Samuel Matthew Alaish, M.D.

• Surgical Director, The Hopkins Resource for Intestinal Vitality and Enhancement (THRIVE)
• Associate Professor of Surgery

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0000115/Samuel-Alaish

The mechanisms underlying the race differences in bone geometry are still unknown cardiovascular disease nursing journal articles purchase 40 mg propranolol amex. However cardiovascular disease on the rise propranolol 20 mg without a prescription, when correcting for muscle size in this study cardiovascular guidelines propranolol 40 mg buy low cost, females have greater cortical area and total bone cross-section than males blood vessels valves in leg veins order on line propranolol. These differences in cortical dimensions probably confer greater bone strength to males cardiovascular outcomes definition cheap 40 mg propranolol free shipping. In an attempt to define the dietary vitamin D requirements for children and adolescents, the committee examined the evidence as it related to skeletal health, with primary outcomes being rickets prevention, calcium absorption, and bone mineral accrual. Notwithstanding, a higher than expected prevalence of children have circulating values < 50 nmol/L [74]. The prevalence of children ages 1­11 and 12­19 years with serum values < 50 nmol/L was 10% and 25%, respectively, with greater deficiencies observed in Hispanic and non-Hispanic blacks. In a study that took place in the southern (Georgia; latitude 34°N) and northern (Indiana; latitude 40°N) United States, 15% of children had values < 50 nmol/L, 6% had values < 40 nmol/L, and 1% had values < 30 nmol/L [5]. Based on standardized serum concentrations using the Vitamin D Standardization Program, a high percentage of children in this report had low vitamin D status with 37%­76% falling <50 nmol/L [86]. Latitude and Season Few foods provide natural sources of vitamin D, and fortification of foods with vitamin D is not practiced worldwide. It is important to note that this seasonal trend in vitamin D status is not restrictive to the wintertime months [93,95]. However, using a multiple logistic regression model and adjusting for age, race, gender, location, obesity, and education, income was no longer an independent predictor of vitamin D deficiency. When grouped by pubertal status, late pubertal adolescents have significantly lower mean values than prepubertal children (75 vs. The mechanism for the decreasing circulating vitamin D concentrations with increasing age and maturation is unknown. Further investigation is warranted to determine the mechanisms associated with declining serum vitamin D during pubertal growth and the health implications of these. Furthermore, the odds of having vitamin D concentrations <50 nmol/L was more than double for females versus males [75]. Obesity One area of vitamin D research that has escalated in recent years, particularly with respect to nonskeletal diseases, is its link with obesity. Obese children have been reported to have more skeletal fractures than nonobese children [105], and efforts to investigate the potential mechanisms have included examining vitamin D status. Additional intervention trials in obese children need to be conducted to better ascertain the responses to vitamin D supplementation. However, recent studies have shown that responses depend on individual and population differences, such as baseline status. However, in a recent pooled analysis of data from three sites including Indiana, Boston, and Texas, no inflection point could be determined [132]. Fractional Calcium Absorption Calcium absorption occurs by an active, carrier-dependent process and a passive, paracellular process. However, this homeostatic regulation mechanism is unable to correct for chronically low calcium intakes. Poor vitamin D status and low calcium intakes in adults lead to secondary hyperparathyroidism, which in turn increases bone remodeling and leads V. Because passive absorption is not vitamin D-dependent, high calcium intakes can mitigate reduced calcium absorption efficiency in the face of low vitamin D status. Low vitamin D status therefore becomes a risk for poor bone health when calcium intakes are low. The gaps in knowledge in children and adolescents involve the calcium intake needed to overcome vitamin D insufficiency and the roles of vitamin D status, among other regulators associated with reduced calcium absorption efficiency, when calcium intakes are low. Calcium absorption efficiency in children is determined in only a few laboratories worldwide. The best method for a double isotope tracer technique is where one calcium tracer is given by oral administration to determine absorption and adjusted for tracer dilution by a second intravenously administered tracer. A single oral isotope tracer method has been validated in adolescents against the double isotope reference methods [136]. Another method is net calcium absorption determined by metabolic balance, which necessitates controlled diets and complete urine and fecal collections. Conducting sequential blood draws following the calcium load allows for calculation of area under the curve. Despite the known role of vitamin D metabolites in calcium absorption pathways, there is little evidence that vitamin D supplementation enhances calcium absorption in clinical trials unless vitamin D status is very low. Conversely, when expressed as total calcium absorbed, the relationship appears positive [88]. Although the above data are meaningful, cross-sectional studies are unable to assign causal effects. In adults, calcium absorption increases when vitamin D status falls below 10 nmol/L [133]. Calcium absorption is influenced by an interaction of calcium intake and genetics, as well as diet. Biochemical Markers of Bone Turnover the difference between bone formation and resorption rates determines bone balance as shown in Table 41. No calcium kinetic studies have been undertaken in children to address the effect of vitamin D supplementation on true bone formation and bone resorption rates. In cross-sectional calcium kinetic studies in adolescents, vitamin D status has not predicted bone turnover rates [46,55,58]. However, the studies have been small and likely lacked statistical power to address the role of vitamin D on bone turnover (Table 41. Biochemical markers of bone turnover are more commonly used to assess bone formation and bone resorption rates because assays are readily available in commercial kits. Although they are correlated with bone formation and resorption rates determined by calcium kinetic studies, these measures are highly variable [139]. Consequently, when diet perturbs bone turnover as measured by kinetics, biochemical markers of bone turnover in the same study may be unable to show a statistically significant effect [46]. This finding reinforces the role of bone turnover as evaluated by biochemical markers in skeletal accretion. Furthermore, this required a larger sample size to find a small effect that was not apparent in the individual studies. Few studies have evaluated the relationships between vitamin D status and biochemical markers of bone turnover. Serum osteocalcin (a bone formation marker) concentrations in early pubertal girls were reported as 17. The conflicting results may relate to the use of different biochemical markers and their high variability, to confounding effects of pubertal status and sex, or to small sample sizes. To date, a relatively small number of prospective and intervention trials have assessed bone