Viral shedding, and distribution of cytomegalovirus glycoprotein H (UL75), glycoprotein B (UL55), and glycoprotein N (UL73) genotypes in congenital cytomegalovirus infection.

BACKGROUND: Children with congenital CMV infection (cCMV) shed virus in urine and saliva for prolonged periods of time. Outcome of cCMV varies from asymptomatic infection with no sequelae in most cases, to severe longterm morbidity. The factors associated with asymptomatic cCMV are not well defined. We evaluated the viral shedding in a cohort of infants with cCMV identified on newborn screening. In addition, we describe the distribution of viral genotypes in our cohort of asymptomatic infants and previous cohorts of cCMV children in the literature. METHODS: Study population consisted of 40 children with cCMV identified in screening of 19,868 infants, a prevalence of 2/1000. The viral shedding was evaluated at 3 and 18 months of age by real-time CMV-PCR of saliva and plasma, and CMV culture of urine. CMV positive saliva samples were analyzed for genotypes for CMV envelope glycoproteins gB (UL55), and gH (UL75) by genotype specific real-time PCR, and gN (UL73) by cloning and sequencing RESULTS: At 3 months age 40/40 saliva and urine samples, and 19/40 plasma samples were positive for CMV. At 18 months age all urine samples tested (33/33), 9/37 of saliva samples, and 2/34 plasma samples were positive for CMV. The genotype distribution did not differ from the published data CONCLUSIONS: The urinary virus shedding is more persistent than salivary shedding in children with cCMV. The genotype distribution was similar to previous literature and does not explain the low disease burden of cCMV in our population.

Metronomic therapy can increase quality of life during paediatric palliative cancer care, but careful patient selection is essential.

AIM: Children with refractory or high-risk malignancies frequently suffer from poor quality of life during palliative care. This study explored the effect of metronomic drug administration on survival and quality of life in paediatric patients with various refractory or high-risk tumours. METHODS: We treated 17 patients with a maintenance therapy that consisted of metronomic thalidomide, etoposide and celecoxib. The endpoints of the study were overall and progression-free survival, changes in the Karnofsky-Lansky scores from baseline to the end of the study therapy and radiological responses. RESULTS: The median overall survival after the start of the study therapy was 6.2 months (range 2.0-57.7), and the six-, 12- and 24-month survival rates were 59%, 18% and 18%, respectively. The median progression-free survival was 3.2 months (range 0.3-17.8). The Karnofsky-Lansky scores increased significantly during the study therapy (p = 0.02), with 35% of the patients having a transient improvement in their clinical status. Radiologically, one partial response and two disease stabilisations were encountered. Grade III-V adverse events occurred in 76% of the patients. CONCLUSION: Metronomic therapy may increase the quality of life during palliative care for childhood cancer, but requires careful patient selection to minimise the risk of serious adverse events.

Fetal radiation dose in computed tomography.

The connection between recorded volumetric CT dose index (CTDI vol) and determined mean fetal dose (Df) was examined from metal-oxide-semiconductor field-effect transistor dose measurements on an anthropomorphic female phantom in four stages of pregnancy in a 64-slice CT scanner. Automated tube current modulation kept the mean Df fairly constant through all pregnancy stages in trauma (4.4-4.9 mGy) and abdomino-pelvic (2.1-2.4 mGy) protocols. In pulmonary angiography protocol, the mean Df increased exponentially as the distance from the end of the scan range decreased (0.01-0.09 mGy). For trauma protocol, the relative mean Df as a function of gestational age were in the range 0.80-0.97 compared with the mean CTDI vol. For abdomino-pelvic protocol, the relative mean Df was 0.57-0.79 and for pulmonary angiography protocol, 0.01-0.05 compared with the mean CTDI vol, respectively. In conclusion, if the fetus is in the primary beam, the CTDI vol can be used as an upper estimate of the fetal dose. If the fetus is not in the primary beam, the fetal dose can be estimated by considering also the distance of the fetus from the scan range.

Postnatal ovarian activation has effects in estrogen target tissues in infant girls.

CONTEXT: Shortly after birth, pituitary gonadotropin secretion transiently activates in both sexes, and this surge is more robust in preterm (PT) than in full-term (FT) infants. In boys, the gonadotropin surge is associated with testicular activity and is considered an important part of normal reproductive development. In contrast, gonadal activation and its consequences in infant girls are poorly understood. OBJECTIVE: Our objective was to evaluate the association of postnatal ovarian activity with simultaneous changes in estrogen target tissues in FT and PT girls. PATIENTS AND METHODS: We measured urinary estradiol (E2) levels in 29 FT and 34 PT girls using a mass spectrometric method from 1 week (D7) to 6 months of age (M1-M6). To assess the contribution of ovarian E2 on urinary E2 levels, the levels in girls were compared with the levels of boys of similar cohorts (29 FT and 33 PT boys). E2 levels were compared with simultaneous changes in estrogenic target tissues including mammary glands in both sexes and uterus and vulvar epithelium in girls. RESULTS: Median urinary E2 levels increased after D7 in girls, but not in boys. Mammary gland diameter was larger in girls than in boys from M4 in FT (P < .001) and M2 in PT infants (P < .0001). In PT girls, E2 levels increased at term and were then higher than those in FT girls (P < .0001). Urinary E2 levels in PT girls were positively associated with mammary gland and uterine growth. CONCLUSIONS: These findings indicate that gonadal steroidogenesis activates during the postnatal gonadotropin surge in girls. In addition, the resulting elevated E2 levels affect target tissues, suggesting that postnatal pituitary-ovarian activation plays a role in normal female reproductive development.

Increased activity of the hypothalamic-pituitary-testicular axis in infancy results in increased androgen action in premature boys.

CONTEXT: Transient activation of the hypothalamic-pituitary-gonadal (HPG) axis is observed in boys during the first months of life. Previous research suggests increased HPG axis activation in premature infants, but the physiological significance of this has not been studied. OBJECTIVE: The objective of this study was to evaluate the differences in reproductive hormone levels and their biological effects between full-term (FT) and preterm (PT) infant boys. STUDY DESIGN AND PARTICIPANTS: Twenty-five FT and 25 PT (gestational age 24.7-36.6 wk) boys were recruited at birth and followed up monthly from 1 wk to 6 months of age (d 7, months 1-6). Nineteen FT and 20 PT boys were reexamined at 14 months of age. MAIN OUTCOME MEASURES: Urinary gonadotropins and testosterone were measured in serial urine samples and compared with testicular and penile growth. Urinary prostate-specific antigen was measured as an androgen biomarker. RESULTS: LH and testosterone levels were higher in PT boys (P < 0.001 for both) than FT boys. Compared with FT boys, FSH levels were lower at d 7 (P = 0.002) but higher from month 1 to month 3 (P = 0.002-0.030) in PT boys. This was associated with significantly faster testicular and penile growth in PT boys compared with FT boys. Transient increase in the prostate-specific antigen levels in both groups indicated androgen action in the prostate. CONCLUSIONS: Postnatal HPG axis activation in infancy is increased in PT boys and associated with faster testicular and penile growth compared with FT boys. Possible long-term consequences of hyperandrogenism in PT infant boys warrant further research.

Osteonecrosis in children treated for lymphoma or solid tumors.

PURPOSE: The purpose of this study was to find out the incidence of and clinical risk factors for magnetic resonance imaging (MRI)-detected osteonecrosis (ON) in children treated for lymphoma or solid tumors. PATIENTS AND METHODS: The development of ON was studied in 32 childhood cancer patients who underwent MRI scanning of the lower extremities at the end of their treatment. The underlying malignancy was Wilms tumor in 8 patients, non-Hodgkin lymphoma (NHL) in 8, Hodgkin disease (HD) in 7, rhabdomyosarcoma in 6, and other occasional solid tumors in 3 patients. RESULTS: Six of the 32 patients (19%) had ON. The mean age of the patients with ON at diagnosis was 12.7 years compared with 5.8 years for the patients without ON (P<0.001). All the patients with ON had either HD (4 patients) or NHL (2 patients). Two (33%) of the patients with ON were symptomatic. CONCLUSIONS: ON in MRI was found to be a common complication in children after treatment for HD or NHL. The risk for ON seems to be very low in patients with other solid tumors even when they receive high cumulative doses of dexamethasone.

High body mass index increases the risk for osteonecrosis in children with acute lymphoblastic leukemia.

PURPOSE: The aim of the study was to determine the incidence of and clinical risk factors for radiographic osteonecrosis (ON) in children treated for acute lymphoblastic leukemia (ALL) using the Nordic ALL protocols. PATIENTS AND METHODS: Ninety-seven consecutive patients with childhood ALL were studied prospectively by magnetic resonance imaging (MRI) of the lower extremities at the end of the treatment. RESULTS: Twenty-three (24%) of the 97 patients had ON. Seven of the patients (30%) were symptomatic, and three patients (13%) required surgical interventions. Multiple logistic regression analysis showed that high body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P < .001), and higher cumulative dexamethasone dose (P = .03) were independent risk factors for radiographic ON. The cumulative prednisone dose did not differ significantly between the patients with and without ON. The incidence of radiographic ON decreased significantly, from 36% to 7%, when the duration of dexamethasone exposure during the delayed-intensification phase was shortened from 3 to 4 weeks to 2 weeks with a taper (P = .001). CONCLUSION: ON as determined by MRI was found to be a common complication in children and adolescents after treatment with the Nordic ALL protocols. Revision of the ALL protocols by shortening the single exposure to dexamethasone has diminished the risk for ON remarkably. High BMI was identified as a new significant risk factor for ON.

Cloacal anomaly simulating megalocystis in the first trimester.

We present a case of cloacal anomaly that simulated megalocystis in the first trimester of gestation of a female fetus. During the second trimester, repeated paracentesis was necessary to treat increasing ascites, oligohydramnios, and hydronephrosis. Our data support findings that ascites presenting with a multiloculated cystic structure on sonography during the second trimester may be typical for cloacal anomalies. Active treatment of the fetal ascites is recommended to improve the child's prospects for survival.