Natural history of growth hormone deficiency in a pediatric cohort.

BACKGROUND/AIMS Controversies still exist regarding the evaluation of growth hormone deficiency (GHD) in childhood at the end of growth. The aim of this study was to describe the natural history of GHD in a pediatric cohort. METHODS This is a retrospective study of a cohort of pediatric patients with GHD. Cases of acquired GHD were excluded. Univariate logistic regression was used to identify predictors of GHD persisting into adulthood. RESULTS Among 63 identified patients, 47 (75%) had partial GHD at diagnosis, while 16 (25%) had complete GHD, including 5 with multiple pituitary hormone deficiencies. At final height, 50 patients underwent repeat stimulation testing; 28 (56%) recovered and 22 (44%) remained growth hormone (GH) deficient. Predictors of persisting GHD were: complete GHD at diagnosis (OR 10.1, 95% CI 2.4-42.1), pituitary stalk defect or ectopic pituitary gland on magnetic resonance imaging (OR 6.5, 95% CI 1.1-37.1), greater height gain during GH treatment (OR 1.8, 95% CI 1.0-3.3), and IGF-1 level <-2 standard deviation scores (SDS) following treatment cessation (OR 19.3, 95% CI 3.6-103.1). In the multivariate analysis, only IGF-1 level <-2 SDS (OR 13.3, 95% CI 2.3-77.3) and complete GHD (OR 6.3, 95% CI 1.2-32.8) were associated with the outcome. CONCLUSION At final height, 56% of adolescents with GHD had recovered. Complete GHD at diagnosis, low IGF-1 levels following retesting, and pituitary malformation were strong predictors of persistence of GHD.

Dental arch relationship in 5-year-olds with complete unilateral cleft lip and palate after early alveolar bone grafting

To evaluate dental arch relationship in preschoolers with unilateral cleft lip and palate after early alveolar bone grafting (ABG).

Short-term response of the Ca cycle of a montane forest in Ecuador to low experimental CaCl 2 additions

The tropical montane forests of the E Andean cordillera in Ecuador receive episodic Sahara-dust inputs particularly increasing Ca deposition. We added CaCl2 to isolate the effect of Ca deposition by Sahara dust to tropical montane forest from the simultaneously occurring pH effect. We examined components of the Ca cycle at four control plots and four plots with added Ca (2 × 5 kg ha–1 Ca annually as CaCl2) in a random arrangement. Between August 2007 and December 2009 (four applications of Ca), we determined Ca concentrations and fluxes in litter leachate, mineral soil solution (0.15 and 0.30 m depths), throughfall, and fine litterfall and Al concentrations and speciation in soil solutions. After 1 y of Ca addition, we assessed fine-root biomass, leaf area, and tree growth. Only < 3% of the applied Ca leached below the acid organic layer (pH 3.5–4.8). The added CaCl2 did not change electrical conductivity in the root zone after 2 y. In the second year of fertilization, Ca retention in the canopy of the Ca treatment tended to decrease relative to the control. After 2 y, 21% of the applied Ca was recycled to soil with throughfall and litterfall. One year after the first Ca addition, fine-root biomass had decreased significantly. Decreasing fine-root biomass might be attributed to a direct or an indirect beneficial effect of Ca on the soil decomposer community. Because of almost complete association of Al with dissolved organic matter and high free Ca2+ : Al3+ activity ratios in solution of all plots, Al toxicity was unlikely. We conclude that the added Ca was retained in the system and had beneficial effects on some plants.

5-ALA complete resections go beyond MR contrast enhancement: shift corrected volumetric analysis of the extent of resection in surgery for glioblastoma

BACKGROUND The technique of 5-aminolevulinic acid (5-ALA) tumor fluorescence is increasingly used to improve visualization of tumor tissue and thereby to increase the rate of patients with gross total resections. In this study, we measured the resection volumes in patients who underwent 5-ALA-guided surgery for non-eloquent glioblastoma and compared them with the preoperative tumor volume. METHODS We selected 13 patients who had received a complete resection according to intraoperative 5-ALA induced fluorescence and CRET according to post-operative T1 contrast-enhanced MRI. The volumes of pre-operative contrast enhancing tissue, post-operative resection cavity and resected tissue were determined through shift-corrected volumetric analysis. RESULTS The mean resection cavity (29 cm(3)) was marginally smaller than the pre-operative contrast-enhancing tumor (39 cm(3), p = 0.32). However, the mean overall resection volume (84 cm(3)) was significantly larger than the pre-operative contrast-enhancing tumor (39 cm(3), p = 0.0087). This yields a mean volume of resected 5-ALA positive, but radiological non-enhancing tissue of 45 cm(3). The mean calculated rim of resected tissue surpassed pre-operative tumor diameter by 6 mm (range 0-10 mm). CONCLUSIONS Results of the current study imply that (i) the resection cavity underestimates the volume of resected tissue and (ii) 5-ALA complete resections go significantly beyond the volume of pre-operative contrast-enhancing tumor bulk on MRI, indicating that 5-ALA also stains MRI non-enhancing tumor tissue. Use of 5-ALA may thus enable extension of coalescent tumor resection beyond radiologically evident tumor. The impact of this more extended resection method on time to progression and overall survival has not been determined, and potentially puts adjacent and functionally intact tissue at risk.

