High-sensitivity cardiac troponin T in young, healthy adults undergoing non-cardiac surgery.

BACKGROUND: It is unclear if isolated postoperative cardiac-troponin elevation, often referred to as myocardial injury, represents a pathological event, as control studies in otherwise healthy adults are lacking. METHODS: In this single-centre prospective observational cohort study, serial high-sensitivity cardiac troponin T (hscTnT) plasma concentrations were obtained from young, healthy adults undergoing elective orthopaedic surgery at three time points: before operation, 2-6 h, and 18-30 h after surgery. End points were hscTnT increases after surgery: ≥20% (exceeding analytical variability), ≥50% (exceeding short-term biological variability), and ≥85% (exceeding long-term biological variability). The secondary end point was myocardial injury, defined as new postoperative hscTnT elevation >99th % upper reference limit (URL) (women >10 ng litre-1; men >15 ng litre-1). RESULTS: Amongst the study population (n=95), no hscTnT increase ≥20% was detected in 68 patients (73%). A hscTnT increase between 20% and 49% was observed in 17 patients (18%), 50-84% in seven patients (7%), and ≥85% in three patients (3%). Twenty patients (21%) had an absolute ΔhscTnT between 0 and 2 ng litre-1, 12 patients (13%) between 2 and 4 ng litre-1, three patients between 4 and 6 ng litre-1, and one patient (1%) between 6 and 8 ng litre-1. Myocardial injury (new hscTnT elevation >99th%) was diagnosed in one patient (1%). The median hscTnT concentrations did not increase after operation, and were 4 (3.9-5, inter-quartile range) ng litre-1 at baseline, 4 (3.9-5) ng litre-1 at 2-6 h after surgery, and 4 (3.9-5) ng litre-1 on postoperative day 1. CONCLUSIONS: One in four young adult patients without known cardiovascular disease developed a postoperative hscTnT increase, but without exceeding the 99th% URL and without evidence of myocardial ischaemia. These results may have important ramifications for the concept of postoperative myocardial injury, as they suggest that, in some patients, postoperative cardiac-troponin increases may be the result of a normal physiological process in the surgical setting. CLINICAL TRIAL REGISTRATION: NCT 02394288.

Osteoarthritis in morbidly obese children and adolescents, an age-matched controlled study.

PURPOSE: Main objective of this study was to investigate the association of pain and early cartilage lesions in morbidly obese children and adolescents. METHODS: A total of 57 subjects were included in the study. Morbidly obese patients (n = 39) were subdivided into two groups: Group A: (11 males and 9 females, 14.2 ± 2.7 years) with permanent knee pain; and Group B: (10 males and 9 females, 14.4 ± 2.2 years) without permanent or without any knee pain. Group C (8 males and 10 females, 15.0 ± 2.9 years) included age-matched children and adolescents of normal weight. MRI examinations were performed in all subjects, and an extensive analysis of the images was conducted according to the condition of the cartilage surface and the meniscus. Patients' subjective health was assessed by means of four well-known knee scores (IKDC, KOOS, Tegner/Lysholm, and VAS). Nonparametric Jonckheere-Terpstra test was used to test the trend of the natural order between the three groups. RESULTS: In 38 of 39 morbidly obese children and adolescents, in at least one region of the knee, a marked cartilage lesion could be shown by MRI. Group A showed significantly (p < 0.001) more cartilage lesions (mean 3.7) compared to Group B (mean 2.8) and Group C (mean 0.8). IKDC, and all the KOOS subunits, showed significantly (p < 0.001, p Bonferroni < 0.001) increasing scores from Group A to B to C, in addition to KOOS symptoms. CONCLUSIONS: Morbid obesity causes early lesions of the knee cartilage, even in young patients. Significantly, more patients with reported pain show more severe damages.

The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue.

