Core trainee boot camp, a method for improving technical and non-technical skills of novice surgical trainees. A before and after study.

INTRODUCTION: The transition to surgical training can be a stressful time for trainees and is most evident during national handover periods where new graduates start and senior trainees rotate to new programmes. During this time, patient mortality can increase and Hospital efficiency reduces. This influence is compounded by the impact of working time directives. Intensive, simulation rich training programmes or "Boot Camps" have been postulated as a solution. This article highlights the development of a surgical boot camp for novice surgical trainees and the impact this can have on training. METHOD: A novel surgical boot camp was developed for all trainees within a surgical training region including nine acute NHS trusts. Participating cohort of trainees completed pre and post course questionnaires to assess technical and non-technical skills. RESULTS: 25 trainees attended and completed the pre and post boot camp questionnaire. Significant improvements were seen with technical skills (p = 0.0429), overall non-technical skills (p < 0.001) including leadership (p = 0.022), communication (p = 0.010), situational awareness (p = 0.022), patient handover (p = 0.003), ward round skills (p = 0.005) and outpatient skill (p = 0.002). Trainees reported significantly increased ability to assess and manage a critically unwell patient (p = 0.001) and a trauma patient (p = 0.001). 96% of trainees have utilised the skills they learnt on Boot Camp and all trainees would recommend it as an induction programme. CONCLUSION: Surgical Boot Camps offer a timely chance to develop technical and non-technical skills whilst enhancing a trainee's confidence and knowledge and reduce the patient safety impact of the handover period.

Lessons learned about prevalence and growth rates of abdominal aortic aneurysms from a 25-year ultrasound population screening programme.

BACKGROUND: This study aimed to assess how the prevalence and growth rates of small and medium abdominal aortic aneurysms (AAAs) (3·0-5·4 cm) have changed over time in men aged 65 years, and to evaluate long-term outcomes in men whose aortic diameter is 2·6-2·9 cm (subaneurysmal), and below the standard threshold for most surveillance programmes. METHODS: The Gloucestershire Aneurysm Screening Programme (GASP) started in 1990. Men aged 65 years with an aortic diameter of 2·6-5·4 cm, measured by ultrasonography using the inner to inner wall method, were included in surveillance. Aortic diameter growth rates were estimated separately for men who initially had a subaneurysmal aorta, and those who had a small or medium AAA, using mixed-effects models. RESULTS: Since 1990, 81 150 men had ultrasound screening for AAA (uptake 80·7 per cent), of whom 2795 had an aortic diameter of 2·6-5·4 cm. The prevalence of screen-detected AAA of 3·0 cm or larger decreased from 5·0 per cent in 1991 to 1·3 per cent in 2015. There was no evidence of a change in AAA growth rates during this time. Of men who initially had a subaneurysmal aorta, 57·6 (95 per cent c.i. 54·4 to 60·7) per cent were estimated to develop an AAA of 3·0 cm or larger within 5 years of the initial scan, and 28·0 (24·2 to 31·8) per cent to develop a large AAA (at least 5·5 cm) within 15 years. CONCLUSION: The prevalence of screen-detected small and medium AAAs has decreased over the past 25 years, but growth rates have remained similar. Men with a subaneurysmal aorta at age 65 years have a substantial risk of developing a large AAA by the age of 80 years.

Vitamin D supplementation trial in infancy: body composition effects at 3 years of age in a prospective follow-up study from Montréal.

BACKGROUND: The impact of vitamin D status on body composition is not well understood. OBJECTIVES: Evaluate how vitamin D supplementation in infancy affects body composition at 3 years of age. METHODS: Double-blind randomized trial of 132, 1-month-old healthy, breastfed infants randomly assigned to receive oral vitamin D3 supplements of 400, 800, 1200 or 1600 IU d-1 for 11 months. In the present analysis, 87 (66%) returned at 3 years of age. Body composition was measured using dual-energy x-ray absorptiometry and plasma 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography tandem mass spectrometry. RESULTS: Anthropometry, body composition, diet, activity and demographics were similar across dosage groups at 3 years. Mean 25(OH)D concentration from 1 month to 3 years was higher (P < 0.001) in the 1200 IU group than 800 and 400 IU groups. Children with 25(OH)D concentrations above 75 nmol L-1 had lower fat mass (~450 g; P = 0.049). In multiple linear regression, mean 25(OH)D was associated with lean mass percent (ß = 0.06; CI: 0.00, 0.12; P = 0.042), fat mass (ß = -11.29; CI: -22.06, -0.52; P = 0.048) and body fat percent (ß = -0.06; CI: -0.12, -0.01; P = 0.045). CONCLUSIONS: Higher vitamin D status from infancy through to 3 years of age associates with leaner body composition.

Vitamin D supplementation in breastfed infants from Montréal, Canada: 25-hydroxyvitamin D and bone health effects from a follow-up study at 3 years of age.

UNLABELLED: Whether infant vitamin D supplementation may have long-term bone benefits is unclear. In this study, breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years. This study provides important data to inform pediatric public health recommendations for vitamin D. INTRODUCTION: North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health. Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization. The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation, vitamin D status, and bone outcomes at 3 years of age. METHODS: This was a double-blind randomized trial of 132, 1-month-old healthy, breastfed infants from Montréal, Canada, between 2007 and 2010. In this longitudinal analysis, 87 infants (66 %) returned for follow-up at 3 years of age, between 2010 and 2013. At 1 month of age, participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400, 800, 1200, or 1600 IU/day until 12 months of age. Lumbar spine vertebrae 1-4 (LS) bone mineral density (BMD), LS and whole body bone mineral content (BMC), and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years. RESULTS: At follow-up, the treatment groups were similar in terms of diet, sun exposure, and demographics. There were no significant differences among the groups in LS or whole body BMC, BMD, or accretion. Although, 25(OH)D concentrations were not different among the groups, higher doses (1200 and 1600 IU/day) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day. CONCLUSIONS: This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age. Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up. Larger studies with more ethnically diverse groups are needed to confirm these results.

Outcome in Men with a Screen-detected Abdominal Aortic Aneurysm Who are not Fit for Intervention.

OBJECTIVE/BACKGROUND: Abdominal aortic aneurysm (AAA) screening in Gloucestershire has been ongoing for 25 years. The aim of this study was to review the outcome of a cohort of men with a large (> 5.4 cm) screen-detected AAA who did not have early intervention for their AAA. METHODS: A prospectively maintained database was interrogated for a 10-year interval from 2001 to 2011. Men who did not have their large AAA repaired within 3 months of the diagnosis were identified. The reasons for initial nonintervention and subsequent outcomes were identified from a combination of hospital case notes and general practitioner records. RESULTS: Of 334 men referred, 59 (median age 71 years, range 62-83 years) did not have intervention within 3 months (initial nonintervention rate 17.6%). The reasons included placed back on surveillance after assessment (n = 34); immediately discharged (n = 12); required further investigations (n = 5); died before complete assessment (n = 3); and incomplete follow-up (n = 5). Sixteen men had delayed AAA repair with no perioperative mortality. Overall mortality in the study was 14/34 (nine from ruptured AAA, the rest from medical conditions). Two further men survived repair of a ruptured AAA. The overall rate of ruptured AAA was 11/59 (18.6%). CONCLUSION: Information from studies such as these can be used to help plan treatment of men with a large AAA and to compare performance of vascular units.

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome.

UNLABELLED: Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. INTRODUCTION: Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. METHODS: VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. RESULTS: Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017). CONCLUSIONS: The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

The development of bone mineral lateralization in the arms.

UNLABELLED: Bone mineral content (BMC) is known to be greater in the dominant arm after the age of 8 years. We studied a group of children and found that BMC sidedness gradually increased up to the age of 6 years and then remained stable into late adolescence. INTRODUCTION: Bone mineral content (BMC) exhibits sidedness in the arms after the age of 8 years, but it is not known whether BMC is greater in the dominant arm from birth or whether lateralization develops in early childhood. To address this, we examined bone mineral status in relation to handedness and age. METHODS: Subjects (N = 158) were children recently initiating glucocorticoids for underlying disease (leukemia 43 %, rheumatic conditions 39 %, nephrotic syndrome 18 %). Handedness was determined by questionnaire and BMC by dual-energy X-ray absorptiometry. RESULTS: Median age was 7.2 years (range, 1.5 to 17.0 years), 49 % was male, and the spine BMD Z-score was -0.9 (SD, 1.3). By linear regression, BMC sidedness in the arms was significantly related to age (r = 0.294, p = 0.0005). Breakpoint analysis revealed two lines with a knot at 6.0 years (95 % CI, 4.5-7.5 years). The formula for the first line was: dominant:nondominant arm BMC ratio = 0.029 × age [in years] + 0.850 (r = 0.323, p = 0.017). The slope of the second line was not different from 0 (p = 0.332), while the slopes for the two lines were significantly different (p = 0.027). CONCLUSIONS: These results show that arm BMC sidedness in this patient group develops up to age 6 years and then remains stable into late adolescence. This temporal profile is consistent with mechanical stimulation of the skeleton in response to asymmetrical muscle use as handedness becomes manifest.

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome.

SUMMARY: Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). INTRODUCTION: Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. METHODS: Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. RESULTS: Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. CONCLUSIONS: Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.

The suitability of thoraco-abdominal aortic aneurysms for branched or fenestrated stent grafts--and the development of a new scoring method to aid case assessment.

OBJECTIVE: To determine the proportion of TAAAs which might be suitable for pure endovascular repair based on aneurysm morphology and to develop an MDCTA based scoring system to grade case complexity. DESIGN: 70 consecutive MDCTA of patients with TAAAs were analysed in relation to specific morphological characteristics. METHODS: The characteristics included potential stent landing zone lengths, arch angulation, thoraco-abdominal aorta angulation, branch vessel origin stenosis, access tortuosity/diameter and aortic dissection. RESULTS: 60% of TAAAs would be suitable for branched/fenestrated stent grafting but 40% are unsuitable due to adverse anatomy. 27% had an aortic arch angulation of ≤ 110° and 24% had descending thoracic aorta angulation of ≤ 90°. Significant ostial stenosis was identified in 31% of celiac arteries, 7% superior mesenteric arteries, 24% left renal artery and 19% right renal arteries. 11% of left common iliac and 7% right common iliac arteries had angulation of ≤ 70°. There were 26 cases with aortic dissection and 54% of these had a true lumen of ≤ 26 mm. CONCLUSION: Successful fenestrated/branched stent graft repair of TAAAs requires adequate landing zones, cannulation of visceral arteries and suitable diameter access vessels. 60% of TAAAs studied were suitable for branched/fenestrated stent graft repair but 40% of TAAAs were unsuitable; aortic angulation, visceral vessel ostial stenosis and dissection true lumen diameter were the principle issues. Development in stent technology may address these anatomical challenges.

Complex abdominal aortic aneurysm repair.

ascular surgery is a challenging discipline and complex aneurysms can present an entire range of technical difficulties. To overcome these problems good technical skills are mandatory. However, it is also worth remembering a few basic rules: The simplest solution is often the best. All cases need careful planning, including that of the approach. A successful anastomosis requires good aortic tissue. Minimal dissection reduces morbidity.

Axillo-iliac conduit for haemodialysis vascular access.

