[Measures to improve the health situation of patients with rare diseases in Germany. A comparison with the National Action Plan]. / Maßnahmen zur Verbesserung der gesundheitlichen Situation von Menschen mit seltenen Erkrankungen in Deutschland. Ein Vergleich mit dem Nationalen Aktionsplan.

BACKGROUND: Approximately 4 million patients with a rare disease live in Germany. The medical care of these patients is problematic because of the rarity and heterogeneity of different clinical pictures. The Federal Ministry of Health has therefore published a research report on "Measures to improve the health situation of people with rare diseases in Germany" in 2009. OBJECTIVE: The aim of this paper is to present the main recommendations of this research report and relate it to current developments in the field of medical care for people with rare diseases. METHODOLOGY: The care situation of patients with rare diseases was determined using questionnaires, expert interviews and focus group discussions with representatives of patients, service providers and stakeholders from the health institutions. RESULTS: The main range of actions that have been identified in the research report were centre and network formation, specialized forms of medical care, diagnosis and treatment, information and experience exchange, performance fees and reimbursement of the costs, guidelines and patient pathways, the research, the implementation of a National Action Alliance and the development of a National Action Plan. DISCUSSION: In March 2010 a National Action League for People with Rare Diseases (NAMSE) was founded. The NAMSE created a national plan of action for people with rare diseases for improving medical care in the field of rare diseases which was approved by the Federal Government in August 2013. Thus, two important areas of the research report have already been implemented. In a comparison of the areas of activity of the research report with those of the National Action Plan it becomes clear that priorities will be in the context of health services research in rare diseases, for example the introduction of centres of reference for rare diseases, measures to accelerate the diagnostic process and the promotion of research and information management in the future.

Is mesenteric panniculitis truely a paraneoplastic phenomenon? A matched pair analysis.

PURPOSE: Mesenteric panniculitis (MP) is an underdiagnosed inflammatory condition of mesenteric adipose tissue. Prior studies suggested an association of MP with malignancy. To reassess this hypothesis, we performed the first matched case-control study comparing prevalence of malignancy and other disease in patients with and without MP. MATERIAL AND METHODS: With a keyword search we identified CT examinations of MP patients between 2010 and 2012. Each MP patient was matched with two control patients for age, gender, abdominal diameter and CT protocol. Manifestation and extent of mesenteric panniculitis was classified independently by two investigators according to established criteria. Concomitant disease, laboratory parameters and follow up CTs were recorded and analyzed for all patients. RESULTS: 77 of 13485 CT patients were diagnosed with MP (prevalence 0.58%). 50.6% of MP patients suffered from malignancy vs. 60.2% in the control group (p=0.157). Over up to 4 years of follow up in 35 of these 77 MP patients no association between development of MP and the course of tumor diseases could be identified. There was also no significant difference in the rate of frequent concomitant diseases such as hypertension, diabetes or previous surgery between the two groups. CONCLUSION: In this first case-control-study we could show that, contrary to previous reports, mesenteric panniculitis is neither paraneoplastic nor is it associated with other diseases.

Factors associated with ruminal pH at herd level.

The objective of this study was to evaluate factors associated with ruminal pH at herd level. Four hundred and thirty-two cows of a Thuringian dairy herd were sampled before claw trimming using a rumen fluid scoop. Volume and pH of the rumen sample were measured, and lactation number, percentage of concentrates in the ration, days in milk (DIM), time of day, and daily milk yield were recorded. Rumen sampling was successful in 99.8% of the cows. The average sample volume was 25 mL. Rumen sample pH decreased with increasing percentage of concentrates in the ration. Ruminal pH decreased from calving to 77 DIM, and grew subsequently to 330 DIM. During the day, rumen pH followed a sinus curve, with maxima in the morning (0915 h) and afternoon (1533 h), and a minimum around noon (1227 h). Ruminal pH decreased with increasing daily milk yield. Lactation number interacted with daily milk yield on rumen pH. The percentage of concentrates in the ration, DIM, time of day, and daily milk yield were significant factors affecting ruminal pH at the herd level.

Automatic bone and plaque removal using dual energy CT for head and neck angiography: feasibility and initial performance evaluation.

