Endovenous laser ablation of saphenous veins - favorable clinical results confirm theoretical advantages of the 1940nm diode laser.

INTRODUCTION: Endovenous laser ablation (EVLA) is a recognized alternative to surgical treatment of varicose veins, although an optimal laser generator and its settings still remain a matter of debate. The aim of our study was to correlate clinical results with the theoretical advantage of the 1940nm diode laser characterized by high absorption of heat in a thin layer of coagulated tissue. METHODS: From 1/2010 to 12/2021 EVLA was performed in a total of 3529 consecutive patients with varicose veins and ultrasonographically documented superficial venous reflux of lower extremities. Three types of laser were used successively with the wavelengths of 1064 nm, 1470 nm and 1940 nm, respectively. All patients were prospectively enrolled in our registry. An early postoperative followup visit was scheduled including an assessment of venous closure; additional visits were performed only in case of complications. RESULTS: The success of venous closure did not differ (p=0.054) between the three laser types and was over 98%. The catheterbased method made it possible to perform multiple ablations in one procedure the trend was 1.08, 1.31 and 1.62. In 2021 the number of ablations per patient with the laser DL Tethys 1940 nm was 1.79. With this laser it was possible to reduce the total energy applied to one half (8 W, 5080 J/cm). The postoperative course of patients treated using the 1940nm laser was smoother - no other but the early followup visit was needed in 95.6% cases (p.

Metformin therapy and risk of cancer in patients after heart transplantation.

BACKGROUND: Diabetes mellitus (DM) and malignancy are recognized among the most common complications increasing mortality in patients after heart transplantation (HTx). Clinical trials have shown a higher risk for different types of tumours in diabetic patients. This risk is potentiated by immunosuppressive therapy in transplant patients. Biguanide metformin has been shown to exhibit anti-tumour activity and we tried to find out whether this effect is valid for heart transplant patients. METHODS: We retrospectively analysed a group of 497 patients, who undergone HTx in our centre between 1998 and 2019. The primary outcome was any malignancy during the 15-year follow-up period and patient's survival. RESULTS: Out of the 497 patients enrolled in the study, 279 (56 %) had diabetes and 52 (19 %) were treated with metformin. Fifteen-year survival in treated patients without malignancy was 93 %, the remainder for the DM patients was 56 %, with survival in non-DM patients being 74 %. Untreated diabetic patients had 4.7 times higher chance of malignancy than those on metformin (p = 0.01). Fifteen-year survival in metformin treated patients was 53 %, in other DM patients 44 %, and in non-DM patients 51 %. CONCLUSION: Our study showed a significantly lower incidence of malignancies in metformin-treated patients and slightly better overall survival (Tab. 2, Fig. 3, Ref. 19) Keywords: biguanide, heart graft, malignancy, diabetes mellitus, survival.

Endovenous laser ablation of saphenous vein - mid-term results confirm permanent closure and possibility to treat more lesions in one procedure.

INTRODUCTION: Endovenous Laser Ablation (EVLA) is a common alternative to surgical treatment of varicose veins. The aim of our study was to demonstrate that laser occlusion is durable, that we can treat all patients in a one day setting, even with veins >10mm in diameter, and that multiple EVLAs can be done at the same time. METHODS: In the period from 1/2017 to 12/2019 EVLA was performed in a total of 1551 consecutive patients with varicose veins and ultrasonographically documented venous reflux. The mid-term results were evaluated in a group of patients operated from 1/2017 to 6/2017 (316 pts.). We compared a risk group that consisted of patients with veins >10mm in diameter (40 pts.) with a control group (the remaining 276 pts.). Patients with veins >10mm are traditionally considered as candidates for conventional surgery. RESULTS: The catheter-based method enabled us to perform more ablations in one procedure. In 2019 we performed 1.44 EVLA procedures per patient. There was only one postoperative follow-up visit, indicating an uncomplicated postoperative course, in 87.5% of patients of the risk group. In the control group 100% of patients had only one follow-up visit including ultrasound examination, showing an uncomplicated postoperative course (p.

Catheter laser ablation of superficial veins of the lower extremities in the symptomatic treatment of venous reflux comparison of the immediate results of two types of laser.