Complete continence after botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity incontinence: patient-reported outcome at 4 weeks

Objective improvement following intradetrusor injections of botulinum neurotoxin type A (BoNTA) is well documented. Although patient-related outcome measures are highly recommended for monitoring overactive bladder symptoms, no study before has dealt with the question of patient-reported complete continence after BoNTA treatment using validated questionnaires.

Craniofacial morphology in complete unilateral cleft lip and palate patients consecutively treated with 1-stage repair of the cleft

OBJECTIVE: To retrospectively evaluate the craniofacial morphology of children with a complete unilateral cleft lip and palate treated with a 1-stage simultaneous cleft repair performed in the first year of life. METHODS: Cephalograms and extraoral profile photographs of 61 consecutively treated patients (42 boys, 19 girls) who had been operated on at 9.2 (SD, 2.0) months by a single experienced surgeon were analyzed at 11.4 (SD, 1.5) years. The noncleft control group comprised 81 children (43 boys and 38 girls) of the same ethnicity at the age of 10.4 (SD, 0.5) years. RESULTS: In children with cleft, the maxilla and mandible were retrusive; the palatal and mandibular planes were more open, and sagittal maxillomandibular relationship was less favorable in comparison to noncleft control subjects. Soft tissues in patients with cleft reflected retrusive morphology of hard tissues--subnasal and supramental regions were less convex, profile was flatter, and nasolabial angle was more acute relative to those of the control subjects. CONCLUSIONS: Craniofacial morphology after 1-stage repair was deviated in comparison with noncleft control subjects. However, the degree of deviation was comparable with that found after treatment with alternative surgical protocols.

Effects of eccentric cycle ergometry in alpine skiers

Eccentric cycling, where the goal is to resist the pedals, which are driven by a motor, increases muscle strength and size in untrained subjects. We hypothesized that it could also be beneficial for athletes, particularly in alpine skiing, which involves predominantly eccentric contractions at longer muscle lengths. We investigated the effects of replacing part of regular weight training with eccentric cycling in junior male alpine skiers using a matched-pair design. Control subjects ( N=7) executed 1-h weight sessions 3 times per week, which included 4-5 sets of 4 leg exercises. The eccentric group ( N=8) performed only 3 sets, followed by continuous sessions on the eccentric ergometer for the remaining 20 min. After 6 weeks, lean thigh mass increased significantly only in the eccentric group. There was a groupxtime effect on squat-jump height favouring the eccentric group, which also experienced a 6.5% improvement in countermovement-jump height. The ability to finely modulate muscle force during variable eccentric cycling improved 50% (p=0.004) only in the eccentric group. Although eccentric cycling did not significantly enhance isometric leg strength, we believe it is beneficial for alpine skiers because it provides an efficient means for hypertrophy while closely mimicking the type of muscle actions encountered while skiing.

Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction activity in patients with relapsed AML. Patients with AML or refractory anemia with excess blasts in first complete remission attained after intensive induction chemotherapy were randomized between 3 cycles of GO (6 mg/m(2) every 4 weeks) or no postremission therapy (control) to assess whether GO would improve outcome. The 2 treatment groups (113 patients receiving GO vs 119 control patients) were comparable with regard to age (60-78 years, median 67 years), performance status, and cytogenetics. A total of 110 of 113 received at least 1 cycle of GO, and 65 of 113 patients completed the 3 cycles. Premature discontinuation was mainly attributable to incomplete hematologic recovery or intercurrent relapse. Median time to recovery of platelets 50 x 10(9)/L and neutrophils 0.5 x 10(9)/L after GO was 14 days and 20 days. Nonhematologic toxicities were mild overall, but there was 1 toxic death caused by liver failure. There were no significant differences between both treatment groups with regard to relapse probabilities, nonrelapse mortality, overall survival, or disease-free survival (17% vs 16% at 5 years). Postremission treatment with GO in older AML patients does not provide benefits regarding any clinical end points. The HOVON-43 study is registered at The Netherlands Trial Registry (number NTR212) and at http://www.controlled-trials.com as ISRCTN77039377.

