Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.     

Quantitative evaluation of liver-specific promoters from retroviral vectors after in vivo transduction of hepatocytes

Hepatic gene therapy could be used to treat a number of inherited blood diseases such as hemophilia or thrombophilia. Although liver-directed retroviral transduction can result in long-term gene expression in vivo, the low level of protein production has limited its clinical application. We reasoned that the insertion of liver-specific promoters into retroviral vectors would increase gene expression in vivo. The 347- bp human alpha 1-antitrypsin (hAAT), the 810-bp murine albumin (mAIb), the 490-bp rat phosphoenolpyruvate carboxykinase (rPECK), and the 596- bp rat liver fatty acid binding protein promoters were inserted into a Moloney murine leukemia retroviral backbone containing the hAAT reporter gene. Vectors that produced appropriately sized RNA and hAAT protein in vitro were tested in vivo by transducing regenerating rat livers. Long-term serum expression of the hAAT reporter gene was normalized to retroviral transduction efficiency as determined by using a polymerase chain reaction-based assay of genomic DNA from transduced rat livers. The hAAT, mAIb, and rPEPCK promoters were, respectively, 35- , 8-, and 0.02-fold as strong as the previously studied constitutive Pol-II promoter. We conclude that the hAAT promoter resulted in the highest expression from a retroviral vector and may result in therapeutically significant expression of other clinically significant blood proteins.     

Association between fruit and vegetable intake and change in body mass index among a large sample of children and adolescents in the United States

OBJECTIVE: To assess whether intake of fruits and vegetables was associated with change in body mass index (BMI) among a large sample of children and adolescents in the United States. DESIGN: Prospective cohort study of children and adolescent who were 9-14 y of age in 1996, when the study began. SUBJECTS: The subjects included 8203 girls and 6715 boys in an ongoing cohort study who completed at least two questionnaires between 1996 and 1999. MEASUREMENTS: Fruit and vegetable intake was assessed in 1996-1998 with a validated food frequency questionnaire designed specifically for children and adolescents. The outcome measure was change in age- and gender-specific z-score of BMI (kg/m(2)). Self-reported weight and height, which were used to calculate BMI, were collected annually from 1996 to 1999. RESULTS: During 3 years of follow-up, annual changes in BMI were slightly greater among the boys than the girls. After controlling for Tanner stage of development, age, height change, activity and inactivity, which are known or suspected predictors of change in BMI, among the girls there was no relation between intake of fruits, fruit juice, or vegetables (alone or combined) and subsequent changes in BMI z-score. Among the boys, intake of fruit and fruit juice was not predictive of changes in BMI, however, vegetables intake was inversely related to changes in BMI z-score (beta per serving=-0.003). However, after adjusting for caloric intake, the magnitude of the effect was diminished and no longer significant. CONCLUSION: Our results suggest that the recommendation for consumption of fruits and vegetables may be well founded, but should not be based on a beneficial effect on weight regulation.     

Systematic review and meta-analysis of preterm birth and later systolic blood pressure

Lower birth weight because of fetal growth restriction is associated with higher blood pressure later in life, but the extent to which preterm birth (<37 completed weeks' gestation) or very low birth weight (<1500 g) predicts higher blood pressure is less clear. We performed a systematic review of 27 observational studies that compared the resting or ambulatory systolic blood pressure or diagnosis of hypertension among children, adolescents, and adults born preterm or very low birth weight with those born at term. We performed a meta-analysis with the subset of 10 studies that reported the resting systolic blood pressure difference in millimeters of mercury with 95% CIs or SEs. We assessed methodologic quality with a modified Newcastle-Ottawa Scale. The 10 studies were composed of 1342 preterm or very low birth weight and 1738 term participants from 8 countries. The mean gestational age at birth of the preterm participants was 30.2 weeks (range: 28.8-34.1 weeks), birth weight was 1280 g (range: 1098-1958 g), and age at systolic blood pressure measurement was 17.8 years (range: 6.3-22.4 years). Former preterm or very low birth weight infants had higher systolic blood pressure than term infants (pooled estimate: 2.5 mm Hg [95% CI: 1.7-3.3 mm Hg]). For the 5 highest quality studies, the systolic blood pressure difference was slightly greater, at 3.8 mm Hg (95% CI: 2.6-5.0 mm Hg). We conclude that infants who are born preterm or very low birth weight have modestly higher systolic blood pressure later in life and may be at increased risk for developing hypertension and its sequelae.     

Family Dinner and Disordered Eating Behaviors in a Large Cohort of Adolescents

We aimed to examine longitudinal associations between family dinner and disordered eating behaviors among adolescents. We studied 7535 females and 5913 males, 9 to 14 years of age in 1996. We performed multivariable logistic regression to assess the associations of previous year family dinner with 1-year incidence of each of 3 outcomes: purging, binge eating, and frequent dieting. Compared to those who ate family dinner “never or some days,” female adolescents who ate family dinner at least most days were less likely to initiate purging, binge eating, and frequent dieting. Estimates of association among males were similar in direction and magnitude, although lower frequency of the outcomes resulted in less precise estimates and fewer statistically significant results.