bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I/II Evaluation of Stavudine (d4T) in Children With Human Immunodeficiency Virus Infection
Authors: Kline Mark W. , Dunkle Lisa M. , Church Joseph A. , Goldsmith Jonathan C. , Harris Alice T. , Federici Marianne E. , Schultze Mary E. , Woods Lin , Loewen Diane F. , Kaul Sanjeev , Cross Anne , Rutkiewicz Victoria L. , Rosenblatt Howard M. , Hanson I. Celine , Shearer William T. 
Published: December 2021

Objectives. To determine the pharmacokinetic properties, tolerance, safety, and preliminary activity of stavudine in human immunodeficiency virus (HIV)-infected children.
Design. Phase I/II, open and dose-ranging (0.125 to 4 mg/kg/day in two divided doses).
Patients. Thirty-seven HIV-infected children (median age, 5.5 years; range, 7 months to 15 years) with a median CD4+ lymphocyte count at baseline of 242 cells/µL (range 2 to 2290 cells/µL). Thirty children had symptomatic HIV disease at entry; seven had HIV-related immunosuppression alone. Twenty-nine subjects had a history of prior zidovudine (ZDV) therapy.
Results. As compared with adults receiving the same weight-adjusted doses, the children we studied had lower maximum observed stavudine plasma concentrations (CMAX) and area under the plasma concentration versus time curves (AUC), and more rapid stavudine elimination. The absolute oral bioavailability of the drug ranged from 61% to 78%. There was no plasma accumulation of the drug between day 1 and week 12. Week 12 cerebrospinal fluid stavudine concentrations in seven subjects, obtained approximately 2 to 3 hours after oral doses, ranged from 16% to 97% of concomitant plasma concentrations.
Stavudine was well-tolerated and there were no dose-related clinical or laboratory adverse events. One subject with baseline neurologic abnormalities experienced a transient episode of apparent pain or discomfort in her fingers, possibly related to stavudine. All other adverse events were attributed to underlying disease. Stavudine activity, measured indirectly by CD4+ lymphocyte count and serum p24 antigen concentration changes, was observed in some subjects. Progression of HIV disease and survival correlated with prior ZDV therapy, HIV disease classification, baseline CD4+ lymphocyte count, and weight growth velocity.
Conclusions. Stavudine appears to hold promise for the treatment of HIV infection in children. Its pharmacokinetic properties are consistent and predictable, and it appears to be remarkably well-tolerated and safe. Although our study was not designed to assess the drug's efficacy, preliminary clinical and laboratory evidence of activity was observed.
Evaluation of a Subsidy Program to Increase Bicycle Helmet Use by Children of Low-Income Families
Authors: Parkin Patricia C. , Hu Xiaohan , Spence Laura J. , Kranz Katherine E. , Shortt Linda G. , Wesson David E. 
Published: December 2021

Objective. We have previously shown that an educational program was not effective in increasing bicycle helmet use in children of low-income families. The objective of this study was to evaluate a combined educational and helmet subsidy program in the same population, while controlling for secular trends. The secondary objective was to complete a third year of surveying children's bicycle helmet use throughout the study community.
Design. A prospective, controlled, before-and-after study.
Subjects. Bicycling children 5 to 14 years of age from areas of low average family income.
Setting. A defined geographic community within a large urban Canadian city.
Intervention. In April 1992, students in three schools located in the area of lowest average family income were offered $10 helmets and an educational program; three other low-income areas served as control areas.
Main Outcome Measure. Helmet use was determined by direct observation of more than 1800 bicycling children.
Results. Nine hundred ten helmets were sold to a school population of 1415 (64%). Reported helmet ownership increased from 10% to 47%. However, observed helmet use in the low-income intervention area was no different from the rate in the three low-income control areas (18% versus 19%). There was no difference in the trend in helmet use during the period of 1990 through 1992 in the intervention area (4% to 18%) compared with the control areas (3% to 19%). Helmet use rates from all income areas have increased from 3.4% in 1990, to 16% in 1991, to 28% in 1992. In 1992, helmet use in the high-income areas was 48% and in the low-income areas was 20%.
Conclusions. There has been a trend toward increasing helmet use in all income areas during the 3-year period. Despite encouraging helmet sales and increases in reported helmet ownership, the results of the observational study do not support the efficacy of a helmet subsidy program in increasing helmet use in children residing in areas of low average family income. Strategies to increase helmet use in children of low average family income remain a priority.
Implementation of the Immunization Policy (S94-26)
Authors:   Committee on Practice and Ambulatory Medicine, 1994 to 1995
Published: December 2021