On the traces of XPD: cell cycle matters - untangling the genotype-phenotype relationship of XPD mutations

Abstract Mutations in the human gene coding for XPD lead to segmental progeria - the premature appearance of some of the phenotypes normally associated with aging - which may or may not be accompanied by increased cancer incidence. XPD is required for at least three different critical cellular functions: in addition to participating in the process of nucleotide excision repair (NER), which removes bulky DNA lesions, XPD also regulates transcription as part of the general transcription factor IIH (TFIIH) and controls cell cycle progression through its interaction with CAK, a pivotal activator of cyclin dependent kinases (CDKs). The study of inherited XPD disorders offers the opportunity to gain insights into the coordination of important cellular events and may shed light on the mechanisms that regulate the delicate equilibrium between cell proliferation and functional senescence, which is notably altered during physiological aging and in cancer. The phenotypic manifestations in the different XPD disorders are the sum of disturbances in the vital processes carried out by TFIIH and CAK. In addition, further TFIIH- and CAK-independent cellular activities of XPD may also play a role. This, added to the complex feedback networks that are in place to guarantee the coordination between cell cycle, DNA repair and transcription, complicates the interpretation of clinical observations. While results obtained from patient cell isolates as well as from murine models have been elementary in revealing such complexity, the Drosophila embryo has proven useful to analyze the role of XPD as a cell cycle regulator independently from its other cellular functions. Together with data from the biochemical and structural analysis of XPD and of the TFIIH complex these results combine into a new picture of the XPD activities that provides ground for a better understanding of the patophysiology of XPD diseases and for future development of diagnostic and therapeutic tools.

Long-term tissue coverage of a biodegradable polylactide polymer-coated biolimus-eluting stent: comparative sequential assessment with optical coherence tomography until complete resorption of the polymer

Biolimus-eluting stents (BESs) with a biodegradable polymer in abluminal coating achieve more complete coverage at 9 months compared with sirolimus-eluting stents (SESs) with a durable polymer, as assessed by optical coherence tomography (OCT). Whether this advantage persists or augments after complete resorption of the polymer (>12 months) is unknown.

Nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate

The objective of this study was to evaluate the association between nasolabial symmetry and aesthetics in children with complete unilateral cleft lip and palate (CUCLP). Frontal and basal photographs of 60 consecutively treated children with CUCLP (cleft group: 41 boys and 19 girls, mean (SD) age 11 (2) years) and 44 children without clefts (control group: 16 boys and 28 girls, mean (SD) age 11(2) years), were used for evaluation of nasolabial symmetry and aesthetics. Nasal and labial measurements were made to calculate the coefficient of asymmetry (CA). The 5-grade aesthetic index described by Asher-McDade et al. was used to evaluate nasolabial appearance. Correlation and regression analysis were used to identify an association between aesthetics and CA, sex, and the presence of CUCLP. Ten measurements in the cleft, and 2 in the control, group differed significantly between the cleft and non-cleft (or right and left) sides, respectively. The significantly higher values of 9 of 11 CA in the children with CUCLP indicated that they had more asymmetrical nasolabial areas than children without clefts. However, the regression analyses showed that only a few CA were associated with nasolabial aesthetics. In conclusion, nasolabial aesthetics and nasolabial symmetry seem to be only weakly associated in patients with CUCLP.

The canine hair cycle - a guide for the assessment of morphological and immunohistochemical criteria

The hair follicle has a lifelong capacity to cycle through recurrent phases of controlled growth (anagen), regression (catagen) and quiescence (telogen), each associated with specific morphological changes. A comprehensive classification scheme is available for mice to distinguish the cycle stages anagen I-VI, catagen I-VIII and telogen. For dogs, such a classification system does not exist, although alopecia associated with hair cycle arrest is common. We applied analogous morphological criteria and various staining techniques to subdivide the canine hair cycle stages to the same extent as has been done in mice. Of all the staining techniques applied, haematoxylin and eosin stain, Sacpic, Masson Fontana and immunohistochemistry for vimentin and laminin proved to be most useful. To evaluate the applicability of our criteria, we investigated skin biopsies from healthy beagle dogs (n=20; biopsies from shoulder and thigh) kept in controlled conditions. From each biopsy, at least 50 hair follicles were assessed. Statistical analysis revealed that 30% of the follicles were in anagen (12% early and 18% late), 8% in catagen (2% early, 5% late and 1% not determinable) and 27% in telogen. Thirty-five per cent of hair follicles could not be assigned to a specific cycle stage because not all follicles within one biopsy were oriented perfectly. In conclusion, this guide will not only be helpful for the investigation of alopecic disorders and possibly their pathogenesis, but may also serve as a basis for research projects in which the comparison of hair cycle stages is essential, e.g. comparative analysis of gene expression patterns.