Median Chronological Age Research Articles

Hurthle cell carcinoma in childhood: A retrospective analysis of five cases and review of pediatric literature.

the available studies on Hurthle cell carcinoma (HCC) in pediatric age are scarce and based on isolated case reports. Aims of the present study were to review the available pediatric literature on HCC (2000-2019), to describe the cohort of children with this cancer histotype, and to estimate its relative prevalence in pediatric age. We retrospectively reconstructed an HCC course in five patients<19 years who were identified in our departments during the period 2000-2019, and we reviewed the available pediatric studies on this differentiated thyroid cancer (DTC) variant. HCC occurred with a relative prevalence of 5.8% at a median chronological age of 12.5 years. None of HCC patients exhibited, at diagnosis, thyroid dysfunction, extensive lateral neck disease, or distant metastases, and all showed a persistent remission over time. Three patients showed, at diagnosis, antecedents of other diseases (Hashimoto's thyroiditis, neurofibromatosis type 1, and osteosarcoma). (1) In childhood, the relative prevalence of HCC among different thyroid cancer histotypes is 5.8%, that is close to the one previously reported both in the general population and in other less numerous children's cohorts; (2) HCC may develop even early, at the age of 7; (3) in childhood, HCC does not seem to have a more aggressive behavior when compared with other DTC histotypes; (4) antecedents of other diseases are not infrequent in the history of children with HCC.

Early Exchange Transfusion to Treat Neonates With Gestational Alloimmune Liver Disease

Exchange transfusion (ET) and intravenous immunoglobulin are potentially life-saving treatment options in newborns with gestational alloimmune liver disease (GALD). Since 2008, early ET has been the standard of care for symptomatic neonates with suspected GALD in our unit. The present study's aim was to investigate the outcomes of this approach. From 2008 to 2018, all neonates who received ET for suspected GALD were identified, and their clinical course and outcomes were analyzed in a descriptive cohort study. In survivors, liver function parameters before ET and maximum values after ET and at discharge were compared. During the 11-year period, 12 infants received ET for suspected GALD at a median (range) chronological age of 11 (1-23) days and gestational age of 38 (32-40) weeks. Signs of impaired liver function, most frequently postnatal hypoglycemia, hyperferritinemia, direct hyperbilirubinemia, and coagulopathy, were present in all infants. Survival without a liver transplant in the overall cohort was 10 of 12 (83.3%) and 7 of 9 (78%) in those fulfilling the criteria of acute liver failure. Two patients died, one of them after liver transplantation. Direct bilirubin typically increased after ET, even in survivors. All survivors recovered and were discharged from the pediatric hepatology outpatient clinic after 8 (3-11) months of follow-up. In newborns with suspected GALD, a limited diagnostic work-up followed by early ET may lead to favorable outcomes. More data are required to develop an evidence-based clinical approach to GALD.

Diuretic use in infants with developing or established chronic lung disease: A practice looking for evidence.

The objective was to assess respiratory efficacy of hydrochlorothiazide and spironolactone and ascertain any adverse effects. Data from 2014 to 2018 was analysed for infants <28 weeks' gestational age (GA) administered oral diuretics. Impact on respiratory support, weight gain and electrolyte status was assessed as a pre-post intervention study. Of 491 infants, 117 (24%) were administered diuretics for evolving or established bronchopulmonary dysplasia. GA and birthweight of the cohort were 25.7 ± 1.1 weeks and 779 ± 172 g, respectively. Median (interquartile range) chronological age and GA at the start of diuretics was 45 (22, 62) days and 32.1 (30.1, 35.1) weeks, respectively. In 71/117 (61%) infants, diuretics were started at <36 weeks GA. Of them 63 (88.7%) went on to develop bronchopulmonary dysplasia. Median duration of diuretics was 38 (18-52) days. Modest improvement was noted in respiratory parameters (ventilator pressure (cm of H2 O), 8.8 ± 0.4 vs. 8.8 ± 0.5, P = 0.39, oxygen requirement (%), 32 ± 1 vs. 30 ± 1, P = 0.07 and pO2 (mm Hg) 34.5 ± 1.3 vs. 36.6 ± 1, P = 0.04. Ninety-eight (84%) infants developed hyponatraemia (<135 mmol/L); sodium supplements were administered in 58/98 (59%) infants. In one third infants, phosphate levels dropped below 1.8 mmol/L, needing supplementation. Weight gain (g/kg/day) slowed down significantly (18.2 ± 2.1 to 10 ± 2.9, P = <0.001). Use of diuretics was associated with modest improvements in respiratory support requirements but was associated with significant electrolyte abnormalities and slowdown in weight gain (or weight loss).

