The hepatocyte growth factor mimetic, ANG-3777, in kidney transplant recipients with delayed graft function: Results from a randomized phase 3 trial.

In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.

The phenomenon of thunderstorm asthma in Bavaria, Southern Germany: a statistical approach.

Higher incidences of asthma during thunderstorms can pose a serious health risk. In this study, we estimate the thunderstorm asthma risk using statistical methods, with special focus on Bavaria, Southern Germany. In this approach, a dataset of asthma-related emergency cases for the study region is combined with meteorological variables and aeroallergen data to identify statistical relationships between the occurrence of asthma (predictand) and different environmental parameters (set of predictors). On the one hand, the results provide evidence for a weak but significant relationship between atmospheric stability indices and asthma emergencies in the region, but also show that currently thunderstorm asthma is not a major concern in Bavaria due to overall low incidences. As thunderstorm asthma can have severe consequences for allergic patients, the presented approach can be important for the development of emergency strategies in regions affected by thunderstorm asthma and under present and future climate change conditions.

NK-cell responses are biased towards CD16-mediated effector functions in chronic hepatitis B virus infection.

BACKGROUND & AIMS: Phenotypic and functional natural killer (NK)-cell alterations are well described in chronic hepatitis B virus (cHBV) infection. However, it is largely unknown whether these alterations result from general effects on the overall NK-cell population or the emergence of distinct NK-cell subsets. Human cytomegalovirus (HCMV) is common in cHBV and is associated with the emergence of memory-like NK cells. We aimed to assess the impact of these cells on cHBV infection. METHODS: To assess the impact of memory-like NK cells on phenotypic and functional alterations in cHBV infection, we performed in-depth analyses of circulating NK cells in 52 patients with cHBV, 45 with chronic hepatitis C virus infection and 50 healthy donors, with respect to their HCMV serostatus. RESULTS: In patients with cHBV/HCMV+, FcεRIγ- memory-like NK cells were present in higher frequencies and with higher prevalence than in healthy donors with HCMV+. This pronounced HCMV-associated memory-like NK-cell expansion could be identified as key determinant of the NK-cell response in cHBV infection. Furthermore, we observed that memory-like NK cells consist of epigenetically distinct subsets and exhibit key metabolic characteristics of long-living cells. Despite ongoing chronic infection, the phenotype of memory-like NK cells was conserved in patients with cHBV/HCMV+. Functional characteristics of memory-like NK cells also remained largely unaffected by cHBV infection with the exception of an increased degranulation capacity in response to CD16 stimulation that was, however, detectable in both memory-like and conventional NK cells. CONCLUSIONS: The emergence of HCMV-associated memory-like NK cells shapes the overall NK-cell response in cHBV infection and contributes to a general shift towards CD16-mediated effector functions. Therefore, HCMV coinfection needs to be considered in the design of immunotherapeutic approaches that target NK cells in cHBV. LAY SUMMARY: In chronic hepatitis B virus infection, natural killer (NK)-cell phenotype and function is altered. In this study, we demonstrate that these changes are linked to the emergence of a distinct NK-cell subset, namely memory-like NK cells. The emergence of these memory-like NK cells is associated with coinfection of human cytomegalovirus that affects the majority of patients with chronic hepatitis B.

New Insights into Weather and Stroke: Influences of Specific Air Masses and Temperature Changes on Stroke Incidence.

