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Biomedical subjects

Mihir S Wagh

Publications and source records attributed to Mihir S Wagh.

10 recordsLinked to original sources
PubMed2006

Survival studies after endoscopic transgastric oophorectomy and tubectomy in a porcine model.

BACKGROUND: Advances in endoscopic equipment have enabled endoluminal techniques to supplant select surgical procedures. Access to extraluminal structures holds the potential to revolutionize flexible endoscopy but, to date, has been limited. The aim of this study was to demonstrate the feasibility of endoscopic transgastric organ resection (oophorectomy and tubectomy) with 2-week survival. METHODS: Female Yorkshire pigs underwent general anesthesia, and a sterile esophageal overtube was placed. Antibacterial gastric lavage was performed, and a sterile gastroscope was passed through the overtube. Subsequently, a transgastric incision was made with a needle knife. The endoscope then was advanced into the peritoneal cavity, and the ovaries and the fallopian tubes were identified. An endoloop was used to secure the ovary, the fallopian tube, and the mesosalpinx. Snare cautery oophorectomy and tubectomy was performed, and the specimen was retrieved through the gastrotomy. The incision was closed with endoclips, and 2-week survival studies were performed. OBSERVATIONS: The peritoneal cavity was accessed in all animals (n = 6) without significant complications. The ovaries and the fallopian tubes were easily identified, and unilateral oophorectomy and tubectomy were successfully performed. Postoperative 2-week survival was uneventful in all animals. At necropsy, the gastric incision was seen as a well-healed scar with giant-cell reaction. There was histologic evidence of chronic inflammation at the resection site, without abscess, hematoma, adhesion, or damage to surrounding viscera. CONCLUSIONS: Endoscopic transgastric oophorectomy and tubectomy with 2-week survival is feasible with meticulous closure of the gastrotomy. This novel technique may extend the applications of flexible endoscopy to include aspects of abdominal surgery.

Animals↗
PubMed2006

Peroral transgastric organ resection: a feasibility study in pigs.

BACKGROUND: The feasibility of peroral transgastric peritoneoscopy, liver biopsy, and tubal ligation has been demonstrated in prior animal studies. This approach has the potential to reduce postoperative morbidity. OBJECTIVE: To explore the technical challenges and complications of performing a transgastric organ resection. DESIGN: Two-week animal survival study. INTERVENTIONS: Five female Yorkshire pigs underwent peroral transgastric partial hysterectomy. With the animals under general anesthesia, a sterile esophageal overtube was placed and a gastric antibiotic lavage was performed. Subsequently, a needle-knife and through-the-scope dilating balloon were used to make an anterior gastric wall incision through which a therapeutic gastroscope was advanced into the peritoneal cavity. Endoscopes and instruments previously had been disinfected in a 2.4% glutaraldehyde bath or were disposable. An endoloop and polypectomy snare were used to resect a portion of the uterus, which was removed through the mouth. Gastric incision closure was attempted with endoclips. After 2 weeks of observation, necropsy was performed. RESULTS: Transgastric partial hysterectomy was performed on all 5 animals. One animal became lethargic and febrile, so necropsy was performed on day 4. An incompletely closed gastric incision and suppurative peritonitis were found. A second animal developed a fever; necropsy performed on day 14 revealed a gastric abscess at the incision site and scattered abdominal pus. No complications were encountered in the 3 remaining animals, and necropsy revealed well-healed gastric incisions and no evidence of peritonitis. CONCLUSION: Endoscopic transgastric partial hysterectomy is technically feasible in a porcine model. Strict sterility seems mandatory but cannot always be assured. Incomplete closure of the gastric incision may lead to significant complications.

Animals↗
PubMed2006

Animal models for endoscopic simulation.