OBJECTIVES: To describe a series of venous surgical procedures performed to maintain vascular access. METHODS: We report eight patients with end-stage renal failure (ESRF) who had complex renal access problems. Three patients had central venous occlusion and underwent veno-venous axillo-iliac bypass. In five further patients with a symptomatic central venous obstruction we performed axillo-iliac arterio-venous grafting (AVGs) in order to achieve haemodialysis access. All patients were assessed pre-operatively with duplex ultrasound and venogram of upper and lower limbs. The axillary artery or vein, and iliac vein were approached via infraclavicular and extra-peritoneal groin incisions, respectively. Non-externally-supported polytetrafluoroethylene (PTFE) was used as a conduit in all patients and anti-coagulation regimen were commenced post-operatively. RESULTS: Following venous diversion surgery, there was a dramatic improvement in the facial and limb swelling experienced by the patients. There was no significant peri-operative morbidity. The veno-venous graft is still patent at 14 months in patient one, at 10 months in patient two, and 5 months in patient three. In the second group, who had arterio-venous grafts, the mean follow-up was 13.2 (7-20) months with a secondary patency rate of 80% at 6 months. Four patients had patent, usable grafts at 12 months. In two cases, graft occlusion was treated with successful thrombectomy. CONCLUSION: Axillary-iliac veno-venous diversion can overcome the symptoms and complications of superior vena cava and innominate vein obstruction. Although, axillo-iliac arterio-venous graft fistulae formation was previously described it has not been widely used. We have found the procedure to have low morbidity and advocate its use in these complex cases.

Action of estradiol on epiphyseal growth plate chondrocytes.

Estrogen plays an important role in the human growth plate by accelerating growth and promoting epiphyseal fusion in both sexes. Nevertheless, the precise mechanisms responsible for these effects are poorly understood. In the present study, we examined the role of 17beta-estradiol (E2) on cell proliferation and viability, type X collagen synthesis, alkaline phosphatase activity, and matrix calcification in primary cultures of resting, proliferating, and prehypertrophic chondrocytes derived from explants of the bovine fetal epiphyseal growth plate. Growth plate chondrocytes were isolated and separated into maturationally distinct subpopulations, which were cultured for 7-21 days to high density in either (1) serum-free medium, (2) 1 nM thyroid hormone (T3), (3) E2 concentrations ranging from 10(-13) M to 10(-7) M, or (4) a combination of T3 and E2. To compare E2 effects in both sexes, chondrocytes were harvested from 8 fetuses of both sexes. After hormone treatment, cell cultures were analyzed for cell number and viability, collagen type X, alkaline phosphatase (ALP), and matrix calcification. Neither DNA content nor cell viability were affected by the duration or type of hormone treatment. By itself, E2 stimulated maturation of all subpopulations only in pharmacologic doses (10(-7) M). Physiologic E2 concentrations were no different than negative controls treated with ITS (insulin, transferrin, and selenite). Regardless of E2 concentrations, the addition of E2 to 1 nM T3 did not appreciably affect the response to T3 alone, which stimulates maturation of the phenotype. All effects were comparable in both male and female chondrocytes, in all cell subpopulations (maturation stages) and fetuses of varying gestational age. These findings indicate that at physiologic concentrations, the effects of E2 on fetal bovine growth plate chondrocyte appear to be indirect and independent of T3, suggesting that, in vivo, E2 acts in concert with other factors or hormones to induce fusion of the growth plate.

Megestrol acetate promotes euglycemia and appetite in a child with persistent hyperinsulinemic hypoglycemia of infancy.

UNLABELLED: This report describes a successful treatment with megestrol acetate in a child with persistent hyperinsulinemic hypoglycemia of infancy (PHHI). An 8-y-old child with PHHI treated with octreotide had marked impairment of appetite sensation and feeding skills. Within 3 wk of starting megestrol acetate (8 mg/kg/d) to stimulate her appetite, she had a significant improvement. By 1 y postinitiation, she had acquired age-appropriate eating habits. The megestrol acetate caused hyperglycemia, necessitating the discontinuation of all other therapy for her hypoglycemia. Her height growth remained normal but she was found to have asymptomatic adrenal suppression. CONCLUSION: Megestrol acetate appeared to stimulate appetite and regulate glucose homeostasis in this child with PHHI. Additional studies will be required to document its efficacy and safety in other children with this disorder.

Multinodular goiter in children.

