An anomalous band originating from the fabella causing semimembranosus impingement presenting as knee pain: a case report.

BACKGROUND: The presentation of patients with knee injuries which can have a significant impact on their ability to work and perform activities of daily living is constantly rising. The posterolateral corner of the knee has a complex anatomy of muscles, tendons, and ligaments, with huge variation in the population. The fabella is one such structure, found in the posterolateral corner of the knee, which can serve as a common origin point of various ligaments. CASE REPORT: We present a case report of a 53-year-old white man who presented with atraumatic, posterior knee pain and was found to have a congenital, anomalous band originating from the fabella, causing semimembranosus impingement. This was diagnosed with magnetic resonance imaging; he underwent division of the anomalous band, which resulted in complete resolution of his symptoms. CONCLUSION: We propose that patients who present with posterior knee pain, without any history of trauma, and have no abnormalities on plain radiographs, should undergo magnetic resonance imaging of their knees. This will help in assessing the ligament complex in the posterior compartment of the knee, and exclude impingement of the semimembranosus as an, albeit rare, cause of posteromedial knee pain.

Extracellular matrix microarrays to study inductive signaling for endoderm specification.

During tissue development, stem and progenitor cells are faced with fate decisions coordinated by microenvironmental cues. Although insights have been gained from in vitro and in vivo studies, the role of the microenvironment remains poorly understood due to the inability to systematically explore combinations of stimuli at a large scale. To overcome such restrictions, we implemented an extracellular matrix (ECM) array platform that facilitates the study of 741 distinct combinations of 38 different ECM components in a systematic, unbiased and high-throughput manner. Using embryonic stem cells as a model system, we derived definitive endoderm progenitors and applied them to the array platform to study the influence of ECM, including the interactions of ECM with growth factor signaling, on the specification of definitive endoderm cells towards the liver and pancreas fates. We identified ECM combinations that influence endoderm fate decisions towards these lineages, and demonstrated the utility of this platform for studying ECM-mediated modifications to signal activation during liver specification. In particular, defined combinations of fibronectin and laminin isoforms, as well as combinations of distinct collagen subtypes, were shown to influence SMAD pathway activation and the degree of hepatic differentiation. Overall, our systematic high-throughput approach suggests that ECM components of the microenvironment have modulatory effects on endoderm differentiation, including effects on lineage fate choice and cell adhesion and survival during the differentiation process. This platform represents a robust tool for analyzing effects of ECM composition towards the continued improvement of stem cell differentiation protocols and further elucidation of tissue development processes. STATEMENT OF SIGNIFICANCE: Cellular microarrays can provide the capability to perform high-throughput investigations into the role of microenvironmental signals in a variety of cell functions. This study demonstrates the utility of a high-throughput cellular microarray approach for analyzing the effects of extracellular matrix (ECM) in liver and pancreas differentiation of endoderm progenitor cells. Despite an appreciation that ECM is likely involved in these processes, the influence of ECM, particularly combinations of matrix proteins, had not been systematically explored. In addition to the identification of relevant ECM compositions, this study illustrates the capability of the cellular microarray platform to be integrated with a diverse range of cell fate measurements, which could be broadly applied towards the investigation of cell fate regulation in other tissue development and disease contexts.

A simple electronic alert for acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is frequently under-recognized and contributes to poor outcomes. Electronic alerts (e-alerts) to highlight AKI based on changes in serum creatinine may facilitate earlier recognition and treatment, and sophisticated algorithms for AKI detection have been proposed or implemented elsewhere. However, many laboratories currently lack the resources or capability to replicate these systems. METHODS: A real-time automated delta check e-alert flags a 50% increase in creatinine to a concentration of >50 µmol/L from the most recent result within a 90-day period and automatically adds the comment '?AKI - creatinine increase >50% from previous' with a link to local AKI guidelines. In addition, creatinine results >300 µmol/L are retrospectively reviewed and phoned if AKI is suspected. For each alert over a 12-day period we manually reviewed previous and subsequent creatinine results to determine baseline creatinine and stage AKI according to Acute Kidney Injury Network (AKIN) criteria. RESULTS: From 11,930 creatinine requests, 63 of 90 (70%) delta check e-alerts were due to AKI, identifying 61 episodes of AKI. Thirty four of 54 (63%) creatinine results >300 µmol/L were due to AKI, identifying a further 10 episodes of AKI. The positive predictive value (PPV) for AKI of a delta check e-alert was greater when the trigger creatinine was >100 µmol/L (PPV 89%) or when the absolute change in creatinine was >50 µmol/L (PPV 93%). CONCLUSION: This study demonstrates that a simple automated delta check can detect and flag AKI in real time, continuously, at little extra cost and without manual input.

