Growth of prepubertal children with inflammatory bowel disease

BACKGROUND: Growth retardation has been reported in children with chronic inflammatory bowel disease, especially in those with Crohn's disease. Most of these studies concern adolescent patients. METHODS: The growth of 47 prepubertal children (20 boys and 27 girls, mean age at diagnosis 7 years) with inflammatory bowel disease was studied at Tampere University Hospital, Department of Paediatrics. The mean height and height velocity standard deviation scores were calculated at diagnosis and, after that, yearly. The cumulative doses of oral and rectal prednisone per year were calculated. The severity of the disease was scored. The statistical analysis was carried out using the analysis of variance for repeated measurements. RESULTS: During the year preceding the diagnosis, children with inflammatory bowel disease had grown more slowly than their healthy peers. At diagnosis, they were slightly shorter as a group than are healthy children. During treatment and follow-up the mean height velocity of children with inflammatory bowel disease increased (change in the mean height velocity standard deviation scores from -0.84 to +1.08), normalizing the mean heights of these children compared with those of their healthy peers (change in the mean height standard deviation scores from -0.32 to +0.05). In the analysis of covariance, the poorest growth was seen in children with Crohn's disease, scored as severe, and the best growth in children with mild ulcerative colitis. No difference was seen in groups with or without prednisone treatment. CONCLUSIONS: Growth retardation is an important sign of chronic inflammatory bowel disease in prepubertal as well as adolescent children. During treatment, increasing growth velocity brings these children as a group to normal heights for age and sex.     

A population-based study of the usefulness of screening for neuroblastoma

BACKGROUND: Neuroblastoma has many characteristics which suggest that preclinical detection might improve outcome. The Quebec Neuroblastoma Screening Project was initiated to determine whether mass screening could reduce mortality in a large cohort of infants. As an early endpoint, we report whether screening could reduce the incidence of poor-prognosis neuroblastoma in children with advanced-stage disease over 1 year of age. METHODS: All 476,603 children born in the province of Quebec during the 5-year period of May 1, 1989, to April 30, 1994, were eligible for urinary assay of homovanillic acid and vanillylmandelic acid at 3 weeks and 6 months of age. Children with a positive screen were referred to one of four paediatric cancer centres in the province for uniform evaluation and treatment if necessary. Standardised incidence ratios (SIRs) were calculated for neuroblastoma in the province and two similar population-based controls, the state of Minnesota and the province of Ontario, during the same period of time and with similar ascertainment procedures. FINDINGS: Compliance with screening in Quebec province was 91% at 3 weeks (n = 425,816) and 74% at 6 months (n = 349,706). Through July 31, 1995, with a follow-up of the birth cohort of 15-75 months, 118 cases of neuroblastoma were diagnosed, 43 detected preclinically by screening, 20 detected clinically before screening at 3 weeks of age, and 55 detected clinically after 3 weeks of age having normal screens (52) or never screened (3). Retrospective analysis of stored samples confirmed that 49 of 52 patients missed by screening had levels of catecholamine metabolites that were too low to be detected at 6 months or earlier. Based on US Surveillance, Epidemiology and End Results data, 54.5 cases of neuroblastoma would have been expected in Quebec province during the study period, for an SIR of 2.17 (95% CI 1.79-2.57, p < 0.0001). For the two control groups, 43 and 80 cases of neuroblastoma were detected, respectively, compared with 37.9 and 85.4 expected, overall SIR 1.00 (not significant). SIRs for Quebec province by age at diagnosis in yearly intervals show a marked increased incidence under 1 year of age (SIR 2.85, 2.26-3.50), with no reduction in incidence in subsequent years. Limiting analysis to only patients diagnosed over 1 year of age with advanced-stage disease, 22 cases were detected in Quebec province versus 14.4 expected (SIR 1.52, 0.95-2.23). Data in the two control groups show no significant increase or decrease in any-stage disease in children under or over the age of 1 year, except for an increase in early-stage disease in Minnesota children over 1 year: 10 versus 3.8 expected (SIR 2.67, 1.27-4.58). INTERPRETATION: Screening for neuroblastoma increases the incidence in infants without decreasing the incidence of unfavourable advanced-stage disease in older children. It is unlikely that screening for neuroblastoma in infants will reduce mortality for this disease.     