Prevention of disease through immunization always has been a priority for pediatricians and a major goal of comprehensive pediatric health care. Before 1994, the recommendation of the American Academy of Pediatrics (AAP) was that children should be completely immunized against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b disease, measles, mumps, and rubella. Universal hepatitis B immunization of all infants and adolescents was recommended in the 1994 Red Book,1 adding a ninth disease to the previous list. Only those children with specific contraindications to one or more of the immunizations should be excluded. Childhood immunizations, per the AAP recommended schedule, must continue to be an essential component of continuous, comprehensive child health care. Furthermore, a child's immunization status warrants evaluation at every health care visit.
In recent years, inadequate immunization rates attributed to multiple causes have indicated that the Academy's original immunization policy (1977) calling for universal immunization of all children has not been fulfilled. From data collected in the National Health Interview Survey in 1993 and 1994, the Centers for Disease Control and Prevention (CDC)2 currently estimates that only about two thirds of 2-year-old children in the United States have received all appropriate immunizations. Vaccine coverage levels include the following ranges: 67% coverage for four doses of diphtheria, tetanus, and pertussis (DPT) vaccine; 76% for three doses of oral polio vaccine (OPV); 90% for one dose of measles, mumps, and rubella vaccine (MMR), and 71% for age-appropriate doses of H influenzae type b vaccine. Recent outbreaks of measles, particularly in preschool children but also in adolescents and young adults, attest to inadequate protection and demonstrate a continuing need for surveillance and modification of current immunization recommendations.
ISOLATION OF A NOVEL GENE MUTATED IN WISKOTT-ALDRICH SYNDROME
Authors: Meer Sanober , Liu Andrew 
Published: December 2021

Purpose of the Study. Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder associated with severe thrombocytopenia, eczema, bloody diarrhea, B & T cell immunodeficiency and increased risk of malignancies. This study describes the isolation of a novel gene, WAS Protein (WASP) which is mutated in four WAS patients.
Methods. The WAS gene had been localized previously by linkage analyses to a &gt;1 Megabase region in chromosome Xp11.22-p11.23. To isolate the WAS gene, a clone contig was constructed in this interval, followed by isolation of cDNA sequences.
Results. A novel gene, WASP, was isolated, which is believed to be the main genetic locus in WAS. This is supported by the following findings. First, the gene was isolated from the chromosome Xp11.22-p11.23 interval previously identified as containing the WAS gene. Second, lymphoblasts from two unrelated patients clinically diagnosed with WAS failed to express WASP on Northern blots. Two additional WAS patients were also found to have point substitution mutations of an arginine residue. Finally, WASP is expressed in lymphocytic and megakaryocytic cell lineages, indicating a close correlation between tissue-specific gene expression and the disease manifestations of WAS.
Reviewer's Comments. This paper succinctly describes a major breakthrough in the identification of the defective gene in WAS, which is found to be mutated in the four WAS patients studied. This finding brings direction and impetus to research on WAS, provides improved methods for detecting WAS, and brings the possibility of gene replacement therapy for WAS much closer.
The Value of Brain Imaging in Children With Headaches
Authors: Maytal Joseph , Bienkowski Robert S. , Patel Mahendra , Eviatar Lydia 
Published: December 2021

