[Medication adverse events: Impact of pharmaceutical consultations during the hospitalization of patients]. / Évènements iatrogènes médicamenteux : impact des consultations pharmaceutiques en cours d'hospitalisation.

The medication iatrogenic events are responsible for nearly one iatrogenic event in five. The main purpose of this prospective multicenter study is to determine the effect of pharmaceutical consultations on the occurrence of medication adverse events during hospitalization (MAE). The other objectives are to study the impact of age, of the number of medications and pharmaceutical consultations on the risk of MAE. The pharmaceutical consultation is associated to a complete reassessment done by both a physician and a pharmacist for the home medication, the hospital treatment (3days after admission), the treatment during chemotherapy, and/or, the treatment when the patient goes back home. All MAE are subject to an advice for the patient, additional clinical-biological monitoring and/or prescription changes. Among the 318 patients, 217 (68%) had 1 or more clinically important MAE (89% drug-drug interaction, 8% dosing error, 2% indication error, 1% risk behavior). The patients have had 1121 pharmaceutical consultations (3.2±1.4/patient). Thus, the pharmaceutical consultations divided by 2.34 the risk of MAE (unadjusted incidence ratio, P≤0.05). Each consultation decreased by 24% the risk of MAE. Moreover, adding one medication increases from 14 to 30% as a risk of MAE on the population. Pharmaceutical consultations during the hospital stay could reduce significantly the number of medication adverse effects.

Ventriculoperitoneal shunts in children on peritoneal dialysis: a survey of the International Pediatric Peritoneal Dialysis Network.

OBJECTIVE: The aim of this study was to inform best evidence-based practice by collating and disseminating the experiences of members of the International Pediatric Peritoneal Dialysis Network with children having concurrent ventriculoperitoneal shunts (VPS) and peritoneal dialysis catheters (PDC). METHODS: An online questionnaire was created and distributed to all 135 centers participating in the International Pediatric Peritoneal Dialysis Network; the overall response rate was 56 %. RESULTS: A total of 18 patients with a concurrent VPS and PDC were reported. The children were 0-12 (mean 6.8) years old at the time of placement of the second indwelling device (PDC or VPS). In 15 cases, the PDC was inserted post-VPS. On average, the two catheters were present concurrently for 23 (range 1-60) months. There were 20 episodes of peritonitis observed in 11 of the 18 patients during a period of 392 months at risk, which is a peritonitis rate of 1/19.6 months. Only one patient developed both a VPS infection and an episode of peritonitis, and these events were temporally unrelated. No episodes of an ascending shunt infection or meningitis occurred in association with any episode of peritonitis, and no other complications of catheter dysfunction were described. CONCLUSIONS: The rate of peritonitis, the absence of any documented ascending or descending infections and the lack of catheter dysfunction during the period of observation suggests that the presence of, or need for, a VPS should not preclude PD as a safe option for children requiring renal replacement therapy.

Metabolic fate of ultratrace levels of GeCl(4) in the rat and in vitro studies on its basal cytotoxicity and carcinogenic potential in Balb/3T3 and HaCaT cell linesdagger.

