Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57Bl/6 mouse heart

Mercury exposure is associated with increased risk of cardiovascular disease and profound cardiotoxicity. However, the correlation between Hg²⁺-mediated toxicity and alteration in cardiac cytochrome P450s (Cyp) and their dependent arachidonic acid metabolites has never been investigated. Therefore, we investigated the effect of acute mercury toxicity on the expression of Cyp-epoxygenases and Cyp-ω-hydroxylases and their associated arachidonic acid metabolites in mice hearts. In addition, we examined the expression and activity of soluble epoxide hydrolase (sEH) as a key player in arachidonic acid metabolism pathway. Mercury toxicity was induced by a single intraperitoneal injection (IP) of 2.5 mg/kg of mercuric chloride (HgCl₂). Our results showed that mercury treatment caused a significant induction of the cardiac hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP); in addition to Cyp1a1, Cyp1b1, Cyp2b9, Cyp2b10, Cyp2b19, Cyp2c29, Cyp2c38, Cyp4a10, Cyp4a12, Cyp4a14, Cyp4f13, Cyp4f15, Cyp4f16 and Cyp4f18 gene expression. Moreover, Hg²⁺ significantly increased sEH protein expression and activity levels in hearts of mercury-treated mice, with a consequent decrease in 14,15-, and 11,12-epoxyeicosatrienoic acids (EETs) levels. Whereas the formation of 14,15-, 11,12-, 8,9-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. In conclusion, acute Hg²⁺ toxicity modulates the expression of several Cyp and sEH enzymes with a consequent decrease in the cardioprotective EETs which could represent a novel mechanism by which mercury causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent Hg²⁺-induced hypertrophy.     

An exploratory analysis of the regionalization policy for the recruitment of health workers in Burkina Faso

Background

Health personnel retention in remote areas is a key health systems issue wordwide. To deal with this issue, since 2002 the government of Burkina Faso has implemented a staff retention policy, the regionalized health personnel recruitment policy, aimed at front-line workers such as nurses, midwives, and birth attendants. This study aimed to describe the policy’s development, formulation, and implementation process for the regionalization of health worker recruitment in Burkina Faso.

Methods

We conducted a qualitative study. The unit of analysis is a single case study with several levels of analysis. This study was conducted in three remote areas in Burkina Faso for the implementation portion, and at the central level for the development portion. Indepth interviews were conducted with Ministry of Health officials in charge of human resources, regional directors, regional human resource managers, district chief medical officers, and health workers at primary health centres. In total, 46 indepth interviews were conducted (February 3 - March 16, 2011).

Results

Development The idea for this policy emerged after finding a highly uneven distribution of health personnel across urban and rural areas, the availability of a large number of health officers in the labour market, and the opportunity given to the Ministry of Health by the government to recruit personnel through a specific budget allocation. Formulation The formulation consisted of a call for job applications from the Ministry of Health, which indicates the number of available posts by region.The respondents interviewed unanimously acknowledged the lack of documents governing the status of this new personnel category. Implementation During the initial years of implementation (2002-2003), this policy was limited to recruiting health workers for the regions with no possibility of transfer. The possibility of job-for-job exchange was then approved for a certain time, then cancelled. Starting in 2005, a departure condition was added. Now, regionalized health workers can leave the regions after undergoing a competitive selection process.

Conclusion

The policy was characterized by the absence of written directives and by targeting only one category of personnel. Moreover, there was no associated incentive—financial or otherwise—which poses the question of long-term viability.

Contexte

Le maintien en poste du personnel de la santé dans des régions éloignées est un des principaux problèmes des systèmes de santé partout dans le monde. Pour tenter de régler ce problème, le gouvernement du Burkina Faso a mis en oeuvre depuis 2002 une politique de rétention du personnel dite politique de recrutement régionalisé du personnel de la santé qui concerne les agents de première ligne que sont le personnel infirmier, les sages-femmes et les accoucheuses. Le présent article a pour objectif de décrire le processus d’émergence, de formulation et de mise en oeuvre de cette politique de régionalisation du recrutement du personnel de la santé au Burkina Faso.

Méthodes

Nous avons mené une étude qualitative. L’unité d’analyse est une étude de cas unique avec plusieurs niveaux d’analyse. L’étude a été menée dans trois régions éloignées du Burkina Faso pour la mise en oeuvre et de façon centralisée pour l’émergence. Des entrevues approfondies ont été menées avec des fonctionnaires du ministère de la Santé qui étaient ou ont été responsables des ressources humaines, des directeurs régionaux, des gestionnaires régionaux des ressources humaines, des médecins-chefs de districts et des travailleurs de la santé dans des centres de soins de santé primaires. Au total, 46 entrevues approfondies ont été menées avec des intervenants de différents groupes entre le 3 février et le 16 mars 2011.

Résultats

Émergence L’idée de cette politique a émergé à la suite du constat de la répartition très inégale entre milieux urbains et ruraux du personnel de la santé d’une part, et d’autre part de la disponibilité d’un grand nombre d’agents de santé sur le marché du travail et de la possibilité offerte au ministère de la Santé de recruter du personnel grâce à l’allocation d’un budget spécifique par le gouvernement. Formulation La formulation consistait en un appel de candidature du ministère de la Santé qui indiquait le nombre de postes disponibles par région.Les participants rencontrés sont unanimes pour reconnaitre l’inexistence de lignes directrices concernant le statut de cette nouvelle catégorie de personnel. Mise en oeuvre Au cours des premières années de sa mise en oeuvre (2002-2003), cette politique se résumait aux recrutements du personnel pour les régions sans aucune possibilité de départ. La possibilité d’effectuer une permutation poste pour poste a été acceptée un certain temps, puis a de nouveau été supprimée. À partir de 2005, une condition de départ a été ajoutée. Désormais, les agents régionalisés peuvent quitter les régions après l’admission à un concours professionnel.

Conclusions

Cette politique est limitée par l’absence de lignes directrices écrites et par le fait qu’elle ne s’adresse qu’à une catégorie de personnel. De plus, aucun incitatif, financier ou non, n’y a été associé, ce qui pose le problème de sa viabilité à long terme.

     

Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results

In 2008, we reported favorable 5-year outcomes of nonmyeloablative allogeneic stem cell transplantation after fludarabine, cyclophosphamide, rituximab (FCR) conditioning for relapsed and chemosensitive follicular lymphoma. However, innovative strategies were still needed to treat patients with chemorefractory disease. We therefore subsequently performed a trial in which (90)Y-ibritumomab tiuxetan (0.4 mCi/kg) was added to the fludarabine, cyclophosphamide conditioning regimen ((90)YFC). Here, we report updated results of the FCR trial and outcomes after (90)YFC. For the FCR group (N = 47), since the last update, one patient developed recurrent disease. With a median follow-up of 107 months (range, 72-142 months), the 11-year overall survival and progression-free survival rates were 78%, and 72%, respectively. For the (90)YFC group (N = 26), more patients had chemorefractory disease than did those in the FCR group (38% and 0%, P < .001). With a median follow-up of 33 months (range,17-94 months), the 3-year progression-free survival rates for patients with chemorefractory and chemosensitive disease were 80% and 87%, respectively (P = .7). The low frequency of relapse observed after a long follow-up interval of 9 years in the FCR group suggests that these patients are cured of their disease. The addition of (90)Y to the conditioning regimen appears to be effective in patients with chemorefractory disease. This trial was registered at www.clinicaltrials.gov as NCT00048737.     

Ectopic Cushing’s syndrome due to a mesenteric neuroendocrine tumour

INTRODUCTION

Neuroendocrine tumours (NETs) are tumours that commonly involve the gastrointestinal system. Common primary sites in the gastrointestinal system include the small intestine, appendix, rectum and pancreas. Mesenteric NETs are extremely rare entities and are sparsely reported in the literature.

CASE HISTORY

We report the case of a 62-year-old woman with ectopic Cushing’s syndrome due to excessive adrenocorticotropic hormone secretion by a primary mesenteric tumour in the small intestine and its liver metastases.

CONCLUSIONS

Although rare, the mesentery can be a primary site for NETs. It can cause similar symptoms and require similar treatment options. Tumour resection and debulking are acceptable ways to improve both the survival and symptoms.     

TKA results are not compromised by previous arthroscopic procedures

This study investigated whether two or more previous arthroscopic procedures had an effect on the outcomes of total knee arthroplasty (TKA). We compared 60 patients (62 knees) who had a mean age of 56 years, a mean follow-up of 39 months (range, 26 to 68 months), and a minimum of two arthroscopic procedures before their TKA with a group of patients (n = 438) who underwent TKAs without any previous knee surgery. Clinical outcome was evaluated using Knee Society objective and function scores. Implant survivorship, with revision for aseptic component failure as an end point, was 98% in both cohorts. In the postarthroscopic group, the mean Knee Society objective and function scores improved to a mean of 92 and 89 points, respectively. Radiographic analysis did not find any differences between the two groups. In conclusion, the authors did not find that earlier arthroscopic procedures negatively affected the outcome of TKA.     

Mechanical,Anatomical, and Kinematic Axis in TKA: Concepts and Practical Applications

Successful total knee arthroplasty (TKA) has often been based on the restoration of the knee to neutral alignment postoperatively. Numerous reports have linked malaligned TKA components to increased wear, poor functional outcomes, and failure. There have been many different alignment philosophies and surgical techniques that have been established to attain the goal of proper alignment, which includes such techniques as computerized navigation, and custom cutting guides. In addition, these methods could potentially have the added benefit of leading to improved functional outcomes following total knee arthroplasty. In this report, we have reviewed and analyzed recent reports concerning mechanical, anatomic, and kinematic axis/alignment schemes used in total knee arthroplasty.