Epigallocatechin 3-gallate suppresses interleukin-1ß-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats.

Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n = 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1ß, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n = 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB.

[Thromboprophylaxis and platelet aggregation inhibitors in spinal surgery: perioperative management]. / Thromboseprophylaxe und Aggregationshemmer in der Wirbelsäulenchirurgie: perioperative Management.

BACKGROUND: The perioperative use of anticoagulants (AC) and platelet aggregation inhibitors (PAI) in the field of spinal surgery suggests an increased rate of epidural bleeding. However, evidence is lacking and these medications are most often indispensable in the prevention of thromboembolic complications. Comprehensive recommendations for the correct use of AC and PAI are lacking. OBJECTIVE: The aim of this study was an analysis of the current situation with regards to the use of AC and PAI in spinal surgery and development of new recommendations. MATERIAL AND METHODS: Two independent surveys on the perioperative use of AC and PAI were obtained from centers for spinal surgery in Germany. The study obtained information on the perioperative use of AC and PAI, risk assessment of thromboembolic and hemorrhagic events as well as on the type and extent of the substance groups used. RESULTS: Almost the entire patient collective (98%) received perioperative low molecular weight heparin. In 64% the medical prophylaxis was started before surgery and in 36% after surgery. The period of prophylaxis was determined arbitrarily. Approximately 40% of interviewees employed paravertebral infiltration and 19% injected into the epidural space in patients on PAI medication. Open spinal canal surgery was performed in 30% of PAI medicated patients and closed spinal canal surgery was executed in 40%. The risk assessment of PAI differed significantly between aspirin and receptor blocker medication as well as dual administration of PAI. DISCUSSION: The use of AC and PAI in spinal surgery in Germany is very heterogeneous and large deviations from the guidelines frequently occurred. Therefore, there is a strong need for further studies to accurately assess the perioperative use of AC and PAI and to formulate precise recommendations.

[On the relevance of the official lists for notified products and measures for disinfection, disinfestation and control of vertebrate pests ordered by an authority on the legal basis of § 18 IfSG (German Protection against Infection Act)]. / Zur Bedeutung der Listen bekannt gemachter Mittel und Verfahren für behördlich angeordnete Entseuchungen, Entwesungen und zur Bekämpfung von Wirbeltieren auf Grundlage des § 18 Infektionsschutzgesetz.

In order to protect human health against communicable diseases, the German Protection against Infection Act (IfSG) requires the use of officially approved products and methods for officially ordered disinfection, disinfestation (control of arthropods) as well as measures for the management of vertebrate pests that spread pathogens. Official approval is granted by registration in lists published by the responsible federal health authorities and only for products and methods that have been tested and found to be sufficiently effective and do not have an unacceptable impact on health and the environment (§ 18 IfSG). It is not compulsory for manufacturers to have their products and methods listed in accordance with § 18 IfSG. In particular listing is not a prerequisite for access to the German market. Users are free to choose a product as long as no officially ordered measure, i.e. disinfection, disinfestation or measures against vertebrate pests, according to § 18 IfSG applies. However, it is highly recommended to use approved products included in the abovementioned lists even for routine application, as these registered products and methods have been tested, i.e. the efficacy has been proven by means of specific, recognized and quality assured testing procedures or by expert reports which have been confirmed by independent institutions.

QTL detection power of multi-parental RIL populations in Arabidopsis thaliana.

A major goal of today's biology is to understand the genetic basis of quantitative traits. This can be achieved by statistical methods that evaluate the association between molecular marker variation and phenotypic variation in different types of mapping populations. The objective of this work was to evaluate the statistical power of quantitative trait loci (QTL) detection of various multi-parental mating designs, as well as to assess the reasons for the observed differences. Our study was based on an empirical data of 20 Arabidopsis thaliana accessions, which have been selected to capture the maximum genetic diversity. The examined mating designs differed strongly with respect to the statistical power to detect QTL. We observed the highest power to detect QTL for the diallel cross with random mating design. The results of our study suggested that performing sibling mating within subpopulations of joint-linkage mapping populations has the potential to considerably increase the power for QTL detection. Our results, however, revealed that using designs in which more than two parental alleles segregate in each subpopulation increases the power even more.

Nonenhanced ECG-gated quiescent-interval single-shot MRA (QISS-MRA) of the lower extremities: comparison with contrast-enhanced MRA.

