bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards Safer Treatments for Benign Anorectal Disease: The Pharmacological Manipulation of the Internal Anal Sphincter
Authors: Jones Oliver M
Published: August 2007

INTRODUCTION

The internal anal sphincter (IAS) is an important structure that is responsible for the majority of resting tone of the sphincter complex. It has a central role in continence and damage to the muscle has serious implications. Injury is most frequently from obstetric trauma though iatrogenic injury from proctological surgery is also common. This review expands on how developments in understanding of the pharmacology of IAS might identify drug treatments as alternatives for proctological conditions such as anal fissure, avoiding the risk of sphincter injury. It also examines the role of pharmacology in treatment of those patients with established incontinence.

RESULTS

Much of the basic physiology and pharmacology of the IAS has been established through in vitro analysis, particularly in the superfusion organ bath. Further analysis has been undertaken using animal models such the pig. Clinical trials have established the efficacy of a number of agents for reducing IAS tone including glyceryl trinitrate and botulinum toxin. These drugs are probably safer, but less effective, than surgery for sphincter spasm, as is seen in anal fissure, though surgery alone or in combination with drug treatment may be appropriate for some patients. In vitro analysis and small-scale clinical trials suggest that phenylephrine and methoxamine may have a role in treating patients with incontinence primarily attributable to inadequate IAS function.

CONCLUSIONS

The pharmacology of IAS has been extensively studied in the laboratory, both in vitro and in animal models. In a short time, this laboratory work has been applied to clinical problems after testing in clinical trials. It is likely, however, that the best drugs and the optimal targets for manipulation have not yet been identified.
The Integrative Physiology of the Bladder
Authors: Drake Marcus John
Published: August 2007

Normal bladder function is complex, resulting from the co-operative interaction of numerous regulatory cell types, of which the interstitial cells and the peripheral neurones are particularly interesting. Collectively, these comprise the myovesical plexus, which appears to confer structural and functional characteristics on the bladder loosely akin to those of the gut. These include functional modularity, which gives rise to the potential for localised and propagating peristalsis-like movements in the bladder wall according to the prevailing physiological conditions. Localised modular activity during filling may contribute to normal generation of sensation and exaggerated modular activity may give rise to urinary urgency. Enhanced co-ordination of modular activity occurs in various models of detrusor overactivity; it leads to surges of contraction over a large part of the bladder wall, generating phasic changes in intravesical pressure. During voiding, the myovesical plexus sustains detrusor contraction at the behest of the brainstem, monitoring state of bladder fullness as it does so, as a guide to the required duration for which it has to keep up the effort. Accordingly, the bladder wall itself may house structures which render the bladder the effector level in a hierarchy of lower urinary tract regulation. Dysfunction in these vital regulatory structures is an underestimated factor in the pathophysiology of clinical bladder problems.
The ABCs of analogical abilities: Evidence for formal analogical reasoning abilities in 24‐month‐olds
Authors: Singer‐Freeman Karen E. , Bauer Patricia J.
Published: August 2007

Solving formal analogy problems requires the identification of an initial term and the transformation that occurs between the initial two terms as well as the determination of the final term. Experiment 1 tested 24‐month‐olds' ability to determine final terms when they were shown the initial term and told the transformation that was to occur. Children selected their responses from an array of two principled distracters. The children were able to determine the correct final term when they were given information about the initial term and transformation. Experiment 2 tested 24‐month‐olds' ability to solve final‐term problems, partial analogies, and complete analogies. The children solved all the three types of problems.
Parenting empathy: Associations with dimensions of parent and child psychopathology
Authors: Psychogiou Lamprini , Daley Dave , Thompson Margaret J. , Sonuga‐Barke Edmund J. S.
Published: August 2007

Background. Parenting empathy, the understanding by parents, and the sharing in their child's perspective, represents an important element of competent parenting. The present study tested the hypotheses that maternal empathy might be lower where mothers or their children display symptoms of psychopathology.

Method. Mothers (N = 268) of school‐aged children completed questionnaires on child‐directed empathy and egoistic personal distress and their own and their child's symptoms of psychopathology across a number of broadly defined domains.

Results. Child conduct problems were associated with decreased child‐directed empathy and increased maternal egoistic distress. Maternal aggressive characteristics and maternal ADHD symptoms were each associated with increased egoistic personal distress.