INTRODUCTION: Catheter-Based Endovenous Laser Ablation (EVLA) is a commonly used alternative to surgical treatment of varicose veins. Recently, catheterization methods have proved to be methods of choice due to the preference of patients who value minimal invasiveness. Research of EVLA currently focuses on optimization of the procedure, which includes study of the benefits of the individual types of laser generators and the wavelengths used. In this observational study we compared our early results in a non-selected population of consecutive patients treated with two different types of lasers. METHODS: In the period from February 2010 to June 2017, EVLA was performed in a total of 1747 consecutive patients (74% were female) with venous reflux. The average vein width was 8.5 mm (525 mm). Our study sought to compare a more economical 1470nm diode laser (DL) generator (Velas 2, China) - used to operate on 630 patients - with a Nd-Yag crystal generator (Fotona - Slovenia) used in 1117 patients. All operations were performed using the same methodology, in an outpatient setting, in one specialized center. All procedures were completed in local tumescent anesthesia under peroperative ultrasound control. Postoperative sonography was performed in all patients. RESULTS: The results did not show a statistically significant difference in early closure rates (98.8% for Nd-Yag versus 99.8 for DL p-ns). Early recurrence was observed in 9 patients (15 vein segments) and managed successfully with early re-intervention and closure in all cases. The causes of incomplete closure included mainly the known risk factors (anticoagulation therapy, history of varicophlebitis). There was no correlation with larger venous diameter. In 6 patients, thrombus prolapse was observed in the deep femoral vein lumen. All cases were successfully cured after a week of low-molecular-weight heparin therapy. Only one case of low-risk pulmonary embolism was reported in a patient who failed to follow the regime recommendations. CONCLUSION: This evidence did not show a significant difference in closure reliability and the amount of complications of the endovenous laser ablation of large and small saphenous vein with a 1060nm Nd-Yag crystal compared to the more economical 1470nm diode laser generator.

Association between the heart rate early after heart transplantation and the long term clinical outcomes.

BACKGROUND: A strong correlation between a lower heart rate and survival has been demonstrated in various patient populations. The optimal heart rate for heart transplant patients is still unknown. The aim of our study was to evaluate the association between an early heart rate and survival after heart transplantation. MATERIAL AND METHODS: We retrospectively analysed a group of 330 patients, who underwent heart transplantation in our institution from 1994 to 2014 and complete datasets, including 24-hour heart rate monitoring one month after the heart transplantation. Patients were divided in 2 groups: Group A (n = 278) with the average 24-hour heart rate <90 bpm, and Group B (n = 52) with ≥ 90 bpm. RESULTS: The average period of monitoring was 7.5 ± 5.3 years. No differences in baseline characteristics were observed in both groups of recipients and respective donors. One-year survival in groups A and B was 92 % and 81 %, respectively; 5-year survival was 79 % and 60 %, respectively; and 10-year survival was 66 % and 50 %, respectively (p = 0.001). CONCLUSION: Increased heart rate in the early post-transplant period was significantly associated with a poorer survival rate in patients after heart transplantation (Tab. 2, Fig. 1, Ref. 25).

Importance of Reversible Attachment in Predicting E. Coli Transport in Saturated Aquifers From Column Experiments.

Drinking water wells indiscriminatingly placed adjacent to fecal contaminated surface water represents a significant but difficult to quantify health risk. Here we seek to understand mechanisms that limit the contamination extent by scaling up bacterial transport results from the laboratory to the field in a well constrained setting. Three pulses of E. coli originating during the early monsoon from a freshly excavated pond receiving latrine effluent in Bangladesh were monitored in 6 wells and modeled with a two-dimensional (2-D) flow and transport model conditioned with measured hydraulic heads. The modeling was performed assuming three different modes of interaction of E. coli with aquifer sands: 1) irreversible attachment only (best-fit ki=7.6 day-1); 2) reversible attachment only (ka=10.5 and kd=0.2 day-1); and 3) a combination of reversible and irreversible modes of attachment (ka=60, kd=7.6, ki=5.2 day-1). Only the third approach adequately reproduced the observed temporal and spatial distribution of E. coli, including a 4-log10 lateral removal distance of ∼9 m. In saturated column experiments, carried out using aquifer sand from the field site, a combination of reversible and irreversible attachment was also required to reproduce the observed breakthrough curves and E. coli retention profiles within the laboratory columns. Applying the laboratory-measured kinetic parameters to the 2-D calibrated flow model of the field site underestimates the observed 4-log10 lateral removal distance by less than a factor of two. This is promising for predicting field scale transport from laboratory experiments.

Rapid genotyping of genetically modified laboratory animals from whole blood samples without DNA preparation.

