Self-reported management among people with rotator cuff related shoulder pain: An observational study.

BACKGROUND: Rotator cuff related shoulder pain is the most common cause of shoulder pain. Whilst guidelines recommend conservative management prior to imaging, injection or surgical management, recent findings suggest that patients experience management contrary to guideline recommendations. OBJECTIVES: The aim of this study was to investigate self-reported management among people with rotator cuff related shoulder pain (RCRSP) and their beliefs towards management. MATERIALS AND METHODS: Cross-sectional survey of people with RCRSP recruited when referred for imaging (n = 120). Electronic survey about demographic factors, management people had had (including imaging, injections, surgery, exercise, adjuncts), and beliefs about treatments. The frequency of various treatments was reported (separately for each cohort and traumatic onset) as well as the timing of interventions related to first-line care. RESULTS: Most people had tried exercise (99/120, 82.5%) but only one in five people reported exercise was helpful, and one in six reported it was unhelpful or made their symptoms worse. Approximately a third of the cohort reported not receiving activity modification advice (34.2%, 41/120), those that did received inconsistent information. People with both traumatic (imaging 31/43, 72.1%; injections 13/24, 54.2%, surgery 8/21, 38.1%) and atraumatic onset pain (imaging 43/77, 55.8%; injections 31/51, 60.8%, surgery 4/19, 21.1%) had similarly high rates of intervention prior to trialling conservative management. Patient beliefs in regards to management showed trends towards interventionalist care. CONCLUSION: Patient reported management of RCRSP is often inconsistent with guideline recommended management.

Physiotherapists deliver management broadly consistent with recommended practice in rotator cuff tendinopathy: An observational study.

BACKGROUND: Rotator cuff tendinopathy is a common and disabling cause of shoulder pain. While conservative treatment is recommended as initial management, recent findings suggest that general practitioners and rheumatologists do not consistently align with recommended care. This study aimed to survey Australian physiotherapists to explore the extent to which recommended management is being applied. METHODS: A cross-sectional online survey. RESULTS: Five hundred and two Australian physiotherapists completed the survey. Results demonstrated the majority of physiotherapists provide conservative management consistent with guideline recommendations, through delivery of exercise and education, comparable to management by physiotherapists in the United Kingdom, Belgium and the Netherlands. Parameters and construction of exercise treatment programs were highly variable within the cohort, qualitative analysis highlighting varied reasoning underpinning these management decisions. CONCLUSIONS: Australian physiotherapists are broadly consistent with providing recommended management, however heterogeneity exists in the methods and parameters of treatment delivery.

Anisotropic behaviour of human gallbladder walls.

Inverse estimation of biomechanical parameters of soft tissues from non-invasive measurements has clinical significance in patient-specific modelling and disease diagnosis. In this paper, we propose a fully nonlinear approach to estimate the mechanical properties of the human gallbladder wall muscles from in vivo ultrasound images. The iteration method consists of a forward approach, in which the constitutive equation is based on a modified Hozapfel-Gasser-Ogden law initially developed for arteries. Five constitutive parameters describing the two orthogonal families of fibres and the matrix material are determined by comparing the computed displacements with medical images. The optimisation process is carried out using the MATLAB toolbox, a Python code, and the ABAQUS solver. The proposed method is validated with published artery data and subsequently applied to ten human gallbladder samples. Results show that the human gallbladder wall is anisotropic during the passive refilling phase, and that the peak stress is 1.6 times greater than that calculated using linear mechanics. This discrepancy arises because the wall thickness reduces by 1.6 times during the deformation, which is not predicted by conventional linear elasticity. If the change of wall thickness is accounted for, then the linear model can used to predict the gallbladder stress and its correlation with pain. This work provides further understanding of the nonlinear characteristics of human gallbladder.

A quasi-nonlinear analysis of the anisotropic behaviour of human gallbladder wall.

