Early pyloric stenosis: a case control study

Pyloric stenosis (PS) is rare in the first 2 weeks of life, often leading to delays in diagnosis and treatment. We conducted a case control study to delineate the characteristics of patients with early PS (EPS). In addition, we tested the hypothesis that patients with EPS present with a smaller pylorus than older patients. A database of all patients presenting with PS to a children’s hospital over a 5-year period (2002–2006) was obtained. Each patient admitted during the first 2 weeks of life (subject) was matched to a patient admitted after 4 weeks of age (control), with the same gender, electrolyte status, and treating surgeon. A single pediatric radiologist, blinded to patient age, reviewed all available ultrasounds retrospectively. Demographic, clinical, diagnostic, therapeutic, and outcome data were compared. During the study period, 278 pyloromyotomies were performed for PS. Sixteen patients (5.8%) presented with EPS between 2 and 14 days of life. EPS patients had a higher prevalence of positive family history (31 vs. 0%, P = 0.043), and breast milk feeding (75 vs. 31%, P = 0.045). Sonographic measurements showed a pylorus that was of significantly less length (17.1 ± 0.6 vs. 20.5 ± 0.9 mm, P = 0.006) and muscle thickness (3.5 ± 0.2 vs. 4.9 ± 0.2 mm, P < 0.001) in patients with EPS. Hospital stay was significantly longer for EPS patients (4.3 ± 0.9 vs. 2.0 ± 0.1 days, P = 0.19) Babies presenting with EPS are more likely to be breast fed and to have a positive family history. EPS is associated with a longer hospital stay. Use of sonographic diagnostic measurements specific to this age group may prevent delays in diagnosis and treatment, and improve outcomes

Valuing breastfeeding: a qualitative study of women's experiences of a financial incentive scheme for breastfeeding

BACKGROUND: A cluster randomised controlled trial of a financial incentive for breastfeeding conducted in areas with low breastfeeding rates in the UK reported a statistically significant increase in breastfeeding at 6-8 weeks. In this paper we report an analysis of interviews with women eligible for the scheme, exploring their experiences and perceptions of the scheme and its impact on breastfeeding to support the interpretation of the results of the trial. METHODS: Semi-structured interviews were carried out with 35 women eligible for the scheme during the feasibility and trial stages. All interviews were recorded and verbatim transcripts analysed using a Framework Analysis approach. RESULTS: Women reported that their decisions about infant feeding were influenced by the behaviours and beliefs of their family and friends, socio-cultural norms and by health and practical considerations. They were generally positive about the scheme, and felt valued for the effort involved in breastfeeding. The vouchers were frequently described as a reward, a bonus and something to look forward to, and helping women keep going with their breastfeeding. They were often perceived as compensation for the difficulties women encountered during breastfeeding. The scheme was not thought to make a difference to mothers who were strongly against breastfeeding. However, women did believe the scheme would help normalise breastfeeding, influence those who were undecided and help women to keep going with breastfeeding and reach key milestones e.g. 6 weeks or 3 months. CONCLUSIONS: The scheme was acceptable to women, who perceived it as rewarding and valuing them for breastfeeding. Women reported that the scheme could raise awareness of breastfeeding and encourage its normalisation. This provides a possible mechanism of action to explain the results of the trial. TRIAL REGISTRATION: The trial is registered with the ISRCTN registry, number 44898617 , https://www.isrctn.com

Short-Term Exposure to Warm Microhabitats Could Explain Amphibian Persistence with Batrachochytrium dendrobatidis

Environmental conditions can alter the outcomes of symbiotic interactions. Many amphibian species have declined due to chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), but many others persist despite high Bd infection prevalence. This indicates that Bd's virulence is lower, or it may even be a commensal, in some hosts. In the Australian Wet Tropics, chytridiomycosis extirpated Litoria nannotis from high-elevation rain forests in the early 1990 s. Although the species is recolonizing many sites, no population has fully recovered. Litoria lorica disappeared from all known sites in the early 1990 s and was thought globally extinct, but a new population was discovered in 2008, in an upland dry forest habitat it shares with L. nannotis. All frogs of both species observed during three population censuses were apparently healthy, but most carried Bd. Frogs perch on sun-warmed rocks in dry forest streams, possibly keeping Bd infections below the lethal threshold attained in cooler rain forests. We tested whether short-term elevated temperatures can hamper Bd growth in vitro over one generation (four days). Simulating the temperatures available to frogs on strongly and moderately warmed rocks in dry forests, by incubating cultures at 33°C for one hour daily, reduced Bd growth below that of Bd held at 15°C constantly (representing rain forest habitats). Even small decreases in the exponential growth rate of Bd on hosts may contribute to the survival of frogs in dry forests

