Biomedical subjects

Christopher K Breuer

Publications and source records attributed to Christopher K Breuer.

8 recordsLinked to original sources

PubMed2026

Serum Proteomic Profiling Implicates a Dysregulated Neurohormonal-Inflammatory Axis in Post-Fontan Sinus Tachycardia.

BACKGROUND: Postoperative sinus tachycardia is a poorly understood complication following the Fontan procedure. The molecular signaling cascades triggering acute tachycardia remain uncharacterized, limiting therapeutic innovation. Here, we present a retrospective study leveraging serum proteomics and machine learning to identify the molecular drivers of postoperative Fontan sinus tachycardia. METHODS: We integrated a clinically relevant ovine Fontan model with continuous telemetric heart rate monitoring and human patient data. Serum proteomics coupled with least absolute shrinkage and selection operator and Boruta machine learning algorithms were used to identify protein panels predictive of postoperative sinus tachycardia. Cross-species validation was performed by comparing proteomic signatures from sheep and pediatric patients undergoing Glenn or Fontan surgery. RESULTS: Ovine Fontan animals demonstrated significant heart rate elevation beginning on postoperative day 1, peaking at postoperative day 3 (159.4±11.7 bpm versus preoperative, 105.3±10.5 bpm; P=0.0002), before trending toward baseline by postoperative day 10. This pattern was mirrored in human patients with a more modest magnitude. Surgical controls did not exhibit tachycardia. The principal component most correlated with heart rate (principal component 1: r=0.78, P=2.2×10-4) was enriched for inflammatory and neural pathways. The Boruta algorithm identified an 11-protein panel with strong predictive power (area under the receiver operating characteristic curve, 0.963). Cross-species comparison demonstrated that angiotensinogen, angiotensin-converting enzyme, and pentraxin 3 were similarly dysregulated in both species postoperatively. CONCLUSIONS: This study provides molecular evidence implicating a dysregulated neurohormonal-inflammatory axis in acute postoperative Fontan sinus tachycardia and establishes a foundation for developing targeted diagnostics and therapeutics for this complication.

Animals↗

PubMed2007

Construction of an autologous tissue-engineered venous conduit from bone marrow-derived vascular cells: optimization of cell harvest and seeding techniques.

BACKGROUND: Currently available vascular grafts for pediatric cardiovascular operations are limited by their inability to grow. Tissue-engineering techniques can be used to create vascular grafts with the potential for repair, remodeling, and growth. This study demonstrates the feasibility of constructing an autologous tissue-engineered venous conduit from bone marrow-derived vascular cells (BMVCs) in the ovine animal model. METHODS: Ovine mononuclear cells were isolated from the bone marrow, cultured in endothelial growth medium, and characterized with immunocytochemistry. Biodegradable tubular scaffolds were constructed from polyglycolic acid mesh coated with a copolymer of poly[epsilon-caprolactone-L-lactide]. Scaffolds were seeded at various cell concentrations and incubation times to optimize seeding conditions for the construction of an autologous venous conduit. Using optimized conditions, 6 tissue-engineered vascular grafts were implanted as inferior vena cava interposition grafts in juvenile lambs. Grafts were assessed for patency at days 1 to 30 postoperatively and explanted for histological and immunohistochemical analysis. RESULTS: A mixed cell population of BMVCs consisting of smooth muscle cells and endothelial cells was cultured from ovine sternal bone marrow. A seeding concentration of 2 x 10(6) cells/cm2 and 7 days of postseeding incubation were optimal for creating a confluent cellular layer on the polyglycolic acid/poly[epsilon-caprolactone-L-lactide]) scaffold. Grafts were explanted up to 4 weeks postoperatively. All grafts were patent without evidence of thrombosis. Histological evaluation of the explanted grafts demonstrated neo-endothelialization. Graft wall was composed of neo-tissue made up of residual polymer matrix, mesenchymal cells, and extracellular matrix without evidence of calcification. CONCLUSIONS: Bone marrow-derived vascular cells, containing endothelial and smooth muscle cells, can be isolated and cultured from ovine sternal bone marrow and used as a cell source for vascular tissue engineering. Our optimized techniques for BMVC harvest and seeding onto biodegradable scaffolds can be used for studying autologous tissue-engineered vascular grafts in the ovine animal model.