Conclusion. The findings indicate that symptoms of psychopathology in children and adults are associated with deficits in empathy and increased maternal egoistic personal distress. The implications of the findings for responsive parenting and child social behaviour are discussed.
Radiation Embrittlement of Cr–Ni–Mo and Cr–Mo RPV Steels
Authors: Nikolaev Yu. A.
Published: August 2007

Radiation embrittlement kinetics of Cr–Mo and Cr–Ni–Mo steels, used for manufacturing VVER-440 and VVER-1000 RPV steels, respectively, are under consideration. Radiation embrittlement of VVER-440 and VVER-1000 RPV steels exposed to irradiation for 17–22 years is analyzed. Extremely high levels of thermal aging of VVER-1000 RPV steels at 320°C is pointed out. The neutron flux effect problem and the problem of accelerated radiation embrittlement of welds with high nickel contents are emphasized. The effect of phosphorus, copper, silicon, manganese, and nickel contents on radiation embrittlement of VVER-440 and VVER-1000 RPV steels is studied using the Russian surveillance database and representative results of research programs. The trend curves for VVER-440 and VVER-1000 RPV steels are proposed. The mechanisms of radiation embrittlement of Cr–Ni–Mo and Cr–Mo RPV steels are supposed.
Evaluation of a standardized short-time calcium suppression test in healthy subjects: interest for the diagnosis of primary hyperparathyroidism
Authors: Titon Isabelle , Cailleux-Bounacer Anne , Basuyau Jean Pierre , Lefebvre Hervé , Savouré Adeline , Kuhn Jean Marc
Published: August 2007

Objective: The diagnosis of primary hyperparathyroidism (PHP) can be difficult in patients with normal plasma calcium or parathyroid hormone (PTH) levels. We perfected a standardized short-time i.v. calcium loading test in healthy controls (HC) and compared the results with those of patients with PHP.

Methods: Sixteen HC received 0.33 mmol/kg calcium gluconate intravenously for 3 h. Plasma calcium and serum PTH levels (assayed with immunoluminescent sandwich methods) were measured before, at the end of the infusion and 3 h later. Results were compared with those of 16 PHP patients.

Results: In HC, basal total plasma calcium (mean ± s.e.m.) was 2.33 ± 0.02 mmol/l. At the end of calcium loading, calcemia reached 3.21 ± 0.05 mmol/l and decreased to 2.94 ± 0.08 mmol/l 3 h later. In PHP patients, basal plasma calcium was 2.54 ± 0.03 mmol/l and reached similar values as in HC during the testing. Basal serum PTH levels were 32.5 ± 3.3 ng/l in HC and 86.9 ± 6.3 ng/l in PHP. At the end of calcium loading, they dropped to 8.8 ± 0.6 ng/l (HC) and to 31.4 ± 4.2 ng/l (PHP). Three hours later, they were 11.6 ± 0.8 and 39.8 ± 4.0 ng/l respectively. There was a cut-off in serum PTH values between the two groups at the end of calcium loading and 3 h later.

Conclusion: The standardized short-time PTH suppression test appears reliable to differentiate healthy subjects from PHP whose serum PTH levels remain >14 and >23 ng/ml respectively at the end of loading and 3 h later. This well-tolerated and easily performed test could be used for the diagnosis of PHP in patients suspected for the disease despite the normality of some basal biological markers.
Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism
Authors: Tauchmanovà Libuse , Pivonello Rosario , De Martino Maria Cristina , Rusciano Andrea , De Leo Monica , Ruosi Carlo , Mainolfi Ciro , Lombardi Gaetano , Salvatore Marco , Colao Annamaria
Published: August 2007

Objective: Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Nevertheless, limited data are available on bone status in patients with endogenous cortisol excess. This study is aimed at investigating the role of sex steroids and severity of hypercortisolism on bone mineral density (BMD) and prevalence of vertebral fractures in female patients.

Design: Cross-sectional, case–control study.

Patients: Seventy-one consecutive women were enrolled: 36 with overt hypercortisolism (26 with ACTH-secreting pituitary adenoma and 10 with cortisol-secreting adrenal tumor) and 35 with subclinical hypercortisolism due to adrenal incidentalomas. They were compared with 71 matched controls.

Methods: At diagnosis, we measured serum cortisol, FSH, LH, estradiol, testosterone, androstenedione and DHEAS, and urinary cortisol excretion. BMD was determined by dual energy X-ray absorptiometry at the lumbar spine and femoral neck. Vertebral fractures were investigated by a semiquantitative scoring method.

Results: Between women with overt and subclinical hypercortisolism BMD values and prevalence of any vertebral (69 vs 57%, P = 0.56), clinical (28 vs 11.4%, P = 0.22), and multiple vertebral fractures (36 vs 31%, P = 0.92) did not differ. Among patients with subclinical hypercortisolism, amenorrhoic women had a lower BMD (P = 0.035) and more frequent vertebral fractures (80 vs 40%; P = 0.043) when compared with the eumenorrhoic ones. Among women with overt hypercortisolism, there was no difference in lumbar BMD (P = 0.37) and prevalence of fractures (81 vs 60%; P = 0.26) between those amenorrhoic and eumenorrhoic. By logistic regression analysis, lumbar spine BMD values and cortisol-to-DHEAS ratio were the best predictors of vertebral fractures (P < 0.01).

