Retrospective analysis supports algorithm as efficient diagnostic approach to treatable intellectual developmental disabilities.

Background: Intellectual developmental disorders (IDD(1)), characterized by a significant impairment in cognitive function and behavior, affect 2.5% of the population and are associated with considerable morbidity and healthcare costs. Inborn errors of metabolism (IEM) currently constitute the largest group of genetic defects presenting with IDD, which are amenable to causal therapy.

Benefit finding in fathers of childhood cancer survivors: a retrospective pilot study.

There is a growing literature examining positive outcomes following traumatic experiences. Although the diagnosis of a child with cancer poses extraordinary challenges for the family, awareness is growing that such a life-changing event can be a catalyst for positive growth. The current mixed methods study investigated benefit finding in fathers (N = 25) of childhood cancer survivors.

Online "spaced education progress-testing" of students to confront two upcoming challenges to medical schools.

Purpose: U.S. medical students will soon complete only one licensure examination sequence, given near the end of medical school.

Shwachman-Diamond syndrome presenting in a premature infant as pancytopenia.

Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized by bone marrow dysfunction, exocrine pancreatic insufficiency, failure to thrive, and skeletal abnormalities. It is most commonly diagnosed in early childhood after the development of hematologic abnormalities. We report a premature infant born at 33 weeks gestation who was small for gestational age and displayed persistent cytopenias requiring transfusion.

Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study.

Background: Survivors of malignant disease in childhood who have had radiotherapy to the head, neck, or upper thorax have an increased risk of subsequent primary thyroid cancer, but the magnitude of risk over the therapeutic dose range has not been well established. We aimed to quantify the long-term risk of thyroid cancer after radiotherapy and chemotherapy.

Methods: In a nested case-control study, 69 cases with pathologically confirmed thyroid cancer and 265 matched controls without thyroid cancer were identified from 14,054 5-year survivors of cancer during childhood from the Childhood Cancer Survivor Study cohort.

The Cri$i$ in academic medicine.

Many believe that academic medicine is failing to meet all of its responsibilities and is in crisis. We interviewed a number of distinguished academicians and, while they held different views, found agreement that academic medical centers in the USA have gradually changed during the past half century from small, cloistered, scholarly institutions to large, complex, corporate-style organizations. These changes were fueled by large contributions of funds for research and great research accomplishments.

Spinal cord compression as a result of Rosai-Dorfman disease of the upper cervical spine in a child.

Background: Rosai-Dorfman disease is characterized by massive painless cervical lymphadenopathy, but can also include nasal obstruction, tonsillar enlargement, or hearing abnormalities. The disease occurs most often in the third and fourth decades. Most authors have suggested that it represents either an autoimmune disease or a reaction to an infectious agent that has yet to be discovered.

Tailored chemotherapy for malignant lymphoma arising in the setting of posttransplant lymphoproliferative disorder after solid organ transplantation.

Posttransplant lymphoproliferative disorder is a clinical challenge. Traditional chemotherapy results in tumor response, but toxicity and transplant rejection limit survival. The authors treated seven patients with malignant lymphoma after organ transplant with chemotherapy tailored to individual patient response.

Psychological outcomes in long-term survivors of childhood leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma: a report from the Childhood Cancer Survivor Study.

Objective: To evaluate and compare psychological outcomes in long-term survivors of pediatric leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma and sibling controls.

Methods: Adult survivors of childhood leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma (N = 5736) and sibling controls (N = 2565) were administered a long-term follow-up questionnaire allowing assessment of symptoms associated with depression and somatic distress.

Results: The majority of respondents in this study did not demonstrate symptomatology indicative of depression or somatic distress.

A model for assessing information retrieval and application skills of medical students.

Purpose: To develop and evaluate a model for assessing information retrieval and application skills, and to compare the performances on the assessment exercises of students who were and were not instructed in these skills.

Method: The authors developed a set of four examination stations, each with multiple subtasks, and administered the exams to students at two medical schools. Students at one school had intensive instruction in literature searching and filtering skills for information quality (instructed group), and those at the other school had minimal instruction in these areas (uninstructed group).

Medical education: creating physicians or medical technicians?

The 20th century witnessed phenomenal growth in scientific medical knowledge and technology, enabling physicians to more accurately diagnose and effectively treat a wide range of diseases. However, these advances led to longer and more complex training periods for physicians and increasing specialization and dependence on the new technology. An adverse outcome of these changes has been the development of many physicians who are less able to communicate with their patients and deal with them in a humanistic and personally caring manner; ie, the development of finely trained medical technologists as opposed to caring physicians.

A national general pediatric clerkship curriculum: the process of development and implementation.

Objective: To describe a new national general pediatrics clerkship curriculum, the development process that built national support for its use, and current progress in implementing the curriculum in pediatric clerkships at US allopathic medical schools. CURRICULUM DEVELOPMENT: A curriculum project team of pediatric clerkship directors and an advisory committee representing professional organizations invested in pediatric student education developed the format and content in collaboration with pediatric educators from the Council on Medical Student Education in Pediatrics (COMSEP) and the Ambulatory Pediatric Association (APA). An iterative process or review by clerkship directors, pediatric departmental chairs, and students finalized the content and built support for the final product.

