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PubMed2005

The prevalence of Helicobacter pylori in the Hispanic population affected by hyperemesis gravidarum.

OBJECTIVE: The purpose of this study was to determine the prevalence of Helicobacter pylori seropositivity in pregnant Hispanics affected by hyperemesis gravidarum. STUDY DESIGN: This was a prospective cross-sectional study conducted over a 22-month period. Serum from pregnant Hispanics affected by hyperemesis gravidarum and unaffected Hispanics matched for age, gravidity, parity, and country of origin were tested for H pylori immunoglobulin G (IgG). IgG levels specific for H pylori were determined by enzyme-linked immunosorbent assay (ELISA). Assuming the background prevalence of H pylori serum positivity in the Hispanic population is approximately 60%, 38 patients in each group were needed to detect a 30% difference in affected patients versus controls with a power of 80% and P = .05. Statistical analysis was performed using Yate's chi-square, Student t test, Mann-Whitney U, and binary logistic regression. RESULTS: A total of 82 patients between the ages of 18 to 39 years were enrolled. Of 40 patients diagnosed with hyperemesis gravidarum, 26 (65%) were seropositive for H pylori compared with 28 of 42 (67%) unaffected controls (P = 1.0). There were no statistical differences in maternal age or countries of origin between the 2 groups. CONCLUSION: The overall prevalence of H pylori seropositivity in this patient population is 66%. In pregnant Hispanics affected by hyperemesis gravidarum, H pylori seropositivity is not increased compared with unaffected controls.

Adult↗
PubMed2005

The effect of simvastatin on polyethylene particle-induced osteolysis.

This study aimed to investigate the effects of the HMG-CoA reductase inhibitor simvastatin on ultra-high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The murine calvarial osteolysis model was used in 21 C57BL/J6 mice randomized to three groups. Group I underwent sham surgery only, group II received UHMWPE particles, and group III, particles and simvastatin treatment. After two weeks, calvaria were processed for histomorphometry. Bone resorption was measured as resorption within the midline suture using Giemsa staining. Osteoclast numbers were determined per high-power field using TRAP-staining. Statistical analysis was performed using one-way ANOVA and Student's t-test. Bone resorption in midline suture was 0.094+/-0.007 mm(2) in sham controls (group I), 0.25+/-0.025 mm(2) after particle implantation without further intervention (group II), and 0.131+/-0.02 mm(2) with particle implantation and additional simvastatin treatment (group III) (p=0.00003). Osteoclast numbers were 15.3+/-3.6 in group I, 48.7+/-7.1 in group II and 6.2+/-3.1 in group III (p=0.00002). In conclusion, simvastatin treatment markedly decreased UHMWPE particle-induced osteolysis in a murine calvarial model. This finding suggests that simvastatin may have a role for noninvasive prevention and treatment of wear debris-mediated periprosthetic osteolysis after total joint arthroplasty.

Animals↗
PubMed2007

Evaluation of the usefulness of bird feathers as a non-destructive biomonitoring tool for organic pollutants: a comparative and meta-analytical approach.

In this study, we investigated whether bird feathers can be used as a non-destructive biomonitor for organic pollutants. We analysed the outermost tail feathers of 8 terrestrial and aquatic bird species from Belgium (8 species, n=108) for polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs). Every compound class could be quantified in one single tail feather of the birds under study (sum PCBs ranging from 5.5 to 510 ng/g feather, sum PBDEs from 0.33 to 53 ng/g feather, sum DDTs from 1.5 to 730 ng/g feather), except for PBDEs in feathers of the common moorhen (Gallinula chloropus). Further, we calculated Pearson correlations between concentrations of organic pollutants in feathers and concentrations in corresponding muscle or liver tissue from the birds. Correlations were found significant in half of the cases of the terrestrial species, but were found not significant for the aquatic species, with the exception of a significant correlation of sum PCBs in the common moorhen. Only for the common buzzard (Buteo buteo) (n=43) all correlations were found significant (0.32<r<0.77). In order to cope for low statistical power, we performed a meta-analysis on all bird species together. This led to significant correlations between levels in feathers and corresponding levels in muscle or liver for all terrestrial birds (p<0.05 in all cases, effect size 0.59 (p,p'-DDE) to 0.71 (Sigma PCB) for levels in feather and muscle). When correlations were recalculated excluding the birds that had died due to starvation, correlation coefficients for the terrestrial birds were found even higher (effect size up to 0.83 (Sigma PCB)). These results have important implications for non-destructive and retrospective biomonitoring. Although our results suggest that exact concentrations in the body cannot be predicted using feathers, bird feathers can give a good estimate of contamination levels in a population and as such are a potential non-destructive biomonitoring tool for organic pollutants. Outermost tail feathers and muscle tissue were also examined for nitrogen (delta15N) and carbon (delta13C) stable isotope content in the different bird species. However, delta15N/delta13C signatures in feather or muscle were not significantly correlated with the corresponding levels of organic pollutants in these tissues. Various confounding factors (such as habitat, condition, age, sex) may have masked a relationship between delta15N values and organic pollutant levels in the birds under study.

