Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Turkey: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Turkey. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 179 S. pneumoniae and 239 H. influenzae isolates were collected. Few (27.9%) pneumococci were penicillin susceptible by CLSI oral or EUCAST low-dose breakpoints, but by EUCAST high-dose or CLSI IV breakpoints 84.4% were susceptible. The most active antibiotics (excluding penicillin IV) by CLSI breakpoints were fluoroquinolones (98.9% of isolates susceptible), ceftriaxone (83.2%), amoxicillin (78.8%) and amoxicillin/clavulanic acid (78.8%). Pneumococcal susceptibility to amoxicillin and amoxicillin/clavulanic acid was lower using EUCAST low-dose breakpoints (49.7%), although susceptibility increased when using EUCAST high-dose (57.0%-58.1%) and PK/PD (78.8%-87.7%) breakpoints. Twenty-three H. influenzae isolates were ß-lactamase positive, with 11 characterized as ß-lactamase negative and ampicillin resistant following EUCAST criteria and 5 by CLSI criteria. Generally antibiotic susceptibility was high using CLSI breakpoints: ≥92.9% for all antibiotics except ampicillin (87% by CLSI and EUCAST breakpoints) and trimethoprim/sulfamethoxazole (67.4% and 72% by CLSI and EUCAST breakpoints, respectively). Susceptibility using EUCAST breakpoints (where these are published) was similar, except for cefuroxime (oral) with 3.8% of isolates susceptible. PK/PD breakpoints indicated low susceptibility to macrolides (5.9%-10%) and cefaclor (13%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. CONCLUSIONS: Antibiotic susceptibility of S. pneumoniae was generally low, which is in keeping with evidence of inappropriate and high antibiotic use in Turkey. H. influenzae susceptibility was high. These data are important for empirical therapy of CA-RTIs.

Results from the Survey of Antibiotic Resistance (SOAR) 2011-13 in Turkey.

OBJECTIVES: Data are presented from the Survey of Antibiotic Resistance (SOAR) for respiratory tract infection pathogens collected in 2011-13 from Turkey. METHODS: MICs were determined using Etest(®). Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) interpretive criteria. RESULTS: Rates of antibiotic susceptibility were very low among 333 isolates of Streptococcus pneumoniae tested: penicillin 38% using CLSI (oral) and EUCAST breakpoints; erythromycin 51% using CLSI and EUCAST criteria; and cefuroxime 64.6% using CLSI and PK/PD and 46.9% using EUCAST. Of the isolates, >90% were susceptible to amoxicillin/clavulanic acid, ceftriaxone (except using EUCAST criteria: 76%), levofloxacin and high-dose intravenous penicillin. Among 339 Haemophilus influenzae isolates, 6.8% were ß-lactamase positive while 9.1% were ß-lactamase negative but ampicillin resistant (BLNAR) by CLSI (14.7% by EUCAST) criteria. Amoxicillin/clavulanic acid susceptibility was ∼90% by CLSI (with or without BLNAR adjustment, EUCAST and high-dose PK/PD) but lower, at 82.9%, by EUCAST with BLNAR adjustment. Levofloxacin susceptibility was 96% using all three breakpoints. Dramatic differences in rates of susceptibility, depending on the breakpoints used, were seen for cefaclor [94% by CLSI (86.4% BLNAR adjusted), 23% by PK/PD] and cefuroxime [97% by CLSI (89.1% BLNAR adjusted), 85% by PK/PD, 15% by EUCAST (13.0% BLNAR adjusted)]. Streptococcus pyogenes (n = 222) and Moraxella catarrhalis (n = 40) isolates remained highly susceptible to amoxicillin/clavulanic acid, cephalosporins and levofloxacin, with only erythromycin susceptibility dropping below 95% for S. pyogenes. CONCLUSIONS: Overall, amoxicillin/clavulanic acid and levofloxacin were the most active antibiotics based on all three breakpoints against these pathogens. Although susceptibility was not universally low in Turkey, high resistance rates were found in S. pneumoniae and, when using PK/PD and EUCAST breakpoints, in other respiratory pathogens.

Does pregnancy-induced hypertension affect the electrophysiology of the heart?

Pregnancy-induced hypertension (PIHT) increases both maternal and neonatal mortality and morbidity in pregnant women. We sought to investigate the electrocardiographic findings in pregnant women with PIHT. Seventeen pregnant women (29.4 ± 5 years) with PIHT and 24 pregnant women (27.3 ± 6.1 years) with normal blood pressure (control group) were included in the study. A 12-lead surface electrocardiogram was used to evaluate the electrocardiographic parameters. Pregnant women with PIHT had higher blood pressure (p = 0.001). The Tp-e interval was longer in PIHT pregnant women at 83.5 ± 7.8 ms versus 75.8 ± 8.4 ms in the control group (p = 0.007). The Tp-e/QTc ratio was higher in pregnant women with PIHT than that in healthy controls (0.19 ± 0.02 vs. 0.18 ± 0.02, respectively). This study demonstrated that Pd, QTd and the P wave durations were similar in the PIHT pregnant women and control group, but the Tp-e and Tp-e/QTc ratio were higher in pregnant women with PIHT than in normotensive pregnant women.

Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and carotid intima-media thickness: Associations in rheumatoid arthritis patients.

AIM: The purpose of this work was to evaluate epicardial adipose tissue (EAT), carotid intima-media thickness (CIMT), and flow-mediated dilatation (FMD) of the brachial artery in rheumatoid arthritis (RA) patients using ultrasonographic methods. Interrelationships between these three parameters in RA patients were also investigated. METHODS: EAT thickness, CIMT, and FMD were measured by ultrasonography. We measured the disease activity score (DAS28), health assessment questionnaire (HAQ) score, and C-reactive protein (CRP) levels. Spearman or Pearson correlation analysis was used to evaluate the association between clinical findings, CIMT, FMD, and EAT. RESULTS: A total of 90 RA patients [19 men, mean age 54 years (range 21-76 years)] and 59 age- and gender-matched control subjects [17 men, mean age 54 years (range 26-80 years)] were included in the study. Patients with RA had a mean 4.34 DAS28 points (range 0-40 points) and the mean duration of the disease was 77.1 months (range 1-360 months). We found that RA patients had thicker EAT (7.7 ± 1.7 mm vs 6.2 ± 1.8 mm, p < 0.001), increased CIMT [0.9 (0.5-1.2) mm vs 0.6 (0.4-0.9) mm, p < 0.001], and decreased FMD values [5.7 % (- 23.5 to 20 %) vs. 8.5 % (- 4.7 to 22.2 %), p = 0.028] when compared to control subjects. CRP levels were significantly higher in the RA group [0.81 (range 0.1-13.5) vs 0.22 (range 0.05-12), p < 0.001]. EAT thickness was negatively correlated with FMD (r = - 0.26, p < 0.001) and positively correlated with CIMT values (r = 0.52, p < 0.001). CIMT also negatively correlated with FMD (r = - 0.29, p < 0.001). CONCLUSION: EAT can be simply measured by echocardiography and correlated with FMD and CIMT. It can be used as a first-line measurement for estimating burden of atherosclerosis in RA patients.

Effect of hypertension on echocardiographic parameters in rheumatoid arthritis.

OBJECTIVE: Hypertension (HTN) is common in rheumatoid arthritis (RA) patients. Both HTN and RA have a negative impact on echocardiographically determined parameters including wall thickness, chamber diameter, diastolic function, epicardial adipose tissue (EAT) and carotid intima media thickness (CIMT). We aimed to demonstrate the effect of HTN on these parameters in RA patients. METHODS: Patients were divided into two groups: one group comprised 39 RA patients with HTN (7 male, mean age 56.3 ± 8.4 years) and the second comprised 38 age- and gender-matched RA patients without HTN (10 male, mean age 55.3 ± 7.4 years). We retrospectively analyzed the RA patients without overt structural heart disease by determining the study parameters from echocardiograph recordings. The two groups were compared in terms of echocardiographic parameters and disease characteristics. RESULTS: RA characteristics, chamber sizes and wall thicknesses did not differ between the groups. CIMT was significantly increased in the RA with HTN group (median 0.9 mm, range 0.6-1.2 mm vs. median 0.8 mm, range 0.6-1.0 mm; p = 0.031). EAT was also significantly increased in the RA with HTN group (8.2 ± 1.8 mm vs. 7.4 ± 1.4 mm; p = 0.022). Septal early diastolic E' wave velocities were significantly decreased in the RA with HTN group (8.8 ± 2.4 cm/s vs. 10.2 ± 1.8 cm/s; p = 0.016). CONCLUSION: HTN has a further negative impact on diastolic functions, CIMT and EAT in RA patients.

Cortical disinhibition in diabetic patients with neuropathic pain.

OBJECTIVES: Motor cortex disinhibition has a role in the mechanism of neuropathic pain. The duration of the cortical silent period (CSP) is used as a measure of excitability in cortical inhibitory circuits. We investigated cortical disinhibition in diabetic patients with and without neuropathic pain. MATERIALS AND METHODS: We studied diabetic patients with (n = 20) and without (n = 50) neuropathic pain, and control subjects (n = 30). Transcranial magnetic stimulation (TMS) was performed on the right hemisphere at rest, and surface electromyography was recorded from the left first dorsal interosseous muscle for evaluation of motor evoked potential (MEP) latency and amplitude. CSP was recorded from the left FDI, and TMS was then delivered while the subject was performing a voluntary contraction. RESULTS: We showed a low resting motor threshold, a short CSP duration, and a low CSP duration/MEP amplitude ratio in patients with neuropathic pain (P < 0.0001, P < 0.0001, P < 0.0001). CONCLUSIONS: Our findings demonstrate that diabetic patients with neuropathic pain have a cortical disinhibition.

Proton pump inhibitor omeprazole use is associated with low bone mineral density in maintenance haemodialysis patients.

OBJECTIVE: Limited studies have shown that proton pump inhibitor (PPI) therapy may decrease bone density or insoluble calcium reabsorption through induction of hypochlorhydria. However, PPI therapy may also reduce bone resorption via inhibition of osteoclastic vacuolar proton pumps. The aim of this study was to determine whether the opposing effects of PPI therapy may cause clinically important alterations in bone mineral densitometry (BMD) parameters in maintenance haemodialysis patients. METHODS: Sixty-eight maintenance haemodialysis patients were enrolled in this study. Patients were classified into two groups involving users of PPI therapy (omeprazole 20 mg/day, group 1, n = 36 patients) and non-users of acid suppression drugs (group 2, n = 32 patients). Patients had radius, hip and spine BMD assessed by dual-energy X-ray absorptiometry. RESULTS: The mean duration of PPI therapy with omeprazole was 27 +/- 5 months. The users of PPI therapy had lower values of bone mineral density and T-scores at the anatomical regions than non-users of acid suppression drugs. Serum calcium and phosphate levels, calcium-phosphate product and serum intact parathormone levels and the ratio of users of vitamin D therapy were similar among groups. A mutivariable adjusted odds ratio for lower bone density associated with more than 18 months of omeprazole, when all the potential confounders were considered, was 1.31 in the proximal radius, 0.982 in the femur neck, 0.939 in the trochanter and 1.192 in the lumbal spine. CONCLUSION: The present data suggest that PPI therapy should be cautiously prescribed in maintenance haemodialysis patients, especially with lower BMD values.

Utility of the Doppler ultrasound parameter, resistive index, in renal transplant histopathology.

BACKGROUND: Doppler ultrasonography is routinely used by many clinicians during long-term follow-up to identify high-risk patients without diagnosing the exact cause of graft dysfunction. Despite a number of studies showing a correlation between intrarenal resistive index (RI) and renal function in patients with kidney diseases, correlations between RI and renal histopathologic characteristics have not been sufficiently evaluated in renal transplant recipients. The aim of this study was to examine this relationship in grafted kidneys. PATIENTS AND METHODS: The intrarenal RI was retrospectively compared with biopsy findings in 28 kidney recipients. All renal biopsy specimens were reviewed by light microscopy and immunofluorescence staining. For glomerulosclerosis, we considered the percentage of glomeruli showing this change; for interstitial fibrosis/tubular atrophy and interstitial infiltration, we graded abnormalities according to the methods of Kliem et al (Kidney Int 49:666, 1996). RESULTS: The percentage of globally sclerosed glomeruli was significantly greater among patients with RI values higher than 0.75 than below this level (23% vs 47%; P = .022). Patients with grade 1 interstitial fibrosis and tubular atrophy (n = 14) showed lower RI values (0.68 +/- 0.03 vs 0.74 +/- 0.06; P = .047) than those with grade 3 fibrosis (n = 12). Similarly, lower RI values (0.66 +/- 0.02 vs 0.73 +/- 0.05; P = .014) were observed among patients with grade 1 (n = 13) compared with grade 3 interstitial infiltration (n = 13). CONCLUSION: RI seemed to provide a prognostic marker for the graft rather than yielding an exact diagnosis of renal graft dysfunction.

