Pediatric RSV Patients: Radiographic Findings on Admission and Clinical Outcomes

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infection in children. This retrospective review attempts to evaluate the association of admission chest radiographs with severity of clinical outcome. Radiographic findings were correlated with ‘severe’ and ’non-severe’ clinical outcomes, whereby a severe outcome was defined as hospitalization > 2 days, PICU admission, or mechanical ventilation during hospitalization. A non-severe outcome was defined as absence of the previous criteria. The most common abnormal chest radiograph findings were: interstitial prominence (n=182 [61.5%]), airspace opacity (n=106 [35.8%]), and hyperinflation (n=78 [26.3%]). The radiographic findings found to be associated with a severe clinical outcome were hyperinflation (p=0.033) and airspace opacity (p<0.001). Clinicians should consider more aggressive treatment and closer monitoring when these findings are present on admission chest radiography.This item is part of the College of Medicine - Phoenix Scholarly Projects 2019 collection. For more information, contact the Phoenix Biomedical Campus Library at [email protected]

Prostate Field Cancerization – Thinking Outside the Tumor

Analysis of tumor adjacent tissue is assumed to reveal a temporal record of molecular pathways that define oncogenesis. The present study determines expression of the key transcription factor and potential marker of field cancerization early growth response 1 (EGR-1) in human prostate tissues derived from prostatectomies and biopsies. Expression was detected using immunofluorescence and quantified using ImageJ software. Accordingly, EGR-1 expression was similar in cancerous and in histologically normal adjacent tissues from prostatectomy and biopsy specimens. EGR-1 could be exploited as pre-surgical disease indicator in false negative biopsies, identify areas of repeat biopsy, and add molecular information to surgical margins

Prostate Field Cancerization -- Thinking Outside the Tumor

Prostate field cancerization (or field effect) is characterized by the presence of molecular alterations in histologically normal tissues adjacent to adenocarcinomas. Accordingly, our research indicates deregulated expression of several proteins that define this type of molecular pathology. The scope of the present study was to determine the expression of the key transcription factor and potential marker of field cancerization early growth response 1 (EGR-1) in human prostate tissues derived from prostatectomies and biopsy cores. EGR-1 was detected by immunofluorescence using a polyclonal anti-human EGR-1 and Alexa Fluor 488-conjugated secondary antibodies. EGR-1 expression was quantitated by determining the pixel count per area (signal intensity) in digitized images using ImageJ software. In this proof-of-concept study, a total of 4 cases consisting each of prostatectomy and matched biopsy material, either containing or devoid of cancerous cells (malignant or benign) were analyzed. Expression levels and data distribution of EGR-1 were similar by region of interest analysis between malignant and benign prostatectomies (p = 0.28), but different between malignant and benign biopsies (p \u3c 0.05). EGR-1 protein expression is similar in cancerous (malignant) and in histologically normal adjacent (benign) tissues from both prostatectomy and biopsy specimens. This supports the concept of field cancerization and indicates a potential organ-wide molecular change, regardless of the presence or absence of cancer cells. Markers of field cancerization, such as EGR-1, could be exploited as pre-surgical disease indicators in false negative biopsies, identify areas of repeat biopsy, and add molecular information to surgical margins

Hallux Motion

Category: Bunion, Trauma, Other Introduction/Purpose: Immobilization is required for management of acute and chronic pathologic states of the hallux metatarsophalangeal (MTP) joint. Traditionally, this was performed using physician applied custom splint or cast and achieved a high degree of immobilization. Braces and orthotics are becoming less expensive and have several advantages, such as light weight and convenience in removal. However, this may come at the expense of ability to restrict movement. We hypothesize that generic braces will provide as much immobilization as custom applied plaster splints. Methods: Healthy volunteers were instrumented with electromagnetic sensors over bony prominences of the right foot. Range of motion exercises and activities of daily living were performed without an immobilization device. The same procedure was repeated with each of three immobilization devices: a post-operative shoe, a walking boot, and a custom applied plaster splint. Position and angular data were collected to determine range of motion primarily of the hallux MTP joint. This study was approved by the hospital IRB Results: Compared to baseline, all three immobilization devices significantly reduced range of motion at the MTP joint in non- weight bearing with the ankle in dorsiflexion and plantarflexion (p<0.05). There was no significant difference detected between the devices. There was no significant difference in hallux motion during the standing exercise in any of the immobilization devices compared to baseline. During stance phase of gait, all three devices reduced range of motion at the MTP joint compared to baseline (p<0.05), though there was no statistically significant difference between devices. Conclusion: Consistent with the hypothesis, data from this study show that all both generic devices and the physician applied splint reduced range of motion compared to baseline. Unfortunately, the study was not powered enough to detect significant differences between the devices, though there was a trend towards the walking boot providing more immobilization

Prostate field cancerization: deregulated expression of macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) in tumor adjacent tissue.