PURPOSE: We sought to evaluate the feasibility and efficiency of dual energy (DE) bone and plaque removal in head and neck CT angiography. MATERIALS AND METHODS: 20 patients with suspected carotid stenoses received head and neck DE-CTA as part of their pre-interventional workup. Visual grading using multiplanar reformations (MPR), thick slab maximum intensity projections (MIP) and quantitative vessel analysis (QVA) of stenoses was performed prior and after DE bone removal. Results were evaluated for the detection of relevant stenoses (vessel area reduction >70%). Vessel segmentation errors were analyzed. RESULTS: Segmentation errors occurred in 19% of all vessel segments. Nevertheless, most post-bone removal artifacts could be recognized using the MPR technique for reading. Compared to MPR reading prior to bone removal, sensitivity, specificity, positive and negative predictive values after bone removal were 100%, 98%, 88% and 100% for MPR reading and 100%, 91%, 63% and 100% for exclusive MIP reading, respectively. There was a good agreement between the QVA results prior and post-DE plaque removal (r(2)=0.8858). CONCLUSION: DE bone and plaque removal for head and neck angiography is feasible and offers a rapid and highly sensitive overview over vascular head and neck studies. Due to a slightly limited specificity of the MIP technique due to segmentation errors, possible stenoses should be verified and graded using MPR techniques.

Accuracy of dual-source CT in the characterisation of non-calcified plaque: use of a colour-coded analysis compared with virtual histology intravascular ultrasound.

Non-invasive assessment of plaque volume and composition is important for risk stratification and long-term studies of plaque stabilisation. Our aim was to evaluate dual-source computed tomography (DSCT) and colour-coded analysis in the quantification and classification of coronary atheroma. DSCT and virtual histology intravascular ultrasound (IVUS-VH) were prospectively performed in 14 patients. 22 lesions were compared in terms of plaque volume, maximal per cent vessel stenosis and percentages of fatty, fibrous or calcified components. Plaque characterisation was performed with software that automatically segments luminal or outer vessel boundaries and uses CT attenuation for a colour-coded plaque analysis. Good correlation was found for per cent vessel stenosis in DSCT (53+/-13%) and IVUS (51+/-14%; r(2) = 0.70). Mean volumes for entire plaque and non-calcified atheroma were 68.5+/-33 mm(3) and 56.7+/-30 mm(3), respectively, in DSCT and 60.8+/-29 mm(3) and 55.8+/-26 mm(3), respectively, in IVUS. Mean percentages of fatty, fibrous or calcified components were 28.2+/-6%, 53.2+/-9% and 18.7+/-13%, respectively, in DSCT and 29.9+/-5%, 55.3+/-12% and 14.4+/-9%, respectively, in IVUS-VH. Significant overestimation was present for the entire plaque and the volume of calcified plaque (p = 0.03; p = 0.0004). Although good correlation with IVUS was obtained for the entire plaque (r(2) = 0.76) and non-calcified plaque volume (r(2) = 0.84), correlation proved very poor and insignificant for percentage plaque composition. Interclass correlation coefficients for non-calcified plaque volume and percentages of fatty, fibrous or calcified components were 0.99, 0.99, 0.95 and 0.98, respectively, and intraclass coefficients were 0.98, 0.93, 0.98 and 0.99, respectively. We found that using Hounsfield unit-based analysis, DSCT allows for accurate quantification of non-calcified plaque. Although percentage plaque composition proves highly reproducible, it is not correlated with IVUS-VH.

Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol.

The efficiency and radiation dose of a low-dose dual-energy (DE) CT protocol for the evaluation of urinary calculus disease were evaluated. A low-dose dual-source DE-CT renal calculi protocol (140 kV, 46 mAs; 80 kV, 210 mAs) was derived from the single-energy (SE) CT protocol used in our institution for the detection of renal calculi (120 kV, 75 mAs). An Alderson-Rando phantom was equipped with thermoluminescence dosimeters and examined by CT with both protocols. The effective doses were calculated. Fifty-one patients with suspected or known urinary calculus disease underwent DE-CT. DE analysis was performed if calculi were detected using a dedicated software tool. Results were compared to chemical analysis after invasive calculus extraction. An effective dose of 3.43 mSv (male) and 5.30 mSv (female) was measured in the phantom for the DE protocol (vs. 3.17/4.57 mSv for the SE protocol). Urinary calculi were found in 34 patients; in 28 patients, calculi were removed and analyzed (23 patients with calcified calculi, three with uric acid calculi, one with 2,8-dihyxdroxyadenine-calculi, one patient with a mixed struvite calculus). DE analysis was able to distinguish between calcified and non-calcified calculi in all cases. In conclusion, dual-energy urinary calculus analysis is effective also with a low-dose protocol. The protocol tested in this study reliably identified calcified urinary calculi in vivo.

