Factors Associated With the Occurrence and Treatment of Supraventricular Tachycardia in a Pediatric Congenital Heart Disease Cohort

In patients with congenital heart disease (CHD), the association between supraventricular tachycardia (SVT), type of pathophysiology, and therapeutic interventions in a population-based cohort warrants further examination. A retrospective, longitudinal 15-year data set (1996–2010) was analyzed. Inclusion criteria included age ≤17 years, enrolled in South Carolina State Medicaid, and diagnosed as having one or more CHDs as well as SVT. SVT was diagnosed in 6.5 % of CHD patients (N = 1,169) during the 15-year epoch investigated. SVT was less likely to occur in African-American (hazard ratio [HR] = 0.76) or male patients (HR = 0.88), but it was significantly more likely to occur in patients age ≤12 months or in adolescents ≥13 years in those undergoing multiple surgeries/medical interventions for their CHD (HR = 1.14), those receiving antiarrhythmic/diuretic/preload-/afterload-reducing medications (HR = 5.46), and those with severe/cyanotic CHDs (HR = 1.52) or chromosomal abnormalities (HR = 1.64). Children who had an atrial septal defect secundum (adjusted odds ratio [aOR] = 3.03) and those treated with diuretic or antiarrhythmic medication (aOR = 1.80) were significantly more likely to undergo SVT ablation, whereas those with late-onset pulmonary hypertension (ages 6–12 years old) were significantly less likely to undergo SVT ablation. SVT recurred in only 14 of 166 patients who underwent SVT ablation. Multiple medical interventions at an early age may increase the risk of SVT occurrence in young CHD patients regardless of the severity/complexity of the CHD.     

Neuropsychological profiles of three sisters homozygous for the fragile X premutation

Fragile X syndrome (fraX) is associated with an amplification of a CGG repeat within the fraX mental retardation (FMR-1) gene. We describe an exceptional family in which 3 adult sisters are homozygous for the FMR-1 premutation. Each sister inherited 2 premutation alleles (ca. 80 CGG repeats) from their biologically unrelated parents. The 3 sisters were administered measures of executive function, visual spatial, memory, and verbal skills. Deficiencies in the first 2 of these domains have been reported among females with the full mutation. The sisters' performances were compared with available normative data and with published group means for females affected by fraX. These women did not appear to have verbal or memory difficulties. None of the women demonstrated a global executive function deficit, and none had global deficits in spatial ability. The profiles of these sisters are consistent with reports that the fragile X premutation does not affect cognitive performance. © 1996 Wiley-Liss, Inc.     

A rapid,reliable, and inexpensive method for detection of di- and trinucleotide repeat markers and disease loci from dried blood spots

We used a rapid and inexpensive method for studying the FMR1 CGG-repeat from dried blood spots, prepared from heel pricks, finger pricks, or an aliquot of blood from a venipuncture. The procedure includes a single tube for preparation of template DNA for PCR and minimal handling, avoiding opportunities for mislabelling specimens and loss of template. We extended the protocol to numerous di- and trinucleotide repeat markers and disease loci, including FRAXE, FRAXF, DXS548, DRPLA, and ZFY. The use of a highly reliable and very inexpensive method which employs blood spots as a source for target DNA means that newborn Guthrie cards can be used to establish allele frequencies for linkage disequilibrium studies, that large populations can be screened for genetic disorders, and that mapping studies can proceed rapidly even when only small amounts of blood are available from key family members. © 1996 Wiley-Liss, Inc.     

The CD6/ALCAM pathway promotes lupus nephritis via T cell–mediated responses

T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6⁺ and ALCAM⁺ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target.     

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943–2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9–2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2–5.3) and leukemia (2.8; 95% CI 2.4–3.2). The AER decreased from 331 (278–383) excess neurologic disorders per 100,000 person-years 5–9 years after diagnosis to 82 (46–118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.     

Cutaneous scar at anterior hair line in mother and child with associated frontal bone defect in child

A large frontal bone defect underlying a “V” shaped scar was noted in a newborn male whose mother had an identical “V” shaped scar at the same location in the anterior hairline. Both had hypertelorism and short palpebral fissures. The mother had no radio-graphic evidence of skull defect and neither mother nor child had other cutaneous or skeletal anomalies. Cranioplasty was performed on the child using the remaining frontal bones with an excellent cosmetic result. Biopsy performed at operation documented scar tissue extending through the dermis and underlain by thickened dura. Mother and child appear to have a variant form of aplasia cutis congenita, an autosomal dominant trait with wide variation in expression. © 1992 Wiley-Liss, Inc.     

Release in vitro of adipsin, vascular cell adhesion molecule 1, angiotensin 1-converting enzyme, and soluble tumor necrosis factor receptor 2 by human omental adipose tissue as well as by the nonfat cells and adipocytes

The relative release in vitro of adipsin, vascular cell adhesion molecule (VCAM) 1, angiotensin 1-converting enzyme (ACE), and soluble tumor necrosis factor alpha receptor 2 (sTNFR2) by explants of human omental and subcutaneous adipose tissue as well as the nonfat cell fractions and adipocytes from morbidly obese gastric bypass women was compared with that by tissue from obese abdominoplasty patients. Release of VCAM-1 and ACE by omental adipose tissue explants was 220% and 80% greater, respectively, over 48 hours of incubation than that by subcutaneous adipose tissue explants. However, this difference was not seen when release by adipocytes derived from omental fat was compared with that by adipocytes from subcutaneous fat. The release of adipsin and sTNFR2 by omental adipose tissue explants did not differ from that by subcutaneous tissue adipose tissue. The release of adipsin by tissue explants over 48 hours was 100-fold greater than that of VCAM-1, ACE, or sTNFR2. Most of the release of all 4 adipokines was due to the nonfat cells because adipsin release by adipocytes was only 13% of that by the nonfat cells derived from the same amount of adipose tissue, whereas ACE release by adipocytes was 7% and release of VCAM-1 as well as sTNFR2 by adipocytes was 4% or less of that by nonfat cells. The total release in vitro of ACE and sTNFR2, but not that of adipsin or VCAM-1, was enhanced in adipose tissue explants from morbidly obese women as compared with those by explants derived from obese women. We conclude that although human adipose tissue explants release appreciable amounts of adipsin and far smaller amounts of VCAM-1, ACE, and sTNFR2 in vitro, more than 87% of the release is due to the nonfat cells present in adipose tissue. Furthermore, the enhanced release of VCAM-1 and ACE seen in omental adipose tissue explants as compared with explants of subcutaneous adipose tissue is due to release by nonfat cells.