Intracranial chondroma of the occipital lobe

A case report of an intracranial chondroma is discussed with emphasis on magnetic resonance imaging.     

Quality improvement in immunization delivery following an unsuccessful immunization recall.

OBJECTIVES: Within a clinic serving disadvantaged children, 1) to evaluate a multifaceted quality improvement (QI) project to improve immunization (IZ) up-to-date (UTD) rates and 2) to assess the efficacy of IZ reminder/recall performed following QI. METHODS: A year-long QI project followed by a trial of reminder/recall. QI interventions were targeted at previously identified barriers to IZ and were designed specifically to improve the efficacy of reminder/recall. QI interventions were designed to 1) increase the use of medical record releases to document IZs received elsewhere; 2) improve the accuracy of parental contact information; and 3) reduce missed opportunities by utilizing chart prompts, provider education, and provider reminders. Following QI, we conducted a randomized trial of reminder/recall. RESULTS: UTD rates for 7-11 month olds increased from 21% before the QI project to 52% after (P <.0001); rates for 12-18 month olds increased from 16% before QI to 44% after (P <.0001); 19-25 month olds 18% before to 33% after (P <.001). After QI, an average of 61 records per month were updated with IZs received elsewhere. However, the accuracy of parental contact information worsened (29% unreachable before QI vs 44% after, P <.001) and missed opportunities did not improve (8% before vs 6% after, P = not significant [NS]). A subsequent trial of reminder/recall did not increase UTD rates, with 17% of recalled children brought UTD vs 16% of controls (P = NS). CONCLUSIONS: Clinic-based QI increased documented UTD rates in a disadvantaged patient population. However, IZ reminder/recall did not further increase UTD rates above the rates achieved by the QI process.     

Neurodevelopmental changes of fetal pain

Pain in the developing fetus is controversial because of the difficulty in measuring and interpreting pain during gestation. It has received increased attention lately because of recently introduced legislation that would require consideration of fetal pain during intentional termination of pregnancy. During development, sensory fibers are abundant by 20 weeks; a functional spinal reflex is present by 19 weeks; connections to the thalamus are present by 20 weeks; and connections to subplate neurons are present by 17 weeks with intensive differentiation by 25 weeks. These cells are important developmentally, but decline as a result of natural apoptosis. Mature thalamocortical projections are not present until 29 to 30 weeks, which has led many to believe the fetus does not experience emotional "pain" until then. Pain requires both nociception and emotional reaction or interpretation. Nociception causes physiologic stress, which in turn causes increases in catecholamines, cortisol, and other stress hormones. Physiological stress is different from the emotional pain felt by the more mature fetus or infant, and this stress is mitigated by pain medication such as opiates. The plasticity of the developing brain makes it vulnerable to the stressors that cause long-term developmental changes, ultimately leading to adverse neurological outcomes. Whereas evidence for conscious pain perception is indirect, evidence for the subconscious incorporation of pain into neurological development and plasticity is incontrovertible. Scientific data, not religious or political conviction, should guide the desperately needed research in this field. In the meantime, it seems prudent to avoid pain during gestation.     

Insights in Public Health: Developing the Ho‘ouna Pono Substance Use Prevention Curriculum: Collaborating with Hawaiian Youth and Communities

This article briefly outlines a collaboration among communities on Hawai‘i Island and a university-based research team to develop, implement, and evaluate a school-based substance use prevention curriculum called Ho‘ouna Pono. In addition to providing a rationale for the project, the goal of this paper is fourfold. First, an overview of the Ho‘ouna Pono research results to date (2007–2013) is provided. Second, within this overview, the ways in which selected results informed program development are highlighted. Third, the curriculum is briefly described, and finally, the role of the students and community in the video production is described.     

Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c- derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid- specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.     

Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

Use of multiple T cell-directed intact ricin immunotoxins for autologous bone marrow transplantation

The monoclonal antibodies (MoAb) T101, G3.7, 35.1, and TA-1 were conjugated to intact ricin using a thioether linkage. These MoAb detect, respectively, the CD5[gp67], CD7[p41], CD2[p50], and [gp95, 170] determinants that are found in the vast majority of cases of T cell acute lymphocytic leukemia (T-ALL). The resulting immunotoxins (ITs) and an equimolar mixture of these ITs were evaluated as potential purgative reagents for autologous transplantation in T-ALL. Leukemic cell lines were used to compare the kinetics of protein synthesis inactivation mediated by each IT. The cells were treated with IT in the presence of lactose in order to block the native binding of ricin. The observed rates of protein synthesis inactivation correlated with target antigen expression detected by fluorescence-activated cell sorter analysis. Of the four ITs, T101-ricin (T101-R) exhibited the fastest rate of inactivation, followed in order by G3.7-ricin, TA-1-ricin, and 35.1-ricin. At concentrations greater than 300 ng/mL, a cocktail containing an equimolar amount of all four ITs (referred to as the four- IT cocktail) exhibited kinetics that were as fast or faster than those of T101-R. The long-term cytotoxic effects of individual ITs and the four-IT cocktail were evaluated using a sensitive clonogenic assay. Each IT was specifically cytotoxic and inhibited 1 to 4 logs of clonogenic leukemic cells at doses (300 to 600 ng/mL) that can be used clinically. The four-IT cocktail was highly cytotoxic; a concentration of 300 ng/mL inhibited greater than 4 logs of leukemic cells while sparing the majority of committed (CFU-GM, CFU-E) and pluripotent (CFU- GEMM) hematopoietic stem cells. The determination of both short-term kinetics of protein synthesis inactivation and longer-term inhibition of clonogenic growth allowed new insight into cell killing by IT. Our results suggest that ITs continue to act on clonogenic target cells for a period of three to five days. Interestingly, the four-IT cocktail was not as potent against clonogenic leukemic cells as T101-R alone, although it exhibited kinetics of protein synthesis inhibition that were as fast as those of T101-R alone. This finding suggests that internalized ITs may differ in the length of time they remain active within the cell. Our results also demonstrate the importance of using several different assays to evaluate IT reagents.