Family history evaluation as a predictive screen for childhood hypercholesterolemia. Pediatric Practice Research Group

A study was conducted to evaluate the efficacy of family history factors as screening criteria for childhood hypercholesterolemia. When they were seen for routine care at one of eight office practices, 1005 prepubertal children underwent random serum cholesterol determinations. Parental and grandparental histories of cardiovascular risk factors and atherosclerotic complications prior to 55 years of age were also obtained. Of the initial group, 274 children had total cholesterol levels greater than or equal to 175 mg/dL, and 175 of these children returned for retesting after an overnight fast. A total of 88 children were found to have low-density lipoprotein-cholesterol (LDL-C) values greater than or equal to 90th percentile for age and sex. Maternal and paternal histories of hypercholesterolemia were significantly associated with elevated LDL-C (odds ratio = 7.3 and 2.9, respectively), but had extremely low sensitivities (0.09, 0.15) despite modest positive predictive values (0.42, 0.22). Grandparental histories of sudden death, peripheral vascular disease, and gout were associated with elevated LDL-C, but sensitivities and positive predictive values for all of these factors were less than 0.22. Family history factors most commonly recommended as criteria for cholesterol screening in children did not identify half of all the children with elevated LDL-C and did not selectively identify the most severely affected children. Adding information concerning the presence of childhood obesity did not result in appreciable improvement in LDL-C detection beyond that achieved by family history factors alone. It was concluded that if thorough identification of young children with elevated LDL-C is desired, inclusive population screening rather than a family history-based strategy would be the most effective approach.     

Sex effects in defensive behavior: Baseline differences and drug interactions

Female rats consistently show a pattern of differences in defensive behaviors compared to males which parallel the effects of exposure to a nonpainful threat stimulus (cat or cat odor) in the same tests and measures. These indications of greater defensiveness for females are particularly common in situations involving potential, as opposed to actual and present, threat, a factor which probably also reflects ceiling or floor effects in situations involving very intense defensiveness. In addition, pharmacological studies indicate sex differences in the effects of selective serotonin (5-HT) receptor agonists and antagonists on defensive responding. These findings indicate that sex effects must be considered in studies of the pharmacological control of defensive behaviors, and suggest that responsivity to sex effects may be an additional criterion for the suitability of animal models of anxiety.     

Incisor trauma in an adolescent Arab population: prevalence, severity, and occlusal risk factors.

INTRODUCTION: Incisor trauma is a significant clinical problem in children and adolescents. The purposes of this study were to report on the prevalence and severity of incisor trauma in a large population-based sample of adolescent Kuwaiti residents in the early permanent dentition, to determine the ages of and reasons for the injuries, and to test for any effects of sex, incisor occlusion, and lip coverage on the prevalence of incisor trauma. METHODS: Presence and type of traumatic injury were scored according to the National Institute of Dental Research index in a population-based sample of 795 girls and 788 boys with a mean age of 13.24 years (SD 0.42). RESULTS: Trauma prevalence was higher (P < .001) in boys (19.3%) than in girls (9.7%), and in the maxilla (13.6%) than in the mandible (1.5%). Most (77.3 %) of the affected subjects had only 1 injured tooth, and most (83.7%) of the traumatized teeth were maxillary central incisors. A total of 90.3% of the injuries were unrepaired enamel or enamel/dentin fractures. The major reasons for the injuries were falls and blows indoors (48.4%) or outdoors (41.6%). Nearly two-thirds (63.0%) of the traumas occurred at age 10 years or later. Mean overjet (OJ) was larger (3.9 v 3.0 mm, P < .01), and lip incompetence more frequent (12.7% v 7.3%, P < .01) among the subjects with injured maxillary incisors than among those without. Logistic regression showed that the odds of maxillary incisor trauma were 2.8 times higher in subjects with OJ between 6.5 and 9.0 mm, and 3.7 times higher in subjects with OJ > or = 9.5 mm than in subjects with OJ < or = 3.5 mm. CONCLUSIONS: Multiple logistic regression showed that the risk of maxillary incisor trauma was about 2 times higher in boys than in girls, and that the risk increased by 13% for every millimeter of increase in OJ. Lip competence was not included in the model. No associations were found between occlusion and mandibular incisor trauma.     