The use of germanium (Ge) and the possibility of exposure to trace and ultratrace amounts of this element is increasing. Germanium is widely used in the industrial field as a semiconductor and also as a dietary supplement, an elixir to 'promote health and cure disease' (e.g. cancer and AIDS). More recently, germanium nanoparticles, ranging in size from 60 to 80 nm, have been developed as a potential spleen imaging agent. Like other metal-based nanoparticles used in nanomedicine, Ge nanoparticles may release trace and ultratrace amounts of Ge ions when injected. The metabolic fate and toxicity of these ions still needs to be evaluated. In this study the metabolic fate of a cationic tetravalent Ge species was studied in vivo by injecting rats i.p. with ultratrace amounts of Ge (80 ng kg(-1)) as [(68)Ge]GeCl(4). The cytotoxicity and carcinogenic potential was assessed in vitro using immortalised human skin keratinocytes and mouse fibroblasts (HaCaT and Balb/c 3T3 cell lines, respectively). At 24 h post-exposure Ge was poorly retained in rat tissues (kidney, liver, intestine, femur, spleen and the heart were the organs with the highest Ge concentration). In the blood, Ge was rapidly cleared, being almost equally distributed between plasma and red blood cells. The excretion was mainly via the urine. The hepatic and renal intracellular distribution showed the highest recovery of Ge in the cytosol and the nuclear fractions. Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed that the bulk of Ge was associated with low molecular weight components, representing a 'mobile pool' of the element in the body. However, a significant part of the element was able to interact with biological macromolecules which could be responsible for the presence of Ge in the liver and kidney after 7 days. The in vitro experiments confirmed the low degree of cytotoxicity of GeCl(4) both in HaCaT and Balb/3T3. The latter model was more sensitive to the toxic effects induced by Ge as shown by a colony forming efficiency (CFE) greater than 70% at 700 microm of exposure. At the highest exposure concentration tested (700 microm) GeCl(4) failed to induce morphological neoplastic transformation of the cells, suggesting for the first time that a cationic form of Ge ions has no carcinogenic potential. This supports the results of the only study reported in mice, treated orally long-term to an anionic species of Ge such as sodium germanate (Kanisawa and Schroeder, 1967).

Altered K+ channel expression in abnormal T lymphocytes from mice with the lpr gene mutation.

The observation that voltage-dependent K+ channels are required for activation of human T lymphocytes suggests that pathological conditions involving abnormal mitogen responses might be reflected in ion channel abnormalities. Gigaohm seal techniques were used to study T cells from MRL/MpJ-lpr/lpr mice; these mice develop generalized lymphoproliferation of functionally and phenotypically abnormal T cells and a disease resembling human systemic lupus erythematosus. The number and predominant type of K+ channels in T cells from these mice differ dramatically from those in T cells from control strains and a congenic strain lacking the lpr gene locus. Thus an abnormal pattern of ion channel expression has now been associated with a genetic defect in cells of the immune system.

In-center daily on-line hemodiafiltration: a 4-year experience in children.

Our daily dialysis program was started in September 2002: in-center daily on-line hemodiafiltration (DIH) was carried out in 3-hour sessions, 5 - 6 times weekly, on-line assessment KT/Vurea of minimal 1.5 per session, polysulfone membranes. 12 children were included: median age 7.4 years (2.10 - 16.8 years), renal residual function less than 3 ml/min/1.73 m2 (Kcreat + Kurea/2), vascular access central catheter (n = 4) or fistula (n = 8), 7/12 being converted from peritoneal dialysis to DIH. Median follow-up on DIH was 11 months (4 - 43 months), endpoint was kidney transplantation (11/12) or transfer to another center (1/12). Monthly assessments of dialysis parameters (KT/Vurea, predialysis phosphatemia), diet survey (3 consecutive days), medications (number of antihypertensive drugs, phosphate chelators, potassium chelators) and statural growth were performed. At start of DIH, diet intake due to medical prescription and limited appetite was restrictive with limitation in water, salt (20 mmol/day), potassium and proteins (median 35 g/day, range 20 - 80 g); only 2/12 children were free of antihypertensive drugs, all received phosphate and potassium chelators, and growth retardation occurred (7/12 in prepubertal children, median height SDS -1.52) despite rhGH therapy (5/12 patients). At the end of DIH, diet was free, protein intake high (2 - 3 g/kg/day, range 30 - 100), 10/12 children were free of antihypertensive drugs, 4/12 received potassium chelators, 1/12 received phosphate chelators. All the prepubertal children at inclusion (n = 7) showed catch-up growth with a median growth rate of 0.8 cm/month (0.5 - 1.6 cm/ month). DIH allowed to maintain predialysis phosphatemia in a low normal range (median 1.23 mmol/l, range 1.65 - 0.63), without (11/12 children) need of phosphate chelators. Thanks to DIH children, parents and team care discovered during DIH a new way of life with motivated children, showing natural compliance (no diet restriction, no or few drugs), and most of all children developing with catch-up of growth.

