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Introduction: Benzotriazoles and benzothiazoles (BTs) are high-production volume chemicals as well as widely distributed emerging pollutants with potential health risk. However, information about human exposure to BTs and associated health outcomes is limited. Objective: We aimed to characterise exposure to BTs among Czech men, including possible occupational exposure among firefighters, its predictors, and its associations with liver function, serum lipids and oxidative stress. Methods: 165 participants (including 110 firefighters) provided urine and blood samples that were used to quantify the urinary levels of 8 BTs (high-performance liquid chromatography-tandem mass spectrometry), and 4 liver enzymes, cholesterol, low-density lipoprotein, and 8-hydroxy-2'-deoxyguanosine. Linear regression was used to assess associations with population characteristics and biomarkers of liver function, serum lipids and oxidative stress. Regression models were adjusted for potential confounding variables and false discovery rate procedure was applied to account for multiplicity. Results: The BTs ranged from undetected up to 46.8 ng/mL. 2-hydroxy-benzothiazole was the most predominant compound (detection frequency 83%; median 1.95 ng/mL). 1-methyl-benzotriazole (1M-BTR) was measured in human samples for the first time, with a detection frequency 77% and median 1.75 ng/mL. Professional firefighters had lower urinary 1M-BTR compared to non-firefighters. Urinary 1M-BTR was associated with levels of γ-glutamyl transferase (β = − 17.54%; 95% CI: − 26.127, − 7.962). Conclusion: This is the first study to investigate BT exposure in Central Europe, including potentially exposed firefighters. The findings showed a high prevalence of BTs in the study population, the relevance of 1M-BTR as a new biomarker of exposure, and an urgent need for further research into associated adverse health outcomes. [ABSTRACT FROM AUTHOR]

Background: To restore sensation after breast reconstruction, a modified surgical approach was employed by identifying the cut fourth intercostal lateral cutaneous branch, elongating it with intercostal nerve grafts, and coapting it to the innervating nerve of the flap or by using direct neurotization of the spared nipple/skin. Methods: This was a retrospective case–control study including 56 patients who underwent breast neurotization surgery. Breast operations included immediate reconstruction after nipple-sparing mastectomy (36 patients), skin-sparing mastectomy (8 patients), and delayed reconstruction with nipple preservation (7 patients) or without nipple preservation (5 patients). Patients who underwent breast reconstruction without neurotization were included as the non-neurotization negative control group. The contralateral normal breasts were included as positive controls. Results: The mean(s.d.) monofilament test values were 0.07(0.10) g for the positive control breasts and 179.13(143.31) g for the breasts operated on in the non-neurotization group. Breasts that underwent neurotization had significantly better sensation after surgery, with a mean(s.d.) value of 35.61(92.63) g (P < 0.001). The mean(s.d.) sensory return after neurotization was gradual; 138.17(143.65) g in the first 6 months, 59.55(116.46) g at 7–12 months, 14.54(62.27) g at 13–18 months, and 0.37(0.50) g at 19–24 months after surgery. Two patients had accidental rupture of the pleura, which was repaired uneventfully. One patient underwent re-exploration due to a lack of improvement 1.5 years after neurotization. Conclusion: Using the lateral cutaneous branch of the intercostal nerve as the innervating stump and elongating it with intercostal nerve grafts is a suitable technique to restore sensation after mastectomy. This method effectively innervates reconstructed breasts and spares the nipple/skin with minimal morbidity. Using an intercostal nerve as the donor and direct suture to the base of the nipple is an efficient and effective method for breast and nipple neurotization. [ABSTRACT FROM AUTHOR]

This study investigated the image quality and choice of ultra-high b-value of two DWI breast-MRI research applications. The study cohort comprised 40 patients (20 malignant lesions). In addition to s-DWI with two m-b-values (b50 and b800) and three e-b-values (e-b1500, e-b2000, and e-b2500), z-DWI and IR m-b1500 DWI were applied. z-DWI was acquired with the same measured b-values and e-b-values as the standard sequence. For IR m-b1500 DWI, b50 and b1500 were measured, and e-b2000 and e-b2500 were mathematically extrapolated. Three readers used Likert scales to independently analyze all ultra-high b-values (b1500–b2500) for each DWI with regards to scan preference and image quality. ADC values were measured in all 20 lesions. z-DWI was the most preferred (54%), followed by IR m-b1500 DWI (46%). b1500 was significantly preferred over b2000 for z-DWI and IR m-b1500 DWI (p = 0.001 and p = 0.002, respectively). Lesion detection was not significantly different among sequences or b-values (p = 0.174). There were no significant differences in measured ADC values within lesions between s-DWI (ADC: 0.97 [±0.09] × 10−3 mm2/s) and z-DWI (ADC: 0.99 [±0.11] × 10−3 mm2/s; p = 1.000). However, there was a trend toward lower values in IR m-b1500 DWI (ADC: 0.80 [±0.06] × 10−3 mm2/s) than in s-DWI (p = 0.090) and z-DWI (p = 0.110). Overall, image quality was superior and there were fewer image artifacts when using the advanced sequences (z-DWI + IR m-b1500 DWI) compared with s-DWI. Considering scan preferences, we found that the optimal combination was z-DWI with a calculated b1500, especially regarding examination time. [ABSTRACT FROM AUTHOR]

