Effect of cholesterol re-supplementation and atorvastatin on plaque composition in the thoracic aorta of New Zealand white rabbits.

BACKGROUND: Effects of re-supplementation of a cholesterol-enriched diet (CEDrs) on size, cholesterol content and morphology of already existing plaques are not known to date. METHODS: A group of rabbits received standard chow (SC) for 6 weeks ("negative control"; for plasma lipid measurements only). Group I-IV received 2% CED (induction) for 6 weeks; thereafter, groups II-IV have been fed a SC (= cholesterol withdrawal) for 68 weeks. Afterwards, feeding of groups II-IV was continued as follows: Group II - 10 weeks SC, group III - 4 weeks 0.5% CED (~re-supplementation), afterwards 6 weeks SC (~withdrawal again); group IV - 4 weeks 0.5% CED (re-supplementation) + atorvastatin (2.5 mg/kg body weight/day), afterwards 6 weeks SC (~withdrawal again) + atorvastatin. Plasma lipids, but also plaque size, morphology and cholesterol contents of thoracic aortas were quantified. RESULTS: After CEDrs, plasma cholesterol levels were increased. However, after withdrawal of CEDrs, plasma cholesterol levels decreased, whereas the cholesterol content of the thoracic aorta was increased in comparison with the group without CEDrs. Plaque size remained unaffected. Atorvastatin application did not change plasma cholesterol level, cholesterol content of the thoracic aorta and plaque size in comparison with the group without drug treatment. However, atorvastatin treatment increased the density of macrophages (MΦ) compared with the group without treatment, with a significant correlation between densities of MΦ (Mac-1+) and apoptotic (TUNEL+; TP53+), antigen-presenting (HLA-DR+) or oxidatively stressed (SOD2+) cells. CONCLUSIONS: In rabbits with already existing plaques, CEDrs affects plaque morphology and cellular composition, but not plaque size. Despite missing effects on plasma cholesterol levels, cholesterol content of the thoracic aorta and size of already existing atherosclerotic plaques, atorvastatin treatment transforms the already existing lesions to a more active form, which may accelerate the remodelling to a more stable plaque.

[Current Situation of Antibiotic Prophylaxis in Obesity and Metabolic Surgery - Data Analysis from the Study for Quality Assurance in Operative Treatment of Obesity in Germany]. / Aktueller Stand der Antibiotikaprophylaxe in der Adipositas- und metabolischen Chirurgie - Datenanalyse aus der Studie zur Qualitätskontrolle der operativen Therapie der Adipositas in Deutschland.

BACKGROUND: Since January 2005, the situation of metabolic and obesity surgery in Germany has been constantly evaluated by the German Bariatric Surgery Registry (GBSR). Data registration is performed using an internet online database with prospective data collection. All registered data were analysed in cooperation with the Institute of Quality Assurance at the Otto-von-Guericke University Magdeburg. METHODS: Data collection includes primary and revision/redo-procedures. A main focus of the current study is the analysis of data regarding the perioperative management, in particular, administration of antibiotics. RESULTS: Since 2005 a significant increase of primary bariatric procedures has been reported. For evaluation of the antibiotic regimen 12 296 primary operations including 684 balloons (BIB), 2950 gastric bandings (GB), 5115 Roux-en-Y-gastric bypasses (RYGBP), 120 Scopinaro's biliopancreatic diversions (BPD), 164 duodenal switches (DS), 3125 sleeve gastrectomies (SG) and 138 other procedures were analysed. In total 77.3 % of the patients with primary procedures received perioperative antibiotics. Patients without concomitant comorbidities received antibiotics significantly less often compared to those with comorbidities. Wound infection rates were comparable for patients who underwent either gastric banding or sleeve gastrectomy. CONCLUSION: Surgery has been accepted step by step as a treatment for morbid obesity and its comorbidities in Germany during the last few years. There is only little experience in the literature regarding antibiotic therapy as well as prophylaxis in bariatric surgery. Based on the results of the current study we recommend rather the selective than the routine use of antibiotics depending on different parameters, e.g., operative time, preoperative BMI and concomitant comorbidities.

The efficacy of prophylactic IVC filters in gastric bypass surgery.