Exercise tolerance and blood pressure response to exercise testing in children and adolescents after renal transplantation

Intrauterine growth retardation (IUGR), defined as birth weight and/or length less than 3rd percentile (P) or less than-2 standard deviations (SD), concerns about 3% of newborns. About 85% born IUGR show spontaneous postnatal catch-up to a height > P3 or > -2 SD during the first two years of life. After the age of 4 year, the children without catch-up will remain short up to final height. Classical growth hormone (GH) deficiency usually does not seem responsible for the absence of catch-up in those children. A two-year GH therapy at supraphysiological doses increases growth velocity. The effect of this treatment on final height remains to be studied, as well as optimal treatment's modalities. Attention should be paid on the possible side-effects. Finally, the evaluation of the psychological impact of GH treatment will be critical.     

Neuroblastoma in children under than 1 year of age

OBJECTIVE: Our objective was to carry out a prospective multicenter study of neuroblastoma patients diagnosed between 0 and 12 months of age. PATIENTS AND METHODS: Diagnostic procedures included histology, catecholamine excretion, bone marrow cytology and MIBG-scan. Staging was evaluated according to the INSS classification. After 1992, Simada criteria were used and also N-myc amplification, DNA index and P-glycoprotein determinations in tumoral tissue. The surgical technique employed and complications derived from it were also evaluated. The patients were treated according to stage with multicenter Spanish protocols N-I-87 and N-II-92. Overall survival and event free survival were calculated by actuarial methods. RESULTS: Between October 1987 and June 1992, a total of 140 infants less than one year of age were registered and diagnosed of neuroblastoma, representing 40% of all neuroblastoma cases. Median age was 0.3 years and 73% were less than 6 months of age at diagnosis. The most frequent stage was 1 (35%) followed by 4-S (20%). The frequency of unfavorable prognostic factors was the following: LDH (21%), NSE (14%), ferritin (18%), Shimada (7%), DNA (35%), NMA (3%), TrakA (23%), P-glycoprotein (19%). Surgery was performed in 133 children: total resection was reported in 94 and > 90% in another 22 cases. Complications attributed to surgery occurred in 12% of the cases. Chemotherapy was given in 73 cases and radiotherapy in 7. The five year total survival is 91% and the event free survival 88%. Survival by stages: Stage 1 = 91%, stage 2A = 88%, stage 2B = 100%, stage 3 = 84%, stage 4 = 56% and stage 4-S = 100%. CONCLUSIONS: 1) The majority of neuroblastoma cases in infants less than one year old are diagnosed before six months of age. 2) For this age group stages 1 and 4-S are the most frequently observed. 3) Unfavorable biological factors are less frequent than for children over one year of age and are associated with disseminated disease (advanced stage). 4) The outcome is excellent, except for stage 4 patients. The cases in stage 1 and 2 may be treated by surgery alone. Chemotherapy may be of benefit for stage 3 patients.     