OBJECTIVE: As multinodular goiter (MNG) is an uncommon pediatric disorder, we decided to evaluate the children with this diagnosis at our center to try to delineate better its etiology, the risk of malignancy and appropriate management strategies. METHODS AND RESULTS: Eighteen patients (12 girls and 6 boys) were the subject of this retrospective review spanning a period of 20 years. All were previously well, except one, and none had had head or neck irradiation. Average age at diagnosis was 12.8 years. Four children belonged to two previously identified kindreds diagnosed with familial MNG. These families had members affected with multiple cases of non-medullary thyroid carcinoma (NMTC). All were euthyroid and had no symptoms. In eight of 18 patients, the clinical examination missed the presence of multiple nodules which were subsequently detected by ultrasound. Twelve patients had tissue diagnosis by fine needle aspirate cytology (FNAC) or surgery. Five of eight patients undergoing surgery had nodular hyperplasia, one had a follicular adenoma and one had a normal thyroid gland on histology. There was one patient with papillary carcinoma combined with nodular hyperplasia. Seven of the patients had evidence of antithyroid autoimmunity. CONCLUSION: The etiology of pediatric MNG appears multifactorial including autoimmune and familial factors. We believe that previously healthy children can usually be managed conservatively. Ultrasound at the time of diagnosis and in follow up seems beneficial. Familial forms appear to warrant close follow up, given the apparent increased risk of malignancy. The risk of malignancy while low remains real.

Bisphosphonates in dialysis and transplantation patients: efficacy and safety issues.

Bisphosphonates are an old class of compounds. They were used in the 1930s as antiscaling and anticorrosion agents in washing powders and water to prevent the deposition of calcium crystals. Those basic functions were later utilized in an attempt to prevent ectopic calcifications in humans. The early studies demonstrated that bisphosphonates had a strong affinity for bone. That property was first exploited when the compounds were used for "bone scans." Currently, the drugs are used for treatment of hypercalcemic conditions, abnormal bone remodelling, Paget disease, malignancy, and osteoporosis. Bisphosphonates have several important toxicities: acute renal failure, worsening renal function, reduced bone mineralization, and osteomalacia. For those reasons and others, this class of drugs has not yet been approved for use in children or in patients with severe renal insufficiency. The present review covers several aspects of bisphosphonates: molecular structure, routes of administration, pharmacology, mechanisms of action, toxicities, and exceptional uses in children with renal disease.

Multicompartment urea kinetics in well-dialyzed children.

BACKGROUND: We have reported catch-up growth with hemodialysis (HD) of approximately 15 hours/week. Without an equilibrated post-treatment blood urea nitrogen, the variable-volume single-pool (VVSP) model will not account for urea rebound, inflating the estimated HD dose (K(d)t/V). A two-pool model (FVDP) predicts rebound, but requires fixed compartment volumes for the equations to be solvable in closed form, also inflating K(d)t/V. METHODS: We developed an approximate perturbation solution (WKB method) to a variable volume, two-pool (VVDP) model. Estimated model parameters were compared with the results of equilibrated kinetic studies using measured clearance K(d) (N = 17). Once the model was validated, we re-analyzed 292 kinetic studies from our earlier cohort, which was considered well-dialyzed on the basis of growth rates (N = 12, mean annual change in height standard deviation score +0.31, mean follow-up of 26 months). RESULTS: For the VVSP, FVDP, and VVDP models, respectively, the mean errors were (1) K(d)t/V, 0.22 +/- 0.07, 0.29 +/- 0.17, 0.06 +/- 0.07 (ANOVA, P < 0.001); (2) urea distribution volume vol/wt (%), -8.2 +/- 4.2, -9.1 +/- 3.0, -2.2 +/- 3.6 (P < 0.001). Sequential studies confirmed reproducibility, with a coefficient of variation < or = 5%. In the earlier cohort, a comparison of the VVSP and VVDP models yielded the following: (1) K(d)t/V, 1.91 +/- 0.35 vs. 1.76 +/- 0.33 (P < 0.001); (2) normalized protein catabolic rate (nPCR, g/kg/day), 1.56 +/- 0.39 vs. 1.52 +/- 0.38 (P < 0.001); and (3) K(d) (whole blood, mL/kg/min), 4.8 +/- 0.9 vs. 4.4 +/- 0.8 (P < 0.001). CONCLUSION: This VVDP model yields reliable estimates of K(d)t/V and other kinetic parameters using standard blood urea nitrogen sampling. Analysis of patients previously characterized as well-dialyzed on the basis of growth rates clarifies the HD dose needed to sustain normal growth.