Objective. To determine the value of performing computed tomography (CT) or magnetic resonance imaging (MRI) studies in children with chronic headaches.
Background. Headache is a common complaint in children, With the proliferation of brain imaging centers and the increasing patient demand for CT or MRI studies, brain imaging has become widely used to evaluate headaches.
Methods. A retrospective chart review was conducted of all children referred to the pediatric neurology clinic for evaluation of headaches over a 2-year period. Charts were reviewed for headache characteristics, clinical indications for performing CT and MRI studies, and imaging results. Particular attention was paid to evidence of brain tumors, vascular anomalies, or hydrocephalus.
Results. A total of 133 records were studied. Subjects ranged in age from 3 to 18 years. Most patients were diagnosed as having either vascular migrainous headaches (52%) or chronic tension headaches (21%). Other headache diagnoses were mixed tension-migraine, psychogenic, and post-traumatic. Headaches were unclassified in 25 patients (19%). Seventy-eight patients (59%) had brain imaging: 45 had MRI, 27 had CT, and 6 patients had both. In most cases, brain imaging studies were performed in patients with atypical headache pattern, presence of neurologic abnormalities during the headache, general symptoms (ie, weight loss or fatigue), or because of parents' or doctors' concerns about brain tumors. Cerebral abnormalities were found on brain imaging in four patients, but none indicated the presence of a treatable disease and all were deemed unrelated to the presenting complaint. Our findings of no relevant abnormalities in a series of 78 brain imaging studies indicate that the maximal rate at which such abnormalities might appear in this population is 3.8%.
Conclusions. These results indicate that brain imaging studies have very limited value in evaluating headaches in pediatric patients without clinical evidence of an underlying structural lesion.
ON SALE NOW AT YOUR HMO: ORGAN TRANSPLANTS DISCOUNT FEVER IS HITTING THE HIGH END OF MEDICINE: THE ORGAN-TRANSPLANT BUSINESS
Authors: L. J. F. 
Published: December 2021

Renowned transplant centers such as the Cleveland Clinic, Duke University, and Johns Hopkins are cutting rates for procedures and follow-up treatments by 30% to 60%. The centers figure that cheaper prices will help them win big contracts with health-maintenance organizations (HMOs) and other powerful insurers that mandate where their millions of members can go for care.
Hospitals often discount their bills by about 20% for their biggest customers. But HMOs lately have been winning much steeper markdowns on fixed-price contracts that cover nearly all the expenses associated with organ transplants.
See Table in the PDF File
The Issues of Hyperbilirubinemia
Authors: Seidman Daniel S. , Stevenson David K. 
Published: December 2021

"Tis with our judgments as our watches, none go just alike, yet each believes his own."
Alexander Pope
An Essay on Criticism, 1711.
The practice parameter published recently by the American Academy of Pediatrics Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia1 introduces clearly the major points for which a consensus exists between experts:
1. "Factors influencing bilirubin toxicity to the brain cells of newborn infants are complex and incompletely understood."
2. "It is not known at what bilirubin concentration or under what circumstances significant risk of brain damage occurs or when the risk of damage exceeds the risk of treatment."
Comparison of 13 Acellular Pertussis Vaccines: Overview and Serologic Response
Authors: Edwards Kathryn M. , Meade Bruce D. , Decker Michael D. , Reed George F. , Rennels Margaret B. , Steinhoff Mark C. , Anderson Edwin L. , Englund Janet A. , Pichichero Michael E. , Deloria Maria A. , Deforest Adamadia 
Published: December 2021