Purpose: Microvascular surgery requires highly specialized and individualized training; most surgical residency training programs are not equipped with microsurgery teaching expertise and/or facilities. The aim of this manuscript was to describe the methodology and clinical effectiveness of an international microsurgery course, currently taught year-round in eight countries. Methods: In the 5-day microsurgery course trainees perform arterial and venous end-to-end, end-to-side, one-way-up, and continuous suture anastomoses and vein graft techniques in live animals, supported by video demonstrations and hands-on guidance by a full-time instructor. To assess and monitor each trainee's progress, the course's effectiveness is evaluated using "in-course" evaluations, and participant satisfaction and clinical relevance are assessed using a "post-course" survey. Results: Between 2007 and 2017, more than 600 trainees participated in the microsurgery course. "In-course" evaluations of patency rates revealed 80.3% (arterial) and 39% (venous) performed in end-to-end, 82.7% in end-to-side, 72.6% in continuous suture, and 89.5% (arterial) and 62.5% (venous) one-way-up anastomoses, and 58.1% in vein graft technique. "Post-course" survey results indicated that participants considered the most important components of the microcourse to be "practicing on live animals", followed by "the presence of a full-time instructor". In addition, almost all respondents indicated that they were more confident performing clinical microsurgery cases after completing the course. Conclusions: Microvascular surgery requires highly specialized and individualized training to achieve the competences required to perform and master the delicate fine motor skills necessary to successfully handle and anastomose very small and delicate microvascular structures. The ever-expanding clinical applications of microvascular procedures has led to an increased demand for training opportunities. By teaching time-tested basic motor skills that form the foundation of microsurgical technique this international microsurgery-teaching course is helping to meet this demand. [ABSTRACT FROM AUTHOR]

Background: Perioperative hemodynamic instability is one of the most common adverse events in patients undergoing adrenalectomy for pheochromocytoma. The aim of this study was to analyze the impact of perioperative severe hemodynamic instability. Methods: We present a retrospective, single-center analysis in a major tertiary hospital of all consecutive patients undergoing elective adrenalectomy from 2005 to 2019 for pheochromocytoma. Severe perioperative hypertension and hypotension were evaluated, defined as changes in blood pressure larger than 30% of the preoperative patient-specific mean arterial pressure (MAP). Results: Unilateral adrenalectomy was performed in 67 patients. Intraoperative episodes of hemodynamic instability occurred in 97% of all patients (n = 65), severe hypertension occurred in 24 patients (36%), and severe hypotensive episodes occurred in 62 patients (93%). Patients with more than five severe hypotensive episodes (n = 29) received higher preoperative alpha-adrenergic blockades (phenoxybenzamine 51 ± 50 mg d−1 vs. 29 ± 27 mg d−1; p = 0.023) and had a longer mean ICU stay (39.6 ± 41.5 h vs. 20.6 ± 19.1 h, p = 0.015). Conclusion: Intraoperative hypotensive, rather than hypertensive, episodes occurred during adrenalectomy. The occurrence of more than five hypotensive episodes correlated well with a significantly longer hospital stay and ICU time. [ABSTRACT FROM AUTHOR]

Background and Objectives: Primary sclerosing cholangitis (PSC) is a rare cholestatic disease of the liver of unknown etiology, severe course and poor prognosis. PSC most often co-occurs with inflammatory bowel diseases (IBD), especially with ulcerative colitis (UC). The aim of the study was the analysis of the clinical course of primary sclerosing cholangitis in children, hospitalized in the Gastroenterology Unit in Katowice. Materials and Methods: The analysis included 30 patients, aged from 7 to 18 years, 21/30 boys (70%) and 9/30 girls (30%), diagnosed with PSC in the years 2009–2019. The analysis included the age at diagnosis, clinical symptoms, course of the disease, coexisting diseases, laboratory and imaging results, and complications. Results: The average age at diagnosis was 13 years. 22/30 (73.3%) patients suffered from UC, 4/30 (13.3%) were diagnosed with Crohn’s disease (CD), 2/30 (6.66%) with Eosinophilic Colitis (EC). 2/30 patients (6.66%) had no clinical evidence of coexistent IBD to date. In addition, 7/30 (23.3%) had an overlap syndrome of primary sclerosing cholangitis/autoimmune hepatitis. When PSC was detected before IBD (6/30–20%), patients had complications more often compared to those diagnosed with IBD first or PSC and IBD at the same time. At the moment of diagnosis 6/30 (20%) patients presented with abdominal pain, which was the most common symptom, 3/30 (10%) jaundice, while 17/30 (56.6%) were asymptomatic but had abnormal results of the laboratory tests. Conclusions: Monitoring liver markers in IBD patients is important since most PSC cases are asymptomatic and their elevation might be the first sign of the disease. Patients diagnosed with PSC before IBD diagnosis are more likely to have a more aggressive course of the disease. [ABSTRACT FROM AUTHOR]

In patients with peripheral arterial occlusive disease (PAOD) a restricted circulation in cutaneous microvessels has been reported. In this study the velocity of erythrocytes (very) in finger nailfold capillaries - a vascular area without upstream macroangiopathy - and also in toe nailfold capillaries - a post-stenotic area –was investigated using capillary microscopy in apparently healthy subjects and patients with PAOD. Already in finger nailfold capillaries very of patients with PAOD under resting conditions was significantly lower than in capillaries of healthy subjects. This was also true for the circulation in toe capillaries. In addition, the erythrocyte velocities under resting conditions in the toe capillaries were significantly lower than in the finger capillaries. Similar results were found for the duration and the maximum velocity of postocclusive hyperemia. It is concluded that the resting blood flow in the skin microcirculation is impaired in PAOD patients, both under resting conditions and during postocclusive hyperemia in finger as well in toe nailfold capillaries. [ABSTRACT FROM AUTHOR]