BACKGROUND: Patients undergoing gastric bypass surgery have a high risk for thromboembolic events. Over the last decade, the use of prophylactic IVC filters (IVCF) has drastically increased for patients who are considered high risk. However, the role and efficacy of prophylactic IVCF placement remain controversial, and the literature is limited to a few retrospective studies. METHODS: We conducted a systematic review of the literature. A total of 21 articles were analyzed, and eight relevant retrospective studies were chosen for review of data. Data from laparoscopic gastric bypass surgery were compared to open gastric bypass surgery RESULTS: The relevant eight retrospective studies included a total of 597 patients. Patients had IVCFs before laparoscopic gastric bypass (41 %) and before open gastric bypass (59 %). There were 5 postoperative pulmonary emboli (PE) (0.84 %), 21 DVTs (3.52 %), 5 minor IVCF-related complications (0.84 %), 2 major IVCF-related complications (0.34 %), and 10 deaths (1.68 %). The rate of postoperative PE was the same in the laparoscopic group and the open group (0.84 %). The rate of DVT in the laparoscopic group was 5.02 %, and in the open group, it was 2.23 %. CONCLUSION: It is estimated that 55 % of bariatric surgeons use IVCF in high-risk patients. Prospective research that supports the use of IVCF is very limited, and individualized placement relies on retrospective studies only. In addition, patient characteristics associated with high risk vary between different studies. Our review showed that most of the published studies support the use of prophylactic IVCF and found it to be safe. On the other hand, the largest and most recent retrospective cohort study does not support their use. The efficacy of prophylactic IVCFs before gastric bypass surgery in high-risk patients has not been established.

[Genetic predisposition and Pediatric Acute Respiratory Distress Syndrome: New tools for genetic study]. / Predisposición genética y síndrome de distrés respiratorio agudo pediátrico: nuevas herramientas de estudio genético.

Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome.

The influence of axial length on confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography size measurements: a pilot study.

PURPOSE: To investigate the influence of axial length on SD-OCT and cSLO size measurements from the Heidelberg Spectralis. METHODS: In this pilot study, eight emmetropic pseudophakic eyes with subretinal visual implant were selected. The axial length was measured in three short (<22.5 mm), three medium (22.51-25.50 mm) and two long (>25.52 mm) eyes. The known size of subretinal implant sensor field (2800 × 2800 µm) was measured on 15 images per eye with cSLO and SD-OCT. RESULTS: The mean axial length was 20.8 ± 0.8 mm in short eyes, 23.3 ± 0.4 mm in medium eyes, and 26.3 ± 0.5 mm in long eyes respectively. We found in short eyes, in medium eyes and in long eyes a mean value of sensor field size measurements from cSLO of 3327 ± 9 µm, 2800 ± 9 µm and 2589 ± 12 µm and from SD-OCT of 3328 ± 9 µm, 2800 ± 12 µm and 2585 ± 19 µm respectively. The size measurements decreased in SD-OCT and cSLO measurements with longer axial lengths significantly (p < 0.0001). CONCLUSION: The present findings demonstrate accuracy of the scaling in cSLO and SD-OCT measurements of the Heidelberg Spectralis for emmetropic medium eyes. The size measurements from SD-OCT to those from cSLO were approximately equal. Caution is recommended when comparing the measured values of short and long eyes with the normative database of the instrument. Further studies with larger sample sizes are needed to confirm findings.

The 100-year evolution of the isolated internal iliac artery aneurysm.

BACKGROUND: Isolated internal iliac artery aneurysms (IIIAA) are a rare form of aneurysm. The incidence increases with age, and the prevalence is higher in men. The clinical presentation can vary, and standard treatment protocols are not established. The first case of an IIIAA was described more than 100 years ago. The purpose of the study is to summarize the various clinical presentations and treatment options that have been reported in the literature in the past 100 years. METHODS: Literature about IIIAA was reviewed using the electronic databank PubMed. All case reports and case series were analyzed, and we included our own data with 2 case reports. RESULTS: Over time, IIIAA diagnosis increasingly resulted from asymptomatic incidental findings on radiologic studies. Various clinical presentations included abdominal pain, back pain, rectal bleeding, hydronephrosis with renal failure, hematuria, and free rupture with shock. Rupture has a mortality rate of 53%. IIIAAs were more common on the left (61.8% left, 27.3% right, 10.9% bilateral). Treatments include open surgical repair and endovascular repair using a variety of methods. One article reported a hybrid method using both endovascular and open surgical technique. CONCLUSIONS: Since its first description 100 years ago, we have gained knowledge about the natural history of IIIAA. Multiple treatment options have been described, but long-term outcome needs further investigation.