Animals↗
PubMed2026

Genetically-predicted placental gene expression links to uterine fibroids and endometriosis.

INTRODUCTION: Mother-to-child disease transmission begins in utero, with the placenta playing a critical role in pregnancy and offspring health. Uterine leiomyomata (fibroids, UFs) and endometriosis (ENDO) are common gynecologic diseases that have substantial overlaps in symptomology and risk factors, however drivers of disease risk remain unclear. The objective of this study was to investigate shared placental genetic associations across ENDO and UFs. METHODS: Genome-wide association study (GWAS) summary statistics were utilized from a published study of UFs (PMID: 40050615) and meta-analyzed for ENDO (24,092 cases and 548,255 controls). To improve our statistical power, we applied Multi-Trait Analysis of GWAS to the ENDO and UF GWAS. We estimated genetically predicted gene expression using S-PrediXcan across 49 tissues using GTEx v7 and a placental tissue expression model. RESULTS: We identified 54 and 14 genes where predicted expression in the placenta was significantly associated with UFs and ENDO, respectively. Twenty-one of these genes were shared between UFs and ENDO. Significant gene associations in placenta tissue were compared to the other 48 GTEx v7 tissue types to identify placenta specific associations. There were 40 and 13 significant gene-tissue associations specific to the placenta across UFs and ENDO, respectively. Eight of the placenta-specific genes were shared across UFs and ENDO. The strongest shared placenta-specific associations included PRKCI and HRH1. CONCLUSIONS: Our findings demonstrate a shared genetic relationship between UFs and ENDO in the placenta. The placenta specific associations suggest that dysregulation of early developmental pathways may contribute to a shared genetic origin of these diseases.

Female↗
PubMed1999

The association between negative muscle work and pedaling rate.

The objective of this research was to use a pedal force decomposition approach to quantify the amount of negative muscular crank torque generated by a group of competitive cyclists across a range of pedaling rates. We hypothesized that negative muscular crank torque increases at high pedaling rates as a result of the activation dynamics associated with muscle force development and the need for movement control, and that there is a correlation between negative muscular crank torque and pedaling rate. To test this hypothesis, data were collected during 60, 75, 90, 105 and 120 revolutions per minute (rpm) pedaling at a power output of 260 W. The statistical analysis supported our hypothesis. A significant pedaling rate effect was detected in the average negative muscular crank torque with all pedaling rates significantly different from each other (p < 0.05). There was no negative muscular crank torque generated at 60 rpm and negligible amounts at 75 and 90 rpm. But substantial negative muscular crank torque was generated at the two highest pedaling rates (105 and 120 rpm) that increased with increasing pedaling rates. This result suggested that there is a correlation between negative muscle work and the pedaling rates preferred by cyclists (near 90 rpm), and that the cyclists' ability to effectively accelerate the crank with the working muscles diminishes at high pedaling rates.

Adult↗
PubMed1997

Alterations in cord blood leukocyte subsets of patients with severe hemolytic disease after intrauterine transfusion therapy.