Animals↗

PubMed2006

The appendix sign: a radiographic marker for irreducible intussusception.

PURPOSE: Radiographic reduction (hydrostatic or pneumatic) of intussusception has become the standard of care in the pediatric population with success rates of more than 80%. Identification of those patients who are likely to fail nonoperative management could lead to earlier operation, a reduction in radiation exposure, and a decreased risk for complications after repeated attempts at enema reduction. During successful radiographic reduction, the small bowel is almost always visualized before the appendix. Visualization of the appendix before visualization of the small bowel during a successful reduction of an intussusception is a rare event. We report a new radiographic sign that we have termed the appendix sign (radiographic visualization of the appendix without reflux of air or contrast into the small intestine), which we hypothesize may have association with failure of nonoperative management. METHOD: We performed a retrospective review of the last 12 years of irreducible intussusception. The associated studies were then reviewed to examine the incidence, sensitivity, and specificity of this radiographic finding. RESULTS: Ninety-one cases of intussusception were identified and had films available for review. Seventy-seven (76%) of the studies included the appropriate image. The appendix sign was visualized in 14 studies for an incidence of 18%. Of 14 patients, 10 failed enema reduction (positive predictive value, 71%). The sensitivity of the appendix sign is 43%. The specificity of the sign is 93%. CONCLUSIONS: Our experience suggests that the presence of an appendix sign is associated with failing enema reduction of an intussusception and may be useful as a marker for determining the end point for further attempts at radiographic reduction.

Appendix↗

PubMed2006

Development of a model system for preliminary evaluation of tissue-engineered vascular conduits.

BACKGROUND/PURPOSE: The ability to construct tissue-engineered neovessels for use as arterial or venous grafts holds great promise for the advancement of pediatric surgical disciplines. Although the feasibility of tissue engineering vascular grafts has been demonstrated, the long-term function, safety, and efficacy of these grafts as well as their capacity to grow and adapt remain largely unknown. In an attempt to further characterize and develop this technology, we used severe combined immunodeficiency beige (SCID/bg) mouse recipients, chosen because such animals accept xenogenic human cells, to create a small animal model that would allow a rapid and cost-effective preliminary evaluation of the function of tissue-engineered vascular grafts. METHODS: Eight CB-17 SCID/bg female mice underwent vascular graft placement. Four of these mice received aortic interposition grafts, 1 mouse received an inferior vena cava interposition graft, and 3 mice underwent aortocaval graft insertion. All grafts were fashioned from decellularized ovine arteriole tissue engineering scaffolds. Grafts were evaluated for patency using clinical examination, ultrasound interrogation, and micro-computed tomography. Animals were killed at various time points after implantation, and grafts were harvested and analyzed histologically using standard hematoxylin and eosin staining. RESULTS: All grafts were patent based on clinical examination for up to 35 days. Patency was confirmed in 5 grafts using ultrasound interrogation. Patency was confirmed in 4 grafts using micro-computed tomography. One animal that underwent arteriovenous grafting had to be euthanized secondary to high-output cardiac failure on postoperative day 2. The remaining animals were killed between postoperative days 12 and 35. Histologic evaluation of the specimens demonstrated patent grafts with cellular ingrowth into the tissue engineering scaffold. CONCLUSIONS: From these results, we conclude that the use of the SCID/bg mouse model for preliminary evaluation of new tissue engineering methodologies for construction of vascular conduits is feasible. Use of this model has the added advantage of evaluating nonautologous and even xenograft tissues, including human cells.