Thrombotic disorders remain the leading cause of mortality and morbidity, despite the fact that anti-platelet therapies and vascular implants are successfully used today. As life expectancy is increasing in western societies, the specific knowledge about processes leading to thrombosis in elderly is essential for an adequate therapeutic management of platelet dysfunction and for tailoring blood contacting implants. This study addresses the limited available data on platelet function in apparently healthy subjects in relation to age, particularly in view of subjects of old age (80–98 years). Apparently healthy subjects between 20 and 98 years were included in this study. Platelet function was assessed by light transmission aggregometry and comprised experiments on spontaneous as well as ristocetin-, ADP- and collagen-induced platelet aggregation. The data of this study revealed a non-linear increase in the maximum spontaneous platelet aggregation (from 3.3% ±3.3% to 10.9% ±5.9%). The maximum induced aggregation decreased with age for ristocetin (from 85.8% ±7.2% to 75.0% ±7.8%), ADP (from 88.5% ±4.6% to 64.8% ±7.3%) and collagen (from 89.5% ±3.0% to 64.0% ±4.0%) in a non-linear manner (linear regression analysis). These observations indicate that during aging, circulating platelets become increasingly activated but lose their full aggregatory potential, a phenomenon that was earlier termed "platelet exhaustion". In this study we extended the limited existing data for spontaneous and induced platelet aggregation of apparently healthy donors above the age of 75 years. The presented data indicate that the extrapolation of data from a middle age group does not necessarily predict platelet function in apparently healthy subjects of old age. It emphasizes the need for respective studies to improve our understanding of thrombotic processes in elderly humans. [ABSTRACT FROM AUTHOR]

BACKGROUND: The laser Doppler fluxmetry (LDF) is a non-invasive method to assess skin blood perfusion, measuring the flow of blood cells inside a tissue volume without harming the tissue. In the diagnosis of skin circulation disorders, the results of the LDF measurement are generally used in such a way that "normal" (or non-ill) or "pathological" values are achieved by comparison with a reference sample, for example of apparently healthy subjects. MATERIAL AND METHODS: In this study, the values of LDF for the diagnosis of microcirculatory disorders in patients with coronary artery disease (n = 20) or in patients with microcirculatory disorders, already diagnosed by capillary microscopy (n = 46), were examined. RESULTS: The mean values of LD amplitudes in the four frequency windows for patients with coronary artery disease were in the reference range. However, some of the patients showed reduced LD values: in eleven of the twenty patients, one or more mean LD amplitudes were below the reference range. Four of the eleven patients had pathologically decreased capillary erythrocyte velocities of very = 0.09–0.21 [mm/s], while the other seven patients had normal blood circulation at rest. For all patients with a proven cutaneous microcirculatory disorder, the mean LD amplitude in at least one of the frequency windows FF2 to FF4 was pathologically reduced. CONCLUSION: The Laser-Doppler fluxmetry method used in the study allows the reliable diagnosis of cutaneous microcirculatory disorders. [ABSTRACT FROM AUTHOR]

This study was designed to characterize morphologic stages during neuroma development post amputation with an eye toward developing better treatment strategies that intervene before neuromas are fully formed. Right forelimbs of 30 Sprague Dawley rats were amputated and limb stumps were collected at 3, 7, 28, 60 and 90 ays ost mputation (DPA). Morphology of newly formed nerves and neuromas were assessed via general histology and neurofilament protein antibody staining. Analysis revealed six morphological characteristics during nerve and neuroma development; 1) normal nerve, 2) degenerating axons, 3) axonal sprouts, 4) unorganized bundles of axons, 5) unorganized axon growth into muscles, and 6) unorganized axon growth into fibrotic tissue (neuroma). At early stages (3 & 7 DPA) after amputation, normal nerves could be identified throughout the limb stump and small areas of axonal sprouts were present near the site of injury. Signs of degenerating axons were evident from 7 to 90 DPA. From day 28 on, variability of nerve characteristics with signs of unorganized axon growth into muscle and fibrotic tissue and neuroma formation became visible in multiple areas of stump tissue. These pathological features became more evident on days 60 and 90. At 90 DPA frank neuroma formation was present in all stump tissue. By following nerve regrowth and neuroma formation after amputation we were able to identify 6 separate histological stages of nerve regrowth and neuroma development. Axonal regrowth was observed as early as 3 DPA and signs of unorganized axonal growth and neuroma formation were evident by 28 DPA. Based on these observations we speculate that neuroma treatment and or prevention strategies might be more successful if targeted at the initial stages of development and not after 28 DPA. [ABSTRACT FROM AUTHOR]

The Laser Doppler technique (Laser-Doppler-Fluxmetry, LDF), a noninvasive method to estimate skin blood flow (LDF), is frequently used in research and clinical routine [1]. Here, the measurements were carried out with a new Laser Doppler system, the DOP-system, which allows to measure frequency spectra in four different frequency windows according to the velocities in venules (low velocity), capillaries (low to medium velocities), and in arteries (with high and very high velocities). However, the diagnostic reliability or the effectiveness of the LDF has not yet been evaluated sufficiently, which is indispensable, where medical diagnostics and therapy controls are concerned. For a valid interpretation of LDF values of individual patients, the knowledge of the reference range and the variability of the measured parameters is required. In four successive studies the reference range (62 apparently healthy subjects), the circadian variability (8 subjects), the variability from day-to-day (6 subjects) and over one year with monthly measurements (6 subjects) were evaluated. With the knowledge of the reference range, microcirculatory disorders can now be diagnosed using the DOP method. Following a standard measurement procedure there was no dependence of the measured data on the day or season of measurement. [ABSTRACT FROM AUTHOR]