Estimation of biomechanical parameters of soft tissues from noninvasive measurements has clinical significance in patient-specific modeling and disease diagnosis. In this work, we present a quasi-nonlinear method that is used to estimate the elastic moduli of the human gallbladder wall. A forward approach based on a transversely isotropic membrane material model is used, and an inverse iteration is carried out to determine the elastic moduli in the circumferential and longitudinal directions between two successive ultrasound images of gallbladder. The results demonstrate that the human gallbladder behaves in an anisotropic manner, and constitutive models need to incorporate this. The estimated moduli are also nonlinear and patient dependent. Importantly, the peak stress predicted here differs from the earlier estimate from linear membrane theory. As the peak stress inside the gallbladder wall has been found to strongly correlate with acalculous gallbladder pain, reliable mechanical modeling for gallbladder tissue is crucial if this information is to be used in clinical diagnosis.

Cross-bridge apparent rate constants of human gallbladder smooth muscle.

This paper studies human gallbladder (GB) smooth muscle contractions. A two-state cross-bridge model was used to estimate the apparent attachment and detachment rate constants, as well as increased Ca2+ concentration from the peak active stress during the isometric contraction. The active stress was computed from a mechanical model based entirely on non-invasive routine ultrasound scans. In the two-state cross-bridge model, the two apparent rate constants, representing the total attached/detached cross-bridges, respectively, were estimated using active stress prediction for 51 subjects undergoing cholecystokinin-provocation test, together with estimates from the four-state cross-bridge model for a swine carotid, bovine tracheal and guinea pig GB smooth muscles. The study suggests that the apparent rate constants should be patient-specific, i.e. patients with a lower stress level are characterized by smaller apparent rate constants. In other words, the diseased GB may need to develop fast cycling cross-bridges to compensate in the emptying process. This is a first step towards more quantitative and non-invasive measures of GB pain, and may provide useful insight in understanding GB motility and developing effective drug treatments.

A mechanical model for CCK-induced acalculous gallbladder pain.

This study investigates the potential correlation between acalculous biliary pain and mechanical stress during the bile-emptying phase. This study is built on the previously developed mathematical model used to estimate stress in the gallbladder wall during emptying [Li, W. G., X. Y. Luo, et al. Comput. Math. Methods Med. 9(1):27-45, 2008]. Although the total stress was correctly predicted using the previous model, the contribution from patient-specific active stress induced by the cholecystokinin (CCK) test was overlooked. In this article, we evaluate both the active and passive components of pressure in a gallbladder, which undergoes isotonic refilling, isometric contraction and emptying during the infusion of CCK. The pressure is estimated from in vivo ultrasonographical scan measurements of gallbladder emptying during CCK tests, assuming that the gallbladder is a thin ellipsoidal membrane. The passive stress is caused by the volume and shape changes during refilling at the gallbladder basal pressure, whereas the active stress arises from the pressure rise during the isometric gallbladder contraction after the CCK infusion. The effect on the stress estimates of the gallbladder to the liver is evaluated to be small by comparing numerical simulations of a gallbladder model with and without a rigid 'flat top' boundary. The model was applied to 51 subjects, and the peak total stress was found to have a strong correlation with the pain stimulated by CCK, as measured by the patient pain score questionnaires. Consistent with our previous study for a smaller sample, it is found that the success rate in predicting of CCK-induced pain is over 75%.

Can intraoperative manometry during laparoscopic fundoplication predict postoperative dysphagia?

BACKGROUND: Many trials have used intraesophageal manometry (IEM) to measure the adequacy of fundoplication. This pilot study aimed to assess the value of IEM in predicting postoperative dysphagia. METHODS: A series of 40 patients underwent IEM studies before operative correction of gastroesophageal reflux disease and repeat studies 3 months after the procedure. During the operation, IEM studies were undertaken before pneumoperitoneum was established, after pneumoperitoneum, after pneumoperitoneum with fundoplication, and after fundoplication without pneumoperitoneum. All the patients were followed up 1, 6, and 12 months after the procedure for assessment to detect persistent reflux and postfundoplication dysphagia. RESULTS: Three patients demonstrated persistent dysphagia at the 12-month follow-up point. No statistically significant differences in preoperative manometry findings were observed in the dysphagic and nondysphagic groups, with the dysphagic group showing higher pressures. However, at the operation, statistically significant differences in the lower esophageal sphincter pressures were observed after anesthesia and no pneumoperitoneum (30.3 vs. 13.4 cm H(2)O; p =0.002), after anesthesia with pneumoperitoneum (40.3 vs. 18.3 cm H(2)O; p < 0.001), and after fundoplication with pneumoperitoneum (47.3 vs. 23.4 cm H(2)O; p = 0.001). No statistically significant differences were demonstrated in postoperative manometry at the 3-month follow-up point. CONCLUSION: Intraoperative manometry may be a useful tool compared with postoperative manometry in identifying patients who may experience postfundoplication dysphagia.