Image quality analysis to reduce dental artifacts in head and neck imaging with dual-source computed tomography.

PURPOSE: Important oropharyngeal structures can be superimposed by metallic artifacts due to dental implants. The aim of this study was to compare the image quality of multiplanar reconstructions and an angulated spiral in dual-source computed tomography (DSCT) of the neck. MATERIALS AND METHODS: Sixty-two patients were included for neck imaging with DSCT. MPRs from an axial dataset and an additional short spiral parallel to the mouth floor were acquired. Leading anatomical structures were then evaluated with respect to the extent to which they were affected by dental artifacts using a visual scale, ranging from 1 (least artifacts) to 4 (most artifacts). RESULTS: In MPR, 87.1 % of anatomical structures had significant artifacts (3.12 +/- 0.86), while in angulated slices leading anatomical structures of the oropharynx showed negligible artifacts (1.28 +/- 0.46). The diagnostic growth due to primarily angulated slices concerning artifact severity was significant (p < 0.01). CONCLUSION: MPRs are not capable of reducing dental artifacts sufficiently. In patients with dental artifacts overlying the anatomical structures of the oropharynx, an additional short angulated spiral parallel to the floor of the mouth is recommended and should be applied for daily routine. As a result of the static gantry design of DSCT, the use of a flexible head holder is essential.

Characterization of coronary atherosclerosis by dual-source computed tomography and HU-based color mapping: a pilot study.

To assess HU-based color mapping for characterization of coronary plaque, using intravascular ultrasound virtual histology (IVUS-VH) as a standard of reference. Dual-source computed tomography and IVUS-VH were prospectively performed in 13 patients. In five lesions, HU thresholds of the color-coding software were calibrated to IVUS-VH. In a 15-lesion verification cohort, volumes of vessel, lumen and plaque or percentages of lipid, fibrous and calcified components were obtained through use of pre-set HU cut-offs as well as through purely visual adjustment of color maps. Calibrated HU ranges for fatty or fibrous plaque, lumen and calcification were -10-69, 70-158, 159-436 and 437+. Using these cut-offs, HU-based analysis achieved good agreement of plaque volume with IVUS (47.0 vs. 51.0 mm(3)). Visual segmentation led to significant overestimation of atheroma (61.6 vs. 51.0 mm(3); P = 0.04) Correlation coefficients for volumes of vessel, lumen and plaque were 0.92, 0.87 and 0.83 with HU-based analysis or 0.92, 0.85 and 0.71 with visual evaluation. With both methods, correlation of percentage plaque composition was poor or insignificant. HU-based plaque analysis showed good reproducibility with intra-class correlation coefficients being 0.90 for plaque volume and 0.81, 0.94 or 0.98 for percentages of fatty, fibrous or calcified components. With use of optimized HU thresholds, color mapping allows for accurate and reproducible quantification of coronary plaque.

Noninvasive coronary angiography using 64-slice spiral computed tomography in an unselected patient collective: effect of heart rate, heart rate variability and coronary calcifications on image quality and diagnostic accuracy.