Hypercalcemia of the newborn: etiology, evaluation, and management.

Hypercalcemia in infants is uncommon but has potentially serious sequelae. This review examines four cases of neonatal hypercalcemia, emphasizing appropriate investigations and treatment of acute and chronic hypercalcemia. The paper provides additional information as to the mechanisms of calcium dysregulation in idiopathic infantile hypercalcemia, Williams syndrome, vitamin D intoxication, and parathyroid and parathyroid-related protein disturbances.

Moderate renal failure in association with prolonged acquired hypothyroidism in children.

We evaluated five children with prolonged primary hypothyroidism and noted a significant reduction in renal function (40%), which was reversible with hormonal replacement. This decline was higher than reported in adults and was of sufficient magnitude to warrant altering drug-dosing schedules. Furthermore, patients with moderately reduced renal function should be carefully evaluated for signs and symptoms of hypothyroidism.

A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations.

Permanent primary congenital hypothyroidism (CH) can be caused by abnormal thyroid differentiation (athyreosis), migration (ectopy), or function (leading to goiter). Goiters follow an autosomal recessive pattern of inheritance, whereas ectopy and athyreosis are considered as a single sporadic entity with a female preponderance. On the other hand, a high prevalence of extrathyroidal malformations has been reported in CH, but without linking specific defects to specific types of CH. On the basis of TSH screening, 273 newborns were referred to an academic pediatric endocrinology clinic in the province of Quebec between 1988 and 1997. Of 230 patients with permanent primary CH who had scintigraphy at diagnosis, 141 had ectopy (104 girls), 36 had athyreosis (21 girls), 42 had goiter (18 girls), 10 (3 girls) had a normal scan, and 1 girl had hemiagenesis. Only in the ectopies was the proportion of girls significantly higher than 0.5 (P<0.001). Isolated cardiac malformations were observed in 7 patients (3.0%), a prevalence 5-fold higher than that in the general population; this was largely due to atrial and ventricular septal defects, which were only observed in ectopy and athyreosis. Our data suggest that the molecular mechanisms that lead to complete absence of thyroid differentiation or defective thyroid migration 1) may be similar, but are modulated by the genetic makeup of the embryo and/or the hormonal milieu of the fetus; and 2) may also be involved in septation of the embryonic heart.

Growth during maintenance hemodialysis: impact of enhanced nutrition and clearance.

Growth of children during maintenance hemodialysis has been reported to be uniformly poor, with a mean annual loss of 0.4 to 0.8 SD in height. We adopted an intensive program of closely monitored energy and protein intake with dialysis urea clearances exceeding conventional recommendations. Twelve prepubertal or early pubertal children (aged 7 months to 14 years) were monitored for an average of 2.2 years (range 4 to 81 months) while receiving maintenance hemodialysis. These children received an average of 90.6% and 155.9% of their recommended energy and protein nutritional intake, respectively. With a prescribed urea clearance of 5 mL/kg/min, we achieved a mean single treatment urea clearance normalized for total body water of 2.00, a urea reduction ratio of 84.7%, and an average time of hemodialysis of 14.8 h/wk, all well beyond current guidelines. Over the course of dialysis treatment, the improvement in height SD score was+0.31 SD/y (+0.32 excluding the 2 children treated with recombinant human growth hormone). Normal growth was achieved without overt obesity and was associated with normal pubertal growth spurt. These findings suggest that the combination of increased dialysis and adequate nutrition can promote normal growth in children treated with long-term hemodialysis.