Comparison of different antinucleic acid antibody spectrotypes in spontaneous, induced, and murine lupus.

Sera from patients with systemic lupus erythematosus and from mice spontaneously developing lupus were subjected to isoelectric focusing by a microsucrose gradient method. The spectrotypes of human antibodies to native DNA, denatured DNA, and polyriboadenylic acid (poly A) were compared. Antibodies to native DNA and denatured DNA focused into two regions whose boundaries were pH 5.0-7.0 and pH 8.5-10.0. Antinative DNA antibodies were more homogeneous than antidenatured DNA antibodies. Anti-DNA antibodies in cryoglobulins showed more restriction than those present in serum. There was no relationship between spectrotype and pattern of disease expression. Murine antibodies to native DNA were more heterogeneous than human anti-DNA antibodies. The spectrotypes of antidenatured DNA antibodies from patients with systemic lupus erythematosus or drug induced lupus, or from an immunized rabbit, were similar. Likewise, antibodies to poly A were similar in both human and murine lupus. In contrast to anti-DNA, antibodies to poly A were restricted and focused only in the alkaline range (pH 9.5-10.0). The spectrotype of antipoly A antibodies induced by lipopolysaccharide were comparable but had an additional small band at pH 6.2. Our results suggest unique antibody spectrotypes with varying degrees of restriction for different nucleic acid antigens. Furthermore, spontaneous and induced autoantibodies have similar spectrotypes. Thus, the B cell clones producing antinucleic acid antibodies may be similar whether they are activated spontaneously, following immunization, or as a consequence of polyclonal stimulation.

An optimised data analysis for the Balb/c 3T3 cell transformation assay and its application to metal compounds.

The Balb/c3T3 cell transformation assay (CTA) is an available in vitro system to detect the carcinogenic potential of chemicals. Currently, the European Centre for the Validation of Alternative Methods (ECVAM) is validating this test, assessing its reliability and relevance. Its endpoint is the formation of type III foci, which is, when using clone A31-1-1, a very rare event that usually does not occur at all for negative controls. The carcinogenic potential of a compound tested is assessed by comparing the number of foci in treated and untreated cells. The objective of the present work is to optimise the data analysis for this endpoint by applying the most commonly used approach by a t-test and the Fisher's exact test as an alternative approach. For this purpose selected metal compounds classified as carcinogenic (NaAsO2, CdCl2, cisPt), as suspected carcinogenic (C6H5)4AsCl, CH3HgCl), or as compounds without evidence of carcinogenic properties in humans ((NH4)2PtCl6, NaVO3) as well as a non-carcinogenic (AgNO3) were analysed. Our evaluation revealed that the t-test approach, which assumes normality of data, is not appropriate. The results demonstrated that the statistical analysis by Fisher's exact test, better reflecting the data properties, greatly facilitates the interpretation of Balb/c3T3 CTA data regarding carcinogenic potential.

[The best of cardiac rehabilitation in 2006]. / L'essentiel de l'année 2006 en réadaptation cardiaque et cardiologie du sport.

The meta-analysis showing the benefits of physical training revisited: Taylor examined only the cardiac rehabilitation trials of exercise intervention alone (versus usual care) and demonstrated that cardiac mortality is 28 % reduced and exercise appears to have an independent mortality benefit. An economic evaluation of cardiac rehabilitation: a systematic review of 15 economic evaluations. Evidence to support the cost-effectiveness of supervised cardiac rehabilitation compared with usual care in myocardial infarction and heart failure was identified. But further well-designed trials are required. Pronostic value of some variables determined by exercise testing entering cardiac rehabilitation and after physical training. A beneficial effect of physical training versus usual care on BNP and neurohormones in patients with chronic heart disease. Patients on beta blockers after myocardial infarction: determination of a more accurate training heart frequency derived from the classical Karvonen's formula. The combination of trimetazidine with exercise training provides greater improvements in functional capacity, left ventricular function and the endothelium-dependent relaxation of the brachial artery than exercise training alone in patients with ischaemic cardiomyopathy referred for cardiac rehabilitation. Guidelines for resistance exercise after cardiac event: a new paradigm less restrictive, safe and efficient to accelerate patients' return to daily activities. Recommendations for participation in leisure-time physical activity and competitive sports for patients with ischaemic heart disease: the result of consensus among experts from the ESC study group of sports cardiology.