OBJECTIVES: The aim of this study was to compare, at delivery, the cord blood mononuclear cells of infants with severe hemolytic disease who received intrauterine transfusion (IUT) therapy with the cord blood mononuclear cells of healthy nonimmunized control neonates. STUDY DESIGN: The expression of leukocyte markers on CBMNC of 14 IUT-treated and 18 control neonates was analyzed by means of a panel of well-defined monoclonal antibodies and flow cytometry. RESULTS: Patients with severe hemolytic disease requiring IUT treatment displayed significant altered expression of some leukocyte markers when compared with control subjects. The circulating CD34+ progenitor cells were significantly increased in comparison with cord blood of nonimmunized neonates. IUT-treated patients also showed a statistically significant decrease in natural killer (NK) cell associated markers (CD16, CD57, and CD69), which correlated with a lower expression of CD56. In these patients an increased expression of CD3/CD45RO and CD3/CD5 was also noted. Although these latter alterations were statistically significant in a single-parameter analysis, the significance disappeared after multi-parameter analysis because of a loss of statistical power. CONCLUSIONS: Compared with nonimmunized healthy newborn infants, patients who underwent IUT also exhibited a down-regulation of NK cells and NK cell associated markers, as well as increased numbers of CD34+ progenitor cells.

Antibodies, Monoclonal↗
PubMed1996

Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: an antiallergic activity.

BACKGROUND: It is well known that allergen-specific nasal challenge (ASNC) is a fruitful tool with which to evaluate antiallergic activity exerted by a drug. Azelastine is a new antihistamine also available in topical form (i.e., nasal spray). OBJECTIVE: The aim of the study was to evaluate the effects of azelastine nasal spray on inflammatory changes after ASNC in both the early-phase reaction and the late-phase reaction. METHODS: The study had a double-blind, placebo-controlled, randomized, and parallel-group design. Twenty patients with pollen allergy were enrolled out of pollen season. ASNC was performed at baseline (TO) and after 1 week of washout (T7). At T7, 10 patients sprayed azelastine (1 puff) into their nostrils, and 10 patients used placebo. ASNC was performed after 30 minutes. The considered parameters (evaluated during early- and late-phase reactions) were: (1) clinical signs and symptoms, (2) cytologic assessment (neutrophils and eosinophils), (3) assay-of mediators (eosinophil cationic protein and myeloperoxidase), and (4) expression of intercellular adhesion molecule-1 (ICAM-1) on nasal epithelial cells. We focused our attention on ICAM-1 because it is the natural ligand of leukocyte functional associated antigen-1 and Mac-1, expressed on eosinophils. In addition, ICAM-1 is expressed on epithelial cells only on allergen exposure (both natural and experimental). RESULTS: Placebo did not exert any modification on the considered parameters. After azelastine administration, significant decreases in total symptom score, eosinophilic and neutrophilic infiltration, and ICAM-1 expression were observed during both early- and late-phase reactions. Furthermore, serum eosinophil cationic protein levels decreased during the late-phase reaction, whereas myeloperoxidase was not affected by the treatment. These findings were confirmed by the powerful Koch's split-plot statistical analysis. CONCLUSION: Azelastine exerts antiallergic activity, mainly affecting eosinophil function and downregulating ICAM-1 expression, on nasal epithelial cells.

Administration, Topical↗
PubMed1998

Genetic linkage to the serotonin transporter protein and 5HT2A receptor genes excluded in generalized social phobia.

Social phobia, particularly the generalized form, is strongly familial and frequently comorbid with major depression, panic disorder, and obsessive-compulsive disorder. It has also recently been shown to be responsive to selective serotonin reuptake inhibitors. We conducted a study to determine if generalized social phobia is genetically linked to either of two candidate genes: the serotonin transporter protein (5HTT) gene, or the 5HT2A receptor (5HT2AR) gene. Rates of social phobia (using several phenotype definitions) were ascertained and blood samples obtained from consenting first-degree family members of generalized social phobic probands. 5HT2AR and 5HTT genotyping was performed using the polymerase chain reaction (PCR). Linkage was tested using LINKAGE and GENEHUNTER software. No evidence of linkage was found; power analysis indicated that failure to find linkage was unlikely due to inadequate statistical power. These findings reasonably exclude linkage between generalized social phobia and the 5HTT or 5HT2AR genes in these samples, although modifier effects cannot be ruled out. Other 5HT receptor subtypes or indirect modulatory effects of 5HT on other neurotransmitter systems may be involved.

Adolescent↗
PubMed2000

Autonomous choice in the learning process of a turtle Chinemys reevesii.

