Epizootiological survey of small mammals as Leptospira spp. reservoirs in Eastern Croatia

In this survey we investigated a population of small mammals in Eastern Croatia in order to determine Leptospira carriage rates and identify circulating serovars. Out of 67 trapped animals, 20 (29.9%) isolates were obtained. Identification of isolates using microscopic agglutination test, pulsed field gel electrophoresis and multi locus sequence typing revealed that 10 (50.0%) isolates belong to serogroup Pomona, serovar Mozdok, 6 (30.0%) isolates to serogroup Australis, serovar Jalna, 2 (10.0%) isolates to serogroup Sejroe, serovar Saxkoebing, and 1 (5.0%) isolate to serogroup Grippotyphosa, serovar Grippotyphosa. One isolate from serogroup Bataviae was unable to be identified to the serovar level. Amplification of a 331-bp region of the locus LA0322 using real-time polymerase chain reaction determined that 12 (60.0%) isolates belong to L. kirschneri, 6 (30.0%) isolates to L. interrogans, and 2 (10.0%) isolates to L. borgpetersenii. Leptospira carriage rate was high (29.9%), which corresponds to a high incidence of human and domestic animal leptospirosis in Eastern Croatia. Furthermore, 90.0% of the isolates belong to serogroups Pomona, Australis and Sejroe which are also the most prevalent serogroups in humans in this area. These findings suggest that small mammals might be an important source of Leptospira spp. infection in Eastern Croatia.     

Inhibitory effects of the nucleoside analogue gemcitabine on prostatic carcinoma cells

Gemcitabine (2≺,2≺difluoro-2≺deoxycytidine, dFdC) is a synthetic antimetabolite of the cellular pyrimidine nucleotide metabolism. In a first series of in vitro experiments, the drug showed a strong effect on the proliferation and colony formation of the human androgen-sensitive tumor cell line LNCaP and the androgen-insensitive cell lines PC-3 and DU-145. Maximal inhibition occurred at a dFdC concentration as low as 30 nM. In contrast to the cell lines which were derived from metastatic lesions of prostate cancer patients, no inhibitory effects were found in normal primary prostatic epithelial cells at concentrations up to 100 nM. The effect of gemcitabine was reversed by co-administration of 10–100 μM of its natural analogue deoxycytidine. In view of a future clinical application of this anti-tumor drug in advanced prostatic carcinoma, we have compared the effect of gemcitabine on prostatic tumor cells with that on bone marrow granulopoietic-macrophagic progenitor cells, because neutropenia is a common side effect of gemcitabine treatment. The time course of action on the two kinds of cells was markedly different. Colony formation of tumor cells was inhibited by two thirds at a gemcitabine concentration of about 3.5 nM. The same effect on granulopoietic-macrophagic progenitor cells required a concentration of 9 nM. Co-administration of deoxycytidine to gemcitabine-treated tumor cell cultures completely antagonized the effect of gemcitabine whereas addition of deoxycytidine after 48 hr of gemcitabine treatment could not prevent gemcitabine action on the tumor cells. In contrast, more than half of the granulopoietic-macrophagic progenitor cells could still be rescued by deoxycytidine administration after 48 hr. These findings and the marked difference in the susceptibility of neoplastic and normal prostatic cells suggest that gemcitabine is a promising substance which should be further evaluated as to its efficacy in the treatment of advanced prostatic carcinoma. © 1996 Wiley-Liss, Inc.     

