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Biomedical subjects

David Mooney

Publications and source records attributed to David Mooney.

9 recordsLinked to original sources
PubMed2006

Tissue engineering of a small hand phalanx with a porously casted polylactic acid-polyglycolic acid copolymer.

In this study, we evaluate a porous polylactic acid-polyglycolic acid (PLGA) polymer in tissue engineering a small hand phalanx. The PLGA polymer was processed with a unique solvent cast/salt-leaching method in the shape of a little finger distal phalanx. An 85% polylactic acid (PLA)/15% polyglycolic acid (PGA) copolymer was determined to be the most favorable mixture for creating a small digital phalanx in precise shape and size. The pore sizes averaged 250-425 microm. Bovine periosteum was wrapped around each phalangeal polymer. Chondrocytes were injected into the articular end. Six constructs were surgically placed into a dorsal subcutaneous pocket of an ethylic mouse. After 8 (n=2) or 16 (n = 4) weeks, all implants demonstrated growth of bone and cartilage in the shape and size of a small hand phalanx, which was maintained throughout the study period. Histologic evaluation showed a homogeneous presence of bone and cartilage, with progressive tissue differentiation and matrix production from 8 to 16 weeks. The tissue-engineered bone formed through an endochondral ossification process. Articular cartilage was maintained where the chondrocytes were placed. These findings suggest that the porous PLGA polymer is an effective synthetic biodegradable device to support and guide tissue growth of bone and articular cartilage in the shape of a human phalanx.

Absorbable Implants↗
PubMed2006

The use of routine laboratory studies as screening tools in pediatric abdominal trauma.

BACKGROUND: Standard laboratory panels were shown to play an important role in the evaluation of pediatric blunt abdominal trauma before the routine use of computed tomography (CT) scan. Recently, only a few relatively limited studies have evaluated the use of these "trauma panels." OBJECTIVE: To evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of routine "trauma panels" for evaluating intra-abdominal injury in pediatric blunt trauma patients. METHOD: We undertook a retrospective medical record review of all children with potential major blunt abdominal trauma who entered the Children's Hospital (Boston, MA) trauma registry from July 1996 to August 1999. Routine laboratory tests during those years included sodium, glucose, white blood cell count, hematocrit, platelets, prothrombin time, activated partial thromboplastin time, aspartate aminotransferase (AST), alanine aminotransferase, amylase, lipase, and urinalysis. Individual findings were considered abnormal if they fell out of the laboratory's respective reference range. We determined sensitivity, specificity, PPV, NPV, and the 95% confidence interval for each test, using abdominal pathology identified by CT scan as the gold standard. RESULTS: Three hundred eighty-two patients were included. Of that, 68% were men. Median age was 115 months (intraquartile range, 60-159 months). In total, 241 of the patients (63%) had an abdominal CT scan performed, 83 of which (33%) had abnormal findings. Abnormal values for glucose, AST, urinalysis, and white blood cell count were the most frequently observed abnormalities (67%, 47%, 43%, and 43%, respectively). Among the 83 patients with abdominal pathology, glucose and AST had the highest sensitivity (75% and 63%, respectively). Lipase had the highest PPV at 75%, and AST had the highest negative predictive at 71%. No routine laboratory test had excellent sensitivity, specificity, PPV, and NPV. CONCLUSIONS: Routine "trauma panels" should not be obtained as a screening tool in children with blunt trauma being evaluated for intra-abdominal injury.

Abdominal Injuries↗
PubMed2005

Combination treatment significantly enhances the efficacy of antitumor therapy by preferentially targeting angiogenesis.