Identification of Phosphoglycerate Kinase 1 (PGK1) as a reference gene for quantitative gene expression measurements in human blood RNA

<p>Abstract</p> <p>Background</p> <p>Blood is a convenient sample and increasingly used for quantitative gene expression measurements with a variety of diseases including chronic fatigue syndrome (CFS). Quantitative gene expression measurements require normalization of target genes to reference genes that are stable and independent from variables being tested in the experiment. Because there are no genes that are useful for all situations, reference gene selection is an essential step to any quantitative reverse transcription-PCR protocol. Many publications have described appropriate genes for a wide variety of tissues and experimental conditions, however, reference genes that may be suitable for the analysis of CFS, or human blood RNA derived from whole blood as well as isolated peripheral blood mononuclear cells (PBMCs), have not been described.</p> <p>Findings</p> <p>Literature review and analyses of our unpublished microarray data were used to narrow down the pool of candidate reference genes to six. We assayed whole blood RNA from Tempus tubes and cell preparation tube (CPT)-collected PBMC RNA from 46 subjects, and used the geNorm and NormFinder algorithms to select the most stable reference genes. <it>Phosphoglycerate kinase 1 (PGK1) </it>was one of the optimal normalization genes for both whole blood and PBMC RNA, however, additional genes differed for the two sample types; <it>Ribosomal protein large, P0 (RPLP0</it>) for PBMC RNA and <it>Peptidylprolyl isomerase B </it>(<it>PPIB) </it>for whole blood RNA. We also show that the use of a single reference gene is sufficient for normalization when the most stable candidates are used.</p> <p>Conclusions</p> <p>We have identified <it>PGK1 </it>as a stable reference gene for use with whole blood RNA and RNA derived from PBMC. When stable genes are selected it is possible to use a single gene for normalization rather than two or three. Optimal normalization will improve the ability of results from PBMC RNA to be compared with those from whole blood RNA and potentially allows comparison of gene expression results from blood RNA collected and processed by different methods with the intention of biomarker discovery. Results of this study should facilitate large-scale molecular epidemiologic studies using blood RNA as the target of quantitative gene expression measurements.</p

Dissecting the Autocrine and Paracrine Roles of the CCR2-CCL2 Axis in Tumor Survival and Angiogenesis

The CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX3CR1+tumor associated macrophages that in the absence of CCR2 hardly migrate. Thus far no in vivo system has been set up to differentiate the selective contribution of each of these features to cancer development. Here we employed a chimera animal model in which all non-malignant cells are CCR2−/−, but all cancer cells are CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX3CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX3CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx3cr1gfp), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX3CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to tumor development and angiogenesis. Showing that aside for their direct pro-angiogenic effect they are essential for the recruitment of other CD11b+ cells to the tumor site. We further show that the administration of CCR2-Ig, that selectively and specifically neutralize CCL2, to mice in which CCR2 is expressed only on tumor cells, further suppressed tumor development, implicating for the key role of this chemokine supporting tumor survival in an autocrine manner. This further emphasizes the important role of CCL2 as a target for therapy of cancer diseases

Pemetrexed Induced Thymidylate Synthase Inhibition in Non-Small Cell Lung Cancer Patients: A Pilot Study with 3 '-Deoxy-3 '-[F-18]fluorothymidine Positron Emission Tomography