The effect of age on DNA methylation in whole blood among Bangladeshi men and women

BackgroundIt is well-known that methylation changes occur as humans age, however, understanding how age-related changes in DNA methylation vary by sex is lacking. In this study, we characterize the effect of age on DNA methylation in a sex-specific manner and determine if these effects vary by genomic context. We used the Illumina HumanMethylation 450 K array and DNA derived from whole blood for 400 adult participants (189 males and 211 females) from Bangladesh to identify age-associated CpG sites and regions and characterize the location of these age-associated sites with respect to CpG islands (vs. shore, shelf, or open sea) and gene regions (vs. intergenic). We conducted a genome-wide search for age-associated CpG sites (among 423,604 sites) using a reference-free approach to adjust for cell type composition (the R package RefFreeEWAS) and performed an independent replication analysis of age-associated CpGs.ResultsThe number of age-associated CpGs (p < 5 x 10− 8) were 986 among men and 3479 among women of which 2027(63.8%) and 572 (64.1%) replicated (using Bonferroni adjusted p < 1.2 × 10− 5). For both sexes, age-associated CpG sites were more likely to be hyper-methylated with increasing age (compared to hypo-methylated) and were enriched in CpG islands and promoter regions compared with other locations and all CpGs on the array. Although we observed strong correlation between chronological age and previously-developed epigenetic age models (r ≈ 0.8), among our top (based on lowest p-value) age-associated CpG sites only 12 for males and 44 for females are included in these prediction models, and the median chronological age compared to predicted age was 44 vs. 51.7 in males and 45 vs. 52.1 in females.ConclusionsOur results describe genome-wide features of age-related changes in DNA methylation. The observed associations between age and methylation were generally consistent for both sexes, although the associations tended to be stronger among women. Our population may have unique age-related methylation changes that are not captured in the established methylation-based age prediction model we used, which was developed to be non-tissue-specific.

Seasonal abundance of the stable fly Stomoxys calcitrans in southwest England.

The stable fly Stomoxys calcitrans (L.) is a cosmopolitan biting fly of both economic and welfare concern, primarily as a result of its painful bite, which can cause blood loss, discomfort and loss of productivity in livestock. Between June and November in 2016 and May and December in 2017, Alsynite sticky-traps were deployed at four Donkey Sanctuary sites in southwest England, which experience recurrent seasonal biting fly problems. The aim was to evaluate the seasonal dynamics of the stable fly populations and the risk factors associated with abundance. In total, 19 835S. calcitrans were trapped during the study period. In both years, abundance increased gradually over summer months, peaking in late August/September. There were no relationships between seasonally detrended abundance and any climatic factors. Fly abundance was significantly different between sites and population size was consistent between years at three of the four sites. The median chronological age, as determined by pteridine analysis of flies caught live when blood-feeding, was 4.67 days (interquartile range 3.8-6.2 days) in males and 6.79 days (interquartile range 4.8-10.4 days) in females; there was no significant, consistent change in age or age structure over time, suggesting that adult flies emerge continuously over the summer, rather than in discrete age-related cohorts. The data suggest that flies are more abundant in the vicinity of active animal facilities, although the strong behavioural association between flies and their hosts means that they are less likely to be caught on traps where host availability is high. The implications of these results for fly management are discussed.

Phonological acquisition in children with early-treated congenital hypothyroidism: association with clinical and laboratory parameters.

To evaluate the phonological characteristics of children with congenital hypothyroidism (CH). Observational, analytical, cross-sectional, ambispective study including prepubertal children with CH (n=100; study group, SG) and controls without CH ( n=100; control group, CG). Assessments included a speech language pathology interview, the phonological evaluation of the ABFW Child Language Test, medical data, and neuropsychological tests in the first three years of life. On treatment onset of the SG, the median chronological age of the participants was 18.0 days and 48.4% had total T4 <2.5 µg/dL (31.75 nmol/L). At the age of 7 years, children in the SG had higher rates of consonant cluster simplification and lower rates of complete phonological system compared to those in the CG. On analysis of combined age groups (4+5 and 6+7 years), the CG had a higher frequency of complete acquisition versus the SG. On multivariate analysis, thyroid agenesis, abnormal scores on the Clinical Linguistic and Auditory Milestone Scale and developmental quotient tests were associated with the occurrence of phonological disorders. Children with CH present delay in phonological acquisition, despite early diagnosis and adequate treatment, especially between the ages of 6-7 years. The etiology of CH and the results of neuropsychological tests in the first years of life seem to be related to this delay.

Echocardiographic assessment of patent ductus arteriosus in very low birthweight infants over time: prospective observational study

Background: We aimed to determine the echocardiographic parameters that can predict the presence of patent ductus arteriosus (PDA) and haemodynamically significant ductus arteriosus (HSDA) at different time points.Methods: Echocardiogram was performed on postnatal days 3 and 7(D3-Echo and D7-Echo, respectively) in 71 very low birthweight infants with a median gestational age of 28.0 weeks. We first assessed the correlation between D3-Echo findings among infants with ductal patency and persistent ductal patency on D7-Echo. We subsequently assessed the correlation between D7-Echo findings and ultimate need for PDA treatment.Results: Forty-nine (69.0%) infants had ductal patency on D3-Echo, and 32(65.3%) of these had persistent PDA on D7-Echo. Twenty of the latter (62.5%) underwent PDA treatment at a median chronological age of 19 days. PDA treatment was significantly correlated with DA size and DA peak-systolic-to-end-diastolic velocity(S/D) ratio on D3- and D7-Echo. Receiver operating characteristic curve analysis revealed that DA size ≥2.040 mm and S/D ratio ≥2.016 had fair sensitivity, specificity, and predictive values for PDA treatment.Conclusion: The significance of different echocardiographic parameters associated with future ductal patency or HSDA depends on the time of assessment. DA size and S/D ratio on day 7 are two reliable indicators of the need for future PDA treatment.

Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects

To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. Retrospective study. Tertiary care center. Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20years and belonging to 10 unrelated families. None. Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.

Estrogen-mediated Height Control in Girls with Marfan Syndrome

This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.

Short Children with CHARGE Syndrome: Do They Benefit from Growth Hormone Therapy?

Aim: The aim of this study was to evaluate the response to recombinant growth hormone (GH) treatment in short children with CHARGE syndrome. Patients: We identified 51 children (28 boys and 23 girls) in KIGS (Pfizer International Growth Database). The median chronological age was 7.6 years at the start of GH therapy and 13.2 years at the latest visit. Evaluation for GH deficiency (n = 33) was based on the following: peak GH level 7.3 μg/l and IGF-I level -2.01 standard deviation score (SDS). Sixteen subjects (9 boys) were followed longitudinally for 2 years. Results: Birth length (median SDS, -0.47) and weight (-0.97) were slightly reduced. At the start of GH therapy, height was -3.6 SDS, BMI -0.7 SDS, and the GH dose was 0.26 mg/kg/week. At the latest visit after 2.7 years of GH therapy, height had increased to -2.2 SDS and BMI to -0.5 SDS. In the longitudinal group, height increased from -3.72 SDS at the start of GH therapy to -2.92 SDS after 1 year to -2.37 SDS after 2 years of therapy (start - 2 years: p < 0.05), height velocity increased from -1.69 to 2.98 to 0.95 SDS, and BMI and GH dose (mg/kg/week) remained almost unchanged. Conclusions: Our data show a positive effect of conventional doses of GH on short-term growth velocity for the longitudinal as well as for the total group, without any safety issues.

Prevalence of hereditary angioedema in untested first-degree blood relatives of known subjects with hereditary angioedema.

Hereditary angioedema (HAE) is a rare autosomal-dominant disease characterized by recurring attacks of nonpruritic, nonpitting edema caused by an inherited deficiency or dysfunction of C1 esterase inhibitor (C1 INH). Symptoms can present years before an accurate diagnosis is made. The objective of this study, the Angioedema Clinical Epidemiology Testing Initiative for the Study of Hereditary Angioedema, was to determine the prevalence and clinical manifestations of HAE in untested first-degree blood relatives of known patients with HAE. Patients with a confirmed diagnosis of HAE recruited first-degree relatives who had not been evaluated for HAE. Enrolled subjects underwent complement testing (C4, C1 INH antigen, and functional C1 INH). If the lab tests were abnormal, the enrolled subjects returned to the site for a follow-up visit and questionnaire. Overall, 31 patients with HAE and 46 first-degree relatives enrolled in the study. Of 46 enrolled relatives, 30 (65%) had lab test results that ruled out a diagnosis of HAE, two (4%) were categorized as "HAE not ruled out," and 14 (30%) were newly diagnosed with HAE. Of 14 newly diagnosed subjects, nine (64%) reported having experienced symptoms that may have been related to HAE, such as swelling in the throat, face, or extremities or abdominal pain. When reported, median age of symptom onset in these 14 subjects was nine years whereas newly diagnosed asymptomatic subjects had a median chronological age of six years. These 14 subjects reported a historic mean standard deviation rate of 2.51 (5.59) swelling episodes per month with a mean standard deviation duration of 1.6 (0.74) days. This study's findings reinforce the importance of testing family members of patients with HAE to detect this hereditary condition.