BACKGROUND/OBJECTIVES: Meteorological factors seem to influence stroke incidence, however, the complex association between weather and stroke remains unclear. Possible explanations from the literature do not categorize into subdivisions of ischemic strokes, only have small patient numbers, or refer to a selection of isolated weather elements without investigating weather changes and more. METHOD: In this exploratory trial, almost 18,000 stroke cases from a single stroke center in Southern Germany were analyzed from 2006 to 2015 and classified into the main subgroups of strokes and subdivisions of ischemic stroke etiologies applying the Trial of Org 10172 in Acute Stroke Treatment classification. For each stroke event, the air mass classification was determined from a subset of 7 air mass categories. Relative excess morbidities were derived for the 7 different air mass categories, taking into account the day of the event and up to 2 and 5 days preceding the stroke event. RESULTS: Statistically significant findings (α ≤0.1) reveal that dry tropical air masses were associated with a lower/higher risk for hemorrhagic (HEM)/macroangiopathic strokes (MAS), respectively. Dry polar air masses were associated with a higher risk for intracerebral bleedings and lower risk for ischemic stroke subtypes. Moist air masses were associated with a reduced incidence of MAS. A strong temperature increase 5 days prior to the event was associated with a lower risk of HEM strokes. Temperature increases were associated with lower risks for MAS and cardio-embolic strokes. Significant temperature decreases were associated with a higher risk of MAS. CONCLUSIONS: Temperature effects were dependent on both air masses and temperature changes within 5 days prior to the event and were associated with statistically relevant changes in stroke incidence. Decisive factors such as etiology, age, sex, and risk factors were also taken into account.

Benign uterine mass-discrimination from leiomyosarcoma by a preoperative risk score: a multicenter cohort study.

PURPOSE: Discrimination of uterine leiomyosarcoma (LMS) and leiomyoma (LM) prior to surgery by basic preoperative characteristics and development of a preoperative leiomyosarcoma score. METHODS: A predominantly prospective cohort of 826 patients with LM from a clinical institution and an outpatient center was included in the study. Further a predominantly retrospective cohort of 293 patients with LMS was included from the counseling database of the German Clinical Center of Excellence for Genital Sarcoma and Mixed Tumors (DKSM, University Medicine Greifswald, Germany). We analyzed and compared anamnestic, epidemiological and clinical findings between both cohorts. Tenfold cross-validated logistic regression and random forest was performed on the 80% training set. The preoperative LMS score (pLMS) was developed based on logistic regression and independently evaluated by analyzing the area under the receiver operating characteristic curve (AUC) with the 20% test set. RESULTS: In the LMS cohort, 63.1% had initially surgery for presumed LM and only 39.6% of endometrial biopsies revealed LMS. Key features for LMS discrimination were found to be bleeding symptoms: intermenstrual bleeding [RRc = 2.71, CI = (1.90-3.49), p < 0.001], hypermenorrhea [RRc = 0.28, CI = (0.15-0.50), p < 0.001], dysmenorrhea [RRc = 0.22, CI = (0.10-0.51), p < 0.001], postmenstrual bleeding [RRc = 2.08, CI = (1.30-2.75), p < 0.001], suspicious sonography [RRc = 1.21, CI = (1.19-1.22), p < 0.001] and the tumor diameter (each centimeter difference: ß = 0.24, SD = 0.04, p < 0.001). pLMS achieved a mean cross-validated AUC of 0.969 (SD = 0.019) in the training set and an AUC of 0.968 in the test set. CONCLUSIONS: The presented score is based on basic clinical characteristics and allows the prediction of LMS prior to a planned surgery of a uterine mass. In case pLMS is between - 3 and + 1, we suggest subsequent diagnostics, such as endometrial biopsy, color Doppler sonography, LDH measurement, MRI and transcervical biopsy.

Levels and drivers of urban black carbon and health risk assessment during pre- and COVID19 lockdown in Augsburg, Germany.