We studied animal's learning of spatial discrimination in an experimental environment. Turtles, Chinemys reevesii, were employed for the study. We focused on two independent aspects: (1) turtle's success rate in the task, which is the most common criterion to estimate the ability of the animals, and (2) the statistical properties of the time interval of the task, which is independent on the spatial criterion. For a statistical analysis, we employed the scheme of power law distributions which was recently used to estimate animal behaviors in relation to the idea of the fractal. We addressed the basic problem of whether these two criteria, or any other criteria for this matter, could or could not exclude an observer who studies the animal behavior. To demonstrate inseparability of an observer and the object, we conducted three different learning experiments: (1) complete spatial discrimination, (2) incomplete spatial discrimination, (3) another, different, complete discrimination, in this order. The incomplete one was taken to mean incomplete only for an observer. Our experiments reveal that the same result (success rate) was perceived differently by the animal if the attitude of the observer to the experiments differed. This observation comes to suggest that the notion of autonomous choice on the part of an animal is contingent upon the inseparability between an observer and the object.

Animals↗
PubMed2001

Applications of population approaches in toxicology.

Many experimental or observational studies in toxicology are best analysed in a population framework. Recent examples include investigations of the extent and origin of intra-individual variability in toxicity studies, incorporation of genotypic information to address intra-individual variability, optimal design of experiments, and extension of toxicokinetic modelling to the analysis of biomarker studies. Bayesian statistics provide powerful numerical methods for fitting population models, particularly when complex mechanistic models are involved. Challenges and limitations to the use of population models, in terms of basic structure, computational burden, ease of implementation and data accessibility, are identified and discussed.

Animals↗
PubMed2003

Use of primidone in low doses (250 mg/day) versus high doses (750 mg/day) in the management of essential tremor. Double-blind comparative study with one-year follow-up.

Essential tremor is the most common involuntary movement; we studied 113 affected subjects (54 men, 59 women) with an average age of 63.9 years and average duration of 9.05 years. These patients participated in a double-blind study with a 1-year follow-up to compare treatment efficiency using primidone dosages of 250 mg/day (G 250, 56 patients) versus 750 mg/day (G 750, 57 patients). The study was designed with an 80% power and 95% confidence level. The statistical analysis used was an ANOVA (with Bonferroni multiple comparison test corrections); a value of p<0.004 was accepted as significant. To compare other values, a chi-square test was used; p<0.05 was considered significant. To evaluate the efficacy of the drug, clinical protocol employed the 'clinical evaluation scale for tremor'. All of the patients were evaluated a total of 13 times, once prior to the introduction of primidone and the other 12 evaluations following the initiation of the treatment. Eighty-seven patients completed the study: 15 patients abandoned the study due to undesirable side effects, five due to negative response, and six who were lost to follow-up. The percentage of patients who didn't complete the study was significantly higher in the group that received 750 mg/day of primidone (p<0.04) and more frequent as well in this same group, due to undesirable side effects (p<0.03). The patients of both G250 and G750 showed a significant improvement in each of the controls compared to the basal value (p<0.0001). No significant differences (p<0.06) were found when the averages of the evaluations of each group were compared. These responses were maintained during the entire treatment period. Low doses of primidone (250 mg/day) were equally or more effective than high doses (750 mg/day) in the control of essential tremor; this response was maintained for 12 months and furthermore, demonstrated fewer undesirable effects.

Administration, Oral↗
PubMed2006

Bench to bedside: the quest for quality in experimental stroke research.

Over the past decades, great progress has been made in clinical as well as experimental stroke research. Disappointingly, however, hundreds of clinical trials testing neuroprotective agents have failed despite efficacy in experimental models. Recently, several systematic reviews have exposed a number of important deficits in the quality of preclinical stroke research. Many of the issues raised in these reviews are not specific to experimental stroke research, but apply to studies of animal models of disease in general. It is the aim of this article to review some quality-related sources of bias with a particular focus on experimental stroke research. Weaknesses discussed include, among others, low statistical power and hence reproducibility, defects in statistical analysis, lack of blinding and randomization, lack of quality-control mechanisms, deficiencies in reporting, and negative publication bias. Although quantitative evidence for quality problems at present is restricted to preclinical stroke research, to spur discussion and in the hope that they will be exposed to meta-analysis in the near future, I have also included some quality-related sources of bias, which have not been systematically studied. Importantly, these may be also relevant to mechanism-driven basic stroke research. I propose that by a number of rather simple measures reproducibility of experimental results, as well as the step from bench to bedside in stroke research may be made more successful. However, the ultimate proof for this has to await successful phase III stroke trials, which were built on basic research conforming to the criteria as put forward in this article.