Conclusions: Vertebral fractures are very common in women with endogenous cortisol excess, regardless of its severity. The deleterious effects of hypercortisolism on the spine may be partly counterbalanced by DHEAS increase at any degree of cortisol excess, and by preserved menstrual cycles in women with subclinical but not in those with overt hypercortisolism.
Maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) levels in post-term pregnancy: effect of prostaglandin administration
Authors: Florio P , Lowry P J , Benedetto C , Galleri L , Torricelli M , Giovannelli A , Battista R , Reis F M , Petraglia F
Published: August 2007

Objective: Placental corticotropin-releasing factor (CRF) affects myometrial contractility and the secretion of several uterotonins such as prostaglandins (PGs); however, the activity of CRF is counteracted by CRF-binding protein (CRF-BP). At term and pre-term labor, CRF levels in maternal plasma are highest whereas those of CRF-BP are falling, and the cause of this fall is unknown. Thus, in this study, we investigated the effect of PG administration for labor induction on maternal plasma CRF and CRF-BP concentrations.

Design: Maternal plasma CRF and CRF-BP levels were assayed before and after (2 h later) induction of labor by intracervical administration of prostaglandin E2 (PGE2), and at delivery in a group of healthy post-term pregnancies (n=18). Controls were women at term out of labor (n=22), who subsequently progressed to deliver a healthy singleton baby.

Methods: CRF was measured by two-site immunoradiometric assay, and CRF-BP was assayed by radioimmunoassay.

Results: Maternal plasma CRF levels were significantly (P<0.0001) lower and CRF-BP significantly (P<0.0005) higher in post-term than in term pregnancies. With respect to induction of labor, 2 mg PGE2 were sufficient to increase maternal plasma CRF levels at delivery (P<0.005). While 0.5 mg PGE2 significantly decreased maternal plasma CRF-BP levels at delivery (P<0.001), 2.0 mg PGE2 significantly reduced CRF-BP concentrations both after 2 h (P<0.05) and at delivery (P<0.0001).

Conclusions: In the light of the well-known stimulation of prostaglandin release by CRF, these data suggest a positive feedback effect of PGE2 on maternal CRF release during induced labor.
Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys
Authors: Wiegand Susanna , Richardt Anna , Remer Thomas , Wudy Stefan A , Tomlinson Jeremy W , Hughes Beverly , Grüters Annette , Stewart Paul M , Strasburger Christian J , Quinkler Marcus
Published: August 2007

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing’s syndrome. The 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1) regenerates active cortisol from inactive cortisone. Altered 11β-HSD1 may cause tissue-specific Cushing’s syndrome with central obesity and impaired glucose homeostasis.

Design, patients, and methods: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12–18 years, Tanner stages 2–5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic–mass spectrometric (GC–MS) analysis.

Results: 11β-HSD1 activity (urinary tetrahydrocortisol (THF) + 5α-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11β-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11β-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11β-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index.

Conclusions: In conclusion, our findings strongly suggest that 11β-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus–pituitary–adrenal axis.
Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and genotype–phenotype correlation
Authors: Vierimaa O , Ebeling T M L , Kytölä S , Bloigu R , Eloranta E , Salmi J , Korpi-Hyövälti E , Niskanen L , Orvola A , Elovaara E , Gynther A , Sane T , Välimäki M , Ignatius J , Leisti J , Salmela P I
Published: August 2007

Objective: The existence of genotype–phenotype correlation in multiple endocrine neoplasia type 1 (MEN1) is controversial. Two founder mutations of the MEN1 gene in Northern Finland gave us an opportunity to compare clinical features among heterozygotes of different mutations.

Design and methods: Study cohort included 82 MEN1 heterozygotes who were tested for MEN1 during the years 1982–2001. Medical records were reviewed for manifestations of MEN1, other tumours and cause of death by the end of August 2003. Logistic regression analysis was used in evaluating the impact of age, gender and mutational status of affected heterozygotes on the likelihood of developing manifestations of MEN1.

Results: Founder mutations 1466del12 and 1657insC were found in 39 and 29 individuals, and D418N, G156R and R527X mutations in 9, 3 and 2 individuals respectively. Except for pituitary adenoma and nonfunctional pancreatic tumour (NFPT), age was a risk factor for all the disease manifestations. For NFPT, frameshift/nonsense mutations (1657insC, R527X) gave an odds ratio (OR) of 3.26 (95% confidence intervals (CI), 1.27–8.33; P = 0.014) compared with in-frame/missense mutations (1466del12, D418N, G156R); including the founder mutation carriers (n = 68) only, the 1657insC mutation gave an OR of 3.56 (CI, 1.29–9.83; P = 0.015). For gastrinoma, in-frame/missense mutations predicted the risk with an OR of 6.77 (CI, 1.31–35.0; P = 0.022), and in the founder mutations group the 1466del12 mutation gave an OR of 15.09 (CI, 1.73–131.9, P = 0.014).

Conclusions: In this study population, NFPT was more common in the frameshift/nonsense or 1657insC mutation carriers, whereas gastrinoma was more common in the in-frame/missense or 1466del12 mutation carriers.
Prevalence of testicular adrenal rest tumours in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Authors: Claahsen-van der Grinten Hedi L , Sweep Fred C G J , Blickman Johan G , Hermus Ad R M M , Otten Barto J
Published: August 2007

Objective: Testicular adrenal rest tumours (TART) are a well-known complication in adult male patients with congenital adrenal hyperplasia (CAH), with a reported prevalence of up to 94%. In adulthood, the tumours are associated with gonadal dysfunction most probably due to longstanding obstruction of the seminiferous tubules. The aim of our study was to determine the presence of TART and their influence on gonadal function in childhood.