A new, rapid method is described which permits the genotyping of genetically modified animals from a microlitre volume of whole blood samples via one step polymerase chain reaction amplification. The major advantage of the presented method is the exclusion of a DNA preparation step, which significantly reduces the time expenditure and work load of the genetic testing. Pilot studies indicate, that this method is efficient and applicable also on tissue biopsies and larger amount of blood providing a rapid and reliable new technique over conventional genotyping approaches.

RING-Type E3 Ubiqitin Ligase Barley Genes (HvYrg1-2) Control Characteristics of Both Vegetative Organs and Seeds as Yield Components.

Previously, studies on RING-type E3 ubiquitin ligases in cereals were preferentially focused on GW2 genes primarily controlling seed parameters in rice and wheat. Here we report cloning two HvYrg genes from barley that share significant homology with rice GW2 gene. In antisense genotypes efficiency of gene silencing varied between genes and transgenic lines: ASHvYrg1: 30-50% and ASHvYrg2: 20-27%. Reduced activity of both genes altered shoot system with increasing number of side shoots. Changes in leaf width, weight, or plant weight and height reached significant levels in some transgenic lines. Lowering expression of the two barley HvYrg genes caused opposite responses in spike development. Plants with ASHvYrg1 gene construct showed earlier heading time and prolonged grain-filling period, while plants from ASHvYrg2 genotype flowered in delay. Digital imaging of root development revealed that down-regulation of HvYrg1 gene variant stimulated root growth, while ASHvYrg2 plants developed reduced root system. Comparison of seed parameters indicated an increase in thousand grain weight accompanied with longer and wider seed morphology. In summary we conclude that in contrast to inhibition of GW2 genes in rice and wheat plants, down-regulation of the barely HvYrg genes caused substantial changes in vegetative organs in addition to alteration of seed parameters.

Hsp90 inhibitor geldanamycin increases the sensitivity of resistant ovarian adenocarcinoma cell line A2780cis to cisplatin.

Ovarian carcinoma is the leading cause of death among gynecological neoplasms in the world. The chemoresistance is a major obstacle in the effective treatment of ovarian and other cancers. We evaluated the effects of Hsp90 inhibitor geldanamycin (GEL) alone and in combination with cisplatin in cisplatin resistant ovarian adenocarcinoma cell line. Our results showed Akt depletion and S-phase arrest of A2780cis cells after GEL treatment. Combined exposure of A2780cis cells to GEL and cisplatin resulted in greater than additive cytotoxic effect.

Neural differentiation potentiated by the leukaemia inhibitory factor through STAT3 signalling in mouse embryonal carcinoma cells.

LIF is a cytokine playing a key role in the regulation of self-renewal and maintenance of undifferentiated state in mouse ES cells. The response of pluripotent cells to LIF is mediated mainly by the STAT3 and ERK signalling pathways. Recently, we have shown that LIF potentiated retinoic acid-induced neural differentiation of pluripotent mouse embryonal carcinoma P19 cells. Here we demonstrate that pro-neural effects of LIF and partially also of retinoic acid are abolished by inhibition of the JAK2->STAT3 signalling pathway. In contrast, inhibition of the MEK1->ERK signalling pathway does not exhibit any effect. These results suggest that in neurogenic regions, cooperative action of LIF and other neuro-differentiation-inducing factors, such as retinoic acid, may be mediated by the STAT3 signalling pathway.

Oldie but goldie: Bristow-Latarjet procedure for anterior shoulder instability.

PURPOSE: To analyse the functional and radiological outcomes of the Bristow-Latarjet procedure in patients with recurrent anterior glenohumeral instability. METHODS: Records of 29 patients were reviewed retrospectively. Date of first dislocation, injury mechanism, and number of recurring dislocations before and after surgery were recorded. The overall function and stability of the shoulder was evaluated. RESULTS: 24 (83%) of the glenohumeral instabilities were caused by trauma. The mean number of recurring dislocations was 8 (95% confidence interval [CI], 0-18); one patient had had 40 recurrences. No dislocation ensued postoperatively. The overall functional outcome was good, with a mean Rowe score of 90 points (95% CI, 78-100). Scores of 17 (59%) of the patients were excellent, 7 (24%) were good, 3 (10%) were fair, and 2 (7%) were poor. CONCLUSION: The Bristow-Latarjet procedure is a good surgical treatment for recurrent anterior-inferior instability of the glenohumeral joint.

Myeloid but not epithelial tissue factor exerts protective anti-inflammatory effects in acid aspiration-induced acute lung injury.

