Utility of fine-needle aspiration in the diagnosis of primary osteosarcoma

Fine-needle aspiration (FNA) is a reliable, safe, and cost-effective procedure with a well-established role in the diagnosis of various solid tissue neoplasms. The role of FNA in the diagnosis of primary bone tumors, including osteosarcoma (OGS), is controversial and has yet to be established. We reviewed our experience with the use of FNA as a diagnostic technique over the past 8 yr at our institution. Diagnosis was conclusive in 26 (65%) of 40 patients, 18 of whom went to neoadjuvant therapy and/or resection based solely on the FNA interpretation of either "high grade sarcoma" or "osteosarcoma." Of the remaining 14 (25%) patients, 12 had inconclusive diagnosis and two (5%) were false-negatives. An inconclusive diagnosis was most likely to be an inadequate or paucicellular aspirate, seen in six (15%) patients. An additional six patients had variants of osteosarcoma (four chondroid, one "giant cell rich," one parosteal) that made definitive diagnosis impossible. The two that were incorrectly classified were diagnosed as fracture callus and plasmacytoma. FNA is an accurate and cost-effective tool for the initial diagnosis of primary osteosarcoma with a sensitivity of 65% and accuracy of 95%. Inconclusive diagnoses are likely to be due to insufficient sample cellularity or the presence of OGS variant. In our experience, FNA is sufficient to provide the diagnosis of OGS prior to definitive treatment when interpreted in conjunction with imaging studies and clinical findings. In those cases where FNA fails to yield a diagnostic sample, a traditional biopsy can be performed.     

Children conceived using ICSI do not have an increased risk of delayed mental development at 5 years of age

BACKGROUND: Concerns about possible adverse outcomes for children conceived using ICSI were highlighted in 1998 when 1-year-old ICSI children were found to be at increased risk (relative risk = 9.2) of delayed mental development compared with children conceived naturally or using IVF. As the findings were biologically plausible, it was considered important to reassess child development when a more accurate measure of long-term cognitive ability could be obtained. METHODS: The mental development of 97 ICSI, 80 IVF and 110 naturally conceived (NC) children at 5 years of age was assessed using intelligence quotients (IQ) obtained from the Wechsler Preschool and Primary Scales of Intelligence. RESULTS: The mean full-scale IQ was 110 +/- 18 for ICSI, 111 +/- 13 for IVF and 114 +/- 13 for NC children (P = 0.21, non-significant). ICSI children were not at increased risk for delayed (full-scale IQ <85) cognitive development (ICSI 5.2%, IVF 2.5%, NC 0.9%; P = 0.18, non-significant). The only significant independent predictor of below-average full-scale IQ on multivariate analysis was lower maternal education level. CONCLUSIONS: These findings suggest that the genetic influence of parental cognitive ability is more important than the mode of conception in determining the long-term intellectual ability of children conceived using ICSI.     

Heritability and Expression of C-Reactive Protein in Type 2 Diabetes in the Diabetes Heart Study

Elevated C-reactive protein (CRP) levels are associated with both prevalent and incident cardiovascular disease. In this study, familial aggregation was estimated, and we tested for association between serum CRP levels and polymorphisms within the CRP and APOE genes in sib-ships with type 2 diabetes mellitus, a population at increased risk for cardiovascular disease. CRP levels were determined in 461 diabetes-affected subjects from 224 sibships from the Diabetes Heart Study (DHS). Heritability estimates of CRP levels were obtained using variance component models. Genetic influence on serum CRP levels by single nucleotide polymorphisms (SNPs) in the CRP and APOE genes was evaluated by association analysis using mixed models. Subjects were Caucasian American (84%) and African-American (16%), 53% female, and had an average age of 62.2 ± 9.2 years. The median CRP level was 3.3 mg/L (range 0 to 59.3 mg/L), and estimated heritability for CRP was approximately 40%. Estimates of heritability were significantly greater than zero (P < 0.0001) and relatively constant, despite adjustments for important modifiers (age, sex, ethnicity, diabetes duration, statin-use and anti-inflammatory use) of CRP. There was no significant evidence for association of CRP levels with CRP gene SNPs; however, consistent with previous reports, there was significant evidence of association of CRP levels with polymorphisms within the APOE gene. These data indicate CRP levels are significantly influenced by genetic (and/or environmental) factors that are shared within DHS families. While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed.     

Establishing procedures for institutional oversight of stem cell research.

Academic health centers (AHCs), which are at the forefront of stem cell research, need to establish institutional stem cell research oversight committees (SCROs) to comply with 2005 National Academy of Sciences (NAS) recommendations and to establish public trust in this sensitive research. Institutional review boards (IRBs) typically lack the expertise and time to adequately review the specific ethical issues raised by stem cell research. To assure careful, timely, and coordinated review of the science and ethics of stem cell protocols, AHCs need to address many practical procedural issues, such as SCRO membership, quorum, conflicts of interest, and procedures for protocol review. The SCRO committee at the University of California San Francisco (UCSF), established in 2003, has developed detailed policies and procedures on these issues. The UCSF SCRO has broad scientific expertise and uses ad hoc reviewers to strengthen the review process. Studies receiving full SCRO review have three lead reviewers: a scientist, a reviewer with ethics expertise, and a public representative. Studies introducing human stem cells into nonhuman blastocysts receive full review, even if the stem cells are anonymized. Some protocols are eligible for expedited review. The SCRO neither replaces nor duplicates review by the IRB and institutional animal care and use committees. Other AHCs can draw on the UCSF experience when developing their own policies and procedures for stem cell research oversight.     