Objective. To compare the immunogenicity of a licensed conventional whole-cell (WCL) and 13 diphtheria-tetanus-acellular pertussis (DTaP) vaccines that differed in source, method of manufacture, and included antigens; all vaccines included diphtheria and tetanus toxoids.
Methods. Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Sera were obtained before the first immunization and 1 month after the third immunization and were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxins. Chinese hamster ovary cell toxin neutralization assays were performed, and levels of agglutinating antibodies were determined.
Results. Of 2342 infants enrolled, 1942 contributed usable preimmunization and postimmunization serum specimens. Each vaccine produced significant increases in antibodies directed against the included antigens; postimmunization antibody titers differed significantly among the DTaP vaccines. For each evaluated antigen, the majority of DTaP vaccines produced antibody responses that equaled or exceeded those produced by WCL. For some antigens (eg, PT), mean antibody levels by vaccine correlated poorly with the quantity of antigen included in each vaccine; for others (eg, fimbriae), there was a close correlation.
Conclusion. Although serologic correlates of pertussis immunity are not defined, it is clear that DTaP vaccines can stimulate immune responses that exceed those of licensed whole-cell vaccine with respect to the measured antibodies. Particularly for PT, immunogenicity seems to depend on factors in addition to antigen concentration, possibly including antigen derivation and formulation. No DTaP was most or least immunogenic with respect to all included antigens.
A Randomized Comparison of Reactogenicity and Immunogenicity of Two Whole-Cell Pertussis Vaccines
Authors: Steinhoff Mark C. , Reed George F. , Decker Michael D. , Edwards Kathryn M. , Englund Janet A. , Pichichero Michael E. , Rennels Margaret B. , Anderson Edwin L. , Deloria Maria A. , Meade Bruce D. 
Published: December 2021

Objective. To compare prospectively the reactogenicity and immunogenicity of two licensed whole-cell pertussis vaccines.
Methods. We conducted a prospective, randomized, double-blinded assessment of two licensed whole-cell pertussis vaccines with diphtheria and tetanus toxoids that were included in a multicenter trial evaluating 13 acellular pertussis vaccines. Infants were immunized at 2, 4, and 6 months of age with a single lot of Lederle (309 infants) or Massachusetts Public Health Biologic Laboratories (MPHBL; 94 infants) vaccine.
Results. The group receiving the Lederle vaccine demonstrated significantly higher antibody titers to pertussis toxin by enzyme-linked immunosorbent assay (ELISA) and by the Chinese hamster ovary cell pertussis toxin neutralization assay, and to fimbrial antigens by ELISA, as well as higher mean agglutinin titers. In contrast, the group receiving the MPHBL vaccine demonstrated higher ELISA antibody levels to filamentous hemagglutinin and pertactin. Similar differences were observed in the proportions of vaccinees seroconverting to these antigens. Rates of systemic and local reactions were relatively low for both vaccines. Although the Lederle product had substantially lower reactogenicity in this study than previously reported for that vaccine, the MPHBL vaccine was significantly less reactogenic in nearly all clinical categories.
Conclusion. The two whole-cell vaccines demonstrated statistically significant differences in postimmunization antibody levels to all six evaluated pertussis antigens. Whether these statistically significant differences in antibody levels have clinical relevance is not clear. Rates of nearly all local and systemic reactions were significantly lower among the MPHBL group than the Lederle group. Licensed whole-cell diphtheria-tetanus-pertussis vaccines produced by different manufacturers cannot be assumed to be similar in reactogenicity or immunogenecity.
Effect of Gender, Race, and Parental Education on Immunogenicity and Reported Reactogenicity of Acellular and Whole-Cell Pertussis Vaccines
Authors: Christy Cynthia , Pichichero Michael E. , Reed George F. , Decker Michael D. , Anderson Edwin L. , Rennels Margaret B. , Englund Janet A. , Edwards Kathryn M. , Steinhoff Mark C. 
Published: December 2021