Determinants of growth in diabetic pubertal subjects

OBJECTIVE: To analyze the relationship among metabolic control, IGF-I, and growth in pubertal diabetic subjects. RESEARCH DESIGN AND METHODS: In 72 diabetic children, we have studied the pattern of change of IGF-I, IGF-I SD score, IGF binding protein (BP)-1, and growth rate in different pubertal stages and have analyzed their relation to age sex, weight/length index, HbA1c, insulin concentration, insulin dose, and dehydroepiandrosteronesulfate (DHEAS). RESULTS: The serum IGF-I values increased up to Tanner stage 4 and thereafter decreased, whereas IGFBP-1 showed the inverse pattern. When transforming the IGF-I values into SD scores, correcting for age, sex, and pubertal stage, it was shown that the deviation from normal values increased with increasing pubertal stage in boys, but was equal in stages 3-5 in girls. Using multiple regression analysis, HbA1c, insulin dose, and DHEAS were significantly correlated to IGF-I SD score (R2 = 0.253, P = 0.001). IGFBP-I levels in the afternoon were within normal range. LogIGFBP-1 showed an inverse correlation, to insulin concentration in single correlation (r = -0.26, P = 0.02). In single correlation, growth rate correlated significantly to insulin dose (r = 0.25, P = 0.03). In a multiple regression analysis, only DHEAS and IGF-I SD score were found to be significantly correlated to growth rate (R2 = 0.370, P < 0.001). The 18 adolescents who had reached their final height did not deviate from their target final height, according to their recorded growth since birth. CONCLUSIONS: In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.     

Age-specific determinants of stunting in Filipino children

This study identifies age-specific factors related to new cases of stunting that develop in Filipino children from birth to 24 mo of age. Data come from nearly 3000 participants in the Cebu Longitudinal Health and Nutrition Survey, a community-based study conducted from 1983 to 1995. Length, morbidity, feeding and health-related data were collected bimonthly during home visits. Stunting (length >2 SD below the WHO age- and sex-specific medians) occurred in 69% of rural and 60% of urban children by 24 mo of age. We used a multivariate discrete time hazard model to estimate the likelihood of becoming stunted in each 2-mo interval. The likelihood of stunting was significantly increased by diarrhea, febrile respiratory infections, early supplemental feeding and low birth weight. The effect of birth weight was strongest in the first year. Breast-feeding, preventive health care and taller maternal stature significantly decreased the likelihood of stunting. Males were more likely to become stunted in the first year, whereas females were more likely to become stunted in the second year of life. Because stunting is strongly related to poor functional outcomes such as impaired intellectual development during childhood, and to short stature in adulthood, these results emphasize the need for prevention of growth retardation through promotion of prenatal care and breast-feeding, as well as control of infectious diseases.     

Repetitive conundrums of centromere structure and function

BACKGROUND: Adult participants in randomized controlled trials often have better outcomes than patients who are eligible but not enrolled. OBJECTIVE: To examine whether newborn infants who were allocated to placebo in an investigational drug trial had better outcomes than infants who were eligible but not randomized (eligible NR). Study design: During a randomized controlled trial of antithrombin therapy in premature infants with respiratory distress syndrome, data were collected prospectively on all 76 infants in the eligible NR group. Study outcomes were compared with those of all 61 infants who were randomized to placebo. The same exogenous surfactant was used in all patients. RESULTS: In the placebo group the mean (SD) birth weight was 1201 (314) g, mean (SD) gestational age was 28.8 (2.3) weeks, and 51% were male. In infants in the eligible NR group, mean (SD) birth weight was 1141 (262) g, mean (SD) gestational age was 28.3 (2. 3) weeks, and 58% were male; 57% of infants in both groups had been exposed to steroids before birth. The median duration of mechanical ventilation was reduced from 6.2 days in the eligible NR group to 4. 8 days in the placebo group (P =.008). There was also a trend toward less frequent and less severe intraventricular hemorrhage in trial participants. CONCLUSIONS: These data are consistent with the hypothesis that sick newborn infants may benefit from participation in a randomized controlled trial.     

Endometrial stromal sarcoma of the vulva arising in extraovarian endometriosis: a case report and literature review