[Best of functional evaluation and cardiac rehabilitation in 2005]. / L'essentiel de l'anné 2005 en évaluation fonctionnelle et réadaptation des cardiaques.

The latest in cardiac rehabilitation has been impacted by: The East German PET publication which showed fewer ischaemic events and progression of the atheromatous disease in symptomatic and stable coronary patients who carry out regular physical exercise in comparison with patients who underwent angioplasty with stenting. Two meta-analyses updated the data showing the benefits of physical training: a 20% reduction in global mortality in coronary disease and 35% in cardiac failure. Two French studies reporting reassuring data for our daily practice: the serious complications of cardiac rehabilitation are exceptionally rare: the register for 2003 with data from 65 French centres, over 25,000 patients and 743,000 patient/exercise hours. Physical training two weeks after mitral valvuloplasty is not harmful for the valve repair and is beneficial in terms of exercise capacity for the patient. Epidemiological studies showing that women and elderly patients are, unfortunately, often excluded from programmes of cardiac rehabilitation.

[Tick-borne encephalitis in a child in a nonendemic country: A case report]. / Méningo-encéphalite à tiques chez l'enfant en France : à propos d'un cas.

Tick-borne encephalitis (TBE) is an arbovirus induced by tick-borne encephalitis virus (TBEV) transmitted by tick bite. The disease is rare in France (two to three cases per year) but endemic zones extend from Western Europe to the east coast of Asia (10,000-15,000 cases per year). An 8-year-old boy was admitted to our pediatric ward in Strasbourg (France) for febrile headache with diplopia. Four days after a tick bite, he declared a febrile headache together with maculopapular rash on the elbows, knees, and cheeks. Fourteen days after the outbreak of symptoms, he showed confusion, drowsiness, and binocular diplopia. Brain MRI was normal and the electroencephalogram found diffuse slow activity with no discharge. Lumbar puncture found meningitis with 92 cells (60% neutrophils, 40% lymphocytes). The diagnosis was made with specific IgM and IgG antibody isolation in the serum (Elisa). Lyme serology was negative. The evolution was slowly favorable and the child remained hospitalized for 8 days. The neurological control examination 2 weeks later was normal except for a moderate left deviation during tandem walk and left Romberg manoeuver. Meningitis or meningoencephalitis in a child must raise the diagnosis of TBE in children, even in nonendemic countries, given the recent increased incidence of TBE and the development of tourism. Recent travel in endemic areas, a history of tick bite, and a clinical course in two phases must be sought. The diagnosis is serologic and prevention is based on vaccination.

[Hodgkin disease revealed by a nephrotic syndrome: A case report]. / Lymphome de Hodgkin révélé par un syndrome néphrotique : à propos d'un cas.

Pediatric nephrotic syndrome (NS) is most often idiopathic or primary but in rare cases, it can be secondary to neoplasia. We report on a case of steroid-resistant NS revealing as a paraneoplastic syndrome of Hodgkin disease (HD) in a 12-year-old boy. The onset of the NS can be earlier, later, or simultaneous to the HD. Treatment of the lymphoma allows the disappearance of the NS. In the case we observed, the diagnosis of HD was delayed because HD presented with an isolated, hilar adenopathy in the absence of retroperitoneal or peripheral locations. In children aged 10 years or more presenting with NS, steroid-resistant or otherwise, a possible paraneoplastic origin such as Hodgkin lymphoma should always be taken into consideration and eventually eliminated.

Hemodialysis in children: principles and practice.

