Validation and calibration of the Kabi Pharmacia International Growth Study prediction model for children with idiopathic growth hormone deficiency

In 1999 a model was published for prediction of growth in children with idiopathic GH deficiency (IGHD) during GH therapy, derived using data from the Kabi Pharmacia International Growth Study (KIGS) database (Pharmacia \\|[amp ]\\| Upjohn, Inc., International Growth Database). We validated and calibrated this KIGS model for growth in the first year of GH therapy using data from 136 Dutch children with IGHD. Observed vs. predicted outcomes were plotted, and the fitted regression line was significantly different from the line of identity (P = 0.03). It appeared that the predictions were too extreme: relatively low predictions were too low, relatively high predictions were too high. This is a well known phenomenon in the context of prediction models, called overoptimism. For valid application to other data the KIGS predictions should be calibrated. Calibrated predictions are obtained using Y(cal) = Y(orig) + (2.153 - 0.192 x Y(orig)), where Y(cal) is the calibrated prediction, and Y(orig) is the KIGS prediction. The calibrated prediction will be higher than the original KIGS prediction when the original prediction is less than 11.2 cm/yr and will be lower otherwise. The variability of the prediction errors of the calibrated predictions was positively related to the value of the prediction (P < 0.001), described by the equation SD(pred err) = -1.017 + 0.286 x Y(cal). Our calibrated model will give better predictions for children with IGHD fulfilling the same criteria

Effect of fetal breathing movements on fetal cardiac hemodynamics

__Abstract__ Maximum flow velocity waveforms were studied at atrioventricular and outflow tract level in 12 cases during fetal breathing activity and in 12 cases during fetal apnea matched for maternal and gestational age and maternal parity. Gestational age ranged between 27 and 40 weeks (median 30 weeks). All flow velocity waveforms were obtained using a mechanical sector scanner with a pulsed Doppler system (carrier frequency 3.5 MHz). Time-averaged flow velocities were clearly different between inspiration and expiration at all four recording levels, reflecting changes in venous return as a result of fluctuations in intrathoracic pressure during fetal breathing activity. Percentage change between inspiration and expiration at outflow tract level was positively correlated with gestational age. Time-averaged flow velocity at mitral level and ascending aorta level was significantly higher during fetal breathing activity than during apnea, suggesting increased shunting of blood flow through the foramen ovale. Acceleration time at outflow tract level demonstrated very little change relative to inspiration and expiration

Effect of dietary fish oil on blood levels of free fatty acids, ketone bodies and triacylglycerol in humans

Although the reduction of serum triacylglycerol concentrations by dietary fish oil is a well-known effect, the exact mechanism of this effect has not been previously studied in human subjects. Therefore, the aim of this study was (i) to examine the effect of short-term fish oil supplementation on blood concentrations of ketone bodies, free fatty acids and triacylglycerol in healthy humans and (ii) to verify whether the observed relationships between these variables would be consistent with reduced lipolysis and/or enhanced hepatic fatty acid oxidation after fish oil supplementation. Twenty subjects (21-23 years, normal liver function tests) were randomly divided into two groups to supplement their usual diet with either 30 g/d of fish oil (n=11) or olive oil (n=9). Venous blood samples were drawn after an overnight fast, before and after 1, 3 and 7 d of fish oil/olive oil supplementation. Blood concentrations of triacylglycerol and free fatty acids decreased consistently after fish oil supplementation; the reduction was already significant after one day of fish oil (P0.10). No significant changes in glucose, insulin or ketone body levels were observed in either group after supplementation. After fish oil, but not after olive oil supplementation, the ratio of blood ketone body levels to free fatty acid levels increased significantly (P<0.05). Furthermore, after fish oil supplementation only, free fatty acid levels were significantly correlated with levels of ketone bodies (day 7 of supplementation: r=0.90, P<0.001) and triacylglycerol (maximum value on day 3: r=0.77, P<0.01). These findings suggest that reduced lipolysis and increased hepatic β-oxidation/ketogenesis may contribute to reduced triacylglycerol levels after ω3 fatty acid supplementation in humans. Turnover studies are needed in order to further quantitate these processes