[Daytime flexible application of Insulin degludec in patients with type 1 diabetes or type 2 diabetes]. / Tageszeitlich flexible Gabe von Insulin degludec bei Patienten mit Typ-1-Diabetes oderTyp-2-Diabetes.

BACKGROUND: Insulin degludec (IDeg) is a basal insulin with a stable, flat action profile and an even distribution of the blood glucose lowering effect over 24 hou rs. The terminal half-life of IDeg is about 25 hours, which reflects a mean prolongation by factor 2 compared to Insulin glargin (lGlar).This may enable for a more flexible daytime dosing versus up to now available basal insulins. METHOD: Two open, randomized, treat-to-target studies enrolled patients with type 1 diabetes (n =493) or type 2 diabetes (n = 687). Both phase 3 studies compared a daytime flexible dosing of IDeg (IDeg-flex) with IDeg at the evening meal (IDeg-evening) and IDler at a fixed daytime. In the IDeg-flex-group dosing intervals were predefined with variations between 8 and 40 hours. RESULTS: In patients with type 1 diabetes IDeg-flex proved to be non-inferior with respect to reduction of HbA1C (-0.40%) versus IDeg-evening (-0.41%) and IGlar (-0.58%) after 26 weeks. In addition, nocturnal hypoglycemic events were reduced by 40% (p < 0.01) with IDeg-flex versus IGlar. In patients with type 2 diabetes reduction of HbA1C with ID)eg-flex (-1.28%) was non-inferior to IDeg-evening (-1.07%) and IGlar (-1.26%), respectively, whereas rates for hypoglycemia were comparable. CONCLUSION: Patients with diabetes mellitus are enabled to dose a basal insulin flexibly when needed (minimum interval of 8 hours after the last injection is necessary). Impacts of this treatment option on quality of life and adherence and outcomes should be examined in observational trials.

[Daytime flexible application of Insulin degludec in patients with type 1 diabetes or type 2 diabetes]. / Tageszeitlich flexible Gabe von Insulin degludec bei Patienten mit Typ-1-Diabetes oderTyp-2-Diabetes.

BACKGROUND: Insulin degludec (IDeg) is a basal insulin with a stable, flat action profile and an even distribution of the blood glucose lowering effect over 24 hou rs. The terminal half-life of IDeg is about 25 hours, which reflects a mean prolongation by factor 2 compared to Insulin glargin (lGlar).This may enable for a more flexible daytime dosing versus up to now available basal insulins. METHOD: Two open, randomized, treat-to-target studies enrolled patients with type 1 diabetes (n =493) or type 2 diabetes (n = 687). Both phase 3 studies compared a daytime flexible dosing of IDeg (IDeg-flex) with IDeg at the evening meal (IDeg-evening) and IDler at a fixed daytime. In the IDeg-flex-group dosing intervals were predefined with variations between 8 and 40 hours. RESULTS: In patients with type 1 diabetes IDeg-flex proved to be non-inferior with respect to reduction of HbA1C (-0.40%) versus IDeg-evening (-0.41%) and IGlar (-0.58%) after 26 weeks. In addition, nocturnal hypoglycemic events were reduced by 40% (p < 0.01) with IDeg-flex versus IGlar. In patients with type 2 diabetes reduction of HbA1C with ID)eg-flex (-1.28%) was non-inferior to IDeg-evening (-1.07%) and IGlar (-1.26%), respectively, whereas rates for hypoglycemia were comparable. CONCLUSION: Patients with diabetes mellitus are enabled to dose a basal insulin flexibly when needed (minimum interval of 8 hours afterthe last injection is necessary). Impacts of this treatment option on quality of life and adherence and outcomes should be examined in observational trials.