Distributed and dynamic modelling of hydrology, phosphorus and ecology in the Hampshire Avon and Blashford Lakes: evaluating alternative strategies to meet WFD standards.

The issues of diffuse and point source phosphorus (P) pollution in the Hampshire Avon and Blashford Lakes are explored using a catchment model of the river system. A multibranch, process based, dynamic water quality model (INCA-P) has been applied to the whole river system to simulate water fluxes, total phosphorus (TP) and soluble reactive phosphorus (SRP) concentrations and ecology. The model has been used to assess impacts of both agricultural runoff and point sources from waste water treatment plants (WWTPs) on water quality. The results show that agriculture contributes approximately 40% of the phosphorus load and point sources the other 60% of the load in this catchment. A set of scenarios have been investigated to assess the impacts of alternative phosphorus reduction strategies and it is shown that a combined strategy of agricultural phosphorus reduction through either fertiliser reductions or better phosphorus management together with improved treatment at WWTPs would reduce the SRP concentrations in the river to acceptable levels to meet the EU Water Framework Directive (WFD) requirements. A seasonal strategy for WWTP phosphorus reductions would achieve significant benefits at reduced cost.

Enhanced 3-epi-25-hydroxyvitamin D3 signal leads to overestimation of its concentration and amplifies interference in 25-hydroxyvitamin D LC-MS/MS assays.

BACKGROUND: 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3) interferes in most liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for 25-hydroxyvitamin D (25OHD). The clinical significance of this is unclear, with concentrations from undetectable to 230 nmol/L reported. Many studies have quantified 3-epi-25OHD3 based on 25OHD3 calibrators or other indirect methods, and we speculated that this contributes to the observed variability in reported 3-epi-25OHD3 concentrations. METHODS: We compared continuous MS/MS infusions of 3-epi-25OHD3 and 25OHD3 solutions, spiked both analytes into the same serum matrix and analysed patient samples to assess the effect of three different quantitation methods on 3-epi-25OHD3 concentration. Experiments were performed on an LC-MS/MS system using a phenyl column which does not resolve 3-epi-25OHD3, and a modified method utilizing a Zorbax SB-CN column that chromatographically resolves 3-epi-25OHD3 from 25OHD3. RESULTS: A greater 3-epi-25OHD3 signal, compared with 25OHD3, was observed during equimolar post-column continuous infusion of analyte solutions, and following analysis of a serum pool spiked with both analytes. 3-epi-25OHD3 signal enhancement was dependent on mobile phase composition. Compared with 3-epi-25OHD3 calibrators, indirect quantitation methods resulted in up to 10 times as many samples having 3-epi-25OHD3 concentrations ≥ 10 nmol/L, and an approximately fourfold increase in the maximum observed 3-epi-25OHD3 concentration to 95 nmol/L. CONCLUSIONS: Enhanced 3-epi-25OHD3 signal leads to overestimation of its concentrations in the indirect quantitation methods used in many previous studies. The enhanced signal may contribute to greater interference in some 25OHD LC-MS/MS assays than others. We highlight that equimolar responses cannot be assumed in LC-MS/MS systems, even if two molecules are structurally similar.

Determination of the optimal stylet strategy for the C-MAC videolaryngoscope.

The C-MAC videolaryngoscope is a novel intubation device that incorporates a camera system at the end of its blade, thereby facilitating obtaining a view of the glottis without alignment of the oral, pharyngeal and tracheal axes. It retains the traditional Macintosh blade shape and can be used as a direct or indirect laryngoscope. We wished to determine the optimal stylet strategy for use with the C-MAC. Ten anaesthetists were allowed up to three attempts to intubate the trachea in one easy and three progressively more difficult laryngoscopy scenarios in a SimMan manikin with four tracheal tube stylet strategies: no stylet; stylet; directional stylet (Parker Flex-It); and hockey-stick stylet. The use of a stylet conferred no advantage in the easy laryngoscopy scenario. In the difficult scenarios, the directional and hockey-stick stylets performed best. In the most difficult scenario, the median (IQR [range]) duration of the successful intubation attempt was lowest with the hockey-stick stylet; 18 s (15-22 [12-43]) s, highest with the unstyletted tracheal tube; 60 s (60-60 [60, 60]) s and styletted tracheal tube 60 s (29-60 [18-60]) s, and intermediate with the directional stylet 21 s (15-60 [8-60]) s. The use of a stylet alone does not confer benefit in the setting of easy laryngoscopy. However, in more difficult laryngoscopy scenarios, the C-MAC videolaryngoscope performs best when used with a stylet that angulates the distal tracheal tube. The hockey-stick stylet configuration performed best in the scenarios tested.