Cerebrovascular diseases are considered in a different way concerning their etiology with regard to arterial and venous occlusion. The role of thrombophilia in this context remains undetermined. For this reason, a case-control study was conducted including a total of 202 patients (154 females, 48 males) aged from 18 to 76 years (mean: 39.8 years) suffering either from cerebral sinus venous thrombosis (n = 101) or from arterial ischemic stroke (n = 101). Study groups were evaluated on the basis of age- and gender-matched pairs. Gene mutations of factor V-1691 (factor V Leiden) and prothrombin-20210 being considered as the most common thrombophilia markers were analyzed in this study. Factor V Leiden-mutations were found in 16.8% of patients with cerebral sinus venous thrombosis (CVT) and in 17.8% of patients with arterial ischemic stroke (AIS), which was significantly more frequent than in controls at a rate of 4.95% (ORs: 3.89 and 4.16). Prothrombin-mutations were significantly more frequent in CVT at a rate of 14.9% versus 2.97% in controls (OR: 5.70). This does not apply for AIS showing a rate of 4.95% prothrombin-mutations. Rates of factor V Leiden-mutations are not different in CVT compared with AIS. In contrast, however, prothrombin-mutations were significantly more frequent in CVT than in AIS with a rate of 14.9% versus 4.95% (OR 3.35). Furthermore, 3 cases with combined heterozygosity of factor V Leiden- and prothrombinmutation have been identified in CVT, but not in AIS or controls. All of the above mentioned mutations were exclusively heterozygous. We conclude from these data that thrombophilia in terms of factor V Leiden genotype is a risk factor for both CVT and AIS in equal measure. In contrast, prothrombin-20210-mutations were different playing a significant role in the pathogenesis of cerebral sinus vein thrombosis, but not in arterial ischemic stroke. Also, the combined occurrence of heterozygous prothrombin- and factor V Leiden-mutation clearly favors the emergence of cerebral sinus venous thrombosis. Therefore, in terms of thrombophilia such as investigated in this study, pathogenesis of arterial and venous occlusions in cerebrovascular disease has to be regarded as different. [ABSTRACT FROM AUTHOR]

Introduction: Microsurgery courses, taught external to surgical training programs, are essential for acquiring the high level of technical skill required for clinical proficiency. Methods: The Frankfurt microsurgery course is a 5-day, intensive course that teaches arterial and venous anastomosis using end-to-end, end-to-side, one-way-up, continuous-suture, and vessel graft techniques. During the course, the instructor records the level of skill (in-course data) achieved by each trainee by assessing anastomosis completion and patency. Demographic information is also collected. Post-course trainees are invited to complete an online survey (post-course data) to get their opinions of the courses' effectiveness. Results: The in-course 'skill achievement' and post-course 'course effectiveness' data are presented below. In-course data: 94.8 and 59.9% of participants completed patent end-to-end arterial and venous anastomoses, respectively, while 85.4% performed a patent end-to-side anastomosis. 96.1 and 57.1% of participants who attempted arterial and venous anastomoses using the one-way-up technique were successful, as were 90.9% of those attempting continuous-suture technique. Patent venous grafts were performed by 54.7% of participants. Post-course data: All respondents indicated significant improvement of their microsurgical skills after taking the course. 66.7% of respondents considered the full-time presence of the instructor to be the most valuable aspect of the course. All respondents would highly recommend the course to colleagues. Conclusion: The microcourse significantly increased trainees' clinical microsurgery skills, confidence, and the number of clinical cases they perform. Of all the anastomosis techniques taught, venous anastomosis and grafting were the most difficult to learn. The presence of a full-time experienced instructor was most important. [ABSTRACT FROM AUTHOR]

Designing diffractive optical elements is crucial for efficient development of THz techniques. Here, we consider paper structures and we analyze their advantages and disadvantages in fast prototyping. The discussion about using material parameters like refractive index and absorption coefficient in designing diffractive optical elements is shown. We analyze the influence of phase step mismatch, of attenuation of real structure, and of nonuniform illumination on the efficiency of the structure. All these features result in worsening of the diffraction efficiency but they do not seem to have such significant influence as shadow effect introduced by fast varying zones. Diffractive elements can be designed with very good accordance with experimental results which makes them ideal for possible applications. Paper optics scan be used more for fast prototyping; nevertheless its performance can be increased by placing it inside water protecting foil. [ABSTRACT FROM AUTHOR]

Activation of coagulation and inflammatory response including the complement system play a major role in the pathogenesis of critical illness. However, only limited data are available addressing the relationship of both pathways and its assessment of a predictive value for the clinical outcome in intense care medicine. Therefore, parameters of the coagulation and complement system were studied in patients with septicaemia and multiple trauma regarded as being exemplary for critical illness. 34 patients (mean age: 51.38 years (±16.57), 15 females, 19 males) were investigated at day 1 of admittance to the intensive care unit (ICU). Leukocytes, complement factors C3a and C5a were significantly (p < 0.0500) higher in sepsis than in trauma, whereas platelet count and plasma fibrinogen were significantly lower in multiple trauma. Activation markers of coagulation were elevated in both groups, however, thrombin-antithrombin-complex was significantly higher in multiple trauma. DIC scores of 5 were not exceeded in any of the two groups. Analysing the influences on mortality (11/34; 32.35%), which was not different in both groups, non-survivors were significantly older, had significantly higher multiple organ failure (MOF) scores, lactate, abnormal prothrombin times and lower C1-inhibitor activities, even more pronounced in early deaths, than survivors. In septic non-survivors protein C was significantly lower than in trauma. We conclude from these data that activation of the complement system as part of the inflammatory response is a significant mechanism in septicaemia, whereas loss and consumption of blood components including parts of the coagulation and complement system is more characteristic for multiple trauma. Protein C in case of severe reduction might be of special concern for surviving in sepsis. Activation of haemostasis was occurring in both diseases, however, overt DIC was not confirmed in this study to be a leading mechanism in critically ill patients. MOF score, lactate, C1-inhibitor and prothrombin time have been the only statistically significant predictors for lethal outcome suggesting that organ function, microcirculation, haemostasis and inflammatory response are essential elements of the pathomechanism and clinical course of diseases among critically ill patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: The role of the microcirculation in the pathophysiology and symptoms of peripheral arterial obliterative disease (PAOD) has been progressively emphasized during the past decades. Under resting conditions, already, the tissue oxygen partial pressure in the m. tibialis anterior (pO2im) is reduced to about 50% compared to healthy subjects.METHODS: In the framework of this study the pO2im of patients with PAOD stage II according to Fontaine (n=16) in the m. tibialis anterior was measured under resting conditions and during walking on a treadmill in comparison to healthy subjects (n=10).RESULTS: Under resting conditions the pO2im only marginally differed between PAOD patients and healthy subjects. But during exercise the pO2im dropped significantly more severely in PAOD patients and a return to baseline values could only be reached when the treadmill was stopped and the patients stood still. The pO2im minima correlated clearly with the clinical symptom of calf pain.CONCLUSION: The data revealed that the pO2im values were lower in PAOD patients and dropped significantly faster during walking compared to the pO2im values in healthy subjects. The pO2im decrease correlated with the calf pain occurring when the pO2im values approached or fell below 10 mmHg. [ABSTRACT FROM AUTHOR]