Design: Retrospective study.

Patients and methods: Scrotal ultrasound was performed in 34 children with CAH due to 21-hydroxylase deficiency who were between 2 and 18 years old. FSH, LH, testosterone and inhibin B concentrations were measured in serum of 27 patients.

Results: TART were detected by ultrasound in 8 out of 34 (24%) children. In two of them, bilateral tumours were found. All lesions were located in the rete testis. Seven patients had the salt-wasting type of CAH; one patient had the simple virilising type of CAH. Mean tumour size was 4.1 mm (range 2–8 mm). In none of the patients were the tumours palpable. Two children with TART were between 5 and 10 years old, the other six children were above 10 years old. In all children with TART, LH, FSH, testosterone and inhibin B levels were similar to the patients without TART.

Conclusion: TART can be found in CAH children before the age of 10 years. The absence of gonadal dysfunction in our group of children suggests that gonadal dysfunction as frequently reported in adult CAH patients with TART develops after childhood.
Cyclic Cushing’s syndrome: a clinical challenge
Authors: Meinardi J R , Wolffenbuttel B H R , Dullaart R P F
Published: August 2007

Cyclic Cushing’s syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with intercyclic phases ranging from days to years. To formally diagnose cyclic CS, three peaks and two troughs of cortisol production should be demonstrated. Our review of 65 reported cases demonstrates that cyclic CS originates in 54% of cases from a pituitary corticotroph adenoma, in 26% from an ectopic ACTH-producing tumour and in about 11% from an adrenal tumour, the remainder being unclassified. The pathophysiology of cyclic CS is largely unknown. The majority of patients with cyclic CS have clinical signs of CS, which can be either fluctuating or permanent. In a minority of patients, clinical signs of CS are absent. The fluctuating clinical picture and discrepant biochemical findings make cyclic CS extremely hard to diagnose. Clinicians should therefore be aware of this clinical entity and actively search for it in all patients with suspected CS but normal biochemistry or vice versa. Frequent measurements of urinary cortisol or salivary cortisol levels are a reliable and convenient screening tool for suspected cyclic CS. Cortisol stimulation or suppression tests may give spurious results owing to spontaneous falls or rises in serum cortisol at the time of testing. When cyclic CS is biochemically confirmed, further imaging and laboratory studies are guided by the presence or absence of ACTH dependency. In cases of suspected ectopic ACTH production, specific biochemical testing for carcinoids or neuroendocrine tumours is required, including measurements of serotonin in platelets and/or urine, chromogranin A and calcitonin.
High phenotypic intrafamilial variability in patients with Pendred syndrome and a novel duplication in the SLC26A4 gene: clinical characterization and functional studies of the mutated SLC26A4 protein
Authors: Fugazzola Laura , Cirello Valentina , Dossena Silvia , Rodighiero Simona , Muzza Marina , Castorina Pierangela , Lalatta Faustina , Ambrosetti Umberto , Beck-Peccoz Paolo , Bottà Guido , Paulmichl Markus
Published: August 2007

Objective: Pendred syndrome (PS) is characterized by the association of sensorineural hearing loss (SNHL) and a partial iodide organification defect at the thyroid level. It is caused by mutations in the SLC26A4 gene. The encoded transmembrane protein, called pendrin, has been found to be able to transport chloride and other anions.

Design: The aim of the present study was to characterize a family with PS, which shows a strong intrafamilial phenotypic variability, including kidney atrophy in one member. The age of disease-onset was significantly different in all three affected siblings, ranging from 2 to 21 years for thyroid alterations and from 1.5 to 11 years for SNHL.

Methods: Clinical and genetic studies were carried out in affected siblings. The functional activity of the novel duplication found was studied by a fluorimetric method in a human renal cell line (HEK293 Phoenix) in which the protein was overexpressed.

Results: All three siblings were found to be compound heterozygotes for the missense mutation (1226G>A, R409H) and for a novel 11 bp duplication (1561_1571CTTGGAATGGC, S523fsX548). The latter mutation creates a frame shift leading to the loss of the entire carboxy-terminus domain. Functional studies of this mutant demonstrated impaired transport of chloride and iodide when expressed in HEK 293 Phoenix cells, when compared with wild type pendrin.

Conclusions: A novel 11 bp duplication was found in a family with Pendred syndrome, showing a high intrafamilial phenotypic variability. An impaired transmembrane anionic transport of the mutated SLC26A4 protein was demonstrated in functional studies using a heterologous cell system.
Genetic variants in the leukemia-associated Rho guanine nucleotide exchange factor (ARHGEF12) gene are not associated with T2DM and related parameters in Caucasians (KORA study)
Authors: Holzapfel C , Klopp N , Grallert H , Huth C , Gieger C , Meisinger C , Strassburger K , Giani G , Wichmann H E , Laumen H , Hauner H , Herder C , Rathmann W , Illig T
Published: August 2007

Objective: The aim of our study was to determine the variant pattern of the leukemia-associated Rho guanine nucleotide exchange factor (LARG, or ARHGEF12) gene and investigate whether LARG variants are associated with diabetes mellitus type 2 (T2DM), the metabolic syndrome (MetS), or related parameters such as insulin sensitivity in German Caucasians.