This study aimed to evaluate the levels and phenomenology of equivalent black carbon (eBC) at the city center of Augsburg, Germany (01/2018 to 12/2020). Furthermore, the potential health risk of eBC based on equivalent numbers of passively smoked cigarettes (PSC) was also evaluated, with special emphasis on the impact caused by the COVID19 lockdown restriction measures. As it could be expected, peak concentrations of eBC were commonly recorded in morning (06:00-8:00 LT) and night (19:00-22:00 LT) in all seasons, coinciding with traffic rush hours and atmospheric stagnation. The variability of eBC was highly influenced by diurnal variations in traffic and meteorology (air temperature (T), mixing-layer height (MLH), wind speed (WS)) across days and seasons. Furthermore, a marked "weekend effect" was evidenced, with an average eBC decrease of ∼35% due to lower traffic flow. During the COVID19 lockdown period, an average ∼60% reduction of the traffic flow resulted in ∼30% eBC decrease, as the health risks of eBC exposure was markedly reduced during this period. The implementation of a multilinear regression analysis allowed to explain for 53% of the variability in measured eBC, indicating that the several factors (e.g., traffic and meteorology) may contribute simultaneously to this proportion. Overall, this study will provide valuable input to the policy makers to mitigate eBC pollutant and its adverse effect on environment and human health.

Evaluation of a structured treatment discontinuation in patients with inoperable alveolar echinococcosis on long-term benzimidazole therapy: A retrospective cohort study.

OBJECTIVES: Alveolar echinococcosis (AE) is an orphan zoonosis of increasing concern in endemic areas, including Europe. It frequently presents in an advanced, inoperable stage, that requires life-long parasitostatic benzimidazole therapy. In some patients, long-term therapy leads to negative anti-Em18 antibody ELISA and PET. It is disputed, whether these patients are truly cured and treatment can be safely discontinued. Our aim was to retrospectively assess long-term outcome of 34 patients with inoperable AE who participated in a previous study to determine feasibility of benzimidazole treatment cessation. METHODS: Retrospective analysis of medical charts was undertaken in all 34 AE patients who participated in our previous study. Of particular interest were AE recurrence or other reasons for re-treatment in patients who stopped benzimidazole therapy and whether baseline clinical and laboratory parameters help identify of patients that might qualifiy for treatment cessation. Additionally, volumetric measurement of AE lesions on contrast-enhanced cross-sectional imaging was performed at baseline and last follow-up in order to quantify treatment response. RESULTS: 12 of 34 patients stopped benzimidazole therapy for a median of 131 months. 11 of these patients showed stable or regressive AE lesions as determined by volumetric measurement. One patient developed progressive lesions with persistently negative anti-Em18 antibody ELISA but slight FDG-uptake in repeated PET imaging. At baseline, patients who met criteria for treatment cessation demonstrated higher lymphocyte count and lower total IgE. CONCLUSION: Treatment cessation is feasible in inoperable AE patients, who demonstrate negative anti-Em18 antibody ELISA and PET on follow-up. Close monitoring including sectional imaging is strongly advised.

Epidemic cystic and alveolar echinococcosis in Kyrgyzstan: an analysis of national surveillance data.