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function.This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network.The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease.These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression. [ABSTRACT FROM AUTHOR]

Strumeň, a town in the Duchy of Těšín, bordering Pština, a strongly Protestant estate, was by the early 18th century a mostly Catholic locality, which provided significant support to the Roman Catholic Church in this part of Upper Silesia. This fact might be attributed to the successful cooperation of state and church offices within the implementation of recatholicisation policies which had been taking place since the 1670s. The successful, long-term pastoral work done by the local parson Jan Isidor Janus is also a likely contributing factor. One of the significant documents aimed towards the restoration of Catholicism in this town is the letter of the Těšín provincial governor Jan Laryš of Lhota to the mayor and council of Strumeň, dating from August 3, 1673. Based on the request by the Strumeň priest Janus, Laryš urges them under penalty of imprisonment to uphold the proper Catholic upbringing of the youth of Strumeň, as well as their regular attendance of catechism and their receiving of penance and the Eucharist. Besides editing this written source, this contribution places it in a wider context within the development of the Strumeň parish. [ABSTRACT FROM AUTHOR]

Background: Endothelial cells secrete different mediators depending on biochemical and/or biophysical conditions, which can lead to vasodilation or vasoconstriction, respectively. Impaired endothelial responsiveness to specific vasodilator stimuli has been used as a surrogate marker of cardiovascular risk. Multiple methods allow testing endothelial responses in both microvessels and conduit arteries, but it is still unclear whether there is a relationship in endothelial function between these two different vascular beds. Material and methods: In order to examine, whether such macrocirculatory data might correlate with data obtained in the supplied microvessels, a parallel investigation in the brachial artery (BA) and the supplied nailfold capillaries was performed. The duration and amplitude of the postischemic hyperemia (stasis in the vasculature of the left arm using a blood pressure cuff for 3 minutes) were measured (ultrasound technique) and simultaneously the amplitude and duration of the postischemic hyperemia in ipsilateral nailfold capillaries (intravital capillaroscopy). Results: There was absolutely no correlation between the duration (n = 153, r = 0.076, p = 0.3493) of the diameter increase in the BA and in ipsilateral nailfold capillaries. Conclusion: The regulation of the cutaneous microcirculation did not follow diameter changes of the conduit artery (BA) but seems to be dominated by the precapillary arterioles. [ABSTRACT FROM AUTHOR]

One thousand two hundred and fifty-six subjects (apparently healthy subjects and patients with cardiovascular diseases) were registered in a prospective study including demographical and clinical data, rheological parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as the erythrocyte velocity in human nailfold capillaries under resting and postischemic conditions. A multivariate regression analysis showed that under resting conditions there was no correlation between rheological parameters and erythrocyte velocity in capillaries. The blood flow regulation seemed to be so effective, that pathological changes of the blood fluidity showed no effect on the velocity of an erythrocyte passing the capillaries. During vessel paralysis in the early phase of the postischemic hyperemia following a stasis of three minutes in the vasculature distal to a pressure cuff at the upper arm a very clear correlation between the plasma viscosity and the maximum postischemic erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p < 0.0001) while none of the other rheological parameters seemed to play a role. In a subgroup of diabetic patients the erythrocyte aggregation (measured during stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the plasma viscosity. This shows that a correlation of rheological parameters with the capillary perfusion could only be found during vessel paralysis. In of diabetic patients besides the plasma viscosity also the erythrocyte aggregation correlated with the mean capillary erythrocyte velocity. Theses results are in agreement with the hypothesis from Barras that plasma viscosity determines the perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also the erythrocyte aggregation plays a role. [ABSTRACT FROM AUTHOR]

The ingredients and the macro- and micro-nutrient contents of diets that are fed to captive kiwi at seven New Zealand holding facilities were subject to analysis. The nutrient compositions were compared across facilities and with an estimate of the nutrient composition of the diets of wild kiwi based on the intake of various dietary ingredients reported in the literature. A total of 20 ingredients were used, the number and proportion of these ingredients varied greatly between facilities. Six of the diets were based primarily on meat and three comprised a mixture of meat and cat biscuits. Just one included a proprietary insectivore mix. Nutrient content varied greatly between the seven diets, organic matter ranging from 91.8 to 95.6%, crude protein from 41.9 to 62.9%, and crude fat from 9.0 to 28.7% of dry matter content. Large variations were found in the total content and profile of amino acids and of fatty acids of the diets. The nutrient content of all seven diets differed from that of the natural diet of wild kiwi. Hence, the presence of nutrient deficiencies in the current formulations cannot be excluded. Zoo Biol 29:537-550, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Changes in haemorheology and haemostasis may contribute to bleeding or thrombosis, which is of concern particularly in surgery. Blood loss itself has a major influence on both parameters being closely involved in the clinical outcome. In order to analyze the underlying interrelations, a prospective study with 122 patients (64 females, 58 males) aged between 18 and 83 years (mean: 51.8 years) was conducted. All patients were electively submitted to orthopaedic surgery. Haemorheological parameters included measurements of plasma viscosity, red body cell (RBC) and platelet aggregation index preoperatively, as well as by day 1 and day 7 after surgery. Additionally hematological and haemostaseological parameters including leukocyte and platelet counts, haematocrit and fibrinogen were investigated. Bleeding was defined as high (>500 ml) or low blood loss (≤500 ml) according to the drainage volume. High but not low blood loss was associated with an increase of RBC aggregation by day 1 and 7 after surgery. Plasma viscosity decreased significantly by day 1, returning to normal 7 days after surgery. Platelet count decreased significantly, concurrent with the haematocrit, by day 1 postoperatively, whereas by day 7 a significant increase was observed, being more distinct in high blood loss. Platelet aggregation index did not change under the influence of blood loss. Plasma fibrinogen, clearly corresponding to the extend of blood loss, showed a continuous postoperative increase, which was significantly higher at day 7. Leukocytes increased moderately but significantly in particular in high blood loss. In conclusion, the postoperative decrease of plasma viscosity and of platelet counts, concurrent with the haematocrit, provides evidence of being clearly dependent on blood loss which is regarded as a dilution effect corresponding with the haemorrhagic risk. The increase of RBC aggregation at the early postoperative stage is solely observed in high blood loss and is esteemed as a result of volume therapy. The marked increase of platelet counts and plasma fibrinogen at the late postoperative stage, being more pronounced in high blood loss, might contribute to an elevated prothrombotic risk and is ascribed to an inflammatory response to surgery. In summary, it is concluded, that bleeding tendency corresponding with haemorheologic parameters is enhanced in the early, whereas the prothrombotic risk, well correlating with haemostaseologic parameters, is elevated in the later stage after surgery. [ABSTRACT FROM AUTHOR]