AIM: To evaluate electrocardiogram (ECG)-gated quiescent-interval single-shot magnetic resonance angiography (QISS-MRA) for nonenhanced assessment of peripheral artery occlusive disease (PAOD) using contrast-enhanced MRA (CE-MRA) as the reference standard. MATERIALS AND METHODS: Twenty-seven patients (mean age 66.6 ± 10.8 years) with PAOD were included in the study. QISS-MRA and CE-MRA of the lower extremity were performed using a 1.5 T MR scanner. In each patient, subjective image quality and the degree of stenosis were evaluated on a four-point scale for 15 predefined arterial segments. RESULTS: Twenty-five of the 27 patients were considered for analysis. Subjective image quality of QISS-MRA was significantly lower for the distal aorta, pelvic arteries, and femoral arteries as compared to CE-MRA (p < 0.01), while no significant difference was found for other vascular segments. The degree of stenosis was overestimated with QISS-MRA in 23 of 365 (6.3%) segments and underestimated in two of 365 (0.5%) segments. As compared to CE-MRA, QISS-MRA had a high sensitivity (98.6%), specificity (96%) as well as positive and negative predictive value (88.7 and 99.6%, respectively) for the detection of significant stenosis (≥50%). CONCLUSION: ECG-gated QISS-MRA is a promising imaging technique for reliable assessment of PAOD without the use of contrast material.

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1ß treated human intervertebral disc cells.

INTRODUCTION: Increased levels of proinflammatory cytokines seem to play a pivotal role in the development of back pain in a subpopulation of patients with degenerative intervertebral disc (IVD) disease. As current treatment options are mostly limited to surgical interventions or conservative treatment, anti-inflammatory substances might offer a novel, more target-orientated therapeutic approach. Triptolide (TPL), a natural substance found in the Chinese medicinal herb Tripterygium wilfordii Hook, has been demonstrated to possess anti-inflammatory effects in various cells, but no studies exist so far for the IVD. Therefore, the aim of this study was to determine the effects of TPL on human IVD cells by analyzing changes in gene expression and underlying molecular mechanisms. MATERIALS AND METHODS: In order to investigate the anti-inflammatory, anabolic and anti-catabolic effect of TPL, dose-dependency experiments (n = 5) and time course experiments (n = 5) were performed on IL-1ß prestimulated human IVD cells and changes in gene expression of IL-6/-8, TNF-α, PGE2S, MMP1/2/3/13, aggrecan and collagen-I/-II were analyzed by real-time RT-PCR. The molecular mechanisms underlying the effects observed upon TPL treatment were investigated by analyzing involvement of Toll-like receptors TLR2/4 (real-time RT-PCR, n = 5), NF-κB, MAP kinases p38, ERK and JNK (immunoblotting and immunocytochemistry, n = 4) as well as RNA polymerase II (immunoblotting, n = 3). RESULTS: Results showed that 50 nM TPL exhibited an anti-inflammatory, anti-catabolic and anabolic effect on the mRNA level for IL-6/-8, PGE2S, MMP1/2/3/13, aggrecan, collagen-II and TLR2/4, with most pronounced changes after 18 h for proinflammatory cytokines and MMPs or 30 h for TLRs and matrix proteins. However, we also observed an up-regulation of TNF-α at higher concentrations. The effects of TPL did not seem to be mediated via an inhibition of NF-κB or a decrease of RNA polymerase II levels, but TPL influenced activity of MAP kinases p38 and ERK (but not JNK) and expression of TLR2/4. CONCLUSIONS: In conclusion, TPL may possess promising potential for the treatment of inflammation-related discogenic back pain in vitro, but its analgetic effect will need to be confirmed in an appropriate in vivo animal model.

Evaluation of a structured report of functional prostate magnetic resonance imaging in patients with suspicion for prostate cancer or under active surveillance.

BACKGROUND: Functional magnetic resonance imaging (MRI) seems to be a useful tool for prostate cancer (PCa) detection in patients with a previous negative biopsy but persistently increased prostate-specific antigen (PSA) values. Additionally, it enables correct cancer localization in patients with known PCa under active surveillance to avoid misclassification on repeat biopsies. Nevertheless, suspicious lesions on MRI findings need verification by biopsy. The aim of the present study was to establish a standardized functional prostate MRI reporting scheme. METHODS: Prostate MRI with T(2)-weighted images, T(1)-weighted images, diffusion-weighted imaging, and dynamic contrast-enhanced MRI of 56 consecutive patients were performed on a 3-T scanner. Patients with prior negative random transrectal ultrasound (TRUS)-guided biopsy and continuous suspicion for PCa as well as patients under active surveillance were included. The MRI localization report of suspicious lesions followed a standardized scheme. TRUS-guided random biopsy with addition of targeted biopsy cores was performed afterwards based on the structured report. RESULTS: Of the 56 patients, 18 had suspicious MRI findings and subsequently underwent repeat biopsy under guidance of the standardized localization scheme. PCa was documented in 72% (13/18). CONCLUSIONS: A standardized reporting scheme of suspicious findings on prostate MRI leads to higher success rates as compared to standard random TRUS-guided biopsy.