BACKGROUND: Human cystic and alveolar echinococcosis are among the priority neglected zoonotic diseases for which WHO advocates control. The incidence of both cystic echinococcosis and alveolar echinococcosis has increased substantially in the past 30 years in Kyrgyzstan. Given the scarcity of adequate data on the local geographical variation of these focal diseases, we aimed to investigate within-country incidence and geographical variation of cystic echinococcosis and alveolar echinococcosis at a high spatial resolution in Kyrgyzstan. METHODS: We mapped all confirmed surgical cases of cystic echinococcosis and alveolar echinococcosis reported through the national echinococcosis surveillance system in Kyrgyzstan between Jan 1, 2014, and Dec 31, 2016, from nine regional databases. We then estimated crude surgical incidence, standardised incidence, and standardised incidence ratios (SIRs) of primary cases (ie, excluding relapses) based on age and sex at country, region, district, and local community levels. Finally, we tested the SIRs for global and local spatial autocorrelation to identify disease hotspots at the local community level. All incidence estimates were calculated per 100 000 population and averaged across the 3-year study period to obtain annual estimates. FINDINGS: The surveillance system reported 2359 primary surgical cases of cystic echinococcosis and 546 primary surgical cases of alveolar echinococcosis. Country-level crude surgical incidence was 13·1 per 100 000 population per year for cystic echinococcosis and 3·02 per 100 000 population per year for alveolar echinococcosis. At the local community level, we found annual crude surgical incidences up to 176 per 100 000 population in Sary-Kamysh (Jalal-Abad region) for cystic echinococcosis and 246 per 100 000 population in Uch-Dobo (Alay district, Osh region) for alveolar echinococcosis. Significant hotspots of cystic echinococcosis were found in four regions: Osh (five local communities in Uzgen district and four in Alay district), Naryn (three local communities in Jumgal district and one in Naryn district), Talas (three local communities in Talas district), and Chuy (one local community in Jayyl district). Significant alveolar echinococcosis hotspots were detected in the Osh region (11 communities in Alay district, including the local community of Sary Mogol, and one in Chong-Alay district) and in the Naryn region (five communities in Jumgal district and three in At-Bashy district), in the southwest and centre of the country. INTERPRETATION: Our analyses reveal remarkable within-country variation in the surgical incidence of cystic echinococcosis and alveolar echinococcosis in Kyrgyzstan. These high-resolution maps identify precise locations where interventions and epidemiological research should be targeted to reduce the burden of human cystic echinococcosis and alveolar echinococcosis. FUNDING: Swiss National Science Foundation.

Sensitivity of proxies on non-linear interactions in the climate system.

Recent climate change is affecting the earth system to an unprecedented extent and intensity and has the potential to cause severe ecological and socioeconomic consequences. To understand natural and anthropogenic induced processes, feedbacks, trends, and dynamics in the climate system, it is also essential to consider longer timescales. In this context, annually resolved tree-ring data are often used to reconstruct past temperature or precipitation variability as well as atmospheric or oceanic indices such as the North Atlantic Oscillation (NAO) or the Atlantic Multidecadal Oscillation (AMO). The aim of this study is to assess weather-type sensitivity across the Northern Atlantic region based on two tree-ring width networks. Our results indicate that nonstationarities in superordinate space and time scales of the climate system (here synoptic- to global scale, NAO, AMO) can affect the climate sensitivity of tree-rings in subordinate levels of the system (here meso- to synoptic scale, weather-types). This scale bias effect has the capability to impact even large multiproxy networks and the ability of these networks to provide information about past climate conditions. To avoid scale biases in climate reconstructions, interdependencies between the different scales in the climate system must be considered, especially internal ocean/atmosphere dynamics.

Emergency diagnosis with spiral CT angiography in case of suspected ventral perforation following lumbar disc surgery.

BACKGROUND: Ventral perforation and vascular lesions are rare but life-threatening complications in lumbar disc surgery. In some cases, however, it remains unclear from the clinical situation whether a laparotomy is necessary to save the patient. The goal of this study is to demonstrate the value of spiral CT (computed tomography) angiography for emergency vascular diagnosis in two cases. METHODS: Spiral CT angiography with an intravenous bolus contrast medium injection and reconstruction with images in sagittal, coronal, and oblique planes was performed. RESULTS: Spiral CT angiography confirms or excludes a vascular lesion, as demonstrated in two case reports. CONCLUSION: In unclear cases when ventral perforation in lumbar disc surgery is suspected, the need for emergency laparotomy can be confirmed quickly by noninvasive spiral CT angiography.

Products of two atoms in Krull monoids and arithmetical characterizations of class groups.

