Considerable variations in growth hormone policy and prescription in paediatric end-stage renal disease across European countries-a report from the ESPN/ERA-EDTA registry.

BACKGROUND: Growth retardation in paediatric end-stage renal disease (ESRD) has a serious impact on adult life. It is potentially treatable with recombinant growth hormone (rGH). In this study, we aimed to quantify the variation in rGH policies and actual provided care in these patients across Europe. METHODS: Renal registry representatives of 38 European countries received a structured questionnaire on rGH policy. Cross-sectional data on height and actual use of rGH on children with ESRD aged <18 years were retrieved from the ESPN/ERA-EDTA Registry. RESULTS: In 21 (75%) of 28 responding countries, rGH is reimbursed for children with ESRD. The specific conditions for reimbursement (minimum age, maximum age and chronic kidney disease stage) vary considerably. Mean height standard deviation scores (SDS) at renal replacement therapy (RRT) [95% confidence interval (CI)] were significantly higher in countries where rGH was reimbursed -1.80 (-2.06; -1.53) compared with countries in which it was not reimbursed [-2.34 (-2.49;-2.18), P < 0.001]. Comparison of the mean height SDS at onset of RRT and final height SDS yielded similar results. Among the 13 countries for which both data on actual rGH use between 2007 and 2011 and data from the questionnaire were available, 30.1% of dialysis and 42.3% of transplanted patients had a short stature, while only 24.1 and 7.6% of those short children used rGH, respectively. CONCLUSION: Reimbursement of rGH associates with a less compromised final stature of ESRD children. In many countries with full rGH reimbursement, the actual rGH prescription in growth-retarded ESRD children is low and obviously more determined by the doctor's and patients' attitude towards rGH therapy than by financial hurdles.

Impact of stimulation dose and personality on autonomic and psychological effects induced by acupuncture.

Acupuncture has been shown to exhibit distinct effects on the autonomic nervous system. We tested whether the autonomic and psychological response to acupuncture depends on the stimulation dose and the personality of the treated subjects. 52 healthy subjects were randomized to receive either low dose (one needle at point Hegu bilaterally) or high dose (additional 4 needles at non-acupoints bilaterally) acupuncture stimulation after stratification according to their personality to "reduce" or "augment" incoming stimuli. Outcomes were changes of electrodermal activity (EDA), high frequency component of heart rate variability, heart rate, mean arterial blood pressure, respiration rate and subjective parameters for psychological well being and perceived intensity of needling. Electrodermal activity increased during needle insertion and decreased under baseline when subjects were resting with the needles in the body for 20 min. The initial EDA increase was significantly (GEE ANCOVA p<0.001) more pronounced during high dose stimulation and independent of personality. All other physiological parameters did not show any significant group effect. Strong stimulated augmenters perceived acupuncture most painful and increased with their psychological activation after the acupuncture session in contrast to the other groups, which showed a decrease of activation in the pre-post comparison (overall group effect p=0.032). The data indicate that during needle insertion high dose acupuncture stimulation leads to a higher increase of sympathetic nerve activity than low dose stimulation independent of personality. After needle insertion subjects who tend to augment incoming stimuli might show a lack of psychological relaxation when receiving high dose stimulation.

Multiple osteolytic lesions of intraosseous adenoid cystic carcinoma in the mandible mimicking apical periodontitis.

AIM: Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumour of the salivary glands in the maxillofacial region. About 40-60% of the patients develop distant metastases, which have been documented most commonly in the lung but also in brain, bone, liver, thyroid, spleen and pancreatic gland. SUMMARY: A 55-year-old women with intraosseous ACC in the mandible mimicking apical periodontitis following curative resection and radiotherapy is presented. Three years later, multiple lung metastases were observed followed by chemotherapy. Five years after curative resection, the patient presented simultaneously with new expansive soft tissue in the pancreas and mammary gland as well as in the kidney found to be metastatic ACC. No case has been reported to date on the manifestation of distant metastases of intraosseous ACC in the breast and the kidney as described by these observations. Metastatic mammary gland ACC stained positive for epithelial growth factor receptor (EGFR) but was negative for HER-2/neu and Cyclooxygenase-2 (COX-2) expression.

Comparison of electrodermal constant voltage and constant current recording techniques using the phase angle between alternating voltage and current.

