A population-based analysis of pediatric breast cancer

Purpose

The purpose of this study was to evaluate trends in demographics and outcomes of pediatric breast cancer in a United States population-based cohort.

Lack of awareness of need to clean CFC-free metered-dose inhalers.

BACKGROUND: Chlorofluorocarbon (CFC)-free metered-dose inhalers (MDIs) were introduced into Australia in 1999. Device care instructions were modified (e.g., CFC-free salbutamol inhalers to be washed weekly), but this information was not communicated directly to health care professionals. OBJECTIVE: This pilot study aimed to assess the level of awareness of device care protocols for CFC-free MDIs by patients and their pharmacists. SETTING AND DESIGN: Purchasers of CFC-free MDIs were recruited from four community pharmacies. They were interviewed regarding information sources, knowledge of propellant change, and awareness of and adherence to device care protocols. The dispensing pharmacists were interviewed for knowledge of CFC-free device care. The primary outcome variable was awareness of the relevant device care protocol. RESULTS: Thirty-nine patients were interviewed. Most patients (77%) were aware of the change to CFC-free propellant. Only nine patients (23%) were aware of the need to wash the device holder, and four patients (10% of total) complied with the specified protocol. One of the ten dispensing pharmacists could describe correct device care protocols for the CFC-free MDIs. CONCLUSIONS: Although most patients are aware that MDIs are now CFC-free, there is a low level of awareness of the device care required for these inhalers, and a very low rate of compliance with recommended practice. Although the clinical impact of failing to wash the device holder is unclear, this added instruction may have substantial implications for patient satisfaction and medication delivery. Pharmaceutical manufacturers need to highlight to health care professionals any clinically important changes in device care instructions, so that appropriate information may be passed on to patients.     

The asymptomatic patient with suspected myocardial contusion

Diagnostic criteria and guidelines for hospital admission for suspected myocardial contusion (MCC) remain unclear. This study defines and examines the clinical sequelae of patients admitted with a suspicion of MCC. Criteria for observation following isolated, minor blunt chest trauma are suggested. Hospital and trauma registry records of patients admitted over a 33-month period with suspected MCC were reviewed. Conventional evaluation criteria, cardiac-related complications, and associated injuries were analyzed for 524 patients. Twenty-eight cardiac-related complications occurred in 27 of 524 patients (5%). These complications included 23 dysrhythmias, 3 infarctions, and 2 pericardial effusions. There were 23 patients with abnormal admission electrocardiograms and 4 with normal ones. Of the latter, one patient developed dysrhythmia 4 hours after admission, and three had other major multi-system injuries requiring admission to the intensive care unit. The overall incidence of cardiac-related complications in minimally injured patients was 0.1%. There were no complications in patients with isolated chest wall contusions, a normal admission electrocardiogram, and a normal rhythm at 4 hours. There was no significant association between creatine phosphokinase isoenzymes or echocardiogram and cardiac-related complications. The complete absence of significant cardiac sequelae in patients with isolated chest wall contusion, normal admission and 4-hour electrocardiograms, and no other associated major injuries suggests that these patients need not be admitted.     

Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype

PEX7 encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Mutations in PEX7 cause rhizomelic chondrodysplasia punctata (RCDP), a distinct peroxisome biogenesis disorder. In previous work we described three novel PEX7 mutant alleles, including one, L292X, with a high frequency due to a founder effect. We have now extended our analysis to 60 RCDP probands and identified a total of 24 PEX7 alleles, accounting for 95% of the mutant PEX7 genes in our sample. Of these, 50% are L292X, 13% are IVS9+1G>C, and the remainder are mostly private. IVS9+1G>C occurs on at least three different haplotypes and thus appears to result from recurrent mutation. The phenotypic spectrum of RCDP is broader than commonly recognized and includes minimally affected individuals at the mild end of the spectrum. To relate PEX7 genotype and phenotype, we evaluated the consequence of the disease mutation on PEX7 RNA by Northern analysis and RT/PCR. We evaluated the function of the encoded Pex7 protein (Pex7p) by expressing selected alleles in fibroblasts from RCDP patients and assaying their ability to restore import of a PTS2 marker protein. We find that residual activity of mutant Pex7p and reduced amounts of normal Pex7p are associated with milder and variant phenotypes.     

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

Flectin, a protein previously described to be expressed in a left‐dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC‐II) protein class. During looping, both NMHC‐IIA and NMHC‐IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC‐IIB, rather than NMHC‐IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full‐length human NMHC‐IIA and ‐IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC‐IIB antibody does not. Abnormally looping hearts of the Nodal^{Δ 600} homozygous mouse embryos show decreased NMHC‐IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC‐II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping. Developmental Dynamics 237:3577–3590, 2008. © 2008 Wiley‐Liss, Inc.     

Phenotypic and functional properties of murine {gamma}{delta} T cell clones derived from malaria immunized, {alpha}{beta} T cell-deficient mice

Six murine T cell clones expressing TCR were generated frommalaria immunized, ß T celldeficient mice. Phenotypiccharacterization of these clones has revealed that, in contrastto conventional ß T cells, there is a considerabledegree of heterogeneity among these clones with regard to theirsurface markers and their lymphokine profile. One clone wasfound to display significant anti-parasite activity in vivoupon adoptive transfer. We attempted to determine whether theprotective clone differs in one or more key characteristicsfrom the non-protective clones. Although no obvious patternpeculiar to the protective clone was observed, it appears thatmore than one parameter may, in combination, define a distinctprotective phenotype, and thus explain the functional differencebetween the protective and non-protective clones.     

Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.     

Hemopoietic stem cell transplantation in rheumatic diseases--an update

Hematopoietic stem cell transplant (HSCT) for autoimmune diseases has been recognized as a potential treatment for patients who have failed conventional therapy. Autologous (self) donor cells have been preferred over allogeneic (HLA-matched) cells for rescue after high dose immunotherapy, given the previous higher rates of mortality, graft versus host disease (GVHD), and the need for more intense myeloablation associated with the latter. The European Group for bone Marrow Transplantation in Basel Switzerland (EBMT) and various groups within the US funded by the NIH (including the Autologous Blood and Marrow Transplant Registry (ABMTR)) have been pivotal in maintaining registries on patients transplanted as well as promoting homogeneity for future studies including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc). Although, patients transplanted for RA show initial success, relapse of the disease is common. In many, however, a second positive result can be obtained with the addition of DMARD therapy to which they were previously unresponsive, suggesting a "debulking" of disease by HSCT. SLE patients also have a high rate of success after HSCT, although current mortality rates appear high. Transplant in SSc patients has offered durable responses with improving transplant-related mortality related to careful patient selection.