Design: We analyzed single nucleotide polymorphisms (SNPs) in the LARG gene in the 55–74-year-old individuals of the population-based German Caucasian Cooperative Health Research in the region of Augsberg (KORA) survey 4 (S4).

Methods: Sequencing of Tyr1306Cys, which was of functional relevance in Pima Indians, in 48 randomly selected individuals and genotyping of 11 additional LARG SNPs in 1653 subjects were performed. Four linkage disequilibrium (LD) blocks (r2≥0.8) were established and each block was statistically analyzed for association with metabolic traits. The association with T2DM and the MetS was analyzed by logistic regression in 1462 subjects, and HOMA-IR (homeostasis model assessment of insulin resistance) as a measure of insulin sensitivity was analyzed by the Kruskal–Wallis test in 1346 fasting subjects.

Results: The polymorphism Tyr1306Cys, which was significantly associated with insulin sensitivity in Pima Indians, was not found in the KORA S4 population. Statistical analysis yielded no significant associations (P>0.05) between the analyzed LARG variants and T2DM, the MetS, or related parameters such as insulin sensitivity.

Conclusions: Caucasian individuals and Pima Indians differ in their genetic variance pattern in the LARG gene region. There is no evidence in the Caucasian KORA study that variants of the LARG gene confer susceptibility for T2DM, insulin sensitivity, or the MetS.
Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients
Authors: Anan Futoshi , Masaki Takayuki , Umeno Yoshikazu , Iwao Tetsu , Yonemochi Hidetoshi , Eshima Nobuoki , Saikawa Tetsunori , Yoshimatsu Hironobu
Published: August 2007

Background: The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients.

Material and methods: The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3–1.0 mg/dl, age: 57±5 years, mean±s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57±6 years). Brachial–ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis.

Results: The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index.

Conclusions: Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.
Healthy Steps for Young Children Program in Pediatric Residency Training: Impact on Primary Care Outcomes
Authors: Niederman Leo G. , Schwartz Alan , Connell Karen J. , Silverman Kathleen
Published: August 2007

OBJECTIVE. Incorporating Healthy Steps for Young Children into pediatric practice has been shown to have positive effects for children and families. Although this model of care has also been integrated into several pediatric and family medicine training programs, published reports to date have focused only on residents’ perceptions of their interactions with the model of care. In this study, we report the impact on primary care outcomes after integrating Healthy Steps for Young Children into residency training.

METHODS. Continuity of care, longitudinal care in the practice, quality of primary care services, and rates of behavioral, developmental, and psychosocial diagnoses were measured for 3 cohorts: (1) Healthy Steps–enrolled children, (2) non–Healthy Steps–enrolled children who were followed at the same site of care, and (3) non–Healthy Steps–enrolled children who were receiving primary care at a similar residency training site within the same training program. All data were extracted from patient charts at the 2 practice sites.

RESULTS. Continuity of care was significantly better for Healthy Steps–enrolled children compared with non–Healthy Steps–enrolled children at the Healthy Steps site for both total visits and health maintenance visits. Longitudinal care and quality of primary care services did not differ within or between sites. The rates of documentation of behavioral, developmental, or psychosocial diagnoses did not differ between Healthy Steps–enrolled and non–Healthy Steps–enrolled children at the Healthy Steps for Young Children site but were significantly different between the Healthy Steps and the non–Healthy Steps for Young Children sites; the effect was driven wholly by differences in psychosocial diagnoses.

CONCLUSIONS. Multiple indices that measure health service outcomes suggest benefits of incorporating Healthy Steps for Young Children into pediatric residency training. Most important, continuity of care in residents’ practices significantly improved, as did the residents’ documentation of psychosocial issues in children.
Healthy Steps for Young Children: Sustained Results at 5.5 Years
Authors: Minkovitz Cynthia S. , Strobino Donna , Mistry Kamila B. , Scharfstein Daniel O. , Grason Holly , Hou William , Ialongo Nicholas , Guyer Bernard
Published: August 2007

OBJECTIVE. We sought to determine whether Healthy Steps for Young Children has sustained treatment effects at 5.5 years, given early findings demonstrating enhanced quality of care and improvements in selected parenting practices.

METHODS. Healthy Steps was a clinical trial that incorporated developmental specialists and enhanced developmental services into pediatric care in the first 3 years of life. A total of 5565 children were enrolled at birth and followed through 5.5 years. Healthy Steps was evaluated at 6 randomization and 9 quasi-experimental sites. Computer-assisted telephone interviews were conducted with mothers when Healthy Steps children were 5.5 years of age. Outcomes included experiences seeking care, parent response to child misbehavior, perception of child's behavior, and parenting practices to promote development and safety. Logistic regression was used to estimate overall effects of Healthy Steps, adjusting for site and baseline demographic characteristics.

