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aFall 2001



Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence

Mary Beth Lake, Boris Birmaher, Susan Wassick, Kimberly Mathos, and Ann Kathryn Yelovich
From the Departments of Child Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and the Department of Psychiatry, Allegheny General Hospital, Pittsburgh, Pennsylvania.
Journal of Child and Adolescent Psychopharmacology 2000;10(1):35–38.

The selective serotonin reuptake inhibitors (SSRIs) are becoming widely used in children and adolescents, with possible unexpected side effects being observed over time. SSRIs have been associated with bleeding in adults who have unremarkable routine hematologic laboratory results except abnormal bleeding time or platelet counts in few cases. Given the increase of pediatric SSRI prescriptions, in this article we describe five children, ages 8 through 15, who developed bruising or epistaxis 1 week to 3 months after starting SSRI treatment. It is possible that the effects of SSRIs on platelet functioning are causing the bleeding observed in some patients and/or that a separate coagulopathy is present and contributing to bleeding. The subject matter deserves future investigation.



Preoperative sonography in presumed thyroglossal duct cysts

Pankaj Gupta and John Maddalozzo
From the Departments of Otolaryngology—Head and Neck Surgery, Northwestern University Medical School, Chicago, Illinois, and the Department of Pediatric Otolaryngology and Communicative Disorders, Children’s Memorial Hospital, Chicago, Illinois.
Archives of Otolaryngology—Head and Neck Surgery 2001; 127: 200–202

Objective: To determine the utility of ultrasonography as a sole diagnostic study in the preoperative preparation of patients with presumed thyroglossal duct cysts.

Design: Retrospective chart review.

Patients: Forty-five pediatric patients with midline masses.

Main Outcome Measure: Accuracy in the determination of a normally positioned thyroid gland excluding the presence of a solitary ectopic thyroid gland.

Results: A retrospective chart review was performed at our institution for the period February 1990 to January 1996. A total of 45 patients with midline masses were identified, 39 of whom had undergone preoperative ultrasonography as their sole diagnostic imaging study. In all 39 patients, both a cyst and a normal thyroid gland were identified. All 39 patients underwent the standard Sistrunk procedure. Thirty-seven patients had pathologically confirmed thyroglossal duct cysts. The remaining two had dermoid cysts. There were no cases of postoperative hypothyroidism.

Conclusions: The incidence of ectopic thyroid in the diagnosis of thyroglossal duct cysts has been reported to be as high as 1% to 2%. In our surgical and clinical experience, the actual incidence of solitary ectopic thyroid tissue is substantially lower. Nevertheless, to prevent the inadvertent removal of the only functioning thyroid tissue, with resultant postoperative hypothyroidism and possible medicolegal consequences, we advocate the routine preoperative identification of normal thyroid gland. We recommend ultrasound as an accurate, cost-effective, non-invasive imaging modality in the preoperative evaluation of all patients with neck masses suspicious for thyroglossal duct cysts. Also, it does not require sedation.



Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment

Renee Smith, Kathleen Malee, Manhattan Charurat, Larry Magder, Claude Mellins, Carol MacMillan, Joan Hittleman, Tamar Lasky, Antolin Llorente, and Jack Moye
From the University of Illinois at Chicago and Northwestern University/Children’s Memorial Hospital, Chicago, Illinois, the Institute of Human Virology, Baltimore, Maryland, Columbia College of Physicians and Surgeons, New York, New York, the State University of New York Health Science Center at Brooklyn, Brooklyn, New York, Baylor College of Medicine, Houston, Texas, and the National Institutes of Health/National Institute of Child Health and Human Development.
The Pediatric Infectious Disease Journal 2000;19(9):862–863

Background: Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e., intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified.

Methods: Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter, natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures.

Results: Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P=0.05) and motor (P=0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 points in the late infected group (P<0.02). Estimated mental scores of the early infected group declined 0.72 points/month, whereas the average decline of the late infected group was 0.30 points/month (P<0.13).

Conclusion: Early HIV-1 infection increases a child’s risk for poor neurodevelopmental functioning within the first 30 months of life.



Attachment, parenting, and marital dissatisfaction as predictors of disruptive behavior in preschoolers

Crystal DeVito and Joyce Hopkins
From the Illinois Institute of Technology, Chicago, Illinois, and the Department of Child and Adolescent Psychiatry, Children’s Memorial Hospital, Chicago, Illinois.
Development and Psychopathology 2001;13:215–231

The aim of this study was to examine if an insecure coercive attachment pattern is associated with disruptive behavior in preschoolers, as well as to examine the effects of attachment pattern, marital dissatisfaction, and ineffective parenting practices on disruptive behavior. Participants included 60 preschoolers and their mothers. The preschool Assessment of Attachment (Crittenden, 1992) was used to measure attachment pattern. Results of an analysis of variance revealed that children in the coercively attached dyads scored significantly higher on the measure of disruptive behavior than either the defended or secure children. The combination of a coercive pattern of attachment, marital dissatisfaction, and permissive parenting practices accounted for a significant proportion of the variance in disruptive behavior in preschoolers. These data suggest that a specific type of insecure attachment, a coercive pattern, is associated with disruptive behavior in preschoolers.

In the “coercive cycle,” the child’s displays of negative behaviors increase as a function of the parent’s inconsistently punishing and giving in to the aversive behaviors. These children exhibit coy and disarming behaviors as often as behaviors that threaten tantrums or aggression. The attachment figure (parent) engages in the struggle which cannot be resolved.



Expression of TNF in muscle fibers in biopsies (MBx) from untreated juvenile dermatomyositis (JDM) is associated with the TNF-308A allele

Tamara Fedczyna, Jennica Lutz, Janice Caliendo, and Lauren Pachman
From the Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, and the Department of Neurology, Northwestern University Medical School, Chicago, Illinois.
Arthritis and Rheumatism 2000;43:1255–1276

We have observed that the TNF-308A allele is associated with increased production of TNF by JDM peripheral blood mononuclear cells, a prolonged disease course (36 months), as well as pathological calcification (Arthritis Rheum, in press). The expression of the proinflammatory cytokine TNF by muscle fibers of untreated JDM patients with the TNF-308 allelic polymorphism was next assessed. MRI directed MBx (vastus lateralis) from 21 untreated children with definite JDM (21 Caucasian, 15 females:6 males, mean age ±7.45 years) were evaluated for TNF expression by immunohistochemistry. The TNF-308 alleles were determined by PCR.

The JDM population was grouped into TNF-308A (11 patients, 9 females: 2 males) and TNF-308G (10 patients, 6 females:4 males). Both groups were categorized by disease duration from time of disease onset (first definite symptom of JDM, proximal muscle weakness and/or characteristic rash) to time of biopsy >9 months or <9 months. Frozen sections (4 µm thick) were routinely processed for immunohistochemical studies using monoclonal antibody to TNF by standard techniques. Surface area (mm²) of muscle section was determined by image analysis; and positive muscle fibers expressing TNF were assessed quantitatively, dividing total number of positive TNF muscle fibers by surface area (mm²) to achieve a muscle fiber/mm² count. The intensity and severity of the inflammation infiltrate was determined objectively by a 0–3 scale.

Patients with the TNF-308A allele had an increased number of muscle fibers expressing TNF, which stained intensely. In comparison, patients with the TNF-308G allele had a relatively decreased number of muscle fibers expressing TNF (p>0.03) with decreased stain intensity. In both the TNF-308A patients and TNF-308G patients, the number of muscle fibers expressing TNF was not associated with the severity of the inflammation or disease duration at time of MBx. These data suggest that the increased numbers of muscle fibers expressing TNF in the TNF-308A JDM children not only reflects immune stimulation but also may play a critical role in the pathophysiology of the disease resulting in a prolonged disease course.



In vivo gene therapy with interleukin-12 inhibits primary vascular tumor growth and induces apoptosis in a mouse model

C Wang, ME Quevedo, BJ Lannutti, KB Gordon, D Guo, W Sun and AS Paller
From the Department of Pediatrics and Dermatology, Northwestern University Medical School, Chicago, Illinois.
Journal of Investigative Dermatology 1999;112(5):775–781

Interleukin-12 is proposed to have anti-neoplastic activity on the basis of both its anti-angiogenic and immunologic effects. Gene gun therapy with interleukin-12 cDNA into the peritumoral area of immunocompetent 129/J mice with life-threatening primary vascular tumors reduced tumor volume 7.5-fold and almost tripled the duration of mouse survival, in contrast with luciferase-bombarded control mice. Epidermal expression of mouse interleukin-12 elevated tumoral and serum levels of interferon-gamma and tumor necrosis factor-alpha, increased the tumoral populations of T lymphocyte and natural killer cells, and induced tumor apoptosis. Gene transfer of interleukin-12 had little effect on tumor volumes and survival of tumor-bearing athymic nude mice, emphasizing the requirement of T cell directed cellular immunity. Peritumoral gene gun introduction of interleukin-12 may be a novel, cost-effective approach to limit the growth and associated mortality of life-threatening tumors.

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