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The formation of bacterial biofilms in the human body and on medical devices is a serious human health concern. Infections related to bacterial biofilms are often chronic and difficult to treat. Detailed information on biofilm formation and composition over time is essential for a fundamental understanding of the underlying mechanisms of biofilm formation and its response to anti-biofilm therapy. However, information on the chemical composition, structural components of biofilms, and molecular interactions regarding metabolism- and communication pathways within the biofilm, such as uptake of administered drugs or inter-bacteria communication, remains elusive. Imaging these molecules and their distribution in the biofilm increases insight into biofilm development, growth, and response to environmental factors or drugs. This systematic review provides an overview of molecular imaging techniques used for bacterial biofilm imaging. The techniques included mass spectrometry-based techniques, fluorescence-labelling techniques, spectroscopic techniques, nuclear magnetic resonance spectroscopy (NMR), micro-computed tomography (µCT), and several multimodal approaches. Many molecules were imaged, such as proteins, lipids, metabolites, and quorum-sensing (QS) molecules, which are crucial in intercellular communication pathways. Advantages and disadvantages of each technique, including multimodal approaches, to study molecular processes in bacterial biofilms are discussed, and recommendations on which technique best suits specific research aims are provided. [ABSTRACT FROM AUTHOR]

Background Context: Cervical disc replacement (CDR) aims to restore motion of the treated level to reduce the risk of adjacent segment disease (ASD) compared with spinal fusion. However, first‐generation articulating devices are unable to mimic the complex deformation kinematics of a natural disc. Thus, a biomimetic artificial intervertebral CDR (bioAID), containing a hydroxyethylmethacrylate (HEMA)—sodium methacrylate (NaMA) hydrogel core representing the nucleus pulposus, an ultra‐high‐molecular‐weight‐polyethylene fiber jacket as annulus fibrosus, and titanium endplates with pins for primary mechanical fixation, was developed. Purpose: To assess the initial biomechanical effect of the bioAID on the kinematic behavior of the canine spine, an ex vivo biomechanical study in 6‐degrees‐of‐freedom was performed. Study Design: A canine cadaveric biomechanical study. Methods: Six cadaveric canine specimens (C3‐C6) were tested in flexion‐extension (FE), lateral bending (LB) axial rotation (AR) using a spine tester in three conditions: intact, after C4‐C5 disc replacement with bioAID, and after C4‐C5 interbody fusion. A hybrid protocol was used where first the intact spines were subjected to a pure moment of ±1 Nm, whereafter the treated spines were subjected to the full range of motion (ROM) of the intact condition. 3D segmental motions at all levels were measured while recording the reaction torsion. Biomechanical parameters studied included ROM, neutral zone (NZ), and intradiscal pressure (IDP) at the adjacent cranial level (C3‐C4). Results: The bioAID retained the sigmoid shape of the moment‐rotation curves with a NZ similar to the intact condition in LB and FE. Additionally, the normalized ROMs at the bioAID‐treated level were statistically equivalent to intact during FE and AR while slightly decreased in LB. At the two adjacent levels, ROMs showed similar values for the intact compared to the bioAID for FE and AR and an increase in LB. In contrast, levels adjacent to the fused segment showed an increased motion in FE and LB as compensation for the loss of motion at the treated level. The IDP at the adjacent C3‐C4 level after implantation of bioAID was close to intact values. After fusion, increased IDP was found compared with intact but did not reach statistical significance. Conclusion: This study indicates that the bioAID can mimic the kinematic behavior of the replaced intervertebral disc and preserves that for the adjacent levels better than fusion. As a result, CDR using the novel bioAID is a promising alternative treatment for replacing severely degenerated intervertebral discs. [ABSTRACT FROM AUTHOR]

Environmental impact assessment (EIA) is implemented in most countries as an administrative procedure. In this context, it is subject to the principles of administrative justice. However, to date, no empirical research has been conducted to determine the extent to which EIA decisions comply with the principles of administrative justice. In this paper, empirical data from 42 EIA cases in South Africa are used to establish EIA compliance with the administrative justice principles of lawfulness, procedural fairness and reasonableness. This is achieved by measuring EIA decisions against specially developed key performance indicators (KPIs). Overall, decisions were found to mostly comply with the principles of administrative justice. However, questions arise with regards to the quality and substance of the information feeding into the decision-making process and on which decisions are ultimately based. [ABSTRACT FROM AUTHOR]

Aims: Previous studies have already shown early proximal ingrowth, fast osseous integration, and a stable fit of the uncemented Symax hip stem, with excellent clinical and radiographic performance. Aims were to evaluate cumulative revision rates and reasons for revision of the Symax hip stem using Dutch Arthroplasty Register (LROI) data and to assess possible associations between patient characteristics and revision rate of the Symax hip stem. Patients and methods: All total hip arthroplasties with the uncemented Symax hip stem registered in the LROI between 2007 and 2017 were included (n = 5,013). Kaplan-Meier survival analysis was performed to assess the cumulative 1, 5 and 7-year revision percentages. Cox proportional hazard regression analysis was performed to assess the association between patient and procedural characteristics, and revision arthroplasty of the stem. Results: Cumulative 1, 5, and 7-year revision rates (with 95% confidence interval (CI)) for revision of any component were 1.5% (CI 1.2%-1.8%), 3.2% (CI 2.7%-3.7%), and 3.8% (CI 3.1%-4.4%) respectively. Cumulative 1, 5, and 7-year stem revision rates of the Symax hip stem were 0.9% (CI 0.6%-1.1%), 1.5% (CI 1.1%-1.9%), and 1.7% (CI 1.3%-2.1%) respectively. Periprosthetic fractures (n = 35) and loosening of the stem (n = 30) were the most common reasons for revision of the stem. Revision of the stem was associated with acute fracture as primary diagnosis (Hazard Ratio (HR) 2.4 (CI 1.3–4.3)), or history of a previous surgery to the affected hip (HR 2.7 (CI 1.4–5.2)). Conclusion: This population-based registry study shows revision rates for the Symax hip stem comparable to those for best performing uncemented total hip arthroplasties in the Netherlands. Primary diagnosis of an acute fracture, and history of previous surgery on the affected hip, were significantly associated risk factors for revision of the Symax hip stem, and we discourage the use of the Symax hip stem in these patients. [ABSTRACT FROM AUTHOR]

Background: Chronic osteomyelitis is caused by bacterial infection of the bone and is a major problem in orthopaedic surgery. Treatment of chronic osteomyelitis requires surgical debridement accompanied by local and systemic administration of antibiotics. A widely established biodegradable local antibiotic carrier is antibiotic-loaded collagen sponges (fleeces). These sponges are commonly used in the treatment of chronic osteomyelitis, but a systematic review of their clinical efficacy and assessment of the quality of evidence have not been conducted, to our knowledge.Methods: This systematic review, performed according to the PRISMA statement, examined the clinical efficacy of and quality of evidence regarding different antibiotic-loaded collagen sponges in the clinical treatment of chronic osteomyelitis. Clinical efficacy was defined as eradication of infection with bone and wound-healing. In addition, the in vivo pharmacokinetics of the various collagen sponges were evaluated. Quality was based on the Level of Evidence, methodological quality, and risks of bias.Results: A total of 813 articles were screened, and 10 were included. Gentamicin-sulfate sponges and gentamicin-sulfate/gentamicin-crobefate sponges were studied. A total of 413 patients were treated, with a success rate of 91%. Reported complications were fistulas, prolonged wound drainage, and wound-healing problems. In vivo pharmacokinetic profiles showed an average local antibiotic concentration that was above the minimum inhibitory concentration for only 5 days. The general quality of the included studies was low to moderate, and there was a moderate to high risk of bias.Conclusions: The evidence quality and Level of Evidence of the included studies were low, and the risk of bias in these studies was high. This makes the evidence regarding these sponges inconclusive, and no clinical decision-making can be based on these studies. Utilization of antibiotic-loaded collagen sponges in the treatment of chronic osteomyelitis should only be carried out with caution; studies with high-level evidence are needed.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Summary: Background: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. Aim: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. Methods: A single‐arm, open‐label, multicentre, intrapatient dose‐escalation, phase 2 study with 4 phases: screening, 3‐month SC (subcutaneous), 3‐month IM (intramuscular) and 6‐month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3‐month SC phase. A ≥50% response rate was considered clinically relevant. Results: Forty‐three patients with late dumping were enrolled; 33 completed the 3‐month SC phase and 23 completed the 12‐month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%‐75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0‐12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). Conclusion: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. [ABSTRACT FROM AUTHOR]