RESULTS. A total of 3165 (56.9%) families responded to interviews (usual care: n = 1441; Healthy Steps: n = 1724). Families that had received Healthy Steps services were more satisfied with care (agreed that pediatrician/nurse practitioner provided support, 82.0% vs 79.0%; odds ratio: 1.25 [95% confidence interval: 1.02–1.53]) and more likely to receive needed anticipatory guidance (54.9% vs 49.2%; odds ratio: 1.33 [95% confidence interval: 1.13–1.57]) (all P < .05). They also had increased odds of remaining at the original practice (65.1% vs 61.4%; odds ratio: 1.19 [95% confidence interval: 1.01–1.39]). Healthy Steps families reported reduced odds of using severe discipline (slap in face/spank with object, 10.1% vs 14.1%; odds ratio: 0.68 [95% confidence interval: 0.54–0.86]) and increased odds of often/almost always negotiating with their child (59.8% vs 56.3%; odds ratio: 1.20 [95% confidence interval: 1.03–1.39]). They had greater odds of reporting a clinical or borderline concern regarding their child's behavior (18.1% vs 14.8%; odds ratio: 1.35 [95% confidence interval: 1.10–1.64]) and their child reading books (59.4% vs 53.6%; odds ratio: 1.16 [95% confidence interval: 1.00–1.35]). There were no effects on safety practices.

CONCLUSIONS. Sustained treatment effects, albeit modest, are consistent with early findings. Universal, practice-based interventions can enhance quality of care for families with young children and can improve selected parenting practices beyond the duration of the intervention.
Perceived Milk Intolerance Is Related to Bone Mineral Content in 10- to 13-Year-Old Female Adolescents
Authors: Matlik Leann , Savaiano Dennis , McCabe George , VanLoan Marta , Blue Carolyn L. , Boushey Carol J.
Published: August 2007

OBJECTIVE. The purpose of this study was to determine associations among lactose maldigestion status, perceived milk intolerance, dietary calcium intake, and bone mineral content in early adolescent girls.

METHODS. Subjects were 291 girls who participated in a substudy of the multiple-site project Adequate Calcium Today. Lactose maldigestion status was determined with hydrogen breath testing, and questionnaires were used to assess perceived milk intolerance. Dietary calcium intake was estimated from a semiquantitative food frequency questionnaire. Anthropometric and dual-energy x-ray absorptiometric measurements (total body, spine L2–L4, total hip, and hip femoral neck) were standardized across sites.

RESULTS. Of the 230 girls who completed breath hydrogen testing, 65 were Asian, 76 were Hispanic, and 89 were non-Hispanic white. A total of 100 girls experienced increases in breath hydrogen levels of >20 ppm and were classified as lactose maldigesters. Of the 246 participants who completed useable perceived milk intolerance questionnaires, 47 considered themselves to be milk intolerant. Of the 47 girls self-reporting perceived milk intolerance, 40 completed breath hydrogen testing and 22 were not maldigesters. Girls with perceived milk intolerance consumed an average of 212 mg of total food calcium per day less than girls without perceived milk intolerance. Spinal bone mineral content was significantly lower in the girls with perceived milk intolerance, compared with the girls without perceived milk intolerance. When girls with lactose maldigestion were compared with girls without lactose maldigestion, there were no significant differences in calcium intake or bone measures.

CONCLUSIONS. These results suggest that, starting as early as 10 years of age, self-imposed restriction of dairy foods because of perceived milk intolerance is associated with lower spinal bone mineral content values. The long-term influence of these behaviors may contribute to later risk for osteoporosis.
Practice-Based Care Coordination: A Medical Home Essential
Authors: McAllister Jeanne W. , Presler Elizabeth , Cooley W. Carl
Published: August 2007

Families who raise children and youth with special health care needs deserve a medical home. They expect a team approach to health care, with coordination across multiple services and settings. Children, youth, and families benefit from the organization of critical information into written care summaries and action plans. If primary care pediatricians, family physicians, and internists are to achieve optimal health care quality and improvement of existing health care delivery, care coordination will be an essential contributing process to their team approach. Several national health policy recommendations identify care coordination as a cross-cutting intervention to fill the gap between what exists and what is needed in health care today. A practice-based care-coordination model, including a definition and vision for care, a framework of structures and processes, and a position description with specific competencies, is needed. Improvement methodology provides an effective means for health care teams to implement and evaluate practice-based care coordination within their medical home. The improvement approach and model must be flexibly applied to have utility across diverse health care organizations. A medical home team approach, with fully developed practice-based care-coordination services, will enhance health and cost outcomes for children, youth, and families and heighten the professional satisfaction of those delivering health care.
Effect of Age and Sedative Agent on the Accuracy of Bispectral Index in Detecting Depth of Sedation in Children
Authors: Malviya Shobha , Voepel-Lewis Terri , Tait Alan R. , Watcha Mehernoor F. , Sadhasivam Senthilkumar , Friesen Robert H.
Published: August 2007

OBJECTIVE. This study evaluated age- and sedative agent–related differences in bispectral index across observed sedation levels in a large sample of children <18 years of age.

