E. O'Brian Smith

Influence of mutation type and X chromosome inactivation on Rett syndrome phenotypes.

We screened 71 sporadic and 7 familial Rett syndrome (RTT) patients for MECP2 mutations by direct sequencing and determined the pattern of X chromosome inactivation (XCI) in 39 RTT patients. We identified 23 different disease‐causing MECP2 mutations in 54 of 71 (76%) sporadic patients and in 2 of 7 (29%) familial cases. We compared electrophysiological findings, cerebrospinal fluid neurochemistry, and 13 clinical characteristics between patients carrying missense mutations and those carrying truncating mutations. Thirty‐one of 34 patients (91%) with classic RTT had random XCI. Nonrandom XCI was associated with milder phenotypes, including a mitigated classic RTT caused by a rare early truncating mutation. Patients with truncating mutations have a higher incidence of awake respiratory dysfunction and lower levels of cerebrospinal fluid homovanillic acid. Scoliosis is more common in patients with missense mutations. These data indicate that different MECP2 mutations have similar phenotypic consequences, and random XCI plays an important role in producing the full phenotypic spectrum of classic RTT. The association of early truncating mutations with nonrandom XCI, along with the fact that chimeric mice lacking methyl‐CpG‐binding protein 2 (MeCP2) function die during embryogenesis, supports the notion that RTT is caused by partial loss of MeCP2 function. Ann Neurol 2000;47:670–679

Body Composition during the First 2 Years of Life: An Updated Reference

Normative body composition during the first 2 y of life was derived from a prospective study of 76 children. We present 1) fat free mass (FFM) and its components, and fat mass (FM), 2) incremental growth rates partitioned into chemical components, and 3) age-specific and gender-specific constants for converting chemical and physical components into FFM for children during the first 2 y of life. A multicomponent model based on measurements of total body water (TBW), total body potassium (TBK) and bone mineral content (BMC) was used to estimate FFM and FM at 0.5, 3, 6, 9, 12, 18, and 24 mo of age. TBW was determined by deuterium dilution, TBK by whole body counting, and BMC by dual energy x-ray absorptiometry. FFM was higher in boys than girls between 0.5–18 mo of age (p ≤ 0.05). Percent FM increased on average from 13 to 31% between 0.5 and 3–6 mo, and then gradually declined. Percent FM was significantly higher in girls than in boys at 6 and 9 mo of age (p ≤ 0.02). The components of FFM on a percentage basis changed with age (p = 0.001), but not gender. The protein content of FFM increased gradually with age, while TBW declined (p = 0.001). As a percentage of FFM, osseous mineral increased from 2.0 to 3.4% in boys and from 2.1 to 3.3% in girls between 0.5 and 24 mo (p = 0.001). Density and potassium content of FFM increased gradually with age (p = 0.001). These normative body composition data provide an updated reference upon which to assess normal growth and nutritional status of pediatric populations representative of mixed feeding groups during the first 2 y of life.

Composition of gestational weight gain impacts maternal fat retention and infant birth weight

OBJECTIVE The purpose of this study was to evaluate how changes in gestational weight and body composition affect infant birth weight and maternal fat retention after delivery in underweight, normal-weight and overweight women. STUDY DESIGN We assessed the body composition of 63 women (low body mass index, 17 women; normal body mass index, 34 women; and high body mass index, 12 women) on the basis of measurements of total body nitrogen by prompt-gamma activation analysis, total body potassium by whole body counting, and a multicomponent model based on total body water by deuterium dilution, body volume by densitometry, and bone mineral content by dual energy x-ray absorptiometry (DXA) before pregnancy, at 9, 22, and 36 weeks of gestation, and at 2, 6, and 27 weeks after delivery. Infant weight and length were recorded at birth; infant anthropometry and body composition by DXA were assessed at 2 and 27 weeks of age. RESULTS Gestational weight gain was correlated significantly with gains in total body water, total body potassium, protein, fat-free mass, and fat mass (P=.001-.003). Gains in total body water, total body potassium, protein and fat-free mass did not differ among body mass index groups; however, fat mass gain was higher in the high body mass index group (P=.03). Birth weight was correlated positively with gain in total body water, total body potassium, and fat-free mass (P<.01), but not fat mass. Postpartum weight and fat retention were correlated positively with gestational weight gain (P=.001) and fat mass gain (P=.001) but not with total body water, total body potassium, or fat-free mass gain. CONCLUSION Appropriate, but not excessive, gestational weight gain is needed to optimize infant birth weight and minimize maternal postpartum fat retention.

Human milk intake and growth in exclusively breast-fed infants

Milk intake and growth in 45 exclusively breast-fed infants were documented during the first 4 months of life. Energy and protein intakes were substantially less than current nutrient allowances. Energy intake declined significantly from 110 +/- 24 kcal/kg/day at 1 month to 71 +/- 17 kcal/kg/day at 4 months. Protein intake decreased from 1.6 +/- 0.3 gm/kg/day at 1 month to 0.9 +/- 0.2 gm/kg/day at 4 months. Infant growth progressed satisfactorily, compared with National Center for Health Statistics standards. A reevaluation of energy and protein intakes and allowances during infancy is merited.