turnover in relation to vitamin D status. For example, in a 3-year prospective study in 9­15-year-old females, Lehtonen-Veromaa et al. As of this writing, eight intervention trials have assessed the impact of vitamin D supplementation on markers of bone turnover in children and adolescents [8,9,11,92,97,115,118,143]. Although data from the cross-sectional studies were mixed, results from the supplementation trials consistently reported no effect of supplementation on bone turnover. Over time, calcium retention determines bone acquisition because more than 99% of the calcium in the body is within the skeleton. Studies evaluating the effect of vitamin D status and supplementation on bone mass acquisition will be discussed in the next section. Metabolic balance studies, by necessity due to their intensive nature, involve a small number of study subjects. This limits their ability to determine predictors of calcium retention other than the primary intervention, for which statistical power was determined. A few predictors that indicate pubertal growth have such a large effect during puberty that they are significant in models predicting calcium retention, even in small metabolic studies. For example, postmenarcheal age was the best predictor in one study (explaining 10% of the variation) of calcium retention after the dietary intervention, calcium intake (15%), in adolescent white girls [144]. In a pooled analysis of metabolic studies in white and black adolescent girls, calcium intake explained 12. In 31 white boys ages 13­15 years, calcium intake (the intervention over the range of 670­2003 mg/day) predicted 21. This section will summarize key vitamin D and bone correlational, prospective observational, and intervention trials conducted to date and address some of the gaps in the current body of evidence. Few studies have been conducted in adolescent populations examining vitamin D status and bone mineral accrual over time. In both studies showing inverse relationships between vitamin D and skeletal outcomes [27,127], mean calcium intakes were approximately 600­900 mg/day, lower than consumed by the Finnish adolescents who had calcium intakes greater than 1300 mg/day [117]. Schools were randomized into three groups: (1) a carton of 330 mL milk fortified with Ca per school day, (2) a carton of 330 mL milk fortified with 5 or 8 mg cholecalciferol, and (3) control. N = 195 [Data were presented for the overall group who started the intervention (N = 181)] Sex: female Age: 10­12 years Race: Finnish, otherwise unspecified Location: Jyva¨skyla¨ and surrounding cities in Central Finland V. Population N = 179 [Data were presented for the overall group (N = 168)] Sex: female Age: 10­17 years Race: Lebanese, otherwise unspecified Location: Greater Beirut, Lebanon area N = 228 [Data were presented for the overall group (N = 212)] Sex: female Age: 11. This 1-year intervention with vitamin D3 (10 and 20 mg/day) included girls (10·1­14·7 years), women (18·1­ 52·7 years), and men (17·9­63·5 years) of Pakistani origin living in Denmark. N = 247 [Data were presented for the girls group only (n = 26)] Sex: male and female Age: 10­63 years Race: of Pakistani origin Location: Copenhagen area, Denmark N = 50 [Data were presented for the overall group (N = 50)] Sex: female Age: 14­15 years Race: Indian Location: Pune, India Khadilkar et al. N = 225 [Data were presented for the overall group (N = 225)] Sex: female Age: 10­11 years Race: Danish-born citizens, otherwise unspecified Location: Copenhagen and Frederiksberg, Denmark V. A randomized trial of vitamin D(3) supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption. Two of the trials identified a significant positive effect on skeletal outcomes but only in compliance-based analyses [117,151]. Subsequent analyses showed that the bone augmentation resulting from vitamin D supplementation was evident in girls who were within the transitional stages of pubertal development but not those who were early pubertal. Collectively, these intervention trials raise several questions with respect to skeletal responses to varying vitamin D inputs. Is there a specific serum vitamin D threshold associated with a positive bone response to supplementation Some of the inconsistencies observed in the aforementioned intervention trials may also be partially explained by gene-environment interactions [156­160]. This is particularly important in order to help better ascertain the mechanisms of this functional effect and to detect gene-environment interactions and potential interactions with other relevant gene polymorphisms. The robust relationship between muscle strength/size and bone strength in the growing skeleton has been well documented [161­164]. It is plausible that an alternative pathway by which vitamin D benefits bone development is facilitated through improvements in skeletal muscle and lean body mass during pubertal growth. Vitamin D deficiency in young children is not only associated with the classic deficiency disease, rickets, but also associated symptoms of muscle weakness and poor muscle function [165­167]. The exact mechanisms by which vitamin D acts on muscle cells and influences muscle function are unknown, though the process is likely mediated through both genomic and nongenomic pathways [169]. Evidence of rickets is unlikely to occur above 30 nmol/L and maximum calcium absorption likely occurs between 20 and 50 nmol/L. As future trials examine the effects of vitamin D on non-skeletal outcomes and in populations of children and adolescents that are considered unhealthy by way of nutritional deficiency or disease, monitoring safety of vitamin D supplements will become paramount. Unlike adults, vitamin D status over a wide range of concentrations is not associated with calcium absorption or retention in adolescents. Thus, criteria established for adults defining vitamin D deficiency, insufficiency, and sufficiency cannot be extrapolated to adolescents. Dose-response studies are needed in at-risk adolescents, including Hispanic or Latino/a and non-Hispanic black participants who are obese or have evidence of cardiometabolic abnormalities. In particular, there has been an escalation of vitamin D studies aiming to determine if poor vitamin D status contributes to insulin resistance and obesity. Race and sex differences in skeletal maturation have been identified, with skeletal size explaining much, but not all, of the differences. Regulators of genetically programmed body size dominate skeletal expansion during this life stage. Modifiable lifestyle factors play important roles in determination of peak bone mass, with calcium intake being the strongest predictor of skeletal calcium accretion in healthy adolescents. Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis. A randomized trial of vitamin D(3) supplementation in children: doseresponse effects on vitamin D metabolites and calcium absorption. Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in adolescents: results from a randomized controlled trial. Effect of vitamin D3 supplementation in black and in white children: a randomized, placebo-controlled trial. Conflicting reports on vitamin D supplementation: evidence from randomized controlled trials. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study. Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Incidence of childhood distal forearm fractures over 30 years: a population-based study. The role of estrogen in pubertal skeletal physiology: epiphyseal maturation and mineralization of the skeleton.