Essentials Tissue factor (TF) represents a central link between hemostasis and inflammation. We studied the roles of myeloid and airway epithelial TF in acid-caused acute lung injury (ALI). TF on myeloid cells displays a non-coagulatory role regulating the inflammatory response in ALI. Airway epithelial TF contributes to hemostatic functions, but is dispensable in ALI pathogenesis. SUMMARY: Introduction Acute lung injury (ALI) is a life-threatening condition characterized by damaged alveolar-capillary structures and activation of inflammatory and hemostatic processes. Tissue factor (TF) represents a crucial link between inflammation and coagulation, as inflammatory mediators induce myeloid TF expression, and TF initiates extrinsic coagulation. Objective As pulmonary inflammation stimulates TF expression and TF modulates immune responses, we aimed to elucidate its impact on ALI. In particular, we wanted to distinguish the contributions of TF expressed on airway epithelial cells and TF expressed on myeloid cells. Methods Mice with different cell type-specific TF deficiency and wild-type littermates were intratracheally treated with hydrochloric acid, and leukocyte recruitment, cytokine levels, thrombin-antithrombin (TAT) complexes and pulmonary protein-rich infiltrates were analyzed. Results Our data demonstrate that a lack of epithelial TF did not influence acute responses, as bronchoalveolar neutrophil accumulation 8 h after ALI induction was unaltered. However, it led to mild, prolonged inflammation, as pulmonary leukocyte and erythrocyte numbers were still increased after 24 h, whereas those in wild-type mice had returned to basal levels. In contrast, myeloid TF was primarily involved in regulating the acute phase of ALI without affecting local coagulation, as indicated by increased bronchoalveolar neutrophil infiltration, pulmonary interleukin-6 levels, and edema formation, but equal TAT complex formation, 8 h after ALI induction. This augmented inflammatory response associated with myeloid TF deficiency was confirmed in vitro, as lipopolysaccharide-stimulated TF-deficient alveolar macrophages released increased levels of chemokine (C-X-C motif) ligand 1 and tumor necrosis factor-α as compared with wild-type macrophages. Conclusion We conclude that myeloid TF dampens inflammation in acid-induced ALI.

Nonlinear adsorption isotherm as a tool for understanding and characterizing molecularly imprinted polymers.

Molecularly imprinted polymers (MIPs) have frequently been characterized by quantities which are easily determined from experiments but have no theoretical foundation. This makes it difficult to compare different MIP preparations or to transfer MIP based methods to different experimental conditions. Since the adsorption isotherms of MIPs are markedly nonlinear, one can build a better characterization strategy on isotherms as shown by examples in this paper.

Selective trace enrichment of chlorotriazine pesticides from natural waters and sediment samples using terbuthylazine molecularly imprinted polymers

Two molecularly imprinted polymers were synthesized using either dichloromethane or toluene as the porogen and terbuthylazine as the template and were used as solid-phase extraction cartridges for the enrichment of six chlorotriazines (deisopropylatrazine, deethylatrazine, simazine, atrazine, propazine, and terbuthylazine) in natural water and sediment samples. The extracted samples were analyzed by liquid chromatography/diode array detection (LC/DAD). Several washing solvents, as well as different volumes, were tested for their ability to remove the matrix components nonspecifically adsorbed on the sorbents. This cleanup step was shown to be of prime importance to the successful extraction of the pesticides from the aqueous samples. The optimal analytical conditions were obtained when the MIP imprinted using dichloromethane was the sorbent, 2 mL of dichloromethane was used in the washing step, and the preconcentrated analytes were eluted with 8 mL of methanol. The recoveries were higher than 80% for all the chlorotriazines except for propazine (53%) when 50- or 100-mL groundwater samples, spiked at 1 microg/L level, were analyzed. The limits of detection varied from 0.05 to 0.2 microg/L when preconcentrating a 100-mL groundwater sample. Natural sediment samples from the Ebre Delta area (Tarragona, Spain) containing atrazine and deethylatrazine were Soxhlet extracted and analyzed by the methodology developed in this work. No significant interferences from the sample matrix were noticed, thus indicating good selectivity of the MIP sorbents used.

Inhibitory neurogenic modulation of histamine-induced cutaneous plasma extravasation in the pigeon.