Ductus Arteriosus Doppler in der ersten Schwangerschaftshälfte

Zusammenfassend stellen wir fest, daß es möglich ist, Flußgeschwindigkeiten durch den ductus arteriosus ab der 11. SSW zu messen. Enddiastolischer Flow tritt an der 13. SSW auf, vermutlich aufgrund abnehmender Afterload. Sowohl eine Abnahme der peripheren Afterload (Plazenta) als auch eine Zunahme der rechtsventrikulären Kontraktilität und das Auswurfvolumen sind für den Anstieg aller Blutflußgeschwindigkeiten im ductus arteriosus verantwortlich

Balloon dilation and stent implantation for treatment of femoropopliteal arterial disease: meta-analysis

PURPOSE: To perform a meta-analysis of long-term results of balloon dilation and stent implantation in the treatment of femoropopliteal arterial disease. MATERIALS AND METHODS: The English-language literature was searched for studies published between 1993 and 2000. Inclusion criteria for articles were presentation of long-term primary patency rates, standard errors (explicitly reported or derivable), and baseline characteristics of the study population. Two reviewers independently extracted data, and discrepancies were resolved by consensus. Primary patency rates were combined by using a technique that allows adjustment for differences across study populations. Analyses were adjusted for lesion type and clinical indication. RESULTS: Nineteen studies met the inclusion criteria, representing 923 balloon dilations and 473 stent implantations. Combined 3-year patency rates after balloon dilation were 61% (standard error, 2.2%) for stenoses and claudication, 48% (standard error, 3.3%) for occlusions and claudication, 43% (standard error, 4.1%) for stenoses and critical ischemia, and 30% (standard error, 3.7%) for occlusions and critical ischemia. The 3-year patency rates after stent implantation were 63%-66% (standard error, 4.1%) and were independent of clinical indication and lesion type. Funnel plots demonstrated an asymmetric distribution of the data points associated with stent studies. CONCLUSION: Balloon dilation and stent implantation for claudication and stenosis yield similar long-term patency rates. For more severe femoropopliteal disease, the results of stent implantation seem more favorable. Publication bias could not be ruled out

Three-dimensional US assessment of hepatic volume, head circumference, and abdominal circumference in healthy and growth-restricted fetuses

PURPOSE: To establish reproducibility and normal values for fetal hepatic volume and its significance in identification of fetal growth restriction relative to head and upper abdominal circumferences according to a cross-sectional study design. MATERIALS AND METHODS: Pregnant women (n = 135) underwent ultrasonography. The coefficient of variation (CV) for hepatic volume scans obtained at 0 and 20 minutes and hepatic area tracings, performed twice for each scan, was determined (n = 20; range, 23-36 weeks). Normal data for hepatic volume and head and upper abdominal circumferences were obtained (n = 85; range, 20-36 weeks) and related to data from growth-restricted fetuses (birth weight < P5 centile; n = 24; range, 22-36 weeks). RESULTS: CV was 2.9% for volume scans and 1.6% for area tracings. In 85 uncomplicated cases, mean fetal hepatic volume (P50 centile) was 9.7 mL +/- 4.4 (SD) at 20 weeks and 96.4 mL +/- 8.2 at 36 weeks of gestation. In 24 growth-restricted fetuses, hepatic volume, head circumference, and upper abdominal circumference expressed as percentages of the normal P50 centile were 45%, 90%, and 82%, respectively. Mean difference in hepatic volume between fetal growth restriction and normal fetal development, as expressed with the z score, -4.32 +/- 1.4, was significantly different (P <.05) from that for head circumference, -3.04 +/- 1.3, but not from that for upper abdominal circumference, -4.7 +/- 1.2. Fetal hepatic measurement was obtained in 109 pregnancies. CONCLUSION: Acceptable reproducibility exists for hepatic volume determinations. In fetal growth restriction, reduction is more pronounced for hepatic volume than for head or upper abdominal circumference; hepatic volume is a better discriminator than head circumference but not upper abdominal circumference

Genetic risk estimation by healthcare professionals

OBJECTIVES: To assess whether healthcare professionals correctly incorporate the relevance of a favourable test outcome in a close relative when determining the level of risk for individuals at risk for Huntington's disease. DESIGN AND SETTING: Survey of clinical geneticists and genetic counsellors from 12 centres of clinical genetics (United Kingdom, 6; The Netherlands, 4; Italy, 1; Australia, 1) in May-June 2002. Participants were asked to assess risk of specific individuals in 10 pedigrees, three of which required use of Bayes' theorem. PARTICIPANTS: 71 clinical geneticists and 41 other healthcare professionals involved in genetic counselling. MAIN OUTCOME MEASURES: Proportion of respondents correctly assessing risk in the three target pedigrees; proportion of respondents who were confident of their estimate. RESULTS: 50%-64% of respondents (for the three targets separately) did not include the favourable test information and inc

Serum inhibin B as a marker of spermatogenesis

Inhibin B is produced by Sertoli cells, provides negative feedback on FSH secretion, and may prove to be an important marker for the functioning of seminiferous tubules. The purpose of the present study was to examine the relationship between the spermatogenic function of the testis of subfertile men and the plasma concentrations of inhibin B and FSH. These parameters were estimated in a group of 218 subfertile men. Serum inhibin B levels were closely correlated with the serum FSH levels (r = -0.78, P < 0.001), confirming the role of inhibin B as feedback signal for FSH production. The spermatogenic function of the testis was evaluated by determining testicular volume and total sperm count. Inhibin B levels were significantly correlated with the total sperm count and testicular volume (r = 0.54 and r = 0.63, respectively; P < 0.001). Testicular biopsies were obtained in 22 of these men. Inhibin B was significantly correlated with the biopsy score (r = 0.76, P < 0.001). Receiver operating characteristic analysis revealed a diagnostic accuracy of 95% for differentiating competent from impaired spermatogenesis for inhibin B, whereas for FSH, a value of 80% was found. We conclude that inhibin B is the best available endocrine marker of spermatogenesis in subfertile men

Does phase 2 of the expiratory PCO2 versus volume curve have diagnostic value in emphysema patients?

It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emphysema is represented by the shape of expiratory carbon dioxide tension versus volume curve. We examined the diagnostic value of this test in patients with various degrees of emphysema. The volumes between 25-50% (V25-50) and 25-75% (V25-75) of the expiratory carbon dioxide tension versus volume curve were determined in 29 emphysematous patients (20 severely obstructed and 9 moderately obstructed), 12 asthma patients in exacerbation of symptoms, and 28 healthy controls. Discriminant analysis was used to examine whether these diagnostic groups could be separated. With regard to phase 2 of the expiratory CO2 versus volume curve (mixture of anatomic deadspace and alveolar air), a plot of intercept versus slope of the relationships of (V25-50) and (V25-75) versus inspiratory volume (VI) from functional residual capacity (FRC), obtained during natural breathing frequency, proved to be most discriminating in the separation between healthy controls and severely obstructed emphysema patients. Separating healthy controls and severely obstructed emphysema patients on the basis of the discriminant line for V25-50, 9 of the 12 asthma patients in exacerbation were classified as normal, and only 5 of the 9 moderately obstructed emphysema patients as emphysematous. For V25-75 involvement of phase 3 of the curve (alveolar plateau) in asthma patients in exacerbation caused a marked overlap with the severely obstructed emphysema patients. In the healthy controls, a fixed breathing frequency of 20 breaths.min-1 led to an increase of both volumes.(ABSTRACT TRUNCATED AT 250 WORDS