Animal models for GI endoscopy are a safe, reliable, and reproducible method for teaching diagnostic and therapeutic procedures and for developing techniques that have the potential to advance GI endoscopy. Although these methods never can replace human endoscopy as a modality for endoscopic training, animal models may serve as an adjunct to standard endoscopic training and safely enhance the hands-on experience.

Animals↗
PubMed2005

In vivo treatment of mice with heat shock protein, gp 96, improves survival of skin grafts with minor and major antigenic disparity.

Immunization with high doses of heat shock protein, gp 6 given in vivo, has been shown to mediate the activation of CD4+ T cell, which in turn suppresses an ongoing CD8+ immune response. Here we demonstrate that high doses of gp 6 (HDgp 6) (100 microg given subcutaneously on days 0 and 7 following skin graft transplantation) improve survival of skin grafts with both minor and major histocompatibility. First, skin from male C57BL/6 donors was grafted onto female C57BL/6 recipients that were subsequently treated with either HDgp 6 or buffer and graft survival was monitored. At 64 days post-transplantation, graft recipients treated with HDgp 6 showed 56% graft survival compared to 10% in those treated with buffer. Further, HDgp 6 down regulates a secondary immune response as well. Skin graft obtained from a male C57BL/6 donor was transplanted to a female C57BL/6 recipient that had previously rejected a male skin graft. Recipients that were treated with HDgp 96 showed a 75% graft survival of the secondary graft at 64 days post-transplantation, whereas recipients treated with buffer rejected their secondary grafts within 37 days. Finally, the effect of HDgp 96 treatment on survival of graft with major histoincompatibility was tested. Skin grafts from female BALB/c donors were transplanted to female C57BL/6 recipients previously treated with either HDgp 96 or buffer. Although all the grafts were ultimately rejected, mice treated with HDgp96 showed a delay in the rejection as compared with buffer controls. Our findings indicate that HDgp 96 improves survival of grafts with both minor and major antigenic disparity and could lead to developing novel therapies in transplant medicine.

Animals↗
PubMed2005

Endoscopic transgastric abdominal exploration and organ resection: initial experience in a porcine model.

BACKGROUND & AIMS: The evolution of flexible endoscopes and endoscopic devices has recently enabled per-oral transgastric abdominal exploration in animal models. This study was undertaken to assess the ability to systematically identify abdominopelvic organs and to determine the feasibility of organ resection via the transgastric route. METHODS: Female Yorkshire pigs were used for the study. Under general anesthesia, a gastroscope was used to place a sterile overtube into the esophagus. After antibacterial lavage, the gastric wall was incised, and a sterile dual-channel endoscope was advanced into the peritoneal cavity. Endoscopic abdominal exploration was then methodically performed in 9 animals with oophorectomy and partial hysterectomy in 6 animals. The gastric incision was closed with endoclips. Of the animals that underwent organ resection, 3 were sacrificed immediately after surgery, and the subsequent 3 survived. RESULTS: The peritoneal cavity was accessed uneventfully, and the stomach, liver, small bowel, colon, urinary bladder, uterus, fallopian tubes, and ovaries were able to be evaluated in all cases. The gallbladder could be visualized in only 5 of the 9 animals, and retroperitoneal structures could not be consistently identified. Oophorectomy with partial hysterectomy was performed in 6 animals. The 3 animals in the survival group did well for 24 hours without sequelae. CONCLUSIONS: This study shows the ability of endoscopic transgastric peritoneal exploration to successfully identify most abdominopelvic organs and demonstrates the technical feasibility of transgastric organ resection.

Abdomen↗
PubMed2005

Surveillance and screening for Barrett esophagus and adenocarcinoma.