Animals↗

PubMed2005

A case report of midgut atresia and spontaneous closure of gastroschisis.

We report a case in which a neonate with a prenatal diagnosis of gastroschisis was born with midgut atresia and the mummified remains of the midgut arising from a spontaneously closed abdominal wall defect. As our ability to prenatally diagnose abdominal wall defects has improved, we have gained some insight into the prenatal natural history of this pathological process. We present a case in which an abdominal wall defect spontaneously closed and was associated with an apparent in utero midgut vascular accident. This unusual case provides some insight into the mechanisms underlying the pathophysiology of gastroschisis.

Adolescent↗

PubMed2005

Neuroblastoma update.

PURPOSE OF REVIEW: The purpose of this paper is to review the most recent medical literature pertaining to neuroblastoma. Clinically, progress continues to be made on the refinement of radiographic staging and risk stratification-based treatment. RECENT FINDINGS: Meanwhile, experimental efforts focus on the continued search for biologic prognostic markers and the development of novel therapies including second-generation retinoids, tumor vaccines, and new modes of drug delivery with improved safety and efficacy. SUMMARY: Review of the recent neuroblastoma literature demonstrates continued progress in our ability to understand and treat this enigmatic tumor.

Biomarkers, Tumor↗

PubMed2002

Extracorporeal membrane oxygenation in piglets using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201).

PURPOSE: The purpose of this study was to determine if the polymerized bovine hemoglobin-based oxygen-carrying solution HBOC-201 is an acceptable substitute for blood in a healthy porcine, extracorporeal membrane oxygenation (ECMO) model. METHODS: Ten piglets (15 to 25 kg) were placed on venoarterial ECMO. Four animals received blood-primed ECMO, and 6 animals received HBOC-201-primed ECMO. Hemodynamic variables, urine output, blood gas analyses, complete blood counts, and lactate levels were followed for 6 hours. Data were analyzed using a nonparametric sign test and repeated measures analysis of variance (ANOVA). RESULTS: All animals survived the 6-hour ECMO procedure. Heart rate, mean arterial pressure, urine output, and serum lactate levels were not significantly different between groups. Postpriming volume was 176 +/- 156 mL in the blood group. None of the animals in the HBOC-201 group required additional volume to maintain target flow during ECMO (P <.05). Arterial pH, pO2, and oxygen content between groups were not significantly different. Hematocrit for the HBOC-201 group was significantly (P <.05) lower than the blood group. CONCLUSIONS: HBOC-201-primed ECMO in a healthy porcine model showed similar hemodynamics and equivalent oxygen carrying capacity to blood-primed ECMO. Postpriming volume requirement was decreased significantly in the HBOC group. ECMO using HBOC-201 instead of blood appears promising and warrants further investigation.

Animals↗

PubMedDate not supplied

Application of tissue-engineering principles toward the development of a semilunar heart valve substitute.

Heart valve disease is a significant medical problem worldwide. Current treatment for heart valve disease is heart valve replacement. State of the art replacement heart valves are less than ideal and are associated with significant complications. Using the basic principles of tissue engineering, promising alternatives to current replacement heart valves are being developed. Significant progress has been made in the development of a tissue-engineered semilunar heart valve substitute. Advancements include the development of different potential cell sources and cell-seeding techniques; advancements in matrix and scaffold development and in polymer chemistry fabrication; and the development of a variety of bioreactors, which are biomimetic devices used to modulate the development of tissue-engineered neotissue in vitro through the application of biochemical and biomechanical stimuli. This review addresses the need for a tissue-engineered alternative to the current heart valve replacement options. The basics of heart valve structure and function, heart valve disease, and currently available heart valve replacements are discussed. The last 10 years of investigation into a tissue-engineered heart valve as well as current developments are reviewed. Finally, the early clinical applications of cardiovascular tissue engineering are presented.

Animals↗