Antiepileptic drugs: Are women aware of interactions with oral contraceptives and potential teratogenicity?

Women with epilepsy (WWE)’s knowledge of the interaction between antiepileptic drugs (AEDs) and oral contraceptives (OCs) and the potential teratogenicity of AEDs has received limited study. We conducted a cross-sectional questionnaire study (English or Spanish) among young WWE (18–44 years) to assess demographic characteristics, current AED use, and knowledge of AED interactions with OCs and teratogenicity. We used the Food and Drug Administration’s classification system to categorize each AED’s teratogenic potential. Participants (n = 148) had a mean age of 32 years (SD 8); 32% spoke Spanish and described themselves as Hispanic. Among women prescribed a cytochrome p450-inducing AED, 65% were unaware of decreased OC efficacy. Forty percent of those prescribed Category D AEDs were unaware of potential teratogenic effects. WWE have limited knowledge of the potential interaction between AEDs and OCs and the teratogenic effects of AEDs. Educational efforts should highlight the reproductive health effects of AEDs in WWE.     

Metallodendrimers and dendrimer nanocomposites

Dendrimers are polymeric compounds with highly branched structures and functionally tunable peripheral groups. Because of their low polydispersity, high degree of molecular uniformity, and precisely controlled structure, dendrimers are excellent models for demonstrating a variety of biological activities. With the attachment of metals ions and/or metals, metallodendrimers or dendrimer nanocomposites, respectively, provide diverse characters for a variety of applications. Functionalization with additional moieties, such as targeted peptides or chromophores, yields metallodendrimers that can find powerful applications and exceed the capabilities of nondendritic molecules or small molecule analogs. This review introduces the background of metallodendrimers and dendrimer nanocomposites. Biomedical applications of metallodendrimers and dendrimer nanocomposites will be discussed, including biomimetic catalysts, imaging contrast agents (especially for MRI imaging), or biomedical sensors and therapeutic agents.     

Massive fetomaternal hemorrhage: clearance of fetal red blood cells after intravenous anti-D prophylaxis monitored by flow cytometry

BACKGROUND: The clearance of D+ red blood cells (RBCs) from the circulation in D- individuals mediated by passively administered anti-D occurs by opsonization with the antibody and subsequent removal in the spleen. Few data exist on the kinetics of clearance of large volumes of D+ RBCs from the maternal circulation by anti-D in clinical cases of massive fetomaternal hemorrhage (FMH). CASE REPORT: A 33-year-old D- woman delivered a D+ female infant by emergency cesarean section for suspected fetal anemia. A massive FMH, initially estimated to be approximately 142 mL of RBCs, was found. In addition to the standard dose of intramuscular (IM) anti-D (300 microg) given immediately after delivery, 2700 microg of anti-D was administered intravenously (IV). The clearance of D+ fetal cells from the maternal circulation was monitored by flow cytometry in samples obtained on a daily basis using anti-D. The mother had no detectable anti-D 6 months after delivery. RESULTS: No clearance of fetal cells was apparent after the insufficient dose of IM anti-D. The IV administration of anti-D caused accelerated clearance of D+ fetal RBCs with a t1/2 of 24.5 hours. D+ reticulocytes comprised 4.2 percent of all D+ cells in the maternal circulation at delivery suggesting acute fetal blood loss. CONCLUSIONS: The approach used in this report allowed a detailed analysis of the kinetics related to the clearance of fetal D+ RBCs. Simultaneous measurements of fetal reticulocytes and fetal RBCs in maternal blood may establish the timing of an FMH.     

Psychometric evaluation of the interpersonal relationship inventory for early adolescents

ABSTRACT The purposes of this methodological study were to factor analyze the short form of the Tilden Interpersonal Relationship Inventory (IPRI) for early adolescents, and to assess construct validity of the social support and conflict subscales with early adolescents. The sample consisted of 147 early adolescents, aged 12–14, who completed instrument packets in classrooms in a suburban middle school. Data obtained on the IPRI were subjected to principal components factor analysis with Varimax rotation. The two factors that emerged are consistent with the theories underlying the instrument. Factor I was social support, and had a coefficient α reliability of .90. Factor II was conflict, and had a coefficient α reliability of .86. Construct validity was assessed by testing hypotheses derived from theoretical propositions linking support or conflict to general humor, self-esteem, and symptom patterns; the results of the hypotheses were statistically significant and in the predicted direction. The findings indicate that the social support and conflict subscales of the IPRI have evidence of reliability and validity for early adolescents.     