PATIENTS AND METHODS. With institutional review board approval and waiver of consent, data from 4 independently conducted studies were combined in a secondary analysis of 3373 observations from 248 children aged 1 month to 18 years. In these studies, bispectral index values of sedated children were recorded in a blinded fashion, and sedation depth was scored using the University of Michigan Sedation Scale (UMSS). Bispectral index was evaluated across UMSS scores for several age groups and during use of each sedative agent (with/without opioids).

RESULTS. There was a moderate inverse correlation between bispectral index and UMSS for all age groups. There were significant differences in bispectral index across UMSS and between each sedation level except UMSS 3 to 4 in all the age groups and UMSS 0 to 1 in infants. The mean bispectral index and the cutoff values on the receiver-operating-characteristic curve for mild, moderate, and deep sedation were significantly lower in infants ≤6 months compared with older children at each sedation level. Bispectral index was reasonably sensitive and specific in differentiating mild (UMSS 0–1) from deeper (UMSS 3–4) levels of sedation but poorly differentiated between moderate and deep levels of sedation in all age groups. There was a moderate correlation between bispectral index and UMSS during the use of chloral hydrate, pentobarbital, propofol, and midazolam but poor correlation during ketamine or opioid use. Bispectral index values were significantly lower during deep sedation with propofol and pentobarbital compared with midazolam and chloral hydrate.

CONCLUSIONS. Our findings suggest that, although bispectral index may differentiate light from deep sedation in most children, bispectral index must be interpreted cautiously in sedated children, with particular consideration given to patient age and use of sedative agents.
Severe Anaphylactic Reaction to Ibuprofen in a Child With Recurrent Urticaria
Authors: Kang Liew Woei , Kidon Mona Iancovici , Chin Chiang Wen , Hoon Lim Siok , Hwee Chan Yoke , Chong Ng Kee
Published: August 2007

An acute anaphylactic reaction after a conventional antipyretic dose of ibuprofen was diagnosed in a child with allergic rhinitis, recurrent idiopathic urticaria, and nonimmunologic cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs and acetaminophen. The patient reported several previous, mild (isolated cutaneous) hypersensitivity reactions after exposure to acetaminophen or ibuprofen. There was no evidence of an underlying inflammatory disease except as described above. Patients with chronic or recurrent idiopathic urticaria and those with atopic disease represent groups at increased risk of nonsteroidal antiinflammatory drug hypersensitivity. Mild hypersensitivity reactions to acetaminophen and/or ibuprofen may precede subsequent, more-severe adverse reactions. Risks and benefits of continued use of nonsteroidal antiinflammatory drugs in these children should be carefully considered.
The Mechanisms of Low Birth Weight in Infants of Mothers With Homozygous Sickle Cell Disease
Authors: Thame Minerva , Lewis Jillian , Trotman Helen , Hambleton Ian , Serjeant Graham
Published: August 2007

OBJECTIVE. A low mean birth weight is a constant finding in pregnancies of women with homozygous sickle cell disease. The factors responsible are largely unknown and have now been investigated in an 11-year retrospective analysis.

METHODS. Records for 126 pregnancies of mothers with homozygous sickle cell disease and 126 pregnancies of control women with an AA phenotype, matched according to age and date of delivery, were examined. Events during pregnancy and outcomes of pregnancy were recorded.

RESULTS. Pregnancy outcomes for mothers with homozygous sickle cell disease confirmed the lower birth weight, gestational age, and placental weight. A low birth weight in infants of mothers with homozygous sickle cell disease was strongly related to gestational age and placental weight and weakly related to reticulocyte counts and a history of preeclampsia in univariate analyses, but only gestational age and placental weight remained significant in multivariate analyses. No relationships were seen with maternal age, parity, anthropometric features, other hematologic features (hemoglobin levels, fetal hemoglobin levels, mean cell volume, and α-thalassemia), pregnancy-induced hypertension, or prepartum hospital admissions (expressed as number or total days). Compared with Jamaican standards, birth weight was affected more than head circumference or length in infants of mothers with homozygous sickle cell disease, indicating asymmetric growth retardation, which occurred for 27% of boys and 38% of girls (compared with 4% and 9%, respectively, among infants of control mothers).

CONCLUSIONS. A chronic condition such as homozygous sickle cell disease might have been expected to cause symmetric growth retardation throughout pregnancy. The finding of asymmetric retardation might indicate adverse factors emerging late in pregnancy and might have relevance for the poor pregnancy outcomes in such mothers.
Family Presence During Pediatric Trauma Team Activation: An Assessment of a Structured Program
Authors: O'Connell Karen J. , Farah Mirna M. , Spandorfer Philip , Zorc Joseph J.
Published: August 2007

OBJECTIVE. When a child presents to a trauma center with a serious injury, family members are often excluded from the initial trauma team evaluation. The objective of this study was to evaluate the outcomes of a structured program of family presence during pediatric trauma team activations by measuring (1) the need for termination of family presence, (2) times to completion of key parts of the trauma evaluation, and (3) the opinions of staff surveyed immediately after conclusion of family presence.

