Aerobic training in adults after atrial switch procedure for transposition of the great arteries improves exercise capacity without impairing systemic right ventricular function.

BACKGROUND: Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). METHODS: 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. RESULTS: At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. CONCLUSIONS: Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov #NCT00837603).

Combined micro-PET/micro-CT imaging of lung tumours in SPC-raf and SPC-myc transgenic mice.

INTRODUCTION: SPC-raf and SPC-myc transgenic mice develop disseminated and circumscribed lung adenocarcinoma respectively, allowing for assessment of carcinogenesis and treatment strategies. The purpose of this study was to investigate the technical feasibility, the correlation of initial findings to histology and the administered radiation dose of combined micro-PET/micro-CT in these animal models. MATERIAL AND METHODS: 14 C57BL/6 mice (4 nontransgenic, 4 SPC-raf transgenic, 6 SPC-myc transgenic) were examined using micro-CT and (18)F-Fluoro-deoxyglucose micro-PET in-vivo. Micro-PET data was corrected for random events and scatter prior to reconstruction with a 3D-FORE/2D-OSEM iterative algorithm. Rigid micro-PET/micro-CT registration was performed. Tumour-to-non-tumour ratios were calculated for different lung regions and focal lesions. Diffuse tumour growth was quantified using a semiautomated micro-CT segmentation routine reported earlier. Regional histologic tumour load was assessed using a 4-point rating scale. Gamma radiation dose was determined using thermoluminescence dosimeters. RESULTS: Micro-CT allowed visualisation of diffuse and circumscribed tumours in SPC-raf and SPC-myc transgenic animals along with morphology, while micro-PET provided information on metabolism, but lacked morphologic detail. Mean tumour-to-non-tumour ratio was 2.47 for circumscribed lesions. No significant correlation could be shown between histological tumour load and tumour-to-nontumour ratio for diffuse tumours in SPC-raf transgenic animals. Calculation of the expected dose based on gamma dosimetry yielded approximately 140 mGy/micro-PET examination additional to approximately 200 mGy due to micro-CT. CONCLUSIONS: Combined micro-PET/micro-CT imaging allows for in-vivo assessment of lung tumours in SPC-raf and SPC-myc transgenic mice. The technique has potential for the evaluation of carcinogenesis and treatment strategies in circumscribed lung tumours.

In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial.

PURPOSE: Particulate contamination due to infusion therapy carries a potential health risk for intensive care patients. METHODS: This single-centre, prospective, randomized controlled trial assessed the effects of filtration of intravenous fluids on the reduction of complications in critically ill children admitted to a pediatric intensive care unit (PICU). A total of 807 subjects were randomly assigned to either a control (n = 406) or filter group (n = 401), with the latter receiving in-line filtration. The primary endpoint was reduction in the rate of overall complications, which included the occurrence of systemic inflammatory response syndrome (SIRS), sepsis, organ failure (circulation, lung, liver, kidney) and thrombosis. Secondary objectives were a reduction in the length of stay on the PICU and overall hospital stay. Duration of mechanical ventilation and mortality were also analyzed. FINDINGS: Analysis demonstrated a significant reduction in the overall complication rate (n = 166 [40.9 %] vs. n = 124 [30.9 %]; P = 0.003) for the filter group. In particular, the incidence of SIRS was significantly lower (n = 123 [30.3 %] vs. n = 90 [22.4 %]; P = 0.01). Moreover the length of stay on PICU (3.89 [95 % confidence interval 2.97-4.82] vs. 2.98 [2.33-3.64]; P = 0.025) and duration of mechanical ventilation (14.0 [5.6-22.4] vs. 11.0 [7.1-14.9] h; P = 0.028) were significantly reduced. CONCLUSION: In-line filtration is able to avert severe complications in critically ill patients. The overall complication rate during the PICU stay among the filter group was significantly reduced. In-line filtration was effective in reducing the occurrence of SIRS. We therefore conclude that in-line filtration improves the safety of intensive care therapy and represents a preventive strategy that results in a significant reduction of the length of stay in the PICU and duration of mechanical ventilation (ClinicalTrials.gov number: NCT00209768).

Lung tumour growth kinetics in SPC-c-Raf-1-BB transgenic mice assessed by longitudinal in-vivo micro-CT quantification.