Animals↗
PubMed1995

Concern, perceived risk and attitudes towards HIV/AIDS in Scottish prisons.

Four hundred and eighty male prisoners and 500 male staff from 7 Scottish prisons took part in a study assessing perception of risk and attitudes towards HIV/AIDS. Prison staff were found to perceive prison as a higher-risk environment for HIV/AIDS than outside prison, whereas prisoners perceived the opposite. Prisoners perceived less personal risk of HIV/AIDS inside prison than staff. Staff and prisoner concern towards HIV/AIDS was greater than perceived risk of HIV/AIDS, and concern was found to be associated with a number of demographic variables, whereas perceived risk was less influenced by such variables. These findings suggest that the process of risk perception may operate on more than one level. Factor analysis of attitudes towards HIV/AIDS produced four factors for both staff and prisoners: 'Interacting with people with HIV/AIDS'; 'Social control of HIV/AIDS'; 'HIV/AIDS prevention for high-risk groups'; and 'Response to HIV/AIDS high-risk behaviour'. For both staff and prisoners, greater concern and perceived risk towards HIV/AIDS was associated with a lower tolerance for interacting with people with HIV/AIDS and more support for strict social control measures against people with HIV/AIDS.

Adult↗
PubMed1999

Estimating linkage disequilibrium between a polymorphic marker locus and a trait locus in natural populations.

Positional cloning of gene(s) underlying a complex trait requires a high-resolution linkage map between the trait locus and genetic marker loci. Recent research has shown that this may be achieved through appropriately modeling and screening linkage disequilibrium between the candidate marker locus and the major trait locus. A quantitative genetics model was developed in the present study to estimate the coefficient of linkage disequilibrium between a polymorphic genetic marker locus and a locus underlying a quantitative trait as well as the relevant genetic parameters using the sample from randomly mating populations. Asymptotic covariances of the maximum-likelihood estimates of the parameters were formulated. Convergence of the EM-based statistical algorithm for calculating the maximum-likelihood estimates was confirmed and its utility to analyze practical data was exploited by use of extensive Monte-Carlo simulations. Appropriateness of calculating the asymptotic covariance matrix in the present model was investigated for three different approaches. Numerical analyses based on simulation data indicated that accurate estimation of the genetic parameters may be achieved if a sample size of 500 is used and if segregation at the trait locus explains not less than a quarter of phenotypic variation of the trait, but the study reveals difficulties in predicting the asymptotic variances of these maximum-likelihood estimates. A comparison was made between the statistical powers of the maximum-likelihood analysis and the previously proposed regression analysis for detecting the disequilibrium.

Genetic Markers↗
PubMed1986

Outcome of cardiopulmonary resuscitation in the neonatal intensive care unit.

This retrospective review of 83 infants undergoing CPR in the neonatal ICU of a teaching hospital found that 12 (14%) patients were discharged from the hospital and seven (8%) were alive at least 1 yr after discharge. Of these seven, five appeared neurologically intact. From another perspective, 41% (12/29) of the patients who survived at least 24 h after CPR were discharged alive. Factors significantly (p less than .05) associated with poor outcome included sepsis, oliguria 24 h before and/or after arrest, prematurity, and intraventricular hemorrhage. Variables significantly (p less than .05) related to good outcome were the need for intubation during resuscitation and the diagnosis of major congenital anomalies. Intraventricular hemorrhage was the single most powerful variable in the regression analysis. Outcome statistics from this study were strikingly similar to currently available adult data.

Cerebral Hemorrhage↗
PubMed2005

Loss of interstitial cells of Cajal and gap junction protein connexin 43 at the vesicoureteral junction in children with vesicoureteral reflux.