Impact of weight loss on the metabolic syndrome

Aim: Individuals with the metabolic syndrome (MS), a clustering of risk factors [triglycerides, glucose, high‐density lipoprotein cholesterol, blood pressure (BP), abdominal obesity] defined by the National Cholesterol Education Program (NCEP), are at high risk for coronary heart disease and type 2 diabetes mellitus, and may benefit from aggressive lifestyle modification.

The Dynamics of Herpesvirus and Polyomavirus Reactivation and Shedding in Healthy Adults: A 14-Month Longitudinal Study

Humans are infected with viruses that establish long-term persistent infections. To address whether immunocompetent individuals control virus reactivation globally or independently and to identify patterns of sporadic reactivation, we monitored herpesviruses and polyomaviruses in 30 adults, over 14 months. Epstein-Barr virus (EBV) DNA was quantitated in saliva and peripheral blood mononuclear cells (PBMCs), cytomegalovirus (CMV) was assayed in urine, and JC virus (JCV) and BK virus (BKV) DNAs were assayed in urine and PBMCs. All individuals shed EBV in saliva, whereas 67% had >or=1 blood sample positive for EBV. Levels of EBV varied widely. CMV shedding occurred infrequently but occurred more commonly in younger individuals (P<.03). JCV and BKV virurias were 46.7% and 0%, respectively. JCV shedding was age dependent and occurred commonly in individuals >or=40 years old (P<.03). Seasonal variation was observed in shedding of EBV and JCV, but there was no correlation among shedding of EBV, CMV, and JCV (P>.50). Thus, adults independently control persistent viruses, which display discordant, sporadic reactivations.

Bone mineral changes in young women with hypothalamic amenorrhea treated with oral contraceptives, medroxyprogesterone, or placebo over 12 months

OBJECTIVES The objectives of this study were to assess (1) whether treatment with oral contraceptives, in comparison with medroxyprogesterone and placebo, improved bone mineral in women with hypothalamic amenorrhea and (2) whether treatment with medroxyprogesterone, in comparison with placebo, improved bone mineral in women with hypothalamic oligomenorrhea. STUDY DESIGN The study was a randomized, controlled clinical trial. Twenty-four white women, aged 14 to 28 years, with hypothalamic amenorrhea or oligomenorrhea were prospectively enrolled for a 12-month intervention period. Amenorrheic subjects were randomized to receive oral contraceptives, medroxyprogesterone, or placebo. Oligomenorrheic subjects were randomized to receive medroxyprogesterone or placebo. Bone mineral was measured by dual-energy x-ray absorptiometry at baseline and at 6 and 12 months. RESULTS In amenorrheic subjects spine and total body bone mineral measurements at 12 months were greater in the oral contraceptive group than in the medroxyprogesterone and placebo groups when baseline bone mineral measurements, body weight, and age were controlled for (p < or = 0.05). There were no differences in hip bone mineral calcium and bone mineral density measurements at 12 months among the three groups. In oligomenorrheic subjects there was no detectable improvement in bone mineral associated with medroxyprogesterone use. CONCLUSIONS This study supports the hypothesis that oral contraceptive use in women with hypothalamic amenorrhea will improve lumbar spine and total body bone mineral.

Longitudinal changes in milk composition of mothers delivering preterm and term infants

The concentrations of protein nitrogen (PN), non-protein nitrogen (NPN), energy, fat, sodium (Na), calcium (Ca), phosphorus (P), magnesium (Mg), and zinc (Zn) were determined in human milk from mothers giving birth to full-term (n = 13) and preterm infants (n = 8). Milk samples were collected under controlled conditions at two-week intervals for 12 weeks postpartum. Statistically significant differences in PN, Ca, and P concentrations were detected between the milk from mothers of preterm and term infants. The mean PN concentration in the preterm milk was statistically higher than that of term milk (198 vs. 164 mg N/dl), in contrast to the lower mean Ca (220 vs. 261 mg/l) and P (125 vs. 153 mg/l) concentrations detected in the preterm milk. No other differences in mean nutrient concentration were observed between the two groups. Concentrations of PN, NPN, Na, P, and Zn decreased over time. The concentration of Mg increased slightly. The content of fat, energy, and Ca did not change.

Ventricular function and long-term pacing in children with congenital complete atrioventricular block

Objective: To determine the sequela of right ventricular pacing in children with congenital complete atrioventricular block.

Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial

BACKGROUND Isoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial. OBJECTIVE Our aim was to test the effect of soy isoflavone supplementation on bone health. DESIGN A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg of soy hypocotyl aglycone isoflavones plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study subjects were tested annually and changes in whole-body and regional bone mineral density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in serum biochemical markers of bone metabolism were also assessed. RESULTS After study site, soy intake, and pretreatment values were controlled for, subjects receiving a daily supplement with 120 mg soy isoflavones had a statistically significant smaller reduction in whole-body BMD than did the placebo group both at 1 y (P < 0.03) and at 2 y (P < 0.05) of treatment. Smaller decreases in whole-body BMD T score were observed among this group of women at 1 y (P < 0.03) but not at 2 y of treatment. When compared with the placebo, soy isoflavone supplementation had no effect on changes in regional BMD, BMC, T scores, or biochemical markers of bone metabolism. CONCLUSION Daily supplementation with 120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow bone loss at common fracture sites in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.