An African horse sickness virus serotype 4 recombinant canarypox virus vaccine elicits specific cell-mediated immune responses in horses.

A recombinant canarypox virus vectored vaccine co-expressing synthetic genes encoding outer capsid proteins, VP2 and VP5, of African horse sickness virus (AHSV) serotype 4 (ALVAC(®)-AHSV4) has been demonstrated to fully protect horses against homologous challenge with virulent field virus. Guthrie et al. (2009) detected weak and variable titres of neutralizing antibody (ranging from <10 to 40) 8 weeks after vaccination leading us to hypothesize that there could be a participation of cell mediated immunity (CMI) in protection against AHSV4. The present study aimed at characterizing the CMI induced by the experimental ALVAC(®)-AHSV4 vaccine. Six horses received two vaccinations twenty-eight days apart and three horses remained unvaccinated. The detection of VP2/VP5 specific IFN-γ responses was assessed by enzyme linked immune spot (ELISpot) assay and clearly demonstrated that all ALVAC(®)-AHSV4 vaccinated horses developed significant IFN-γ production compared to unvaccinated horses. More detailed immune responses obtained by flow cytometry demonstrated that ALVAC(®)-AHSV4 vaccinations induced immune cells, mainly CD8(+) T cells, able to recognize multiple T-epitopes through all VP2 and only the N-terminus sequence of VP5. Neither VP2 nor VP5 specific IFN-γ responses were detected in unvaccinated horses. Overall, our data demonstrated that an experimental recombinant canarypox based vaccine induced significant CMI specific for both VP2 and VP5 proteins of AHSV4.

[French 2008 guidelines on peritoneal dialysis: indications and non-indications]. / Indications et non-indications de la dialyse péritonéale chronique chez l'adulte. Recommandations françaises en 2008.

The new French guidelines on Peritoneal Dialysis (PD) were published in october 2008 by the "Haute Autorité de Santé (HAS)". The field of these guidelines concerned the choice between PD and Hemodialysis (HD), on a strict medical point of view. This paper summarizes the main French PD guidelines, highlighting the new insights compared to previous guidelines. For the first time, guidelines described 5 clinical situations requiring the choice between PD or HD : 1) criteria for choosing PD in a new dialysis patient ; 2) criteria for switching a patient from PD to HD ; 3) criteria for switching a patient from HD to PD ; 4) PD or HD before kidney transplantation ; 5) PD or HD after graft failure. For a new dialysis patient, PD is recommended, more than HD, for cirrhotic patients with ascites, kidney failure due to cholesterol embolism, difficulties for HD-vascular access. PD is not recommended in only a few cases : morbid obesity (BMI>45 kg /m(2)), irreparable abdominal hernias. It is recommended to switch from PD to HD, patients with more than 3 peritonitis/year, due to digestive bacteria ; weight gain > 15 % per year ; triglycerid serum level > 10 g/l ; loss of peritoneal efficiency. It is recommended to switch from HD to PD patients with vascular access failure ; hemodynamic instability during HD sessions ; severe congestive heart failure. PD or HD can be indistinctly used before kidney or combined pancreas-kidney graft. These new French guidelines are more complete and more accurate than the previous French or international guidelines.

[Hand allografts: experience from Lyon team]. / Allogreffe de mains: expérience lyonnaise.

Hand allograft is a method in the stage of clinical experimentation, which is reserved in France for the treatment of bilateral traumatic amputees. This study reports the Lyon team experience, which is pioneer in this domain. Four patients (3 males and 1 female) underwent seven (one unilateral and three bilateral) hand transplantations from September 1998 to February 2007. The level of amputation was at the wrist or at the mid-forearm. Delay since hand loss ranged from 2.5 to 9 years. The surgical protocol was elaborated and planned case by case. All recipients received the same immunosuppressive treatment. Episodes of acute rejection were observed in the first 3 months after transplantation, which were easily managed after a few days increasing oral prednisone doses and applying topical immunosuppressants. Currently the patients receive the doses of immunosuppressants comparable to those in kidney-grafted patients. We have not registered any severe complication of immunosuppressive treatment up till now (7 years follow-up for the earliest graft). We performed analytical and functional clinical, as well as questionnaire evaluation of patients. The first case (unilateral graft) resulted in graft failure at 2 years due to non-compliance of the patient. The three bilateral graftees demonstrate a favorable evolution despite some immunological (hyperglycemia, serum sickness) and surgical (thrombosis, osteomyelitis, skin loss) complications, which could be managed. The middle and long-term follow-up evaluation revealed good to excellent sensorimotor recovery of 4 hands in both male recipients (4 and 7 years) with satisfactory social adaptation, higher or equal to those expected after post-traumatic replantations at the equivalent level and higher to those obtained with currently available myoelectric prosthesis. The last patient, a young female who has been grafted in February 2007, receives ongoing reeducation course and shows normal progress of functional restoration of both hands. The encouraging results of this clinical experimentation make us currently consider hand allografting as reasonable and useful both for the patients and for evolution of research in composite tissues allotransplantation (CTA). Further long-term careful research and worldwide monitoring of all patients with hand allografts is required to, on the one part, state on the authorization of this surgery, and, on the other part, to better elucidate the mechanisms of successful CTA.