Adolescents cardiovascular nurse propranolol 80 mg buy line, particularly those with the benefits of formal education heart disease young adults names cheap 20 mg propranolol otc, tend to extend logical principles to increasingly diverse problems arteries used for angioplasty 20 mg propranolol purchase with mastercard. They can generate multiple logical possibilities systematically when faced with scientific experiments cardiovascular disease webmd 80 mg propranolol purchase mastercard, and they can also consider hypothetical problems cardiovascular examination cheap propranolol 20 mg amex. These principles of reasoning are applied not only to schoolwork but also to social situations. Assessing Cognitive Development the pediatric office assessment of cognitive ability in the preverbal child is best accomplished by observation of play. Beyond the toddler stage, the physician typically relies on conversation and language ability to assess levels of cognitive skill. Screening tests are particularly useful for determining whether cognitive and language skills are within the normal range. Children with language delays may need a formal nonverbal assessment of cognitive abilities by a psychologist. If a child does show delays in cognitive development, the physician should generate a differential diagnosis (Table 3. Pediatricians serve a critical role in referring children to early intervention or special education programs and in monitoring their progress. Active communication between the providers of early intervention and the physician assists a comprehensive and cohesive approach. Physicians frequently need the consultation of colleagues in psychology and education to assess the cognitive abilities of their older preschool and school-age patients. A 15-month-old child turns the key of the music box atop the mobile to make it play. Clearly, the child has a mental image of the event and uses it to generate the delayed imitation. As children develop the capacity for pure mental activity, they use objects to represent other objects or ideas. Genuine pretending begins; the child engages in playful representation of commonplace activities, using objects for their actual purpose but accompanied by exaggerated sounds or gestures. The next stage in development allows the child to plan pretend activities in anticipation of the play theme to come, combining many steps into the play. Preparing for play indicates an advance in pretending beyond that of improvising with the objects at hand. For example, the child might be seen preparing the play area or searching for needed objects and announcing what the objects are meant to represent. Development of Logical Thinking the preschool child has well-developed capabilities for mental representation and symbolic thinking. However, the dominance of sensory input, limited life experience, and a lack of formal education lead to a unique and charming logic during this period. A car and a tricycle, for example, may be seen as alive, perhaps because they are capable of movement. The logic of the preschooler is in large part influenced by the appearance of objects. Because an airplane appears to become smaller as it takes off, the preschooler may assume that all the people on the plane become smaller as well. Under certain circumstances a 4-year-old child may show understanding that a quantity remains invariant unless something is added or subtracted. That same child, however, may insist that two rows of pennies are different in number simply because of a compelling visual difference between them. The immature logic of the preschooler is gradually replaced by conventional logic and wisdom. School-age children follow logic akin to adult reasoning, at least when the stimuli are concrete. The 3- or 4-year-old child agrees that the two rows in A have the same number of pennies. After seeing the pennies moved into the configuration in B, the child claims that the top row has more because it is longer. Low scores may also reflect poor social adjustment or limitations in test-taking capabilities, such as sitting in a chair at a table and applying maximal effort to a task requested by an unfamiliar authority figure. Frequently, low scores result from a combination of difficulties in several areas. If children with sensory or motor impairments are tested with instruments normalized on able-bodied children, they often obtain low scores. A diversified and individualized assessment process should precede any educational recommendation. Language skills are subdivided into two realms: (1) receptive skills-the ability to comprehend communication, and (2) expressive skills-the ability to produce communication. Neonates demonstrate skills that are useful in the eventual development of receptive language abilities. Even before birth, fetuses detect sounds and show preferences for some sounds over others. At birth, the newborn is particularly attuned to the human voice and may turn toward a parent who is gently whispering. Frequent exposure to the native language alters speech perception such that by late infancy it becomes difficult for children to differentiate sounds that are not meaningful distinctions in their own language. Even in the early stages, children can establish reciprocal patterns, similar to the rhythm of conversation. By about 6 months old, children place consonant sounds with vowel sounds, creating what is known as babble. In this period, the infant says "ma-ma" or "da-da" without necessarily referring to the loving parent. A 3-month-old infant responds to interesting sounds by looking in the direction of the sound. Later Development In the second half of the first year, the child develops early skills in true receptive language. By 6 months old, children reliably respond to their names, and at about 9 months old, they can follow verbal routines, such as waving bye-bye or showing how big they are. At about the same age, they also learn that pointing shares the focus of attention. The young infant looks at the point, whereas the older infant looks at the object to which the point is directed. Receptive language can be demonstrated as children follow increasingly complex commands. For example, children will understand one-step commands such as "throw the ball" by approximately 1 year old. The labeling of commonplace items in pictures is slightly more complex and begins after 1 year old. By 30 months old, receptive language skills have advanced beyond the understanding of simple labels. Continued advances in receptive language occur during the preschool years and are highly susceptible to environmental stimulation or deprivation. Many 9- to 10-montholds can communicate that their juice or cereal is "all gone" by placing their hands palms up, at shoulder height. Even older children gesture to make themselves understood, because gross and fine motor skills develop faster than the oropharyngeal muscle skills used in articulation. After 18 to 24 months old, word usage increases rapidly, standard forms replace baby talk, and word combinations begin. This two-word phase has been called telegraphic speech because, like a telegram, the child leaves out nonessential articles and prepositions. Once the child is capable of three- and four-word utterances, length limitations do not appear to be a significant barrier. By age 3 the child has developed complex language with the use of pronouns and prepositions. However, it may be the effect rather than the cause, because in some children the frenulum of the tongue may be tight due to not being sufficiently exercised by early verbal practice. For children who want a particular food, for example, a point toward the cupboard door may not specify precisely what is wanted. Delays in the development of intelligibility might include any of the following: · Lack of intelligible speech by age 3 · Frequent omission of initial consonants after age 4 · Continued substitution of easy sounds for more difficult ones after age 5 · Persistent articulation errors after age 7 If any of these delays persist for 6 months or more, a referral should be initiated. During the period in which articulation and vocabulary are being mastered, speech dysfluencies are common. Noticeable stuttering or rapid speech beyond age 4 should prompt further attention. The problems of nasality, inaudibility, and unusual pitch sometimes may be helped by a speech pathologist. Furthermore, children of any age who are embarrassed by their speech are appropriate candidates for referral. Therapy for speech and language disorders helps improve the communication skills of children with language delays and problems of intelligibility. A child whose unusual language pattern is destined to be outgrown will not suffer from monitoring by a communication disorders specialist; the child whose language impairment will not be outgrown has much to lose when help is delayed. By age 5 the child uses all parts of speech, as well as clauses and complex sentences. The rate of language development appears to be associated with both biologic and environmental factors. About half or more of children with first-degree relatives with language and speech delays also show delays. The amount of child-directed speech in the environment is a good predictor of the rate of development for vocabulary and grammar. For this reason, health supervision of infants and toddlers should encourage parents to speak or read to their children. Mastering Intelligibility and Fluency Sounds required in language are mastered at different rates. Children who are attempting to say words containing sounds they cannot yet produce have a variety of choices on how to proceed: by omission of the difficult sound (ba for bottle), by substitution of a different sound (fum for thumb), or by distortion (goyl for girl). The social smile is another innate behavior, although it may not appear until 4 to 6 weeks of life. Infants with visual impairment who cannot appreciate a smile on the faces of their caregivers nonetheless smile at ages comparable with sighted children. Assessing Language Development In the early stages of prelinguistic and linguistic development, direct assessment by the pediatrician may be difficult. Children are likely to remain quiet in new situations, especially in the office where they received an injection. It is usually easy to engage a normally developing child of age 3 in conversations. Standardized parent reports are available for office use, and parental reports contribute to the assessment of language in screening tests. The differential diagnosis for delayed expressive language development includes impaired hearing, global developmental delay or intellectual disability, environmental deprivation, autism, emotional maladjustment, or specific language impairment. Keeping this in mind, worrisome clinical situations include the 4- to 6-month-old infant who fails to coo responsively, the 9- to 10-month-old child who does not babble or whose cooing and babbling have diminished, and the 18-month-old child whose repertoire of words includes only mama or dada. Beyond 18 months old, a convenient rule of thumb is that children 2 years old should use two-word utterances, at least half of which should be intelligible. By 3 years old, children should use phrases of three or more words, three-quarters of which should be intelligible. Children who fail to achieve these developmental milestones should undergo evaluation for hearing loss, as well as for cognitive and emotional impairment. Families often attribute language delays in their youngster to superficial and easily remediable physiologic or social factors. Infants develop a sense that their parents exist when out of sight sooner than they learn inanimate objects are permanent. As infants begin to recognize faces of familiar caregivers, they may squirm and cling in the company of unfamiliar people, exhibiting stranger awareness. Extreme reactions, known as stranger anxiety, may occur in children who have not had routine care from alternative caregivers. Pediatricians are advised to refrain from holding the 9- to 12-month-old child at the well-child visit. By 1 year of age, most children have experienced periods of separation from a parent, whether for minutes or hours. Infants who have developed a secure attachment to their parents show signs of recognition and pleasure when they are reunited with them. While progressing in gross motor development, the child initiates separation by walking away independently and exploring at greater distances from parents. Typically, infants return regularly for some verbal encouragement, eye contact, or hugging and then venture farther. In contrast, infants who have not developed secure attachments may show indifference, ambivalence, or disorganization at reunion with their parents. These children are at risk for troubled social relationships and difficulties achieving independence in functional domains (such as sleep) as they become older. At this age, rules are seen as variable, to be made and broken at the discretion of the players. For example, getting through a board game with preschoolers who decide not to follow the rules, once they discover that the rules are not working in their favor, is often a challenge. With superior logical capabilities, they realize that rules are invariant and must be followed regardless of the personal implications. As they progress through the elementary-school years, board games and sports become preferred activities for groups of peers. Development of Sense of Self Self-awareness and independence develop gradually throughout life.