Utility of c2 monitoring in prediction of diastolic dysfunction in renal transplant recipients.

BACKGROUND: A number of experimental studies have suggested that cyclosporine (CsA) toxicity induces cardiac modifications which may cause diastolic dysfunction over the course of time. Doppler echocardiography with tissue Doppler imaging (TDI) could consistently detect diastolic dysfunction. The purpose of this study was to assess diastolic dysfunction using C2 monitoring of CsA exposure in stable renal transplant patients. PATIENTS AND METHODS: Seventy-eight kidney recipients including 42 men and 36 women of overall mean age of 52 +/- 9 years were obtained in 47 living and in 31 cases from cadaveric donations over 12 or more months after transplantation using cases from CsA, mycophenolate mofetil, and steroid. C2 levels were measured by an enzyme multi-immune assay technique. The patients underwent conventional and Doppler echocardiography with TDI. RESULTS: The patients were divided into 2 groups according to C2 levels less than 500 mug/L (group 1, n = 40) versus greater than 500 mug/L (group 2, n = 38). The demographic parameters, serum creatinine and lipid levels, systolic and diastolic blood pressures, number and type of antihypertensive medications, and conventional echocardiographic parameters did not differ significantly between the groups. However, group 1 patients showed significantly higher isovolumic relaxation time (109 +/- 27 vs 86 +/- 14 ms), early diastolic deceleration time (189 +/- 52 vs 137 +/- 59 ms), and lower values of E velocity (56 +/- 32 vs 92 +/- 27 cm/s) and E/A ratios (0.81 +/- 0.23 vs 1.15 +/- 0.46) than group 2. TDI studies revealed significantly lower E'/A' (0.76 +/- 0.25 vs 1.09 +/- 0.32, P < .05) in group 1 versus group 2. CONCLUSION: The data suggested that the higher C2 levels may induce diastolic dysfunction in the hearts of kidney recipients without impairment of contractile performance.

Urinary Type III Procollagen Is Associated With Chronic Allograft Dysfunction and Predicts Graft Survival.

BACKGROUND: Chronic allograft dysfunction (CAD) is the most important clinical problem in solid organ transplantation. Interstitial fibrosis and tubular atrophy contribute to long-term renal allograft failure. Urinary type III procollagen N-terminal propeptide (PIIINP), has been shown to associate fibrotic processes. METHODS: One hundred sixty patients with CAD who underwent allograft biopsies were evaluated, and 52 patients with chronic or sclerosing allograft nephropathy were enrolled in the study. The subjects were divided into 2 groups according to the level of urinary PIIINP to creatinine (u-PIIINP-to-Cr): high procollagen group and low procollagen group. The association between u-PIIINP-to-Cr level at the time of biopsy and renal endpoints during 36 months of follow-up was assessed by multivariate Cox analysis. RESULTS: Interstitial fibrosis and proteinuria were higher in the high procollagen group compared with the low urinary procollagen group. Correlation analysis showed that levels of u-PIIINP-to-Cr were positively associated with fibrosis scores. During the follow-up, glomerular filtration rate (GFR) decreased in both study groups; however, GFR declined more in the high procollagen group than in low procollagen group. Cox regression model showed that the u-PIIINP-to-Cr levels, GFR, and proteinuria were independent risk factors associated with graft survival. CONCLUSION: u-PIIINP-to-Cr level is a potentially useful noninvasive marker for graft survival in patients with CAD.

The role of proinflammatory cytokine gene polymorphisms for development of insulin resistance after renal transplantation.