Spinal surgery for gallstones disease - Case report of a rare differential diagnosis.

INTRODUCTION AND IMPORTANCE: Abdominal pain in the right upper quadrant is very common for patients to present in the emergency department. Finding the correct diagnosis seems straightforward in most cases but can be challenging. CASE PRESENTATION: We present the case of a 75-year-old male with a rare differential diagnosis for right upper quadrant and back pain, initially diagnosed as symptomatic cholelithiasis. After referral to an abdominal surgeon, detailed history taking prior to planned cholecystectomy revealed a record of back pain due to spinal degeneration and fusion surgery, as well as a bulb of the right abdominal wall with hypesthesia in a dermatomal area in the right upper quadrant. Considering these "new" facts, a spinal surgeon was consulted and a foraminal disc hernia of the thoracic vertebrae 11/12 was identified as the cause of symptoms. Instead of the initially planned cholecystectomy, a right-sided facetectomy Th11/12, sequestrectomy and unilateral transpedicular stabilization to decompress the nerve root was successfully performed. CLINICAL DISCUSSION: Although, symptomatic cholelithiasis is one of the most common diagnoses for patients presenting with right upper quadrant pain in the presence of gallstones, other differential diagnoses have to be considered. Thoracic disc herniations can present with atypical symptoms that mimic other non-spinal causes and may pose a diagnostic challenge, sometimes even leading to unnecessary surgery. CONCLUSION: This case highlights a rare differential diagnosis for one of the most common diseases seen by emergency physicians. It emphasizes the risk of working under time pressure, especially in an emergency setting, which may lead to premature diagnostic error and treatment, endangering patient's care and safety.

[Modern CT and PET/CT imaging of the liver]. / Moderne CT- und PET/CT-Bildgebung der Leber.

Computed tomography (CT) is now widely available and represents an important and rapid method for the diagnostics of acute liver disease, characterization of focal liver lesions, planning of interventional therapy measures and postintervention control. In recent years CT has not become less important despite the increasing value of magnetic resonance imaging (MRI). By the use of different contrast medium phases good characterization of space-occupying lesions can be achieved. For the diagnostics of hepatocellular carcinoma (HCC) a triphasic examination protocol should always be implemented. The introduction of dual energy CT increased the sensitivity of imaging of hypervascularized and hypovascularized liver lesions and by the use of virtual native imaging it has become possible to avoid additional native imaging which reduces the x-ray exposition of patients. Positron emission tomography (PET) has an advantage for imaging in oncology because nearly the complete body of the patient can be screened and this is the main indication for PET/CT (whole-body staging). For purely hepatic problems 18F-fluorodeoxyglucose (FDG)-PET/CT using diagnostic CT data has a higher precision than CT alone but is inferior to MRI.

Examination of computer assisted prescribing of an initial calculated antibiotic treatment.

The objective of this prospective clinical usage study was to examine the value of the rule based 'Therapeutic Assistant' integrated into an existing Patient Data Management System (PDMS) in helping to prescribe a initial antibiotic regime in accordance with the requirements of accepted guidelines. A prospective study comparing data before and after the introduction of the 'Therapeutic Assistant' was carried out. An adequate therapy resulted significantly more often after the introduction of the 'Therapeutic Assistant' [p<0.05]; however no difference between the regimes with and without the 'Therapeutic Assistant' in the period after its introduction could be established. Whether the 'Therapeutic Assistant' influenced the prescriptions made without it will have to be established in a further study.

Influence of extracellular osmolarity and mechanical stimulation on gene expression of intervertebral disc cells.

Intervertebral discs (IVD) have a higher extracellular osmolarity than most other tissues; moreover their osmolarity changes by around 25% during each diurnal cycle. In this study, changes in aggrecan, collagen I and collagen II expression of IVD cells were examined after exposure to osmotic environment alterations or mechanical stimulation under different osmotic conditions. Human and bovine IVD cells seeded in three-dimensional (3D) collagen type I matrices were cultured under hypo-osmotic (300 mOsm), iso-osmotic (400 mOsm), or hyperosmotic (500 mOsm) conditions. Osmolarity-induced changes in gene expression of IVD cells were measured after 5 days. Load-induced changes in gene expression under the different osmotic conditions were measured after application of hydrostatic pressure (0.25 MPa, 0.1 Hz, 30 min) or cyclic strain (4%, 1 Hz, 24 h). The results showed that IVD cells respond strongly to changes in the osmotic environment by altering mRNA expression. Human cells cultured over 5 days increased expression of aggrecan and collagen II in both nucleus and annulus cells under increasing osmolarity. In contrast, collagen I expression was inhibited at high osmolarity in both cell types. Mechanically induced alterations in gene expression appear to have only modest effects on matrix protein expression, but the same stimulus partly resulted in an inhibition or stimulation of gene expression, depending on the osmotic conditions. This study showed that the osmotic environment does not only have an appreciable effect on gene expression but also affects responses to mechanical stimuli. This suggests that the osmotic conditions cannot be ignored when examining physiological and pathological behavior of IVD cells.