Prognostic value of KIT expression in small cell lung cancer

BACKGROUND: Small cell lung cancer (SCLC) is a very aggressive disease, with poor survival rates despite standard treatment with combination chemotherapy with or without radiotherapy. Further insights into the molecular biology of this malignant tumour are needed to improve the therapeutic approaches and outcome. KIT protein is expressed in SCLC, and its kinase activity has been implicated in the pathophysiology of many tumours, including SCLC. The purpose of this study was to evaluate the prevalence of KIT expression in patients with SCLC and its prognostic value. METHODS: We performed an inmunohistochemical analysis of 204 SCLC samples to determine KIT protein expression. The relationship between KIT expression and clinicopathological parameters was evaluated. Univariate and multivariate analyses were performed to define its prognostic significance. RESULTS: KIT expression was observed in 149 of 204 tumour tissues (73%). KIT expression was associated with advanced disease and with decreased incidence of bone metastases. No significant differences were observed for time to disease progression (TTP) (9.1% versus 6.2% at 3 years, p=0.6) or overall survival (OS) (10.7% versus 6.9% at 3 years, p=0.37) among patients with KIT positive versus negative tumours, respectively. Multivariate analysis showed that sex, tumour stage, albumin levels and response to therapy were the only independent predictors for survival. CONCLUSION: KIT protein is expressed in a high percentage of SCLC tumours. In our study population, however, the expression of KIT had no significant impact on survival.     

Long-term deposition of inhaled antigen in lung resident CD11b-CD11c+ cells

In this study we report the characterization of a population of lung resident CD11b(-)CD11c(+) cells that are able to take up inhaled antigen and retain it for extended periods of time. Ovalbumin conjugated to fluorescein-isothiocyanate (FITC-OVA) administered intranasally to mice was taken up by two main populations of cells in the lung, a migratory CD11c(+)CD11b(+) population consisting of dendritic cells (DC), which rapidly transported antigen to the draining lymph node (LN), and a resident CD11b(-)CD11c(+) population that retained engulfed antigen without apparently degrading it for up to 8 wk after administration. The FITC(+)CD11b(-)CD11c(+) cells did not migrate to draining LN at a detectable rate, and did not up-regulate expression of costimulatory molecules in response to LPS treatment. FITC(+)CD11b(-)CD11c(+) cells were found in the lung and bronchoalveolar lavage fluid, and their distribution was compatible with macrophages. Although FITC(+)CD11b(-)CD11c(+) cells expressed the DC marker DEC205 and other molecules associated with antigen-presenting cell function, they did not induce proliferation of antigen-specific CD4(+) T cells in vitro or acute cytokine production by activated CD4(+) T cells in vivo. Thus, FITC(+)CD11b(-)CD11c(+) cells appear to represent an intermediate cell type sharing properties with DC and macrophages. These cells may have a role in modulating the responses of lung resident T cells to inhaled antigens.     

Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBL–Activated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia

BackgroundAcute myeloid leukemia (AML) accounts for approximately 20% of pediatric leukemia cases; 30% of these patients experience relapse. The antileukemia properties of natural killer (NK) cells and their safety profile have been reported in AML therapy. We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBL–activated and expanded NK (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk AML in first complete remission after chemotherapy (NCT02763475).Patients and MethodsBefore the NKAE cell infusion, patients underwent a lymphodepleting regimen. After the NKAE cell infusion, patients were administered low doses (1 × 10⁶/IU/m²) of subcutaneous interleukin-2. The primary study endpoint was AML relapse-free survival. We needed to include 35 patients to demonstrate a 50% reduction in relapses.ResultsSeven patients (median age, 7.4 years; range, 0.78-15.98 years) were administered 13 infusions of NKAE cells, with a median of 36.44 × 10⁶ cells/kg (range, 6.92 × 10⁶ to 193.2 × 10⁶ cells/kg). We observed chimerism in 4 patients (median chimerism, 0.065%; range, 0.05-0.27%). After a median follow-up of 33 months, the disease of 6 patients (85.7%) remained in complete remission. The 3-year overall survival was 83.3% (95% confidence interval, 68.1-98.5), and the cumulative 3-year relapse rate was 28.6% (95% confidence interval, 11.5-45.7). The study was terminated early because of low patient recruitment.ConclusionThis study emphasizes the difficulties in recruiting patients for cell therapy trials, though NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions regarding efficacy because of the small number of included patients and insufficient biological markers.