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The high rates of bone mineral accrual and the ability of bone to alter its shape and geometry during childhood and adolescence provide a unique opportunity to intervene and potentially reduce the risk of fractures later in life coronary heart quilts buy 40 mg propranolol with visa. Data from one of the few long-term childhood bone studies support the idea of sustaining effects of lifestyle interventions on adult bone 2 cardiovascular diseases discount propranolol 80 mg visa, and because of the interdependency of calcium and vitamin D for the regulation of bone blood vessels from throwing up propranolol 40 mg low cost, more research is warranted to understand the impact of their interactions on bone heart disease vs cancer deaths generic propranolol 20 mg otc. When comparing white boys and girls in metabolic balance studies using a range in calcium intakes of 700­2100 mg/ day cardiovascular guidelines for fitness walking best 20 mg propranolol, boys were more efficient in skeletal calcium accretion than girls over the whole range of intakes by 171 ± 38 mg/day calcium retention [54]. In a similarly designed study, Asian boys retained more calcium than Asian girls on similar intakes [55]. In contrast, there were no sex differences in calcium retention in Mexican American adolescents [56]. In a similar study, black girls were shown to be more efficient than white girls in calcium retention across a wide range in calcium intakes [57]. Black versus white girls on the same calcium intake were shown to have increased calcium absorption, decreased urinary excretion, and greater bone formation rates [58]. Interestingly, Asian girls were shown to have even higher calcium absorption efficiency than black and white girls, especially at lower calcium intakes [55]. Does vitamin D status or supplementation play a role in modifying calcium metabolism during puberty beyond sex and racial differences Skeletal Accretion the prevalence of osteoporotic fractures differs by race and sex, where white and female groups characteristically experience more fractures than black and male groups, respectively V. Much of the research into sex and race differences in bone mass has focused on childhood and adolescence in an effort to verify if the divergence in bone masses among the race and sex groups occurs early in life and if these differences track into adulthood. For example, in boys and girls ages 8­18 years, black children had higher vertebral cancellous bone density than white children, specifically by late maturity [67]. From the existing data, it appears as though the greater bone strength in blacks versus whites is apparent in the cortical bone measures by the prepubertal years, and later maturity for the axial skeleton, and this greater bone strength persists into adulthood. Adolescent milk consumption, menarche, birth weight, and ethnicity influence height of women in Hawaii. Age at menarche and the evidence for a positive secular trend in urban South Africa. Growth and bone mineral accretion during puberty in Chinese girls: a five-year longitudinal study. A comparison of Asian Asian and American Asian populations: calcium and bone accretion during formation of peak bone mass. A longitudinal study of the relationship of physical activity to bone mineral accrual from adolescence to young adulthood. Nutrient intake in communitydwelling adolescent girls with anorexia nervosa and in healthy adolescents. Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche. Dairy versus calcium carbonate in promoting peak bone mass and bone maintenance during subsequent calcium deficiency. The reduction of physical activity reflects on the bone mass among young females: a follow-up study of 142 adolescent girls. Jump starting skeletal health: a 4-year longitudinal study assessing the effects of jumping on skeletal development in pre and circum pubertal children. Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial. International longitudinal pediatric reference standards for bone mineral content. Bone acquisition in healthy children and adolescents: comparisons of dual-energy x-ray absorptiometry and computed tomography measures. Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. Randomized trial of physical activity and calcium supplementation on bone mineral content in 3- to 5-year-old children. Dietary calcium requirements do not differ between MexicanAmerican boys and girls. Racial differences in skeletal calcium retention in adolescent girls with varied controlled calcium intakes. Daily supplementation with 25 micrograms of cholecalciferol does not increase calcium absorption or [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] skeletal retention in adolescent girls with low serum 25-hydroxyvitamin D. Calcium absorption measured by stable calcium isotopes ((42)Ca & (44)Ca) among Northern Chinese adolescents with low vitamin D status. Lack of insulin-like growth factor I exaggerates the effect of calcium deficiency on bone accretion in mice. Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study. Effects of sex, race, and puberty on cortical bone and the functional muscle bone unit in children, adolescents, and young adults. Comparisons of trabecular and cortical bone in late adolescent black and white females. Change in cortical bone density and its distribution differs between boys and girls during puberty. Importance of lean mass in the interpretation of total body densitometry in children and adolescents. Males have larger skeletal size and bone mass than females, despite comparable body size. A prospective analysis of plasma 25-hydroxyvitamin D concentrations in white and black prepubertal females in the southeastern United States. Difference in bone mass between black and white American children: attributable to body build, sex hormone levels, or bone turnover Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, El-Hajj Fuleihan G. Short-term, long-term safety of weekly high-dose vitamin D3 supplementation in school children. Childhood obesity is associated with increased risk of most lower extremity fractures. Vitamin D deficiency and childhood obesity: interactions, implications, and recommendations. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, Choucair M, Arabi A, Vieth R. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies Vitamin D levels in prepubertal children in Southern Tasmania: prevalence and determinants. Vitamin D insufficiency in adolescent males in Southern Tasmania: prevalence, determinants, and relationship to bone turnover markers. Effect of gender, puberty, and vitamin D status on biochemical markers of bone remodedeling. Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls. Wintertime vitamin D deficiency in male adolescents: effect on parathyroid function and response to vitamin D3 supplements. A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls ­ a cross-sectional study. Serum 25-hydroxyvitamin D concentrations in girls aged 4­8 y living in the southeastern United States. Sun exposure [96] [97] [98] [99] [100] [101] [102] [103] [104] [105] [106] [107] [108] [109] [110] [111] [112] [113] [114] V. Plasma concentrations of vitamin D metabolites in puberty: effect of sexual maturation and implications for growth. A positive dose-response effect of vitamin D supplementation on sitespecific bone mineral augmentation in adolescent girls: a doubleblinded randomized placebo-controlled 1-year intervention. Vitamin D supplementation to healthy children does not affect serum osteocalcin or markers of type I collagen turnover. Association of low 25-hydroxyvitamin D concentrations with elevated parathyroid hormone concentrations and low cortical bone density in early pubertal and prepubertal Finnish girls. Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density. Risk factors for low serum 25-hydroxyvitamin D concentrations in otherwise healthy children and adolescents. Low levels of 25-hydroxy vitamin D are associated with elevated parathyroid hormone in healthy adolescent females. An inflection point of serum 25-hydroxyvitamin D for maximal suppression of parathyroid hormone is not evident from multi-site pooled data in children and adolescents. Clinical approaches for studying calcium metabolism and its relationship to disease. Simple isotopic method using oral stable or radioactive tracers for estimating fractional calcium absorption in adult women. Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty. Quantification of biochemical markers of bone turnover by kinetic measures of bone formation and resorption in young healthy females. Low vitamin D status has an adverse influence on bone mass, bone turnover, and muscle strength in Chinese adolescent girls. Effects of usual nutrient intake and vitamin D status on markers of bone turnover in Swiss adolescents. Vitamin D and attainment of peak bone mass among peripubertal Finnish girls: a 3-y prospective study. Bone turnover is not influenced by serum 25-hydroxyvitamin D in pubertal healthy black and white children. Calcium retention in relation to calcium intake and postmenarcheal age in adolescent females. Vitamin D status and its relationship to body fat, final height, and peak bone mass in young women. Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial. Vitamin D supplementation and bone mass accrual in underprivileged adolescent Indian girls. School-milk intervention trial enhances growth and bone mineral accretion in Chinese girls aged 10­12 years in Beijing. Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebocontrolled intervention study. Vitamin D receptor gene polymorphisms modulate the skeletal response to vitamin D supplementation in healthy girls. Vitamin D receptor start codon polymorphism (FokI) is related to bone mineral density in healthy adolescent boys. Vitamin D receptor gene polymorphism is related to bone density, circulating osteocalcin, and parathyroid hormone in healthy adolescent girls. Vitamin D receptor gene start codon polymorphism (FokI) is associated with forearm bone mineral density and calcaneal ultrasound in Finnish adolescent boys but not in girls. Vitamin D receptor gene Fok1 polymorphism predicts calcium absorption and bone mineral density in children. Peak lean tissue mass accrual precedes changes in bone strength indices at the proximal femur during the pubertal growth spurt. The development of the skeletal system in children and the influence of muscular strength. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Estimation of the dietary requirement for vitamin D in healthy adolescent white girls. Adequacy of vitamin D intakes in children and teenagers from the base diet, fortified foods and supplements. Vitamin D intakes of children differ by race/ethnicity, sex, age, and income in the United States. Vitamin D and bone mineral density status of healthy schoolchildren in northern India. Intestinal calcium absorption doubles during pregnancy, whereas skeletal resorption predominates during lactation. These adjustments enable the mother to meet her own needs as well as those of the fetus and infant without requiring increased intake of calcium, and without long-term adverse effects on the maternal skeleton. In addition to human data from observational studies, clinical trials, and associational studies, this chapter also relies on data from animal models of disrupted vitamin D physiology. The focus is on maternal physiology and outcomes; the related subjects of fetal and neonatal outcomes are addressed in Chapter 39. For a more detailed discussion and extensive citation of primary literature, the reader is directed to two recent comprehensive reviews about pregnancy and lactation [1] and fetal and neonatal development [2]. The magnitude of demand can be appreciated as the amount of mineral present in the average human skeleton at term, specifically 30 g of calcium, 20 g of phosphorus, and 0. The thickness of arrows indicates a relative increase or decrease with respect to the normal and nonpregnant state.

Decreased or absent steroid sulfatase activity during fetal life may result in decreased placental estrogen and a delay in onset of maternal labor blood vessels visible on face cheap 20 mg propranolol with visa. X-Linked Ichthyosis X-linked ichthyosis occurs in 1 in 6000 males as a result of a mutation in the enzyme steroid sulfatase capillaries exchange what purchase 80 mg propranolol with mastercard, although findings are occasionally present in hemizygous female carriers capillaries wall thickness best purchase for propranolol. The central face and Lamellar Ichthyosis Lamellar ichthyosis is a rare autosomal dominant disorder occurring in fewer than 1 in 250 cardiovascular disease powerpoint discount propranolol 40 mg on-line,000 births as a result of a mutation in keratinocyte transglutaminase-1 arteries elasticity and contractility generic propranolol 40 mg buy online. During the first month of life, thick, brownish gray, sheet-like scales with raised edges appear. B, Thick tenacious scale on a red base extends from the forehead to the scalp of this 10-year-old girl. D, In this child, lesions are prominent over the pressure point of the knee and the distal fingers. E, the skin of the palms is markedly thickened, with silvery fissuring of the palmar creases. Removal of the thick scale from a psoriatic plaque produces small points of bleeding from tortuous capillaries. Small droplike plaques with typical scales quickly developed in a generalized distribution in this child following streptococcal pharyngitis. Microscopically, these disorders are characterized by infiltration of the dermis with inflammatory cells, edema, variable thickening of the epidermis, and scaling. Some improvement of