Septic and haemorhagic shock carry the risk of high mortality. Failure of microcirculation secondary to alterations of haemostasis and fibrinolysis play a major role in the pathogenesis of shock. The aim of this study was to evaluate the clinical relevance of procoagulatory and fibrinolytic activities referring to survival. Therefore, 39 patients (23 to 80 yrs, 16 females, 23 males) suffering from haemorrhagic (n = 21) and septic shock (n = 18) were screened prospectively for plasmatic coagulation and fibrinolysis parameters. Thirteen patients (33.3%) developed lethal outcome. Concerning fibrinolysis, plasminogen was significantly lower in non-survivors by day 1 and plasmin–antiplasmin complex significantly higher by day 4 compared to survivors. Consecutive increase of plasminogen over day 4 and 7 was significantly stronger in survivors. Concerning haemostasis activation, thrombin–antithrombin complex was higher and D-dimers or fibrinogen levels were lower, but not significantly different, in non-survivors compared to survivors. We conclude from these data, that procoagulant activities are increased, but not significantly predictive for the clinical outcome in septic and haemorrhagic shock. By contrast, fibrinolysis, as measured by enhanced capacity and responsiveness, is clearly predictive and plays a significant role for survival, possibly due to its clearing function in microcirculation. [ABSTRACT FROM AUTHOR]

Despite increasing advances in microvascular free tissue transfer, flap failures, most commonly resulting from thrombosis at the anastomotic vascular site, remain a significant concern. Although several experimental and clinical studies have been carried out, no consensus has been reached so far on the efficacy, dosage and timing of anticoagulant agents available for the prevention and treatment of thrombosis in microvascular surgery. Inhibition of fibrin formation and platelet function or the use of thrombolytic agents is a common approach in the antithrombotic management. However, some agents exhibit serious side effects and all of them carry the risk of bleedings. The current literature on the use of antithrombotic agents, targeting at clinical trials in microvascular surgery, is therefore reviewed, to provide an informative basis for recommendations for an appropriate pharmacological approach. [ABSTRACT FROM AUTHOR]

Background: Oral anticoagulants are routinely used for prevention of thromboembolism in cardiac, arterial or venous diseases. Hemorrhages are serious treatment complications, frequently occurring under long-term and/or high-dose regiments. From animal experiments it is known that coumarin-type anticoagulants may cause capillary dilatation and increased permeability, red blood cell extravasation and punctate bleeding. Controlled human trials are lacking. Methods: 31 patients under oral anticoagulation were examined by video capillary microscopy. 52 patients with comparable diseases and treatment but without oral anticoagulation served as controls. Nailfold capillaries of four fingers of each hand were examined and analyzed off-line according to the following criteria: (1) numbers of capillaries investigated, (2) numbers of capillary bleedings, and (3) bleeding incidence (bleedings per 100 capillaries). Results: In 23 out of 31 patients (74.2%) capillary bleedings were observed. The bleeding incidence ranged from 0.33 to 4.29 per 100 capillaries. In contrast, only 4 out of 52 controls were detected with capillary bleedings (2.1%, p<0.001). The bleeding incidence was 0.34–2.41. In patients on anticoagulation there was no correlation between the number of capillary bleedings and the INR or Quick values. During a two year follow-up of patients on oral anticoagulation no significant difference was found in terms of clinically obvious bleedings in patients with or without capillary bleedings. Conclusion: This study shows that capillary bleedings can be demonstrated in patients on oral anticoagulation. Bleedings occur independent of the INR-value. Thus, other factors than the vitamin-k-dependent coagulation effect seem to be causal for the damage of microvessels. Further, the evidence of capillary bleedings is not a prognostic indicator for future hemorrhage. [ABSTRACT FROM AUTHOR]

Genetic polymorphisms in plasminogen activator inhibitor-1 gene-675 4G/5G (PAI-1 4G/5G) are claimed to contribute to an increased risk of venous thromboembolism. Inherited thrombophilia, on the other hand, is associated with the occurrence of spontaneous abortions. The objective of this study was, to explore the significance of genetic polymorphisms of PAI-1 4G/5G with particular emphasis on 4G alleles in pregnant women suffering from venous thromboembolism or early spontaneous abortion, respectively. Therefore genetic PAI-1 4G/5G polymorphisms were studied in 108 pregnant females suffering from venous thromboembolism (n=69) or from spontaneous abortion (<20 week, n=39), respectively. Healthy volunteers (n=238) were taken as controls. The frequencies of 4G alleles (4G/4G or 4G/5G genotypes) of PAI-1 were significantly higher in venous thromboembolism (OR: 3.40, p=0.0088) and slightly higher, but not significantly, in abortions (RR: 2.33; p=0.1162) compared to controls. The incidence of 4G-carriers in females with abortion was 0.68 (-32%) compared to women suffering from venous thromboembolism alone. We conclude from these data, that the occurrence of PAI-1 4G/4G or 4G/5G genotypes, respectively, is clinically significant for the pathogenesis of venous thromboembolism in pregnancy but not for early abortion. [ABSTRACT FROM AUTHOR]