OBJECTIVES: To better characterize intrarenal neuroblastoma. METHODS: We retrospectively reviewed the records of 5 children with neuroblastoma initially diagnosed as Wilms' tumor. RESULTS: Five patients, aged 11 months to 3.5 years, were preoperatively diagnosed as having intrarenal Wilms' tumor, prior to operative or histopathologic diagnosis of neuroblastoma. In 3 children the diagnosis of neuroblastoma involving the kidney was confirmed; in the fourth child subcutaneous metastatic disease precluded biopsy confirmation of the intrarenal tumor; and in the fifth child the kidney was severely displaced but not actually involved by neuroblastoma. All patients were hypertensive and 4 patients had elevated urinary catechol levels. Molecular genetic studies showed N-myc amplification in both patients who were evaluated. All patients had poorly differentiated histopathology. One patient is presently alive at 8 months with recurrent disease and another patient is free of disease 13 years after diagnosis. The remaining 3 patients died of the malignancy. CONCLUSIONS: Intrarenal neuroblastoma is a rare entity that clinically and radiographically may resemble Wilms' tumor. Our limited experience indicates that intrarenal neuroblastoma is an aggressive malignancy, and long-term survival is rare.     

Reference values for height and weight in Prader-Willi syndrome based on 315 patients

The spontaneous growth of 315 patients (109 girls and 208 boys) with Prader-Willi syndrome (PWS) was analysed in a mixed longitudinal and cross-sectional manner. 33 patients were seen in the department between 1970 and 1994; height and weight of 76 patients from Germany were evaluated by means of a questionnaire with detailed measuring instructions, and 206 definite cases were added from the literature. Mean ( SD) length of newborn babies with PWS was 50.2+/-2.8 cm (145 boys) and 48.9 3.3 cm (79 girls). Mean weight at birth was 2945 570 g in boys and 2782+/-594 g in girls. During the 1st year, the children's growth was nearly normal, thereafter short stature was present in approximately 50% of PWS patients. Between 3 and 13 years of age, the 50th percentile for height in PWS is roughly identical with the 3rd percentile in healthy controls. Body weight was normal for all boys and girls during the first 2 years. Thereafter, a rapid weight gain occurred; after an age of 10 years weight-for-height index in nearly all patients exceeded the normal range. The extent of pubertal growth was reduced for the group. Mean adult height was 161.6+/-8.1 cm (23 males) and 150.2+/-5.5 cm (21 females). Head circumference for age was normal for boys and girls. CONCLUSION: Reference data on spontaneous development of growth and weight gain of children with Prader-Willi syndrome are described allowing a better counselling of patients and parents.     

Catch-up growth during childhood among very low-birth-weight children

OBJECTIVES: To examine growth attainment and correlates of catch-up growth at 8 years of age in a cohort of very low-birth-weight (VLBW) children (< 1500 g), including appropriate and small-for-gestational-age children, and to compare their growth with normal-birth-weight (NBW) children. DESIGN: Eight-year longitudinal follow-up of a cohort of VLBW children. A geographically based, randomly selected sample of NBW children was recruited at 8 years of age. SETTING: Tertiary perinatal center. PARTICIPANTS: Two hundred forty-nine VLBW children born between January 1, 1977, and December 31, 1979 (78% of survivors), of whom 199 were born appropriate for gestational age and 50 were small for gestational age (< -2 SD). The NBW population included 363 children. MAIN OUTCOME MEASURES: For the VLBW population, rates of subnormal weight (below the third percentile) and height were obtained at birth, at 40 weeks (term), and at 8 and 20 months. For the VLBW and NBW populations, mean weight, height, and percentile distribution at 8 years were derived from the National Center for Health Statistics standards. RESULTS: Catch-up growth to above the third percentile occurred between 40 weeks and 8 months, 8 and 20 months, and up to 8 years of age among the VLBW children. At 40 weeks, 54% were subnormal in weight and 60% were subnormal in height; at 8 months, 33% and 22%, respectively, and at 8 years, 8% were subnormal in weight and height. Small-for-gestational-age children had lower rates of catch-up growth. Multivariate analyses disclosed maternal height, race, birth weight, and neurologic abnormality to predict percentile distribution of height; and maternal height, small for gestational age, and neurologic abnormality to predict subnormal height. CONCLUSIONS: Catch-up growth occurs during childhood among VLBW children. These results have implications when counseling parents about the potential growth attainment of their children.     

Mass screening for neuroblastoma at 6 months of age: difficult to justify

BACKGROUND/PURPOSE: A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. METHODS: The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. RESULTS: From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). CONCLUSIONS:These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.     