In the field of orthopaedic surgery, bacterial invasion of implants and the resulting periprosthetic infections are a common and unresolved problem. Antimicrobial susceptibility testing methods help to define the optimal treatment and identify antimicrobial resistance. This review discusses proven gold-standard techniques and recently developed models for antimicrobial susceptibility testing, while also providing a future outlook. Conventional, gold-standard methods, such as broth microdilution, are still widely applied in clinical settings. Although recently developed methods based on microfluidics and microdroplets have shown advantages over conventional methods in terms of testing speed, safety and the potential to provide a deeper insight into resistance mechanisms, extensive validation is required to translate this research to clinical practice. Recent optical and mechanical methods are complex and expensive and, therefore, not immediately clinically applicable. Novel osteoblast infection and tissue models best resemble infections in vivo. However, the integration of biomaterials into these models remains challenging and they require a long tissue culture, making their rapid clinical implementation unlikely. A method applicable for both clinical and research environments is difficult to realise. With a continuous increase in antimicrobial resistance, there is an urgent need for methods that analyse recurrent infections to identify the optimal treatment approaches. [ABSTRACT FROM AUTHOR]

We developed a semi-automated algorithm for the detection of cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT). Here, we tested its reliability compared to microCT (µCT) as gold standard. Nineteen joints of 10 female anatomic index fingers were imaged by HR-pQCT and µCT (82 and 18 µm isotropic voxel sizes, respectively). The algorithm was applied for detection of cortical interruptions of different minimum diameters (range >0.16 to >0.50 mm). Reliability was tested at the joint level with intra-class correlation coefficient (ICC) for the number of interruptions and interruption surface, and at the level of a single interruption for matching between HR-pQCT and µCT with a fixed interruption diameter (>0.10 mm) on µCT. The positive predictive value (PPV0.10mm) and sensitivity0.10mm were evaluated. The mean number of interruptions per joint depended on the diameter cut-off and ranged from 3.4 to 53.5 on HR-pQCT and from 1.8 to 45.1 on µCT for interruptions >0.50 to >0.16 mm, respectively. Reliability at the joint level was almost perfect (ICC ≥0.81) for both the number and surface of interruptions >0.16 and >0.33 mm. As expected, the PPV0.10mm increased with increasing interruption diameter from 84.9 to 100%, for interruptions >0.16 and >0.50 mm, respectively. However, the sensitivity0.10mm decreased with increasing interruption diameter from 62.4 to 4.7%. This semi-automated algorithm for HR-pQCT in finger joints performed best for the detection of cortical interruptions with a minimum diameter of >0.16 or >0.33 mm, showing almost perfect reliability at the joint level and interruptions matched with those on µCT. [ABSTRACT FROM AUTHOR]

Background: Despite growing evidence in the literature, there is still a lack of consensus regarding the use of the mobile-bearing (MB) design total knee arthroplasty (TKA).Methods: In a prospective, comparative, randomised, single centre trial, 106 patients with end-stage osteoarthritis of the knee were randomised to either an MB or fixed-bearing (FB) group to receive posterior stabilised (PS)-TKA using a standard medial parapatellar approach and patellar resurfacing with follow-up (FU) for 5 years. The primary outcome was anterior knee pain (AKP) during the chair rise test and the stair climb test 5 years after surgery. The secondary outcome was the ability to rise from a chair and to climb stairs, range of motion (ROM), Knee Society Score (KSS), RAND-36 scores and radiological analysis of the patellar tilt.Results: No statistically significant difference was found between the two groups at 5 years FU in terms of median AKP during the chair rise test and the stair climb test (p = 0.5 and p = 0.8, respectively). There was no significant difference in any of the other secondary outcome parameters between the groups at 5 years FU.Conclusion: A mobile-bearing TKA does not decrease AKP compared to fixed bearings.Trial Registration Number: ClinicalTrials.gov NCT02892838 .Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Background: In inflammatory bowel disease (IBD), a new biological therapy has recently been approved. Vedolizumab is a humanised IgG1 monoclonal antibody to α4β7 integrin that modulates gut lymphocyte trafficking. Although an exclusively local effect of vedolizumab could be expected based on the restricted presence of the α4β7-mucosal vascular addressin cell adhesion molecule 1 complex in the gut, past combined success with anti-tumour necrosis factor, and previous demonstration of α4β7 integrin in the joint, led to the expectation of a therapeutic efficacy in spondyloarthritis. Nonetheless, the effect of vedolizumab on extraintestinal manifestations-and especially the joint-has not been reported so far.Case Report: A series of five patients with IBD who were treated with vedolizumab and promptly developed new onset or exacerbation of sacroiliitis or arthritis are reported.Conclusions: Vedolizumab therapy does not seem to show any efficacy in and might even induce arthritis and/or sacroiliitis. However, larger cohort studies are needed to provide information on the prevalence, the evolution and underlying mechanism. [ABSTRACT FROM AUTHOR]

Objectives: To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). Methods: Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. Results: The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. Conclusion: The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT. [ABSTRACT FROM AUTHOR]

Osteomyelitis is a common occurrence in orthopaedic surgery, which is caused by different bacteria. Treatment of osteomyelitis patients aims to eradicate infection by debridement surgery and local and systemic antibiotic therapy. Local treatment increases success rates and can be performed with different antimicrobial bone graft substitutes. This review is performed to assess the level of evidence of synthetic bone graft substitutes in osteomyelitis treatment. According to the PRISMA statement for reporting systematic reviews, different types of clinical studies concerning treatment of osteomyelitis with bone graft substitutes are included. These studies are assessed on their methodological quality as level of evidence and bias and their clinical outcomes as eradication of infection. In the fifteen included studies, the levels of evidence were weak and in ten out of the fifteen studies there was a moderate to high risk of bias. However, first results of the eradication of infection in these studies showed promising results with their relatively high success rates and low complication rates. Due to the low levels of evidence and high risks of bias of the included studies, these results are inconclusive and no conclusions regarding the performed clinical studies of osteomyelitis treatment with antimicrobial bone graft substitutes can be drawn. [ABSTRACT FROM AUTHOR]