Radiotherapy is one of the most widely used cancer treatments, but it is often unsuccessful due to the development of radioresistance by tumor cells and endothelial cells (ECs) lining the tumor blood vessels. We have previously shown that ECs are protected against ionizing irradiation primarily via the activation of the phosphoinositide 3-kinase (PI3 K)-Akt-Bcl-2 survival pathway. Here we report that combination treatment with low doses of PI3 K inhibitor (LY294002), cisplatin and gamma-irradiation resulted in significantly higher (61%) EC death as compared to each agent used alone (17, 17 and 11%, respectively). This combination treatment was equally effective in inducing tumor cell death (72%). Combination treatment also significantly inhibited EC tube formation in Matrigel (75%) as compared to each of the agents used alone (8, 8 and 18% for LY294002, cisplatin and gamma-irradiation, respectively). In our in vivo severe combined immunodeficient mouse model of human tumor growth and angiogenesis, combination treatment with low doses of LY294002, cisplatin and irradiation significantly inhibited the growth of human oral squamous carcinoma (OSCC-3) as well as prostate cancer (LnCap). The combination therapy was also very effective in inhibiting tumor angiogenesis where it showed a greater than 90% decrease in neovascularization. In contrast, combination treatment showed only a 29% inhibition of physiological angiogenesis. Taken together, these results suggest a potentially novel strategy to overcome the resistance in ECs lining tumor blood vessels, thereby enhancing the effectiveness of the radiation and chemotherapy. Moreover, this strategy of using a combination of low doses of PI3K/Akt inhibitor, cisplatin and radiation has the potential of significantly decreasing untoward side effects associated with the maximum tolerated doses of radiation and chemotherapy while maintaining their therapeutic efficacy.

Animals↗
PubMed2005

A randomized clinical trial of the management of esophageal coins in children.

CONTEXT: Children frequently ingest coins. When lodged in the esophagus, the coin may cause complications and must either be removed or observed to pass spontaneously. OBJECTIVES: (1) To compare relatively immediate endoscopic removal to a period of observation followed by removal when necessary and (2) to evaluate the relationship between select clinical features and spontaneous passage. DESIGN/SETTING: Randomized, prospective study of children <21 years old who presented to an emergency department with esophageal coins in the esophagus. Exclusion criteria were (1) history of tracheal or esophageal surgery, (2) showing symptoms, or (3) swallowing the coin >24 hours earlier. Children were randomized to either endoscopic removal (surgery) or admission for observation, with repeat radiographs approximately 16 hours after the initial image. OUTCOME MEASURES: Proportion of patients requiring endoscopic removal, length of hospital stay, and the number of complications observed. RESULTS: Among 168 children who presented with esophageal coins lodged in the esophagus, 81 were eligible. Of those eligible, 60 enrolled, 20 refused consent, and 1 was not approached. In the observation group, 23 of 30 (77%) children required endoscopy compared with 21 of 30 (70%) in the surgical group. Total hospital length of stay was longer in the randomized-to-observation group compared with the randomized-to-surgery group (mean: 19.4 [SD: +/-8.0] hours vs 10.7 [SD: +/-7.1] hours, respectively). There were no complications in either group. Spontaneous passage occurred at similar rates in both groups (23% vs 30%). Spontaneous passage was more likely in older patients (66 vs 46 months) and male patients (odds ratio: 3.7; 95% confidence interval: 0.98-13.99) and more likely to occur when the coin was in the distal one third of the esophagus (56% vs 27% [95% confidence interval: 1.07-5.57]). CONCLUSIONS: Because 25% to 30% of esophageal coins in children will pass spontaneously without complications, treatment of these patients may reasonably include a period of observation, in the range of 8 to 16 hours, particularly among older children and those with distally located coins.

Child↗
PubMed2003

Tissue-engineered neomucosa: morphology, enterocyte dynamics, and SGLT1 expression topography.

BACKGROUND: The standard therapy for short bowel syndrome is total parenteral nutrition, which is expensive and associated with significant morbidity and mortality. New therapeutic approaches for this disorder are needed. We have applied the techniques of tissue engineering to develop a prototype neointestine. We hypothesized that anastomosis of this neointestine to the native bowel would result in regeneration of mucosal morphology and enterocyte dynamics. METHODS: Biodegradable polymers seeded with neonatal rat intestinal organoid units were implanted into the omenta of adult rats to form neointestinal cysts. Five weeks after implantation, side-to-side cyst-jejunal anastomoses were fashioned in one cohort of rats. Tissues were harvested from all rats at 5 months after implantation. Native jejunal (J) and non-anastomosed (N-N) and anastomosed (A-N) neointestinal tissues were assessed for morphology, epithelial cell proliferation (5-bromo-2-deoxyuridine immunohistochemistry), apoptotic rates (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay), and SGLT1 in situ hybridization. RESULTS: Mucosal morphology, rates and topography of enterocyte proliferation, and transporter expression in A-N neointestine recapitulated those of native jejunum. Each of these features was rudimentary in N-N neointestine. CONCLUSIONS: These results suggest that the tissue-engineered neomucosa can develop structural and dynamic features of the normal jejunum. Anastomosis to the native intestine is an essential step for neomucosal development. Tissue engineering offers promise as a novel approach to the treatment of patients suffering from short bowel syndrome.