The TGF-ß-Smad3 pathway inhibits CD28-dependent cell growth and proliferation of CD4 T cells.

Transforming growth factor-ß (TGF-ß) maintains self-tolerance through a constitutive inhibitory effect on T-cell reactivity. In most physiological situations, the tolerogenic effects of TGF-ß depend on the canonical signaling molecule Smad3. To characterize how TGF-ß/Smad3 signaling contributes to maintenance of T-cell tolerance, we characterized the transcriptional landscape downstream of TGF-ß/Smad3 signaling in resting or activated CD4 T cells. We report that in the presence of TGF-ß, Smad3 modulates the expression of >400 transcripts. Notably, we identified 40 transcripts whose expression showed Smad3 dependence in both resting and activated cells. This 'signature' confirmed the non-redundant role of Smad3 in TGF-ß biology and identified both known and putative immunoregulatory genes. Moreover, we provide genomic and functional evidence that the TGF-ß/Smad3 pathway regulates T-cell activation and metabolism. In particular, we show that TGF-ß/Smad3 signaling dampens the effect of CD28 stimulation on T-cell growth and proliferation. The impact of TGF-ß/Smad3 signals on T-cell activation was similar to that of the mTOR inhibitor Rapamycin. Considering the importance of co-stimulation on the outcome of T-cell activation, we propose that TGF-ß-Smad3 signaling may maintain T-cell tolerance by suppressing co-stimulation-dependent mobilization of anabolic pathways.

Vesicular transfer of membrane components to bovine epididymal spermatozoa.

Epididymosomes (apocrine secreted epididymal vesicles) are assumed to play a crucial role in sperm maturation. Our aim has been to analyze the fusogenic properties of bovine epididymosomes and their involvement in the transfer of membrane components (lipids, proteins, plasma membrane Ca(2+)-ATPase 4 [PMCA4]) into bovine sperm. The fusogenic properties of epididymosomes with spermatozoa were investigated in vitro by using octadecyl rhodamine-B (R18)-labeled epididymosomes. Spermatozoa isolated from the epididymal caput showed a higher fusion rate than those taken from the cauda. The fusion rate was dependent on pH and time. Furthermore, the lipid and protein content in spermatozoa changed during epididymal transit and after in vitro fusion with epididymosomes. Following the in vitro fusion of caput spermatozoa with epididymosomes, the cholesterol/total phospholipid ratio of the sperm plasma membrane decreased. The effect was comparable with the cholesterol/total phospholipid ratio of native cauda spermatozoa. Co-incubation experiments of spermatozoa with biotinylated epididymosomes additionally revealed that proteins were transferred from epididymosomes to sperm. To examine the potential transfer of epididymis-derived PMCA4 to spermatozoa, immunofluorescence analysis and Ca(2+)-ATPase activity assays were performed. In caput spermatozoa, the PMCA4 fluorescence signal was slightly raised and Ca(2+)-ATPase activity increased after in vitro fusion. Thus, our experiments indicate significant changes in the lipid and protein composition of epididymal sperm following interaction with epididymosomes. Moreover, our results substantiate the presumption that PMCA4 is transferred to spermatozoa via epididymosomes.

[Assessment of contrast vision by the Mars letter contrast sensitivity test - which illumination should be used?]. / Bestimmung des Kontrastsehens mit der MARS-Tafel - bei welcher Beleuchtung?