OBJECTIVES: Pemetrexed is a thymidylate synthase (TS) inhibitor and is effective in non-small cell lung cancer (NSCLC). 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT), a proliferation marker, could potentially identify tumor specific TS-inhibition. The aim of this study was to investigate the effect of pemetrexed-induced TS-inhibition on ¹⁸F-FLT uptake 4 hours after pemetrexed administration in metastatic NSCLC patients. METHODS: Fourteen NSCLC patients underwent dynamic ¹⁸F-FLT positron emission tomography (PET) scans at baseline and 4 hours after the first dose of pemetrexed. Volumes of interest were defined with a 41%, 50% and 70% threshold of the maximum pixel. Kinetic analysis and simplified measures were performed. At one, two, four and six hours after pemetrexed, plasma deoxyuridine was measured as systemic indicator of TS-inhibition. Tumor response measured with response evaluation criteria in solid tumors (RECIST), time to progression (TTP) and overall survival (OS) were determined. RESULTS: Eleven patients had evaluable ¹⁸F-FLT PET scans at baseline and 4 hours after pemetrexed. Two patients had increased ¹⁸F-FLT uptake of 35% and 31% after pemetrexed, whereas two other patients had decreased uptake of 31%. In the remaining seven patients ¹⁸F-FLT uptake did not change beyond test-retest borders. In all patients deoxyuridine levels raised after administration of pemetrexed, implicating pemetrexed-induced TS-inhibition. ¹⁸F-FLT uptake in bone marrow was significantly increased 4 hours after pemetrexed administration. Six weeks after the start of treatment 5 patients had partial response, 4 stable disease and 2 progressive disease. Median TTP was 4.2 months (range 3.0-7.4 months); median OS was 13.0 months (range 5.1-30.8 months). Changes in ¹⁸F-FLT uptake were not predictive for tumor response, TTP or OS. CONCLUSIONS: Measuring TS-inhibition in a clinical setting 4 hours after pemetrexed revealed a non-systematic change in ¹⁸F-FLT uptake within the tumor. No significant association with tumor response, TTP or OS was observed

Optical Coherence Tomography and Fibrous Cap Characterization

The pathophysiology of acute coronary syndromes has long been associated with atherosclerotic plaque rupture. Inflammation, thinning, and disruption of the fibrous cap have been implicated with the final processes leading to plaque rupture, but confirmation of these mechanisms of coronary thrombosis in humans has been hampered by the lack of imaging methods with sufficient resolution to resolve fibrous cap characterization and thickness in vivo. Intravascular optical coherence tomography (OCT) provides images with micron-level axial and lateral resolution, enabling detailed visualization of micro-structural changes of the arterial wall. The present article provides an overview of the potential role of OCT in identifying and characterizing fibrous cap morphology, thickness, and inflammation in human coronary plaques

Seasonal Pattern of Batrachochytrium dendrobatidis Infection and Mortality in Lithobates areolatus: Affirmation of Vredenburg's “10,000 Zoospore Rule”

To fully comprehend chytridiomycosis, the amphibian disease caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), it is essential to understand how Bd affects amphibians throughout their remarkable range of life histories. Crawfish Frogs (Lithobates areolatus) are a typical North American pond-breeding species that forms explosive spring breeding aggregations in seasonal and semipermanent wetlands. But unlike most species, when not breeding Crawfish Frogs usually live singly—in nearly total isolation from conspecifics—and obligately in burrows dug by crayfish. Crayfish burrows penetrate the water table, and therefore offer Crawfish Frogs a second, permanent aquatic habitat when not breeding. Over the course of two years we sampled for the presence of Bd in Crawfish Frog adults. Sampling was conducted seasonally, as animals moved from post-winter emergence through breeding migrations, then back into upland burrow habitats. During our study, 53% of Crawfish Frog breeding adults tested positive for Bd in at least one sample; 27% entered breeding wetlands Bd positive; 46% exited wetlands Bd positive. Five emigrating Crawfish Frogs (12%) developed chytridiomycosis and died. In contrast, all 25 adult frogs sampled while occupying upland crayfish burrows during the summer tested Bd negative. One percent of postmetamorphic juveniles sampled were Bd positive. Zoospore equivalents/swab ranged from 0.8 to 24,436; five out of eight frogs with zoospore equivalents near or >10,000 are known to have died. In summary, Bd infection rates in Crawfish Frog populations ratchet up from near zero during the summer to over 25% following overwintering; rates then nearly double again during and just after breeding—when mortality occurs—before the infection wanes during the summer. Bd-negative postmetamorphic juveniles may not be exposed again to this pathogen until they take up residence in crayfish burrows, or until their first breeding, some years later

Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells

MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1−/− mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1−/− mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1−/− mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1−/− mice. Transplantation of MCP-1−/− bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1−/− mice increased lung metastasis. The primary tumors of MCP-1−/− mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1−/− mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment