Association and relaxation of supra-macromolecular polymers.

This paper describes the structures created by assembling functionalised entangled polymers and the effect these have on the rheology of the material. A polybutadiene (PBd) linear polymer precursor of sufficient molecular weight to be entangled is used. This is end functionalised with the self-associating group 2-ureido-4pyrimidinone (UPy). Interestingly, despite the relatively high molecular weight of the precursor diluting the UPy concentration, the effect on the material's properties is significant. To characterise the assembled microstructure we present linear rheology, extensional non-linear rheology and small angle X-ray scattering (SAXS). The linear rheology shows that the functionalised PBd assembles into large macro-structures where the terminal relaxation time is up to seven orders of magnitude larger than the precursor. The non-linear rheology shows strain-hardening over a broad range of strain-rates. We then show by both SAXS and modelling of the extensional data that there must exist clusters of UPy associations and hence assembled polymers with branched architecture. By modelling the supra-molecular structure as an effective linear polymer, we show that this would be insufficient in predicting the strain-hardening behaviour at lower extension-rates. Therefore, in this flow regime the strain-hardening is likely to be caused by branching. This is backed up by SAXS measurements which show that UPy clusters larger than pair-pair groups exist.

Prior Generic Arthroscopic Volume Correlates with Hip Arthroscopic Proficiency: A Simulator Study.

BACKGROUND: Changing trends in surgical education and patient expectation are leading to proficiency models of progression and the use of simulators. Hip arthroscopy is increasingly performed and has a steep learning curve mainly addressed during fellowship training. The aim of this study was to assess the impact of previous generic arthroscopic experience on performance at a simulated hip arthroscopy task to both estimate the minimum case numbers that correlate with expert proficiency levels and help to guide selection for hip arthroscopy fellowships. METHODS: Fifty-two participants were recruited to a cross-sectional study. Four consultants (expert hip arthroscopists), 28 trainees (residents and fellows), and 20 novices (interns and medical students) performed a standardized bench-top simulated hip arthroscopy task. A validated global rating scale (GRS) score and motion analysis were used to assess surgical performance. Prior arthroscopic experience was recorded from surgical electronic logbooks. Receiver operating characteristic (ROC) curve analyses were conducted to identify optimum cut-points for task proficiency at both expert and competent GRS levels. RESULTS: There were significant differences (p < 0.05) between the arthroscopic ability of all experience groups based on GRS assessment and for all motion analysis metrics. There was a significant positive correlation between logbook numbers and GRS scores (p < 0.0001). ROC curve analysis demonstrated that a minimum of 610 prior arthroscopic procedures were necessary to achieve an expert GRS score, and 78 prior arthroscopic procedures were necessary for a competent score. CONCLUSIONS: Performing a basic hip arthroscopy task competently requires substantial previous generic arthroscopic experience. The numbers identified in this study provide targets for residents. Program directors appointing to hip arthroscopy fellowship training posts may find these results useful as a guide during the selection process.

Delivery of TLR7 agonist to monocytes and dendritic cells by DCIR targeted liposomes induces robust production of anti-cancer cytokines.

Tumor immune escape is today recognized as an important cancer hallmark and is therefore a major focus area in cancer therapy. Monocytes and dendritic cells (DCs), which are central to creating a robust anti-tumor immune response and establishing an anti-tumorigenic microenvironment, are directly targeted by the tumor escape mechanisms to develop immunosuppressive phenotypes. Providing activated monocytes and DCs to the tumor tissue is therefore an attractive way to break the tumor-derived immune suppression and reinstate cancer immune surveillance. To activate monocytes and DCs with high efficiency, we have investigated an immunotherapeutic Toll-like receptor (TLR) agonist delivery system comprising liposomes targeted to the dendritic cell immunoreceptor (DCIR). We formulated the immune stimulating TLR7 agonist TMX-202 in the liposomes and examined the targeting of the liposomes as well as their immune activating potential in blood-derived monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs). Monocytes and mDCs were targeted with high specificity over lymphocytes, and exhibited potent TLR7-specific secretion of the anti-cancer cytokines IL-12p70, IFN-α 2a, and IFN-γ. This delivery system could be a way to improve cancer treatment either in the form of a vaccine with co-formulated antigen or as an immunotherapeutic vector to boost monocyte and DC activity in combination with other treatment protocols such as chemotherapy or radiotherapy. STATEMENT OF SIGNIFICANCE: Cancer immunotherapy is a powerful new tool in the oncologist's therapeutic arsenal, with our increased knowledge of anti-tumor immunity providing many new targets for intervention. Monocytes and dendritic cells (DCs) are attractive targets for enhancing the anti-tumor immune response, but systemic delivery of immunomodulators has proven to be associated with a high risk of fatal adverse events due to the systemic activation of the immune system. We address this important obstacle by targeting the delivery of an immunomodulator, a Toll-like receptor agonist, to DCs and monocytes in the bloodstream. We thus focus the activation, potentially avoiding the above-mentioned adverse effects, and demonstrate greatly increased ability of the agonist to induce secretion of anti-cancer cytokines.

Genes regulated by potassium channel tetramerization domain containing 15 (Kctd15) in the developing neural crest.

Neural crest (NC) development is controlled precisely by a regulatory network with multiple signaling pathways and the involvement of many genes. The integration and coordination of these factors are still incompletely understood. Overexpression of Wnt3a and the BMP antagonist Chordin in animal cap cells from Xenopus blastulae induces a large number of NC specific genes. We previously suggested that Potassium Channel Tetramerization Domain containing 15 (Kctd15) regulates NC formation by affecting Wnt signaling and the activity of transcription factor AP-2. In order to advance understanding of the function of Kctd15 during NC development, we performed DNA microarray assays in explants injected with Wnt3a and Chordin, and identified genes that are affected by Kctd15 overexpression. Among the many genes identified, we chose Duf domain containing protein 1 (ddcp1), Platelet-Derived Growth Factor Receptor a (pdgfra), Complement factor properdin (cfp), Zinc Finger SWIM-Type Containing 5 (zswim5), and complement component 3 (C3) to examine their expression by whole mount in situ hybridization. Our work points to a possible role for Kctd15 in the regulation of NC formation and other steps in embryonic development.

Elucidating the role of free polycations in gene knockdown by siRNA polyplexes.

Future improvements of non-viral vectors for siRNA delivery require better understanding of intracellular processing and vector interactions with target cells. Here, we have compared the siRNA delivery properties of a lipid derivative of bPEI 1.8kDa (DOPE-PEI) with branched polyethyleneimine (bPEI) with average molecular weights of 1.8kDa (bPEI 1.8kDa) and 25kDa (bPEI 25kDa). We find mechanistic differences between the DOPE-PEI conjugate and bPEI regarding siRNA condensation and intracellular processing. bPEI 1.8kDa and bPEI 25kDa have similar properties with respect to condensation capability, but are very different regarding siRNA decondensation, cellular internalization and induction of reporter gene knockdown. Lipid conjugation of bPEI 1.8kDa improves the siRNA delivery properties, but with markedly different formulation requirements and mechanisms of action compared to conventional PEIs. Interestingly, strong knockdown using bPEI 25kDa is dependent on the presence of a free vector fraction which does not increase siRNA uptake. Finally, we have investigated the effect on lysosomal pH induced by these vectors to elucidate the differences in the proton sponge effect between lipid conjugated PEI and conventional PEI: Neither DOPE-PEI nor bPEI 25kDa affected lysosomal pH as a function of time, underlining that the possible proton sponge effect is not associated with changes in lysosomal pH. STATEMENT OF SIGNIFICANCE: Gene silencing therapy has the potential to treat diseases which are beyond the reach of current small molecule-based medicines. However, delivery of the small interfering RNAs (siRNAs) remains a bottleneck to clinical implementation, and the development of safe and efficient delivery systems would be one of the most important achievements in medicine today. A major reason for the lack of progress is insufficient understanding of cell-polyplex interaction. We investigate siRNA delivery using polyethyleneimine (PEI) based vectors and examine how crucial formulation parameters determine the challenges associated with PEI as a delivery vector. We further evaluate how lipid conjugation of PEI influences formulation, cytotoxicity and polymer interaction with cells and cargo as well as the proton sponge capabilities of the vectors.

Management of achalasia in the UK, do we need new guidelines?

AIM: It is recommended that management of complex benign upper gastrointestinal pathology is discussed at multi disciplinary team (MDT) meetings. American College of Gastroenterology (ACG) guidelines further recommend that treatment delivery is provided by high volume centres, with objective post-procedural investigations, in order to improve patient outcomes. We aimed to survey the current UK practice in the management of achalasia. METHODS: 443 Upper gastrointestinal (UGI) specialist surgeons throughout the UK were sent a surveymonkey.com questionnaire about the management of achalasia. RESULTS: 100 responses were received. The majority of patients with achalasia are referred directly to surgeons (80%) and only 15% of units have a MDT meeting for discussing such patients. Diagnosis was mainly with oesophagogastroduodenoscopy (OGD) and contrast swallow, and only 61% of units have access to high resolution manometry (HRM). 89% of younger patients were offered surgery initially, whilst in the elderly surgery was offered as first line treatment in 55%. Partial fundoplication was carried out by 91% of responders as part of the operation, and 58% responders carry out an intraoperative OGD. The average number of operations carried out per annum is 4 per responder. Most responders (66%) did not perform routine post-intervention investigations and follow-up varied from none to lifelong. CONCLUSION: Diagnosis and management of achalasia within the UK is relatively standardised, although there remains limited access to HRM. Discussion at benign MDTs however is poor and follow-up differs widely. UK guidelines may help to make these more uniform.

Hip chondropathy at arthroscopy: prevalence and relationship to labral pathology, femoroacetabular impingement and patient-reported outcomes.

BACKGROUND: This study aimed to describe chondropathy prevalence in adults who had undergone hip arthroscopy for hip pain. The relationships between chondropathy severity and (1) participant characteristics; and (2) patient-reported outcomes (PROs) at initial assessment (∼18 months postsurgery) and over a further 12 months (∼30 months postsurgery) were evaluated. Finally, the relationships between chondropathy and coexisting femoroacetabular impingement (FAI) and labral pathology at the time of surgery were evaluated. METHODS: 100 consecutive patients (36±12 years) who underwent hip arthroscopy 18 months previously participated. Hip Osteoarthritis and Disability Outcome Score (HOOS) and International Hip Outcome Tool (iHOT-33) data were collected prospectively at 18 months postsurgery and at 30 months postsurgery. Surgical data were collected retrospectively. Participants were grouped: Outerbridge grade 0, no chondropathy; Outerbridge grade I-II, mild chondropathy; Outerbridge III-IV, severe chondropathy. The presence of FAI or labral pathology was noted. RESULTS: The prevalence of chondropathy (≥grade I) at hip arthroscopy was 72%. Participants with severe chondropathy were significantly worse for all HOOS subscales and the iHOT-33 at 18 months postsurgery (HOOS-symptoms (p=0.017); HOOS-pain (p=0.024); HOOS-activity (p=0.009); HOOS-sport (p=0.004); HOOS-quality-of-life (p=0.006); iHOT-33 (p=0.013)) than those with no chondropathy. At 12-month follow-up, HOOS-quality-of-life in those without chondropathy was the only PRO that improved. Relative risk of coexisting chondropathy with labral pathology or FAI was 40%. CONCLUSIONS: Chondropathy was prevalent, and associated with increasing age, coexisting labral pathology or FAI. Severe chondropathy was associated with worse pain and function at 18 months postsurgery. Little improvements were observed in participants over a further 12 months, regardless of chondropathy status.

Simulated hip arthroscopy skills: learning curves with the lateral and supine patient positions: a randomized trial.

BACKGROUND: Hip arthroscopy can be performed with the patient in the lateral or supine position, but it remains technically demanding. We aimed to objectively quantify and compare learning curves between two groups of orthopaedic trainees randomized to learn simulated hip arthroscopy with the patient in either a lateral or a supine position. We also compared learning curves between senior and junior trainees. METHODS: A hip arthroscopy simulator with anterolateral and anterior portals, a 70° arthroscope, and fixed distraction was used. Rotation of the simulator by 90° enabled arthroscopy with the patient in a supine or lateral position. Twenty orthopaedic trainees with minimal hip arthroscopy experience were randomized into lateral and supine position groups, and were asked to perform a diagnostic hip arthroscopy of the central compartment on twelve occasions. Each episode involved a change in the portal and repetition of the diagnostic round. A validated motion analysis system objectively measured surgical performance by recording time taken, total path-length of the hands, and number of hand movements. RESULTS: Both groups demonstrated learning with objective improvement in all parameters (p < 0.001). Initially, the lateral group was significantly slower and more variable in their performance during the second diagnostic round, after portal exchange (p = 0.006). However, they achieved parity with the supine group in all parameters by nine episodes. During the first three episodes, the junior trainees performed significantly worse for the first diagnostic round (p = 0.005) but not for the second diagnostic round (p = 0.200), and they rapidly achieved parity with the senior trainees, performing at a similar level by the end of the study period. CONCLUSIONS: Trainees with minimal experience with hip arthroscopy progressively learn and objectively improve their performance when using a hip simulator. Orientation after portal exchange is difficult for all trainees but particularly for those learning with a simulated patient lateral position. Trainees are likely to benefit from simulator training to learn orientation and basic competence prior to performing hip arthroscopy on patients.

In Silico Molecular Design, Synthesis, Characterization, and Rheology of Dendritically Branched Polymers: Closing the Design Loop.

It has been a long held ambition of both industry and academia to understand the relationship between the often complex molecular architecture of polymer chains and their melt flow properties, with the goal of building robust theoretical models to predict their rheology. The established key to this is the use of well-defined, model polymers, homogeneous in chain length and architecture. We describe here for the first time, the in silico design, synthesis, and characterization of an architecturally complex, branched polymer with the optimal rheological properties for such structure-property correlation studies. Moreover, we demonstrate unequivocally the need for accurate characterization using temperature gradient interaction chromatography (TGIC), which reveals the presence of heterogeneities in the molecular structure that are undetectable by size exclusion chromatography (SEC). Experimental rheology exposes the rich pattern of relaxation dynamics associated with branched polymers, but the ultimate test is, of course, did the theoretical (design) model accurately predict the rheological properties of the synthesized model branched polymer? Rarely, if ever before, has such a combination of theory, synthesis, characterization, and analysis resulted in a "yes", expressed without doubt or qualification.

The association between hip morphology parameters and nineteen-year risk of end-stage osteoarthritis of the hip: a nested case-control study.

OBJECTIVE: Subtle deformities of the hip joint are implicated in the etiology of osteoarthritis (OA) of the hip. Parameters that quantify these deformities may aid understanding of these associations. We undertook this study to examine relationships between such parameters and the 19-year risk of total hip arthroplasty (THA) for end-stage OA. METHODS: A new software program designed for measuring morphologic parameters around the hip was developed and validated in a reliability study. THA was the outcome measure for end-stage OA. A nested case-control study was used with individuals from a cohort of 1,003 women who were recruited at year 1 in 1989 and followed up to year 20 (the Chingford Study). All hips with THA by year 20 and 243 randomly selected control hips were studied. Pelvis radiographs obtained at year 2 were analyzed for variations in hip morphology. Measurements were compared between the THA case group and the control group. RESULTS: Patients with THA had a higher prevalence of cam deformity than did their respective controls (median alpha angle 62.4° versus 45.8° [P = 0.001]; mean modified triangular index height 28.5 mm versus 26.9 mm [P = 0.001]) as well as a higher prevalence of acetabular dysplasia (mean lateral center edge angle 29.5° versus 34.3° [P = 0.001]; median extrusion index 0.25 versus 0.185 [P = 0.009]). Logistic regression analyses clustering by subject and adjusting for radiographic hip OA at year 2 showed that these morphologic parameters were still significantly associated with THA by year 20. The alpha angle and lateral center edge angle predicted the risk of THA independently when included in the same model. CONCLUSION: This investigation describes measurements that predict the risk of THA for end-stage OA by year 20, independently of the presence of radiographic hip OA at year 2. These measurements can be made on an anteroposterior pelvis radiograph, which is an inexpensive and commonly used clinical method of investigation.

Femoroacetabular impingement and classification of the cam deformity: the reference interval in normal hips.

BACKGROUND AND PURPOSE: Most patients with femoroacetabular impingement (FAI) have a cam deformity, which may be quantified by measuring the alpha angle and anterior offset ratio (AOR). Knowledge of what constitutes a "normal" alpha angle and AOR is limited. We defined the reference intervals of these measurements from normal hips in the general population. PATIENTS AND METHODS: 157 individuals from the general population were reviewed clinically and radiographically. 74 individuals with clinical evidence of hip disease or radiographic evidence of osteoarthritis (OA) were excluded, leaving a study group of 83 individuals (mean age 46 (22-69) years, 44 females) with normal hips. The alpha angles and AORs were measured from cross-table lateral radiographs taken in 15 degrees internal rotation. A validation study consisting of a cadaver study and a measurement reliability study was also performed. RESULTS: The mean alpha angle was 48 degrees in men and 47 degrees in women. The mean AOR was 0.19, the same in men and women. Thus, sexes were combined to derive 95% confidence intervals for the population mean alpha angle (46-49 degrees ) and AOR (0.18-0.20). The 95% reference interval for the alpha angle was 32-62 degrees degrees, and for the AOR it was 0.14-0.24. The validation study confirmed that these measurements were resistant to a reasonable degree of variation in positioning and that the repeatability and reproducibility of the measurements was good. INTERPRETATION: These reference intervals indicate that clinically and radiographically normal hips may have alpha angles and AORs that have previously been considered "abnormal". The thresholds provided by this study will aid classification of individuals involved in longitudinal studies of FAI and OA, and may be of use to the practicing clinician in evaluating the young adult with hip pain.

Delayed presentation of lateral femoral circumflex artery injury post cannulated hip screw surgery--a case report.

An elderly patient underwent cannulated hip screw surgery for a subcapital neck of femur fracture. Nine days post surgery, she was noted to have collapsed with a falling haemoglobin level. Computed tomography revealed a large haematoma to the thigh. Further angiography showed active bleeding from one of the branches of the lateral femoral circumflex artery (LFCA), which we postulate was caused by the sharp tip of a version guidewire used during fracture fixation surgery. Iatrogenic injury during hip fracture fixation is a rare event, particularly to the circumflex branches of the profunda femoris artery (PFA), and may occur from hard wire use intra-operatively or from the fracture itself. The LFCA branches laterally from the PFA, runs anterior to the femoral neck, where we suspect it was injured in our case. Whilst a version wire is a useful radiological guide intra-operatively, manually clearing a passage for its insertion into the femoral head/neck junction and using the blunt end is recommended. A combination of acute swelling in the operated region and falling haemoglobin post surgery should alert the clinician to possible vascular injury. Compared to duplex ultrasonography, CT angiography remains the gold standard in its specificity and sensitivity for diagnosing arterial injuries. With early recognition and prompt radiological intervention, this rare complication of fracture fixation surgery can be treated without the need for further surgery.

Endogenous DNA damage and testicular germ cell tumors.

Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case-case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR(50th percentile) = 3.31, 95% CI: 1.00, 10.98; OR(75th percentile) = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR(50th percentile) = 2.27, 95% CI: 0.75, 6.87; OR(75th percentile) = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

Does laparoscopic antireflux surgery improve quality of life in patients whose gastro-oesophageal reflux disease is well controlled with medical therapy?

OBJECTIVE: Both medical therapy and laparoscopic antireflux surgery have been shown to improve quality of life in gastro-oesophageal reflux disease. Although patients with poor symptom control or side effects on medical therapy might be expected to have improved quality of life after surgery, our aim was to determine, for the first time, whether patients whose symptoms are well controlled on medical therapy but who decide to undergo surgery (patient preference) would experience improved quality of life. METHODS: Retrospective analysis of our patient database (1998-2003, n=313) identified 60 patients who underwent laparoscopic antireflux surgery for the indication of patient preference. Two generic quality-of-life questionnaires (Short Form 36 and Psychological General Well-Being index) and a gastrointestinal symptom questionnaire (Gastrointestinal Symptom Rating Scale) were completed preoperatively, while on medical therapy, and 6 months after surgery. RESULTS: Thirty-eight patients completed all three questionnaires at both time intervals: 31 males, seven females; mean age 42 (15-66) years. Preoperative scores while on medical therapy were significantly improved after surgery: Short Form 36 median physical composite scores 52.0 and 54.0 (P=0.034) and mental composite scores 51.0 and 56.0 (P=0.020); Psychological General Well-Being median total scores 78.0 and 90.0 (P=0.0001); Gastrointestinal Symptom Rating Scale median total scores 2.13 and 1.73 (P=0.0007) and reflux scores 2.50 and 1.00 (P<0.0001). CONCLUSION: Laparoscopic antireflux surgery significantly improved quality of life in reflux patients whose symptoms were well controlled on medical therapy. Although on the basis of a noncomparative trial with a relatively short follow-up period, we believe such patients should be considered for laparoscopic antireflux surgery.

Laparoscopic anti-reflux surgery is effective in obese patients with gastro-oesophageal reflux disease.