OBJECTIVE: The aim of this study was to assess the impact of heart rate, heart rate variability and calcification on image quality and diagnostic accuracy in an unselected patient collective. SUBJECTS AND METHODS: One hundred and two consecutive patients with known or suspected coronary artery disease underwent both 64-MSCT and invasive coronary angiography. Image quality (IQ) was assessed by independent observers using a 4-point scale from excellent (1) to non-diagnostic (4). Accuracy of MSCT regarding detection or exclusion of significant stenosis (>50%) was evaluated on a per segment basis in a modified AHA 13-segment model. Effects of heart rate, heart rate variability, calcification and body mass index (BMI) on IQ and accuracy were evaluated by multivariate regression. IQ and accuracy were further analysed in subgroups of significant predictor variables and simple regression performed to calculate thresholds for adequate IQ. RESULTS: Mean heart rate was 68.2+/-13.3 bpm, mean heart rate variability 11.5+/-16.0 beats per CT-examination (bpct) and median Agatston score 226.5. Average IQ score was 2+/-0.6 whilst diagnostic quality was obtained in 89% of segments. Overall sensitivity, specificity, PPV or NPV was 91.2%, 99.2%, 95.3% or 98.3%. According to multivariate regression, overall IQ was significantly related to heart rate and calcification (P=0.0038; P<0.0001). The effect of heart rate variability was limited to IQ of RCA segments (P=0.018); BMI was not related to IQ (P=0.52). Calcification was the only predictor variable with significant effect on the number of non-diagnostic segments (P<0.0001). In a multivariate regression, calcification was also the single factor with impact on diagnostic accuracy (P=0.0049). CONCLUSION: Whilst heart rate, heart rate variability and calcification all show an inverse correlation to IQ, severe calcium burden remains the single factor with translation of such effect into decrease of diagnostic accuracy.

[Patient-centred care in rare diseases. A patient organisations' perspective]. / Patientenzentrierte Versorgung bei seltenen Erkrankungen. Perspektive von Patientenorganisationen.

Patients living with rare diseases have special common needs. Although the 5,000-6,000 rare diseases are very different, many patients share the experience of a time-consuming and sometimes frustrating journey towards diagnosis, the lack of established standards of care and foremost the search for competent physicians. Because of their complexity, rare diseases mostly demand an interdisciplinary and cross-sectional medical care. The model of the "patient-centred health-care value chain" explains how primary (prevention, diagnosis, treatment) and secondary activities (exchange of information, quality management, identification of unmet needs, research and development) contribute to the patient benefit applying a holistic approach. This model thereby prevents an isolated view from the perspective of single health-care providers. A survey to which 21 German patient-organisations in the rare-disease field contributed, was performed to obtain insight into preferred medical care concepts and preferences in the way that care is provided. The results clearly suggest that the patient organisations have a clear view on how disease-specific care should be delivered; however, in reality those preferences seem to be met to a minor extent in Germany at present. According to patient organisations, rare-disease patient care should always be a patient- centred, interdisciplinary and holistic effort. The solidaric health-care system in Germany provides an excellent basis for this kind of medical care. However, a new patient- rather than system-oriented approach is needed to make it work in reality.

Sixty-four-slice CT in the assessment of global and regional left ventricular function: comparison with MRI in a porcine model of acute and subacute myocardial infarction.

The purpose was to assess 64-slice CT in the analysis of global and regional ventricular function, using a model of acute and subacute myocardial infarction in comparison with cine-MRI. Seven pigs underwent standard MSCT and MRI examination a median 1 and 21 days following creation of reperfused myocardial infarction. Endocardial and epicardial contours were manually defined and ventricular volumes calculated according to Simpson's method. Results were compared by Pearson's correlation coefficient and Blant-Altman analysis. Wall motion was assessed on cine-images and evaluated by kappa statistics. MSCT revealed a strong correlation with cine-MRI regarding quantification of end-diastolic volume (EDV; r = 0.97), end-systolic volume (ESV; r = 0.97), stroke volume (SV; r = 0.94), ejection fraction (EF; r = 0.95) or myocardial mass (MM; r =0.94 ). Minor overestimation was observed for EDV and ESV (bias -1.7 ml; -1.5 ml; P=0.095; 0.025), whilst the mean difference for EF was found to be negligible (bias 0.9%; P = 0.18). Both modalities showed a 96.2% segmental agreement in regional wall motion (weighted-kappa 0.91 for 238 segments). This was true for both acute and subacute infarct phase and MSCT, and thereby enabled accurate intraindividual follow-up of segmental dysfunction. Sixty-four-slice CT allows for reliable analysis of global cardiac function and, moreover, provides accurate evaluation of wall motion in acute and subacute myocardial infarct.

Late myocardial enhancement assessed by 64-MSCT in reperfused porcine myocardial infarction: diagnostic accuracy of low-dose CT protocols in comparison with magnetic resonance imaging.