Prevalence and Characteristics of Rib Fractures in Ex-preterm Infants

This study aimed to identify the prevalence and characteristics of rib fractures in ex-preterm infants. Infants born at <37 weeks' gestation and admitted before 2011 to 3 regional neonatal units were identified from admission registers. For 2 centers, these data were available from 2000 onward and, for another center, from 2005. Electronic records were searched to identify chest radiographs performed up to age 1 year. Chest radiograph reports were then reviewed for evidence of rib fractures, and the case notes of all affected individuals were scrutinized. Of the 3318 eligible preterm infants, 1446 had a total of 9386 chest radiographs. Of these infants, 26 (1.8%) were identified as having a total of 62 rib fractures. Their median (range) gestation at birth was 26 weeks (23-34). The median chronological age of these infants at the time of the radiograph was 14 weeks (5 weeks to 8 months). The median corrected gestational age at the time of the radiograph was 39 weeks (34 weeks to 4 months). Of the 62 fractures, 27 (36%) were sited posteriorly, and 15 (53%) of the infants with posterior rib fractures were diagnosed with osteopathy of prematurity. Classic risk including conjugated hyperbilirubinemia and diuretics, were present in 23 of 26 (88%) infants. A full skeletal survey was performed in 8 of 26 (31%). Investigations for nonaccidental injury occurred in 4 of 26 (15%) cases. Evidence of rib fractures is present in ~2% of ex-preterm infants. The evaluation of these fractures in infancy requires a detailed neonatal history irrespective of the site of rib fracture.

Menarche in Pediatric Patients with Crohn’s Disease

The timing of menarche in Crohn's disease (CD) is poorly described. Our objectives were to study age at menarche onset in CD, and factors associated with this. We compared the age at menarche of 34 CD patients with that for 545 controls, using data in the National Health and Nutrition Examination Survey (NHANES). Mean chronological age (CA) of CD patients (15.6 years) did not differ from that of the NHANES cohort (15.7 years; P = 0.91). The median CA at menarche (13.9 years) in CD was older than in the NHANES sample (12.0 years) (P < 0.00005). In CD patients, the cumulative incidence of menarche was 10 % at CA 12 years, 51 % at CA 14 years, and 100 % at CA 16 years. Sixty-eight percent reached menarche by bone age (BA) 13.5 years and 100 % by BA greater than 14.0 years. Menarche occurred earliest in South Asians, followed by East Asians, and then Caucasians (P = 0.02). CA at menarche is delayed in CD compared with the NHANES cohort. BA at menarche in CD is similar to BA at menarche reported for healthy children. CA at menarche in CD differs by race. If menarche has not occurred by BA greater than 14.0 years, endocrinology referral should be considered.

Menarche in Pediatric Patients With Crohn's Disease

The timing of menarche in Crohn’s disease (CD) is poorly described. Our objectives were to study age at menarche onset in CD, and factors associated with this. We compared the age at menarche of 34 CD patients with that for 545 controls, using data in the National Health and Nutrition Examination Survey (NHANES). Mean chronological age (CA) of CD patients (15.6 years) did not differ from that of the NHANES cohort (15.7 years; P = 0.91). The median CA at menarche (13.9 years) in CD was older than in the NHANES sample (12.0 years) (P < 0.00005). In CD patients, the cumulative incidence of menarche was 10 % at CA 12 years, 51 % at CA 14 years, and 100 % at CA 16 years. Sixty-eight percent reached menarche by bone age (BA) 13.5 years and 100 % by BA greater than 14.0 years. Menarche occurred earliest in South Asians, followed by East Asians, and then Caucasians (P = 0.02). CA at menarche is delayed in CD compared with the NHANES cohort. BA at menarche in CD is similar to BA at menarche reported for healthy children. CA at menarche in CD differs by race. If menarche has not occurred by BA greater than 14.0 years, endocrinology referral should be considered.

Correlation of bone age, dental age, and chronological age in survivors of childhood acute lymphoblastic leukaemia

There is little information about oncotherapy-related dental development in childhood acute lymphoblastic leukaemia (ALL). The objective of this study was to compare bone age (BA) and dental age (DA) to chronological age (CA) in childhood ALL survivors. We retrospectively reviewed hand-wrist and panoramic radiographs of patients treated on contemporary single institution protocols for ALL between 1991 and 2004. We recorded patient demographics, therapeutic protocol, CA, DA, and BA. The cohort was divided into three categories based on age at diagnosis (< 6 years, 6-9 years, > 9 years). Of 73 patients, 39 (53.4%) were boys; 55 (75.3%) were Caucasian. Median CA at diagnosis was 4.5 years (range: 0.1-11.0 years); time to study was 4.1 years (range: 0.3-11.4 years). BA was normal in 61 (83.6%), delayed in 10 (13.7%), and advanced in 2 (2.7%). DA was normal in 41 (56.9%), delayed in 8 (11.1%), and advanced in 23 (31.9%). Abnormal BA, abnormal DA, and discrepancy between BA and DA are not statistically significantly associated with investigated patient or treatment factors. DA may be altered in 43.1% of patients treated for ALL. A large prospective study is warranted to better define our observations and to determine their impact on dental and orthodontic management.

The Effects of Recombinant Human Growth Hormone on Linear Growth in Children with Crohn's Disease and Short Stature

The efficacy of recombinant human growth hormone (rhGH) in treating the growth failure associated with Crohn's disease (CD) is unclear. Retrospective data analysis at 12 months before (T-12), 6 months before (T-6), at baseline (T+0), 6 months after (T+6) and 12 months after (T+12) rhGH treatment in seven patients with CD (five males). Median chronological age (CA) and median difference between CA and bone age was 15.9 yr (range, 13.0 to 17.9) and 1.7 yr (-0.7 to 3.3), respectively. Median dose of rhGH at T+0 was 0.23 mg/wk (0.15 to 0.31). Pubertal status remained unchanged in 6/7 patients. Median albumin and C-reactive protein (CRP) were similar at T+0 and T+6. Median height SDS at T+0, T+6 and T+12 was -2.2 (-4.0 to -1.5), -1.9 (-4.1 to -0.8), -1.9 (-4.1 to -0.7), respectively (NS). Median height velocity (HV) SDS at T+0 and T+6 was -2.5 (-4.8 to 1.4) and -0.9 (-5.3 to 3.4), respectively (NS). There was a positive correlation between percentage change in HV SDS at T+6 and dose of rhGH at T+0 (r = 0.8, p = 0.03). Introduction of rhGH therapy was associated with a cessation in the deterioration in linear growth. However, an improvement in height SDS was not observed over the period of the study. Future studies should explore the efficacy of a higher dose of rhGH in CD.

Growth in pre-pubertal children with myelomeningocele (MMC) on growth hormone (GH): The KIGS experience

To analyse the auxological data of children with myelomeningocele (MMC) on growth hormone (GH) therapy whose growth data was documented within KIGS (Pfizer International Growth Database). Longitudinal growth data of a sub-group of pre-pubertal children were studied after a treatment period of 3 years. Eighty patients (38 m, 42 f) with MMC with a median chronological age (CA) of 11.6 years (at latest visit) on GH were registered in the KIGS database. In 52 patients, GH deficiency was documented. GH therapy started with a median dose of 0.23 mg kg(-1) per week. The 3-year longitudinal growth was analysed in 21 patients (13 m, 8 f; median CA 9.2 years, latest visit), all of whom were pre-pubertal at start and during GH therapy. GH therapy started at 7.5 years with a dose of 0.23 mg kg(-1) per week. Birth length SDS (-0.51) and mid-parental height SDS (+0.07) were in the normal range. BMI SDS at start was +0.24, at latest visit -0.03. After a median treatment duration of 3.0 years (latest visit), height SDS improved from -2.97 (start of GH) to -2.01. The sub-group of pre-pubertal MMC patients started GH therapy (dose 0.22 mg kg(-1) per week) at 6.2 years. Growth velocity (GV) SDS increased significantly (at start: -1.77; 1 year: +2.60, 2 years: +2.25, 3 years: +1.24), thus height SDS improved from -3.25 at start to -1.87 at 36 months. BMI SDS was in the normal range and remained unchanged during GH therapy. No major side effects of GH were recorded. GH had positive effects on height SDS in MMC patients. The analysis of the longitudinal growth data of pre-pubertal MMC patients showed a significant increase in GV SDS and improvement of height SDS.