Nowadays, S53P4 bioactive glass is indicated as a bone graft substitute in various clinical applications. This review provides an overview of the current published clinical results on indications such as craniofacial procedures, grafting of benign bone tumour defects, instrumental spondylodesis, and the treatment of osteomyelitis. Given the reported results that are based on examinations, such as clinical examinations by the surgeons, radiographs, CT, and MRI images, S53P4 bioactive glass may be beneficial in the various reported applications. Especially in craniofacial reconstructions like mastoid obliteration and orbital floor reconstructions, in grafting bone tumour defects, and in the treatment of osteomyelitis very promising results are obtained. Randomized clinical trials need to be performed in order to determine whether bioactive glass would be able to replace the current golden standard of autologous bone usage or with the use of antibiotic containing PMMA beads (in the case of osteomyelitis). [ABSTRACT FROM AUTHOR]

Natural antibodies (NAb) are defined as antibodies present in individuals without known antigenic challenge. Levels of NAb binding keyhole limpet hemocyanin (KLH) in chickens were earlier shown to be heritable, and to be associated with survival. Selective breeding may thus provide a strategy to improve natural disease resistance. We phenotyped 3,689 white purebred laying chickens for KLH binding NAb of different isotypes around 16 weeks of age. Heritabilities of 0.12 for the titers of total antibodies (IgT), 0.14 for IgM, 0.10 for IgA, and 0.07 for IgG were estimated. We also estimated high, positive genetic, and moderate to high, positive phenotypic correlations of IgT, IgM, IgA, and IgG, suggesting that selective breeding for NAb can be done on all antibody isotypes simultaneously. In addition, a relatively substantial non-genetic maternal environmental effect of 0.06 was detected for IgM, which may reflect a transgenerational effect. This suggests that not only the genes of the mother, but also the maternal environment affects the immune system of the offspring. Breaking strength and early eggshell whiteness of the mother’s eggs were predictive for IgM levels in the offspring, and partly explained the observed maternal environmental effects. The present results confirm that NAb are heritable, however maternal effects should be taken into account. [ABSTRACT FROM AUTHOR]

Background Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit ( HT) and pulse rate ( PR) and delayed hypoglycemia ( HG). Treatment is based on dietary measures and somatostatin analogs ( SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping. Methods Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47 ± 4 years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing ( OGTT), abdominal ultrasound, and dumping symptom severity score ( DSSS). Patients were treated for 2 weeks with placebo or pasireotide 300 μg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying ( GE) were obtained. Key Results Baseline OGTT was pathological in all patients based on PR ( n = 5), HT ( n = 1) or HG ( n = 7). Compared to placebo, pasireotide suppressed the increase in PR (17.1 ± 2.8 vs 8.2 ± 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 ± 4.3 vs 83.3 ± 9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 ± 33.3 vs 221.0 ± 23.1 mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 ± 23 vs 43 ± 9 min; p = 0.05) and liquids (t1/2 70 ± 10 vs 40 ± 4 min, p = 0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide. Conclusions & Inferences Pasireotide affects pathophysiological features of both early and late dumping syndrome. [ABSTRACT FROM AUTHOR]

Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Several studies have reported symptom relief in gastro-esophageal reflux disease (GERD) patients treated with radiofrequency delivery (Stretta procedure) at the gastro-esophageal junction (GEJ), but the mechanism underlying this improvement is unclear. The objective of this study was to test the hypothesis that Stretta alters GEJ resistance.METHODS:We conducted a double-blind randomized cross-over study of Stretta and sham treatment. Consecutive GERD patients were included in the study. The study was conducted in a tertiary care center. Patients underwent two upper gastrointestinal endoscopies with 3 months interval, during which active or sham Stretta treatment was performed in a randomized double-blind manner. Symptom assessment, endoscopy, manometry, 24-h esophageal pH monitoring, and a distensibility test of the GEJ were done before the start of the study and after 3 months.RESULTS:Barostat distensibility test of the GEJ before and after administration of sildenafil was the main outcome measure. In all, 22 GERD patients (17 females, mean age 47±12 years) participated in the study; 11 in each group. Initial sham treatment did not affect any of the parameters studied. Three months after initial Stretta procedure, no changes were observed in esophageal acid exposure and lower esophageal sphincter (LES) pressure. In contrast, symptom score was significantly improved and GEJ compliance was significantly decreased. Administration of sildenafil, an esophageal smooth muscle relaxant, normalized GEJ compliance again to pre-Stretta level, arguing against GEJ fibrosis as the underlying mechanism.CONCLUSIONS:The limitation of this study was reflux evaluation did not include impedance monitoring. In this sham-controlled study, Stretta improved GERD symptoms and decreased GEJ compliance. Decreased GEJ compliance, which reflects altered LES neuromuscular function, may contribute to symptomatic benefit by decreasing refluxate volume. [ABSTRACT FROM AUTHOR]

Background Rumination is an eating disorder clinically suspected in the presence of chronic regurgitation of recently ingested food with subsequent re-mastication and swallowing. Oesophageal manometry is currently used to confirm the diagnosis, however, it is difficult to distinguish rumination from postprandial belching-regurgitation, being the manometric pattern identical in both situations. Oesophageal impedance allows recognition between liquid and gas gastro-oesophageal reflux. Our aims were (i) to improve diagnosis of rumination using combined impedance–manometry (ii) to assess the gastro-oesophageal pressure-flow pattern in rumination events. Methods Sixteen patients with clinically suspected rumination underwent impedance–manometry monitoring for 1 h after a solid liquid meal. Manometry was first analysed blindly to the impedance pattern. All events marked by the patients and straining episodes were identified. After the manometric analysis, impedance tracings were unblinded and each straining episode was analysed for presence of liquid and/or gas oesophageal retrograde flow. Only rumination events were included for additional evaluation. Key results Postprandial manometry showed a pattern compatible with rumination in 12/16 patients. In total, impedance–manometry confirmed the clinical diagnosis of rumination in eight of the 16 patients with clinical suspicion of rumination. In 102 clearly identified rumination events, the onset of gastric strain (manometry) occurred before the onset of oesophageal liquid retroflow (impedance) in 58% of cases or simultaneously in 37% of cases. In most cases (86%), oesophageal retrograde flow started after an initial increase in abdominal pressure but before the peak gastric strain pressure. Conclusions & Inferences Postprandial impedance–manometry monitoring improves diagnosis of rumination because it allows distinction between rumination and postprandial belching and regurgitation. During rumination, oesophageal liquid retrograde flow is first driven by an early small rise in intragastric pressure preceding the peak pressure observed during straining. [ABSTRACT FROM AUTHOR]

The patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire was recently developed and validated for the evaluation of therapeutic responsiveness in functional dyspepsia (FD). Functional dyspepsia is a heterogeneous disorder, with different pathophysiological mechanisms underlying the symptom pattern. The relationship between PAGI-SYM scores and putative pathophysiological mechanisms has not been studied. The aim of this study was to evaluate the relationship between PAGI-SYM subscales and gastric emptying, gastric sensitivity and gastric accommodation in FD. A total of 161 consecutive FD patients underwent Helicobacter pylori (HP), gastric barostat and standardized gastric emptying testing ( n = 126), and completed the PAGI-SYM questionnaire. Relationships between scores for the six subscales (heartburn/regurgitation, nausea/vomiting, fullness/satiety, bloating, upper abdominal pain, lower abdominal pain) and gastric function were analysed using Pearson’s linear correlation, multiple regression analysis, chi-square and Student’s t-tests. Gastric emptying was significantly correlated with scores for heartburn/regurgitation ( r = 0.26), nausea/vomiting ( r = 0.19), fullness/satiety ( r = 0.20), bloating ( r = 0.21) and lower abdominal pain ( r = 0.22; all P < 0.05). Patients with delayed emptying had significantly higher scores for each of these subscales (all P < 0.05). Discomfort volume during gastric distension was significantly correlated with scores for fullness/satiety ( r = −0.27), bloating ( r = −0.23), heartburn/regurgitation ( r = −0.21), and upper abdominal pain ( r = −0.20). Patients with hypersensitivity to distension had significantly higher scores for fullness/satiety ( P < 0.05). At different cut-off levels of symptom severities, consistent associations were found between fullness/satiety and gastric discomfort volume, between preprandial volumes and upper abdominal pain, compliance and upper abdominal pain, and between bloating and gastric discomfort volume. Multiple regression analysis revealed that gastric emptying rate contributed significantly to models for the severity of these subscales. The importance of discomfort volume disappeared in favour of gender when sex was included in the model. No significant correlations were found with HP status or with gastric accommodation. PAGI-SYM scores are mainly correlated with gastric emptying rate and with gastric hypersensitivity. Multivariate analysis suggests that the questionnaire may be useful in the evaluation of gastroprokinetics. Its role in the evaluation of drugs that alter gastric sensitivity is less clear. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a B-cell malignancy, which often remains incurable because of the development of drug resistance governed by the bone marrow (BM) microenvironment. Novel treatment strategies are therefore urgently needed. In this study, we evaluated the anti-MM activity of JNJ-26481585, a novel 'second-generation' pyrimidyl-hydroxamic acid-based histone deacetylase inhibitor, using the syngeneic murine 5TMM model of MM. In vitro, JNJ-26481585 induced caspase cascade activation and upregulation of p21, resulting in apoptosis and cell cycle arrest in the myeloma cells at low nanomolar concentrations. Similar results could be observed in BM endothelial cells using higher concentrations, indicating the selectivity of JNJ-26481585 toward cancer cells. In a prophylactic and therapeutic setting, treatment with JNJ-26481585 resulted in an almost complete reduction of the tumor load and a significant decrease in angiogenesis. 5T2MM-bearing mice also developed a MM-related bone disease, characterized by increased osteoclast number, development of osteolytic lesions and a reduction in cancellous bone. Treatment of these mice with JNJ-264815 significantly reduced the development of bone disease. These data suggest that JNJ-26481585 has a potent anti-MM activity that can overcome the stimulatory effect of the BM microenvironment in vivo making this drug a promising new anti-MM agent. [ABSTRACT FROM AUTHOR]

Backgound and aims: A subset of functional dyspepsia (FD) patients report meal-related symptoms, possibly representing a pathophysiologically homogeneous subgroup. The aim of the present study was to establish the time-course of symptoms in relation to meal ingestion, and to assess the relationship between self-reported meal-related symptoms and pathophysiological mechanisms in FD. Methods: 218 FD patients (149 women, mean (SEM) age 39 (1) years) filled out a symptom questionnaire, including meal-induced aggravation. All patients underwent a gastric emptying breath test with severity (0-4) scoring of six symptoms (pain, fullness, bloating, nausea, burning and belching) at each sampling (15 mm interval for 4 h). In 129 patients, gastric sensitivity and accommodation were assessed by barostat. Results: The intensity of each FO symptom was significantly increased 15 mm after the meal, compared with the premeal score, and remained elevated until the end of the measurement period (all p

Background Radiofrequency (RF) energy delivery is an endoscopic procedure developed for the treatment of gastro-oesophageal reflux disease. Aim To compare RF and a proton pump inhibitor strategy (PPI) in PPI-dependent patients by carrying out a prospective, randomized trial. Methods Patients with PPI-dependent typical reflux symptoms were randomly allocated to either RF or PPI regimen alone. The primary endpoint, evaluated at 6-month, was defined as the possibility for the patient to stop or to decrease PPI use to <50% of the effective dose required at baseline. Results In the RF group, 18/20 patients stopped ( n = 3) or decreased ( n = 15) PPI use as compared to eight of 16 in the PPI group ( P = 0.01). None of the control patients could stop PPI. Health-related quality of life scores were not different between groups. No significant change in oesophageal acid exposure (OAE) was noted between baseline and 6-months after RF. No severe complication was reported. Conclusions Radiofrequency energy delivery is a safe and effective therapeutic option, allowing reduction in or discontinuation of PPI therapy in patients with PPI-dependent symptoms, without loss of quality of life. However, in a majority of patients, PPI therapy cannot be completely stopped. The efficacy of RF does not seem to be related to a decrease in OAE. [ABSTRACT FROM AUTHOR]

Aim: We conducted a prospective survey of the use, relationship to existing guidelines and outcome of empirical treatment by general practitioners (GPs) in gastroesophageal reflux disease (GERD) patients. Methods: In total 815 GPs completed a questionnaire on consecutive GERD patients in whom they started empirical therapy without additional investigation. Results: The study population included 4,177 patients (50.3% men, mean age 39.3 ± 11.0 years) without previous endoscopy presenting with typical GERD symptoms (96%). According to Belgian-French guidelines, endoscopic examination was recommended in 2,083 patients, but all received empirical therapy. Data were collected for 3,955 patients (94.7%) at 1-month follow-up; 3,360 patients (85.0%) were responders to empirical therapy (no symptoms during the last 7 days), which was not significantly influenced by the type of treatment. Presence of alarm symptoms (15.5%), alcohol consumption, failure of previous treatment or recurrence after previous treatment were significant predictors of nonresponsiveness to empirical therapy. Follow-up endoscopy in 521 patients showed reflux esophagitis in 70.6%, peptic ulcer in 5.9% and Barrett’s in 0.2%. Conclusions: Empirical treatment of typical symptomatic GERD by GPs is highly successful. Predictors of nonresponsiveness to empirical therapy are the presence of alarm symptoms, alcohol consumption and failure of or recurrence after a previous treatment. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) accelerate bone repair in experimental and clinical conditions. Impacted Morsellized Cancellous Bone grafts (MCB) are successfully used to reconstruct bone defects after failed hip implants. The main question in this study was if BMP‐7 (OP‐1) mixed with MCB could accelerate the incorporation of MCB and prevents the formation of a soft tissue interface after remodeling of the MCB. A large loaded defect in the acetabulum of goats was reconstructed with a wire mesh and with MCB or MCB mixed with OP‐1. After 6 weeks, no differences were found in the revascularization process, in the number of osteoclasts resorbing the MCB, and in the thickness and appearance of the fibrous interface between MCB with or without OP‐1. After 6 weeks, enchondral bone had formed in the bone graft layer and on the periosteal anterior and superior rim in the OP‐1 group only. More periosteal bone and more bone in the holes of the mesh had been formed in most OP‐1 goats. Most MCB was replaced by new lamellar bone after 15 weeks in both groups. We speculate that during or directly after impaction most of the OP‐1 is released from the carrier inducing an early effect outside the reconstructive layer at the periosteal side of the acetabulum. Probably most OP‐1 has left the reconstruction by the time new vessels and progenitors reached the bone graft. These results do not support the use of OP‐1 in impaction bone grafting in patients. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [ABSTRACT FROM AUTHOR]

R306465 is a novel hydroxamate-based histone deacetylase (HDAC) inhibitor with broad-spectrum antitumour activity against solid and haematological malignancies in preclinical models. R306465 was found to be a potent inhibitor of HDAC1 and -8 (class I) in vitro. It rapidly induced histone 3 (H3) acetylation and strongly upregulated expression of p21waf1,cip1, a downstream component of HDAC1 signalling, in A2780 ovarian carcinoma cells. R306465 showed class I HDAC isotype selectivity as evidenced by poor inhibition of HDAC6 (class IIb) confirmed by the absence of downregulation of Hsp90 chaperone c-raf protein expression and tubulin acetylation. This distinguished it from other HDAC inhibitors currently in clinical development that were either more potent towards HDAC6 (e.g. vorinostat) or had a broader HDAC inhibition spectrum (e.g. panobinostat). R306465 potently inhibited cell proliferation of all main solid tumour indications, including ovarian, lung, colon, breast and prostate cancer cell lines, with IC50 values ranging from 30 to 300 nM. Haematological cell lines, including acute lymphoblastic leukaemia, acute myeloid leukaemia, chronic lymphoblastic leukaemia, chronic myeloid leukaemia, lymphoma and myeloma, were potently inhibited at a similar concentration range. R306465 induced apoptosis and inhibited angiogenesis in cell-based assays and had potent oral in vivo antitumoral activity in xenograft models. Once-daily oral administration of R306465 at well-tolerated doses inhibited the growth of A2780 ovarian, H460 lung and HCT116 colon carcinomas in immunodeficient mice. The high activity of R306465 in cell-based assays and in vivo after oral administration makes R306465 a promising novel antitumoral agent with potential applicability in a broad spectrum of human malignancies. [ABSTRACT FROM AUTHOR]

Background Uncontrolled studies suggest benefit of intrapyloric injection of botulinum toxin (botox) for the treatment of gastroparesis, but controlled data are lacking. Aim To perform a controlled study of botox injection in gastroparesis. Methods Twenty-three gastroparesis patients (five men, age 45 ± 3, 19 idiopathic) underwent two upper endoscopies with 4-week interval, with injection of saline or botox 4 × 25 U in a randomized double-blind-controlled crossover fashion. Before the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal-related symptom scores, and filled out the Gastroparesis Cardinal Symptom Index. Results (mean S.E.M.) were compared using Student’s t-test. Results Twelve patients received botox and 11 saline as the first injection. Significant improvement in emptying and Gastroparesis Cardinal Symptom Index was seen after initial injection of saline or botox. No further improvement occurred after the second injection (respectively, botox and saline). Pooled data for both treatment groups showed no significant difference in improvements of solid t1/2 (3.4 ± 7.4 vs. 16.3 ± 8.3, N.S.) and liquid t1/2 (8.2 ± 13.7 vs. 22.5 ± 7.7, N.S.), meal-related symptom scores or Gastroparesis Cardinal Symptoms Index (GCSI; 6.1 ± 1.5 vs. 3.8 ± 1.5, N.S.). Conclusion In a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying. [ABSTRACT FROM AUTHOR]

Background In the evaluation of several endoscopic antireflux procedures, a discrepancy in the degree of improvement between symptoms and objective reflux parameters as measured by pH-metry has been reported. Aim To assess the additional value of impedance monitoring in the evaluation of endoscopic gastroplication for gastro-oesophageal reflux disease. Methods Eighteen patients with gastro-oesophageal reflux disease were treated with three endoscopic gastroplications, and underwent 24 h pH-impedance monitoring before and 3 months after treatment. Results Total reflux exposure time as assessed by pH-metry and impedance monitoring was significantly decreased after treatment ( P = 0.047 and <0.001, respectively). When assessed with impedance monitoring, the mean number of reflux episodes was significantly decreased after the procedure (82 vs. 56, pre vs. post, P < 0.001). Furthermore, the mean numbers of liquid and acid reflux episodes in patients with symptomatic improvement were significantly reduced after treatment ( P = 0.04 and 0.02, respectively). After treatment, mean volume clearance time (s) and mean number of proximal reflux episodes were significantly decreased ( P < 0.001 and 0.002, respectively). Conclusions Impedance monitoring can identify the specific effect of endoscopic gastroplication on the different types of reflux episodes with regard to gas–liquid composition and pH, as well as on volume clearance and the proximal extent of the refluxate. [ABSTRACT FROM AUTHOR]

Reconstruction of bone defects with impacted morsellized cancellous bone grafts (MCB) is a popular method. Because of a shortage of human bone, mixing with biomaterials may be attractive. Ceramics may be used as bone graft extenders. In this study, various volume mixtures of biphasic tri‐calciumphosphate/hydroxyl‐apatite (TCP‐HA) granules (1.5–2 mm) with MCB were examined in a non‐loaded defect model in rabbits. Direct post‐operatively, many 10–150 μm TCP‐HA particles were present due to impaction. Irrespective to the group, after 8 weeks, virtually all MCB was resorbed and most TCP‐HA granules were osseous‐integrated with newly formed bone. The cross‐sectional areas of TCP‐HA after 8 weeks was generally smaller compared with direct post‐operatively and the number of small 10–150 μm TCP‐HA particles seemed reduced. Macrophages and giant cells were sparse after 8 weeks. In conclusion, the osteoconductivity of various mixtures of MCB and TCP‐HA granules is not dependent on the ratio of TCP‐HA over MCB. The reduced number of the 10–150 μm TCP‐HA particles after 8 weeks, may suggest that a cellular mediated resorption process of TCP‐HA granules took place. Based on these favorable biological findings subsequent in‐vivo experiments are warranted in load‐bearing conditions to investigate whether these findings hold for joint reconstruction purposes. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [ABSTRACT FROM AUTHOR]

Background: Idiopathic gastroparesis is a syndrome characterised by severely delayed gastric emptying of solids without an obvious underlying organic cause. Although delayed gastric emptying is traditionally considered the mechanism underlying the symptoms in these patients, poor correlations with symptom severity have been reported. Aims: To investigate proximal stomach function and to study the correlation of delayed gastric emptying and proximal stomach dysfunction with symptom pattern and severity in idiopathic gastroparesis. Methods: 58 consecutive patients (19 men, mean (standard deviation) age 41 (2) years) with severely delayed solid gastric emptying (gastric half-emptying time (t½)>109 mm) without an organic cause were recruited. They filled out a symptom-severity questionnaire and underwent a gastric barostat study for assessment of gastric sensitivity and accommodation. Correlation of these mechanisms with symptom pattern and overall symptom severity (sum of individual symptoms) was analysed. Results: At two different cut-off levels for gastric emptying (upper limit of normal t½ up to 1.5 and 2 times), no significant change in symptom pattern occurred. 25 (43%) patients had impaired accommodation, and this was associated with higher prevalence of early satiety (p<0.005) and weight loss (p = 0.009). 17 (29%) patients had hypersensitivity to gastric distension, and this was associated with higher prevalences of epigastric pain (p = 0.005), early satiety (p = 0.04) and weight loss (p<0.005). Overall symptom severity was not correlated with gastric emptying or accommodation, but only with sensitivity to gastric distension (R= -0.3898, p =0.003) and body weight (R= -0.4233, p=0.001). Conclusions: In patients with idiopathic gastroparesis, the symptom pattern is determined by proximal stomach dysfunction rather than by the severity of delayed emptying. [ABSTRACT FROM AUTHOR]

The hdm-2 oncogene is overexpressed in several types of malignancies including osteosarcomas, soft tissue sarcomas and gliomas and hdm-2 has been associated with accelerated tumor formation in both hereditary and sporadic cancers. Among the other key binding partners, hdm-2 forms a complex with the tumor suppressor p53, resulting in a rapid proteasome-mediated degradation of the p53 protein. This positions the hdm-2–p53 complex as an attractive target for the development of anticancer therapy and recently the first small molecule hdm-2 antagonist has been reported. Development of hdm-2 antagonists is currently focused on malignancies containing a wild-type p53 genotype, which is the case in approximately half of human cancer indications. However, hdm-2 has also been implicated in oncogenesis in the absence of p53. We therefore studied the effect of hdm-2 antagonists in p53-deficient human H1299 lung carcinoma cells. The hdm-2 antagonistic peptide caused G1 cell cycle arrest, inhibited colony growth and induced expression of G1 checkpoint regulatory proteins, such as p21waf1,cip1. These data demonstrate that hdm-2 regulates the G1 cell cycle checkpoint in a p53-independent manner, suggesting that hdm-2 antagonists represent a novel class of anticancer therapeutics with broad applicability towards tumors with different p53 genetic backgrounds.Oncogene (2006) 25, 6672–6677. doi:10.1038/sj.onc.1209667; published online 29 May 2006 [ABSTRACT FROM AUTHOR]

The effect of couch sag on treatment delivery accuracy has been investigated by modelling the variation of delivered dose from planned dose due to the difference between the treatment and simulation couches. The couch sag of the Siemens (Concord, USA) Primus linac was determined relative to the couch sag of the Siemens (Germany) Sensation 4 CT Scanner. A phantom planning study was then undertaken to evaluate the likely clinical impact of the couch sag through an evaluation of changes in dose distribution, dose volume histograms and monitor units. The couch sag was simulated by altering the angle of the CT gantry when obtaining image studysets. A second investigation into the effects of couch sag was undertaken using an existing patient CT studyset. For this investigation, the couch sag was simulated by appropriate rotation of the gantry and collimator angles. The effect of couch sag on calculated monitor units (MU) was found to be statistically insignificant. The small monitor unit changes observed were likely to result from differences in the average linear attenuation coefficient along the beam path to the isocentre. The major differences seen however were in the regions away from the central axis. The dose volume histograms showed that both the bladder and rectum were further spared with increasing tilt angle whilst the PTV dose was unchanged. The only issue at South West Sydney Cancer Services (SWSCS) in terms of patient position variation arises from the angle induced by the couch sag (or more precisely, the difference in couch sag angle between the CT and Linac couches). Due to the relatively uniform structures (of PTV, bladder and rectum), and the proximity of these critical structures to the isocentre, this angular rotation about the isocentre did not cause any major variations to the DVH, MU and isodoses for realistic levels of couch sag (i.e. less than 20mm). [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the clinical and radiographic outcomes of revision of the femoral component of a hip arthroplasty with use of an impaction bone-grafting technique and a cemented polished stem.Methods: Thirty-three consecutive femoral reconstructions that were performed between March 1991 and February 1996 with use of the X-change femoral revision system, fresh-frozen morselized allograft, and a cemented polished Exeter stem were followed prospectively. Femoral bone stock defects were classified according to the Endoklinik classification. The average age of the patients at the time of the femoral component revision was sixty-three years. No patient was lost to follow-up, which was performed at a minimum of eight years, but eight patients had died. None of the deaths was related to the surgery.Results: No femoral reconstruction had been rerevised at a mean of 10.4 years postoperatively. There was one unrecognized intraoperative fracture, which healed following nonoperative treatment. There were three postoperative femoral fractures, all through cortical defects at the level of the tip of the prostheses. All fractures healed after plate fixation, and all femoral implants were left in situ. The average subsidence of the stem within the cement mantle was 3 mm; seven stems migrated 5 mm. The average Harris hip score improved from 49 points prior to surgery to 85 points (range, 68 to 100 points) at the time of this review. Subsidence did not affect the Harris hip score. Kaplan-Meier analysis, with an end point of femoral revision for any reason, showed a survival rate of 100% (one-sided 95% confidence interval, 100% to 91.3%).Conclusions: Femoral revision with use of an impaction bone-grafting technique and a cemented polished stem resulted in an excellent prosthetic survival rate at eight to thirteen years postoperatively. The major problem that occurred was a femoral fracture in four patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: The purpose of this study was to evaluate the clinical and radiographic outcomes of revision of the femoral component of a hip arthroplasty with use of an impaction bone-grafting technique and a cemented polished stem. METHODS: Thirty-three consecutive femoral reconstructions that were performed between March 1991 and February 1996 with use of the X-change femoral revision system, fresh-frozen morselized allograft, and a cemented polished Exeter stem were followed prospectively. Femoral bone stock defects were classified according to the Endoklinik classification. The average age of the patients at the time of the femoral component revision was sixty-three years. No patient was lost to follow-up, which was performed at a minimum of eight years, but eight patients had died. None of the deaths was related to the surgery. RESULTS: No femoral reconstruction had been rerevised at a mean of 10.4 years postoperatively. There was one unrecognized intraoperative fracture, which healed following nonoperative treatment. There were three postoperative femoral fractures, all through cortical defects at the level of the tip of the prostheses. All fractures healed after plate fixation, and all femoral implants were left in situ. The average subsidence of the stem within the cement mantle was 3 mm; seven stems migrated 5 mm. The average Harris hip score improved from 49 points prior to surgery to 85 points (range, 68 to 100 points) at the time of this review. Subsidence did not affect the Harris hip score. Kaplan-Meier analysis, with an end point of femoral revision for any reason, showed a survival rate of 100% (one-sided 95% confidence interval, 100% to 91.3%). CONCLUSIONS: Femoral revision with use of an impaction bone-grafting technique and a cemented polished stem resulted in an excellent prosthetic survival rate at eight to thirteen years postoperatively. The major problem that occurred was a femoral fracture in four patients. [ABSTRACT FROM AUTHOR]

Background Recent observations in limited numbers of patients suggest a potential benefit of intrapyloric injection of botulinum toxin in the treatment of gastroparesis. Aim To characterize the effect of botulinum toxin on solid and liquid gastric emptying and on meal-related symptoms. Methods In 20 gastroparesis patients (17 women, mean age 37 ± 3 years, three diabetic and 17 idiopathic), gastric emptying for solids and liquids was measured before and one month after intrapyloric botulinum toxin 4 × 25 units. Before the meal and at 15-min intervals up to 240 min postprandially, the patient graded the intensity of six gastroparesis symptoms, and a meal-related severity score was obtained by adding all intensities. Data (mean ± S.E.M.) were compared using paired Student's t-test. Results Treatment with botulinum toxin significantly enhanced solid ( t1/2 132 ± 16 vs. 204 ± 35 min, P < 0.05) but not liquid (92 ± 10 vs. 104 ± 11 min, N.S.) emptying. This was accompanied by a significant decrease in cumulative meal-related symptom score (73.5 ± 16.3 vs. 103 ± 17.1 baseline, P = 0.01) as well as individual severity scores for postprandial fullness, bloating, nausea and belching (all P < 0.001, two-wayanova). Conclusions Botulinum toxin improves solid but not liquid gastric emptying in gastroparesis, and this is accompanied by significant improvement of several meal-related symptoms. [ABSTRACT FROM AUTHOR]