PURPOSE: Symmetrical muscular contractions and unidirectional peristalsis are prerequisites for competent valve function at the ureterovesical junction. Interstitial cells of Cajal (ICCs) are pacemaker cells that create and coordinate peristaltic motility. We investigated ureteral endings immunohistochemically to elucidate the presence of c-kit positive ICCs as well as the occurrence of gap junction protein connexin 43 in children with vesicoureteral reflux (VUR) to identify a possible pathogenic factor of an insufficient antireflux mechanism. MATERIALS AND METHODS: Distal ureteral specimens were obtained from 27 children undergoing antireflux surgery. Routine histological paraffin embedded sections were immunostained detecting the c-kit proto-oncogene to study the presence of ICCs as well as connexin 43 positive cells to determine the gap junction density within the ureteral wall. Age matched nonrefluxing ureteral endings served as controls. All investigations were done using high power field magnification for semiquantitative analysis and statistically analyzed. RESULTS: ICCs were present in refluxing and nonrefluxing ureteral endings. Healthy individuals displayed significantly more ICCs than children with VUR. Connexin 43 immunoreactivity was significantly decreased in all refluxing ureteral specimens, whereas it was homogeneously distributed in normal controls. CONCLUSIONS: C-kit positive ICCs are found at the ureterovesical junction. Refluxing ureteral endings significantly lack these pacemaker cells, implying a malfunctioning valve mechanism permitting VUR. A substantial decrease in gap junctions in this region adversely affects intercellular signaling, aggravating coordinated peristalsis, which is essential for a competent anti-reflux mechanism.

Biomarkers↗
PubMed2005

Investigation of protein refolding using a fractional factorial screen: a study of reagent effects and interactions.

A recurring obstacle for structural genomics is the expression of insoluble, aggregated proteins. In these cases, the use of alternative salvage strategies, like in vitro refolding, is hindered by the lack of a universal refolding method. To overcome this obstacle, fractional factorial screens have been introduced as a systematic and rapid method to identify refolding conditions. However, methodical analyses of the effectiveness of refolding reagents on large sets of proteins remain limited. In this study, we address this void by designing a fractional factorial screen to rapidly explore the effect of 14 different reagents on the refolding of 33 structurally and functionally diverse proteins. The refolding data was analyzed using statistical methods to determine the effect of each refolding additive. The screen has been miniaturized for automation resulting in reduced protein requirements and increased throughput. Our results show that the choice of pH and reducing agent had the largest impact on protein refolding. Bis-mercaptoacetamide cyclohexane (BMC) and tris (2-carboxyethylphosphine) (TCEP) were superior reductants when compared to others in the screen. BMC was particularly effective in refolding disulfide-containing proteins, while TCEP was better for nondisulfide-containing proteins. From the screen, we successfully identified a positive synergistic interaction between nondetergent sulfobetaine 201 (NDSB 201) and BMC on Cdc25A refolding. The soluble protein resulting from this interaction crystallized and yielded a 2.2 Angstroms structure. Our method, which combines a fractional factorial screen with statistical analysis of the data, provides a powerful approach for the identification of optimal refolding reagents in a general refolding screen.

Crystallography, X-Ray↗
PubMed2005

Growth on stimulant medication; clarifying the confusion: a review.

AIMS: To get an overview of the studies of growth in height in children with attention deficit hyperactivity disorder (ADHD) treated with stimulant medication, to establish the consistencies and to try to resolve the discrepancies. METHODS: Twenty nine studies were reviewed following a Medline search: 22 related to children, six to late adolescents or adults, and one to children and adults. RESULTS: Children: Eleven studies gave results consistent with height attenuation on stimulant medication: eight were longitudinal, one was cross-sectional, and two showed growth rebound on ceasing medication. Studies with negative findings were inadequately powered (n = 3), lacked controls or statistical analysis (n = 3), measured height velocity without reference to treatment duration (n = 2), or used inappropriate growth parameters (n = 1), controls (n = 1), or normative data (n = 1). Late adolescents/adults treated with stimulant medication in childhood: Two studies associated childhood gastrointestinal side effects with attenuated late adolescent or adult height; all six cross-sectional studies had negative findings. The methodologies varied widely but there was some consistency in the degree of attenuation shown in studies with positive findings. The most sensitive methods analysed the changes in z-scores (standard deviation scores) or calculated the height deficits from paired measurements taken before and after an initial period of treatment with stimulant medication. The height deficit amounted to approximately 1 cm/year during the first 1-3 years of treatment. CONCLUSIONS: Further research is needed into the causal mechanisms, the rate of physical maturation, and the long term implications for final stature.

Attention Deficit Disorder with Hyperactivity↗