Animals↗
PubMed2003

Tissue-engineered large intestine resembles native colon with appropriate in vitro physiology and architecture.

OBJECTIVE: Novel production and in vitro characterization of tissue engineered colon. SUMMARY BACKGROUND DATA: The colon provides important functions of short chain fatty acid production, sodium and water absorption, and storage. We report the first instance of tissue-engineered colon (TEC) production from autologous cells and its in vitro characterization. METHODS: Organoid units, mesenchymal cell cores surrounded by a polarized epithelia derived from full thickness sigmoid colon dissection from neonatal Lewis rats, adult rats, and tissue engineered colon itself, were implanted on a polymer scaffold into the omentum of syngeneic hosts. TEC was either anastomosed at 4 weeks or excised for Ussing chamber studies or histology, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling assay. RESULTS: TEC was generated by 100% of all animals without regard to tissue source, the first instance of engineered intestine from adult cells or an engineered tissue. TEC architecture is identical to native with muscularis propria staining for actin, acetylcholinesterase detected in a linear distribution in the lamina propria, S100-positive cells, ganglion cells, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling assay similar to native colon. Ussing chamber data indicated in vitro function consistent with mature colonocytes, and a positive short circuit current response to theophylline indicating intact ion transfer. TEM showed normal microarchitecture. Colon architecture was maintained in anastomosis with gross visualization of fluid uptake. CONCLUSIONS: TEC can be successfully produced with fidelity to native architecture and in vitro function from neonatal syngeneic tissue, adult tissue, and TEC itself.

Animals↗
PubMed2002

Hepatic exstrophy complicating Poland's anomaly.

Poland's anomaly is comprised of a constellation of anomalies. To be included in the syndrome, a child must have a deficiency of the pectoralis major and minor muscles and an associated anomaly of either the ipsilateral breast or hand. Associated defects may include syndactyly osseous and cartilagenous costal aplasia and adactyly. A case of hepatic exstrophy through a full-thickness chest wall defect in an infant with Poland's anomaly is reported.

Echocardiography↗
PubMed2002

Tissue-engineered colon exhibits function in vivo.

BACKGROUND: Postcolectomy morbidities include important changes in enterohepatic circulation, stool microbiology, and absorption. The surgical substitution of an ileal pouch for the absent colon also has a number of serious complications. We report in vivo colon replacement by tissue-engineered colon (TEC) in lieu of an ileal pouch. METHODS: End-ileostomies were created in 22 male Lewis rats. In 11 animals, side-to-side ileum-TEC anastomosis was performed 1 cm from the stoma. This group was compared with end-ileostomy alone. Serial weights were measured, and animals were harvested sequentially for assessment of histologic signs of pouchitis. Transit times, stool dry and wet weights, and serum and stool colon function markers were collected. RESULTS: Animals survived 41 days. Weight loss was more than 1.5 times greater in the end-ileostomy alone group compared with the ileum-TEC group. Transit times were significantly longer in the ileum-TEC group than the end-ileostomy alone group, with lower stool moisture content and higher total serum bile acids. Animals without TEC had statistically significant hyponatremia, elevated serum urea nitrogen, and lower stool short chain fatty acids (13.5 micromol/kg vs 84.2) with an abnormal distribution. CONCLUSIONS: TEC successfully recapitulates some major physiologic functions of native large intestine in vivo.

Anastomosis, Surgical↗