the scaling occurs with age, and topical keratolytics (such as lactic acid and salicylic acid) may provide some benefit. Severe cases may respond to the administration of systemic retinoids, but it is important to note that these are known to be teratogenic and should only be given with careful monitoring by an experienced expert in ichthyosis and assurance of patient compliance with contraception. Atopic Dermatitis Atopic dermatitis is one of the most common and stressful of all chronic skin disorders in children. It is now known that mutations in filaggrin, in addition to causing ichthyosis vulgaris, cause the barrier dysfunction, which is characteristic of atopic dermatitis in about 50% of patients. Atopic dermatitis can be divided into three general phases on the basis of the age of the patient, but it is worth noting that these stages may overlap in any given patient. The infantile phase of atopic dermatitis begins between birth and 6 months old and lasts about 2 or 3 years. Characteristically, the rash is manifest by erythematous, pruritic papules, and plaques that ooze and crust. Many infants with atopic dermatitis have overlapping seborrheic dermatitis of the scalp and/ or intertriginous areas, such as the neck folds. Histologically, massive hyperkeratosis is associated with ballooning of squamous cells and formation of microvesicles. The mainstay of treatment includes use of keratolytics, lubricants, and antibiotics for secondary infection, which is common and usually caused by Staphylococcus aureus. It also underscores the importance of comprehensively treating these patients not just for their visible skin findings but also for their systemic and behavioral comorbidities. Remission may occur at any time, or the disorder may evolve into a more chronic type of adult dermatitis. Of children with atopic dermatitis, 75% improve between the ages of 10 and 14; the remaining children may go on to develop chronic dermatitis. The adult phase of atopic dermatitis begins around age 12 and continues indefinitely. Eruptions are sometimes seen on the dorsal surfaces of the hands and feet and between the fingers and toes. B, Flexural involvement helps differentiate lamellar ichthyosis from ichthyosis vulgaris. C, Ectropion (note the eversion of the lower lids) is a unique finding in this form of the disorder. B and C, Involvement of the trunk and the extremities, with erythema, scaling, and crusting, is evident. In childhood, eczema involves the flexural surfaces of the upper and lower extremities. A, A 10-year-old atopic child has lichenification of the skin over the dorsum of his fingers and "buff" nails from chronic rubbing. As a result of their altered immunity in the skin, more than 90% of patients with atopic dermatitis are colonized with S. Parents of children with eczema who themselves have recurrent herpes simplex lesions should be taught hygienic techniques that reduce the risk of transmitting the virus, even when asymptomatic, because shedding can still occur to their children. Consideration can be given to daily suppressive therapy for parents of children with severe atopic dermatitis. In the rash of pityriasis alba, which is common in patients with atopic dermatitis, inflammatory changes are minimal. These patches fail to enhance with Wood lamp examination, which distinguishes them from vitiligo. Lesions are more prominent in children with dark skin and are more noticeable during spring and summer, because they do not tan like surrounding skin after sun exposure. The etiology is unknown, but it is clearly more common in children with an atopic diathesis. Because the disorder is usually asymptomatic and spontaneously resolves in several months to a few years, treatment is usually unnecessary, although moisturizers may help reduce surface scaling. Often parents are most concerned cosmetically with the hypopigmentation; so if the condition does not resolve with emollients alone, then it can be helpful to add a prescription topical immunomodulatory, such as pimecrolimus cream or tacrolimus ointment. An immunologic etiology is suggested by the chronic elevation of immunoglobulin E (IgE) seen in a majority of patients. Atopic dermatitis does occur in families in association with other atopic conditions in the atopic triad, including asthma, allergic rhinitis, and food allergies, as well as eosinophilic esophagitis, suggesting some degree of genetic predisposition. Erythematous excoriated plaques with indistinct borders are seen in the antecubital areas. In addition, this patient demonstrates significant postinflammatory hyperpigmentation. A, Diffuse fine follicular papules and sandpaper scaling are seen on the extensor surface of the arm of this adolescent. B, In this 5-year-old boy, characteristic white follicular papules are more widely spaced and more prominently seen on the extensor surface of his thighs and upper arms. The resultant scratching leads to the acute and chronic changes typical of atopic dermatitis. The differential diagnosis of atopic dermatitis includes seborrheic dermatitis, contact dermatitis, pityriasis rosea, psoriasis, fungal infections, Langerhans cell histiocytosis, and acrodermatitis enteropathica. It can be distinguished from seborrheic dermatitis on the basis of the distribution of lesions and associated pruritus; atopic dermatitis tends to spare moist, intertriginous areas (such as the axillae and perineum), where seborrheic dermatitis is more prominent in these locations. Exposure history and distribution help differentiate it from contact dermatitis, as does the discreteness of lesions and their distribution in pityriasis rosea. The thick, silvery scale and Koebner phenomenon help distinguish psoriasis, and central clearing with an active border of red papules, vesicles, and/or pustules helps differentiate tinea corporis. In some atopic individuals, subtle inflammation may result in the development of poorly demarcated, hypopigmented patches that are covered by a fine superficial scale. The acral and periorificial distribution of lesions and gastrointestinal symptoms help in distinguishing eczema from acrodermatitis enteropathica. The mainstays of atopic dermatitis treatment are elimination or avoidance of predisposing factors; hydration and lubrication of the skin; the use of antipruritic agents to relieve itching, break the itch/ scratch cycle, and normalize sleep patterns; and the intermittent use of topical steroids to further relieve itching and decrease inflammation. Pimecrolimus cream and tacrolimus ointment are two agents in the class of nonsteroidal topical immunomodulators that may also dramatically interrupt the itch/scratch cycle. They have been approved as second-line therapy for the management of atopic dermatitis in children older than 2 years old. Use of these agents should be accompanied by an explanation of the boxed warning regarding