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Biomedical subjects

William C Meyers

Publications and source records attributed to William C Meyers.

10 recordsLinked to original sources

Protein kinase C-alpha regulation of gallbladder Na+ transport becomes progressively more dysfunctional during gallstone formation.

Gallbladder Na+ absorption and biliary Ca2+ are both increased during gallstone formation and may promote cholesterol nucleation. Na+/H+ exchange (NHE) is a major pathway for gallbladder Na+ transport. Ca2+-dependent second messengers, including protein kinase C (PKC), inhibit basal gallbladder Na+ transport. Multiple PKC isoforms with species- and tissue-specific expression have been reported. In this study we sought to characterize Ca2+-dependent PKC isoforms in gallbladder and to examine their roles in Na+ transport during gallstone formation. Gallbladders were harvested from prairie dogs fed either nonlithogenic chow or 1.2% cholesterol-enriched diet for varying periods to induce various stages of gallstone formation. PKC was activated with the use of phorboldibutyrate, and we assessed gallbladder NHE regulation by measuring unidirectional Na+ flux and dimethylamiloride-inhibitable 22Na+ uptake. We measured gallbladder PKC activity with the use of histone III-S phosphorylation and used Gö 6976 to determine PKC-alpha contributions. Gallbladder PKC isoform messenger RNA and protein expression were examined with the use of Northern- and Western-blot analysis, respectively. Prairie dog and human gallbladder expresses PKC-alpha, betaII, and delta isoforms. The PKC activation significantly decreased gallbladder J(Na)(ms) and reduced baseline 22Na+ uptake by inhibiting NHE. PKC-alpha mediated roughly 42% of total PKC activity under basal conditions. PKC-alpha regulates basal gallbladder Na+ transport by way of stimulation of NHE isoform NHE-2 and inhibition of isoform NHE-3. PKC-alpha blockade reversed PKC-induced inhibition of J(Na)(ms) and 22Na+ uptake by about 45% in controls but was progressively less effective during gallstone formation. PKC-alpha contribution to total PKC activity is progressively reduced, whereas expression of PKC-alpha mRNA, and protein increases significantly during gallstone formation. We conclude that PKC-alpha regulation of gallbladder NHE becomes progressively more dysfunctional and may in part account for the increased Na+ absorption observed during gallstone formation.

Animals↗

Robotic surgery: a current perspective.

OBJECTIVE: To review the history, development, and current applications of robotics in surgery. BACKGROUND: Surgical robotics is a new technology that holds significant promise. Robotic surgery is often heralded as the new revolution, and it is one of the most talked about subjects in surgery today. Up to this point in time, however, the drive to develop and obtain robotic devices has been largely driven by the market. There is no doubt that they will become an important tool in the surgical armamentarium, but the extent of their use is still evolving. METHODS: A review of the literature was undertaken using Medline. Articles describing the history and development of surgical robots were identified as were articles reporting data on applications. RESULTS: Several centers are currently using surgical robots and publishing data. Most of these early studies report that robotic surgery is feasible. There is, however, a paucity of data regarding costs and benefits of robotics versus conventional techniques. CONCLUSIONS: Robotic surgery is still in its infancy and its niche has not yet been well defined. Its current practical uses are mostly confined to smaller surgical procedures.

Cardiac Surgical Procedures↗

Effect of hepatic artery flow on bile secretory function after cold ischemia.

These studies evaluated the influence of hepatic arterial flow on biliary secretion after cold ischemia. Preparation of livers for transplantation or hepatic support impairs biliary secretion. The earliest indication of cold preservation injury during reperfusion is circulatory function. Arterial flow at this time may be critical for bile secretion. Porcine livers were isolated, maintained at 4 degrees for 2 h and connected in an extracorporeal circuit to an anesthetized normal pig. The extracorporeal livers were perfused either by both the hepatic artery and portal vein (dual) or by the portal vein alone (single). Incremental doses of sodium taurocholate were infused into the portal vein of both the dual and single perfused livers, and the bile secretion was compared. Most endogenous bile acids are lost during hepatic isolation. After supplementation, the biliary secretion of phosphatidyl choline and cholesterol was significantly better in the dual than single vessel-perfused livers; however, no difference was seen in bilirubin output. Single perfused livers were completely unable to increase biliary cholesterol in response to bile acid. The dependence of bile cholesterol secretion on arterial flow indicates the importance of this flow to the detoxification of compounds dependent on phosphatidyl choline transport during early transplantation.

Animals↗

Porcine hepatic phospholipid efflux during reperfusion after cold ischemia.

BACKGROUND: Cold preservation produces hepatic injury that is difficult to assess during early reperfusion. The value of reperfusion plasma choline phospholipid in predicting subsequent organ function is documented in these studies. MATERIALS AND METHODS: Livers of female Yorkshire pigs were prepared for transplantation. After 2 h of cold ischemia the reperfusion plasma was evaluated for choline phospholipid and cholesterol. These values were correlated with bile secretion, hepatic hemodynamics, oxygen uptake, and plasma sorbitol dehydrogenase levels. RESULTS: The isolated porcine liver demonstrates a rapid efflux of choline phospholipids into plasma during early reperfusion after cold preservation. After this initial efflux no subsequent plasma increment occurred. These choline-phospholipid increments were isolated in plasma higher density (d > 1.063) lipoproteins and were not accompanied by equivalent increases in cholesterol. Neither biliary reflux nor lecithin cholesterol acyl transferase abnormalities contributed appreciably to the phospholipid increments in reperfusion plasma. Livers with the largest efflux of choline phospholipids had the most impaired circulatory and bile secretory function at 4 h of reperfusion. CONCLUSION: The immediate increase of choline phospholipids, particularly lysophosphatidylcholine, in reperfusion plasma after cold ischemia provides an index of the injury occurring during this interval and correlates with early organ function.