Let [Formula: see text] be a Krull monoid with finite class group [Formula: see text] such that every class contains a prime divisor and let [Formula: see text] be the Davenport constant of [Formula: see text]. Then a product of two atoms of [Formula: see text] can be written as a product of at most [Formula: see text] atoms. We study this extremal case and consider the set [Formula: see text] defined as the set of all [Formula: see text] with the following property: there are two atoms [Formula: see text] such that [Formula: see text] can be written as a product of [Formula: see text] atoms as well as a product of [Formula: see text] atoms. If [Formula: see text] is cyclic, then [Formula: see text]. If [Formula: see text] has rank two, then we show that (apart from some exceptional cases) [Formula: see text]. This result is based on the recent characterization of all minimal zero-sum sequences of maximal length over groups of rank two. As a consequence, we are able to show that the arithmetical factorization properties encoded in the sets of lengths of a rank [Formula: see text] prime power order group uniquely characterizes the group.

Regional differences of glycaemic control in patients with type 2 diabetes mellitus in Switzerland: a national cross-sectional survey.

AIMS: We investigated contemporary diabetes care, quality of glycaemic control, and progression of obesity in patients with diabetes mellitus in different cultural regions within Switzerland. METHODS: Overall, 1121 patients treated for type 2 diabetes mellitus by 134 general practitioners were enrolled in this representative, national, cross-sectional survey and were followed retrospectively from the start of diabetes treatment. Patients were classified into four cultural regions; the German, French, Italian and Romansh speaking parts of Switzerland. RESULTS: During 5.5 ± 5.1 years of diabetes treatment (retrospective survey), mean HbA1c decreased from 8.28 ± 2.01% to 7.03 ± 1.24%, fasting glucose decreased from 9.97 ± 3.86 to 7.52 ± 2.23 mmol/l, and BMI decreased from 30.2 ± 5.5 to 29.8 ± 5.6 kg/m² (p <0.001 for all parameters). Insulin therapy was associated with a larger improvement of mean HbA1c (-1.66 ± 2.33% vs. -1.15 ± 1.91%, p = 0.001) and an increase in BMI (+0.36 ± 2.92 vs. -0.63 ± 2.60 kg/m2, p <0.001). At the time when the cross-sectional survey was conducted, the mean HbA1c and fasting glucose were higher in the Italian part compared to other regions (7.72 ± 1.60% and 9.03 ± 2.49 mmol/l, respectively, p <0.001), and lower in the German part (6.89 ± 1.02% and 7.25 ± 2.02 mmol/l, respectively, p <0.001). In comparison to other regions, biguanides were more often used in the French part (86.1% versus 75.7%), insulin secretagogues in the Italian part (69.9% versus 37.8%), thiazolidinediones in the Romansh part (34.1% versus 17.8%), and insulin was more often used in the German part of Switzerland (27.0% versus 17.1%) (p <0.01 for all parameters). CONCLUSIONS: Efforts to identify regional-cultural differences and attempts to overcome associated potential barriers should be emphasised in any health care system when aiming for better diabetic patient care.

Classifications of atmospheric circulation patterns: recent advances and applications.

We review recent advances in classifications of circulation patterns as a specific research area within synoptic climatology. The review starts with a general description of goals of classification and the historical development in the field. We put circulation classifications into a broader context within climatology and systematize the varied methodologies and approaches. We characterize three basic groups of classifications: subjective (also called manual), mixed (hybrid), and objective (computer-assisted, automated). The roles of cluster analysis and principal component analysis in the classification process are clarified. Several recent methodological developments in circulation classifications are identified and briefly described: the introduction of nonlinear methods, objectivization of subjective catalogs, efforts to optimize classifications, the need for intercomparisons of classifications, and the progress toward an optimum, if possible unified, classification method. Among the recent tendencies in the applications of circulation classifications, we mention a more extensive use in climate studies, both of past, present, and future climates, innovative applications in the ensemble forecasting, increasing variety of synoptic-climatological investigations, and steps above from the troposphere. After introducing the international activity within the field of circulation classifications, the COST733 Action, we briefly describe outputs of the inventory of classifications in Europe, which was carried out within the Action. Approaches to the evaluation of classifications and their mutual comparisons are also reviewed. A considerable part of the review is devoted to three examples of applications of circulation classifications: in historical climatology, in analyses of recent climate variations, and in analyses of outputs from global climate models.