OBJECTIVE/BACKGROUND: Matrix metalloproteinases (MMPs) play a pivotal role in the development and progression of abdominal aortic aneurysms (AAAs). The action of MMPs depends on a balance between tissue inhibitors of MMPs (TIMPs) and compounds that may prolong protease activity, such as neutrophil gelatinase-associated lipocalin (NGAL). METHODS: The study was designed to analyse gene expression and protein concentration of MMPs, TIMPs, and NGAL in AAA walls and intraluminal thrombi (ILTs) of patients on simvastatin (n = 10) and not on statins (n = 10). The patients were matched by age, sex, and AAA diameter. Expression of MMP2, MMP9, TIMP1, TIMP2, and NGAL was investigated by real time polymerase chain reaction, and MMP2, MMP9, MMP9/TIMP1, MMP9/TIMP2, and MMP9/NGAL protein levels by enzyme-linked immunosorbent assay. RESULTS: MMP2 and MMP9 protein and mRNA levels were comparable in the simvastatin and non-statin groups (p > .05); however, there was a significant decrease in TIMP1 mRNA in AAA tissue (p = .04). Moreover, a significant increase in MMP9/TIMP2 complex concentration in ILTs of patients on simvastatin was noted (median 94.71 ng/mL in the simvastatin group vs. 36.80 ng/mL in the non-statin group; p = .01). No significant difference was observed for NGAL mRNA or protein content in AAA and ILT. CONCLUSION: Simvastatin treatment in patients with AAAs may influence the concentration of proteases and their inhibitors (TIMPs) in aneurysmal wall tissue and ILTs. Thus, further studies should be undertaken to understand the different influence of statin therapy on the components of the MMP/TIMP system in AAAs and ILTs.

The multigene signature MammaPrint impacts on multidisciplinary team decisions in ER+, HER2- early breast cancer.

BACKGROUND: Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER(+), HER2(-) early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations. METHODS: We prospectively recruited 75 ER(+), HER2(-) breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness. RESULTS: The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients, discordance between clinical and molecular risk was observed. Decision changes were recorded in half of these cases (18.6%) and resulted in two out of three patients not requiring chemotherapy. The use of MP was also found to be more cost effective. CONCLUSIONS: The multigene signature MP revealed clinical and molecular risk discordance in a third of patients. The impact of this on MDT recommendations was most profound in cases where few clinical risk factors were observed and enabled some women to forgo chemotherapy. The use of MGS is unlikely to have an impact in either clinically low-risk women or in patients with more than one relative indication for chemotherapy.

Decreased tissue levels of cyclophilin A, a cyclosporine a target and phospho-ERK1/2 in simvastatin patients with abdominal aortic aneurysm.

BACKGROUND: Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown. MATERIAL AND METHODS: The study was performed on AAA wall-tissue samples obtained from 30 simvastatin-treated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. RESULTS: The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression. CONCLUSION: Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA.

Monitoring neutrophils and platelets during casein-induced anaphylaxis in an experimental BALB/c mouse model.

BACKGROUND: With respect to the cellular players, mast cells and basophils have been well studied in experimental murine systemic anaphylaxis models, but the role of neutrophils and platelets is not fully understood today. OBJECTIVE: We tested the hypothesis that neutrophils and platelets might participate in an antigen-induced anaphylaxis model. METHODS: BALB/c mice were sensitized intraperitoneally with alum-adsorbed casein. A period of 2 weeks later, mice were challenged with 100 µg casein intravenously and immediate hypersensitivity reactions were assessed by rectal temperature measurements and monitoring the physical activity. Subsequently, leucocytes were counted in the peripheral blood as well as quantified in situ in typical shock organs like lung, liver and spleen, heart and kidney. RESULTS: Mice sensitized with casein showed casein-specific IgG1, IgE, and IgG2a. When sensitized mice were specifically challenged with casein they developed immediate hypersensitivity reactions including drop of temperature and reduced activity. Furthermore, pronounced peripheral neutropenia and reduced platelet counts correlated with the severity of the hypersensitivity reactions. In the histological analyses of collected tissues we observed lung interstitial neutrophilia using Gr-1 staining. These events occurred specifically in mice sensitized and challenged with casein, in contrast to control groups. CONCLUSIONS: On the basis of our data we suggest that in addition to mast cells and basophils, neutrophils and platelets participate in the anaphylactic response in this BALB/c mouse model. Platelet and neutrophils expressing relevant immunoglobulin receptors may therefore have a synergistic effect with allergen specific IgE as well as IgG antibodies in food-induced anaphylaxis. We suggest that management of these cells could be of clinical importance to handle anaphylaxis.