Animals↗

Regulation of NFkappaB in hepatic ischemic preconditioning.

BACKGROUND: The second messengers tyrosine kinase (TK) and protein kinase C (PKC) have been implicated in mediating the cellular signaling cascade during hepatic ischemic preconditioning (IPC). We evaluated the role of TK and PKC on the modulation of the transcription factor nuclear factor kappa B (NFkappaB) and its inhibitor IkappaB alpha during IPC. STUDY DESIGN: Yorkshire pigs underwent routine harvest. IPC livers underwent 15 minutes of ischemia and 15 minutes of in situ perfusion before harvest, with or without pretreatment with a TK inhibitor (genistein) or a PKC inhibitor (chelerythrine). During cold storage and reperfusion, tissue extracts were analyzed for IkappaB alpha phosphorylation and NFkappaB levels and for TK and PKC activity by Western blot. RESULTS: Control pig livers demonstrated no change in the levels of TK, PKC, IkappaB alpha, or NFkappaB before cold ischemia. IPC grafts demonstrated activation of TK and PKC with increased IkappaB alpha phosphorylation and NFkappaB levels before cold ischemia. IPC grafts pretreated with genistein demonstrated inhibition of TK activation but not of PKC activation. Genistein-pretreated grafts also demonstrated inhibition of IkappaB alpha phosphorylation and a lack of NFkappaB translocation to the nucleus throughout the entire experiment. IPC grafts pretreated with chelerythrine demonstrated inhibition of PKC activation but not TK activation. Chelerythrine-pretreated grafts also demonstrated IkappaB alpha phosphorylation before cold ischemia and enhanced nuclear levels of NFkappaB. CONCLUSIONS: Data suggest that the role of TK in IPC might be mediated in part by NFkappaB, but PKC does not depend on NFkappaB for its effect. Two parallel signaling pathways might explain these data.

Alkaloids↗

Surgical management of chronic lower abdominal and groin pain in high-performance athletes.

Formerly, most of the causes and treatments of chronic lower abdominal and groin pain in high-performance athletes eluded sports medicine specialists. Now we are much better at identifying and managing the different syndromes. Most of the advances are based on empiric evidence, although many pitfalls remain with respect to diagnosis and management of the various syndromes. This article reviews our current understanding of several of these clinical entities. We focus on lessons learned from a large 15-year experience.

Abdominal Pain↗

Hand-Assisted laparoscopic Surgery.

Hand-assisted laparoscopic surgery (HALS) has been sporadically described in the past to assist the surgeon during operations of complexity or when operations require specimen removal. The hand will offer the surgeon an advantage in terms of tactile feedback, exposure, retraction, or orientation so that it will enable him or her to operate with greater safety and efficiency. The fundamental pre-requisite for successful HALS is a reliable hand-assist device. We perform HALS for complex advanced laparoscopic surgery where it may save time, increase accuracy and improve safety. Additionally, this approach is considered for any operation that requires specimen removal, since an enlarged incision may be required. Early introduction of the hand may facilitate dissection and specimen removal.

Journal Article↗

New Device for Hand-Assisted Laparoscopic Surgery.

Laparoscopic surgery has undergone a rapid evolution since the first laparoscopic cholecystectomy of Erich Mühe in 1985. Many surgeons felt that further technological success would be related not only to increasing experience and skill of surgeons, but also technological advances which would enable surgeons to perform increasingly more difficult and complex tasks. Progress has been rapid for some, but broad acceptance by surgeons has been slow.

Journal Article↗

Donor hepatic function: a factor in postreperfusion syndrome.

Reperfusion of support livers after cold preservation produces hemodynamic instability (i.e., postreperfusion syndrome) in the recipient during both orthotopic liver transplantation and extracorporeal liver perfusion. We evaluated the effect of the normal porcine cold-preserved support liver on healthy recipient hemodynamics and in situ liver function during extracorporeal liver perfusion. Support livers were harvested from Yorkshire pigs and reperfused in an extracorporeal circuit with a healthy, anesthetized recipient pig. Correlation analyses were performed between support liver variables of function (oxygen consumption, bile flow, and biliary phospholipid and cholesterol output) and both recipient hemodynamic stability (heart rate, blood pressure, urine output, and vasopressor use) and hepatic function (bile flow and biliary phospholipid secretion). The data indicate that optimally functioning support livers are associated with improved recipient hemodynamic stability manifested by decreased recipient heart rate and vasopressor use and increased recipient urine output. Support livers exhibiting poor biliary secretory function (i.e., bile flow and phospholipid output) were associated with similarly diminished recipient liver biliary secretory function. These data indicate that the functional condition of the support liver after harvest and cold preservation may influence both recipient hemodynamic parameters and the endogenous function of the recipient liver.

Animals↗

Postoperative hypoxemia from clinically suspected pulmonary embolism complicated by patent foramen ovale.

Postoperative hypoxemia can be a challenging diagnostic and management dilemma for the clinician. We present here a case of postoperative hypoxemia following laparoscopic gastric bypass surgery secondary to presumed pulmonary embolism complicated with a patent foramen ovale. The diagnostic pitfalls associated with a negative spiral computed tomography scan and the impact of coexisting medical conditions aggravating the pulmonary dysfunction are reviewed.

Adult↗