Quantitative immunoblotting assay of blood coagulation factor XII

The immunoblotting technique was applied to the study of Factor XII (F.XII) in plasma. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole plasma followed by electroblotting of the electropherograms to nitrocellulose (NC) membranes and immunologic detection by a double antibody technique was used. ¹²⁵-F.XII was transferred to the NC membrane in amounts proportional to the amount applied to the gel provided that a constant amount of carrier protein was present. Based on this, a quantitative assay was developed using either normal plasma or F.XII dilutions in F.XII-deficient plasma as standards. The measurement of F.XII antigen by immunoblotting was reproducible and gave values similar to those obtained by radial immunodiffusion. Two normal plasma pools contained 26 and 29 μ/ml of F.XII according to the immunoblotting assay. Compared to other immunoassays, immunoblotting has the advantage of directly estimating the apparent molecular weight (MW) of the protein of interest. Thus, we could confirm the normal apparent MW (80,000) of a F.XII-like molecule previously isolated from a cross reacting material (CRM)-positive F.XII-deficient plasma. None of eight CRM-negative F.XII-deficient plasmas showed an 80,000 MW immunoreactive molecule. However, five of these eight plasmas had a faint autoradiographic band at 115,000 MW that was similarly seen in only three out of 43 individual normal plasmas. The nature of this 115,000 MW band remains to be defined.     

Cytomegalovirus induces T-cell independent apoptosis in brain during immunodeficiency.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic viral pathogen associated with HIV/AIDS or immunosuppressive therapy. Systemic pathology may be caused either through direct virus-mediated infection or by indirect mechanisms such as 'by-stander' apoptosis. CMV infection of the central nervous system (CNS) occurs late in disease progression and understanding of pathology in the brain is fundamental for selection of appropriate therapies. OBJECTIVES: Using a model of disseminated neurotropic CMV disease, these experiments are designed to identify cellular predilection of murine CMV (MCMV) within mature brain and to determine, if CMV induces apoptosis within CNS cells. STUDY DESIGN: Adult immunodeficient (SCID) and normal BALB/c mice were infected via the tail vein with 4.5 x 10(5)pfu recombinant MCMV expressing a green fluorescent protein reporter. Animals were perfused at various time periods from 3 to 35 days post inoculation and tissues were stained for MCMV, GFAP, NEU-N, MBP, TUNEL, and caspase-3. RESULTS: CMV infection within brain was observed in multiple, independent foci affecting several different cell types, including neurons, glial cells, meninges, ependymal cells, and cerebral vessels. Cellular changes included nuclear karyopyknosis and karyorrhexis, and associated meningitis, choroiditis, encephalitis, vasculitis, and necrosis. TUNEL and caspase-3 staining of brain-demonstrated apoptosis of nearby 'by-stander' meningial, glial, and neuronal cells, but only in immunodeficient mice lacking T- and B-lymphocytes. Generally, only large CMV infection foci were associated with apoptosis of non-infected adjacent cells. CONCLUSIONS: These results indicate that MCMV may cause both direct and indirect pathology to brain and that T-cell independent apoptosis of surrounding cells of the CNS may be an important mechanism of disease in the pathogenesis of neurotropic CMV.     

Estimated research and development costs of rotavirus vaccines

Diseases like rotavirus afflict both upper- and lower-income countries, but most serious illnesses and deaths occur among the latter. It is a vital public health issue that vaccines for these types of global diseases can recover research and development (R&D) costs from high-priced markets quickly so that manufacturers can offer affordable prices to lower-income nations. Cost recovery depends on how high R&D costs are, and this study attempts to replace high, unverified estimates with lower, more verifiable estimates for two new vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline or GSK), based on detailed searches of public information and follow-up interviews with senior informants. We also offer a new perspective on “cost of capital” as a claim for recovery from public bodies. Our estimates suggest that companies can recover all fixed costs quickly from affluent markets and thus can offer these vaccines to lower-income countries at prices they can afford. Better vaccines are a shared project between companies and public health agencies; greater transparency and consistency in reporting of R&D costs is needed so that fair prices can be established.