BACKGROUND: SPC-c-Raf-1-BxB transgenic mice develop genetically induced disseminated lung adenocarcinoma allowing examination of carcinogenesis and evaluation of novel treatment strategies. We report on assessment of lung tumour growth kinetics using a semiautomated region growing segmentation algorithm. METHODS: 156 non contrast-enhanced respiratory gated micro-CT of the lungs were obtained in 12 SPC-raf transgenic (n = 9) and normal (n = 3) mice at different time points. Region-growing segmentation of the aerated lung areas was obtained as an inverse surrogate for tumour burden. Time course of segmentation volumes was assessed to demonstrate the potential of the method for follow-up studies. RESULTS: Micro-CT allowed assessment of tumour growth kinetics and semiautomated region growing enabled quantitative analysis. Significant changes of the segmented lung volumes over time could be shown (p = 0.009). Significant group differences could be detected between transgenic and normal animals for time points 8 to 13 months (p = 0.043), when marked tumour progression occurred. CONCLUSION: The presented region-growing segmentation algorithm allows in-vivo quantification of multifocal lung adenocarcinoma in SPC-raf transgenic mice. This enables the assessment of tumour load and progress for the study of carcinogenesis and the evaluation of novel treatment strategies.

Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement.

OBJECTIVES: Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. METHODS: DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. RESULTS: DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. CONCLUSIONS: In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. KEY POINTS: • DWI MR imaging may detect early CNS involvement in haemolytic uraemic syndrome • Different pathogenetical mechanisms may contribute to the CNS disease in HUS • Early MRI findings do not seem to allow prediction of clinical outcome.

Procalcitonin and valuable clinical symptoms in the early detection of neonatal late-onset bacterial infection.

AIM: To evaluate which clinical symptoms indicate proven neonatal bacterial infection (NBI) and whether measuring procalcitonin aside from C-reactive protein and interleukin 6 improves sensitivity and specificity in diagnosis. METHODS: In a prospective observational study, clinical symptoms and procalcitonin, C-reactive protein and interleukin 6 were simultaneously determined from the 4th day of life in 170 preterm and term neonates at the first time of suspicion of NBI. Proven NBI was defined as a positive culture of otherwise sterile body fluids or radiologically verified pneumonia in combination with elevated inflammatory markers. RESULTS: Fifty-eight (34%) patients were diagnosed with proven late-onset NBI. In case of proven NBI, odds ratio and 95% confidence intervals were 2.64 (1.06-6.54) for arterial hypotension, 5.16 (2.55-10.43) for feeding intolerance and 9.18 (4.10-20.59) for prolonged capillary refill. Sensitivity of combined determination of C-reactive protein (>10 mg/L) and interleukin 6 (>100 pg/mL) was 91.4%, specificity 80.4%, positive predictive value 70.7% and negative predictive value 94.7%. The additional determination of procalcitonin (>0.7 ng/mL) resulted in 98.3%, 65.2%, 58.8% and 98.6%, respectively. CONCLUSION: Arterial hypotension, feeding intolerance and especially prolonged capillary refill indicate proven neonatal late-onset bacterial infection, even at the time of first suspicion. Additional measurement of procalcitonin does indeed improve sensitivity to nearly 100%, but is linked to a decline in specificity. Nevertheless, in the high-risk neonatal population, additional procalcitonin measurement can be recommended because all infants with NBI have to be identified.

International pneumococcal clones match or exceed the fitness of other strains despite the accumulation of antibiotic resistance.

A few international pneumococcal clones dominate the population of antibiotic-resistant pneumococci. Despite the scientific paradigm that a loss in fitness is the price for acquisition of resistance, these clones spread successfully. One hundred fifty-four isolates from adult patients with community-acquired pneumonia (CAP) were analyzed. Thirty percent showed a close relationship to international clones and had fitness equal to or exceeding that of other strains (P = 0.015); these factors may result in the endurance of these strains despite a reduction of antibiotic usage.

Effect of tacrolimus on energy metabolism in human umbilical endothelial cells.