The neurohumoral modulation of the permeability increasing effect of histamine was studied in pigeon skin. Substances were administered through plasmapheresis capillaries inserted into the dorsal wing skin and the protein contents of the perfusates were determined by a quantitative method. The vascular labelling technique was also utilized to histologically identify leaky blood vessels. In the innervated skin histamine evoked a significant, dose-dependent plasma extravasation which was markedly augmented by the coadministration of a specific galanin receptor antagonist, galanin-1-16-bradykinin-2-9-amide (M35). Chronic cutaneous denervation per se resulted in a significant elevation of the permeability-enhancing effect of histamine. In the denervated skin this response was not affected by M35 but was significantly inhibited by galanin. It is concluded that in the normally innervated skin endogenous galanin may exert a neurogenic tonic inhibitory effect on histamine-induced plasma leakage. It is suggested that sensory nerves possess not only pro-inflammatory, but also anti-inflammatory (inhibitory) sensory-efferent functions.

Determination of deramciclane and N-desmethylderamciclane in human plasma by liquid chromatography-tandem mass spectrometry using off-line robotic sample pretreatment.

A rapid and highly sensitive LC-MS-MS method using deuterium-labelled internal standards was developed and evaluated for the simultaneous determination of deramciclane and its pharmacologically active metabolite (N-desmethylderamciclane). The sample preparation based on liquid-liquid extraction was carried out with an off-line robotic system. Evaluation of this analytical method shows that samples can be assayed with acceptable accuracy and precision in the 0.1 to 50 ng/ml concentration range for both compounds. The method was applied for the quantitative determination of deramciclane and its metabolite in human plasma samples during a food interaction pharmacokinetic study.

Determination of phenytoin in plasma by molecularly imprinted solid-phase extraction.

A molecularly imprinted polymer (MIP) using phenytoin as template and methacrylamide as the functional monomer was prepared. The selectivity was measured by comparing capacity factors of phenytoin and other structurally related compounds. The polymer was evaluated as a selective sorbent in molecularly imprinted solid-phase extraction (MISPE). Several washing solvents were tested to study their ability to disrupt the non-specific interactions occurring between the sample and the polymer matrix and the role of water in the recognition process was also investigated. It was shown that the key step of successful sample extraction is the right choice of the washing solvent. Plasma samples spiked with phenytoin were analyzed by the MISPE methodology developed in this work. Method validation (intra- and inter-day precision, recovery, specificity) was carried out. The calibration curve showed good linearity in the 2.5-40 microg/ml range corresponding to therapeutically relevant plasma levels. The intra- and inter-day precision values were below the 15% limit established for bioanalytical methods. The results showed that the method could be successfully applied for the determination of phenytoin in plasma samples.

Re-evaluation of conditions required for measurement of true alanine:glyoxylate aminotransferase activity in human liver: implications for the diagnosis of hyperoxaluria type I.

In this paper we studied the glyoxylate-dependent transamination of L-alanine and L-glutamate in human liver homogenates in order to develop a reliable method for the determination of true alanine:glyoxylate aminotransferase activity in liver homogenates from patients suspected to suffer from hyperoxaluria type I. Measurements were made according to two protocols described in literature in control human liver homogenates which were either untreated or treated with an antiserum raised against purified alanine:glyoxylate aminotransferase. The results obtained show that enzyme activity can best be determined at pH 8.0 as compared to pH 7.4 since the former leads to a higher sensitivity of the method. Alanine:glyoxylate aminotransferase activities measured at pH 8.0 are approximately 50% higher compared to the enzyme activities measured at pH 7.4. Accordingly, it is proposed to measure alanine:glyoxylate aminotransferase activity at pH 8.0 using the newly determined correction factor as described in this paper.

Induction of cytotoxicity and ssDNA breaks by 9-bromo-5-morpholino-tetrazolo[1,5-c]quinazoline in tumor cells cultured in vitro.

9-Bromo-5-morpholino-tetrazolo[1,5-c]quinazoline (BMTQ) acted cytotoxically on murine leukemia cell line L1210 and human colon carcinoma cells Caco-2. We found the two highest concentrations of BMTQ (149.2 and 74.6 microM) induced an acute cytotoxic effect, however other tested concentrations (<74.6 microM) manifested a concentration/dependent and time/dependent cytotoxic effect. The sensitivity of murine leukemia cells L1210 and human colon carcinoma cells Caco-2 was expressed in the same order. The cytotoxicity of BMTQ was not accompanied by changes of the cell cycle profile. Following the cytotoxicity-related effects of BMTQ we observed the induction of ssDNA breaks after BMTQ treatment. All the concentrations of BMTQ increased the level of ssDNA breaks 1.3-2.9 times (after 2 h of treatment) and 1.6-2.8 times (after 4 h of treatment) in Caco-2 cells compared to the control. No apoptotic DNA fragmentation induced by BMTQ in Caco-2 cells was recorded.