Background Bone defects after failed total hip arthroplasty can be reconstructed with impacted morselized bone grafts and a cemented cup. On the acetabular side, the effects on initial cup stability of washing bone grafts prior to impaction and bone graft size remain unclear. Related to these variables, cement penetration and inter-particle shear resistance have been suggested to be critical factors to ensure initial cup stability. Methods Using a synthetic acetabular model, we studied the effects of (1) washing bone grafts prior to impaction, and (2) bone graft size on the initial stability of cemented cups. In addition, cement penetration was measured using CT scans. Results Reconstructions with large, washed bone grafts provided the highest stability during mechanical compression and in a lever-out situation. Washing of the bone grafts had a positive effect on initial cup stability, but the size of the bone grafts appeared to be more important. Cement penetration was affected by bone graft size but not by washing. Interpretation From a mechanical standpoint, large bone grafts that have been washed prior to impaction may be preferable in order to obtain optimal cup stability using the bone impaction grafting technique. ? [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the clinical and radiographic outcomes of revision of the femoral component of a hip arthroplasty with use of an impaction bone-grafting technique and a cemented polished stem.Methods: Thirty-three consecutive femoral reconstructions that were performed between March 1991 and February 1996 with use of the X-change femoral revision system, fresh-frozen morselized allograft, and a cemented polished Exeter stem were followed prospectively. Femoral bone stock defects were classified according to the Endoklinik classification. The average age of the patients at the time of the femoral component revision was sixty-three years. No patient was lost to follow-up, which was performed at a minimum of eight years, but eight patients had died. None of the deaths was related to the surgery.Results: No femoral reconstruction had been rerevised at a mean of 10.4 years postoperatively. There was one unrecognized intraoperative fracture, which healed following nonoperative treatment. There were three postoperative femoral fractures, all through cortical defects at the level of the tip of the prostheses. All fractures healed after plate fixation, and all femoral implants were left in situ. The average subsidence of the stem within the cement mantle was 3 mm; seven stems migrated > or =5 mm. The average Harris hip score improved from 49 points prior to surgery to 85 points (range, 68 to 100 points) at the time of this review. Subsidence did not affect the Harris hip score. Kaplan-Meier analysis, with an end point of femoral revision for any reason, showed a survival rate of 100% (one-sided 95% confidence interval, 100% to 91.3%).Conclusions: Femoral revision with use of an impaction bone-grafting technique and a cemented polished stem resulted in an excellent prosthetic survival rate at eight to thirteen years postoperatively. The major problem that occurred was a femoral fracture in four patients. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the clinical and radiographic outcomes of revision of the femoral component of a hip arthroplasty with use of an impaction bone-grafting technique and a cemented polished stem. Methods: Thirty-three consecutive femoral reconstructions that were performed between March 1991 and February 1996 with use of the X-change femoral revision system, fresh-frozen morselized allograft, and a cemented polished Exeter stem were followed prospectively. Femoral bone stock defects were classified according to the Endoklinik classification. The average age of the patients at the time of the femoral component revision was sixty-three years. No patient was lost to follow-up, which was performed at a minimum of eight years, but eight patients had died. None of the deaths was related to the surgery. Results: No femoral reconstruction had been rerevised at a mean of 10.4 years postoperatively. There was one unrecognized intraoperative fracture, which healed following nonoperative treatment. There were three postoperative femoral fractures, all through cortical defects at the level of the tip of the prostheses. All fractures healed after plate fixation, and all femoral implants were left in situ. The average subsidence of the stem within the cement mantle was 3 mm; seven stems migrated ≥5 mm. The average Harris hip score improved from 49 points prior to surgery to 85 points (range, 68 to 100 points) at the time of this review. Subsidence did not affect the Harris hip score. Kaplan- Meier analysis, with an end point of femoral revision for any reason, showed a survival rate of 100% (one-sided 95% confidence interval, 100% to 91.3%). Conclusions: Femoral revision with use of an impaction bone-grafting technique and a cemented polished stem resulted in an excellent prosthetic survival rate at eight to thirteen years postoperatively. The major problem that occurred was a femoral fracture in four patients. [ABSTRACT FROM AUTHOR]

Aim: A subset of functional dyspepsia patients respond to acid suppressive therapy, but the prevalence of non-erosive reflux disease in functional dyspepsia and its relevance to symptoms have never been established. The aim of the present study was to study 24 hour pH monitoring in consecutive functional dyspepsia patients. Methods: A total of 247 patients with dyspeptic symptoms (166 women, mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and without dominant symptoms of heartburn participated in the study. In all patients, the severity of dyspeptic symptoms and the presence of heartburn was assessed by a questionnaire and a 24 hour oesophageal pH monitoring study was performed. All patients underwent a gastric emptying breath test and in 113 a gastric barostat study was performed. Results: Abnormal pH monitoring (acid exposure >5% of time) was found in 58 patients (23%). Of 21 patients with a positive heartburn questionnaire, 76% had pathological pH monitoring, while this was the case in only 18.5% of patients with a negative heartburn questionnaire. Demographic characteristics and the prevalence of other pathophysiological mechanisms did not differ between heartburn negative patients with normal or abnormal acid exposure. Pathological acid exposure in heartburn negative patients was associated with the presence of epigastric pain (65 v 84%, p<0.005) and of moderate or severe pain (48 v 69%, p=0.005). Conclusion: Pathological oesophageal acid exposure is only present in a subset of heartburn negative functional dyspepsia patients, which are characterised by a higher prevalence of epigastric pain. [ABSTRACT FROM AUTHOR]

Background and aims: Although delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia, the efficacy of prokinetic drugs has not been established. Recent studies using macrolide prokinetics were negative but receptor desensitisation may have played a role. The aim of the present study was to evaluate the influence on meal induced symptoms of acutely administered erythromycin in patients with gastroparesis. Methods: In 20 patients with functional dyspepsia, gastric emptying was studied twice using the 14C octanoic acid and 13C glycin breath test to establish the reproducibility of the test. Breath samples were taken before the meal and at 15 minute intervals for a period of 240 minutes postprandially. At each breath sampling, the patient was asked to grade the intensity (0-3) of six dyspeptic symptoms. Twenty four patients (three men, mean age 43.5 (3) years) with dyspeptic symptoms and delayed gastric emptying were studied twice after pretreatment with saline or erythromycin intravenously. Results: Meal related symptom severity scores were reproducible. Treatment with erythromycin significantly enhanced solid and liquid gastric emptying (t½ 146 (27) v 72 (7) minutes, respectively (p<0.01), and 87 (6) v 63 (5) minutes (p<0.001 )). Only the severity of bloating was significantly improved by erythromycin (23 (3.9) v 14.5 (2.7); p<0.01); all other symptoms and the cumulative meal related symptom score were not altered by erythromycin. Conclusions: In a setting where desensitisation played no role, erythromycin enhanced gastric emptying was not associated with a beneficial effect on meal related symptom severity. [ABSTRACT FROM AUTHOR]

