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W C Meyers

Publications and source records attributed to W C Meyers.

At least 19 recordsLinked to original sources
PubMed2001

Protective effects of ischemic preconditioning on the cold-preserved liver are tyrosine kinase dependent.

BACKGROUND: Little data exist regarding the use of ischemic preconditioning before sustained hepatic cold storage. We hypothesized that ischemic preconditioning protects hepatic grafts via a tyrosine kinase-dependent pathway. METHODS: Six porcine livers underwent routine harvest (control). Five other livers underwent 15 min of in situ ischemia followed by 15 min of reflow before harvest (ischemic preconditioning). Another five livers were pretreated with a tyrosine kinase inhibitor (genistein) before preconditioning. Upon reperfusion and after 2 hours of cold storage, graft function, graft circulatory impairment, and markers of cellular damage were analyzed. Tissue cytoplasmic extracts were analyzed for tyrosine phosphorylation with Western blot. Significance was determined with t tests. RESULTS: Ischemic-preconditioned grafts demonstrated enhanced bile production, augmented responses to a bile acid challenge, and elevated O2 consumption (P<0.05) compared to controls. Also, preconditioned grafts demonstrated improved hepatic tissue blood flow and decreased hepatic vascular resistance (P<0.005) compared to controls. Endothelial cell preservation (factor VIII immunostain) was improved in preconditioned graft biopsies compared to controls. With genistein pretreatment, all observed improvements returned to control levels. Analysis of cytoplasmic extracts demonstrated an increase in tyrosine phosphorylation before cold ischemia in preconditioned grafts only, but not in control or genistein-pretreated grafts. CONCLUSIONS: The data indicate that ischemic preconditioning protects the liver from sustained cold ischemia and that tyrosine kinases are involved in preconditioning responses.

Alanine Transaminase↗
PubMed2001

Protein kinase C inhibition abrogates hepatic ischemic preconditioning responses.

INTRODUCTION: A transient period of warm ischemia prior to a longer ischemic episode (ischemic preconditioning) protects the hepatic graft from cold ischemia. The mechanism for this protection is unknown, as is the role of protein kinase C in ischemic preconditioning responses. METHODS: Livers from 40 kg Yorkshire pigs were harvested and subjected to 2 h of cold ischemia (n = 6) (control). Another group of harvested livers was pretreated with a 15-min ischemic period followed by 15 min of in situ perfusion with (n = 5) or without (n = 5) a protein kinase C inhibitor, chelerythrine. Following cold ischemia, all grafts were reperfused on a perfusion circuit and the following variables evaluated: (1) hepatic graft function, (2) graft circulatory impairment, (3) hepatocellular damage, and (4) endothelial cell damage. Protein kinase C levels were also evaluated by Western blot in the cytoplasm of all grafts. RESULTS AND DISCUSSION: Ischemic preconditioned grafts demonstrate improved graft function, reduced graft circulatory impairment, and reduced endothelial cell damage as compared to cold ischemia controls. When preconditioned grafts were pretreated with chelerythrine, graft function, graft circulatory impairment, and endothelial cell damage were no different than cold ischemia controls. Ischemic preconditioned grafts demonstrated decreased levels of protein kinase C prior to cold ischemia. There was no change in protein kinase C levels in cold ischemia controls or chelerythrine-pretreated grafts prior to cold ischemia. These data indicate that modulation of protein kinase C is essential for ischemic preconditioning responses in the cold preserved hepatic graft.

Alkaloids↗
PubMed2001

Elevated intrahepatic pressures and decreased hepatic tissue blood flow prevent gas embolus during limited laparoscopic liver resections.

BACKGROUND: As new techniques are emerging for laparoscopic liver resections, concerns have been raised about the development of gas embolus related to the CO(2) pneumoperitoneum. We hypothesized that elevated intrahepatic vascular pressures and decreased hepatic tissue blood flow (LQB) would prevent gas embolus during laparoscopic liver resections under conventional pneumoperitoneum. METHODS: Intrahepatic vascular pressures and LQB were measured in nine pigs with varying CO(2) pneumoperitoneum. Gas embolus was determined after hepatic incision by monitoring pulmonary arterial pressure (PAP), hepatic venous PCO(2), systemic blood pressure (SBP), and suprahepatic vena cava ultrasound. RESULTS: As the pneumoperitoneum was increased from 0 to 15 mmHg, intrahepatic vascular pressures increased significantly (p < 0.05), while LQB decreased significantly (p < 0.05). A 2.0-cm hepatic incision at 4, 8, 15, and 20mmHg produced no ultrasound evidence of gas embolus and no changes in PAP, SBP, or hepatic venous PCO(2) (p = NS). CONCLUSION: These data suggest that the risk of significant embolus under conventional pneumoperitoneum is minimal during laparoscopic liver resections.

Animals↗
PubMed2001

V-PYRRO/NO: an hepato-selective nitric oxide donor improves porcine liver hemodynamics and function after ischemia reperfusion.