BACKGROUND: For expert opinions on mesopic and contrast vision as stipulated in the recent version of the German driving licence regulations (2011), a standardised implementation of the relevant test method is crucial. DIN 58220, part 7, regulates the assessment of mesopic vision and the required parameters of evaluation are guaranteed by the respective test instruments. Because no standard exists for photopic contrast vision, it is recommended that it conform to that of DIN EN ISO 8596 for visual acuity. For test equipment with integrated viewing fields, the application of such tests may not be difficult. But if visual charts are used the question of standardised illumination arises. The present paper investigates this question when using the Mars Letter Contrast Sensitivity Test in the light of the recommendations by the producer to use a desk lamp for illumination. METHODS: The Mars Chart was illuminated by three different commercially available desk lights from different directions at a distance of 50 cm, which is the test distance recommended by the producer. The luminance distribution was measured on the chart at twelve equally distributed test points. RESULTS: For all conditions, the asymmetric illumination produced by a single light source leads to an extremely inhomogeneous luminance distribution over the chart. Adherence to the tolerance ranges for brightness, as well as the homogeneity of illumination from such light sources is left to chance and a subjective judgment of both parameters is not adequate. CONCLUSION: Illumination of the Mars Chart with a desk light only does not necessarily satisfy the requirement of reproducible test conditions that is mandatory for expert evaluations. For comparable test outcomes for contrast vision, illumination devices that produce a uniform illumination should be employed.

[Assessment of mesopic and contrast vision for driving licences: which cut-off values, which methods are appropriate?]. / Untersuchung des Dämmerungs- und Kontrastsehens nach Fahrerlaubnisverordnung: Welche Grenzwerte, welche Verfahren sind geeignet?

BACKGROUND: Hitherto recommendations and thresholds for contrast tests are available for mesopic but not for photopic methods. While mesopic tests are widespread in ophthalmology, in occupational medicine photopic contrast tests are often used. With regard to the attachment 6 of the German Fahrerlaubnisverordnung (FeV) which is relevant since July 2011 we tested the specificity and sensitivity as well as the test-retest reliability of available test devices and defined cut-off values. METHODS: We examined patients with medium opacities, healthy volunteers and a sample of employees. Optovist EU, Binoptometer 4P and Pelli-Robson charts with standardised illumination were applied for contrast sensitivity testing. All these methods were compared to the Mesotest II as gold standard. We followed the recommendations of the German Qualitätssicherungs-Kommission der Deutschen Ophthalmologischen Gesellschaft (DOG) for contrast vision testing and definition of cut-off values. RESULTS: 64 patients with cataract (age 42-70 years, median 62 years), 50 pilots (age 40-69 years, median 53.5 years) and 109 employees of a transportation company (age 40-59 years, median 50 years) were included in the trial. All contrast sensitivity tests showed a good sensitivity and specificity (AUC 0.86 to 0.99). For Optovist EU and Binoptometer 4P a threshold of 15 % Weber contrast is recommended for examinations according to FeV. The test-retest reliability was high in all methods with highly significant Pearson correlation coefficients of 0.77 to 0.94 and a repeatability coefficient between 0.08 und 0.4. The standard distance of 1 m common for the Pelli-Robson chart cannot be recommended for FeV examinations, while the results at 3 m distance are comparable to those of the other contrast vision tests. The preliminary cut-off for the Pelli-Robson chart at 3 m distance is 1.65. CONCLUSIONS: Cut-off values for the lawful assessment of applicants are now available. Both Binoptometer 4P and Optovist EU proved to be appropriate and - as expected due to comparable technical properties - the same cut-off can be recommended. At 1 m distance the Pelli-Robson chart is not sensitive enough. Because the new distance of 3 m for the Pelli-Robson chart was investigated in 55 cataract patients and 10 pilots in this trial, a confirmatory trial for this distance is planned.

Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function.

AIMS: The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy. METHODS: Forty-four patients with Type 2 diabetes were included in the study. Main inclusion criteria were: pretreatment with metformin on a stable dosage, HbA(1c) < 53 mmol/mol (7.0%), age 30-65 years. Patients were randomized to receive additional liraglutide or to remain on metformin monotherapy. After 6 weeks (1.2 mg) and after 12 weeks (1.8 mg), venous blood was taken for the measurement of several laboratory markers characterizing vascular and endothelial function. In addition, retinal microvascular endothelial function and arterial stiffness were measured. RESULTS: HbA(1c) levels declined from 45 ± 4 mmol/mol (6.3 ± 0.4%; mean ± SD) to 40 ± 3 mmol/mol (5.8 ± 0.3%) during liraglutide treatment. Asymmetric dimethylarginin was reduced by liraglutide treatment from 0.39 ± 0.08 to 0.35 ± 0.06 µmol/l, E-selectin from 43.6 ± 15.4 to 40.8 ± 15.1 ng/ml, plasminogen activator inhibitor 1 from 861.6 ± 584.3 to 666.1 ± 499.4 ng/ml and intact proinsulin from 9.0 ± 7.2 to 7.0 ± 4.8 pmol/l at 12 weeks of treatment. The microvascular response to flicker light increased from 7.0 ± 15.1 to 15.4 ± 11.5% after 6 weeks and to 11.1 ± 9.9% after 12 weeks. No change could be observed for high-sensitivity C-reactive protein, monocyte chemotactic protein 1, vascular cell adhesion molecule or arterial stiffness parameters. CONCLUSIONS: In patients with Type 2 diabetes, well controlled with metformin monotherapy, addition of liraglutide improves several cardiovascular risk markers beyond glycaemic control.

