Identification of the calcitonin receptor in osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA). However, the presence of the calcitonin receptor (CTR) in articular cartilage chondrocytes is yet to be identified. In this study, we sought to further investigate the expression of the CTR in naïve human OA articular chondrocytes to gain further confirmation of the existents of the CTR in articular cartilage.</p> <p>Methods</p> <p>Total RNA was purified from primary chondrocytes from articular cartilage biopsies from four OA patients undergoing total knee replacement. High quality cDNA was produced using a dedicated reverse transcription polymerase chain reaction (RT-PCR) protocol. From this a nested PCR assay amplifying the full coding region of the CTR mRNA was completed. Western blotting and immunohistochemistry were used to characterize CTR protein on protein level in chondrocytes.</p> <p>Results</p> <p>The full coding transcript of the CTR isoform 2 was identified in all four individuals. DNA sequencing revealed a number of allelic variants of the gene including two potentially novel polymorphisms: a frame shift mutation, +473del, producing a shorter form of the receptor protein, and a single nucleotide polymorphism in the 3' non coding region of the transcript, +1443 C>T. A 53 kDa protein band, consistent with non-glycosylated CTR isoform 2, was detected in chondrocytes with a similar size to that expressed in osteoclasts. Moreover the CTR was identified in the plasma membrane and the chondrocyte lacuna of both primary chondrocytes and OA cartilage section.</p> <p>Conclusions</p> <p>Human OA articular cartilage chondrocytes do indeed express the CTR, which makes the articular a pharmacological target of salmon calcitonin. In addition, the results support previous findings suggesting that calcitonin has a direct anabolic effect on articular cartilage.</p

High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France

BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management

Be careful with triage in emergency departments: interobserver agreement on 1,578 patients in France

<p>Abstract</p> <p>Background</p> <p>For several decades, emergency departments (EDs) utilization has increased, inducing ED overcrowding in many countries. This phenomenon is related partly to an excessive number of nonurgent patients. To resolve ED overcrowding and to decrease nonurgent visits, the most common solution has been to triage the ED patients to identify potentially nonurgent patients, i.e. which could have been dealt with by general practitioner. The objective of this study was to measure agreement among ED health professionals on the urgency of an ED visit, and to determine if the level of agreement is consistent among different sub-groups based on following explicit criteria: age, medical status, type of referral to the ED, investigations performed in the ED, and the discharge from the ED.</p> <p>Methods</p> <p>We conducted a multicentric cross-sectional study to compare agreement between nurses and physicians on categorization of ED visits into urgent or nonurgent. Subgroups stratified by criteria characterizing the ED visit were analyzed in relation to the outcome of the visit.</p> <p>Results</p> <p>Of 1,928 ED patients, 350 were excluded because data were lacking. The overall nurse-physician agreement on categorization was moderate (kappa = 0.43). The levels of agreement within all subgroups were variable and low. The highest agreement concerned three subgroups of complaints: cranial injury (kappa = 0.61), gynaecological (kappa = 0.66) and toxicology complaints (kappa = 1.00). The lowest agreement concerned two subgroups: urinary-nephrology (kappa = 0.09) and hospitalization (kappa = 0.20). When categorization of ED visits into urgent or nonurgent cases was compared to hospitalization, ED physicians had higher sensitivity and specificity than nurses (respectively 94.9% versus 89.5%, and 43.1% versus 30.9%).</p> <p>Conclusions</p> <p>The lack of physician-nurse agreement and the inability to predict hospitalization have important implications for patient safety. When urgency screening is used to determine treatment priority, disagreement might not matter because all patients in the ED are seen and treated. But using assessments as the basis for refusal of care to potential nonurgent patients raises legal, ethical, and safety issues. Managed care organizations should be cautious when applying such criteria to restrict access to EDs.</p