An unusual surface peroxiredoxin protects invasive Entamoeba histolytica from oxidant attack

Peroxiredoxins are an important class of antioxidant enzymes found from Archaea to humans, which reduce and thereby detoxify peroxides and peroxynitrites. The major thiol-containing surface antigen of the invasive ameba, Entamoeba histolytica, is a peroxiredoxin and is likely to be important during the transition from the anaerobic environment of the large intestine to human tissues. The closely related species, Entamoeba dispar, is incapable of invasion and more sensitive to hydrogen peroxide, yet also has a peroxiredoxin. We cloned and expressed the two active recombinant enzymes and found that their activity was similar by a fluorometric stopped-flow assay, giving a Km of <10 microM for hydrogen peroxide. Three monoclonal antibodies produced to recombinant E. histolytica peroxiredoxin cross-reacted with Entamoeba dispar.E. histolytica contains as much as 50 times more peroxiredoxin than E. dispar as demonstrated by a sensitive capture ELISA. In addition, the peroxiredoxin is present largely on the outer surface of the cell, in contrast to E. dispar. This unusual peroxiredoxin localizes to the site of parasite-host cell contact where it can effectively counteract oxidants generated by host cells, thus facilitating invasion.     

CLARION: a novel interprofessional approach to health care education.

The authors describe the development and impact of CLARION, a student-run organization at the University of Minnesota founded in 2001 and dedicated to furthering interprofessional education for health professions students. CLARION's student founders recognized that three recent reports from the Institute of Medicine will fuel significant changes in health professions education. Moreover, they deduced that targeted, interprofessional education in the preclinical years could provide fundamental skills and understanding needed to make today's patient care safer and more effective. By engaging health care professionals and faculty, CLARION creates and conducts extracurricular, interprofessional experiences for students that are reflective of the six IOM aims for health care. Student members are from four separate schools of the university's academic health center: medicine, nursing, pharmacy, and public health. The organization's capstone event, the Interprofessional Case Competition, challenges interprofessional teams of students to compete in conducting and presenting a root cause analysis of a fictitious sentinel event. The interprofessional organizational structure of the CLARION board models the kind of interprofessional equality needed to effectively solve problems in the health care system. The interaction among students from different health professions has led them to many new understandings about health care and the realization that many fundamental biases about other professions are firmly rooted in students before they enter the workplace. CLARION has enabled continued professional development of students, faculty, and practitioners, leading individual students to enhanced understanding of the health care system. It is a grassroots catalyst that has prompted faculty to reexamine traditional health professions curricula and look for ways to integrate more interprofessional opportunities into it.     

In-vitro translation of mitochondrial mRNAs by yeast mitochondrial ribosomes is hampered by the lack of start-codon recognition

Summary In an attempt to reconstitute an homologous in-vitro translation system for yeast mitochondrial mRNAs, we have isolated ribosomes, supernatant factors, and tRNAs from mitochondria of Saccharomyces carlsbergensis. While poly(U) is translated faithfully in this system, no translation of in-vitro synthesised cytochrome c oxidase subunit II (COX2) mRNA could be detected. Formation of formylmethionyl-puromycin on mitochondrial ribosomes is stimulated by ApUpG, but not by COX2 mRNA, although mitochondrial small ribosomal subunits bind to this mRNA in vitro, even without added tRNA and initiation factors. We conclude, therefore, that the inability to faithfully translate mitochondrial mRNAs in vitro may be the result of an inability of mitochondrial ribosomes to recognize the initiation codon.     

BCL-2 expression in adult and embryonic non-haematopoietic tissues

The B-cell leukaemia/lymphoma-2 (bcl-2) proto-oncogene is unusual as its product appears to provide survival advantage to B cells by blocking apoptosis. In this study, the expression of bcl-2 has been examined in normal nonhaematopoietic tissues, embryos, and psoriatic skin by immunohistochemical staining. Bcl-2 protein expression is mainly observed in cell populations with a long life and/or proliferating ability such as duct cells in exocrine glands, basal keratinocytes, cells at the bottom of colon crypts, and neurons. In the skin of both adult and embryo and also embryonic kidney and cartilage, bcl-2 expression was observed in cells which were undergoing morphological transition from undifferentiated stem cells to committed precursor cells. The finding of bcl-2 expression in the terminal differentiated syncytial trophoblast, but not cytotrophoblast, and in some cells responsive to hormone stimulation such as in the endometrium and myometrium suggests that the gene expression may be related too hormone responsiveness. As no bci-2 localization was seen in the benign hyperproliferative skin condition psoriasis, this does not suggest a straightforward link to proliferation. These observations support the view that the bcl-2 gene may have an important role in cell development, maturation, and the path to terminal differentiation.     

Impairments in spatial generalization of visual skills after V4 and TEO lesions in macaques (Macaca mulatta)

The authors tested the spatial generalization of shape and color discriminations in 2 monkeys, in which 3 visual field quadrants were affected, respectively, by lesions in area V4, TEO, or both areas combined. The fourth quadrant served as a normal control. The monkeys were trained to discriminate stimuli presented in a standard location in each quadrant, followed by tests of discrimination performance in new locations in the same quadrant. In the quadrant affected by the V4 + TEO lesion, the authors found temporary but striking deficits in spatial generalization of shape and color discriminations over small distances, suggesting a contribution of areas V4 and TEO to short-range spatial generalization of visual skills.