A Phase I trial of bryostatin-1 in children with refractory solid tumors: a Pediatric Oncology Group study.

Bryostatin-1, a macrocyclic lactone, appears to elicit a wide range of biological responses including modulation of protein kinase C (PKC). PKC, one of the major elements in the signal transduction pathway, is involved in the regulation of cell growth, differentiation, gene expression, and tumor promotion. Because of the potential for a unique mechanism of interaction with tumorgenesis, a Phase I trial of bryostatin-1 was performed in children with solid tumors to: (a) establish the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD); (b) establish the pharmacokinetic profile in children; and (c) document any evidence of antitumor activity.

Retinal toxicity associated with cisplatin and etoposide in pediatric patients.

Cisplatin is an effective chemotherapeutic agent used in the treatment of many pediatric solid tumors. Retinal toxicity is a side effect of the drug reported in adults, but is not well described in pediatric patients. We present the cases of two children treated with cisplatin and etoposide who experienced retinal toxicity documented by visual evoked response (VER) and electroretinogram (ERG).

Chronic granulomatous disease in two children with recurrent infections: family studies using dihydrorhodamine-based flow cytometry.

We employed a recently published technique, flow cytometry using the cell permeant dye dihydrorhodamine, to analyze families of two patients with X-linked chronic granulomatous disease. The results illustrate the utility of this method in the diagnosis of this serious immunodeficiency disease and also in the identification of carriers.

Triosephosphate isomerase deficiency: repetitive occurrence of point mutation in amino acid 104 in multiple apparently unrelated families.

The molecular basis of triosephosphate isomerase (TPI) deficiency was studied in 3 patients from three separate families. In all 3 patients, genomic DNA directly sequenced after amplification by the polymerase chain reaction exhibited the point mutation TPI315C amino acid 104 Glu-->Asp. Although other mutations known to cause TPI deficiency have been restricted to single families, the amino acid 104 defect has now been described in nine apparently unrelated families throughout the world and is clearly the most frequently occurring form of the disorder.

Prevention of tumor lysis syndrome using continuous veno-venous hemofiltration.

Tumor lysis syndrome (TLS) and renal failure remain significant causes of morbidity and mortality in children with newly diagnosed Burkitt's lymphoma and high white blood cell count acute lymphocytic leukemia (ALL) despite conventional management with aggressive hydration, alkalinization, allopurinol, and the slow introduction of chemotherapy. A subgroup of patients at very high risk for TLS and renal failure can be identified based on the level of serum lactate dehydrogenase (LDH) and urine output. We evaluated the prospective use of continuous veno-venous hemofiltration (CVVH), in addition to conventional management to prevent renal failure from tumor lysis, in three children with advanced abdominal Burkitt's lymphoma and in two children with high white blood cell count T-cell ALL who were at very high risk based on LDH and urine output.

Diabetes insipidus and histiocytosis X: a case of isolated pituitary involvement.

Diabetes insipidus is associated with histiocytosis X in approximately 50% of cases with multiple lesions that involve both intracranial and extracranial structures. Although approximately 8% of cases of diabetes insipidus in children are caused by involvement of the hypothalamus or pituitary infundibulum (or both) by histiocytosis X, diabetes insipidus can be the initial manifestation in many disorders most commonly, intracranial neoplasms. Herein we report a case of isolated histiocytosis X of the pituitary gland in a child for whom medical assistance was sought because of symptoms of diabetes insipidus.

Isolated CNS metastasis as the first site of recurrence in a child with germ cell tumor of the mediastinum.

We describe a 2-year-old black female who was previously in complete remission from a stage 4 mediastinal germ cell tumor (stage 4 because of a single pulmonary parenchymal lesion). She presented with headaches, obtundation, and brain herniation, and suffered sudden death 12 months after completing high-dose chemotherapy. Autopsy revealed a large intraventricular lesion with mixed germ cell tumor elements, but no other evidence of malignancy was found.

A clinically applicable technique to study cytoskeletal dynamics in normal and abnormal polymorphonuclear leukocytes isolated from small volume blood samples.

Shape change and motility of polymorphonuclear leukocytes (PMNs) are essential for host defense and require dynamic reorganizations of microfilamentous cytoskeleton by reversible polymerization of G-actin into filaments (F-actin). Although clinical disorders of actin polymerization are rare, recently described simple methodologies for assaying actin dynamics in PMNs make the technique readily applicable to clinical studies. To develop a clinically useful F-actin assay, the authors investigated the optimal preparation conditions for PMN isolation that resulted in the least in vitro cytoskeletal activation and evaluated the variability in actin dynamics in acutely and chronically infected patients.

Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: a Pediatric Oncology Group study.

Purpose: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting.