Donor transmission of malignant melanoma to a liver graft recipient: case report and literature review

Abstract:  Post-transplant malignancy of donor origin is a rare complication of organ transplantation, most likely transmitted as micrometastases within the parenchyma of the donor organ or from circulating tumor cells contained within the organ. Patient survival is dependent upon early diagnoses, and differentiation of the malignancy as of donor or recipient derivation is important in developing a treatment modality. The utilization of fluorescent in situ hybridization chromosome analysis and DNA sequence analysis of the tumor cells can assist in this determination. This case report describes the management of donor transmitted malignant melanoma in a liver graft recipient and a review of the current literature.     

Brief Report: Brain Activation to Social Words in a Sedated Child with Autism

A functional magnetic resonance imaging (fMRI) study was performed on a 4-year-old girl with autism. While sedated, she listened to three utterances (numbers, hello, her own first name) played through headphones. Based on analyses of the fMRI data, the amount of total brain activation varied with the content of the utterance. The greatest volume of overall activation was in response to numbers, followed by the word ‘hello’, with the least activation to her name. Frontal cortex activation was greatest in response to her name, with less activation for numbers, and the least for the word ‘hello.’ These findings indicate that fMRI can identify and quantify the brain regions that are activated in response to words in children with autism under sedation.     

A psychometric evaluation of the CDRS and MADRS in assessing depressive symptoms in children

OBJECTIVE: This study compared the psychometric properties of the Children's Depression Rating Scale-Revised (CDRS-R) and the Montgomery-Asberg Depression Rating Scale (MADRS) in children with major depressive disorder. METHOD: Children (N = 96; ages 8 to 11 years inclusive) with nonpsychotic major depressive disorder were enrolled. Participants were part of a multisite, outpatient, randomized, placebo-controlled, 9-week trial of fluoxetine (10 mg/day for the first week and 20 mg/day thereafter). The CDRS-R and MADRS were completed based on clinician interviews with both parents and children. Classic test theory and item response theory analyses were conducted. RESULTS: The MADRS and CDRS-R total scores were correlated at baseline (r = 0.51) and at study exit (r = 0.85). Cronbach's alpha was .86 (CDRS-R) and .82 (MADRS) at exit. The effect sizes for change from baseline to exit between the fluoxetine and placebo groups were 0.78 (CDRS-R) and 0.61 (MADRS). There was agreement between the CDRS-R and MADRS in the declaration of treatment response (50% improvement from baseline to exit) in 84.2% of children. Test information function favored the CDRS-R. CONCLUSIONS: The CDRS-R showed greater effect size for differentiating drug and placebo and better test information than the MADRS in this study of depressed children.     

Validity of electronically monitored medication adherence and conventional adherence measures in schizophrenia

OBJECTIVE: This study evaluated the validity of prescriber, patient, and research assistant ratings of adherence to prescribed oral antipsychotic medication among outpatients with schizophrenia or schizoaffective disorder in comparison with electronic monitoring. METHODS: Adult outpatients with schizophrenia (N=35) or schizoaffective disorder (N=26) received adherence assessments via electronically monitored medication vial caps as well as by monthly prescriber, patient, and research assistant report for up to six months. RESULTS: Electronic monitoring detected greater nonadherence rates (57%) than either prescribers (7%) or patients (5%), though the research assistant ratings were 54%. No directional bias was found between electronic monitoring and assignment of adherence by research assistants, although disagreement occurred in 36% of cases. CONCLUSIONS: Both patients and prescribers grossly overestimated medication adherence, which may interfere with or reduce the effectiveness of diligent medication management.     

Cyclooxygenase-2 expression is not associated with clinical outcome in synovial sarcoma

Several studies have identified cyclooxygenase-2 (COX-2) expression in a variety of sarcomas, including rhabdomyosarcoma, osteosarcoma and chondrosarcoma. Although overexpression of COX-2 has been associated with poor prognosis and decreased survival in chondrosarcoma and osteosarcoma, no relationship between COX-2 expression and patient outcome has been demonstrated in rhabdomyosarcoma or adult soft tissue sarcomas. Little is known concerning the expression of COX-2 in synovial sarcoma. Therefore, the aim of this study was to examine the expression of COX-2 in synovial sarcoma and if shown, to identify any association with tumor stage and oncologic outcome. Paraffin-embedded specimens from 27 patients with synovial sarcoma who were treated with surgical resection or biopsy were obtained. Specimens were evaluated for the degree of COX-2 expression after immunohistochemical staining. Specimens were assigned an immunoreactivity score (IS) based on the percent positivity of the specimen. A retrospective chart analysis was performed to determine the clinical stage at presentation, incidence of local recurrence, presence of metastatic disease and overall survival. Statistical analysis was then performed to determine whether there was a significant relationship between IS and stage at presentation or patient outcomes. COX-2 expression was detected in 18 of 27 (66.67%) of the pathological specimens. There was a statistically significant relationship between COX-2 expression and patient clinical stage at presentation; however, we were unable to identify a significant relationship between IS and patient survival. We also found no significant relationship between IS and development of metastases or local recurrence. COX-2 was expressed to some degree in 67% of the tumor specimens. There was a significant relationship between IS and patient stage at presentation, but no significant relationship between COX-2 expression and clinical outcome could be identified. The fact that these tumors do express COX-2, however, suggests the potential for an additional target for more effective therapy.     

Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents

OBJECTIVE: The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents. METHOD: After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale. RESULTS: Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group. CONCLUSIONS: Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.     

Lymphangiomyomatosis: CT, chest radiographic, and functional correlations

Eight patients with the diagnosis of lymphangiomyomatosis were evaluated with computed tomography (CT), chest radiography, and pulmonary function tests to determine the relationship between the extent of disease seen on imaging studies and functional status. Chest radiographic assessment included the subjective determination of disease extent and measurements of lung length and the arc of the right hemidiaphragm. Disease extent on CT scans was scored as a percentage of lung that was abnormal on the basis of visual assessment of the degree of cystic replacement of the lung parenchyma. Significant correlations were observed between CT scores and percentages of predicted forced expiratory volume in 1 second/forced vital capacity (r = -.92, P less than .002) and diffusing capacity of the lungs for carbon monoxide (r = -.80, P less than .017). No significant correlations were observed between subjective chest radiographic scores and pulmonary function tests, although measurements of lung length and percentage of predicted total lung capacity were correlated (r = .76, P less than .045). CT was more accurate than chest radiography in defining the presence and extent of parenchymal cysts and provided for greater morphologic-physiologic correlation. CT, particularly high-resolution CT, may be useful in the diagnosis and longitudinal evaluation of patients with this disease and may be more sensitive than pulmonary function tests in the early stages of lung damage.     

A reversible monoamine oxidase inhibitor, toloxatone: Structural and electronic properties

Toloxatone is a reversible MAO_A-inhibitor, marketed as antidepressant (Humoryl^®), with an original chemical structure. It differs from first generation irreversible MAOIs, known to induce covalent bonds with the enzyme active site. In order to understand the mechanism of the reversible inactivation of the MAO, as a first step, a detailed structural and electronic analysis was undertaken. An X-ray diffraction-crystallographic study showed that toloxatone is a planar molecule and brought to light hydrogen bonds and π-π interactions. MO calculations confirmed the planar structure as energetically favoured. Electronic analysis demonstrated a delocalization of both ring systems. The combined results give evidence for the potential of toloxatone to participate in reversible, long distance interactions with an appropriate partner.