[Infection peritonitis in patients undergoing continuous ambulatory peritoneal dialysis: microbiological review during an four-year period]. / Péritonites infectieuses chez les patients traités par dialyse péritonéale: bilan microbiologique sur quatre ans.

The purpose of this study was to analyse the microbiological characteristics of infectious peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. This study was conducted at the CHU Nancy from 1999 to 2002. The diagnosis of peritonitis was based on cloudy peritoneal effluent (>100 cells per mm(3)) with an elevated leukocyte count (>50%), on isolation of bacteria or fungi and on symptoms such as abdominal discomfort or pain. The majority of infections associated with continuous ambulatory peritoneal dialysis were caused by Gram-positive bacteria (68%), Gram-negative bacteria (31%), and Candida (1%). The coagulase-negative staphylococci were the most common cause of peritonitis. The antibiotic sensitivity of species corresponded to community-acquired isolation.

Evaluation of low-pressure arterial and venous clamps: electron microscopic study and possible clinical applications.

These authors report on validating their choice of disposable clamps in arterial and venous microsurgery in a comparative and experimental study using the scanning electron microscope. This appears to be the first evaluation of venous endothelial clamping lesions. Early intimal clamping lesions were studied using three different clamps and two protocols in 18 femoral arteries and veins in rabbits. Results were evaluated using a new classification that can be applied to both arterial and venous lesions: Grade I: cellular disorientation and disorganization; endothelial lamination; and absent or very few platelet deposits; Grade II: alterations of the cytoplasmic membranes in fusiform cells; presence of at least one breach of endothelial continuity; and moderate number of platelet deposits; Grade III: presence of endothelial detachment; and large numbers of platelet deposits. They showed that in arteries, all the clamps tested caused only low-grade lesions. In contrast, in veins, they demonstrated both the very fragile nature of the endothelium, and also the comparative safety of the low-pressure venous clamp. Their choice of specific clamps for venous anastomoses was validated.

Mobilization of lead from bone in end-stage renal failure patients with secondary hyperparathyroidism.

BACKGROUND: It is now recognized that long-term exposure to even low levels of lead may increase bone lead content. Lead can then be released in toxicologically significant amounts during critical states of increased bone turnover. METHODS: Two patients with end-stage renal failure, one on haemodialysis and the other on continuous ambulatory peritoneal dialysis (CAPD), had been exposed to lead and developed secondary hyperparathyroidism. An edetate calcium disodium (EDTA) test was performed in combination with haemofiltration or CAPD before and after parathyroidectomy. RESULTS: Before parathyroidectomy, both patients had low delta aminolaevulinic acid dehydrase (ALA-D) and high concentrations of chelated lead. After parathyroidectomy, there was a dramatic decrease in chelated lead and the ALA-D returned to normal. CONCLUSION: Secondary hyperparathyroidism increases mobilization of bone lead in dialysis patients with an elevated lead burden. This may cause toxic effects.

[Adequate peritoneal dialysis: limitations of continuous ambulatory peritoneal dialysis (CAPD), place of automated peritoneal dialysis (APD)]. / Dialyse péritonéale adéquate: limites de la dialyse péritonéale continue ambulatoire (DPCA), place de la dialyse péritonéale automatisée (DPA).

Recent epidemiological studies show a slowing down of the global growth of CAPD which is not compensated by the considerable development of APD. These modifications are the result of the arrival of technologies which allow new strategies as well as an improved knowledge of the adequate dialysis dose for PD. The re-evaluation of the adequate clearance targets show that CAPD does not deliver an adequate dialysis dose for anuric patients but it remains an excellent technique for patients with residual renal function. APD and mixed techniques (APD with automated diurnal exchange(s), CAPD with automated nocturnal exchange) can deliver an adequate dialysis dose if the peritoneal permeability is not too low and if the prescription is adapted to each patient. The growth of CAPD seems to be slowing down due to a better knowledge of its limitations. However the development of APD does not seem to be related to the increasing knowledge of its possibilities. The development of automated techniques, prescribed as substitute treatments, depends on a precise evaluation of the cost/efficiency/quality of life index, compared to the reference treatment which is iterative hemodialysis.