The purpose was to assess the practicability of low-dose CT imaging of late enhancement in acute infarction. Following temporary occlusion of the second diagonal branch, seven pigs were studied by multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). Thus, 64-slice CT was performed at 3, 5, 10 and 15 min following the injection of contrast medium according to a bolus/low-flow protocol. Standard parameters of 120 kV and 800 mAs were compared with 80 kV and 400 mAs in various combinations. Infarct volumes were assessed as percentage of the ventricle for both MSCT and MR images. CT density values for viable and infarcted myocardium were obtained and image quality assessed. Mean infarct volume as measured by MRI was 12.33+/-7.06%. MSCT achieved best correlation of volumes at 5 and 10 min. Whilst lowering of tube current resulted in poor correlation, tube voltage did not affect accuracy of infarct measurement (r (2)=0.92 or 0.93 at 5 min, 800 mAs and 80 or 120 kV). In terms of image quality, greater image noise with 80 kV was compensated by significantly better contrast enhancement between viable and non-viable myocardium at lower voltage. Myocardial viability can accurately be assessed by MSCT at 80 kV, which ensures higher contrast for late enhancement and yields good correlation with MRI.

Sixty-four-MSCT in the characterization of porcine acute and subacute myocardial infarction: determination of transmurality in comparison to magnetic resonance imaging and histopathology.

OBJECTIVE: The aim of this study was to assess the accuracy of MSCT in characterizing myocardial infarction (MI) and, thereby, determine the extent of early perfusion defect (ED), microvascular obstruction (MO) and transmural depth of late enhancement (LE) in comparison to MRI and histology. MATERIALS AND METHODS: Seven pigs were studied with MSCT (Somatom Sensation 64) and MRI (Magnetom Sonata) a median 1 and 21 days following temporary occlusion of a diagonal branch and creation of small reperfused infarction. For depiction of ED, CT images were acquired in the early arterial phase and following 35 s; LE and MO were evaluated on images obtained at 3, 5, 10 and 15 min. Thereby, a bolus/low-flow contrast injection protocol was used. Triphenyltetrazolium-chloride (TTC) stain and histology were obtained. Volumes of enhancement patterns were assessed as percentage of the ventricle and compared by Bland-Altman analysis. Segmental co-localization and graded transmurality was evaluated with weighted-kappa-test. RESULTS: Close spatial agreement was observed for MRI-MO and MSCT-MO (bias=0.55; CI=-1.49 to 2.60 at 5 min MSCT), TTC and MSCT-LE (bias=-1.28; CI=-3.76 to 1.19) or MRI-LE and MSCT-LE (bias=-0.79; CI=-4.19 to 2.60). There was good segmental co-localization for MO (weighted kappa=0.93) and high agreement for transmural extent of TTC, MRI-LE and MSCT-LE (weighted kappa=0.84 TTC versus MSCT; 0.86 MRI versus MSCT). Arterial and 35s ED significantly underestimated infarct size and showed poor segmental or transmural agreement (weighted kappa=0.33; 0.44). CONCLUSIONS: MSCT late-scans not only reliably depict size of MO and LE in acute or subacute infarct phases but, moreover, allow for accurate determination of LE transmurality.

Non-invasive coronary angiography with 16-slice spiral computed tomography: image quality in patients with high heart rates.

The purpose of this study was to assess segment image quality at high heart rates using 16-slice computed tomography and differential reconstruction for major coronary vessels. According to the following protocol, 16-slice CT coronary angiography in 46 patients with a mean heart rate of 86.3+/-11.8 was reconstructed. At three transverse planes, preview series were obtained and motion artifacts evaluated in 5% increments from 0-95% within the cardiac cycle. Relying on image quality in the previews, reconstructions were performed at three z-positions for each patient. Segment image quality was assessed in terms of artifacts and visibility. The effects of heart rate and trigger delay on image quality were analyzed. Optimal image quality was achieved at 25 to 35% of the cardiac cycle for the left circumflex (CX) and right coronary artery (RCA) or 30 to 40% for the left main (LM) and left anterior descending artery (LAD). Sixteen-slice CT and differential reconstruction produced good image quality with a low percentage of motion-degraded proximal and middle segments (8.8%). Grades were 1.5 for the LM, 1.9 for the LAD, 2.0 for the CX and 2.3 for the RCA. At high heart rates, good image quality of the coronary arteries is achieved by 16-slice CT and a sophisticated reconstruction strategy at peak to late systole.