[Glaucoma screening by means of pupil campimetry]. / Glaukomerkennung mittels der Pupillenkampimetrie.

BACKGROUND: The aim of the study was to find out if pupillographic assessment of the visual field by means of pupil campimetry can identify glaucomatous visual field defects and as such be used for glaucoma screening purposes. PATIENTS AND METHODS: 20 patients with open angle glaucoma and 30 healthy persons were examined by means of pupil campimetry. All glaucoma patients had a glaucomatous visual field defect in at least one eye. The stimulus pattern consisted of 17 white-light stimuli which were presented within the 30° visual field, particularly in the Bjerrum region. The stimulus diameter was 6°. Each stimulus was presented for 200 ms and the interval between the stimuli was 1800 ms. Three stimulus intensities (16.4 cd/m2; 27.1 cd/m2 and 40.5 cd/m2) were tested. The individual pupil light reaction (PLR) amplitudes at all examined locations in the visual field, their sums and partial sums were compared between both groups by the two-sided two-sample t test. The diagnostic performance of the method in glaucoma diagnosis was evaluated by ROC curves (receiver operating characteristics). RESULTS: The average PLR at all locations in the visual field was reduced in glaucoma patients compared to healthy persons. The sums of the PLR were reduced in glaucoma patients as well. Significant differences in the PLR were found especially in the central and paracentral visual fields. The best AUC values (area under the curve) were reached with the highest stimulus intensity, the highest AUC value overall was 0.769. CONCLUSION: Although the difference in PLR between glaucoma patients and the control group was significant, the reached AUC values fell short of being ideal for screening purposes. A surprising finding was that the most central pupil response was reduced by the same amount as that in the Bjerrum region.

[Once daily insulin detemir in patients with type 2 diabetes: results of German centers in a 6-month international observational study (SOLVE)]. / Einmal täglich Insulin detemir bei Patienten mitTyp-2-Diabetes. Ergebnisse deutscher Zentren aus einer 6-monatigen internationalen Beobachtungsstudie (SOLVE).

BACKGROUND: Hypoglycemic risk and improved glycemic control have to be weightened when a decision on intensification of treatment of type 2 diabetes mellitus with basal insulin is made. Findings from randomized studies are available in this respect, and should be complemented by data from routine treatment. METHODS: The international, prospective, open-label, observational study SOLVE (Study of Once-Daily Levemir) investigated add-on treatment with basal insulin in type 2 diabetes mellitus using once daily insulin detemir in patients currently receiving oral antidiabetic drugs (OAD). Data were collected between initiation of insulin treatment and the final visit after approximately 24 weeks. The primary objective of the study was to evaluate the incidence of serious adverse drug reactions (SADR), including major hypoglycemic events. RESULTS: In Germany, 2,090 patients were eligible for the full analysis set and 1,671 patients for the effectiveness analysis set. The mean age was 64.9 years, mean duration of diabetes 9.36 years, and mean duration of OAD treatment 7.29 years. Three patients (0.14%) experienced a SADR (1 fall resulting in death, 2 major hypoglycemic events). At the final visit, there was a significant reduction in major hypoglycemic events if compared with the period before starting insulin treatment (0.002 versus 0.120 events per patient year, p < 0.001), as were minor hypoglycemic events (0.880 versus 1.588 events per patient year, p = 0.006). The mean body weight and BMI decreased by -0.9 kg (p < 0.001) and-0.35 kg/m2 (p < 0.001) respectively and the mean HbA(1c) level improved from 8.45 +/- 1.19% to 7.30 +/- 0.92% (-1.15 +/- 1.08%; p < 0.001). The mean fasting plasma glucose level and plasma glucose variability were significantly reduced. CONCLUSION: Baseline data of the study underline the need for earlier intensification of antidiabetic therapy in type 2 diabetes in Germany. Study results show that within the German diabetes care system, initiation of basal insulin therapy with insulin detemir is able to result in significant HbA(1c) improvements without increased risk of hypoglycemia and/or weight gain.