Prevalence and epidemiology of hepatitis C infection in patients on peritoneal dialysis in France. French PD centers.

We performed a cross-sectional study to establish the hepatitis C virus (HCV) serologic status for all French patients undergoing peritoneal dialysis (PD) on January 1, 1995. We listed a total of 1508 patients, and the exhaustiveness rate was about of 75% of the whole French PD population treated at this date. Only 47 of the 1508 patients were anti-HCV positive (HCV+): the global HCV prevalence was 3.12%. HCV+ patients were treated by PD for a longer time than HCV-patients (4 +/- 4 vs 2 +/- 2 years; p < 0.001); 89% of the HCV+ patients received blood transfusions; 60% had been previously treated by hemodialysis, and 26% previously received a kidney transplantation. In 49% of the HCV+ patients, HCV antibodies were discovered before the start of the peritoneal dialysis program, and a seroconversion was observed in only 4 (0.27%) of them during the PD treatment. All these patients received blood transfusion. In patients without past history of hemodialysis or transplantation (exclusively treated by PD), HCV prevalence was 1.5%, not far off that of the general population. Peritoneal dialysis seems not to be an additional risk factor for hepatitis C infection in France.

Measurement of hydrostatic intraperitoneal pressure: a necessary routine test in peritoneal dialysis.

This paper summarizes our clinical studies on hydrostatic intraperitoneal pressure (IPP), showing the interest of this measurement in routine clinical practice. IPP can easily be measured routinely be a simple and safe method: the measure of the column of dialysate in the peritoneal dialysis (PD) line before drainage, with point 0 located on the midaxillary line. The normal value is 12 +/- 2 cm of water (cm H2O) with an intraperitoneal volume (IPV) of 2 L, with linear increases of 2.2 cm H2O for each additional liter. IPP must be measured to estimate the tolerance of IPV: the maximal permissible IPV is reached for an IPP of 18 cm H2O, squaring with a decrease of 20% in vital capacity and sometimes arising before clinical symptomatology. However, IPP measured at rest could not predict PD mechanical complications (hernias, dialysis leakages, hemorrhoids, etc.), which are more dependent on parietal previous history or predisposition. IPP is significantly higher during the first three days after peritoneal catheter implantation (17 +/- 3 cm H2O) than during the 12 following days (10 +/- 4 cm H2O). It is recommended to postpone the start of PD until after catheter implantation, and patients should remain supine for the first three days. On the other hand, IPP strongly reduces the overall ultrafiltration (UF) volume: an increase of 1 cm H2O in IPP caused a decrease of 70 mL in global UF after two hours. Therefore, IPP should be measured in diagnosis of losses of UF. However, UF loss during peritonitis is not due to an increase of IPP.

How to reach optimal creatinine clearances in automated peritoneal dialysis.

This paper summarizes the basis of prescription for automated peritoneal dialysis (APD) established during a French national conference on APD. Clinical results and literature data show that peritoneal clearances are closely determined by peritoneal permeability and hourly dialysate flow rate, independently of dwell time or number of cycles. With APD, peritoneal creatinine clearance increases according to the hourly dialysate flow rate to a maximum (plateau), then decreases because of the multiplication of the drain-fill times. The hourly dialysate flow giving the maximum peritoneal creatinine clearance is defined as the "maximal effective dialysate flow" (MEDF). MEDF is higher for high peritoneal permeabilities: MEDF is 1.8 and 4.2 L/hr with nocturnal tidal peritoneal dialysis (TPD) for a 4-hr creatinine dialysate-to-plasma ratio (D/P) of 0.50 and 0.80, respectively. With nightly intermittent peritoneal dialysis (NIPD), MEDF is 1.6 and 2.3 L/hr for a D/P of 0.50 and 0.78, respectively. Under these conditions, tidal modalities can only be considered as a way to increase the MEDF. Using the MEDF concept for an identical APD session duration, the maximal weekly normalized peritoneal creatinine clearance can vary by 340% when 4-hr D/P varies from 0.41 to 0.78. APD is not recommended when 4-hr creatinine D/P is lower than 0.50. However, the limits of this technique may be reached at higher peritoneal permeabilities in anurics because of the duration of sessions and/or the additional exchanges required by these patients.

213 elderly uremic patients over 75 years of age treated with long-term peritoneal dialysis: a French multicenter study.