Prostate field cancerization denotes molecular alterations in histologically normal tissues adjacent to tumors. Such alterations include deregulated protein expression, as we have previously shown for the key transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS). Here we add the two secreted factors macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) to the growing list of protein markers of prostate field cancerization. Expression of MIC-1 and PDGF-A was measured quantitatively by immunofluorescence and comprehensively analyzed using two methods of signal capture and several groupings of data generated in human cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and PDGF-A expression in tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01 to p = 0.23, respectively). In support of field cancerization, MIC-1 and PDGF-A expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x, respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC-1 and PDGF-A expression were similar in tumor and adjacent tissues (0.3x to 1.0x; p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for PDGF-A). All analyses indicated a high level of inter- and intra-tissue heterogeneity across all types of tissues (mean coefficient of variation of 86.0%). Our data shows that MIC-1 and PDGF-A expression is elevated in both prostate tumors and structurally intact adjacent tissues when compared to disease-free specimens, defining field cancerization. These secreted factors could promote tumorigenesis in histologically normal tissues and lead to tumor multifocality. Among several clinical applications, they could also be exploited as indicators of disease in false negative biopsies, identify areas of repeat biopsy, and add molecular information to surgical margins

MIC-1 detection and quantitation in human prostate tissues (commercial tissue microarray).

<p>(A-B) Immunofluorescence with anti-MIC-1 antibody in a representative prostate tumor (A) and tumor adjacent tissue (B); pictures represent overlays of nuclear staining by DAPI (blue) and Alexa Fluor 488 immunostaining (yellow/white); the insets are Alexa Fluor 488 immunostaining only; white bars represent 10 micrometers. The diamond, closed arrow, and open arrow in B denote a typical lumen, epithelial cell compartment, and stromal cell compartment, respectively. (C-D) MIC-1 expression levels (indicated as signal intensities [pixel count]) in matched tumor adjacent and tumor tissues; the types of analysis were the following (as per <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119314#sec002" target="_blank">Materials and Methods</a>): (C) Whole slide analysis (WSA), (D) region of interest (ROI) analysis. Individual data points are shown as small black squares (partially overlapping); the boxes represent group medians (line across middle) and quartiles (25th and 75th percentiles) at its ends; lines above and below boxes indicate 10th and 90th percentiles, respectively. For each analysis, the number of images and cases is indicated; p values above the panels denote the level of statistical significance for the differences between groups, as calculated by the student’s t-test (p(t)) and by the Wilcoxon rank sums test (p(WRS)).</p

Quantitative immunofluorescence of MIC-1 in human prostate tissues.

<p>(A-D) MIC-1 expression levels (indicated as signal intensities [pixel count]) in disease-free, tumor adjacent, and tumor tissues; the types of analysis were the following (as per <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119314#sec002" target="_blank">Materials and Methods</a>): (A and B) Whole slide analysis (WSA) for all (A) and non-matched (B) cases in the UNMH/CHTN cohort; (C and D) region of interest (ROI) analysis for all (C) and non-matched (D) cases in the UNMH/CHTN cohort. Individual data points are shown as small black squares (partially overlapping); the boxes represent group medians (line across middle) and quartiles (25th and 75th percentiles) at its ends; lines above and below boxes indicate 10th and 90th percentiles, respectively. For each analysis, the number of images and cases is indicated; p values above the panels denote the level of statistical significance for the differences between groups, as calculated by the student’s t-test (p(t)) and by the Wilcoxon rank sums test (p(WRS)).</p

MIC-1 (A-C) and PDGF-A (D-F) detection in human prostate tissues (UNMH/CHTN cohort).

<p>Representative cases of prostate tumors (A and D) and adjacent tissues (B and E), as well as cases of disease-free control tissues unrelated to cancer (C and F) are shown; pictures represent overlays of nuclear staining by DAPI (blue) and Alexa Fluor 633 immunostaining (yellow/white); the insets are Alexa Fluor 633 immunostaining only; white bars represent 10 micrometers. The diamonds, closed arrows, and open arrows in B and E denote a typical lumen, epithelial cell compartment, and stromal cell compartment, respectively.</p

Quantitative immunofluorescence of PDGF-A in human prostate tissues.

<p>(A-D) PDGF-A expression levels (indicated as signal intensities [pixel count]) in disease-free, tumor adjacent, and tumor tissues; the types of analysis were the following (as per <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119314#sec002" target="_blank">Materials and Methods</a>): (A and B) Whole slide analysis (WSA) for values above (A) and below (B) the median of the values of all cases in the UNMH/CHTN cohort; (C and D) region of interest (ROI) analysis for values above (A) and below (B) the median of the values of all cases in the UNMH/CHTN cohort. Individual data points are shown as small black squares (partially overlapping); the boxes represent group medians (line across middle) and quartiles (25th and 75th percentiles) at its ends; lines above and below boxes indicate 10th and 90th percentiles, respectively. For each analysis, the number of images and cases is indicated; p values above the panels denote the level of statistical significance for the differences between groups, as calculated by the student’s t-test (p(t)) and by the Wilcoxon rank sums test (p(WRS)).</p