Human recombinant anti-Rh(D) monoclonal antibodies: improvement of biological properties by in vitro class-switch

The aim of this study was to investigate how intrauterine growth retardation affects body proportions in VLBW infants. The cohort consisted of 135 surviving and 80 deceased preterm infants weighing less than 1250 grams at birth. Gestational age varied between 24 and 36 weeks (mean age 29.7 and 27.5 weeks, respectively). Birth weight was more than 2 SD below the mean birth standard values in 32% of the surviving, and in 27% of the deceased infants. Reduction of weight, length and head circumference at birth was analysed using Z scores based on Swedish birth standards. Z scores of weight, length and head circumference were highly correlated in the surviving and the deceased infants (r = 0.78 to 0.94 and 0.65 to 0.97, respectively). Length was significantly more affected by growth retardation than weight. Weight and head circumference were proportionately reduced. Intrauterine growth retardation influences body proportions in VLBW infants differently than in larger preterm and term infants.     

Growth graphs for the clinical assessment of infants of varying gestational age

Two graphs are presented showing means and 1 and 2 SD for growth in weight, length, and head circumference: (1) a fetal-infant graph with lines of growth from 26 weeks of gestational age until one year of age after "term' has been reached: and (2) a similarly constructed graph for children ages one through ten years. The standards of growth were obtained from published data in which the subjects received optimal health care. The graphs allow comparisons of infants of varying gestational age with standards for that age. Normal and abnormal deviations in growth are easily identified. Some examples of common variations in physical growth are described.     

Comparison of midazolam with propofol for sedation in outpatient bronchoscopy

Two children are described who had microphthalmia (one with unilateral and one with bilateral) noted at birth, and whose early onset of poor linear growth and weight gain led to a diagnosis of hypopituitarism prior to two years of age. Both children had growth hormone and thyroid-stimulating hormone deficiencies, and evidence of partial ACTH deficiency. Administration of growth hormone resulted not only in rapid linear growth but it also reversed the poor weight gain and head growth noted in these children. These cases suggest that hypopituitarism and microphthalmia may be associated with each other more frequently than has been recognized previously.     

Twenty years of childhood coeliac disease in the Netherlands: more diagnoses and a changed clinical picture

OBJECTIVE: To assess the incidence of childhood coeliac disease in the Netherlands and to study the clinical features. DESIGN: Prospective. SETTING: Leiden University Medical Centre, Leiden, the Netherlands. METHOD: Cases of childhood coeliac disease in the Netherlands in 1993-1995 were identified by means of the Dutch Paediatric Surveillance Unit. Inclusion criteria were: birth in the Netherlands, diagnosis with at least one small bowel biopsy in 1993-1995 and age at diagnosis 0-14 years. The data were cross checked with the Dutch Network and National Database of Pathology and compared with data from a previous study on childhood coeliac disease, 1975-1990. RESULTS: 297 Coeliac patients were identified by means of the Surveillance Unit, another 32 through the National Database of Pathology. The mean crude incidence rate of diagnosed childhood coeliac disease was 0.51/1000 live births, which was in the range of rates found in other West European countries and significantly higher than the mean crude incidence rate of 0.18/1000 live births found in the Netherlands in 1975-1990. The clinical presentation was classic up to 1990: chronic diarrhoea, abdominal distention and growth failure. From 1993 onward, however, the number of children with chronic diarrhoea and abdominal distention decreased significantly and the number with weight loss, anaemia and abdominal pain increased. Associated disorders were present in 13.7% of the cases. CONCLUSIONS: The incidence of diagnosed childhood coeliac disease in the Netherlands showed a tendency to increase significantly during the past decade. In a period of 20 years a significant trend toward change in the clinical presentation of coeliac disease in Dutch children was observed.     