24-Hour Electrocardiogram before and during Cisapride Treatment in Neonates and Infants

We studied prospectively the effects of cisapride on heart rate and rhythm using standard ECG and 24-hour ECG recordings in term and preterm neonates and infants. We studied subjects with gastroesophageal reflux disease (apparent life-threatening events, apneas, bradycardias) before and 3 days after starting cisapride (0.8 mg/kg/day in 4 doses). We performed standard ECGs for determination of corrected Q-T interval (QTc) and Q-T dispersion (QTd) and 24-hour ECG recordings for analysis of heart rate, heart rate variability, and heart rhythm. Fourteen term and 17 preterm subjects (gestational age range 28–36 weeks) were studied at a median chronological age of 29 (range 3–132) days. Cisapride significantly increased the QTc in preterm infants (before vs. after: 408 ± 7 vs. 433 ± 7 ms, p = 0.001). Two preterm and 1 term infant had a QTc >450 ms before cisapride. Four preterm (4/15 = 27%) and 2 term (2/13 = 15%) subjects had a QTc >450 ms on cisapride. After cisapride the QTd remained normal, and no relevant arrhythmias were documented on Holter recordings. Cisapride significantly decreased peak and mean heart rates of all study subjects without affecting the heart rate variability, while it increased the minimal heart rate of preterm infants only (before vs. after: 66 ± 5 vs. 78 ± 5 bpm, p = 0.02). The maximally measured R-R intervals (pauses) decreased after cisapride in preterm infants (before vs. after: 1.33 ± 0.2 s vs. 1.05 ± 0.2 s, p = 0.04). Although cisapride did cause a significant prolongation of the ventricular action potential duration in preterm infants, the QTd remained unaffected, and no clinically relevant arrhythmias were documented in this small sample. On the other hand, cisapride had a direct lowering effect on the maximal and mean heart rates of both term and preterm infants, while the drug increased the minimal heart rate and reduced the severity of bradycardia episodes in preterm infants.

Effects of bilateral upper first premolar extraction on the mandible

The purpose of this study was to evaluate the effects of bilateral upper premolar extraction on mandibular growth. Twenty-six subjects (eight males, 18 females) in maximum pubertal growth with an Angle Class II molar relationship, normal to mild overjet increase, mild or no lower arch length discrepancy but severe upper arch discrepancy and no severe skeletal discrepancy were divided into two groups equal in number and gender, as extraction and control groups. The median chronological age was 11.2 years in the extraction group and 12.6 years in the controls. The subjects were observed for a median period of 1.1 years in the extraction group after bilateral extraction of the upper premolars and 1.2 years in the controls until termination of pubertal growth (DP3u) without any orthodontic treatment. Twenty-nine linear and angular measurements were made on 52 lateral cephalograms and hand-wrist radiographs taken before and after the study period. The increase in SNB measured on the total superimposition was significantly greater in the controls than in the extraction group (P < 0.05). In addition, anterior mandibular (counter-clockwise) rotation was only significant (P < 0.05) in the control group. Thus, it might be suggested that bilateral upper premolar extractions might affect the mandibular rotation tendency.

Effects of Cisapride on Ventricular Depolarization-Repolarization and Arrhythmia Markers in Infants

To study prospectively the effects of cisapride on ventricular repolarization, depolarization, and arrhythmia markers in neonates, we determined before and three days after starting cisapride (1 mg/kg/day): corrected QT interval (QTc) and QT dispersion (QTd) on standard ECGs, and duration of filtered QRS (fQRS) and of low amplitude (<40 µV) terminal signals (LAS40, ms) and root mean square of the last 40 ms (RMS40, µV) using high-gain signal-averaged ECG (SAECG). Twenty-four term and 11 preterm infants (gestational age 23–35 weeks) were studied at a median chronological age of 32 days. QTc and QTd were not different between term and preterm infants. Cisapride lengthened QTc (mean ± SD; ms: 396.6 ± 24.8 before vs. 417.0 ± 35.2 after, p < 0.001). Three term and two preterm infants (5/35 = 14%; 95% CI: 5–30%) had a QTc >450 ms after cisapride. QTd after cisapride increased significantly in all infants with prolonged QTc. Filtered QRS, LAS40, and RMS40 before and after cisapride were within our normal values. We conclude that cisapride prolongs ventricular repolarization in neonates and infants without altering depolarization. Although no clinical arrhythmias were observed the dose of 0.8 mg/kg/day should not be exceeded.