BACKGROUND: The role of nitric oxide (NO) in ischemia reperfusion (I/R) injury is controversial as both beneficial and harmful effects have been reported. We explored the potential role of a pharmacological agent recently shown to generate NO metabolically in the liver in an animal model of transplantation. METHODS: The effect of a selective hepatic NO donor, O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), on hepatic hemodynamics and biliary function was evaluated in both the in situ and I/R pig liver. RESULTS: V-PYRRO/NO significantly reduced in situ hepatic vascular resistance (HVR) without altering systolic blood pressure. Portal vein flow was essentially unchanged during in situ infusions while hepatic artery flow nearly doubled (P=0.03). After I/R, V-PYRRO/NO infusions significantly reduced both portal vein pressure (PVP) and HVR (P=0.04). Also, serum bile acid clearance increased from 15% when taurocholate (TC) was infused alone to 46% (P=0.007) when infused simultaneously with V-PYRRO/NO. Aqueous bile production tripled with TC and V-PYRRO/NO as compared to TC alone (P=0.04). Analysis of bile outputs revealed a significant increase in biliary cholesterol, biliary phospholipid, and biliary bile acid (P<0.05) with V-PYRRO/NO infusion. CONCLUSIONS: The hepato-selective nitric oxide donor, V-PYRRO/NO, reduced hepatic resistance parameters of the pig liver both before and after I/R and improved the plasma clearance of bile acid and biliary outputs of bile acid-dependent compounds. The augmented function observed after I/R may be due to improvements in hepatic blood flow secondary to altered hepatic hemodynamics.

Animals↗
PubMed2001

Hemodynamic and metabolic variables predict porcine ex vivo liver function.

Early recognition of hepatic function during initial graft reperfusion is important in beginning hepatic support perfusions as well as in liver transplantation. We hypothesized that both hemodynamic and metabolic perfusion variables obtained immediately after reperfusion predict eventual function during liver support or transplantation. Specific hemodynamic variables, i.e., portal vein pressure and hepatic vascular resistance, as well as metabolic variables, i.e., O(2) consumption and P(CO(2)) gradients, were compared with indices of hepatic function and damage, i.e., aqueous bile production, bile lipid outputs, lactate dehydrogenase levels, and histopathology, during an ex vivo support perfusion. O(2) consumption during early reperfusion correlated directly with unstimulated bile flows (P < 0.02) and histopathology scores (P < 0.05). Hepatic venous P(CO(2)) gradients correlated inversely with unstimulated bile flows (P < 0.05). Hemodynamic variables, i.e., portal vein pressure and hepatic vascular resistance, were inversely related with taurocholate-stimulated bile flows (P < 0.05). Hemodynamic and metabolic variables of early reperfusion are useful parameters in predicting eventual effectiveness of the harvested liver for ex vivo hepatic support perfusions.

Animals↗
PubMed2001

MR findings in athletes with pubalgia.

OBJECTIVE: To describe the MR findings in athletes with pubalgia. DESIGN AND PATIENTS: Pelvic MR images of 32 athletes (30 men, 2 women) with pubalgia were studied. T1-weighted and T2-weighted (SE and FSE) and STIR images in the axial and coronal planes were obtained on a 1.5-T system. Images were reviewed for general pelvic pathology. Special attention was given to the pubic symphysis, groin and pelvic musculature, and to the abdominal wall musculature. RESULTS: Thirty surgically confirmed cases comprise the study group. Abnormalities in the following were found: pubic symphysis (21/30), abdominal wall (27/30), groin musculature, including rectus abdominis (21/30), pectineus (6/30), and adductor muscle group (18/30). CONCLUSIONS: Pubalgia is a complex process which is frequently multifactorial. The MRI findings can alter the surgical approach.

Adolescent↗
PubMed2001

Immediate and long-term outcomes after lateral pancreaticojejunostomy for chronic pancreatitis.

Lateral pancreaticojejunostomy (LPJ) is the recommended surgical treatment of intractable pain from chronic pancreatitis (CP) with obstruction and ductal dilatation. This study evaluated the etiology, morbidity, mortality, hospital costs, and quality of life (QL) for patients with LPJ for CP. Medical records of 60 patients undergoing LPJ for CP between 1988 and 1996 were reviewed. Long-term QL was assessed by the Short Form 36 Health Survey and analyzed against control populations of patients who underwent pancreatic debridement for necrosis and patients with laparoscopic cholecystectomy for cholelithiasis. CP etiologies included 52 per cent alcoholic, 28 per cent idiopathic, 13 per cent pancreatic divisum, and 7 per cent familial pancreatitis. Peri- and postoperative morbidity and mortality were 25 and 0 per cent respectively. Average hospital cost was $13,530 with mean postoperative hospital stay of 12.1 days. Overall physical and mental QL were diminished compared with both the debridement group and cholecystectomy group with particular detriments in areas of physical role (P < 0.05), bodily pain (P < 0.001), social function (P < 0.001), and mental health (P < 0.001). We conclude that LPJ for CP is a relatively safe procedure with low morbidity and mortality but results in a significantly diminished long-term QL relative to other surgical patients with pancreatic or biliary disease. This difference prevails in both physical and mental aspects of health.

Adult↗
PubMed2000

Bile acids in xenogeneic ex-vivo liver perfusion: function of xenoperfused livers and compatibility with human bile salts and porcine livers.