BACKGROUND: Insulin resistance, a frequent prediabetic metabolic complication after renal transplantation, is generally linked to immunosuppressive drugs including corticosteroids, cyclosporine (CsA) or tacrolimus, as well as to age, cadaveric donors and ethnic factors. Cytokines are known to be inflammation modulatory substances that contribute to metabolic derangements after transplantation. The present study investigated the effects of cytokine gene polymorphisms on insulin resistance in renal transplant recipients. PATIENTS AND METHODS: Sixty-one renal transplant recipients (37 men, 24 women; mean age: 39.3 +/- 10.8 years) who attended regular clinical visits without a known history of diabetes were enrolled in the study. All patients were on a regimen of steroid, CsA, and mycophenolate mofetil. Venous blood samples were collected for biochemical analyses after an overnight fast at 08:00 pm. CsA trough levels, C-reactive protein, and fibrinogen were also estimated. Additional 10 mL of blood was withdrawn into an ethylenediamine tetraacetic acid-containing tube to determine cytokine genotypes (tumor necrosis factor-alpha [TNF-alpha] -238 G/A, transforming growth factor-beta [TGF-beta] codon 10 -869 T/C). Insulin resistance was calculated by the homeostasis model assessment (HOMA) method using the values of fasting blood glucose (FBG) and insulin levels. Anthropometric indices as well as body height, weight, waist and hip circumferences were measured simultaneously to calculate body mass index (kg/m2) and waist-to-hip ratio. Impaired fasting glucose (IFG) was described as an FBG > or = 110 but < 126 mg/dL. RESULTS: IFG was detected in 27.9% of this study group. The HOMA index was significantly higher among patients with IFG compared with normal FBG (NoGT) (6.3 +/- 4.5 vs 3.7 +/- 1.5; P = .01). Neither FBG and insulin nor HOMA values correlated with antrophometric, metabolic, or inflammatory parameters. Cytokine genotype allele frequencies, age, sex, immunosuppressive and antihypertensive drug type and doses, CsA trough levels, and donor source (cadaveric/living) were similar for patients with IFG and NoGT. Mutant allele carrier genotypes (AA + GA) for TNF-alpha -238 G/A showed higher fasting insulin (14.0 +/- 7.9 vs 34.1 +/- 17.7 microIU/mL; P = .04) and HOMA (4.01 +/- 2.01 vs 7.95 +/- 5.44; P = .002) levels than GG homozygote subjects. FBG, HOMA, and other metabolic and anthropometric indices were similar between TGF-beta codon 10 -869 T/C genotypes. The daily dose of steroid (mg/d) and A allele frequency for TNF-alpha -238 G/A genotype were significant predictors of HOMA index in linear regression analysis. CONCLUSION: The present study revealed that beside the daily dose of steroids, TNF-alpha -238 G/A genotype may contribute to insulin resistance in renal transplant recipients. Further investigations may highlight the effects of cytokine gene heterogenity on insulin resistance in those patients.

Relationship between blood pressure variability and renal activity of the renin-angiotensin system.

Local renin-angiotensin system (RAS) activity in the kidneys is a pathogenetic factor in patients with primary hypertension. This study aimed to determine the relationship between local kidney RAS activity and blood pressure variability, as the literature currently lacks any such study. The study included 73 consecutive primary hypertensive patients. All patients underwent 24-h ambulatory blood pressure monitoring to determine the average real variability (ARV) index, as an indicator of blood pressure variability. Local RAS activity was determined using the urine angiotensinogen/creatinine (UAGT/UCre) ratio. The high UAGT/UCre ratio group had significantly higher mean 24-h systolic ARV than the low UAGT/UCre ratio group (13.2±3.4 vs 11.0±2.6, P=0.003). Similarly, the high UAGT/UCre ratio group had significantly higher mean 24-h diastolic ARV than the low UAGT/UCre ratio group (10.8±3.2 vs 8.7±2.2, P=0.001). Multivariate regression analysis showed that Log(UAGT/UCre) was an independent predictor of both 24-h diastolic ARV and 24-h systolic ARV. Local RAS activity in the kidneys might have a role in blood pressure variability. On the basis of these findings, we think that additional prospective studies are needed to more fully discern the effect of local RAS activity on blood pressure variability.

Endothelial dysfunction in renal transplant recipients: role of vitamin D and fibroblast growth factor-23.