The effect of argon plasma coagulation ablation on esophageal motility and chemoreceptor sensitivity in Barrett's esophagus patients.

Patients with Barrett's esophagus usually demonstrate impaired esophageal motility, which affects acid clearance, together with reduced chemo-receptor sensitivity and symptom severity. Ablative endoscopic techniques are now used to eliminate Barrett's cells. The hypothesis for this study was that ablation with argon plasma coagulation (APC) may affect esophageal sensitivity and motility in patients with Barrett's esophagus, and the aim of this study was to assess differences in these parameters before and after APC treatment. Twenty patients with Barrett's esophagus were investigated before and after APC therapy. After standard pull through manometry, water bolus aliquots were given to assess primary peristalsis and rapid water and air bolus injections to assess secondary peristalsis. Sensitivity studies were carried out using weak solutions of either hydrochloric acid or sodium hydroxide, together with saline washouts. Onset time for typical symptoms (t), sensory intensity rating (I), and a sensory score (SS) = (t) x (I)/100 was observed. There were no significant differences in the lower esophageal sphincter pressures (13.6 mm Hg versus 12.6 mm Hg, P= 0.8) and successful test swallows (3 mm Hg versus 5 mm Hg, P= 0.5) before and after treatment, but there was a trend for secondary peristalsis to improve (air bolus 0 versus 2, P= 0.05, water bolus 0 versus 1, P= 0.07). Sensitivity studies showed a smaller sensitivity intensity rating to both acid (61 versus 31, P= 0.02) and alkaline (91 versus 64, P= 0.03) after treatment. In conclusion, we have shown no substantive changes in esophageal motility after ablation of Barrett's esophagus cells, but have demonstrated reduced sensitivity to reflux type solutions.

The NS3 proteins of global strains of bluetongue virus evolve into regional topotypes through negative (purifying) selection.

Comparison of the deduced amino acid sequences of the genes (S10) encoding the NS3 protein of 137 strains of bluetongue virus (BTV) from Africa, the Americas, Asia, Australia and the Mediterranean Basin showed limited variation. Common to all NS3 sequences were potential glycosylation sites at amino acid residues 63 and 150 and a cysteine at residue 137, whereas a cysteine at residue 181 was not conserved. The PPXY and PS/TAP late-domain motifs were conserved in all but three of the viruses. Phylogenetic analyses of these same sequences yielded two principal clades that grouped the viruses irrespective of their serotype or year of isolation (1900-2003). All viruses from Asia and Australia were grouped in one clade, whereas those from the other regions were present in both clades. Each clade segregated into distinct subclades that included viruses from single or multiple regions, and the S10 genes of some field viruses were identical to those of live-attenuated BTV vaccines. There was no evidence of positive selection on the S10 gene as assessed by reconstruction of ancestral codon states on the phylogeny, rather the functional constraints of the NS3 protein are expressed through substantial negative (purifying) selection.

The effect of photodynamic therapy (PDT) on oesophageal motility and acid clearance in patients with Barrett's oesophagus.

BACKGROUND: Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. It is proposed that long-term re-epithelialisation, which has been achieved following ablation using 5-aminolaevulinic acid (5-ALA) photodynamic therapy (PDT) may reduce the risk of malignant change. However, it is not known whether PDT modifies oesophageal motility. AIM: To assess oesophageal pH and motility before and after PDT ablation in treated and untreated areas of the oesophagus. METHODS: Twelve patients (10 male) with Barrett's oesophagus, median segment length 4 cm, were treated with PDT ablation. Twenty-four hours pH assessment and oesophageal manometry were performed before and 4-6 weeks after ablation. PDT was carried out using 635 nm red light, 4-6h after administration of 30 mg/kg 5-ALA. Proximal (untreated) and distal (treated) oesophageal resting pressure, wave amplitude, percentage peristalsis and percentage study time oesophageal pH<4, were assessed. Proton pump inhibitors (PPI) were administered throughout the study. RESULTS: There were no significant differences in oesophageal motility in treated or untreated areas of the oesophagus after PDT compared to pre-treatment values. Patients who continued to experience oesophageal acid exposure required more treatments to achieve complete Barrett's ablation. CONCLUSIONS: Oesophageal motility following ALA-PDT suggests a trend toward enhanced wave propagation however continued oesophageal acid exposure may affect PDT efficacy.

