Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: a pilot study.

Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option.     

Interruption of the infra-renal inferior vena cava with azygos continuation. Case report]

The authors report a case of congenital interruption of the inferior vena cava with azygos continuation with a deep venous thrombosis of the left lower extremity. It is a rare congenital abnormality which is most of the time asymptomatic. However such an abnormality may be a problem in case of cardiac catheterization or thoracic surgery.     

Closed tibial pilon fractures treated with external fixation

Fractures of tibial pilon are due to a high energy trauma. Associated skin complications are frequent as those of surgery of this pattern. Thus we performed external fixation as treatment for these fractures. Authors report a retrospective study of 17 closed fracture of tibial pilon, type C of Ruedi and Heim classification, treated by osteotaxis using external fixation of Hoffman with osteosynthesis of fibula by screwed plate. Our patients are of a mean age of 34 years with 11 men and 6 women. The right side was most frequently involved (12 patients). Skin injuries as phlyctena were seen in 6 patients. Delay of treatment did not exceed 72 h. We performed a closed reduction of the fracture of tibial pilon after internal fixation of fibula by screwed plate. Results were assessed after 24 months of study. Track pins infection was noted in three cases. Reduction was usually good, despite one case of recurvatum, one case of valgus, one case of Sudeck’s atrophy, three cases of arthritis have been noticed. Mobility decreased at about 30%. External fixation is a real alternative solution for treatment of these fractures for which osteosynthesis is not suitable. It allows us to avoid skin complications despite mobility decreasing.      

Permanent access to the portal system for cellular transplantation using an implantable port device.

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.     

Foscarnet salvage therapy efficacy is associated with the presence of thymidine-associated mutations (TAMs) in HIV-infected patients

BACKGROUND: Salvage therapy based on foscarnet plus a thymidine analog is effective in patients with advanced-stage HIV disease and viruses harbouring multiple drug-resistance mutations. OBJECTIVE: To identify viral genetic determinants associated with the virological efficacy of foscarnet salvage therapy. STUDY DESIGN: Thirteen patients received foscarnet at a fixed dose of 80mg/kg twice daily for 14 days, in combination with zidovudine or stavudine. RESULTS: The baseline median HIV viral load and CD4 cell count were 5.10log(10)copies/ml and 23cells/mm(3), respectively. Following foscarnet therapy, viral load fell by a median of 1.84log(10)copies/ml (range: -0.29 to -2.82), and by at least 1log(10)copies/ml in 11 patients, all of whom harboured viruses with at least three thymidine-associated mutations (TAMs). The two patients with smaller declines in viral load (<0.50log(10)copies/ml) harboured viruses with only one or zero TAMs. CONCLUSIONS: These findings corroborate, in vivo, the impact of TAMs on HIV susceptibility to foscarnet. The virological response to foscarnet salvage therapy in multiclass-experienced patients may thus differ according to the number of TAMs.     

Tolerance to self gangliosides is the major factor restricting the antibody response to lipopolysaccharide core oligosaccharides in Campylobacter jejuni strains associated with Guillain-Barré syndrome

Guillain-Barré syndrome following Campylobacter jejuni infection is frequently associated with anti-ganglioside autoantibodies mediated by molecular mimicry with ganglioside-like oligosaccharides on bacterial lipopolysaccharide (LPS). The regulation of antibody responses to these T-cell-independent antigens is poorly understood, and only a minority of Campylobacter-infected individuals develop anti-ganglioside antibodies. This study investigates the response to gangliosides and LPS in strains of mice by using a range of immunization strategies. In normal mice following intraperitoneal immunization, antibody responses to gangliosides and LPS are low level but can be enhanced by the antigen format or coadministration of protein to recruit T-cell help. Class switching from the predominant immunoglobulin M (IgM) response to IgG3 occurs at low levels, suggesting B1-cell involvement. Systemic immunization results in poor responses. In GalNAc transferase knockout mice that lack all complex gangliosides and instead express high levels of GM3 and GD3, generation of anti-ganglioside antibodies upon immunization with either complex gangliosides or ganglioside-mimicking LPS is greatly enhanced and exhibits class switching to T-cell-dependent IgG isotypes and immunological memory, indicating that tolerance to self gangliosides is a major regulatory factor. Responses to GD3 are suppressed in knockout mice compared with wild-type mice, in which responses to GD3 are induced specifically by GD3 and as a result of polyclonal B-cell activation by LPS. The anti-ganglioside response generated in response to LPS is also dependent on the epitope density of the ganglioside mimicked and can be further manipulated by providing secondary signals via lipid A and CD40 ligation.     

Synthesis and physical properties of telechelic monodispersed diols 4. Monoaddition of 10-undecenol to novel dithiols

The synthesis of novel telechelic monodispersed diols produced from the radical monoaddition of an excess of 10-undecenol with novel α, ω-dithiols, initiated by peroxides, is presented. The telechelic dithiols employed were prepared from nonconjugated dienes and a commercially available dithiol, or by esterification of adipic acid with 2-mercaptoethanol. From these dithiols, the diols were selectively obtained in high yields. Such α, ω-dihydroxylated compounds were characterized by both ¹H and ¹³C NMR spectroscopy. The diol which exhibits the ester functions shows excellent solubility in common organic solvents contrarily to the other ones. The physical properties (T_g, T_m and decomposition temperatures) of these diols were compared and it is noted that the thermostability of these monodispersed telechelic diols is much better than those of the polydispersed commercially available ones such as poly(ethylene glycol)s or poly(tetramethylene glycol)s.     

Hybrid Approach to Estimation of Underreporting of Tuberculosis Case Notification in High-Burden Settings With Weak Surveillance Infrastructure: Design and Implementation of an Inventory Study

BackgroundThe greatest risk of infectious disease undernotification occurs in settings with limited capacity to detect it reliably. World Health Organization guidance on the measurement of misreporting is paradoxical, requiring robust, independent systems to assess surveillance rigor. Methods are needed to estimate undernotification in settings with incomplete, flawed, or weak surveillance systems. This study attempted to design a tuberculosis (TB) inventory study that balanced rigor with feasibility for high-need settings.ObjectiveThis study aims to design a hybrid TB inventory study for contexts without World Health Organization preconditions. We estimated the proportion of TB cases that were not reported to the Ministry of Health in 2015. The study sought to describe TB surveillance coverage and quality at different levels of TB care provision. Finally, we aimed to identify structural-, facility-, and provider-level barriers to notification and reasons for underreporting, nonreporting, and overreporting.MethodsRetrospective partial digitalization of paper-based surveillance and facility records preceded deterministic and probabilistic record linkage; a hybrid of health facilities and laboratory census with a stratified sampling of HFs with no capacity to notify leveraged a priori knowledge. Distinct extrapolation methods were applied to the sampled health facilities to estimate bacteriologically confirmed versus clinical TB. In-depth interviews and focus groups were used to identify causal factors responsible for undernotification and test the acceptability of remedies.ResultsThe hybrid approach proved viable and instructive. High-specificity verification of paper-based records in the field was efficient and had minimal errors. Limiting extrapolation to clinical cases improved precision. Probabilistic record linkage is computationally intensive, and the choice of software influences estimates. Record absence, decay, and overestimation of the private sector TB treatment behavior threaten validity, meriting mitigation. Data management demands were underestimated. Treatment success was modest in all sectors (R=37.9%–72.0%) and did not align with treatment success reported by the state (6665/8770, 75.99%). One-fifth of TB providers (36/178, 20%) were doubtful that the low volume of patients with TB treated in their facility merited mastery of the extensive TB notification forms and procedures.ConclusionsSubnational inventory studies can be rigorous, relevant, and efficient in countries that need them even in the absence of World Health Organization preconditions, if precautions are taken. The use of triangulation techniques, with minimal recourse to sampling and extrapolation, and the privileging of practical information needs of local decision makers yield reasonable misreporting estimates and viable policy recommendations.