Current recommendations for screening and surveillance of Barrett esophagus and related lesions are based on recent guidelines by the Practice Parameters Committee of the American College of Gastroenterology. The purpose of this review is to critically examine the rationale and evidence behind these recommendations. There is strong rationale for vigorous initial testing to document the baseline status and identify early adenocarcinoma, and for surveillance of high-grade dysplasia. Recommendations for esophagectomy in patients with high-grade dysplasia need to be individualized. However, recommendations for surveillance of low-grade dysplasia and specialized intestinal metaplasia without dysplasia are largely opinion statements not well supported by objective data. Although cancers identified by surveillance are at earlier stages than those diagnosed without prior endoscopic evaluation, surveillance failures are common. Recommendations for screening and surveillance are not evidence-based and unlikely to alter national mortality from esophageal adenocarcinoma. Their impact on individual patients depends on individual circumstances. Current recommendations are limited by inconsistent endoscopic findings and sampling errors, inconsistent histologic diagnoses of Barrett esophagus and dysplasia, and our poor understanding of the natural history of various histologic lesions. Future directions include validation of methods that reduce these inconsistencies by in vivo detection of abnormalities and by objective diagnostic markers besides grades of dysplasia, such DNA content analysis and molecular markers, and improved understanding of the disease progression. Effective screening programs depend on development of simple, inexpensive, and reliable methods to identify the small group of patients truly at high risk for adenocarcinoma for endoscopic screening.

Adenocarcinoma↗
PubMed2004

Life-threatening acute airway obstruction in achalasia.

Acute airway obstruction from mega-esophagus is an extremely rare presentation of achalasia. We present the case of an 82-year-old woman without previously diagnosed achalasia who presented with shortness of breath. Her respiratory status deteriorated rapidly, with development of stridor. Prompt nasogastric tube placement decompressed the dilated esophagus and relieved airway obstruction. This case illustrates an unusual presentation of achalasia and underscores the need for emergent life-saving esophageal decompression. Hypotheses regarding the mechanism of airway compromise as well as treatment options are reviewed.

Acute Disease↗
PubMed2004

Immune modulation with high-dose heat-shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis.

Immunization with heat-shock protein (HSP) gp96 elicits protective immunity to the cancer or virus-infected cells from which it is derived. Low doses of gp96 generate immunity, while doses 10 times the immunizing dose do not. We show here that injection of high doses of gp96 generates CD4(+) T cells that down-regulate a variety of ongoing immune responses. Immunization with high doses of gp96 prevents myelin basic protein- or proteolipid protein-induced autoimmune encephalomyelitis in SJL mice and the onset of diabetes in non-obese diabetic mice. The suppression of immune response can be adoptively transferred with CD4(+) cells and does not partition with the CD25 phenotype. The immunomodulatory properties of gp96 (and possibly other HSP) may be used for antigen-specific activation or suppression of cellular immune responses. The latter may form the basis for novel immunotherapies for autoimmune diseases.

Adoptive Transfer↗
PubMedDate not supplied

In vivo delivery of heat shock protein 70 accelerates wound healing by up-regulating macrophage-mediated phagocytosis.

Injury causes tissue breakdown, which releases large quantities of intracellular contents into the extracellular space. Some of these materials are well-established activators of the immune system and include heat shock proteins (HSPs), uric acid, nucleotides, High Mobility Group Box-1 protein (HMGB-1), and DNA. Here, we show that in vivo delivery of HSPs into BALB/cJ mice with full-thickness wounds accelerates the rate of wound closure by 60% as compared with control-treated mice. The onset is rapid and the effect is sustained, dose dependent, and protein specific. Adoptive transfer of RAW264 macrophages pretreated with HSP70 into naïve recipients with a wound transfers the HSP-mediated effect on the rate of wound closure. Further, we demonstrate that part of the mechanism by which HSP70 accelerates wound closure is through the stimulation of macrophage-mediated phagocytosis of wound debris. Disabling the HSP70-mediated enhancement of phagocytosis abrogates the HSP-mediated acceleration of the healing process. These findings create two opportunities: one, therapeutic, wherein HSP70 could be used in the clinical management of wounds; and two, pathophysiologic, to decode signals by which the host defenses recognize and respond to injury.

Animals↗