BACKGROUND: Tacrolimus has a wide spectrum of adverse effects, including neurotoxic and vascular events. Vascular dysfunction due to interference of tacrolimus with mitochondrial function in endothelial cells may contribute to these adverse reactions. MATERIAL/METHODS: We evaluated the impact of clinically relevant tacrolimus concentrations after 48 hours on energy metabolism in cultured human umbilical vein endothelial cells (HUVEC): Global fatty acid oxidation (FAO), activities of respiratory chain complexes I-V (RC), citratesynthase (CS), glycolytic enzymes and energy rich phosphates were measured. RESULTS: RC-complexes II+III were significantly compromised at 100 nmol/L and CS at 10, 25 and 50 nmol/L, while global FAO was not significantly impaired. Cellular lactate-dehydrogenase (LDH)-, hexokinase- and phosphofructokinase-activities were not altered; AMP levels increased after 48 hours at 200 nmol/L while energy charges remained stable. No cellular toxicity, assessed by light microscopy and LDH leakage was observed even at highest tacrolimus concentrations. CONCLUSIONS: Tacrolimus partially impaired mitochondrial function in HUVEC at the level of RC-complexes II+III and CS. Part of tacrolimus toxicity and vascular dysfunction may arise from these metabolic alterations. To some extent, energy balance could be maintained by FAO and cytosolic energy production; energy consumption might be economized. Although only demonstrated for endothelial cells, it is conceivable that such effects will alter energy metabolism in different tissues with high oxidative demands.

Surgical therapy of exocrine pancreatic carcinoma--results at an academic teaching hospital and evaluation of prognostic factors.

BACKGROUND/AIMS: Pancreatic cancer is among the top five cancer related death causes in countries like the US and Germany. Many studies have shown favorable results of pancreatic carcinoma resection at high-volume hospitals. It was the aim of this study to compare the results of pancreatic resection of exocrine pancreatic carcinoma at an academic teaching hospital with those of international centers for pancreatic surgery and to identify prognostic factors for survival. METHODOLOGY: Ninety-eight patients with exocrine pancreatic carcinoma were treated at our hospital, 42 of those underwent a resection. The data was collected from the patient files and statistically analyzed. A complete follow-up was reached. RESULTS: The resection rate was 42.9%, of which 83.3% were R0-resections. Mortality was 2.4%, morbidity 31%. Median survival after R0-resection was 14 months and 57.1% of the patients received adjuvant chemotherapy with gemcitabine. The performed surgical procedure and adjuvant chemotherapy were identified as independent determinants of long-term survival. CONCLUSION: This study shows that morbidity, mortality and survival rates reported in studies from international centers for pancreatic surgery can be reached at an academic teaching hospital as well. Adjuvant chemotherapy prolongs survival.

The impact of deep and moderate body temperatures on end-organ function during hypothermic circulatory arrest.

OBJECTIVE: Hypothermic circulatory arrest (HCA) at different temperatures is a protection technique for operations involving the aortic arch. In combination with selective cerebral perfusion, higher arrest temperatures for the remaining body may be permitted. However, the ischaemic/reperfusion injury (I/R) in various organ systems, other than the brain, related to the specific HCA temperature has so far not been evaluated. METHODS: Fourteen pigs were randomly assigned to 60 min of sole HCA at 20 or 30 °C temperature, weaned from cardiopulmonary bypass (CPB) and followed 4h after HCA. Besides complex haemodynamic monitoring, laser-Doppler spectrophotometry for measuring capillary blood flow, tissue oxygen saturation and post-capillary venous filling pressures of the bowel was installed. At the end of experiment, organs were perfusion fixated and harvested. RESULTS: During the entire experiment, haemodynamics revealed no differences between the groups. CPB bypass times were 177 ± 12 min in the 20 °C and 158 ± 11 min in the 30 °C group, respectively (p = 0.02). During reperfusion, lactate levels were initially significantly higher in the 30 °C animals (p = 0.001) but subsequently declined. Microcirculatory blood flow and velocity in the bowel were significantly reduced during cooling and reperfusion (p < 0.05), but were independent of final HCA temperature. Histological evaluation revealed significantly more oedema formation in the bowel wall of the 30 °C animals (p = 0.05). CONCLUSIONS: Higher levels of circulating lactate levels during reperfusion indicate less effective organ protection at 30 than at 20 °C after 60 min of HCA. This is further substantiated by histological evidence for a more pronounced oedema inflammatory response within the bowel wall.

Conventional aortic valve replacement in patients with concomitant coronary artery disease and previous coronary artery bypass grafting in the era of interventional approaches.