Simvastatin decreases free radicals formation in the human abdominal aortic aneurysm wall via NF-κB.

OBJECTIVES: Statins have been reported to suppress the progression of abdominal aortic aneurysm (AAA). However, the effects of statins on inflammatory processes and free radicals generation are poorly understood. METHODS: Wall samples from 51 patients (simvastatin patients, n = 34; non-statin patients, n = 17; matched by sex, age and aneurysm size) subjected to elective open AAA repair were analysed. We examined the effects of simvastatin on lipid peroxidation (4-hydroxy-trans-2-nonenal (4-HNE)), hydrogen peroxide (H(2)O(2)), tumour necrosis factor alpha (TNF-α) concentration, superoxide dismutase (SOD) and catalase (CAT) activity as well as nuclear factor kappa B (NF-κB) pathway activation in human AAA wall samples. RESULTS: Treatment with simvastatin resulted in a decrease in 4-HNE and TNF-α concentration (median 4.18 µg/mg protein vs. 4.75, p = 0.012; median 10.33 pg/ml vs. 11.81, p = 0.026, respectively). CAT activity was higher in the simvastatin group (median 3.98 U ml vs. 3.19, p = 0.023). NF-κB expression was lower (p = 0.018) in the simvastatin group. However, simvastatin had little effect on H(2)O(2) concentration (p = 0.832) and SOD activity (p = 0.401). CONCLUSION: Simvastatin inhibits free radicals and TNF-α generation and improves antioxidant capacity of human AAA wall tissue, possibly through the suppression of NF-κB activity. This may be one possible explanation how statins can inhibit AAA oxidative stress.

Comparison of PHMB-containing dressing and silver dressings in patients with critically colonised or locally infected wounds.

OBJECTIVE: This study compares treatment with a polihexanide-containing biocellulose wound dressing (BWD+PHMB) versus the best local standard of silver dressings (Ag) in painful, critically colonised (wounds-at-risk) or locally-infected wounds. METHOD: Patients with wounds of various aetiologies, a baseline VAS pain score >4 and a semi-quantitative bacterial load of ++ or higher were randomly allocated to receive treatment with either BWD+PHMB or Ag. Patients with systemic infections and/or using systemic antibiotics were excluded. The primary endpoint, patient-reported pain (VAS total pain, including the sub-scores pain at night, during the day, before, and 15min after dressing changes), was compared between treatment groups and scored on days 0, 1, 3, 7, 14, 21 and 28. Secondary outcomes of bacterial load, wound bed and periwound skin condition, quality of life and dressing handling were assessed at the same visits. RESULTS: Thirty-eight patients (BWD+PHMB, n=21 [24 wounds]; Ag, n=17 [18 wounds]) were included in the analyses. Baseline variables showed no significant differences. Wound pain was reduced significantly in both groups, with a better pain reduction noted for BWD+ PHMB (p<0.001) before dressing changes. Compared with Ag, in the BWD+PHMB group critical colonisation and local wound infection had been reduced significantly faster and better (p<0.001) over the 28-day study period. Improved quality of life, good tolerability and no adverse events were demonstrated for both groups. CONCLUSION: Both BWD+PHMB and AG were effective in reducing pain and bacterial burden. However, that BWD+PHMB was significantly faster and better in removing the critical bacterial load, makes this dressing an attractive therapeutic option to treat critically colonised and locally-infected wounds.

Emotional associations with skin: differences between burned and non-burned individuals.