Bethanechol provocation testing does not predict symptom relief after cholecystectomy for acalculous biliary pain.

BACKGROUND: The currently accepted hypothesis to explain acalculous gallbladder pain is the lack of contractile co-ordination between the body and neck. We have previously shown that bethanechol, a muscarinic stimulant causes differential stimulation of these two regions. AIM: To evaluate the reliability of bethanechol-induced gallbladder contraction in predicting symptom relief after cholecystectomy in patients with acalculous gallbladder disease. METHODS: Fifty-one patients underwent a bethanechol provocation test together with serial ultrasound to determine gallbladder emptying. McGill pain questionnaires were completed, and patients positive for pain (bethanechol provocation test +ve) were offered cholecystectomy, and patients negative for pain (bethanechol provocation test -ve) were reassessed at 6 months and offered cholecystectomy if symptoms persisted. All patients answered pain questionnaires either 6 months after surgery or as follow-up. RESULTS: There was no difference in the percentage of gallbladder emptying between the bethanechol provocation test +ve and bethanechol provocation test -ve groups. Fifty-three percent of bethanechol provocation test +ve patients and 54% of bethanechol provocation test -ve patients still remained symptomatic 6 months after surgery. Conclusion. Gallbladder pain provoked by bethanechol does not predict symptom relief after cholecystectomy.

Querion de celso ulcerado por trichophyton mentagrophytes var. mentagrophytes / Ulcerated celso's kerion caused by trichophyton mentagrophytes var. mentagrophytes

La tiña del cuero cabelludo o tinea capitis es una de las enfermedades fúngicas más comúnmente observada en niños, originada frecuentemente por hongos dermatofitos del género microsporum y trichophyton. Clínicamente la tinea capitis se presenta de formas no inflamatorias a formas inflamatorias. Las formas inflamatorias se presentas desde una foliculitis pustular a querión de Celso. Se reporta un caso de un escolar de 10 años de edad, el cual acude al Instituto de Biomedicina de Hospital Vargas de Caracas por representar lesiones ulcerosas en cuero cabelludo. Sobre la base de la clínica observada y el estudio micológico, se establece el diagnóstico de querión de Celso, y el agente aislado al realizar el cultivo micológico fue Trichophyton mentagrophytes var. mentagrophytes. Recibe tratamiento con griseofulvina sistémica por 10 semanas, con resolución ad integrum del cuadro clínico. Esta variedad, cuya manera de presentación fue una gran úlcera en cuero cabelludo, representa una forma clínica muy infrecuente de queríon, que generalmente es originado por otros agentes causales como microsporum canis y microsporum gyseum.

Phylogenetic analysis of Alloglossidium (Digenea: Macroderoididae) and related genera: life-cycle evolution and taxonomic revision.

A phylogenetic analysis was performed on 13 species of digenetic trematodes in the Macroderoididae, including 10 species of Alloglossidium, 2 species of Alloglossoides, and Hirudicolotrema richardsoni. The evolution of the unusual life-cycle patterns in the group was assessed in light of the proposed phylogeny. The results support previous hypotheses that taxa with a 3-host life cycle involving catfish as definitive hosts are basal to taxa with a 2-host life cycle involving invertebrates such as crustaceans and leeches as definitive hosts. Our results also strongly suggest that species maturing in leeches evolved from an ancestor that matured in crustaceans. Our phylogeny places Alloglossoides and Hirudicolotrema within Alloglossidium, showing Alloglossidium to be paraphyletic. To achieve a natural classification, Alloglossoides and Hirudicolotrema are synonymized with Alloglossidium, and a revised generic diagnosis for Alloglossidium is given.

Phase I clinical trial of the chimeric monoclonal antibody (c30.6) in patients with metastatic colorectal cancer.