If electrodermal activity is recorded with direct current, constant voltage and constant current measurements result in different dependencies of electrodermal reactions on the actual electrodermal level. The present study demonstrates empirically that such a problem does not exist when instead the phase angle changes between alternating current and voltage are obtained. Forty subjects were subjected to a 20-trial habituation series on two different occasions, in which electrodermal level variations were induced by room temperature changes. A multiplexing system was used to enable quasi-simultaneous constant current and constant voltage recording under both direct and alternating current measurement conditions. If the alternating current technique was applied and electrodermal responses were expressed as changes of phase angle between voltage and current, electrodermal recordings with constant voltage and with constant current provided equivalent results, even if electrodermal levels were considerably different. Therefore, using the phase angle method instead of the conventional direct current methods will finally resolve the problem of differential level dependency in electrodermal recording. A further advantage will be that electrode and skin polarization are prevented by the use of alternating current.

Effects of stimulus intensity, risetime, and duration on autonomic and behavioral responding: implications for the differentiation of orienting, startle, and defense responses.

The effects of stimulus intensity, duration, and risetime on the autonomic and behavioral components of orienting, startle, and defense responses were investigated. Six groups of 10 students were presented with 15 white noise stimuli at either 60 or 100 dB, with controlled risetimes of either 5 or 200 ms, and at stimulus durations of 1 or 5 s (1 s only in the case of the 60-dB groups). A dishabituation stimulus consisting of a 1000 Hz tone was also presented. Measures consisted of skin conductance and heart rate, together with ratings of facial expressions and upper torso movement obtained using video recording. Increased intensity resulted in greater amplitudes and frequencies of electrodermal and behavioral responses, and a change from cardiac deceleration to acceleration. Faster risetimes elicited larger electrodermal responses, greater frequencies of eye-blinks, head and body movements, and larger cardiac accelerations. The effects of duration for the 100-dB stimuli were less clear-cut. Overall, the results are discussed in relation to the differentiation of orienting, startle, and defense responses.

Current practice of peritoneal dialysis in children: results of a longitudinal survey. Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS).

Since 1993, the Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS) has been accumulating epidemiological data regarding the practice of peritoneal dialysis (PD) in children. More than 200 children have been evaluated to date. While treatment modalities were evenly distributed in 1993, automated peritoneal dialysis (APD) has emerged as the preferred mode of therapy during the last few years. Technique survival was 95% at 2 years, but decreased to 65% after 4 years of treatment, the main reasons for treatment failure being recurrent peritonitis, ultrafiltration failure, or both. Most centers use double-cuff curled Tenckhoff catheters with an upward pointing exit site. The first catheter was still functioning in 82% of patients after 1 year, and in 57% of patients after 4 years of treatment. While the overall peritonitis incidence between 1993 and 1997 was 1 episode per 17 months, it was much higher in children below 6 years of age. Empirical PD prescription resulted in a mean total weekly creatinine clearance of 57 L/1.73 m2/week in both continuous ambulatory peritoneal dialysis (CAPD) and APD patients, while average total weekly Kt/V urea was higher in APD-treated (2.45) than in CAPD-treated children (1.96). Antihypertensive treatment was required in 40%-50% of patients; oral phosphate binders in 75%-80%; bicarbonate substitution in 30%; potassium binders in 7%-14%; and NaCl supplementation in 9%-21% of patients. While growth retardation had a prevalence of 57%, body mass relative to height was in the normal range. After one year of dialysis, 20% of patients received growth hormone treatment. In conclusion, peritoneal dialysis in children, preferably performed as APD, achieves technique survival rates similar to those reported for adults. Young children are at increased risk for peritonitis. The current empirical PD prescription is of limited efficacy in terms of small-solute and fluid removal.

Inappropriate elevation of serum leptin levels in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

Decreased spontaneous nutrient intake is a frequent clinical problem in patients with chronic renal failure (CRF). Leptin, the recently characterized gene product of the obese gene, is produced by adipocytes and is thought to act as an afferent satiety signal on the appetite and satiety centers of the brain. Serum leptin levels were investigated in 134 pediatric patients in different stages of CRF to evaluate a possible relationship between leptin, GFR, and spontaneous energy intake. Serum leptin levels, measured by a specific RIA, were elevated above the 50th percentile of the normal range in 78% of CRF patients and above the 95th percentile in 45% of patients. Gel chromatography of CRF sera yielded only one single immunoreactive peak at 16 kD, indicating that the increase of immunoreactive leptin levels in CRF serum was not due to accumulation of leptin degradation products. Multiple stepwise regression analysis revealed the percentage of body fat as assessed from skinfold measurements (r = 0.79, P < 0.0001) and GFR (r = -0.17, P < 0.005) as independent predictors of serum leptin levels, accounting for 66% of total statistical variability. There was an inverse linear correlation between standardized leptin levels (leptin z-score) and the spontaneous energy intake quantified from written dietary diaries (r = -0.36, P < 0.001). These data suggest that the percentage of body fat remains the main determinant of serum leptin in CRF patients, but their levels increase with declining GFR, presumably by reduced renal clearance. Leptin levels in CRF serum that are inappropriately elevated in relation to the percentage of body fat might lead to a dysregulation of the normal peripheral-central leptin feedback loop, thereby contributing to decreased nutrient intake in uremia.

Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood.

BACKGROUND: Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF. METHODS: A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study. FINDINGS: The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year. INTERPRETATION: A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.

Growth charts for prepubertal children with chronic renal failure due to congenital renal disorders. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

Despite the high prevalence of and therapeutic attention to growth failure in children with chronic renal failure (CRF), systematic evaluations of spontaneous growth in CRF are lacking. Therefore, we collected retrospectively longitudinal growth and biochemical data in 321 prepubertal patients treated for CRF due to congenital renal disorders. Data were recorded at 3-month intervals during the first 2 years of life and 6-monthly thereafter, up to the age of 10 years. Around 100 measurements were available per age interval. Mixed-longitudinal percentile curves of height and height velocity were constructed. Moreover, a statistical comparison with the heights and height velocities of healthy children and an evaluation of the effect of biochemical parameters on growth was performed. The CRF children had normal heights at birth but dropped below the 3rd normal percentile during the first 15 months of life. Thereafter, growth patterns usually were percentile parallel, with a mean height standard deviation score (SDS) of -2.37 +/- 1.6. Height velocities were consistently lower in patients with glomerular filtration rates (GFRs) below one-third of the lower normal limit (25 ml/min per 1.73 m2 for patients > 1 year) than in patients with better renal function. This difference in growth rates resulted in a mean height SDS of -1.65 +/- 1.5 SDS and -2.79 +/- 1.4 SDS (age 1-10 years) in the subgroups with relatively better and worse GFR, respectively. Regression analysis confirmed that GFR was a weak but significant predictor of height velocity SDS in most age groups.

Early age-dependent growth impairment in chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

We report early linear growth in 73 children (51 boys, 22 girls) with early onset of chronic renal failure (CRF). The inclusion criteria was onset of CRF before 6 months of age, two or more height measurements during the 1st year of life, follow-up for at least 3 years and continuously impaired renal function with a glomerular filtration rate below 50 ml/min per 1.73 m2 at 1 year or later. Only height measurements taken during conservative treatment or dialysis were included. The data were analysed in terms of the infancy-childhood-puberty growth model. There was an age-dependent growth failure in early life leading to an attained height of -3 standard deviation score (SDS) at 3 years of age. Approximately one-third of the reduction in height occurred during fetal life and one-third during the first postnatal months. Between 0.75 and 1.5 years of age height also decreased by 1 SD as a consequence of a delayed onset of the second, the 'childhood', phase of growth in 36% of the patients and by an 'offset childhood' growth pattern--i.e. a return to the infancy phase pattern after onset of the childhood phase--in 60% of the patients. Growth between 0.25-0.75 and 1.5-5 years of age was generally percentile parallel and thus less likely to be affected in CRF with early disease onset. The glomerular filtration rate was not related to the height gain in early life. We speculate that the growth failure during fetal life and the first postnatal months reflects metabolic and/or nutritional influences and the impaired growth at 0.75-1.5 years of age is related to a partial insensitivity to growth hormone.

Serial subcultivation of Giardia lamblia in Keister's modified TYI-S-33 medium containing ultroser G.

The ability of Giardia strains of the duodenalis type to grow in Keister's modified TYI-S-33 medium varies with serum lot. Recently, strains of Giardia including MR4, WB, and Human-1-Portland, have been cultivated in Keister's modified TYI-S-33 medium containing the serum substitute Ultroser G and have been cultured serially as least 40 times. An optimal concentration of 8% Ultroser G promotes maximal growth in Keister's modified TYI-S-33 medium for all three strains. This concentration of Ultroser G will produce a two-log increase in the number of trophozoites in approximately three days post-inoculation. Generation times for the trophozoites ranging from 6 to 11 h have been achieved in Keister's modified TYI-S-33 containing 10% adult bovine serum and from 8 to 13 h in Keister's modified TYI-S-33 with 8% Ultroser G. Despite the excellent growth of Giardia strains in medium containing Ultroser G, the maximum trophozoite density is only about half of that achieved in Keister's modified TYI-S-33 medium supplemented with 10% adult bovine serum. Comparisons of trophozoites grown with serum or the serum substitute reveal no discernable differences in morphology and motility. Additionally, these strains have been successfully cryopreserved and revived in Keister's modified TYI-S-33 medium supplemented with Ultroser G. Because Ultroser G is a characterized mixture of six main groups of ingredients (growth factors, adhesion factors, mineral trace elements, hormones, binding proteins, and vitamins), the variability in cell proliferation that may occur when changing serum lots should be minimized when using this product.