A systematic review/meta-analysis of primary research investigating swine, pork or pork products as a source of zoonotic hepatitis E virus.

The objectives of our study were to identify and categorize primary research investigating swine/pork as a source of zoonotic hepatitis E virus (HEV) using the relatively new technique of scoping study, and to investigate the potential association between human exposure to swine/pork and HEV infection quantitatively using systematic review/meta-analysis methodology. From 1890 initially identified abstracts, 327 were considered for the review. Five study design types (cross-sectional, prevalence, genotyping, case-report and experimental transmission studies) were identified. A significant association between occupational exposure to swine and human HEV IgG seropositivity was reported in 10/13 cross-sectional studies. The association reported between pork consumption and HEV IgG seropositivity was inconsistent. The quantification of viral load in swine and retail pork, viral load required for infection in primates, cohort and case-control studies in humans, and formal risk assessment are recommended before specific public-health policy actions are taken.

[Relative afferent pupillary defect in glaucoma]. / Relativer afferenter Pupillendefekt bei Glaukom.

BACKGROUND: The aim of this retrospective study was to estimate the frequency of relative afferent pupillary defect (RAPD) in glaucoma and whether its occurrence relates to the severity of the visual field defect and its side asymmetry as detected by standard automated perimetry. PATIENTS AND METHODS: Among patients with primary open angle glaucoma examined at the glaucoma unit of our university eye hospital patients were identified in whom a swinging-flashlight test as part of their routine examination was carried out. The central 30° visual field was examined by means of static perimetry using the Tübinger Automatic Perimeter or the Octopus Perimeter. The visual field findings and their side difference were compared between patients with and without RAPD by means of the Wilcoxon rank-sum test. RESULTS: After having taken into consideration the inclusion criteria, 100 glaucoma patients were included in the study, 34 of them had an RAPD (34 %). For the visual field analysis only the data of 85 patients, who received the same perimetric strategy, were used. 25 of them had an RAPD (29 %). The calculated visual field scores in patients with RAPD were significantly higher than those in patients without RAPD (p < 0.01), that means their visual field loss was generally more advanced. Also the side difference in visual field of both eyes was significantly greater in patients with RAPD (p < 0.01). A receiver operating characteristics (ROC) curve showed that the side difference in visual field defect is a good predictor for RAPD with an area under curve (AUC) of 0.81. CONCLUSION: RAPD can be diagnosed in about one third of patients with primary open angle glaucoma. It can be found especially with more advanced visual field defects and visual field defects with greater side asymmetry. Its absence does not mean that there is no visual field defect at all. We advise to include the swinging-flashlight test in glaucoma diagnostics.

Recent and historical pollution legacy in high altitude Lake Marboré (Central Pyrenees): A record of mining and smelting since pre-Roman times in the Iberian Peninsula.