Comparison of the C-MAC videolaryngoscope with the Macintosh, Glidescope, and Airtraq laryngoscopes in easy and difficult laryngoscopy scenarios in manikins.

The C-MAC comprises a Macintosh blade connected to a video unit. The familiarity of the Macintosh blade, and the ability to use the C-MAC as a direct or indirect laryngoscope, may be advantageous. We wished to compare the C-MAC with Macintosh, Glidescope and Airtraq laryngoscopes in easy and simulated difficult laryngoscopy. Thirty-one experienced anaesthetists performed tracheal intubation in an easy and difficult laryngoscopy scenario. The duration of intubation attempts, success rates, number of intubation attempts and of optimisation manoeuvres, the severity of dental compression, and difficulty of device use were recorded. In easy laryngoscopy, the duration of tracheal intubation attempts were similar with the C-MAC, Macintosh and Airtraq laryngoscopes; the Glidescope performed less well. The C-MAC and Airtraq provided the best glottic views, but the C-MAC was rated as the easiest device to use. In difficult laryngo-scopy the C-MAC demonstrated the shortest tracheal intubation times. The Airtraq provided the best glottic view, with the Macintosh providing the worst view. The C-MAC was the easiest device to use.

Pair potential of charged colloidal stars.

We report on the construction of colloidal stars: 1 microm polystyrene beads grafted with a dense brush of 1 microm long and 10 nm wide charged semiflexible filamentous viruses. The pair interaction potentials of colloidal stars are measured using an experimental implementation of umbrella sampling, a technique originally developed in computer simulations in order to probe rare events. The influence of ionic strength and grafting density on the interaction is measured. Good agreements are found between the measured interactions and theoretical predictions based upon the osmotic pressure of counterions.

Recovery of older patients undergoing ambulatory anaesthesia with isoflurane or sevoflurane.

BACKGROUND: Delayed recovery of cognitive function is a well-recognized phenomenon in older patients. The potential for the volatile anaesthetic used to contribute to alterations in postoperative cognitive function in older patients following minor surgical procedures has not been determined. We compared emergence from isoflurane and sevoflurane anaesthesia in older surgical patients undergoing urological procedures of short duration. METHODS: Seventy-one patients, 60 yr of age or older, undergoing anaesthesia expected to last less than 60 min for ambulatory surgery, were randomly assigned to receive isoflurane or sevoflurane. A standardized anaesthetic protocol was used, with intravenous fentanyl 1 microg kg(-1) and propofol 1.5-2.0 mg kg(-1) administered to induce anaesthesia. Anaesthesia was maintained with either sevoflurane or isoflurane in 65% nitrous oxide and oxygen. Early and intermediate recovery times were recorded. The Mini Mental State Examination and digit repetition forwards and backwards were administered at baseline, and at 1, 3 and 6 h postoperatively, to assess cognitive function. RESULTS: There were no between-group differences in (sevoflurane vs. isoflurane, mean +/- standard error of the mean) times to removal of the laryngeal mask airway (7.7 +/- 0.6 vs. 7.1 +/- 0.4 min), verbal response time (10.1 +/- 0.7 vs. 9.9 +/- 0.7 min) and orientation (12.1 +/- 0.7 vs. 12.1 +/- 0.7 min). Intermediate recovery, as measured by time to readiness for discharge from the post anaesthesia care unit (44.9 +/- 1.5 vs. 44.3 +/- 1.5 min), was similar in the two groups. Postoperative indices of cognitive function and attention were comparably reduced at 1 h, but returned to baseline in both groups at 6 h. CONCLUSIONS: Isoflurane and sevoflurane anaesthesia resulted in similar clinical and neurocognitive recovery profiles in older patients undergoing ambulatory surgical procedures of short duration.

Unmet need for recommended preventive health services among clients of California syringe exchange programs: implications for quality improvement.

BACKGROUND: Comprehensive preventive services are recommended for injection drug users (IDU), including screening tests, vaccinations, risk reduction counseling, and sterile syringes. Syringe exchange programs (SEP) may facilitate receipt of preventive services by IDUs, but whether SEP clients receive recommended preventive care is not known. We examined use of recommended preventive services by clients of 23 SEPs throughout California. METHODS: Five hundred and sixty SEP clients were recruited from 23 SEPs throughout California between March and September 2003. Receipt of 10 recommended preventive services and source of care (SEP versus non-SEP providers) was ascertained from client interviews. RESULTS: On average, SEP clients received only 13% of recommended preventive services and 49% of clients received none of the recommended services. Of services that were received, 76% were received from SEPs. In multivariate analysis, use of drug treatment and more frequent SEP visits were associated with receipt of recommended preventive services by clients. CONCLUSIONS: SEPs are often the only source of preventive care for their IDU clients. Still, SEP clients fail to receive most recommended preventive services. Interventions to increase use of preventive services and improve the quality of preventive care received by IDUs, such as increased access to drug treatment and SEPs, are needed.

The metabolic basis of arginine nutrition and pharmacotherapy.

As an essential precursor for the synthesis of proteins and other molecules with enormous biological importance (including nitric oxide, urea, ornithine, proline, polyamines, glutamate, creatine, agmatine, and dimethylarginines), arginine displays remarkable metabolic and regulatory versatility. Evidence available to date provides a sound reason to classify arginine as an essential amino acid for young mammals (including parenterally fed human infants) and as a conditionally essential amino acid for adults under such conditions as trauma, burn injury, massive small-bowel resection, and renal failure. Arginine administration reverses endothelial dysfunction, enhances wound healing, prevents the early stages of tumorigenesis, and improves cardiovascular, reproductive, pulmonary, renal, digestive, and immune functions. Arginine or its effective precursor citrulline may hold great promise as a nutritional or pharmacotherapeutic treatment for a wide array of human diseases.

On modelling the impacts of phosphorus stripping at sewage works on in-stream phosphorus and macrophyte/epiphyte dynamics: a case study for the River Kennet.

A new model of in-stream phosphorus and macrophyte dynamics, 'The Kennet model', was applied to a reach of the River Kennet, southern England. The reach, which is 1.5 km long, is immediately downstream of Marlborough sewage treatment works, where phosphorus reduction by tertiary effluent treatment began in September 1997. The model is used to simulate the flow, water chemistry and macrophyte biomass within the reach, both before and after phosphorus removal from the effluent. Monte Carlo experiments coupled with a general sensitivity analysis indicate that the model offers a feasible explanation for the salient aspects of the system behaviour. Model simulations indicate that epiphyte smothering is an important limitation to macrophyte growth, and that higher stream and pore water soluble reactive phosphorus (SRP) concentrations allow the earlier onset of growth for the epiphytes and macrophytes, respectively. Higher flow conditions are shown to reduce the simulated peak epiphyte biomass; though at present, the effect of flow on the macrophyte biomass is unclear. Another simulation result suggests that phosphorus will not be released from the bed sediments in this reach following phosphorus removal from the effluent.

Necrotizing fasciitis associated with injection drug use.

We studied cases of necrotizing fasciitis among injection drug users (IDUs) and non-IDUs who presented at the University of California Davis Medical Center from 1984 through 1999. Of 107 patients, 59 (55%) were IDUs and 48 (45%) non-IDUs. Among IDUs, 32 (54%) recently injected at the site of infection, and 17 patients (29%) presented with an abscess. Among non-IDUs, 17 (35%) reported a recent insect bite and 9 (19%) reported a wound or abrasion at the site of infection. Overall, seventy cases (65%) had > or = 3 debridements, and 31 patients (29%) had > 5% of their total body surface area debrided. Of all patients with necrotizing fasciitis, 16 (15%) did not survive. Among the 59 IDUs, 6 (10%) did not survive, while among non-IDUs, 10 (21%) did not survive. Our results indicate the need for a high index of suspicion for necrotizing fasciitis among patients presenting with cellulitis, a recent insect bite, wound, or recent injection drug use. Preventive interventions for necrotizing fasciitis among IDUs should include street-based education and treatment for abscesses and cellulitis.

Hepatitis C in methadone maintenance patients: prevalence and public policy implications.

OBJECTIVE: This study measured the extent and examined implications of hepatitis C (HCV) infection in a methadone maintenance treatment (MMT) population. METHOD: Four hundred and sixty patients were tested for HCV-Ab, hepatic enzymes and bilirubin, HCV-RNA, and hepatitis B antibody. RESULTS: Overall, 87% of this population had evidence of HCV-Ab. Among drug injectors (IDU), 96% were HCV-Ab positive. Among a subset of Laotian opium-smoking patients prevalence was only 11%. Sixty-two percent of patients with HCV-Ab had detectable HCV-RNA. Only 41% had elevated hepatic enzymes, and 5% had elevated bilirubin levels. All age groups were equally infected. Systemic problems in screening and treating HCV in drug users were identified. CONCLUSION: HCV infection poses significant long-term health risks for this population. Harm reduction interventions aimed at reducing transmission of HCV and other needle-related infectious disease deserves more consideration.