Objective. To determine whether gender, race (black or white), or level of parental education influenced serologic responses or reporting of clinical reactions after immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined.
Methods. Healthy infants were prospectively randomized to receive one of 13 DTaP, Lederle DTP, or another DTP. Parents recorded the occurrence of adverse reactions for 2 weeks after each inoculation. Sera obtained before the first immunization and 1 month after the third immunization were analyzed for antibody to pertussis toxin, filamentous hemagglutinin, fimbriae, and pertactin (PRN). Chinese hamster ovary cell pertussis toxin neutralization assays were performed, and levels of agglutinating antibodies determined.
Results. Prevaccination antibody levels did not differ by race, gender, or parental education. Postimmunization geometric mean titers (GMTs) were strongly and consistently associated with race. For both DTaP and DTP and for every included antigen, postimmunization GMTs were about twice as high for black as for white infants. Among DTaP recipients, these differences were significant for pertussis toxin, Chinese hamster ovary cell pertussis toxin neutralization assay, filamentous hemagglutinin, and agglutinins; among the much smaller sample of WCL recipients, the differences achieved or approached statistical significance for agglutinins, PRN, and fimbriae. These findings were confirmed by regression analyses that controlled for gender, parental education, study site, and preimmunization antibody level. Reported reactions were not correlated with parental education level and showed no material correlation with gender. Black infants were reported to have had more pain than white infants after receiving WCL and DTaP and were reported to be more fussy after receiving WCL.
Conclusions. The consistently higher postimmunization GMTs among black infants seems to be a real finding for which we have no explanation; the infants did not significantly differ by race in vaccine assignment, preimunization antibody levels, age at immunization, or interval from immunization to phlebotomy. These observations should be confirmed and further evaluated in future pertussis vaccine trials. Reported differences by race in pain and fussiness after receiving WCL might reflect chance, differences by race in the occurrence of reactions, or differences by race in the reporting of reactions.
Corporal Punishment
Authors: Trumbull Den A. , Ravenel DuBose , Larson David 
Published: December 2021

The supplement to Pediatrics entitled "The Role of the Pediatrician in Violence Prevention" is timely, given the increasingly serious violence problem in the United States.1 Many of the supplement's recommendations are well-conceived and developed. However, the recommendation to "work toward the ultimate goal of ending corporal punishment in homes" (page 580)2 is unwarranted and counterproductive.
Before one advises against a practice approved by 88% of American parents3 and supported by 67% of primary care physicians,4 there should be sufficient scientific evidence to support the proposed change in social policy.
Dietary Fiber in Weaning Foods of Young Children
Authors: Agostoni Carlo , Riva Enrica , Giovannini Marcello 
Published: December 2021

Objective. An evaluation of the opportunity to introduce fiber in the diet of weaning infants.
Methods. A descriptive review of the literature to assess the role of fiber in the following dietary interventions: (1) definition of the nutrient amounts that meet the weaning infant's physiologic needs; (2) modulation of digestive and absorption processes; and (3) improving the nutritional balance between the 6th and the 12th months of life and setting habitual dietary patterns for subsequent years.
Findings. Whole cereals, nonstarchy vegetables, fruits, and legumes lower the caloric and proteic density of meals, modulate nutrient and antigen absorption, and provide bulk material. They supply proteins of low biological value, minimal amounts of lipids (mostly essential polyunsaturated), complex carbohydrates, and soluble fiber, which are fermented into short-chain fatty acids by the colonic flora, and insoluble fiber that modulates intestinal function. Minerals, trace elements, and vitamins add to the value of fiber-containing foods in the diet. Recent nutritional surveys indicate that the diets of 12-month-old infants tend to include too much animal proteins and to be too protein-dense, which could be corrected with an increase of fiber-containing foods.
Conclusions. Fiber-containing foods share unique characteristics with nutritional and metabolic implications for the weaning infant. Whole cereals, green vegetables, and legumes should be routinely introduced during the weaning process to achieve a better nutritional balance and to accustom children to diets with fiber content. The daily intake of fiber should be gradually increased to 5 g/d during the second semester of life.