Impact of different sampling strategies on score results of the Nine Equivalents of Nursing Manpower Use Score (NEMS).

OBJECTIVE: Prospective observational study to assess the impact of two different sampling strategies on the score results of the NEMS, used widely to estimate the amount of nursing workload in an ICU. METHODS: NEMS scores of all patients admitted to the surgical ICU over a one-year period were automatically calculated twice a day with a patient data management system for each patient day on ICU using two different sampling strategies (NEMS(individual): 24-hour intervals starting from the time of admission; NEMS(8 a.m.): 24-hour intervals starting at 8 a.m.). RESULTS: NEMS(individual) and NEMS(8 a.m.) were collected on 3236 patient days; 687 patients were involved. Significantly lower scores were found for the NEMS(8 a.m.) (25.0 +/- 8.7) compared to the NEMS(individual) (26.1 +/- 8.9, p < 0.01); the interclass correlation coefficient (ICC) was good but not excellent: 0.78. The inter-rater correlation between the two NEMS scores was high or very high (kappa = 0.6-1.0) for six out of nine variables of the NEMS. CONCLUSIONS: Different sampling strategies produce different score values, especially due to the end of stay. This has to be taken into account when using the NEMS in quality assurance projects and multi-center studies.

Inter-reader agreement of multi-parametric MR imaging for the detection of prostate cancer: evaluation of a scoring system.

PURPOSE: Functional prostate MR is performed in varying combinations of T2-weighted images with diffusion-weighted imaging (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and spectroscopic imaging (MRSI). Recently, a European consensus meeting proposed the use of a simple 5-point scale for estimating the probability of a lesion being malignant. The aim of the present study was to determine the inter-reader agreement of MR imaging using a scoring system based on the recommendations of the consensus. MATERIALS AND METHODS: The appearance of 108 predefined lesions in three different MR sequences (T2-weighted images, DWI, and DCE-MRI) in 50 functional prostate MR examinations were retrospectively scored by three blinded radiologists using a 5-point scale for each MR sequence. After scoring T2/DWI and T2/DWI/DCE-MRI, every lesion was graded based on its probability for malignancy. The inter-observer reliability was evaluated using Kappa statistics (ĸ). RESULTS: With respect to T2-weighted images, DWI and DCE-MRI ĸ was 0.49, 0.97, and 0.77, respectively. Combined scoring of T2-weighted images and DWI demonstrated correct tumor diagnosis (true positive) in 71-88% (depending on reader) of cases (ĸ=0.78). The accuracy was further improved to 88-96% after scoring all three MR sequences including DCE-MRI (ĸ=0.90). CONCLUSION: The use of a simple 5-point scoring system for T2-weighted images, DWI, and DCE-MRI is feasible in functional prostate MRI and has high inter-observer reliability.

[MR imaging of the abdomen in pregnancy]. / MR-Diagnostik des Abdomens in der Schwangerschaft.

Sonography is still the method of choice for imaging diseases in pregnant women. The changed physiognomy of the women increases the known limitations of sonography while the advantages of MRI (large field of view, excellent soft-tissue contrast, sensitive diagnosis of edema) are not affected. The available sequences allow the differentiation of various pathologies. Most of these can frequently be visualized without intravenous administration of contrast material. Although the significance of techniques like DWI and ASL has not yet been explored, initial descriptions are promising and MR imaging in pregnancy will be increasingly important in the future. Therefore, knowledge of the most frequent diseases in pregnancy and their image appearance is relevant to radiologists. The advantages of MRI in comparison to sonography and its important role in imaging pathologies of the acute abdomen in pregnancy are illustrated and discussed.

[Fornix rupture caused by a ureteral stone during pregnancy: non-contrast-enhanced MR urography]. / Harnleitersteinbedingte Fornixruptur in der Schwangerschaft : Kontrastmittelfreie MR-Urographie.