OBJECTIVE: In patients with symptomatic aortic valve stenosis and a high estimated operative risk due to previous coronary artery bypass grafting (CABG) procedures, interventional aortic valve implantation techniques may ultimately prove superior. However, recent studies have revealed increased mortality and impaired survival in patients with concomitant coronary artery disease (CAD). METHODS: Between January 1996 and May 2010, 60 patients (73 ± 6 years, 15 female (25%)) underwent conventional operation 9 ± 6 years after CABG for symptomatic aortic valve stenosis (European System for Cardiac Operative Risk Evaluation, EuroSCORE) standard 11 ± 3%, logistic 27 ± 17%, Society of Thoracic Surgeons (STS) Score 19 ± 8%). Coronary angiography revealed open grafts and no need for further revascularization in all patients. High-risk patients were identified (log. EuroSCORE≥ 20%, n = 34) and divided by age (< 75 years, n=15; ≥ 75 years, n=19) for sub-group analysis. Follow-up for all 60 patients was performed according to the current guidelines: quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: Thirty-day-mortality was 5% (n=3). During follow-up (100% complete), 18 patients died. Thus, 1-, 3- and 5-year survival was 91%, 77%, and 69%, respectively. No differences in survival could be detected between the two high-risk groups. Quality of life revealed excellent results for the entire cohort, as well as both high-risk groups. CONCLUSIONS: Conventional surgery in patients with symptomatic aortic valve stenosis after previous CABG can be performed with excellent results despite a high calculated risk, independent of age. Although conventional surgery is technically more demanding and associated with substantial surgical trauma, it is justified by the excellent survival and high quality of life in this high-risk patient cohort.

Cyclosporine A: impact on mitochondrial function in endothelial cells.

INTRODUCTION: Although cyclosporine A (CSA) is considered to be an efficient immunosuppressive compound in transplantation, vascular side effects like arterial hypertension, neurologic complications and other adverse reactions occur. Interference of CSA with mitochondrial function may be responsible for these side effects. METHODS: We evaluated the effect of CSA on mitochondrial and glycolytic function by measuring fatty acid oxidation (FAO), activities of respiratory chain complexes (RC) and citratesynthase (CS), lactate/pyruvate-ratios, energy-rich phosphates as well as activities of some glycolytic enzymes in human umbilical vein endothelial cells. RESULTS: After 48 h of CSA incubation, global FAO, RC-complexes 1 + 3; 4 and 5 as well as CS were compromised while energy charges were not reduced. Lactate/pyruvate-ratios increased; cellular lactate dehydrogenase (LDH)-, hexokinase- and phosphofructokinase-activities were not impaired by CSA. Moderate cellular toxicity, assessed by LDH leakage, appeared only at the highest CSA concentration. CONCLUSION: Part of CSA toxicity may arise from alterations in mitochondrial function as judged by impaired FAO and respiratory chain enzymes. To some extent, energy balance seems to be maintained by cytosolic energy production. Although only demonstrated for endothelial cells, it is conceivable that such effects will alter energy metabolism of different organs with high oxidative energy demands.

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-ß1.

BACKGROUND: Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. METHODS: Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. RESULTS: We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. CONCLUSIONS: Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.

Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach.

AIMS: Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. Our aim was to establish novel diagnostic markers distinguishing MCs from hormone receptor-negative high-grade IDCs. METHODS AND RESULTS: Sixty-one MCs and 133 hormone receptor-negative IDCs were analysed in a comparative immunohistochemical study. Applied markers included a comprehensive panel of cytokeratins (CKs), vimentin, smooth muscle actin (SMA), p63, p53, cell adhesion molecules [N-CAM (CD56), syndecan-1 (CD138), E-cadherin and P-cadherin] and development associated transcription factors (AP-2 alpha, AP-2 gamma). A significantly higher proportion of IDCs displayed increased expression of CK7, AP-2 alpha and HER2 in contrast to MCs (CK7: 91% of IDCs versus 77% of MCs; AP-2 alpha: 77% versus 57%; and HER2: 26% versus 7%, each P < 0.01). Vice versa, MCs were slightly more frequently positive for SMA and vimentin (P > 0.05). CONCLUSIONS: Hormone receptor-negative high-grade IDCs are significantly associated with luminal differentiation, Her2 and AP-2 alpha overexpression, whereas MCs tend to display myoepithelial features. Markers analysed in this study are of diagnostic value regarding the differential diagnosis of MCs.