Image quality and diagnostic accuracy of 16-slice multidetector computed tomography for the detection of coronary artery disease in obese patients.

BACKGROUND: Cardiac multislice spiral computed tomography (MSCT) scanners permit visualization of the coronary arteries with an overall good sensitivity (sens) and specificity (spec). However, in obese patients (pts), who are at higher risk to develop coronary artery disease (CAD), image quality of MSCT is supposed to be limited. At present, there are no data whether the accuracy of MSCT depends on the body mass index (BMI). Thus, we compared the catheter-controlled MSCT results from normal weight and obese pts in a cohort of 117 pts with regard to sens, spec, positive predictive value (PPV), negative predictive value (NPV) and image quality. METHODS AND MATERIAL: In all, 21 normal weight pts (group I: BMI<25, 64.6+/-11.1 years, number of risk factors 2.1+/-1.1), 60 pts with mild overweight (group II: BMI 25-30, 64.6+/-8.9 years, number of risk factors 3.4+/-1.0) and 36 obese pts (group III: BMI >30, 63.0+/-8.5 years, number of risk factors 3.4+/-0.9) were examined by MSCT (Sensation 16 Speed 4 D((R)), Siemens, Germany, gantry rotation time 375 ms) and invasive coronary angiography. MSCT results were compared blinded to the results of the coronary angiography with regard to the presence or absence of a significant stenosis (>50%) in a modified AHA 13 segment (sgt) model. Image quality was assessed on a qualitative scale between 1 (very good) and 5 (insufficient image quality) for each sgt. RESULTS: Sens, spec, PPV and NPV were statistically not different in all three groups (I: 0.88/0.97/0.91/0.96, II: 0.83/0.97/0.88/0.95, III: 0.87/0.99/0.96/0.96). 3 pts (group I 1, group II 2) had to be excluded from analysis due to technical problems. Group I had significantly less risk factors (P < 0.001) and image quality was significantly better than in group II and III (P < 0.05). Group II and III did not differ with regard to risk factors or image quality. CONCLUSIONS: Overweight and obesity have an impact on MSCT image quality but did not hamper the diagnostic accuracy. Thus, MSCT is a noninvasive method to detect or rule out CAD also in pts with higher BMI. These retrospective data have to be confirmed in larger prospective trials.

Age-dependent expression of advanced glycation end product receptor genes in the human heart.

BACKGROUND: Advanced glycation end products (AGEs) are formed by the reaction of sugars and NH2 groups of lysine and arginine residues and have been shown to accumulate in tissues, including the heart, with normal ageing. The interaction of AGEs with their receptors is known to cause changes in cell function, leading, for example, to the production of pro-inflammatory cytokines and free radicals. OBJECTIVE: This study investigated the gene expression of the five known AGE receptors: AGE-R1, AGE-R2, AGE-R3, the scavenger receptor II, and the receptor for AGEs (RAGE) in human heart tissue. METHODS: Tissue samples were taken from the right cardiac auricles from three patient groups: children (2.4 +/- 1.1 years), adults (45.3 +/- 0.8 years) and elderly subjects (76.4 +/- 0.4 years). Analysis of gene expression of the five AGE receptors was performed using the reverse transcription-polymerase chain reaction (RT-PCR) and 18S mRNA levels as loading controls. RESULTS: Our results show an age-dependent upregulation of the genes for AGE-R3 and the scavenger receptor II, but a downregulation for RAGE and no significant differences for AGE-R1 and AGE-R2. CONCLUSION: This study supports a pathophysiological function for AGE receptors such as AGE-R3 and RAGE in the ageing heart.

Age associated changes of AGE-receptor expression: RAGE upregulation is associated with human heart dysfunction.

The binding of advanced glycation endproducts (AGEs) to their receptors is known to cause changes in cell function during normal ageing and is implicated in the pathogenesis of cardiovascular disease. In this study, expression of the AGE-receptor 3 (AGE-R3) and the receptor for AGEs (RAGE) was compared on the mRNA and protein level in the ageing human heart. Western blot and RT-PCR analysis of the AGE receptors from the cardiac auricles in senescent and adult patients was performed and compared with young controls. Whereas the expressions of AGE-R3 as well as RAGE protein were significantly upregulated in the senescent population, only the upregulation of RAGE is associated with reduced heart function. Therefore, our results support a pathophysiological function for RAGE in the ageing human heart.