All near-infrared multiparametric luminescence thermometry using Er3+, Yb3+-doped YAG nanoparticles

This paper presents four new temperature readout approaches to luminescence nanothermometry in spectral regions of biological transparency demonstrated on Yb³⁺/Er³⁺-doped yttrium aluminum garnet nanoparticles. Under the 10 638 cm⁻¹ excitation, down-shifting near infrared emissions (>10 000 cm⁻¹) are identified as those originating from Yb³⁺ ions'' ²F_5/2 → ²F_7/2 (∼9709 cm⁻¹) and Er³⁺ ions'' ⁴I_13/2 → ⁴I_15/2 (∼6494 cm⁻¹) electronic transitions and used for 4 conceptually different luminescence thermometry approaches. Observed variations in luminescence parameters with temperature offered an exceptional base for studying multiparametric temperature readouts. These include the temperature-dependence of: (i) intensity ratio between emissions from Stark components of Er^{3+ 4}I_13/2 level; (ii) intensity ratio between emissions of Yb³⁺ (²F_5/2 → ²F_7/2 transition) and Er³⁺ (⁴I_13/2 → ⁴I_15/2 transition); (iii) band shift and bandwidth and (iv) lifetime of the Yb³⁺ emission (²F_5/2 → ²F_7/2 transition) with maximal sensitivities of 1% K⁻¹, 0.8% K⁻¹, 0.09 cm⁻¹ K⁻¹, 0.46% K⁻¹ and 0.86% K⁻¹, respectively. The multimodal temperature readout provided by this material enables its application in different luminescence thermometry setups as well as improved the reliability of the temperature sensing by the cross-validation between measurements.

Four completely new NIR luminescence temperature readouts in the second and third biological windows are demonstrated with YAG:Er³⁺, Yb³⁺ nanoparticles.     

In reply to Swain et al.: Re-evaluation of updated meta-analysis including trials RTOG 1016 and De-ESCALaTE

European Archives of Oto-Rhino-Laryngology -     

Evaluation of ventricular synchrony using novel Doppler echocardiographic indices in patients with heart failure receiving cardiac resynchronization therapy.

Cardiac resynchronization therapy improves hemodynamics in selected patients with heart failure. Mechanic asynchrony parameters that may guide patient selection or therapy optimization are still being investigated. A biventricular (BiV) pacemaker was implanted in 34 patients with dilated ischemic, idiopathic, or valvular cardiomyopathy, and a QRS duration of > or =130 milliseconds. Two-dimensional standard and Doppler tissue echocardiography was performed during right ventricular (RV), left ventricular (LV), BiV, and no pacing in a random and blinded manner. LV and BiV pacing increased stroke volume (P <.02 for both) and ejection fraction (P <.001 for both). Regional contractility assessed by displacement, strain rate, and peak systolic strain was improved in some segments (P <.05) during LV and BiV pacing. A homogenization of segmental contractions was observed during LV and BiV pacing as evaluated by net systolic displacement and segmental myocardial performance index. LV and BiV pacing provides benefits that can be quantified by echocardiography.     

Atypical presentation of distal renal tubular acidosis in two siblings

Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.     

Cardiac events after combined surgery for coronary and carotid artery disease

Objective: To evaluate serious cardiac events after combined (either single or two stage) coronary artery surgery (CAS) and carotid endarterectomy (CEA) for concomitant coronary and carotid artery disease. Methods: We have analyzed our 15 year experience (January 1981–September 1996) with 201 consecutive patients operated on using both approaches. Group A consisted of 48 patients with the single-stage procedure, while in group B (153 patients), two stage procedure was carried out, either as carotid endarterectomy (CEA), followed by coronary artery bypass surgery (CAS) (group B₁⁻ 103 patients), or as CAS followed by CEA (group B₂⁻ 50 patients). Five patients from B₁ group died after the CEA procedure, but were included, despite the fact they never reached the second stage. Left main coronary artery disease was found in 41 patients (20.4%), poor left ventricular function in 49 (24.4%) previous MI in 133 (66.2%), while 136 (67.7%) were in NYHA functional class III or IV. Bilateral carotid involvement was present in 61 patients (30.3%). Unstable angina was more prevalent in groups A and B₂ (P<0.0001), NYHA class III/IV in group A (versus B₁, P=0.001 and versus B₂, P=0.02), low ejection fraction in groups A and B₂ (P<0.0001), bilateral carotid stenosis in group B₁ (versus A, P=0.003 and versus B₂, P<0.0001), and ulcerated plaque in group B₁ (P<0.0001). These differences dictated the surgical strategy, which resulted in different protocols for clinical and operative management. Results: Early mortality for the entire group was 5.5% (11/201) 6.2% in group A, 7.8% in group B₁ and 0% in group B₂, respectively; (P>0.05). Serious morbidity occurred in 7.5% of patients (8.3% in group A, 7.8% in group B₁ and 6% in group B₂, respectively; P>0.05). Univariate analysis revealed only bilateral carotid stenosis to influence early outcome (P=0.04). Conclusion: Patients with concomitant coronary and carotid artery disease have relatively good immediate operative results, providing all existing lesions are corrected. Despite it did not reach the statistical significance, cardiac events were less frequent in groups A and B₂ indicating possible protective effect of prior CAS in patients with concomitant disease.     