Fornix rupture during pregnancy is rare. To be able to initiate the optimal therapy it is important to distinguish the spontaneous fornix rupture from the rupture caused by an obstruction. We report on a patient in the 18th week of pregnancy with strong flank pain on the left side. By means of MR urography the diagnosis of a left fornix rupture due to an obstructive stone could be made. A double-J catheter was placed in the left ureter and the patient received oral antibiotics.

[Anesthesia and sleep apnea syndrome]. / Anästhesie und Schlaf-Apnoe-Syndrom.

The perioperative risk for patients with obstructive sleep apnea syndrome and the optimal anaesthesiological management of these patients have not been well elucidated. The prevalence of obstructive sleep apnea with significant symptoms is estimated to be 4% in men and 2% in women. However, in 80-95% of patients this syndrome is not sufficiently diagnosed. Thus identification of patients at risk and a thorough multidisciplinary diagnostic approach are essential for optimal perioperative management. The risk of perioperative complications, like cardiopulmonary compromise, and difficulties in airway management is elevated. The most important aspects of perioperative management include evaluation of intubating conditions, careful search for cardiopulmonary morbidity, permanent control of patient airways, sensible use of anaesthetics, sedatives, and narcotics, and strict monitoring of vital signs. If ambulatory nasal continuous positive airway pressure (CPAP) therapy has been established preoperatively, this should be continued in the perioperative period. Postoperative monitoring should be performed in an intensive care or intermediate care unit. Controlled clinical studies on the best perioperative management of patients with obstructive sleep apnea are urgently required.

Impact on postoperative pain of long-lasting pre-emptive epidural analgesia before total hip replacement: a prospective, randomised, double-blind study.

Clinical studies on pre-emptive analgesia have produced inconsistent results. We conducted a clinical study investigating the effect of long-lasting pre-emptive epidural analgesia on consumption of analgesics and acute pain. Forty-two patients scheduled for elective hip replacement for osteo-arthritis were randomly assigned to receive, on the day before operation, either 5 ml.h(-1) ropivacaine 0.2% (study group, n = 21) or 5 ml.h(-1) saline (control group, n = 21). Postoperative analgesia was achieved in both groups by patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2%. The main outcome measure was consumption of local anaesthetics. Additional parameters included visual analogue pain scale (VAS) scores, consumption of rescue analgesics, requests for PCEA boluses, and side-effects. The pre-operative parameters and pain scores were similar in the two groups. Epidural blocks provided sufficient operative analgesia in all patients. Pre-emptive analgesia was continued for 11-20 h and led to significantly decreased pain scores before surgery. The consumption of local anaesthetics was decreased postoperatively in the study group (194 mg vs. 284 mg in the postoperative period). Furthermore, bolus requests occurred more frequently in the control group. VAS scores did not differ significantly between groups. Long-lasting "pre-emptive" epidural analgesia decreases postoperative pain with improved pain control.

Shorter discharge time after regional or intravenous anaesthesia in combination with laryngeal mask airway compared with balanced anaesthesia with endotracheal intubation.

BACKGROUND AND OBJECTIVE: The efficiency of operating room times can be significantly improved using rapid changes between operative procedures. We performed a retrospective analysis using electronic anaesthesia charts that compared anaesthesia-related times between the three most frequently performed types of anaesthesia (for orthopaedic surgery) to evaluate the potential for a quicker turn-around between cases. METHODS: A total of 5614 anaesthetic procedures in trauma-related orthopaedic surgery were performed from 1997 to 1999. All were documented with an automatic record-keeping system. Data were compared for intravenous anaesthesia with the laryngeal mask airway, balanced anaesthesia with tracheal intubation and regional anaesthesia. The primary outcome measure was the time needed for emergence from anaesthesia after the end of surgery. Statistical evaluation was performed with matched triples for all three types of anaesthesia (155 triples for ambulatory surgery, 249 triples for in-patient care). RESULTS: For ambulatory surgery, the induction time was significantly shorter for general anaesthesia (23.7 min for intravenous anaesthesia, 22.7 min for balanced anaesthesia techniques) compared with regional anaesthesia (27.2 min). The time from the end of the surgical procedure to transfer of the patient out of the operating room was shortest for regional anaesthesia (6.3 min) compared with intravenous anaesthesia (9.0 min) and balanced anaesthesia (12.5 min) techniques. Results were comparable for in-patients: regional anaesthesia required significantly longer for its induction, but less time for patient discharge from the operating room. CONCLUSIONS: The use of a regional anaesthesia technique or one involving intravenous anaesthesia in combination with the laryngeal mask airway may lead to a reduction in discharge time compared with a balanced anaesthesia technique with endotracheal intubation. Thus, improved use of resources may be achieved.