INTRODUCTION: The appearance of skin is crucial for our physical and psychological integrity, and is strongly associated with our emotional self-awareness. Burn victims have to cope with negative and even threatening sensations resulting from the changed appearance of their skin after injury and also linked to experiences during the treatment. The aim of this study was to analyse differences regarding the emotional associations with skin in burn victims (burn group) to persons not having subdued any burn (control group). METHODS: In the first instance over 960 volunteers were recruited for the rating of emotional associations with skin in the control group and thereby a representative profile for non-injured individuals. In the second part, 44 burn patients of the Vienna Burn Center answered the same questionnaire. The quantitative rating of emotional associations with skin was performed with a newly designed questionnaire using a semantic differential on eight dimensions with a 5-point scale system. RESULTS: Both groups have positive associations with skin. One significant difference (p=0.0090, Chi-square test for trend) was the overall rating of the item "importance": for burn victims skin is more "important" than for controls. Patients with visible burns tended to put more emphasize on the possible exposure to danger ("threatened") of skin, and patients with >/=20% TBSA rated skin as more "noticeable" and "strong" as compared to small burns (<20% TBSA). Patients with burns to the face, hands and neck ("visible burns") were more likely to judge skin as threatened item. DISCUSSION: Our poll suggests that despite long treatment, rehabilitation and even near-death experiences burn patients continue to have positive associations with skin. This in turn, should encourage all specialists dealing with burns to engage in a continuous follow-up as well as enhance psychological and social support.

Reduced hands-off-time and time to first shock in CPR according to the ERC Guidelines 2005.

BACKGROUND AND AIM: Chest compressions and early defibrillation are crucial in cardiopulmonary resuscitation (CPR). The Guidelines 2005 brought major changes to the basic life support and automated external defibrillator (BLS-AED) algorithm. We compared the European Resuscitation Council's Guidelines 2000 (group '00) and 2005 (group '05) on hands-off-time (HOT) and time to first shock (TTFS) in an experimental model. METHODS: In a randomised, cross-over design, volunteers were assessed in performing BLS-AED over a period of 5min on a manikin in a simulated ventricular fibrillation cardiac arrest situation. Ten minutes of standardised teaching and 10min of training including corrective feedback were allocated for each of the guidelines before evaluation. HOT was chosen as the primary and TTFS as the secondary outcome parameter. RESULTS: Forty participants were enrolled; one participant dropped out after group allocation. During the 5-min evaluation period of adult BLS-AED, HOT was significantly (p<0.001) longer in group '00 [273+/-3s (mean+/-standard error)] than in group '05 (188+/-3s). The TTFS was significantly (p<0.001) longer in group '00 (91+/-3s) than in group '05 (71+/-3s). CONCLUSION: In this manikin setting, HOT and TTFS improved with BLS-AED performed according to Guidelines 2005.

Intraoperative frozen section analysis for breast-conserving therapy in 1016 patients with breast cancer.

OBJECTIVE: We evaluate the number of surgical two-stage procedures after FSA during breast-conserving therapy (clinical false negative result of FSA) and investigate the influence of microcalcifications, small tumour diameter, neoadjuvant therapy and preoperative biopsy on the clinical false negative rate of FSA. SUBJECTS: We retrospectively examined 1016 patients after intraoperative FSA during breast-conserving therapy for breast cancer operated between 1995 and 2001 at the Medical University Vienna. RESULTS: Only 9% of all patients had to undergo a two-stage operation due to a false negative intraoperative FSA result. The annual local recurrence rate was 1.2% in all patients with no difference between one- and two-stage operated patients. In situ and pT1 lesions were similarly distributed between one-stage and two-stage operated patients. The use of neoadjuvant therapy and stereotactic biopsy (reflecting non-palpable lesions and microcalcifications) were significantly predictive for a false negative FSA result. The use of a preoperative core biopsy, however, reduced the necessity of performing a two-stage operation. CONCLUSION: Our study demonstrates that FSA leads to a low rate of two-stage operations. Small lesions and microcalcifications as well as the occurrence of intraductal cancer cells and neoadjuvant therapy increased while preoperative core biopsy reduced the false negative rate of FSA. Overall local recurrence rates after FSA were acceptable.

Prediction of non-sentinel node status and outcome in sentinel node-positive melanoma patients.

