Pediatric Cranio-spinal Axis Irradiation: Comparison of Radiation-induced Secondary Malignancy Estimations Based on Three Methods of Analysis for Three Different Treatment Modalities.

Pediatric cranio-spinal axis irradiation (CSI) is a valuable treatment for many central nervous system (CNS) diseases, but due to the life expectancies and quality of life expectations for children, the minimization of the risk for radiation-induced secondary malignancies must be a high priority. This study compared the estimated CSI-induced secondary malignancy risks of three radiation therapy modalities using three different models. Twenty-four (n = 24) pediatric patients previously treated with CSI for tumors of the CNS were planned using three different treatment modalities: three-dimensional conformal radiation therapy (3D-CRT), volume modulated arc therapy (VMAT), and Tomotherapy. Each plan was designed to deliver 23.4 Gy (1.8 Gy/fraction) to the target which was defined as the entire brain and spinal column with a 0.7 cm expansion. The mean doses as well as the dose volume histograms (DVH) of specific organs were analyzed for secondary malignancy risk according to three different methods: the effective dose equivalent (EDE), the excess relative risk (ERR), and the linear quadratic (LQ) models. Using the EDE model, the average secondary risk was highest for the 3D-CRT plans (37.60%), compared to VMAT (28.05%) and Tomotherapy (27.90%). The ERR model showed similarly that the 3D-CRT plans had considerably higher risk (10.84%) than VMAT and Tomotherapy, which showed almost equal risks (7.05 and 7.07%, respectively). The LQ model requires organ-specific cell survival parameters, which for the lungs, heart, and breast relevant values were found and applied. The lung risk for secondary malignancy was found to be 1.00, 1.96, and 2.07% for 3D-CRT, VMAT, and Tomotherapy, respectively. The secondary cancer risk for breast was estimated to be 0.09, 0.21, and 0.27% and for heart it was 9.75, 6.02 and 6.29% for 3D-CRT, VMAT, and Tomotherapy, respectively. Based on three methods of secondary malignancy estimation, the 3D-CRT plans produced highest radiation-induced secondary malignancy risk, and the VMAT and Tomotherapy plans had nearly equal risk. Pediatric patients must be treated with reducing long term sequelae as a priority.

The prevalence of sexually transmitted diseases in children and adolescents evaluated for sexual abuse in Cincinnati: rationale for limited STD testing in prepubertal girls.

OBJECTIVE: To determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, syphilis, and human immunodeficiency virus (HIV) infection in sexually abused children and to develop selective criteria for sexually transmitted disease (STD) testing in these children in our community. DESIGN: Prospective. SETTING: University-affiliated children's hospital in Ohio. PARTICIPANTS: All children evaluated at our hospital for sexual abuse were eligible. Eight hundred fifty-five children were evaluated over a 1-year period. The study included 704 girls and 151 boys. Children ranged in age from 3 weeks to 18 years old. METHODS AND RESULTS: Standard STD testing (American Academy of Pediatrics recommendations) was defined as serum rapid plasma reagin test, examination for Trichomonas, N gonorrhoeae culture of the throat, rectum, and genitalia and C trachomatis culture of the rectum and genitalia. STD testing in this study was recommended in children with 1) a history of genital discharge or contact with the perpetrator's genitalia, 2) examination findings of genital discharge or trauma, and 3) all adolescents. HIV testing was obtained in children with risk factors for HIV infection, those with contact with a perpetrator with HIV risk factors, or if the family was concerned about HIV acquisition. A total of 423 children were tested for N gonorrhoeae, 415 for C trachomatis, 275 for syphilis, 208 for Trichomonas, and 140 for HIV. Twelve children were determined to have N gonorrhoeae infection, 11 had C trachomatis infection, and four had Trichomonas infection. Overall, the prevalence of STDs in prepubertal girls was 3.2% and 14.6% in pubertal girls. The prevalence of N gonorrhoeae in prepubertal girls with vaginal discharge was 11.1% and 0% in prepubertal girls without discharge (P < .001). C trachomatis infection was diagnosed in 0.8% of prepubertal girls compared with 7.0% of pubertal girls (P < .001). None of the children tested positive for syphilis or HIV and no males had a STD. CONCLUSIONS: In our community, N gonorrhoeae testing in prepubertal girls can be limited to those with a vaginal discharge on examination unless other risk factors are present. The prevalence C trachomatis and Trichomonas in prepubertal girls is low and may be omitted from routine evaluations. All pubertal girls evaluated for sexual abuse should be tested for STDs because of the high prevalence of asymptomatic infection in this patient population.

Vaginal discharge as an indicator of gonorrhea and Chlamydia infection in girls under 12 years old.

Cultures for sexually transmitted diseases (STDs) are frequently obtained as part of an evaluation for alleged sexual abuse, but the prevalence of STDs in abused children is very low. Furthermore, STDs in children may not be identified if the clinician does not maintain a high index of suspicion in the symptomatic child. A retrospective review was done to study the symptoms and presenting complaints of girls under 12 with gonorrhea and chlamydia infections and to examine the prevalence of STDs in asymptomatic girls. The charts of 622 patients were reviewed. All patients were females under 12, Tanner I or II, who were initially seen for evaluation of sexual abuse or who were diagnosed with an STD. During the study period, 28 girls were found to have STDs. Twenty-two of these girls had vaginal gonorrhea; vaginal chlamydia was diagnosed in eight. Twenty-three of the 28 girls (82%) with an STD were initially seen and cultured for a chief complaint of vaginal discharge. Of the 581 patients who were cultured for evaluation of abuse, only five STDs were diagnosed (0.7%). All 22 girls with gonorrhea had a vaginal discharge on examination. Of the eight girls with chlamydia, two also had vaginal gonorrhea. Of the six who had chlamydia without gonorrhea, asymptomatic infection was common; four gave histories of discharge but only one had a discharge on examination. Our review indicates that girls under 12 who present for evaluation of vaginal discharge may have an STD and should be cultured for gonorrhea and chlamydia whether or not sexual abuse is suspected.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiographic characteristics of skull fractures resulting from child abuse.

