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Biomedical subjects

M R Bonnell

Publications and source records attributed to M R Bonnell.

3 recordsLinked to original sources

Detection of Barrett's adenocarcinoma of the gastric cardia with sucrase isomaltase and p53.

BACKGROUND: Routine surveillance for dysplastic epithelium in patients with Barrett's esophagus has markedly improved prognosis. Many patients with short segments of Barrett's mucosa near the esophagogastric junction remain undiagnosed and at risk for the development of Barrett's adenocarcinomas (BA). Sucrase isomaltase (SI), an intestinal enzyme, is highly expressed in intestinal-type Barrett's mucosa and frequently expressed in dysplastic Barrett's mucosa and BA. Sucrose isomaltase is not expressed in normal esophageal or gastric mucosa. Alterations in the p53 tumor suppressor gene are frequent events in dysplastic Barrett's mucosa and BA and result in nuclear protein accumulation. The purpose of this study was to determine the presence or absence of these markers of Barrett's mucosa in adenocarcinoma of the esophagogastric junction or cardia. METHODS: Expression of SI and p53 were examined in 40 BAs and 25 cardia adenocarcinomas using immunohistochemical techniques. RESULTS: Sucrose isomaltase analysis revealed positive staining in 55% (22/40) of the BAs and 44% (11/25) of the cardia adenocarcinomas. Of 14 cardia adenocarcinomas that were SI negative, 100% (14/14) had no associated Barrett's mucosa. However, in 21 cardia adenocarcinomas with no associated Barrett's mucosa, 7/21 (33%) were SI positive. This suggests that SI-positive tumors may represent BA without the standard definition of Barrett's esophagus being met. P53 was present in 65% of BAs and 64% of cardia adenocarcinomas, demonstrating the importance and similarity of this gene alteration in both tumor types. Staining was positive for SI or p53 in 77% (50/65) of all tumors. Tumors of lower stage expressed SI more often than higher stage tumors. CONCLUSIONS: These data suggest that a subset of cardia adenocarcinomas represent BAs. Surveillance endoscopy incorporating additional esophagogastric junction biopsies and assessment of SI or p53 may improve detection of intestinalized Barrett's mucosa and early dysplastic changes.

Adenocarcinoma↗

An intrapleural lung prosthesis: rationale, design, and testing.

Extracorporeal life support (ECLS or ECMO) is standard treatment for severe respiratory failure but poses many contraindications to future lung transplantation. The solution to this dilemma is the implantable gas exchange device (IGED) or artificial lung. Preliminary efforts to create such an artificial lung have been made since 1970 and include designs involving single devices, intravascular devices (i.e., IVOX), and combination heart-lung devices. Stringent requirements govern the design of such a device, the most important of which are high gas exchange efficiency, low resistance to blood flow, and size. This paper describes such a device. It incorporates large diameter inflow and outflow ports in close proximity and a low resistance wound hollow fiber core encapsulated in a compliant outer shell which conserves the work of the right ventricle. In a large animal model (adult sheep) this device was connected in line with the main pulmonary artery in series with the native lungs. This configuration has the advantages of using the lungs as an embolic filter, perfusing the lungs with fully oxygenated blood, and maintaining the integrity of the anatomy necessary for transplant. Laboratory experiments have run > 8 h. Preliminary data show that the animals have remained hemodynamically stable while the devices have supported the animals completely by supplying 100% O2 saturation with PO2 values ranging from 250-350 mm Hg. Additionally, this model makes possible the study of respiratory failure without introducing other variables such as extracorporeal circuits or pumps. The other metabolic, endocrine, and reticuloendothelial functions of normal and injured lungs can now be studied more precisely by excluding these variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The development of an implantable artificial lung.

This report describes the development of an implantable gas exchange device. The device is composed of hollow fiber elements wound around a central open core enclosed in a compliant outer casing, offering very low resistance to blood while providing adequate gas exchange. The purpose of this study was to determine if this device design can completely support the gas exchange requirements of a large animal when the device is placed in series with the main pulmonary artery (PA). Six 40-80 kg adult sheep were used. The device was placed with vascular grafts anastomosed end to side on the proximal and distal main PA. The study began with the entire right ventricular blood flow being diverted through the device by occlusion of a snare around the PA between the vascular grafts. Total gas exchange then was provided by the device and the endotracheal tube was clamped. Results showed that this pumpless potentially implantable device is capable of completely supporting the gas exchange requirements of the experimental animals for up to 8 hours in the acute setting without significant change in cardiac index (CI) and oxygen consumption (VO2) compared with baseline. CI = 55.0 +/- 17.0 cc/min/kg versus 45.0 +/- 17.3 cc/min/kg. VO2 = 1.90 +/- 0.96 cc O2/min/kg versus 2.08 +/- 0.54 cc O2/min/kg.

Animals↗