Pain reduction in children during port-à-cath catheter puncture using local anaesthesia with EMLA™.

INTRODUCTION: Alleviating pain is of high importance for children undergoing chemotherapy. Eutectic mixture of lidocain-prilocain cream (EMLA) is assumed to require 60 min application time. MATERIALS AND METHODS: We prospectively compared the pain during port-à-cath punctures after 40 min compared to 60 min of application time. A prospective, unblinded, cross-over study was performed. The children received two punctures during their chemotherapy protocol. Patients in group 1 had the first puncture after 40 min EMLA application time. Their second puncture (approximately a week later) was done after 60 min. Patients in group 2 started after 40 min. Pain was scored using the visual analogue scale (VAS) and the Bieri scale. Patients, parents and a nurse scaled the pain after the intervention. Eighty-seven children between 2 and 18 years with different malignant diseases were included. RESULTS AND DISCUSSION: On the VAS pain scale, the mean pain was 2.3 (minimum 0, maximum 9.2) after 40 min and 1.9 (minimum 0, maximum 9.4) after 60 min according to the observations of the nurse and very similarly according to the parents' observations. The children expressed more pain after 40 min of EMLA application time (mean pain, 3.5) and a significant pain reduction after 60 min application time (mean pain 1.7). CONCLUSION: In this study children experienced less pain after 60 min application time, but pain reduction was already seen after 40 min. The child's perception of pain differed from observers' point of view and should therefore always be included in pain management.

Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children.

OBJECTIVES: The aim of this study was to analyze a possible association between cesarean delivery and enteric inflammatory diseases in children. METHODS: A retrospective, multicenter, case-control study that included 1950 children was performed in cooperation with 26 university and 16 nonacademic children's hospitals. Information on intestinal disease manifestation, together with mode of delivery and gestational age at birth, postnatal complications, and breastfeeding, was collected by the attending physician from children and their parents who were visiting a gastrointestinal outpatient clinic for Crohn disease (CD; 516 cases), ulcerative colitis (250 cases), celiac disease (157 cases), and other gastrointestinal diseases (165 cases) and control subjects who were visiting ophthalmologic, orthodontic, and dental outpatient clinics (862 cases). RESULTS: Whereas the rate of cesarean delivery of children with Crohn disease or ulcerative colitis was similar to that of control subjects, a significantly enhanced likelihood of being born by cesarean delivery was found in children with celiac disease compared with control subjects (odds ratio: 1.8 [95% confidence interval: 1.13-2.88]; P = .014). CONCLUSIONS: The mode of delivery and associated alterations in the development of the enteric homeostasis during the neonatal period might influence the incidence of celiac disease.

Acupuncture induces a pro-inflammatory immune response intensified by a conditioning-expectation effect.

BACKGROUND: In a previous study it has been shown that acupuncture activates the respiratory burst (RB) of neutrophils as measured by the differences to baseline of the mean channel number of fluorescence intensity (mfi) in volunteers. Since this result could have been affected by a placebo effect, a study has been designed that controls for the different facets of placebo mechanisms such as expectancy, suggestibility, and conditioning. PARTICIPANTS AND METHODS: 60 healthy volunteers were randomized either to acupuncture of the acupoint Large Intestine 11 (LI 11) (groups 1 and 2) or relaxation (group 3) twice a week for 4 weeks. Only acupuncture group 1 and the relaxation group were provided with the additional suggestion that the treatment may strengthen the immune system. RESULTS: The repeated measurement analysis for differences of follow-ups to baseline showed significantly different treatment effects for neutrophils but not for monocytes (unprimed neutrophils: p = 0.004; neutrophils primed with TNF-alpha/FMLP or with FMLP only: p = 0.026 and p = 0.019, respectively) between groups. For both cell types post-hoc Dunnett's t-tests using the relaxation group as control showed significantly stronger treatment effects for acupuncture group 1. Combining all priming procedures, the average increase in mfi for both cell types was about 30% greater in acupuncture group 1 than in the relaxation group. Plasma concentrations of pro-inflammatory cytokines only increased significantly in the acupuncture groups. CONCLUSION: Repetitive acupuncture increases the cytotoxicity of leukocytes in healthy volunteers, which might be intensified by a conditioning-expectation effect.

