A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation

We assessed the effectiveness and safety of 3 yr combined GH and GnRH agonist (GnRHa) treatment in a randomized controlled study in children with idiopathic short stature (ISS) or intrauterine growth retardation (IUGR). Gonadal suppression, GH reserve, and adrenal development were assessed by hormone measurements in both treated children and controls during the study period. Thirty-six short children, 24 girls (16 ISS/8 IUGR) and 12 boys (8 ISS/4 IUGR), with a height SD score of -2 SD or less in early puberty (girls, B2-3; boys, G2-3), were randomly assigned to treatment (n = 18) with GH (genotropin 4 IU/m(2). day) and GnRHa (triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the start of the study mean (SD) age was 11.4 (0.56) or 12.2 (1.12) yr whereas bone age was 10.7 (0.87) or 10.9 (0.63) yrs in girls and boys, respectively. During 3 yr of study height SD score for chronological age did not change in both treated children and controls, whereas a decreased rate of bone maturation after treatment was observed [mean (SD) 0.55 (0.21) 'yr'/yr vs. 1.15 (0.37) 'yr'/yr in controls, P < 0.001, girls and boys together]. Height SD score for bone age and predicted adult height increased significantly after 3 yr of treatment; compared with controls the predicted adult height gain was 8.0 cm in girls and 10.4 cm in boys. Furthermore, the ratio between sitting height/height SD score decreased significantly in treated children, whereas body mass index was not influenced by treatment. Puberty was effectively arrested in the treated children, as was confirmed by physical examination and prepubertal testosterone and estradiol levels. GH-dependent hormones including serum insulin-like growth factor I and II, carboxy terminal propeptide of type I collagen, amino terminal propeptide of type III collagen, alkaline phosphatase, and osteocalcin were not different between treated children and controls during the study period. Thus, a GH dose of 4 IU/m(2) seems adequate for stabilization of the GH reserve and growth in these GnRHa-treated children. We conclude that 3 yr treatment with GnRHa was effective in suppressing pubertal development and skeletal maturation, whereas the addition of GH preserved growth velocity during treatment. This resulted in a considerable gain in predicted adult height, without demonstrable side effects. Final height results will provide the definite answer on the effectiveness of this combined treatment

Long-term and large-scale multispecies dataset tracking population changes of common European breeding birds

Around fifteen thousand fieldworkers annually count breeding birds using standardized protocols in 28 European countries. The observations are collected by using country-specific and standardized protocols, validated, summarized and finally used for the production of continent-wide annual and long-term indices of population size changes of 170 species. Here, we present the database and provide a detailed summary of the methodology used for fieldwork and calculation of the relative population size change estimates. We also provide a brief overview of how the data are used in research, conservation and policy. We believe this unique database, based on decades of bird monitoring alongside the comprehensive summary of its methodology, will facilitate and encourage further use of the Pan-European Common Bird Monitoring Scheme results.publishedVersio

The Joles Jewish Hospital: A Short-lived Dutch Small City Hospital With an Unusual Resurrection

The Joles Jewish Hospital in Haarlem (a small city in the Netherlands) was established in 1930 to provide a Jewish milieu for local patients. Mozes Joles, a wealthy Jewish businessman, bequeathed his fortune to the Haarlem Jewish community to accomplish this objective, and its spiritual leader, Rabbi Simon Philip de Vries, was the driving force in successfully achieving this goal. The Joles Hospital was forcibly closed by the Nazis in 1943, and the postwar leadership of the Haarlem Jewish community decided not to reopen it. Instead, they used the Joles inheritance to build old age homes in both Haifa, Israel, and Haarlem, thus ensuring a Jewish environment for elderly care in both locales. The realization of one man\u27s charitable act bettered the lives of both ill and elderly individuals

Diagnostic value of laboratory monitoring to predict severe hemolytic disease of the fetus and newborn in non-D and non-K-alloimmunized pregnancies

BACKGROUND: Pregnant women are routinely screened for red blood cell (RBC) antibodies early in pregnancy. If RBC-alloantibodies are detected, repeated laboratory testing is advised to timely identify pregnancies at high risk for severe hemolytic disease of the fetus and newborn (HDFN). We assessed for RBC alloantibodies, other than anti-D or anti-K, cut-offs for the titer and the antibody dependent cellular cytotoxicity (ADCC) test to select high-risk cases. To advise on test repeat intervals, and to avoid unnecessary testing, we evaluated the chance for exceeding the cut-offs for Rh antibodies other than anti-D, Jk, Fy, and S/s antibodies. STUDY DESIGN AND METHODS: Diagnostic value of antibody titer and ADCC test was determined with data from a prospective index-cohort study, conducted in 2002-2004. Laboratory test outcomes were from a recent observational cohort (2015-2016). RESULTS: A titer cut-off of ≥16 showed a sensitivity of 100% (95% CI:73-100%) and a positive predictive value (PPV) of 17% (95% CI:14%-20%). The percentage of pregnancies reaching a titer above the cut-off of ≥16 varied from 0% for anti-Jka/Jkb (n = 38) to 36% for anti-c (n = 97). The ADCC test showed no cut-off with a 100% sensitivity. However, in cases with a titer ≥16 and an ADCC test ≥30% a PPV of 38% was obtained to detect severe HDFN. CONCLUSION: A titer cut-off of ≥16 is adequate to detect all cases at risk for severe HDFN; the ADCC test may add a more accurate risk estimation. Repeated testing is recommended in pregnancies with anti-c. In pregnancies with other Rh antibodies a repeated test in the third trimester is recommended

<i>KIF1A</i> variants are a frequent cause of autosomal dominant hereditary spastic paraplegia

Variants in the KIF1A gene can cause autosomal recessive spastic paraplegia 30, autosomal recessive hereditary sensory neuropathy, or autosomal (de novo) dominant mental retardation type 9. More recently, variants in KIF1A have also been described in a few cases with autosomal dominant spastic paraplegia. Here, we describe 20 KIF1A variants in 24 patients from a clinical exome sequencing cohort of 347 individuals with a mostly 'pure' spastic paraplegia. In these patients, spastic paraplegia was slowly progressive and mostly pure, but with a highly variable disease onset (0-57 years). Segregation analyses showed a de novo occurrence in seven cases, and a dominant inheritance pattern in 11 families. The motor domain of KIF1A is a hotspot for disease causing variants in autosomal dominant spastic paraplegia, similar to mental retardation type 9 and recessive spastic paraplegia type 30. However, unlike these allelic disorders, dominant spastic paraplegia was also caused by loss-of-function variants outside this domain in six families. Finally, three missense variants were outside the motor domain and need further characterization. In conclusion, KIF1A variants are a frequent cause of autosomal dominant spastic paraplegia in our cohort (6-7%). The identification of KIF1A loss-of-function variants suggests haploinsufficiency as a possible mechanism in autosomal dominant spastic paraplegia

Postponing Early intrauterine Transfusion with Intravenous immunoglobulin Treatment; the PETIT study on severe hemolytic disease of the fetus and newborn

BACKGROUND: Intrauterine transfusion for severe alloimmunization in pregnancy performed <20 weeks' gestation is associated with a higher fetal death rate. Intravenous immunoglobulins may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. OBJECTIVE: We evaluated whether maternal treatment with intravenous immunoglobulins defers the development of severe fetal anemia and its consequences in a retrospective cohort to which 12 fetal therapy centers contributed. STUDY DESIGN: We included consecutive pregnancies of alloimmunized women with a history of severe hemolytic disease and by propensity analysis compared index pregnancies treated with intravenous immunoglobulins (n = 24) with pregnancies managed without intravenous immunoglobulins (n = 28). RESULTS: In index pregnancies with intravenous immunoglobulin treatment, fetal anemia developed on average 15 days later compared to previous pregnancies (8% less often <20 weeks' gestation). In pregnancies without intravenous immunoglobulin treatment anemia developed 9 days earlier compared to previous pregnancies (10% more <20 weeks), an adjusted 4-day between-group difference in favor of the immunoglobulin group (95% confidence interval, -10 to +18; P = .564). In the subcohort in which immunoglobulin treatment was started <13 weeks, anemia developed 25 days later and 31% less <20 weeks' gestation (54% compared to 23%) than in the previous pregnancy. Fetal hydrops occurred in 4% of immunoglobulin-treated pregnancies and in 24% of those without intravenous immunoglobulin treatment (odds ratio, 0.03; 95% confidence interval, 0-0.5; P = .011). Exchange transfusions were given to 9% of neonates born from pregnancies with and in 37% without immunoglobulin treatment (odds ratio, 0.1; 95% confidence interval, 0-0.5; P = .009). CONCLUSION: Intravenous immunoglobulin treatment in mothers pregnant with a fetus at risk for hemolytic disease seems to have a potential clinically relevant, beneficial effect on the course and severity of the disease. Confirmation in a multicenter randomized trial is needed.status: publishe