the theoretical risk of lymphoma and skin cancer. However, these tumors have been seen only with prolonged systemic use at very high doses and true risk has not been associated with the use of the topical preparations in otherwise healthy children. All children with atopic dermatitis should be monitored closely for secondary bacterial infection, which must be treated promptly with topical or systemic antibiotics to prevent progression to cellulitis. The use of a hyperdiluted bleach (1 to 2 ounces in a 30-gallon tub of water) bath several times per week is a cost-effective way of preventing infection in patients with atopic dermatitis. Further, patients should be treated with antiviral agents at the first sign of infection with herpes simplex. Dyshidrotic eczema and nummular eczema are clinical patterns of atopic dermatitis, and juvenile palmoplantar dermatosis and liplicking and thumb-sucking eczema represent irritant dermatitides that may be associated with atopic dermatitis. Chronic cracking, oozing, and scaling develop after the initial tiny pruritic vesicles have been scratched. This variant of atopic dermatitis is usually localized to the plantar surfaces of the toes and feet. Dyshidrotic Eczema Dyshidrotic eczema is a severely pruritic, chronic, recurrent, vesicular eruption affecting the palms, soles, and lateral aspects of the fingers and toes. Characteristically, the vesicles are symmetrical, multilocular, and 1 to 3 mm in diameter and have been described as "tapioca" papules, lichening them to the lumps in tapioca pudding. Pathologically, this eruption demonstrates spongiotic vesicles and normal eccrine sweat glands. The cause is unknown; however, frequent exposure to water, wet or sweat-soaked shoes, or chemicals (on the hands) may trigger or exacerbate the condition. Hyperhidrosis, or excessive sweating of the palms and soles, may also play a role. Treatment is similar to that for acute atopic dermatitis, although often a higher potency topical steroid may be needed to abort the flare of dyshidrotic eczema. Although the rash is often resistant to therapy, it may respond to the treatment for acute dermatitis outlined previously. Juvenile Plantar/Palmar Dermatosis Juvenile plantar/palmar dermatosis ("sweaty sock syndrome") is common in toddlers and school-age children. The pads of the fingertips and palms may be involved as well, although less severely. Some children experience flares in the summer, whereas in others the flares occur in winter. Consequently, the mainstay of treatment consists of emollients for prevention and occasional application of topical steroids when intense inflammation is present during flares. Nummular Eczema Nummular eczema is an acute papulovesicular eruption named for its annular or coin-shaped configuration and probably also represents another clinical pattern found in atopic individuals. A, Round- to oval-shaped lesions studded with tiny vesicles are typically located over the extensor thighs or abdomen. The perioral skin is inflamed, scaly, and thickened as a result of repetitive licking of the lips. In infants and young children, atopic dermatitis can have a greasy, scaly appearance and can have overlapping features with seborrhea. However, infantile atopic dermatitis produces intense pruritus and invariably spares moist sites, such as the diaper area and axillae. The differential diagnosis of seborrhea includes Langerhans cell histiocytosis (in which the rash is more generalized, in part petechial, and can be associated with chronic draining ears and hepatosplenomegaly) and tinea corporis (in which lesions usually are more circumscribed, with an active border and central clearing). Scalp lesions may be difficult to differentiate from psoriasis, and in fact there seems to be a spectrum of presentation from mild scaling in seborrhea to moderate scaling in what is termed sebopsoriasis to much more thick and resistant scaling in full-fledged psoriasis. Lip-licking eczema can be the result of a habit or can be a manifestation of anxiety, and sources of stress should be explored on history taking. Once the process begins, it can become a vicious cycle as the child licks with increasing frequency to moisten the dry skin. Job Syndrome Job syndrome, or hyper-IgE syndrome, is a rare genetic disorder with prominent cutaneous manifestations. Affected patients have chronic eczema, recurrent staphylococcal infections, retained primary teeth, hyperextensible joints, fractures, and coarse facial features, including a broad nose. They also have variably but significantly elevated levels of serum IgE and circulating eosinophils. Dermatologic features include a pruritic dermatitic rash that shares features with both atopic dermatitis and seborrhea, which tends to develop shortly after birth (earlier than seborrhea and atopic dermatitis). In contrast to furuncles in patients with a normal immune response, the abscesses in children with Job syndrome are termed "cold," meaning they cause little pain and show few signs of inflammation. Other clinical manifestations include recurrent/chronic infections, such as bronchitis, pneumonia (with pneumatoceles), sinusitis, otitis, gingivitis, dental abscesses, septic arthritis, and osteomyelitis. Decreased bone density is the source of multiple fractures, which cause remarkably little pain. Seborrhea Seborrheic dermatitis is characterized by erythema and scaling predominantly on hair-bearing and intertriginous areas, such as the scalp; eyebrows; eyelashes; perinasal, presternal, and, postauricular areas; and the neck, axillae, and groin. In adolescents, the dermatitis may manifest as dandruff or flaking of the eyebrows, postauricular areas, or flexural areas. Although the pathogenesis of seborrheic dermatitis is unknown, Pityrosporum and Candida species have been implicated as causative agents. A role for neurologic dysfunction is suggested by the increased incidence and severity in neurologically impaired individuals. Pityriasis Rosea Pityriasis rosea is a benign, self-limited disorder that can occur at any age but is more common in adolescents and young adults. A prodrome of malaise, headache, and mild constitutional symptoms occasionally precedes the rash but is not crucial for diagnosis. On occasion, lesions predominate on the face, groin, and/or distal extremities, including the palms and soles, a phenomenon known as inverse pityriasis, which is more common in AfricanAmerican patients. Pityriasis lesions begin as small, oval to round papules that enlarge to oval plaques up to 1 to 2 cm in size, with a scaly surface. They are usually somewhat raised but can be macular, and they can be erythematous, hyperpigmented, or hypopigmented. Repeated wetting and drying from persistent thumb sucking result in eczematoid changes with cracking, fissuring, and lichenification.

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