The murine antibody 30.6 recognizes an antigen that is expressed on a high proportion of colorectal carcinomas and their metastases. We report the results of single-dose escalation studies of the chimeric 30.6 (c30.6) monoclonal antibody in metastatic colorectal cancer, to evaluate its safety, pharmacokinetics, and biodistribution. Recombinant c30.6 (IgG1kappa) antibody was secreted from Chinese hamster ovary cells and purified by a multistep chromatography process. Seventeen patients with metastatic colorectal cancer were enrolled in this dose escalation study. The first four patients were treated with 3 mg of 123I-labeled c30.6, whereas the next 13 received a single dose of unlabeled antibody (maximum dose, 50 mg/m2). The most frequent side effect was a novel syndrome of severe burning and erythema of the face, chest, neck, ears, palms, soles, and genitalia. The frequency of this syndrome was markedly reduced in those patients premedicated with high doses of histamine receptor 1 and histamine receptor 2 blockers. Other side effects were mild and predictable. Biodistribution studies showed a rapid and intensive hepatic uptake. At the 50 mg/m2 level the half-life and maximum serum concentration were 81 +/- 15 h and 7.9 microg/ml, respectively. One patient developed a low-level human anti-c30.6 response. Tumor response was assessed by computed tomography, positron emission tomography scanning, and serial carcinoembryonic antigen measurements. There were no partial responses, although positron emission tomography scanning demonstrated some reduction in tumor activity in three individuals. The chimerized c30.6 antibody is not immunogenic in humans and appears worthy of further study. It does, however, produce a unique profile of side effects that can be well controlled with premedication.

A requiem for the cholecystokinin provocation test?

BACKGROUND: The cholecystokinin provocation test (CCKPT) has been claimed to predict a better symptomatic result after cholecystectomy in patients with acalculous biliary pain. AIMS: To examine the predictive value of the CCKPT for symptom relief after cholecystectomy in both CCKPT positive and negative patients. PATIENTS AND METHODS: Fifty eight patients with acalculous biliary pain underwent CCKPT with serial ultrasound gall bladder volumetry. CCKPT positive patients were offered cholecystectomy; negative patients were reassessed and were offered a cholecystectomy if symptoms persisted. Six months after cholecystectomy, the CCKPT was repeated. RESULTS: Of 32 CCKPT positive patients, 27 underwent cholecystectomy and of these, 18 (67%) became symptom-free. Postoperatively, 20 of 25 patients converted to CCKPT negative but five remained CCKPT positive and were symptomatic. Of the 26 CCKPT negative patients, nine became symptom-free without cholecystectomy; six of 14 (42.8%) patients undergoing cholecystectomy became asymptomatic and remained CCKPT negative. Cholecystectomy seemed to reduce symptoms in both groups, but there was no significant difference in the symptomatic outcome between preoperative CCKPT positive and negative patients. CONCLUSIONS: In this study, cholecystokinin provocation testing did not predict symptomatic benefit from cholecystectomy and we suggest it should no longer be used in the evaluation of patients with acalculous biliary pain.

A recombinant GM-CSF-PE40 ligand toxin is functionally active but not cytotoxic to cells.

A granulocyte/macrophage colony-stimulating factor (GM-CSF)-Pseudomonas exotoxin (PE) 40 fusion protein was constructed for potential use in the treatment of myeloid leukaemias, as a conditioning agent prior to allogeneic bone marrow transplantation or for ex vivo purging of malignant cells prior to autologous bone marrow transplantation. The GM-CSF-PE40 fusion protein successfully binds to the GM-CSF receptor and is capable of initiating a mitogenic signal similar to native GM-CSF in the GM-CSF-dependent TF1 cell line. The toxin component also appears to be fully functional as determined by an in vitro adenosine diphosphate-ribosylation assay. The GM-CSF-PE40 fusion protein, however, was not cytotoxic to a number of myeloid leukaemia cell lines. It is suggested that the mechanism of internalization of the GM-CSF receptor is not appropriate for the translocation of PE to the cytosol where it can fulfil its cytotoxic potential.

Effect of cisapride on oesophageal motility and duodenogastro-oesophageal reflux in patients with Barrett's oesophagus.