UNLABELLED: We report our experience in 213 elderly patients over 75 years treated by peritoneal dialysis (PD) as first and exclusive dialysis therapy. The mean age at start of PD was 79.4 +/- 3.6 years, and the cumulative time on PD was 4551 months (mean time: 21.4 +/- 19.8 months). Twenty-six patients lived in institutions and 187 lived at home. Thirty patients had an effective autonomy with the ability to carry on normal activities. One hundred and two patients were cared for by a private nurse at home, and 46 patients were cared for in a family environment. Most cases were treated by three exchanges per day (152 cases) and used a nondisconnect system (175 cases) on account of absence of autonomy. The rate of peritonitis per patient-month was one episode per 16.8 patient-months. Patient survival (Kaplan-Meier curves) was 74%, 59%, 45%, and 19% at one, two, three, and five years, respectively. The causes of death were various with a higher frequency of cardiovascular causes (48.3% of the 116 deaths). Thirty-three patients died in less than six months including 18 patients in less than three months. IN CONCLUSION: elderly uremic patients can be treated with long-term PD with relatively good results. Mortality is high but essentially due to age and poor general status-the dedication of private home nursing is very important in treating elderly PD patients. This fact often is a necessary condition in maintaining these elderly patients at home.

Elevated body lead burden from drinking water in end-stage chronic renal failure.

Delta aminolaevulinic acid dehydratase (ALA-D) who assayed in 66 patients with end-stage renal failure who live in a region where there is a high risk of lead poisoning from drinking water (Vosges mountains). Sixty patients received dialysis and six underwent renal transplantation. Results were compared to those obtained in 366 control subjects with normal renal function hospitalized in a department of Internal Medicine and living in the same geographical area. The ALA-D level was significantly lower in dialysed patients (0.40 +/- 20) than in controls (0.57 +/- 0.31) (P = 0.0014). Transplant recipients had ALA-D levels comparable to subjects with normal renal function (0.59 +/- 0.37). In this high-risk population an EDTA test was performed in 74 subjects (with normal renal function and 17 dialysis patients in combination with haemofiltration for the latter patients. In the two study groups a negative correlation was found between ALA-D and the amount of lead chelated during the 24 h following administration of EDTA (r = -0.77 and -0.88 respectively). In subjects who live in an area of endemic lead poisoning, the incidence of elevated body lead burden from drinking water was similar in the group with normal renal function and in the group of dialysed patients (18.6 and 8.3% respectively). This study shows (i) that in dialysis patients, measurement of ALA-D represents an accurate screening test for lead overload, provided that the lower threshold of normal is lowered from 0.40 to 0.20, and (ii) that diagnosis and treatment are possible by administering EDTA in conjunction with haemofiltration or CAPD.

[Connectology for treatment by peritoneal dialysis for chronic renal insufficiency]. / La connectologie pour le traitement par dialyse péritonéale de l'insuffisance rénale chronique.

With the exception of the simple Luer or Spike type systems all of the presently used CAPD devices have a system for intraluminal sterilization and/or an handling assist device. The sterilizing process can be chemical (antiseptics), physical (heat or ultraviolet (UV) light) or mechanical (flush effect). Studies comparing various peritoneal dialysis devices have led to results which diverge greatly, and are not always controlled. Synthesis of these studies shown that disconnect systems (DS) seemed to be not more effective against bacteriological contamination than the last generations of UV non-disconnect (NDS) systems. Efficacy of heat sterilization NDS must be confirmed. The choice of a NDS does not result only from a medical indication.

APD: clinical measurement of the maximal acceptable intraperitoneal volume.

In automated peritoneal dialysis (APD) patients treated with 3-L dwell, intraperitoneal volumes can easily be increased up to 4 or 4.5 L using hypertonic solutions without objective control of their good tolerance. In 20 adult patients treated with continuous ambulatory peritoneal dialysis (CAPD) in good conditions, hydrostatic intraperitoneal pressure (IPP) and pulmonary vital capacity (VC) were measured in strict supine position, after infusing isotonic dialysate in 0.5-L increments from 2 up to 5 L as tolerated, according to intraperitoneal volumes (IPV). None of the patients had cardiac or pulmonary dysfunction. IPP was measured following a routine method previously described. In all cases, experience was stopped when IPP increased over 20 cm H2O and/or VC decreased over 25%. IPV is linearly and positively correlated with IPP (p < 0.0001), and negatively with VC (p = 0.0012), but the reliability of VC is less than that of IPP, particularly in old patients. Clinical symptomatology of bad IPV tolerance never occurred alone and was always associated with an increase in IPP over 20 cmH2O and/or a decrease in VC over 25%. The maximal acceptable IPV is better defined by an IPP less than 18 cmH2O, according with a decrease in VC of less than 20%. Routine measurement of IPP can be used to determine maximal IPV and for optimal PD prescription.