In a subset of patients with gastroesophageal reflux disease (GERD), symptoms persist in spite of proton pump inhibitor (PPI) therapy. Endoscopic gastroplication (EG) was reported to provide a novel therapeutic option in GERD. To evaluate symptomatic and objective outcome of EG in PPI refractory GERD, consecutive GERD patients with persisting reflux symptoms during at least 2 months double dose PPI were recruited for EG (Endocinch). Exclusion criteria were high-grade esophagitis, Barrett's esophagus, and hiatal hernia > 3 cm. Symptoms and PPI use were evaluated before and 1, 3, and 12 months after the EG; 24-hr pH monitoring off PPI was performed before and after 3 and 12 months. All data are given as mean +/- SD and were analyzed by Student's t test. Twenty patients (10 females; mean age, 45 +/- 11 years) were recruited. Under conscious sedation with midazolam (6 +/- 2 mg) and pethidine (53 +/- 5 mg), a mean of 2.0 +/- 0.2 sutures was applied during a procedure time of 33 +/- 6 min. Throat ache and mild epigastric pain for up to 3 days after the procedure were the only adverse events. At 3 and 12 months symptom score (11.6 +/- 6 vs. 6.4 +/- 3.7 [P < 0.01] and 7.1 +/- 4.5 [P < 0.05]) as well as pH monitoring (% time pH < 4: 17.0 +/- 11.1 vs. 8.1 +/- 5.7% [P < 0.01] and 9.8 +/- 4.1% [P < 0.01]) significantly improved. Ph monitoring was normalized (< 4% of time) in seven patients after 3 months. PPIs could be stopped in 13 patients, with 2 patients still using H2-blockers and 1 using cisapride after 3 months. After 12 months only six patients were free of PPI use and pH monitoring was normalized in six patients. We conclude that EG provides short- and medium-term symptomatic and objective relief to a subset of GERD patients refractory to high-dose PPI. [ABSTRACT FROM AUTHOR]

Gastro-oesophageal reflux disease (GORD) is a common chronic disorder that has severe impact on quality of life. Moreover, GORD may also cause reflux oesophagitis and sometimes severe complications, such as ulceration, strictures, Barrett's mucosa, and adenocarcinoma of the oesophagus. Laparoscopic fundoplication is often proposed as an alternative and more definitive option, especially in young patients, because it is intended to cure the disorder and the laparoscopic approach makes surgery more acceptable.

A new sample of radio sources, with the designated name CENSORS (A Combined EIS–NVSS Survey Of Radio Sources), has been defined by combining the National Radio Astronomy Observatory Very Large Array Sky Survey (NVSS) at 1.4 GHz with the ESO Imaging Survey (EIS) Patch D, a 3° by 2° region of sky centred at RA , Dec. −21°00′00′ (J2000). New radio observations of 199 NVSS radio sources with NVSS flux densities are presented, and are compared with the EIS I-band imaging observations which reach a depth of ; optical identifications are obtained for over two-thirds of the ∼150 confirmed radio sources within the EIS field. The radio sources have a median linear size of 6 arcsec, consistent with the trend for lower flux density radio sources to be less extended. Other radio source properties, such as the lobe flux density ratios, are consistent with those of brighter radio source samples. From the optical information, 30–40 per cent of the sources are expected to lie at redshifts . One of the key goals of this survey is to accurately determine the high-redshift evolution of the radio luminosity function. These radio sources are at the ideal flux density level to achieve this goal; at redshifts they have luminosities which are around the break of the luminosity function and so provide a much more accurate census of the radio source population at those redshifts than the existing studies of extreme, high radio power sources. Other survey goals include investigating the dual-population unification schemes for radio sources, studying the radio luminosity dependence of the evolution of radio source environments, and understanding the radio power dependence of the K– z relation for radio galaxies. [ABSTRACT FROM AUTHOR]

In the present study the effects of a 3-day inhalation exposure to model compounds for ambient particulate matter were investigated: ammonium bisulfate, ammonium ferrosulfate, and ammonium nitrate, all components of the secondary aerosol fraction of ambient particulate matter (PM), and carbon black (CB, model aerosol for primary PM). The objective of this study was to test the hypothesis that secondary model aerosols exert acute pulmonary adverse effects in rats, and that rats with pulmonary hypertension (PH), induced by monocrotaline (MCT), are more sensitive to these components than normal healthy animals. An additional aim was to test the hypothesis that fine particles exert more effects than ultrafines. Healthy and PH rats were exposed to ultrafine (mass median diameter [MMD] ≈ 0.07-0.10 µm; 4 × 10[sup 5] particles/cm[sup 3] ) and fine (MMD ≈ 0.57-0.64 µm; 9 × 10[sup 3] particles/cm[sup 3] ) ammonium aerosols during 4 h/day for 3 consecutive days. The mean mass concentrations ranged from 70 to 420 µg/m[sup 3] , respectively, for ultrafine ammonium bisulfate, nitrate, and ferrosulfate and from 275 to 410 µg/m[sup 3] for fine-mode aerosols. In an additional experiment, simultaneous exposure to a fine CB aerosol (0.6 µm; 2-9 mg/m[sup 3] ) and ammonium nitrate (0.4-18 mg/m[sup 3] ) was performed. Bronchoalveolar lavage fluid (BALF) analysis and histopathological examination were performed on animals sacrificed 1 day after the last exposure. Histopathology of the lungs did not reveal test atmosphere-related abnormalities in either healthy or PH rats exposed to the ammonium salts, or to a combination of CB + nitrate. Alveolar macrophages in rats exposed to CB only revealed the presence of black material in their cytoplasm. There were no signs of cytotoxicity due to the aerosol exposures (as measured with lactate dehydrogenase [LDH], protein, and albumin contents in BALF). Macrophages were not activated after MCT treatment or the test atmospheres, since no changes were observed in N-acetyl glucosaminidase (NAG). Cell differentiation profiles were inconsistent, partly caused by an already present infection with Haemophilus sp. However, we believe that the test atmospheres did not affect cell differentiation or total cell counts. The results show that at exposure levels of ammonium salts at least one order of magnitude higher than ambient levels, marked adverse health effects were absent in both healthy and PH rats. [ABSTRACT FROM AUTHOR]

In this study the effects of inhalatory exposure to coal fly ash on lung pathology and the immune system in rats were examined. Rats were exposed to 0, 10, 30, or 100 mg/m 3 coal fly ash (6 h/day, 5 days/ wk) for 4 wk, or to 0 and 100 mg/ m 3 for 1 wk, and for 1 wk followed by a recovery in clean air of 3 wk. A concentration-related increase in lung weight was found starting from 30 mg/ m3 coal fly ash. After exposure to 100 mg/m 3, a time-related deposition of free particles in the lungs was observed as well as a timerelated number of coal fly ash particles phagocytized in alveolar macrophages. Histological examination revealed increased cellularity in alveolar septa, consisting mainly of mononuclear cell infiltrate, proliferated type II cells, and a slight fibrotic reaction. After a recovery period of 3 wk the histological picture was identical to that after 1 wk of exposure, indicating no significant recovery. No toxicological significant changes were found in the hematological, clinical chemistry, or urine parameters. Effects both on nonspecific defense mechanisms and on specific immune responses were noted. With regard to the immune function in the draining lymph nodes of the lung, a significantly increased number of both T and B lymphocytes was observed. The ratio of both cell types was not changed in either of the groups. In serum of exposed rats a significant increase of up to 150% of the immunoglobulin A (IgA) content was found. The number and phagocytic capacity of macrophages were significantly increased, while the killing of Listeria bacteria per cell ex vivo/in vitro remained unchanged. Natural killer (NK) activity in pulmonary cell suspensions was slightly stimulated in rats exposed for 4 wk to 10 and 30 mg/m 3, whereas an exposure to 100 mg/m 3 resulted in a slight decrease; however, both changes were not significant. In conclusion, the alterations in lung histopathology and immunity, observed in a dose and exposure time relation at concentrations up to and including 100 mg/m 3 coal fly ash, may be considered an adverse response of the host to inhalation of particulate matter. Whether these observed alterations may effect the host resistance must be learned from infection studies. [ABSTRACT FROM AUTHOR]