We have analyzed potential harmful trace elements (PHTE; Pb, Hg, Zn, As and Cu) on sediment cores retrieved from lake Marboré (LM) (2612 m a.s.l, 42°41'N; 0° 2'E). PHTE variability allowed us to reconstruct the timing and magnitude of trace metal pollutants fluxes over the last 3000 years in the Central Pyrenees. A statistical treatment of the dataset (PCA) enabled us to discern the depositional processes of PHTE, that reach the lake via direct atmospheric deposition. Indeed, the location of LM above the atmospheric boundary layer makes this lake an exceptional site to record the long-range transport of atmospheric pollutants in the free troposphere. Air masses back-trajectories analyses enabled us to understand the transport pathways of atmospheric pollutants while lead isotopic analyses contributed to evaluate the source areas of metal pollution in SW Europe during the Late Holocene. PHTE variability, shows a clear agreement with the main exploitation phases of metal resources in Southern Europe during the Pre-Industrial Period. We observed an abrupt lead enrichment from 20 to 375 yrs CE mostly associated to silver and lead mining and smelting practices in Southern Iberia during the Roman Empire. This geochemical data suggests that regional atmospheric metal pollution during the Roman times rivalled the Industrial Period. PHTE also increased during the High and Late Middle Ages (10-15th centuries) associated to a reactivation of mining and metallurgy activities in high altitude Pyrenean mining sites during climate amelioration phases. Atmospheric mercury deposition in the Lake Marboré record mostly reflects global emissions, particularly from Almadén mines (central Spain) and slightly fluctuates during the last three millennia with a significant increase during the last five centuries. Our findings reveal a strong mining-related pollution legacy in alpine lakes and watersheds that needs to be considered in management plans for mountain ecosystems as global warming and human pressure effects may contribute to their future degradation.

Arrangement of PMCA4 in bovine sperm membrane fractions.

The plasma membrane Ca(2+) -ATPase (PMCA) is the main restorer of Ca(2+) balance in sperm. Particularly, PMCA isoform 4 has an essential function in sperm fertility by its participation in gaining sperm hypermotility. PMCA activity is influenced by its lipid environment. Sperm membranes exhibit lipid raft microdomains or detergent-resistant membrane domains, enriched in sphingolipids and cholesterol, forming functional specialized areas. Lipid and protein composition of lipid rafts alters during the capacitation process, which is characterized by a cholesterol efflux. In this study, the localization of PMCA4 in lipid membrane fractions of the sperm plasma membrane was investigated. We identified PMCA4 in both the detergent-resistant membrane (DRM) and in the detergent-soluble (DS) fraction of caput and cauda sperm, respectively. Capacitation did not influence PMCA4 localization. In immunocytochemical studies PMCA4 was co-localized with the lipid raft/DRM marker caveolin in the mid piece of caput and cauda sperm. Functional studies with seminal vesicle major protein PDC-109 showed that the Ca(2+) -ATPase activity in DS fractions of cauda sperm and capacitated cauda sperm was stronger enhanced than in the DRMs. In both fractions the effect was statistically significant. In contrast, in lipid overlay experiments PDC-109 interacted stronger with the lipids extracted from DRMs than with lipids extracted from DS. Our results indicate a possible functional compartmentalization of PMCA in bull sperm membranes and point to a presumptive, yet unknown interaction partner of Ca(2+) -ATPase and PDC-109, mediating the PDC-109 action from DRMs to the DS fraction of sperm plasma membrane.

[The eye of the inner clock - pupil research in a new light]. / Das Auge der Inneren Uhr - Pupillenforschung in neuem Licht.

BACKGROUND: Pupillary research has received a new impetus since the discovery of the melanopsin containing ganglion cell subpopulation ipRGC (intrinsically photosensitive retinal ganglion cells). These specific ganglion cells have a maximum spectral sensitivity at 480 nm and affect predominantly the day-night cycle (inner clock) and the pupil reaction. They control above all the adjustment of the pupil width during continuous lighting, as well as during particularly bright and above all short wavelength light. Our results from blind patients with retinitis pigmentosa also showed clear pupil light reactions when examined with standard pupillographic equipment (CIP, AMTech, Dossenheim) with a yellow stimulus. These results are difficult to explain with the previous hypotheses. Up till now, there have been only few investigations in groups of patients with ophthalmological diseases. These studies indicate that with modified pupillographic stimuli, a clear distinction between lesions of the outer and inner retina is possible. METHODS: It is of interest for future applied pupillary research to ascertain how the pupillary light reaction alters with the wavelength, duration and intensity of the light stimulus. For such studies it is necessary not only to use well-defined spectral stimuli but also to develop special recording techniques and methods of analysis. CONCLUSIONS: It is to be expected that the results of such research will have consequences not only for the differential diagnosis of pathologies of the outer and inner retina, but also on the functional testing of retinal implants. This article gives an overview of the current state of knowledge.