AIMS: Sentinel lymph node (SLN) -positive melanoma patients are usually recommended completion lymph node dissection (CLND) with the aim to provide regional disease control and improve survival. Nevertheless, only 20% these patients have additional metastases in non-sentinel lymph nodes (NSLN), indicating that CLND may be unnecessary in the majority of patients. In this retrospective study, we (i) sought to identify clinico-pathological features predicting NSLN status, as well as disease-free (DFS) and -specific (DSS) survival and (ii) evaluated the applicability of previously published algorithms, which were able to define a group of patients at zero-risk for NSLN-metastasis. METHODS: This analysis included 504 consecutive melanoma patients stage I and II who underwent successful SLN-biopsy (SLNB) at our institute between 1998 and 2005. Metastatic SLN were re-evaluated for tumor burden and categorized according to two different micro-anatomic classifications and the S/U-score (Size of the sentinel node metastasis > 2 mm/Ulceration of the primary melanoma) was assessed. DFS and DSS were calculated for all analyses. RESULTS: Out of 504 melanoma patients stage I or II, 85 (17%) were SLN-positive and 18 of 85 (21%) were found with positive NSLN in the CLND specimen. Median follow-up was 31 months. Neither primary tumor characteristics (age, gender, Clark level, Breslow thickness, ulceration of the primary melanoma, site and histological subtype of the primary melanoma), nor features of the sentinel node tumor (number and site of draining lymph node basins, number of positive sentinel nodes and size of sentinel node tumor (< 2 mm vs. > or = 2 mm) were able to predict additional positive lymph nodes in the CLND specimen. Likewise the implementation of published algorithms was not able to identify patients at negligible risk for harboring NSLN metastases. Upon univariate analysis, disease-free survival in SLN-positive patients was correlated with Breslow thickness, sentinel node tumor size > 2 mm and S/U score. In respect to disease-specific survival the significant prognostic parameters were Breslow thickness, ulceration, sentinel node tumor size > 2 mm and the S/U score. After a median follow-up of 31 months recurrence rates (37% vs. 78%, p=0.02) and death from disease (24% vs. 50%, p<0.01) were significantly different in patients with SLN-metastasis only as compared to patients with NSLN-metastasis. CONCLUSION: NSLN status cannot be predicted in this data analysis by using clinico-pathological characteristics. Therefore, CLND is recommended for all patients after positive SLNB pending the results of the second Multicenter Selective Lymphadenectomy Trial.

Death in correctional facilities: opportunities for automated external defibrillation.

BACKGROUND: Death due to cardiovascular disease occurs more frequently in prisons than the national average. Due to close surveillance 24 h/day, the ability to reach the patient within 3 min and time consuming access for the EMS crews, it was hypothesised that the deployment of automated external defibrillators (AEDs) might make improvements regarding Call-to-the-First-AED-Prompt (CTP) interval and formed the aim of this study. METHODS: Our investigation was analysed on an intention to treat basis and conducted in a prospective, open and observational design. As the primary outcome, the CTP-intervals were compared to the arrival intervals of the EMS. As a secondary outcome, an analysis of all deceased inmates was described. RESULTS: The average daily population of inmates in Austrian correctional facilities is 7714. During a period of 13 months, 10 instances in which an AED was activated and electrodes attached to a collapsed inmate, were reported. The CTP-interval (median+/-S.D.) was 2.3+/-1.6 S.D. min. It took the EMS 10.0+/-4.3 S.D. min. to arrive at the patient's side. Four out of 10 cases of cardiac arrest occurred due to myocardial infarction. Of 39 deceased inmates, a post mortem examination was completed in 34 cases. In 13 cases, cardiovascular disease was the cause of death. DISCUSSION: The main finding was a four-fold reduction of the CTP-interval. This fact indicates the potential improvements which could be achieved with the deployment of AEDs. Our secondary objective revealed that death due to cardiovascular disease was found in a high proportion and could be considered to be a strong incentive to initiate programmes to counter cardiovascular death in prison.

Practical impact of the European Resuscitation Council's BLS algorithm 2005.