Vascular calcification and atherosclerosis in hemodialysis patients: what can we learn from the routine clinical practice?

BACKGROUND: Hemodialysis (HD) patients are at increased risk for arterial intimal (AIC) and medial calcification (AMC). METHODS: In a cross-sectional study on 153 HD patients we evaluated the presence of AIC and AMC using plain radiography of the pelvis and the presence of atherosclerotic lesions using high-resolution B-mode ultrasonography of the common carotid arteries (CCA). RESULTS: The radiography of the pelvis confirmed the frequent presence of AIC (35.3%) and AMC (35.9%) in our HD patients. Arterial calcification was absent (non calcified-NC) in a minority of patients (28.8%). Patients with AIC had significantly higher prevalence of atherosclerotic plaques on CCA (78.6%) compared with both other groups and a higher number of documented atherosclerotic complications, such as cardiovascular (85.2%), cerebrovascular (33.3%) and peripheral arterial disease (38.9%) in comparison with the NC patients. According to the 1-year calculated data from patient records, there were no significant differences in the specific HD risks, such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of calcium, phosphate, calcium-phosphate product and intact parathyroid hormone. All four bone metabolism markers within the range proposed by K/DOQI guidelines were achieved in 9.3%, 14.5% and 20.4% in the AIC, AMC and NC group, respectively. CONCLUSIONS: Patients with AIC and AMC are frequently found in the HD population. Screening for arterial calcifications in chronic kidney disease patients is suggested even in the early pre-dialysis period. The highest proportion of patients within the guidelines proposed range for bone and mineral metabolism markers was observed in the NC group. A longer period of data analysis is required in order to evaluate the possible role of some traditional and HD-specific risk factors for the development of arterial calcifications. The achievement of the K/DOQI guidelines is an important issue in the prevention of those conditions.     

Voxel‐wise quantification of myocardial perfusion by cardiac magnetic resonance. Feasibility and methods comparison

The purpose of this study is to enable high spatial resolution voxel‐wise quantitative analysis of myocardial perfusion in dynamic contrast‐enhanced cardiovascular MR, in particular by finding the most favorable quantification algorithm in this context. Four deconvolution algorithms—Fermi function modeling, deconvolution using B‐spline basis, deconvolution using exponential basis, and autoregressive moving average modeling —were tested to calculate voxel‐wise perfusion estimates. The algorithms were developed on synthetic data and validated against a true gold‐standard using a hardware perfusion phantom. The accuracy of each method was assessed for different levels of spatial averaging and perfusion rate. Finally, voxel‐wise analysis was used to generate high resolution perfusion maps on real data acquired from five patients with suspected coronary artery disease and two healthy volunteers. On both synthetic and perfusion phantom data, the B‐spline method had the highest error in estimation of myocardial blood flow. The autoregressive moving average modeling and exponential methods gave accurate estimates of myocardial blood flow. The Fermi model was the most robust method to noise. Both simulations and maps in the patients and hardware phantom showed that voxel‐wise quantification of myocardium perfusion is feasible and can be used to detect abnormal regions. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.