OBJECTIVE: Both gastric acid and duodenal juice have been implicated in Barrett's oesophagus. The aim of this study was to look at duodenal reflux in the oesophagus together with motility characteristics in a group of patients with Barrett's oesophagus and compare them with a mild oesophagitis group and to assess the effect of cisapride on any abnormalities. DESIGN: A prospective study comparing the two groups of patients was carried out. METHODS: Twenty patients with histologically proven Barrett's oesophagus and 20 patients with Savary-Miller grade 2 oesophagitis were studied. Standard oesophageal manometric measurements were carried out and on a separate occasion duodenogastro-oesophageal reflux (DGOR) was measured over a 4-h period using a sodium ion selective electrode. Patients with more than 5% DGOR were given cisapride (10 mg four times daily) and the studies repeated after 7 days of treatment. RESULTS: Barrett's patients showed more DGOR, 12.2% of the study time compared to 5.1% in the mild oesophagitis group, P = 0.012, but manometric findings were not significantly different. Sixteen patients were treated with cisapride. DGOR was reduced in 8 out of 12 Barrett's patients and 2 out of 4 oesophagitis patients, and proximal amplitude and distal oesophageal pressures were significantly elevated (P = 0.05 and P = 0.03, respectively). CONCLUSION: Monitoring of sodium ions in the oesophagus shows that patients with Barrett's oesophagus have significantly more DGOR than patients with uncomplicated oesophagitis and cisapride may be effective in removal of this reflux.

Detection of duodenal fluid in the oesophagus with a sodium ion selective electrode.

The assessment of duodeno-oesophageal reflux is difficult as, until recently, no technique has been readily available for continuous ambulatory monitoring. A sodium ion selective electrode placed in the stomach has been previously shown to detect duodenogastric reflux by using sodium as a marker. This relies on the difference in sodium concentration between gastric (5-60 mmol/L) and duodenal, biliary and pancreatic (150 mmol/L) fluids. In this pilot study to assess the efficacy of the electrode in the distal oesophagus, eight subjects without symptomatic gastro-oesophageal reflux and eight subjects with known duodenogastric reflux were studied. Thirty millilitre volumes of varying sodium solutions (40, 80, 100 and 140 mmol/L) were swallowed to assess the response of the electrode to sodium ions. In both groups, this revealed a constant and reproducible rise in response with increasing concentration (P < 0.0001). The stomachs of subjects with duodenogastric reflux were aspirated via a nasogastric tube to obtain 12 different samples of gastric fluid. This was assayed for sodium and bile acid concentration. The fluid was then reinfused as a 30 mL bolus into the oesophagus through a tube to simulate oesophageal reflux. A rise equivalent to 40-72 mmol/L Na+ was recorded by the electrode in response to samples that contained 58-81 mmol/L Na+ and 0.4-16 mmol/L bile acids, recorded by quantitative analysis, and a response of up to 20 mmol/L Na+ was recorded by the electrode to sodium concentrations < 49 mmol/L and bile acid concentrations of 0.005-0.6 mmol/L. The response was appropriate to the assayed bile acid concentration in all but one sample. The sodium ion selective electrode responds to bile containing fluids introduced into the oesophagus. Further investigation is warranted to determine its ability to measure duodeno-oesophageal reflux continuously.

Randomised, prospective, single-blind comparison of laparoscopic versus small-incision cholecystectomy.

BACKGROUND: We report a prospective randomised comparison between laparoscopic and small-incision cholecystectomy in 200 patients which was designed to eliminate bias for or against either technique. METHODS: Patients were randomised in the operating theatre and anaesthetic technique and pain-control methods were standardised. Four experienced surgeons did both types of procedure. Identical wound dressings were applied in both groups so that carers could be kept blind to the type of operation. FINDINGS: There was no significant difference between the groups for age, sex, body mass index, and American Society of Anaesthesiologists grade. Laparoscopic cholecystectomy took significantly longer than small-incision cholecystectomy (median 65 [range 27-140] min vs 40 [18-142] min, p<0.001). The operating time included operative cholangiography which was attempted in all patients. We found no significant difference between the groups for hospital stay (postoperative nights in hospital, median 3-0 [1-17] nights for laparoscopic vs 3-0 [1-14] nights for small-incision, p=0.74), time back to work for employed persons (median 5-0 weeks vs 4.0 weeks; p=0.39), and time to full activity (median 3-0 weeks vs 3.0 weeks; p=0.15). INTERPRETATION: Laparoscopic cholecystectomy takes longer to do than small-incision cholecystectomy and does not have any significant advantages in terms of hospital stay or postoperative recovery.