Introduction: To reduce intraoperative blood loss in liver resections surgical bleeding control is often performed by a complete inflow obstruction of the liver called Pringle manoeuvre leading to a portal venous stasis. Platelet aggregability may be affected by this circulatory stasis. Materials and methods: A study population of 11 patients (37–67 years old, 7 females and 4 males) with hepatic tumours underwent elective liver resection. Pringle manoeuvre of up to 50 min duration was used in 4 patients. The other 7 patients were operated using selective vascular clamping. Platelets were aggregated before and after liver resection with adenosine diphosphate, collagen and ristocetin (according to Born). Results: Mean maximal amplitudes of platelet aggregation were comparable before and after liver resection. Statistic analysis did not detect a significant difference between the values before and after liver resection as well as between Pringle manoeuvre and selective vascular clamping. Conclusion: Induced platelet aggregability is not affected by the method of surgical bleeding control used in liver resection. Platelet aggregability seems to be resistant even to portal venous stasis of up to 50 min during Pringle manoeuvre. [ABSTRACT FROM AUTHOR]

Purpose: It was the aim of this study to evaluate antiphospholipid antibodies (APA), i.e. lupus anticoagulants (LA) and anticardiolipin (ACA) IgG and IgM, in ophthalmic occlusive disease. Methods: Over a 3.5-year period, APA were evaluated in 368 patients. Results: Eighty-six patients (23.4%), compared to 5% in the general population, tested positive for APA. APA did not differ significantly between patients with venous (20.6%) or arterial (25.5%) occlusive disease. This included 93 patients with central retinal vein occlusion (18% APA positive), 67 with retinal branch vein occlusion (24% APA positive), 41 with central retinal artery occlusion (22% APA positive), 53 with retinal branch artery occlusion (32% APA positive), 71 with anterior ischemic optic neuropathy (23% APA positive), 12 with posterior ischemic optic neuropathy (33% APA positive) and 31 patients with amaurosis fugax (23% APA positive). Excluding patients with accepted main risk factors, APA were positive in 15.3% of 85 patients. Conclusion: The high APA prevalence confirms its relevance in ocular occlusive disorders. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Argatroban ist ein direkter, selektiver und reversibler „Active-site-Thrombininhibitor“. Die Substanz leitet sich chemisch vom L-Arginin ab und hemmt sowohl freies als auch bereits fibringebundenes Thrombin. Argatroban hat eine vorteilhafte Pharmakokinetik mit einer β-Eliminationshalbwertszeit von 40–50 min, wird hepatisch metabolisiert, überwiegend biliär eliminiert und kumuliert nicht bei Patienten mit Niereninsuffizienz. In Japan und in den USA ist die Substanz seit mehreren Jahren im klinischen Gebrauch und wurde erfolgreich als Antikoagulans zur koronaren Angioplastie sowie zur extrakorporalen Zirkulation bei herzchirurgischen Eingriffen und bei Nierenersatzverfahren angewendet. Insbesondere bei Patienten mit heparininduzierter Thrombozytopenie (HIT-Typ II), die eine suffiziente und gut steuerbare Antikoagulation benötigen, stellt Argatroban eine attraktive therapeutische Alternative zu den bisher verwendeten Antikoagulanzien, wie Lepirudin oder Heparinoiden, dar. Die Überwachung der Antikoagulation kann mit der aktivierten partiellen Thromboplastinzeit (aPTT) erfolgen. Argatroban ist in Deutschland seit Juni 2005 zur Antikoagulation bei Patienten mit HIT-Typ II zugelassen und somit für das Fachgebiet Anästhesiologie von zunehmender Bedeutung. Die vorliegende Übersicht beschreibt die Pharmakologie von Argatroban, bisherige klinische Erfahrungen sowie mögliche Indikationsgebiete in Anästhesie und Intensivmedizin. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate homocysteine and methylentetrahydrofolat reductase (MTHFR 677 C → T) mutations as risk factors in ocular arterial and venous occlusive disease. Materials and methods: Over a period of 3.5 years (1/1999–8/2002) 410 patients with ocular occlusive disease presented to our tertiary care center. Of these, 362 patients (195 male, 167 female) were screened for hyperhomocysteinemia and MTHFR 677 C → T mutation. Results: Among these 362 patients, venous occlusions (45%) were less frequent than arterial occlusions (55%). Age between these subgroups did not differ significantly (p = 0,109). The following subgroups were analyzed: central retinal vein occlusion (n: 93), retinal branch vein occlusion (n: 70), central retinal artery occlusion (n: 41), retinal arterial branch occlusion (n: 49), anterior ischemic optic neuropathy (n: 68), posterior ischemic optic neuropathy (PION, n: 11) and amaurosis fugax (n: 30). A moderate hyperhomocysteinemia (≥12 μ mol/l) and a higher percentage of heterocygote MTHFR 677 C → T mutations was observed in the subgroup with PION. However, this difference was not significant when compared to the other subgroups. The homocysteine level did not differ significantly between patients without a MTHFR 677 mutation and those with a heterocygote or homocygote MTHFR 677 C→T mutation (p = 0,188). Conclusion: An increase in homocysteine levels has been discussed as an independent risk factor for thrombotic events. Evaluation of the MTHFR 677 C → T mutation does not seem necessary as, in vivo, such a mutation is known to only increase the level of homocysteine in the absence of sufficient folic acid. In our population the average homocysteine level was only elevated in PION which points against the need to routinely evaluate this parameter. However, as hyperhomocysteinemia is easily amenable to therapy through substitution of vitamin B6, B12 and folic acid, we recommend its evaluation in the absence of cardiovascular thrombotic risk factors. [ABSTRACT FROM AUTHOR]