Preeclampsia and HELLP syndrome: impaired mitochondrial function in umbilical endothelial cells.

Preeclampsia (PE) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome have been linked to congenital fetal disorders of mitochondrial fatty acid oxidation (FAO). Different incidences may argue for the association of noncongenital alterations of mitochondrial energy metabolism with PE/HELLP syndrome. We studied human umbilical vein endothelial cells [HUVEC] as selected part of the feto-placental unit from uncomplicated (n = 46) and diseased (n = 27; 17 PE and 10 HELLP) pregnancies by measuring the overall FAO, carnitine palmitoyltransferase 2 (CPT2), respiratory chain (RC) complexes I-V, citratesynthase (CS), lactatedehydrogenase (LDH), hexokinase (HK), phosphofructokinase (PFK), and energy rich phosphates. Maternal and infantile acylcarnitines in blood were investigated post partum. Overall FAO, RC complexes II-V, and CS were significantly compromised in HUVEC from complicated pregnancies; impairment of complexes I + III was not significant. CPT2 and energy charges were unaffected. Lactatedehydrogenase and PFK from complicated pregnancies were upregulated, and HK remained constant. In blood, carnitine was elevated in diseased women and their children, acylcarnitines were higher in affected infants. Impaired mitochondrial function in HUVEC is associated with PE/HELLP syndrome and may be involved in the pathophysiology of these diseases.

Aerosol delivery by an ultrasonic nebulizer during different mechanical ventilation settings in a lung model--a pilot study.

UNLABELLED: Aerosol delivery of Iloprost is a promising therapeutic approach. The aim of this study was to determine the output of an ultrasonic nebulizer in different ventilation set-ups at the tip of different endotracheal tubes. METHOD: In set-up A, an ultrasonic nebulizer was connected directly to the endotracheal tube. In set-up B, the nebulizer was incorporated into the inspiratory limb of the ventilator circuit; a bypass arrangement allowed to selectively direct the expiratory air discharged from the model lung. The test lungs were ventilated through a standard endotracheal tube (ET) and through a double-lumen tube (DLT). The nebulizer was filled with 5 ml of a Tc-99m 0.9%-NaCl solution. After nebulization, distribution of radioactivity was detected by gamma scintigraphy. RESULTS: Set-up A, ventilation in volume-controlled mode (VCV) via an ET: Delivered dose (1.61 +/- 0.41 ml), nebulization time 10.13 +/- 1.71 min. Set-up A, pressure-controlled ventilation (PCV), via a DLT: Delivered dose (1.33 +/- 0.88 ml), nebulization time 13.27 +/- 2.58 min. Set-up B, VCV mode via an ET: Delivered dose (1.57 +/- 0.44 ml), nebulization time (25.9 +/- 3.8 min). Set-up B, PCV mode, via a DLT: Delivered dose (1.3 +/- 0.17 ml), nebulization time (25.6 +/- 4.0 min). Set-up B did not yield a significantly higher output (p < 0.05), but the nebulization time was significantly longer (p > 0.05) compared with set-up A. CONCLUSION: Set-ups which involve connecting the nebulizer directly to an ET or a DLT exhibit sufficient output of aerosol and short nebulization times.

S100B serum levels and word memory processing in remitted major depression as reflected by brain potentials.

OBJECTIVE: Memory processes, as reflected by 'old/new' effects of event-related potentials (ERPs), have been shown to be impaired in depressed patients. This variability might be partly explained by biological factors. S100B is a glial calcium-binding protein with neuroplastic properties; S100B serum levels have been shown to be increased in depressive patients. The pathophysiologic role of S100B in depression, however, is not yet sufficiently understood. METHODS: In the present study, ERPs recorded in a visual continuous word recognition paradigm were therefore investigated in patients with remitted major depression in relation to S100B serum levels. RESULTS: Patients with moderately increased S100B serum levels (n = 6) showed a normal old/new effect in contrast to a reduced old/new effect in patients with normal S100B levels (n = 6) compared to aged-matched controls. CONCLUSIONS: These findings provide evidence of an association between S100B levels and memory processes in patients with recurrent depression and further suggest a neuroprotective role of moderately increased S100B serum levels in the course of affective disorders.