Re-endothelialization of punctured ePTFE graft: an in vitro study under pulsed perfusion conditions.

BACKGROUND: When used as arteriovenous (AV) shunts for haemodialysis, small diameter expanded polytetrafluoroethylene (ePTFE) grafts have a high failure rate in vivo. Attempts to improve graft patency are various, and focus on either improvement of implantation techniques or graft tissue engineering. The tissue engineering approach attempts to reproduce in grafts the properties of pristine vasculature. As shown in previous experiments, it is possible to grow on ePTFE grafts under shear stress in vitro an autologous endothelial cell layer, which will withstand physiological stress under in vivo conditions of blood flow. The aim of this study was to investigate in an in vitro model the regenerative potency of a tissue-engineered prosthetic vascular graft after repeated cannulation with a haemodialysis cannula. METHODS: Pig endothelial cells were harvested from an external jugular vein. Following processing of the endothelial cells, seven ePTFE grafts were coated with an inner cell layer and were kept under pulsed perfusion. Each graft was then cannulated three times with a standard shunt needle. The endothelium was then left to regenerate for a maximum of 48 h. The grafts were stained with haematoxylin/eosin before histological study. RESULTS: All grafts were endothelialized over the puncture sites within 48 h. Histological analysis revealed a confluent endothelial cell lining at each puncture site. Cell morphology and cell pattern over puncture sites were not different from randomly picked locations over the graft lumen. CONCLUSION: Our results underline the potential of endothelial tissue engineering in vascular shunt surgery. Vascular bio-hybrids that have the properties of pristine vascular endothelium may be a key step forward in maintaining angio-access in patients who require haemodialysis.

Surgical treatment of fractures of the distal clavicle with polydioxanone suture tension band wiring: an alternative osteosynthesis.

Fracture of the distal clavicle type II (Neer) is an indication for surgical intervention. We report our experience in 12 patients with acute clavicular fractures and operative treatment with polydioxanone suture (PDS) tension band wiring. The patients were assessed 6 and 12 weeks postoperatively by radiological and clinical evaluation and with the Constant Murley score. All 12 patients had an excellent functional result 12 weeks postoperatively. The Constant Murley score was excellent in all patients. The PDS band can be considered as an alternative osteosynthesis. In the context of the current literature, the advantages and disadvantages of this new procedure are discussed.

Intraperitoneal administration of the angiogenesis inhibitor thalidomide does not impair anastomotic healing following large bowel resection in a rabbit model.

The effects of thalidomide after intraperitoneal instillation on the healing of colonic anastomoses are not known. A series of 40 New Zealand White rabbits underwent an end-to-end colonic anastomosis. The animals were randomized into four groups. Groups 1 (n = 10) and 2 (n = 10) were treated with dissolved thalidomide 200 mg/kg intraperitoneally, whereas groups 3 (n = 10) and 4 (n = 10) were treated only with the dissolver. Animals were sacrificed at day 3 (groups 1, 3) and day 7 (groups 2, 4). Anastomotic healing was tested by measuring the bursting pressure in vitro. Immunohistochemical staining of the anastomotic site was performed with polyclonal antibodies against CD31 and Mib-1, to determine a possible antiangiogenic or antiproliferative effect. Statistical analysis was performed using Spearman's log rank correlation and paired t-test. On postoperative day 3 (p > 0.19) and postoperative day 7 (p > 0.73), there was no difference in bursting pressure in the treatment and the control groups. Angiogenesis scores were reduced at day 3 in the thalidomide group (p < 0.05), but did not differ between the groups at day 7. White blood cell counts were decreased in the treatment groups at day 3 (p < 0.01) and day 7, compared to control groups (p < 0.01). There was no difference in the expression of Mib-1 in either group at day 3 or day 7. The intraperitoneal administration of thalidomide does not interfere with the healing of colonic anastomosis. Although the angiogenesis score is diminished at day 3, this did not lead to a reduced bursting pressure at day 3 or day 7.

