Michio Numata

Systemic effects of transdermal testosterone for the treatment of microphallus in children

Abstract Objectives : To elucidate the metabolic effects of topical testosterone for the treatment of microphallus in children.

Effects of early intervention with inhaled sodium cromoglycate in childhood asthma

International and Japanese guidelines classify childhood asthma as mild, moderate, or severe, and recommend treatment with “as needed” bronchodilators, inhaled sodium cromoglycate, and inhaled corticosteroids, respectively. Alternatively, some investigators proposed inhaled corticosteroids as first-line therapy to prevent airway inflammatory obstruction. This article describes a clinical study assessing the effect of early intervention with inhaled sodium cromoglycate in childhood asthma. This was a retrospective study of 189 asthmatic children treated with inhaled sodium cromoglycate for five years and whose age of onset of asthma was six year of age or younger. An end-of-study questionnaire completed the examination. Children administered oral or inhaled corticosteroids simultaneously with sodium cromoglycate, were excluded. Asthma scores as defined by the Japanese Pediatric Allergic Committee, were reduced continuously during the five years after the start of sodium cromoglycate treatment. The frequency of emergency department visits and hospitalizations also decreased. Significant between-period intervention differences showed improvement of clinical outcomes for children with severe asthma during the five years of sodium cromoglycate inhalation. The early intervention regime of starting sodium cromoglycate inhalation within two years of the onset of asthma shows a large improvement in the long-term prognosis of childhood asthma, especially for children with severe asthma. It is possible that starting inhaled sodium cromoglycate earlier than the present recommendation of corticosteroids could further improve clinical outcomes, but a prospective study should be performed to verify our results.

Issues in interpreting lipoprotein (a) value as a risk indicator for early cardiovascular disease.

Sir, In their recent study comparing the plasma concentrations, distribution and frequency of lipoprotein (a) [Lp(a)] of children with premature parental and/or grandparental cardiovascular disease (CVD), Dirisamer, et al. (1) reported that it seemed possible to identify children who are at high risk for later CVD either with or without an elevated low-density lipoprotein (LDL) cholesterol level. Contrary to expectation, their data also showed a higher prevalence of increased Lp(a) ( 25 mg/dl) in the control group than in the risk group having a CVD family history; however, the reason for this could not be explained. Here we present our views regarding this point and discuss the issue of estimating Lp(a) values in children as a means of predicting future occurrence of CVD. First, permit us to point out the relationship between LDL particle size and Lp(a) levels. Since a reduction in LDL particle size is closely related to insulin-resistant states, which underlie the progression of atherosclerosis, a reduction in LDL particle size is considered a metabolic marker of insulin resistance (2, 3). In fact, it has been demonstrated that the prevalence of small dense LDL (SDLDL) particles (diameter 25.5 nm) in plasma is increased in patients with CVD, and SDLDL particles have been reported to be present even in children who suffer from obesity or hypertriglyceridemia (4). Persistence of insulin-resistant state from childhood to adulthood may be responsible for the subsequent occurrence of CVD. The relationship between LDL particle size and the Lp(a) levels in 238 schoolchildren aged 8–10 y in our birth cohort is shown in Fig. 1 (5). The method used to measure LDL size has been described in an earlier paper (4). As shown in the figure, the Lp(a) levels seemed to be inversely related to LDL particle size although statistically not significant, and an LDL particle size of less than 25 nm (the definition of small, dense LDL) was associated with a low range of Lp(a) values. Investigation of the relationship between LDL particle size and other atherogenic risk factors showed that body mass index (BMI) and triglyceride values were inversely correlated with LDL particle size and that highdensity lipoprotein (HDL) cholesterol level was positively correlated with LDL particle size. This means that Lp(a) levels do not reflect insulin-resistant metablic states well. Second, we will now touch on the polymorphism of Lp(a), because Lp(a) occurs in more than 10 polymorphic forms (phenotypes) that are dependent on the molecular weight of apolipoprotein(a), which is the main structural component of Lp(a). These polymorphic forms are determined by variations in the apo(a) gene on chromosome 6 (6) and in some reports it is suggested

Precocious Puberty Resulting from Congenital Hypothalamic Hamartoma: Persistent Darkened Areolae After Birth as the Hallmark of Estrogen Excess

C entral precocious puberty due to congenital hypothalamic hamartoma may cause isosexual precocity from early infancy. Failure to recognize the physical findings occasionally delays the diagnosis of the disease until the patient is more than 1 to 2 years old.14 This delay may reduce the patients potential for adult height because of remarkably advanced skeletal age that is induced by the bone-maturing action of estrogen.5-7 To emphasize the importance of early diagnosis of this disease, we present a patient in whom persistent darkened areolae from birth, a hallmark of estrogen excess, was overlooked.

High Density Lipoprotein Particle Size in Children: Relation to Atherogenic Dyslipidemia

Atherosclerosis begins in childhood. Protection from atherosclerosis is provided by high-density lipoprotein (HDL), a heterogeneous particle, which includes several subclasses differing in size, density and apolipoprotein content. The objective of this study was to document the relevance of assessing HDL particle size as another feature of dyslipidemia related to the develpment of atheosclerosis during childhood. For that purpose, HDL particle size in 268 community-based children (137 boys and 131 girls), 7–13 years old, was measured by gradient gel electrophoresis, and relationships of HDL particle size to plasma lipids parameters and the anthropometric indices were analyzed. There was no gender difference in HDL particle diameter. The results of analysis revealed significant positive correlations between HDL particle diameter and HDL-cholesterol level (r=0.363, p<0.01), apolipoprotein AI level (r=0.310, r<0.05) and low-density lipoprotein particle (LDL) size (r=0.290, p<0.05), while there was an inverse correlation with atherogenic index (r=–0.316, p<0.05). There was no significant correlation between HDL particle size and triglyceride levels in the overall analysis (n=268), however, when this relation was analyzed in the limited HDL size range below 11 nm, a significant inverse relation appeared between particle size and TG levels (r =–0.546, P<0.01, n=75). These findings indicate that the general shift toward smaller HDL particle size was associated with dyslipidemia characterized by higher atherogenic index and triglyceride level, lower HDL-C level and smaller LDL particle size. Therefore, HDL size may represent another relevant marker of atherogenic lipid metabolism.