INTRODUCTION: Obesity has long been regarded as a risk factor for the development of gastro-oesophageal reflux disease (GORD). It has been claimed that surgical efficacy of laparoscopic anti-reflux operations is decreased in obese patients. The aim of this study was to assess whether laparoscopic anti-reflux surgery is effective in obese patients with GORD compared to non-obese patients. PATIENTS AND METHODS: A total of 366 patients (mean age 44 years; range, 12-86 years) underwent laparoscopic anti-reflux surgery between 1997-2003. Of these, 74 patients were considered obese; 58 patients had a body mass index (BMI) of 30-34 kg/m(2) and 16 were classified as morbidly obese with a BMI >or= 35 kg/m(2). Pre-operative symptomatic scoring, indications for surgery, pH studies, operative times and complications were compared between obese and non-obese patients. Symptomatic outcome and Visick score between the two groups were assessed at 6 weeks, 6 months and 1 year following surgery. RESULTS: Failure of medical treatment was the main reason for surgery in all groups. Operative time was longer in obese patients (mean time 93 min compared to 81 min; P = 0.0007), the main difficulty being gaining access because of their body habitus. All groups found the procedure to be effective in symptomatic outcome, 91% of obese patients compared to 92% of non-obese patients scored Visick I or II at 6 weeks' postoperatively. Similar Visick scoring was shown between the two groups at 6 months and 1 year, and in the morbidly obese group. CONCLUSIONS: The outcome of laparoscopic anti-reflux surgery is similar between obese and non-obese patients with no trend towards a worse outcome in the obese or morbidly obese. Obesity should not be seen as a contra-indication, although it may be more technically challenging in this group of patients. Good results can be achieved in obese patients.

Oesophageal pH monitoring using the Bravo catheter-free radio capsule.

OBJECTIVES: Oesophageal pH monitoring is the current standard for the diagnosis of gastro-oesophageal reflux disease. The Bravo capsule allows 48-h monitoring without the need for a naso-oesophageal catheter. Our aim was to assess the Bravo capsule in terms of patient discomfort and interference with daily activities, and to determine if 48-h Bravo pH studies facilitate the diagnosis of gastro-oesophageal reflux disease. METHODS: Ambulatory pH studies were performed at two hospitals using either the Bravo capsule (n=100) or a conventional naso-oesophageal catheter (n=100). Participants were selected either for investigation of symptoms suggestive of gastro-oesophageal reflux disease, or to follow-up antireflux surgery. All participants completed questionnaires to assess discomfort and interference with daily activities. RESULTS: Eighty-nine Bravo studies recorded at least 48 h of data, and 95 were diagnostic. Bravo participants reported significantly less discomfort during insertion (P<0.0001) and monitoring (P<0.0001), and less interference with daily activities (P<0.0001), eating (P<0.005), sleeping (P<0.0001) and work (P<0.0001). No significant difference was observed between day 1 and 2 median total time pH<4 (4.0 and 4.3%, P=0.64), erect time pH<4 (5.0 and 5.0%, P=0.56), supine time pH<4 (0.5 and 0.5%, P=0.23), and Johnson-DeMeester scores (15.9 and 16.2, P=0.90). Ten Bravo participants (10%) were diagnosed with gastro-oesophageal reflux disease using day 2 data after a normal day 1. CONCLUSIONS: The Bravo capsule significantly reduces the patient discomfort and interference with normal daily activities during pH monitoring associated with a naso-oesophageal catheter. Moreover, 48-h Bravo studies offer an advantage over conventional 24-h studies in diagnosing gastro-oesophageal reflux disease.

Calcific tendinitis: natural history and association with endocrine disorders.

A retrospective, observational cohort study of 102 consecutive patients (125 shoulders) with calcific tendinitis is presented. Of the patients, 73 (71.6%) were women and 29 (28.4%) were men. Compared with population prevalences, significant levels of endocrine disorders were found. We compared 66 patients (62 women [93.9%] and 4 men [6.1%]; mean age, 50.3 years) (81 shoulders) with associated endocrine disease with 36 patients (11 women [30.6%] and 25 men [69.4%]); mean age, 52.4 years) (44 shoulders) without endocrine disease. The endocrine cohort was significantly younger than the non-endocrine cohort when symptoms started (mean, 40.9 years and 46.9 years, respectively), had significantly longer natural histories (mean, 79.7 months compared with 47.1 months), and had a significantly higher proportion who underwent operative treatment (46.9% compared with 22.7%). Disorders of thyroid and estrogen metabolism may contribute to calcific tendinitis etiology. Classifying calcific tendinitis into type I (idiopathic) and type II (secondary or endocrine-related) aids prognosis and management.