BACKGROUND: Endothelial dysfunction can be detected at early stages of chronic kidney disease. Although endothelial functions improve after successful renal transplantation, renal transplant recipients have still worse endothelial functions compared to healthy subjects. Vitamin D deficiency and high fibroblast growth factor-23 (FGF-23) levels may have a role on endothelial dysfunction in chronic kidney disease patients. The aim of this study is to investigate the association between endothelial functions, vitamin D, and FGF-23 levels in renal transplant recipients. METHODS: One hundred nine renal transplant recipients (71 male, 38 female) underwent brachial flow-mediated dilatation (FMD), serum 25-OH vitamin D, and FGF-23 level measurements. Vitamin D and FGF-23 levels were compared between patients with normal and abnormal endothelial functions. Correlations between FMD, vitamin D, and FGF-23 were also investigated. RESULTS: Endothelial functions were abnormal in 72.5% of the patients. Prevalence of vitamin D deficiency was 80.7%. Vitamin D levels were significantly lower in patients with endothelial dysfunction compared to patients with normal endothelial functions (12.6 ± 6.6 µg/L vs 17.3 ± 10.0 µg/L respectively, P = .02). FGF-23 levels were not different between the two groups. 25-OH vitamin D levels had a significant positive correlation with amount of FMD (r = 0.218 and P = .02) and were an independent predictor of FMD after adjusting for potential confounding factors including age, transplantation duration, body mass index, mean blood pressure, glomerular filtration rate, proteinuria, hemoglobin, and FGF-23 in multivariate regression analysis (beta = 0.194, P = .04). FGF-23 levels were not predictive of FMD in this model (beta: -0.125, P = .197) CONCLUSION: Vitamin D deficiency is associated with endothelial dysfunction in renal transplant recipients. Further clinical and experimental studies are necessary to define a causal relationship between the parameters, discover the potential mechanisms, and observe the effect of vitamin D replacement on endothelial functions in renal transplant recipients.

Association between urinary angiotensinogen, hypertension and proteinuria in pregnant women with preeclampsia.

INTRODUCTION: Preeclampsia is a life-threatening disorder of pregnancy. The pathogenic mechanisms of preeclampsia remain uncertain. The aim of this study is to investigate the relation between urinary angiotensinogen (UAGT) levels, an indicator of local renin-angiotensin system (RAS) activity in the kidney, and blood pressure and urinary protein excretion in preeclampsia. MATERIALS AND METHODS: For this study, 90 women aged between 20-39 years were recruited. Spot urine samples were collected to measure urinary angiotensinogen/creatinine ratio (UAGT/UCre). Log(UAGT/UCre) was compared in pregnancies with and without preeclampsia and non-pregnant controls. Factors affecting log(UAGT/UCre) in pregnancies were also investigated. RESULTS: In all pregnancies log(UAGT/UCre) levels were significantly higher than in non-pregnant controls (0.58±0.19 vs. 0.33±0.14, respectively, p=0.002). However, log(UAGT/UCre) levels in pregnancies with preeclampsia were slightly lower than in normal pregnancies (0.52±0.18 vs. 0.64±0.19, respectively, p=0.012). Log(UAGT/UCre) levels were correlated positively with blood pressure and proteinuria in pregnancies with preeclampsia. However, log(UAGT/UCre) levels were not correlated with age, height, body weight, gestational age, body mass index, and serum creatinine. CONCLUSION: This study showed that elevated local RAS activity in kidney was correlated with high blood pressure and proteinuria in preeclampsia. Local RAS activation in the kidneys may be one of the contributing factors in the development of preeclampsia.

Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension.

Abnormalities in fibrinolysis have been reported in hypertension. Angiotensin converting enzyme (ACE) inhibitors have been shown to improve altered fibrinolytic balance in hypertensive patients. It has not been documented, however, whether this is due to a decrease in angiotensin II (Ang-II) generation or is a consequence of elevated local levels of bradykinin. Accordingly, the aim of this study was to determine the effects of an ACE inhibitor (perindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic kinetics. We have examined the serum levels of the plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity, soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) before and after reaching the target blood pressure (<140/90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40+/-11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38+/-9 years, 6 women, 6 men). We also compared the baseline fibrinolytic activity of hypertensive patients with that of 12 normotensive control persons (mean age 40+/-9 years, 6 women, 6 men). The mean basal plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in the hypertensive patients than in normal controls (P<.005). The values of other analytes were similar in both groups. Increased plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P<.005); the reductions in losartan-receiving group were more pronounced (P<.05). There were no significant effects on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patients receiving the two therapeutic regimens (P>.05). In conclusion, chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to play a major role.

In vitro activities of new quinolones against Brucella melitensis isolated in a tertiary-care hospital in Turkey.