Is capillary ketone determination useful in clinical practice

A new method is now available to measure capillary levels of 3-hydroxybutyrate (3HB), one of the three ketone bodies. It is a quantitative and enzymatic test that uses the same equipment as for home capillary blood glucose determination but with specific strips. In comparison to urine ketone test, there is no false negative or false positive results, it is highly correlate to standard automate assays and patients find it more acceptable. Clinical implementations of this new test begin to be reported. Some studies showed an advantage of ketonemia versus ketonuria measurement to detect and to treat diabetic ketoacidosis in the emergency room. In diabetic patients treated with continuous subcutaneous insulin infusion, ketonemia seems to be more relevant to detect lack of insulin. In the current care of patient with type 1 diabetes and especially in children blood ketone test is more effective than urine ketone test to prevent hospitalisation during sick days. For other situations such as diabetic pregnancy or type 2 diabetes, more data are needed to determine if capillary measurement of 3HB is really useful. This new test is easier and less unpleasant than doing urinary test but it is still far more expensive. Further clinical studies are needed to define whether self 3HB monitoring should substitute urinary test in outpatient care. Key-words: Ketonemia · 3-hydroxybutyrate · Ketonuria · Ketoacidosis · Self-monitoring. R É S U M É La mesure des concentrations capillaires de 3-hydroxybutyrate (3HB), un des trois corps cétoniques, est maintenant disponible. Elle repose sur une méthode enzymatique quantitative réalisée par un appareil identique à un lecteur glycémique avec des bandelettes spé-cifiques. Comparativement au test urinaire, il n&apos;y a pas de faux néga-tif ou de faux positif, les résultats sont hautement corrélés à ceux obtenus par automates standards et les patients la trouvent plus acceptable. Les intérêts cliniques de cette nouvelle méthode commencent à être rapportés dans la littérature. Certaines études ont montré un avantage de la mesure de la cétonémie par rapport à celle de la cétonurie pour détecter et traiter la céto-acidose diabétique aux Urgences. Chez les patients traités par pompe sous cutanée d&apos;insuline, la mesure de la cétonémie capillaire semble plus intéressante pour détecter la carence en insuline. Dans la prise en charge courante des patients diabétiques de type 1, en particulier chez l&apos;enfant, la mesure de la cétonémie capillaire est plus efficace que celle de la cétonurie pour prévenir une hospitalisation en cas d&apos;affection intercurrente. Dans d&apos;autres situations telles que le diabète au cours de la grossesse ou le diabète de type 2, des données supplémentaires sont nécessaires pour déterminer si la mesure capillaire du 3HB est vraiment utile. Ce nouveau test est simple et moins pénible que la réalisation des tests urinaires mais il est beaucoup plus cher. D&apos;autres études sont nécessaires pour savoir si l&apos;auto-surveillance du 3HB doit supplanter les tests urinaires dans le suivi ambulatoire des patients

Treatment of acute chloroquine poisoning: A 5-year experience

Objective: To describe various aspects of prognostic and therapeutic importance in patients treated for acute chloroquine poisoning, Design: Retrospective study, Setting: Toxicology intensive care unit (ICU) of a university hospital, interventions: None, Patients: One hundred sixty seven consecutive patients with acute chloroquine overdose admitted to our toxicology ICU, Measurements and Main Results: The mean amount ingested by history was 4.5 +/- 2.8 g, and 43 (26%) of 167 patients ingested >5 g, The mean blood chloroquine concentration on admission was 20.5 +/- 13.4 mu mol/L, The majority (87%) of our patients received at least one arm of a combination therapy regimen (epinephrine, mechanical ventilation, diazepam), Cardiac arrest occurred in 25 patients before hospital arrival; in seven of these patients, cardiac arrest occurred immediately after injection of thiopental, The mortality rate was 8.4% overall, and was 9.3% in patients with massive ingestions (NS vs. the group as a whole), We did not find a meaningful correlation between the amount ingested as estimated by history and the peak blood chloroquine concentration; the latter was highly correlated with the mortality rate, Conclusions: The mortality rate in patients with acute chloroquine poisoning, including those patients sick enough to be referred to a specialty unit such as ours, can be limited to less than or equal to 10%, This finding appears to be true even in patients with massive ingestions, We were not able to correlate mortality with amount ingested by history, although the mortality rate does correlate with blood chloroquine concentration, While early use of diazepam, epinephrine, and mechanical ventilation in most of our patients may have contributed to the excellent overall results, these elements, either singly or in combination, do not appear to have a truly antidotal effect in acute chloroquine poisoning, Thiopental, on the other hand, should be used with great caution, if at all, in such cases