Expression of the melanocortin receptors MC2-R (ACTH-receptor) and MC5-R during embryonic development of ovine adrenals

Two melanocortin receptors MC2-R (ACTH-receptor) and MC5-R are expressed in the adult lamb adrenal cortex. In this work, we have studied the time-course of expression of these two receptors during ovine fetal development. MC2-R expression progressively increases from day 60 to day 140 of gestation (x3), then more rapidly before parturition and remains constant in the newborn. In contrast, the pattern of MC5-R expression is totally different. A strong increase is observed between days 60 and 120 (x7) then followed by a decrease until parturition and after birth. This peak of MC5-R expression precedes that of MC2-R, suggesting that MC5-R might be involved in alpha-MSH- and/or ACTH-stimulated corticosteroid synthesis during early embryonic life.     

Improvement of cyclosporin A-induced cholestasis by tauroursodeoxycholate in a long-term study in the rat

Cyclosporin A is an essential immunosuppressive drug, but it is potentially toxic to the kidney and liver. Ursodeoxycholic acid, a hydrophilic bile acid, has been reported to improve cholestasis in liver disease in man. The purpose of this work was to examine whether tauroursodeoxycholate could reduce cyclosporin A-induced hepatic or renal injuries in the rat. After randomization into three groups (N=8), rats received daily for 17 days: cyclosporin A intraperitoneally alone (30 mg/kg) or cyclosporin A intraperitoneally and tauroursodeoxycholate (60 mg/kg) by gavage; controls received the cyclosporin A excipient. Under tauroursodeoxycholate, cholestastic parameters (bile flow, bile salt secretion, serum bile salts, serum bilirubin) improved significantly without affecting cyclosporin A blood levels, and excretion of the drug and its metabolites in bile increased by 47%. Serum creatinine levels were better preserved, although not significantly. These results show that tauroursodeoxycholate prevents cyclosporin A-induced cholestasis in long-term treatment in rats, possibly by facilitating the drug elimination in bile.This work was supported by grants from the Caisse Régionale d'Assurance Maladie du Sud-Est and Houdé Laboratories.     

Assessment of prognosis of cirrhosis

Once patients with cirrhosis experience decompensation, early mortality risk increases sharply. Liver transplantation has transformed the prognosis of decompensated cirrhosis. Child-Pugh score has been the reference for many years for assessing the prognosis of cirrhosis. However, Child-Pugh score has important limitations among which is subjective interpretation of some of its variables, making it difficult to categorize patients according to their own disease severity. The model for end-stage liver disease (MELD) score, which was originally designed for assessing the prognosis of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), is a continuous score relying on three objective variables. Along with TIPS, MELD score proved to be a robust marker of early mortality across a wide spectrum of causes of cirrhosis, even though 10 to 20% of patients are still misclassified. MELD is especially useful for prioritizing candidates for transplantation according to a "sickest first" policy. However, MELD is not a universal prognostic marker of cirrhosis and several MELD exceptions require more specific approaches.     

Coagulation disorders in patients with cirrhosis and severe sepsis

Background: In patients with cirrhosis, severe sepsis may stimulate the extrinsic coagulation pathway resulting in thrombin generation and fibrin formation. Aims: To compare 23 patients with severe sepsis to 13 infected patients without severe sepsis and 18 patients without infection. Methods: Zymogen forms of clotting factors involved in the extrinsic pathway (i.e., factors VII+X, V, prothrombin), and the presence of soluble fibrin were assessed. Results: Zymogen forms of clotting factors were significantly lower, while Child–Pugh score and the proportion of patients with soluble fibrin were higher in the severe‐sepsis group than in the other groups. Decreased zymogen levels were independently correlated with an elevated Child–Pugh score and the presence of severe sepsis. In the severe‐sepsis group, after adjustment for the severity of cirrhosis, decreased zymogen levels were associated with significant increases in the relative risk ratios of in‐hospital death. Conclusions: Cirrhotic patients with severe sepsis have decreased blood levels of zymogen forms of factors VII+X, V, and prothrombin, which may be due not only to the severity of cirrhosis but also, at least in part, to the consumption of these zymogens by the extrinsic coagulation pathway.     

Cardiovascular disorders in patients with congenital portosystemic shunts: 23 years of experience in a tertiary referral centre

Central illustration. Time of occurrence and outcome of cardiovascular disorders in patients (pts) with congenital portosystemic shunt (CPSS). Patients with normal anatomy and those with congenital heart disease (CHD) were distinguished. Heart failure (HF) was the main symptom in both the prenatal and neonatal periods, whereas portopulmonary hypertension (PPH) and hepatopulmonary syndrome (HPS) represented the major concerns beyond the first months of life. CV: cardiovascular; NAS: no additional symptoms; PH: pulmonary hypertension; RD: respiratory distress. ^aFetal diagnosis of CPSS. ^bNeonatal diagnosis of CPSS. ^cDiagnosis of CPSS > 1 month of age

     

Idiopathic thrombotic thrombocytopenic purpura or Moschowitz syndrome: current physiopathologic and therapeutic perspectives

INTRODUCTION: The objective of this work was to review current data about the physiopathology, clinical features, and treatment of thrombotic thrombocytopenic purpura (Moschowitz's syndrome). CURRENT KNOWLEDGE AND KEY POINTS: Thrombotic thrombocytopenic purpura is a rare disorder characterized by widespread thrombotic injuries of platelets in the microcirculation. Its physiopathology has been elucidated recently. Evidence of a deficiency of Von Willebrand's factor-cleaving protease would be due to either IgG antibodies in the acute form of the disease or constitutional deficiency in the chronic form of the disease. FUTURE PROSPECTS AND PROJECTS: Plasma exchange is the current reference treatment. However, in the light of recent publications, either infusions of concentrates of purified enzyme or more intensive immunosuppressive therapy would be more specific.     

Interspecies differences with in vitro and in vivo models of vascular tissue engineering

In arterial replacement there is a clear clinical need for a functional substitute possessing appropriate haemocompatible properties to be implanted as small diameter artery. Endothelial cell seeding constitutes an appreciated method to improve blood compatibility on the condition that cells firmly adhere to the support. Along this way, an innovative technique based on multilayered polyelectrolyte films (PEM) as cell adhesive substrate was previously validated in vitro and in vivo in a small-animal model. In this study, we extended the work on a larger animal (sheep) to validate furthermore the paradigm of PEM functionalization for vascular substitutes. We tested in vitro: the efficiency of PEM to induce endothelial progenitor differentiation in sheep endothelial cells; the ability of PEM to sustain cell proliferation and allow resistance to shear stress; the fate of PEM-coated de-endothelialized human saphenous veins under flow conditions, a prerequisite step before in vivo experiments. Despite in vitro differences we were encouraged by testing in vivo PEM-coated prosthesis as carotid replacement in sheep, but without success. In order to explain the implantation failure, an in vitro haemocompatibility evaluation was performed that highlighted interspecies differences able to explain, at least in part, the graft failure obtained.     

Option Grids: Shared decision making made easier

Objective

To describe the exploratory use of short decision support tools for patients, called Option Grids. Option Grids are summary tables, using one side of paper to enable rapid comparisons of options, using questions that patients frequently ask (FAQs) and designed for face-to-face clinical encounters. To date, most evidence about ‘patient decision aids’ has been based on tools with high content levels, designed for patients to use independently, either before or after visits.

Methods

We studied the use of Option Grids in a quality improvement project, collecting field notes and conducting interviews with clinical teams.

Results

In the ‘Making Good Decisions in Collaboration’ (MAGIC) program, clinicians found that using Option Grids made it easier to explain the existence of options and reported a ‘handover’ effect, where patient involvement in decision making was enhanced.

Conclusion

Option Grids made options more visible and clinicians found it easier to undertake shared decision making when these tools were available. Used in a collaborative way, they enhance patients’ confidence and voice, increasing their involvement in collaborative dialogs.

Practice implications

Further work to confirm these preliminary findings is required, to measure processes and to assess whether these tools have similar impact in other clinical settings.