METHODS. This was a cross-sectional study that combined prospectively obtained data and surveys from trauma team evaluations in which family presence occurred, with retrospective chart review of all trauma activations during an 18-month study period. The study was conducted at a level 1 pediatric trauma center with a preestablished family presence program that assigns a staff member to screen family members for family presence, provide support, and record events. Times to completion of key components of the trauma evaluation were calculated and compared for cases with and without family presence. Cross-sectional surveys were performed immediately after each trauma team evaluation.

RESULTS. A total of 197 family members participated in family presence. There were no cases of interference with medical care by family members. Seven family members were asked to leave the trauma area by staff after initiation of family presence for various reasons. Times to completion of key components of the trauma evaluation did not differ significantly between enrolled patients with family presence and those without family presence. Surveys were completed for 136 cases, and the majority of providers reported that family presence either had no effect on or improved medical decision-making (97%), institution of patient care (94%), communication among providers (92%), and communication with family members (98%).

CONCLUSIONS. This prospective study suggests that there is an overall low prevalence of negative outcomes associated with family presence during pediatric trauma team evaluation after implementation of a structured family presence program. Excluding family members as a routine because of provider concerns about negative impact on clinical care does not seem to be indicated.
The Impact of Parents' Medication Beliefs on Asthma Management
Authors: Conn Kelly M. , Halterman Jill S. , Lynch Kathleen , Cabana Michael D.
Published: August 2007

BACKGROUND. Previous studies suggest a relationship between parental beliefs about asthma medications and medication adherence. It is not clear how parents' positive and negative feelings about medications interact to influence medication adherence.

OBJECTIVES. The objectives of this study were to describe parents' perceived need for and concerns about their child's asthma medications and to assess the weighted impact of these positive and negative beliefs on parent-reported adherence.

METHODS. We conducted a cross-sectional survey of parents of children with asthma in southeast Michigan; response rate was 71%. Children with reported use of a preventive asthma medication were included (n = 622). We used a validated Beliefs About Medications Questionnaire (2 subscales: necessity and concern) to assess parents' positive and negative attitudes about their child's medications. To measure how parents weigh these beliefs, we also calculated a necessity-concern differential score (difference between necessity and concern subscales). We used a 4-item parent-report scale to measure medication adherence.

RESULTS. The majority of children were nonminority. Overall, 72% of parents felt that their child's asthma medications were necessary, and 30% had strong concerns about the medications. For 77% of parents, necessity scores were higher than concern scores, and for 17%, concern exceeded necessity. Nonminority parents were more likely to have necessity scores exceed concern scores compared with minority parents (79% vs 68%). Mean adherence scores increased as the necessity-concern differential increased. In a multivariate mixed-model regression, a greater necessity-concern differential score and being nonminority predicted better adherence.

CONCLUSIONS. These findings confirm a relationship between medication beliefs and adherence among parents of children with asthma. A better understanding of parents' medication beliefs and their impact on adherence may help clinicians counsel effectively to promote adherence.
Defect Size Determines Survival in Infants With Congenital Diaphragmatic Hernia
Authors:   The Congenital Diaphragmatic Hernia Study Group
Published: August 2007

OBJECTIVES. Congenital diaphragmatic hernia is a significant cause of neonatal mortality. The objective of this study was to evaluate the clinical factors associated with death in infants with congenital diaphragmatic hernia by using a large multicenter data set.

METHODS. This was a prospective cohort study of all liveborn infants with congenital diaphragmatic hernia who were cared for at tertiary referral centers belonging to the Congenital Diaphragmatic Hernia Study Group between 1995 and 2004. Factors thought to influence death included birth weight, Apgar scores, size of defect, and associated anomalies. Survival to hospital discharge, duration of mechanical ventilation, and length of hospital stay were evaluated as end points.

RESULTS. A total of 51 centers in 8 countries contributed data on 3062 liveborn infants. The overall survival rate was 69%. Five hundred thirty-eight (18%) patients did not undergo an operation and died. The defect size was the most significant factor that affected outcome; infants with a near absence of the diaphragm had a survival rate of 57% compared with infants having a primary repair with a survival rate of 95%. Infants without agenesis but who required a patch for repair had a survival rate of 79% compared with primary repair.

CONCLUSIONS. The size of the diaphragmatic defect seems to be the major factor influencing outcome in infants with congenital diaphragmatic hernia. It is likely that the defect size is a surrogate marker for the degree of pulmonary hypoplasia. Future research efforts should be directed to accurately quantitate the degree of pulmonary hypoplasia or defect size antenatally. Experimental therapies can then be targeted to prospectively identify high-risk patients who are more likely to benefit.