We have evaluated the in vitro activities of seven fluoroquinolones against 69 strains of Brucella melitensis. According to their minimum inhibitory concentration for 90% growth (MIC(90)) values, the most active agent was found to be sparfloxacin (MIC(90) 0.12 mg/L) followed by levofloxacin, ciprofloxacin, ofloxacin (MIC(90) 0.50 mg/L) and grepafloxacin (MIC(90) 1 mg/L), gemifloxacin (MIC(90) 2 mg/L) and gatifloxacin (MIC(90) 4 mg/L).

Interactions of nitric oxide and superoxide dismutase in Behçet's disease.

OBJECTIVE: Nitric oxide (NO) is produced in increased amounts in inflammatory conditions and may cause tissue injury by reacting with superoxide to yield peroxynitrite, a powerful toxin. Superoxide dismutase (SOD) scavenges superoxide and inhibits the formation of peroxynitrite, thereby suppressing the resulting injury and regulating the bioavailability of NO. We conducted a study to assess serum NO and SOD in patients with Behçet's disease (BD) and correlate their levels with disease activity. METHODS: Serum NO concentrations and SOD activities were determined in 25 BD patients (mean age: 36 years; male/female: 13/12) and in 15 healthy controls. BD patients were allocated into two groups according to disease activity (active/inactive: 11/14). RESULTS: In patients with active disease, NO levels were found to be significantly elevated, while SOD activities were comparable to the control group. Conversely, patients with inactive disease exhibited markedly high SOD activities and normal NO levels. Moreover, there was a positive correlation between SOD activity and NO levels in patients with inactive BD (r = 0.562, p < 0.05). CONCLUSION: We propose that NO-associated injury of tissues, particularly the endothelium, may be important in the etiopathogenesis of vasculitis in BD, and SOD may play a protective role against inflammation.

Thrombopoietin and thrombospondin in renal allograft recipients.

Recipients of renal transplants appear to be at increased risk of thromboembolic events. Despite accumulating evidence for the hyperreactivity of platelets, the primary regulator of thrombopoiesis, thrombopoietin (TPO), has not yet been studied in renal transplant recipients. Thus, the aim of the present study was to quantify the levels of TPO and to assess its contribution to increased platelet reactivity in recipients of renal allografts. Serum concentrations of thrombospondin (TSP) were also determined in patients undergoing renal transplants in order to evaluate the role of this multifunctional protein in platelet hyperaggregability. Serum levels of TPO were significantly lower in renal transplant recipients (n = 27) than in healthy controls (30.8+/-20.6 pg/ml versus 129.9+/-113.6 pg/ml, P = 0.001). Serum concentrations of TPO were correlated neither with serum levels of creatinine nor duration of transplantation. However, levels of TPO were negatively correlated with platelet counts (r = -0.50, P = 0.007) in recipients of renal transplants. Plasma levels of TSP were higher in renal transplant patients than in the control group (104.5+/-54.7 ng/ml versus 63.4+/-41.5 ng/ml, P = 0.003). No significant correlation was found between levels of TPO and TSP. We conclude that, rather than the allograft function, the platelet mass determines the levels of TPO in recipients of renal transplants. Despite the low serum levels of TPO, and increased concentrations of TSP, TPO might still play a role in the hyperaggregability of platelets in patients undergoing renal transplants.

Cyclical acute renal failure due to bilateral ureteral endometriosis.

Endometriosis is a common disease but ureteral involvement is relatively rare. Ureteric endometriosis is mostly unilateral. Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. We present the cyclical acute renal failure associated with menstruation in a patient who developed severe bilateral ureteral obstruction due to endometriosis. Physicians should be aware of this uncommon but serious manifestation of endometriosis, especially if the clinical presentation is cyclical acute renal dysfunction in a premenopausal woman.

Rapidly progressive glomerulonephritis associated with hepatitis C virus infection.

Glomerular disease often accompanies a wide variety of liver diseases, including acute or chronic hepatitis. A striking association between hepatitis B virus and glomerulonephritis particularly membranous glomerulonephritis has been reported by various authors. It is not surprising, therefore, that hepatitis C virus (HCV) infection has been recently associated with the development of various types of glomerulonephritis. The principal type of glomerulonephritis associated with HCV infection is either cryoglobulinemic or non-cryoglobulinemic membranoproliferative glomerulonephritis. However, other types of glomerular lesions were seen in the clinical course of HCV infection. We report a rare case of a 20-year-old woman who developed rapidly progressive glomerulonephritis (RPGN) during the course of the active HCV infection. Whether this case represents a true association or a coincidental association is not known.