Hemodialysis has benefited from major progress over the last decade, improvements in technology and in clinical management. The morbidity over the sessions have decreased, seizures being exceptional, hypotensive episodes or headaches rare and pain related to the fistula puncture is effectively prevented by xylocaine ointment. The development of urea kinetic modeling allows the calculation of the dialysis dose Kt/V, and an indirect assessment of the protein intake. Even if the validity of these parameters are questioned their analyse provides an assessment and therefore is a "good thing." The patient also benefited from the technological revolution. The newer machines provide for precise control of ultrafiltration volumetrically assessed, buffered bicarbonate became a standard technique, biocompatible and highly efficient membranes and specific material available for infants have been developed. More recently the concept of ultrapure dialysate, ie, free of microbiological contamination, germs and endotoxins was developed, as was the availability of continuous blood volume monitoring during the session. The hemodiafiltration modality especially with the on line concept, because of all the advantages, should not be limited only to patients at risk.

Systemic sclerosis in 3 US ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants.

OBJECTIVE: To determine whether ethnic factors influence the presentation, serologic expression and immunogenetics of systemic sclerosis (SSc), patients from 3 ethnic groups were compared for clinical features, SSc-associated autoantibodies, and human leukocyte antigen (HLA) class II alleles. METHODS: Fifty-four Hispanics, 28 African Americans, and 79 whites from Texas with recent-onset (less than 5 years) SSc enrolled in a prospective longitudinal study were assessed for sociodemographic, clinical, immunologic, immunogenetic, behavioral, and psychologic parameters using validated instruments and standard laboratory techniques. Serologic and immunogenetic characteristics from these patients and larger retrospective SSc cohorts of the same ethnic groups also were examined. RESULTS: Hispanics and African Americans in the prospective cohort were more likely to have diffuse skin involvement, skin pigmentary changes, digital ulcers, pulmonary hypertension (African Americans), and an overall lower sociodemographic status than whites, who had more facial telangiectasia and hypothyroidism. In the larger combined prospective and retrospective groups of SSc patients, whites were likely to have more anticentromere antibodies (ACA) and African Americans more anti-U1-ribonucleoprotein (RNP) and anti-U3-RNP (fibrillarin) autoantibodies. HLA-DQB1*0301 was significantly associated with SSc per se in all 3 ethnic groups; HLA-DRB1*11 correlated with the anti-topoisomerase I antibody response, and HLA-DRB1*01, DRB1*04, and DQB1*0501 with ACA. CONCLUSIONS: Important sociodemographic, clinical, and serologic differences exist between whites, African Americans, and Hispanics, despite shared genetic (HLA class II) predisposing factors. The impact of these differences on prognosis remain to be determined.

Are randomized control trial outcomes influenced by the inclusion of a placebo group?: a systematic review of nonsteroidal antiinflammatory drug trials for arthritis treatment.

Placebo groups are often included in randomized control trials evaluating drug therapy, yet we know little about the placebo effect. The purpose of our study was to evaluate how the presence of a placebo group in a randomized control trial (RCT) influences the patients' ratings of the efficacy of an active drug therapy and their reporting of its adverse effects. We identified studies published between 1966 and 1994 using MEDLINE. Randomized control trials evaluating acetylsalicylic acid, diclofenac, or indomethacin for the treatment of osteo or rheumatoid arthritis were included in our sample. Two investigators independently extracted data. Fifty-eight treatment arms met our inclusion criteria and were available for analysis. Twenty-five treatment arms evaluated a nonsteroidal antiinflammatory drug (NSAID) in placebo control trials and 33 in comparative trials. Using a logistic regression model to adjust for the differences between the evaluated drugs and between the types of arthritis, we found that patients receiving an NSAID in a placebo control trial were more likely to withdraw due to inefficacy (OR=1.3; 95% CI, 1.0 to 1.6; P=0.04). Using a similar model, withdrawals due to adverse effects were found to be more common when the NSAID was given in trials that did not include a placebo group (OR=1.5; 95% CI, 1.1 to 1.9; P=0.002) as were reports of cutaneous (OR=4.2; 95% CI, 1.7 to 9.9), gastrointestinal (OR=1.6; 95% CI, 1.3 to 2.0), and other types (OR=5.3; 95% CI, 3.8 to 7.4) of adverse effects. Although reports of central nervous system adverse effects were more frequent in the comparative trials, this difference was not significant. Including a placebo group in a RCT changes how patients rate the efficacy and adverse effects of their therapy. Our results highlight the need to consider the placebo effect in the design and analyses of clinical trials.