When patients with von Willebrand's disease were given a single injection of desmopressin (0.4 μg/kg body weight), there was a considerable increase in platelet reactivity (from 0.95±0.19 to 1.44±0.42; p=0.0033). On flow cytometry, increased glycoprotein Ib/IX expression in the platelets was found after the desmopressin injection; when phycoerythrin‐marked anti‐CD62 antibodies were used, the mean fluorescence rose from 428.9±56.6 to 440.7±51.4 (p=0.0056), and from 425.9±55.0 to 437.4±53.9 (p=0.0018) when phycoerythrin‐marked anti‐thrombospondin antibodies were used. Apart from the rise in the von Willebrand factor, this could explain the increased platelet reactivity. However, the surface expression of CD62, CD63 and thrombospondin on platelets did not change following the desmopressin injection. [ABSTRACT FROM AUTHOR]

In this paper we consider multiple criteria decision aid systems based on decision rules generated from examples. A common problem in such systems is the over-abundance of decision rules, as in many situations the rule generation algorithms produce very large sets of rules. This prolific representation of knowledge provides a great deal of detailed information about the described objects, but is appropriately difficult to interpret and use. One way of solving this problem is to aggregate the created rules into more general ones. e.g. by forming rules of enriched syntax. The paper presents a generalization of elementary rule conditions into linear combinations. This corresponds to partitioning the preference-ordered condition space of criteria with non-orthogonal hyperplanes. The objective of this paper is to introduce the generalized rules into the multiple criteria classification problems and to demonstrate that these problems can be successfully solved using the introduced rules. The usefulness of the introduced solution is finally demonstrated in computational experiments with real-life data sets. [ABSTRACT FROM AUTHOR]

Melagatran is a direct inhibitor of thrombin and-like its oral prodrug ximelagatran-a newly developed dipetide with high antithrombotic efficacy. They present a linear dose-response, a short plasma half-life and the therapeutic range may be advantageous compared with classic anticoagulants such as heparins or vitamin K antagonists. The results of clinical studies for prevention and treatment of thromboembolic complications are encouraging. The use of melagatran and ximelagatran will gain significance in the perioperative management, thus being of particular importance for anaesthesiology and critical care medicine in the near future. [ABSTRACT FROM AUTHOR]

Zusammenfassung Melagatran ist ein direkter Thrombininhibitor. Es handelt sich zusammen mit seiner peroral wirksamen Vorstufe Ximelagatran um neu entwickelte synthetische Dipeptide mit hohem antithrombotischen Potenzial. Sie weisen eine lineare Dosis-Wirkungs-Beziehung auf, haben eine kurze Halbwertzeit und zeichnen sich durch eine vorteilhafte therapeutische Breite gegenüber herkömmlichen Antikoagulanzien (Heparine, Vitamin-K-Antagonisten) aus. Die Ergebnisse von klinischen Studien zur Prophylaxe und Therapie von Thromboembolien sind viel versprechend. Die Anwendung von Melagatran und Ximelagatran wird im perioperativen Management an Bedeutung gewinnen und damit für den Bereich der Anästhesiologie und Intensivmedizin von besonderem Interesse sein. [ABSTRACT FROM AUTHOR]

The induction of rules is one of the key issues of the Rough Sets Theory (RST). Generally, this problem is equivalent to finding prime implicants of a Boolean function, which is an NP-hard combinatorial problem. In practice, the NP-hardness makes solving medium-sized and large real-life problems difficult. To counteract this we propose a new algorithm, in which representation of relations between objects are represented in the form of binary vectors. The relations considered are: indiscernibility and dominance. It is an important enhancement of the classic RST approach, in which only indiscernibility was taken into account. Evaluation of the proposed algorithm in experiments with numerous real-life data sets produced satisfactory results. [ABSTRACT FROM AUTHOR]

Focuses on a medical case report on the dissection of the proximal subclavian artery with consecutive thrombosis and embolic occlusion of the hand arteries after playing golf. Information on the patient; Treatment administered to the patient; Mechanisms capable of inducing an occlusion of the hand arteries.

Heparin-induced thrombocytopenia (HIT) is a rare but dangerous complication of heparin prophylaxis or treatment. The present laboratory tests to measure heparin-associated antibodies are not specific. The diagnosis of HIT mainly depends on the decrease in platelet count and on clinical symptoms. To evaluate clinical outcome, bleeding complications and platelet counts were evaluated in 45 patients with HIT type II (HIT II) treated prophylactically (subcutaneous injections) or therapeutically (intravenous infusion) with danaparoid. Group I included 24 patients with HIT II without thromboembolic complications who received danaparoid twice daily subcutaneously (10 IU/kg) for a mean of 16 days. Group II included 21 patients with thromboembolic complications. They were treated with intravenous danaparoid (2.6 IU/kg/h ± 1.1) for a mean of 17 days. During subcutaneous prophylaxis, mean anti-Xa levels of 0.2 U/mL and during intravenous treatment, mean anti-Xa levels of 0.4 U/mL were reached. No deaths, amputations, or serious bleeding complications occurred, and no new thromboses were observed in both patient groups. Treatment with danaparoid led to a fast normalization of the platelet counts. This normalization occurred earlier and the concentration of platelets was higher in patients treated with intravenous doses. Danaparoid with subsequent vitamin K-antagonist treatment effectively prevents thromboembolic complications in patients with HIT. [ABSTRACT FROM AUTHOR]