Thalidomide given intraperitoneally reduces the number of postoperative adhesions after large bowel resection in rabbits.

OBJECTIVE: To investigate the effect of thalidomide given intraperitoneally on the formation of adhesions after colonic resection in rabbits. DESIGN: Controlled, randomised prospective study. SETTING: University hospital, Germany. ANIMALS: 40 female New Zealand White rabbits. INTERVENTIONS: After an end-to-end colonic anastomosis the animals were given thalidomide 200 mg/kg in 1% carboxymethylcellulose intraperitoneally or carboxymethylcellulose alone (n = 20 in each group). OUTCOME MEASURES: The adhesion score according to Tyrell on day 3 (n = 20) and day 7 (n = 20) postoperatively, weight, behaviour, and white cell count (WCC). RESULTS: There was no difference in behaviour or weight. On the third postoperative day WCCs and on the seventh postoperative day WCCs and adhesion scores, were lower in the thalidomide group (p < 0.01). CONCLUSION: The number of postoperative adhesions was reduced in the group given thalidomide intraperitoneally. Our results suggest that thalidomide may be helpful in the prevention of postoperative adhesions.

Serum vascular endothelial growth factor levels correlate better with tumour stage in small cell lung cancer than albumin, neuron-specific enolase or lactate dehydrogenase.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an important cytokine in the process of angiogenesis. Elevated serum levels of the cytokine may determine cancer patients who will benefit from adjuvant anti-angiogenic therapy in the future. To correlate serum levels of VEGF with tumour stage and established prognostic markers in patients with small cell lung cancer (SCLC), a prospective study was performed on 70 patients. METHODOLOGY: From August 1999 to May 2000, 70 consecutive patients (51 male, 19 female) with histologically proven SCLC were enrolled into the study. Staging of the disease included clinical investigation, bronchoscopy, chest X-ray, thoracic computed tomography and ultrasound. The patients were grouped into five stages according to the Marburg classification (very limited disease (VLD), limited disease (LD), extensive disease I (EDI), extensive disease II (EDII) and extensive disease III (EDIII)). Prior to treatment, a 10 mL serum sample from each patient was examined by ELISA to quantify levels of VEGF and neuron-specific enolase (NSE). Lactate dehydrogenase (LDH) and albumin levels were determined by photomorphometric analysis. Statistical analysis was performed using the Waller-Duncan k ratio t-test and Pearson's correlation test. RESULTS: Serum VEGF levels correlated well with tumour stage (P < 0.0001). Albumin levels were not correlated with tumour stage, but levels of NSE and LDH increased with stage progression. When patients were divided into two groups (VLD and LD vs EDI-III), VEGF levels were significantly lower in the initial stages of the disease compared with extensive disease (P < 0.0001). Serum levels of VEGF correlated better with tumour stage than did concentrations of NSE, LDH or albumin. CONCLUSION: Serum VEGF levels may serve as an additional prognostic marker in the course of patients with SCLC. Further studies are needed to determine whether these patients may benefit from additional anti-angiogenic therapy in the future.

In vivo measurement of oxygen-derived free radicals during reperfusion injury.

By use of an optimized cytochrome c-based biosensor, superoxide radical production was measured continuously in vivo. The aim of this study was the online detection of superoxide concentration during reperfusion after a variable time of ischemia. Measurements were performed by placing the detecting sensor into gastrocnemius muscle tissue. Ischemia was induced by clamping the vena and arteria femoralis. Current response of the sensor was recorded continuously as an equivalent for superoxide concentration. Ischemia times varied from 5 to 120 minutes. The minimum ischemia time to record superoxide production was 10 minutes. By inducing longer periods of ischemia, an increase in superoxide concentration reached its highest levels at 2 hours. Furthermore, the total time of superoxide production after reperfusion depended on the total time of ischemia.