A systematic review of the evidence for hypodermoclysis to treat dehydration in older people.

BACKGROUND: The purpose of the study was to evaluate the evidence supporting the use of hypodermoclysis (i.e., subcutaneous infusion of fluids) to treat dehydrated elderly patients, and to discuss clinical applications of this mode of therapy in the long-term care setting. METHOD: Articles reporting the use of hypodermoclysis were identified using a systematic MEDLINE search between January 1966 and May 1996. Articles were included in our sample if they contained original patient data that evaluated either the efficacy or adverse effects associated with the use of subcutaneous infusions to treat dehydration in adults, whether hyaluronidase was required to facilitate the absorption of subcutaneous fluid, or if potassium could be added to the solution. RESULTS: Eighteen articles met the inclusion criteria. Since we hypothesized that adverse effects associated with hypodermoclysis may have been related largely to the use of nonelectrolyte or hypertonic solutions, the studies were evaluated according to the type of fluid administered. Six hundred and eighty-five patients were described in 13 studies evaluating the efficacy and toxicity of subcutaneously administered fluid. Four studies evaluated hypodermoclysis using electrolyte-containing solutions in 25 patients. Two of these were randomized control trials (RCT) that compared hypodermoclysis to intravenous therapy. Both reported similar absorption of fluids. In the single RCT that evaluated adverse effects, 4 of 17 patients receiving hypodermoclysis reported minor side effects similar to those reported with intravenous therapy. Adverse effects were more severe when electrolyte-free or hypertonic solutions were evaluated. Of the 639 patients who may have received electrolyte-free solutions, 16 patients (2.5%) reported adverse effects, 8 of which were severe. Both patients reported to have received hypertonic solutions noted adverse effects, one of which was severe. The use of hyaluronidase to facilitate absorption was evaluated in 74 patients. These studies suggest that hyaluronidase improves the speed of fluid absorption but may not change the patient's comfort level. A single case report of 350 subcutaneous infusions in 67 patients investigated the administration of up to 34 mmol/L of potassium chloride (KCl) by hypodermoclysis. The only adverse reaction observed was discomfort at the infusion site. CONCLUSIONS: Hypodermoclysis can be used to most safely provide fluids when electrolyte-containing fluids are administered. Hypodermoclysis may have fallen into disuse because of reports of severe adverse reactions related to infusions of electrolyte-free or hypertonic solutions that would likely be considered inappropriate today. Whether or not hyaluronidase is required to promote subcutaneous fluid absorption remains unresolved. Limited evidence suggests that potassium chloride may, with caution, be safely added to subcutaneous infusions. The majority of the available studies evaluating hypodermoclysis are of poor quality. Because of the tremendous potential benefits of administering fluid subcutaneously, there is a need for good quality studies to evaluate the efficacy of hypodermoclysis.

The French version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

Normal statural growth in 2 infants on chronic peritoneal dialysis: anecdotal or whole management-related.