Detoxification of lignocellulose hydrolysates with ion-exchange resins.

Lignocellulose hydrolysates contain fermentation inhibitors causing decreased ethanol production. The inhibitors include phenolic compounds, furan aldehydes, and aliphatic acids. One of the most efficient methods for removing inhibiting compounds prior to fermentation is treatment of the hydrolysate with ion-exchange resins. The performance and detoxification mechanism of three different resins were examined: an anion exchanger, a cation exchanger, and a resin without charged groups (XAD-8). A dilute acid hydrolysate of spruce was treated with the resins at pH 5.5 and 10.0 prior to ethanolic fermentation with Saccharomyces cerevisiae. In addition to the experiments with hydrolysate, the effect of the resins on selected model compounds, three phenolics (vanillin, guaiacol, and coniferyl aldehyde) and two furan aldehydes (furfural and hydroxymethyl furfural), was determined. The cation exchanger increased ethanol production, but to a lesser extent than XAD-8, which in turn was less effective than the anion exchanger. Treatment at pH 10.0 was more effective than at pH 5.5. At pH 10.0, the anion exchanger efficiently removed both anionic and uncharged inhibitors, the latter by hydrophobic interactions. The importance of hydrophobic interactions was further indicated by a substantial decrease in the concentration of model compounds, such as guaiacol and furfural, after treatment with XAD-8.

Influence of lignocellulose-derived aromatic compounds on oxygen-limited growth and ethanolic fermentation by Saccharomyces cerevisiae.

Phenolic compounds released and generated during hydrolysis inhibit fermentation of lignocellulose hydrolysates to ethanol by Saccharomyces cerevisiae. A wide variety of aromatic compounds form from lignin, which is partially degraded during acid hydrolysis of the lignocellulosic raw material. Aromatic compounds may also form as a result of sugar degradation and are present in wood as extractives. The influence of hydroxy-methoxy-benzaldehydes, diphenols/quinones, and phenylpropane derivatives on S. cerevisiae cell growth and ethanol formation was assayed using a defined medium and oxygen-limited conditions. The inhibition effected by the hydroxy-methoxy-benzaldehydes was highly dependent on the positions of the substituents. A major difference in inhibition by the oxidized and reduced form of a diphenol/quinone was observed, the oxidized form being the more inhibitory. The phenylpropane derivatives were examined with respect to difference in toxicity depending on the oxidation-reduction state of the gamma-carbon, the presence and position of unsaturated bonds in the aliphatic side chain, and the number and identity of hydroxyl and methoxyl substituents. Transformations of aromatic compounds occurring during the fermentation included aldehyde reduction, quinone reduction, and double bond saturation. Aromatic alcohols were detected as products of reductions of the corresponding aldehydes, namely hydroxy-methoxy-benzaldehydes and coniferyl aldehyde. High molecular mass compounds and the corresponding diphenol were detected as products of quinone reduction. Together with coniferyl alcohol, dihydroconiferyl alcohol was identified as a major transformation product of coniferyl aldehyde.

Use of an intraaortic balloon pump in patients with impaired left ventricular function.

Prophylactic use of an intraaortic balloon pump (IABP) prior to open-heart surgery in patients with impaired left ventricular function is still under debate. Patients with left ventricular ejection fraction (LVEF) < 40% were therefore compared according to time of IABP placement, viz. preoperative (n = 56), intraoperative (n = 40) or postoperative (n = 17), and also with patients who did not receive mechanical support despite LVEF < 40% (n = 78). The main indication for preoperative IABP insertion was severely impaired left ventricular function (80%), while patients with intraoperative or postoperative IABP placement mainly presented with low cardiac-output syndrome (70%/53%). Preoperative IABP was associated with a low mortality rate (8.9%), whereas patients with intraoperative or postoperative IABP placement had a high mortality risk and an increased catecholamine requirement. Of the patients scheduled for surgery without prophylactic IABP, 19% required intra- or postoperative insertion. Prophylactic placement of IABP thus reduced the mortality rate as well as the postoperative need for mechanical and catecholamine support. Need for intraoperative IABP insertion was associated with high mortality, whereas the outcome after postoperative IABP placement depended on the indication for the measure.