BACKGROUND: The European Resuscitation Council (ERC) guidelines 2005 have brought major changes in the BLS algorithm. The aim of our investigation was to look for the practical impact of these modifications. METHODS: In a randomized cross-over design we evaluated how adults would adhere to the BLS algorithm of the ERC guidelines 2000 (group A) compared to the guidelines 2005 (group B). The secondary endpoint was to determine the amount of time that elapsed before the start of the chest compressions in the two different groups. Participants were recruited from the streets and an office building of the Austrian Red Cross and were randomized to commence either with A or B. The volunteers were taught the allocated BLS sequence according to their group placement, and before evaluation each of the two groups was given the opportunity to train until they felt confident in using the algorithm. Performance during evaluation was documented automatically with a recording resuscitation manikin (Resusci-Anne, Skill Reporter). RESULTS: Sixty people were included in the study, one individual dropped out after randomisation. In group A 9/59 (15.25%) participants followed the algorithm correctly versus 24/59 (40.68%) in group B (p=0.006). The time to start of chest compressions was significantly shorter in group B (21.31+/-7.11s), compared to group A (36.68+/-11.75s, p<0.01). CONCLUSION: Compared to the 2000 BLS algorithm, the 2005 BLS sequence seems to be easier to learn and to retain, though nearly 60% of participants did not follow the new algorithm correctly. As expected, there was a significantly shorter time elapsing before the start of chest compressions when applying the 2005 algorithm. These findings should translate to better survival after cardiac arrest.

Early detection of preeclampsia by determination of platelet aggregability.

Preeclampsia is still a leading cause of maternal and fetal morbidity and mortality. There is evidence for the involvement of platelets. Therefore, we investigated the suitability of corrected whole blood impedance aggregometry as an early predictor of preeclampsia in 71 consecutive, high-risk pregnancies. According to the occurrence of preeclampsia, defined postpartum by an independent investigator, and the stage of pregnancy (early and late, cutoff: 25 weeks of gestation), four study groups were defined. Platelet aggregation data were corrected for the influence of hematocrit and platelet count by a special purpose software package. Women developing preeclampsia showed significantly higher platelet aggregation response compared to controls in early and late pregnancy. In early pregnancy, all women developing preeclampsia had aggregation responses to collagen higher than the highest responses among the controls. Hence, this test had a 100% positive predictive value of subsequent preeclampsia. Despite being significantly increased, platelet aggregability was of minor predictive value in late pregnancy. We conclude that preeclampsia is accompanied by exaggerated platelet aggregability, particularly perceptible early in the course of pregnancy. We propose collagen-induced whole blood platelet aggregation with correction for the influence of hematocrit and platelet count for early detection of preeclampsia.

The role of magnetic resonance imaging in routine decision making for meniscal surgery.

This clinical study evaluated factors affecting the decision for meniscal surgery in a patient population seen routinely at a trauma clinic. The study hypothesis was that patients who sustain a traumatic injury to the knee or have a long history of clinical symptoms are likelier to be operated on. We investigated 149 patients clinically and by magnetic resonance imaging (MRI). Group A (n = 62) underwent arthroscopic surgery and group B (n = 87) were treated conservatively. Multiple logistic regression analysis was used to examine correlations with regard to age, gender, injury pattern, period between the injury and first clinical examination, and MRI results. We found no significant difference between the two groups with regard to gender (P = 0.1), injury pattern (P = 0.44), or period between injury and first clinical examination (P = 0.5). Patients in group A were significantly older than those in group B (P = 0.044), and, as expected, MRI signal alterations were significantly higher in group A than in group B (P = 0.001). In acutely injured patients MRI helps to establish an accurate diagnosis, and in cases of positive MRI findings in a symptomatic patient, the surgeon should not wait 4-6 weeks but should immediately recommend surgery.

Anterior cruciate ligament reconstruction alters the patellar alignment.

Although there are many articles dealing with anterior cruciate ligament (ACL) reconstruction, there are none dealing with the possibility of changes of the patellofemoral alignment after these procedures. Forty-six patients were evaluated preoperatively and 1 year postoperatively, after undergoing intra-articular ACL reconstruction, for changes of the patellofemoral alignment. Patella-tilt and congruence angles were measured on tangential view radiographs that were taken in the supine position. Analysis of covariance was performed and revealed a significant change of the congruence angle 1 year postoperatively. The patella-tilt did not change. One year postoperatively, the patella shifted on average 5 degrees medially after ACL grafting. It can be deduced that anterior knee pain after ACL reconstruction could be caused by distinct changes in the patellofemoral alignment.

Immunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression.

Cytokines play a pivotal role in the pathogenesis of septic shock. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) stimulate the progression of septic shock whereas the anti-inflammatory cytokine IL-10 has counterregulative potency. The amino acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF-alpha production. In the current study we investigated the role of GLY on lipopolysaccharide (LPS) -induced cell surface marker expression, phagocytosis, and cytokine production on purified monocytes from healthy donors. GLY did not modulate the expression of HLA-DR and CD64 on monocytes, whereas CD11b/CD18 expression (P<0.05) and E. coli phagocytosis (P<0.05) decreased significantly. GLY decreased LPS-induced TNF-alpha production (P<0.01) and increased IL-10 expression of purified monocytes. Similarly, in a whole blood assay, GLY reduced TNF-alpha (P<0.0001) and IL-1beta (P<0.0001) synthesis and increased IL-10 expression (P<0.05) in a dose-dependent manner. The inhibitory effects of GLY were neutralized by strychnine, and the production of IL-10 and TNF-alpha was augmented by anti-IL-10 antibodies. Furthermore, GLY decreased the amount of IL-1beta and TNF-alpha-specific mRNA. Our data indicate that GLY has a potential to be used as an additional immunomodulatory tool in the early phase of sepsis and in different pathophysiological situations related to hypoxia and reperfusion.

Diagnostic value of tissue polypeptide-specific antigen (TPS) in neuroblastoma and Wilms' tumour.

Although tissue polypeptide-specific antigen (TPS) has been described as a potentially useful serum marker of tumour activity in adult epithelial tumours, few data are available for childhood malignancies. Neuroblastomas and Wilms' tumours are the commonest types of solid malignancies found in the retroperitoneum of children. At this time, a widely used marker for Wilms' tumour is not available. Using an enzyme-linked immunosorbent assay (ELISA) kit, serum TPS levels in 23 children with neuroblastomas, nine with Wilms' tumours and 22 with benign tumours were evaluated to test the usefulness of the marker in identifying malignancies. Compared with healthy children (n = 110), the preoperative least-square means (LSM) of serum TPS were considerably elevated in both neuroblastoma (LSM = 209 U l(-1)) and Wilms' tumour (LSM = 235 U l(-1)), whereas values in benign tumours were only slightly elevated. Although the Wilms' tumours were associated with higher preoperative serum TPS levels, there was no statistically significant difference compared with neuroblastomas. Receiver operating characteristic analysis (ROC curves) showed a high sensitivity and specificity for both malignancies. Successful treatment resulted in decrease in TPS serum values. Serum TPS measurements in children presenting with abdominal masses can help in diagnosing the two commonest extracranial solid malignancies of childhood. Furthermore, TPS could acquire a pivotal role in monitoring therapy.

It is possible to omit postoperative irradiation in a highly selected group of elderly breast cancer patients.

The purpose of this study was the evaluation of the necessity of routinely applied postoperative radiotherapy in a highly selected patient-group after breast conserving surgery. Between 1983 and May 1994, 356 women over 60 years of age with Stage I or II breast cancer were treated by quadrantectomy and axillary dissection followed by either adjuvant irradiation or no radiotherapy. We have analysed our data retrospectively to investigate whether irradiation has any benefit in elderly patients with respect to locoregional recurrence rates. After a median follow-up of 60 months the multivariate model revealed lymph node status (p = 0.002) as highly significant with regard to local recurrence free survival. We were not able to identify a positive effect of adjuvant irradiation in patients with negative lymph nodes and positive receptor status: both patient groups with or without irradiation had similar locoregional recurrence rates of 3%. In a subgroup of patients who were lymph node negative, receptor positive, and received adjuvant tamoxifen therapy, the local recurrence rates were as low as 2% in both groups. Concerning these results it may be possible to avoid the morbidity and potential psychological side effects of radiotherapy in breast cancer patients over 60 years of age treated by breast conserving surgery (T1, N0, positive hormone receptor, adjuvant tamoxifen) without increasing risk of locoregional recurrence. These data have to be confirmed in a prospectively randomized fashion.