AIMS: Growth retardation is usual in children on chronic peritoneal dialysis (CPD). Despite attention to many contributing factors (nutrition, dialysis dose, hemoglobin level, adynamic bone disease, hyperparathyroidism or rickets, growth hormone resistance, etc.), normal growth is rarely obtained in infants on CPD. MATERIALS AND METHODS: We had the chance to observe normal growth over a 1 year period in 2 consecutively treated infants on CPD. Louise (renal hypodysplasia) required CPD at the age of 1 month: creatinine 430 micromol/l; oliguric, creatinine clearance lower than 5 ml/min/1.73 m2. Nutrition was achieved orally with human milk during the first 6 months of life. Tidal peritoneal dialysis allowed a high dialysis dose Kt/V urea 3.8/week and Kcreatinine 105 l/week/1.73 m2. Hemoglobin was maintained over 13 g/dl and low levels of vitamin D analogue were prescribed to avoid adynamic bone disease. At the age of 1 year her height was 75 cm. i.e. in the normal range for age. Madeline (renal hypodysplasia) commenced on CPD at the age of 6 weeks and managed similarly. Her height at 1 year of age was 74 cm. RESULTS: In our 20 years of experience with children on dialysis, these 2 cases of normal statural growth for age at 1 year warrant discussion. As well as nutritional support, the new and recent therapeutic options in our team were: firstly, to avoid high doses of activated vitamin D to control PTH, as high doses are able to induce both a risk of adynamic bone disease and a direct bone cartilage toxicity: secondly, to maintain normal hemoglobin level; and thirdly, to deliver a high dialysis dose (urea, creatinine clearance) based on an individually adapted prescription. CONCLUSION: We feel this management approach is necessary to achieve optimal statural growth in children on chronic peritoneal dialysis. But this management concept only based on clinical anecdotal observations needs further evaluation before its use in clinical guidelines.

Use of intraperitoneal pressure, ultrafiltration and purification dwell times for individual peritoneal dialysis prescription in children.

Tolerance of peritoneal dialysis is, in a part, dependent on intraperitoneal dialysate volume. Measurement of intraperitoneal pressure (IPP) in cm of water is easy to perform especially with the twin bag Y set (Baxter). Today we use IPP for following surgical catheter implantation (delaying, starting and progressing with peritoneal dialysis) and for optimizing ultrafiltration and purification. Efficiency of peritoneal dialysis is dependent on adequate ultrafiltration (UF) and on adequate purification (solute clearances). These two goals seem apparently conflicting in terms of duration of dwells: short dwell time enhances UF capacity and conversely long dwell time enhances solute clearance. Peritoneal equilibration test (PET) allows an approach to the ultrafiltration time: the point at which the overtime dialysate urea saturation and glucose desaturation curves cross, called APEX time. PET allows also an approach of the purification time: the point at which dialysate (D) to plasma (P) concentration ratios over time are high. Because the value of phosphate as uremic factor of morbidity, we have chosen the time for D/P phosphate equal to 0.6 as a purification phosphate dwell time (PPT). A total of 17 patients were studied, over a five-year period allowing 142 determinations. APEX times (range 18 to 71 min) and PPT (range 105 to 238 min) were spread over a wide distribution. PPT and APEX times were significantly shorter in children younger than 3 years of age than in children older than 10 years of age. PPT were nearly four times longer than APEX times. The knowledge of these conflicting ultrafiltration and purification times should help, in our view, in the individual choice of the PD modality: if UF is the major goal, short dwell times should be used (automatic PD); if purification is the major goal, long dwell times should be used (CAPD); if both are the target goal, tidal PD should be discussed.

Genetic variations of the SLC7A9 gene: allele distribution of 13 polymorphic sites in German cystinuria patients and controls.

Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3A1 gene cause type I cystinuria, patients with non-type I cystinuria carry mutations in the SLC7A9 gene. Both gene products form the renal amino acid transporter rBAT/b0,+AT affected in cystinuria. In the present study a total of 59 patients with different ethnic background were screened for sequence variations in SLC7A9, out of these 32 were of German origin. For determination of allele frequencies of detected polymorphisms, 58 healthy German controls were investigated. Molecular-genetic analysis was performed using single-strand conformation polymorphism analysis, restriction assays and sequencing. Allele frequencies were analyzed statistically for the detected polymorphisms. In addition to the 6 already known variants we identified 7 new polymorphisms. Statistical analyses showed a significantly different distribution of alleles between German patients and German controls in case of the polymorphisms c. 147C>T (exon 2), c.386C>T (exon 3), IVS3+22T>G, c.584C>T (exon 4), c.610T>C (exon 4), c.692C>T (exon 5), c.852C>A (exon 6) and c.872C>T (exon 6). In summary, our results show that cystinuria is a complex disease which is not only caused by mutations in SLC7A9 and SLC3A1, but also influenced by other modifying factors such as variants in SLC7A9.