Radiographic characteristics of skull fractures in 39 cases of documented child abuse were compared with skull fractures in 95 cases of accidental injury to determine if differential features could be identified. All children were less than 2 years old. Emergency room and hospital records for these patients were also reviewed. The results of this study show that clinical features did not provide any clues as to whether the children had been injured by abuse or by accident. However, it was found that multiple fractures, bilateral fractures, and fractures crossing sutures occurred significantly more often in abuse cases than in accidental injury. When such fractures are present, abuse should be suspected.

Comparisons of 12-tetradecanoylphorbol-13-acetate (TPA) and PHA as mitogens in the T-lymphocyte colony assay.

12-O-tetradecanoylphorbol-13-acetate (TPA) has multiple effects on the capacity of human T-lymphocytes to form colonies in soft agar. This compound is directly mitogenic for T-lymphocytes; the optimal concentration (100 ng/ml) stimulates an average of 2862 +/- 583 colonies/7.5 X 10(5) cells plated. Furthermore, TPA can act synergistically with PHA to induce a greater number of colonies than can either mitogen alone. Sephadex G10 nonadherent (NA) cells can be directly stimulated by TPA; by contrast, these isolated T cells do not respond to PHA alone. These data indicate that the phorbol ester is able to provide an inductive signal for T cells, allowing them to respond to the plant lectin. Using T-cell subsets isolated by monoclonal antibodies and complement cytotoxicity, PHA is able to induce colony growth of T4 cells; T8 cells fail to respond unless cocultured with exogenous IL-2. TPA can directly stimulate colony formation by both subsets. In cultures stimulated with either TPA or PHA, approximately equal numbers of colonies are generated in the presence of IL-2, suggesting that T4 and T8 cells have similar proliferative capabilities. Phenotypic studies of cells contained in colonies showed differences between the two mitogens. With PHA, more than 98% are both T11 and T3 positive; by contrast, approximately one-third of the cells stimulated by TPA are T11 +, T3-.

Cranial computed tomography in the abused child with head injury.

Cranial computed tomographic (CT) findings are described in 37 children with head injuries resulting from physical abuse. CT findings included subarachnoid hemorrhage (27 patients), cerebral edema (24), cerebral hemorrhage (11), and subdural hematoma (nine). Intravenous contrast material was administered in 10 children in whom there were neurologic symptoms or signs but no history or physical signs of trauma or abuse. In five of these children, increased vascularity was seen in areas that later showed infarction. Eight children were studied by both CT and sonography. Sonography detected 50% fewer abnormalities than did CT. It was found that children with skull fracture had the same range of injuries as children without fracture, and they had a higher incidence of subarachnoid hemorrhage. In acutely traumatized children, cranial CT should be the method of choice to provide the most accurate diagnosis and documentation of injury. Skull radiographs should also be obtained because they sometimes show fractures not recognized by CT.

Serious head injury in infants: accident or abuse?

The medical records and computed tomography (CT) scans of all children less than 1 year of age admitted to the hospital with head injury over a 2-year period were reviewed. Sixty-four percent of all head injuries, excluding uncomplicated skull fracture, and 95% of serious intracranial injuries were the result of child abuse. The occurrence of intracranial injury in infants, in the absence of a history of significant accidental trauma, such as a motor vehicle accident, constitutes grounds for an official child abuse investigation.

Developmental milestones in abused children, and their improvement with a family-oriented approach to the treatment of child abuse.

Few objective measures of the efficacy of intervention programs in the treatment of child abuse exist. One such measure may be improvement in the developmental delays often seen in abused children. Using the Learning Assessment Profile, we tested 53 abused children, ages 2.5-5 years, just before and after involvement in our Family Development Center Program (FDC). The FDC emphasizes therapy-group-interaction for parents, where alternative ways of expressing anger are explored. Children attend daily preschool classes, and take occasional outside field trips. Of the 53 children tested 42 (79%) showed greater than expected developmental skills gains. Six children demonstrated no improvement in developmental skills, four of whom had severe developmental delays in one or two areas. Fine motor and language skills were significantly delayed for the group as a whole; these areas showed the greatest improvement after FDC. There did not appear to be an overall association between increased improvement in developmental skills and length of time in the FDC program, although certain subgroups of children appeared to improve with time while others appeared to lose ground. A five-year follow-up study of these children is presently underway. We conclude that a program which involves both parent and child, and focuses on their interaction, appears to be effective in dealing with abusive families; monitoring developmental levels in the abused children is one means of assessing their progress in such a program. Further controlled prospective trials are needed in this area.

A site-specific single-strand endonuclease from the eukaryote Chlamydomonas.

We have found a unique deoxyribonuclease in extracts of the eukaryotic green alga Chlamydomonas. When incubated with viral DNA from adenovirus-2, this enzyme produces discrete fragments that form bands upon electrophoresis in an agarose gel. Site specificity of the enzymatic cleavage examined by identifying the 5'-terminal nucleotides in cleaved adenovirus-2 DNA and by studies with synthetic polynucleotides of defined sequence, indicates that the initial endonucleolytic cleavage occurs at a site containing a deoxythymidine residue. Electron microscopy of cleaved adenovirus-2 DNA revealed single-strand segments within duplex DNA. We propose that the enzyme acts by making initial site-specific single-strand incisions, followed by subsequent excision on the same strand, producing a gapped duplex molecule; and that double-strand scissions result from limited occurrence of overlapping single-strand gaps on complementary strands.