Neonatal diagnosis of familial hypercholesterolemia in newborns born to a parent with a molecularly defined heterozygous familial hypercholesterolemia

This study was designed to compare blood lipid levels in newborn individuals with molecularly defined heterozygous familial hypercholesterolemia [FH] to those in non-affected babies and to clarify the value of lipid determinations in assessment of diagnosis of FH at birth and 1 year of age. Twenty-five babies were born to 21 parents with DNA-documented heterozygous FH. Analysis of their cord blood samples revealed 11 newborns with the FH-North Karelia [FH-NK] mutation, 3 newborns with the FH-Helsinki [FH-HKI] mutation, and 11 nonaffected newborns. Cord serum total [TC] and LDL cholesterol [LDL-C] levels (mean +/- SD) in affected newborns (2.60 +/- 0.70 and 1.77 +/- 0.56, respectively) were significantly (P < .001) higher than those in nonaffected ones (1.54 +/- 0.23 and 0.78 +/- 0.15, respectively) and another cohort of 30 randomly selected control samples from apparently healthy newborns (1.84 +/- 0.46 and 1.03 +/- 0.30, respectively). However, there was overlapping of individual lipid levels in these three groups precluding the use of TC or LDL-C determinations in neonatal diagnosis of FH. In contrast, 1 year follow-up samples from 10 affected and 7 nonaffected individuals, as well as additional samples collected from another group of 8 affected and 9 nonaffected individuals, indicated that serum cholesterol levels showed much greater increment in children with FH. Thus, at the age of 1 year the mean serum TC and LDL-C levels in the affected infants (8.38 +/- 1.18 and 7.02 +/- 1.07, respectively) were much higher (P < .001) than the corresponding levels (4.40 +/- 0.66 and 2.89 +/- 0.68, respectively) in the nonaffected infants, and the individual ranges of TC and LDL-C levels were nonoverlapping in these two groups. Serum HDL cholesterol [HDL-C] levels in 1-year-old children with FH (0.95 +/- 0.14) were approximately 20% lower than those of their similar at birth. In conclusion, phenotypic expression of heterozygous FH, as defined by molecular analysis of genomic DNA, is evident in serum LDL-C (but not HDL-C) levels already at birth, but for diagnostic purposes blood lipid determinations carried out at the age of 1 year are highly superior to those performed at birth.     

Giardiasis in children with chronic diarrhea. Incidence, growth, clinical symptoms and changes in the small intestine

During a six-year period, 29 children (aged 0.7-13.5 years, mean 3.3 years) suffering from chronic diarrhoea due to giardiasis were studied. The incidence of this illness was 81 per 1,000,000 per year among children aged 0- < 7 years. According to growth charts, relative height and weight of the patients decreased significantly (both approximately 0.5 SD) from before the onset of diarrhoea to the time of diagnosis and subsequently increased up to the end of catch-up growth. Small intestinal mucosal specimens were studied. Two patients had severe villous atrophy, 8 moderate abnormalities, 6 only slight changes and 13 biopsies were normal. D-xylose or lactose malabsorption was detected in 25% of the patients. The lactose malabsorption was due to hereditary low lactase levels. None of the patients with a Danish ethnic background showed lactose malabsorption. D-xylose absorption and the relative weight loss of the patients correlated with the degree of mucosal damage. Patients with persistent diarrhoea (n = 19) were younger and had a shorter duration of diarrhoeal illness and a more significant weight reduction than those with intermittent diarrhoea (n = 10). However, the age at onset of symptoms was similar in the two groups (medians 1.3 years). Seven patients contracted the disease abroad. They all developed persistent diarrhoea and had a more severe course of the illness than those who acquired the disease in Denmark.     

Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience

BACKGROUND: The Quebec Neuroblastoma Screening (QNS) Project completed a 5-year program for measuring urinary vanillylmandelic acid (VMA)/homovanillic acid (HVA) levels at age 3 weeks and/or 6 months in 89% of 476,603 Quebec-born infants from 1989-1994; 45 screening positive preclinical cases (S-positive cases) and 20 congenital/neonatal (C/N) cases were identified. As of April 1997, an additional 59 cases in the same birth cohort were diagnosed clinically; these neuroblastomas developed after screening verified normal VMA/HVA levels (S-negative cases). METHODS: Pathology specimens from 45 of 59 S-negative cases were reviewed centrally and classified according to the Shimada system. Results were compared with clinical data and also with S-positive and C/N cases. RESULTS: Of 45 S-negative cases, 27 tumors had favorable histology (FH) and 18 had unfavorable histology (UH). Approximately 52% of FH tumors were diagnosed before age 1 year, whereas UH tumors were nearly exclusively (94%) diagnosed after age 1 year (P < 0.01). Approximately 89% of FH tumors were Stage I, II, or IV-S, whereas 72% UH tumors were Stage III or IV (P < 0.001). All children with FH tumors were alive at last follow-up (range of follow-up period: 9-79 months; median, 35 months), whereas 8 children with UH tumors died of disease even after limited follow-up (range of follow-up period: 0-60 months; median, 20 months). By contrast, S-positive and C/N cases were predominantly (97%) FH tumors, often (76%) Stage I, II, or IV-S, with excellent clinical outcome (survival rate of 98%). CONCLUSIONS: The majority of the UH neuroblastomas that developed in the birth cohort of the QNS Project were included in the group of S-negative cases and could not be detected by the screening at age 3 weeks and/or 6 months.     

Diabetes during pregnancy does not alter whole body bone mineral content in infants

A previous study using single photon absorptiometry has reported low bone mineral density of the radius in infants of diabetic mothers. The aim of this study was to assess by dual x-ray absorptiometry the whole body bone mineral content (WbBMC) and the body composition of 40 infants of diabetic mothers at birth (mean gestational age +/- SD, 37.5 +/- 1.3 weeks; mean birth weight +/- SD, 3815 +/- 641 g). WbBMC was not correlated with gestational age, but was well correlated with birth weight (r = 0.73; P = 0.0001) and also with fat mass (r = 0.87; P = 0.0001) and lean mass (r = 0.42; P = 0.008). The z-scores +/- SD adjusted for weight for WbBMC and fat mass were significantly increased (1.3 +/- 0.9 and 2.6 +/- 1.3, respectively (P < 0.0001), but were not significantly influenced either by in utero growth or by the type of the diabetes mellitus of the mother. Bone mineralization and fat mass studied by whole body dual x-ray absorptiometry are increased at birth in these infants compared with reference curves.     

Early surgery in patients with mitral regurgitation due to flail leaflets: a long-term outcome study

BACKGROUND: The optimal timing for surgery in patients with mitral regurgitation is disputed. Because of the frequency of left ventricular dysfunction, which is difficult to predict, early surgery has been recommended, but its potential benefits have not been demonstrated. METHODS AND RESULTS: The outcomes of 221 patients (mean age, 65 +/- 13 years; 71% males) with flail leaflets diagnosed with two-dimensional echocardiography between 1980 and 1989 who were eligible for operation were analyzed. Group I comprised 63 patients who had early mitral valve surgery (within 1 month after diagnosis). Group II comprised 158 patients initially treated conservatively (80 of whom were operated on later). Group I patients were younger (P=.009), had more symptoms (P<.0001), and were more frequently in atrial fibrillation (P=.023) than group II patients. There was no difference in ejection fraction between the groups. The early surgery strategy was followed by an improved overall survival rate (P=.028) and a lower incidence of cardiovascular deaths (P=.025), congestive heart failure (P=.046), and new chronic atrial fibrillation (P=.032), as confirmed by multivariate analysis (adjusted risk ratios of 0.31, 0.18, 0.38, and 0.05, respectively; all P<.02). CONCLUSIONS: In patients with mitral regurgitation due to flail leaflets, the strategy of early surgery versus conservative management is associated with an improved long-term survival rate, decreased cardiac mortality, and decreased morbidity after diagnosis. This outcome advantage suggests that early surgery is a reasonable treatment option to be considered in low-risk candidates with repairable valves and severe mitral regurgitation.