. MEASURES AND MAIN RESULTS: Univariate and multivariate versions of repeated-measures analysis were used to assess the influences of temperature, weight, and stage of the experimental protocol on CCO, COTD, and the differences between them. The two measures CCO and COTD were assessed for agreement by using methods proposed by Bland and Altman. Two hundred and fifty pairs of measurements were obtained during sinus rhythm. The range for COTD measures was 0.5-4.67 L/min and for CCO measures 1.0-5.40 L/min. Of the 250 cardiac outputs estimated by the continuous method, 73.4% of the values were within +/-15% of that estimated by the repetitive, single thermodilution method. The mean bias for the entire protocol was 0.01 (SD = 0.51) with a range of 4.33 L/min. CONCLUSION: Agreement between the two measures may be the function of biological variability, responses to anesthesia, and technique. Bland and Altman evaluation demonstrated low bias and precision and similar levels of agreement when compared with previous studies in an experimental model where the cardiac output was low and the range was narrow.