BACKGROUND: In recent years, hepatic support systems using xenogeneic cells have been developed to support patients in fulminant hepatic failure. The extent to which xenogeneic hepatocytes metabolize and excrete human organic anions is unclear. In these studies we examined the ability of the ex vivo porcine liver to clear human bile acids during extracorporeal liver perfusion (ELP). METHODS: Four patients with fulminant hepatic failure underwent extracorporeal liver perfusion with 9 porcine livers. The venovenous circuit was designed as previously described (NEJM,1994,331:234) as were the immunologic features (Transplantation 1994,58:1162). Bile from the porcine liver and serum samples were collected hourly during perfusion. Three bile acids (glycocholic, glycodeoxycholic, taurodeoxycholic acid) were selected as markers for human bile and three (glycohyocholic, glycohyodeoxycholic, and glyco-3alpha-hydroxy-6-oxo-5beta-cholanoic acid) for markers of pig bile. Bile acids from both serum and bile were processed and analyzed through high performance liquid chromatography. The Students' t test was used for statistical analysis. RESULTS: The mean duration of perfusions was 4.1+/-1.5 hr. The mean total bile acid clearance from serum (243+/-44 micromol/h) was similar to the total bile acid biliary excretion (286+/-84 micromol/hr, P = 0.06). After 1 hr of perfusion, bile samples demonstrated a predominance of pig bile salts (65%). After 3 hr of perfusion, human bile acids made up 85% of total biliary bile acids. Pig bile acids appeared in patients' sera after 1 hr of perfusion, and after 3 hr, 35% of serum bile salts were pig-specific. CONCLUSIONS: Porcine livers perfused with human blood can clear the serum of potentially toxic human bile acids and excrete them into bile. Simultaneously, the percentage of pig-specific bile acids in patient serum increases during xenogeneic perfusion for unknown reasons. The relative hepatic uptake of bile acid from serum is similar to bile acid excretion in bile. Further development of systems using porcine livers or hepatocytes is warranted.

Animals↗
PubMed2000

NFkappaB expression during cold ischemia correlates with postreperfusion graft function.

In liver transplantation, activation of NFkappaB occurs upon reperfusion, yet few data exist regarding NFkappaB activation during cold ischemia. We hypothesized that activation of NFkappaB may initially occur during cold ischemia, prior to reperfusion, and serve as an important determinant of postreperfusion function. To test this hypothesis, serial biopsies during porcine liver harvest were obtained immediately upon laparotomy, upon completion of dissection, after 45 and 120 min of cold ischemia, and 60 and 180 min after reperfusion. Nuclear extracts were isolated for Western blot analysis of NFkappaB. Hepatic function was assessed through bile output and sorbitol dehydrogenase (SDH) activity. NFkappaB expression was maximal at 45 min of cold ischemia and decreased by 120 min. The expression at 120 min of cold ischemia correlated with markers of postreperfusion function, namely bile flow and SDH activity. During reperfusion a second distinct peak occurred at 180 min. Increased expression of NFkappaB at 180 min of reperfusion correlated directly with prior expression at 120 min during cold ischemia and with increased SDH activity. These data indicate that nuclear expression of NFkappaB demonstrate two distinct peaks of activity, one during cold ischemia and one after reperfusion. Enhanced expression of NFkappaB during cold ischemia not only correlates directly with NFkappaB expression during reperfusion, but also correlates inversely with postreperfusion graft function.

Animals↗
PubMed2000

Viral infection abrogates CD8(+) T-cell deletion induced by costimulation blockade.

BACKGROUND: Treatment with a single donor-specific transfusion (DST) plus a brief course of anti-CD154 monoclonal antibody (mAb) prolongs skin allograft survival in mice. It is known that prolongation of allograft survival by this method depends in part on deletion of alloreactive CD8(+) T cells at the time of tolerance induction. Recent data suggest that infection with lymphocytic choriomeningitis virus (LCMV) abrogates the ability of this protocol to prolong graft survival. METHODS: To study the mechanism by which viral infection abrogates allograft survival, we determined (1) the fate of tracer populations of alloreactive transgenic CD8(+) T cells and (2) the duration of skin allograft survival following treatment with DST and anti-CD154 mAb in the presence or absence of LCMV infection. RESULTS: We confirmed that treatment of uninfected mice with DST and anti-CD154 mAb leads to the deletion of alloreactive CD8(+) T cells and is associated with prolongation of skin allograft survival. In contrast, treatment with DST and anti-CD154 mAb in the presence of intercurrent LCMV infection was associated with the failure to delete alloreactive CD8(+) T cells and with the rapid rejection of skin allografts. The number of alloreactive CD8(+) cells actually increased significantly, and the cells acquired an activated phenotype. CONCLUSIONS: Interference with the deletion of alloreactive CD8(+) T cells mediated by DST and anti-CD154 mAb may in part be the mechanism by which viral infection abrogates transplantation tolerance induction.

Animals↗
PubMed2000

Liver metastases from breast cancer: long-term survival after curative resection.

BACKGROUND: Liver metastases from breast cancer are associated with a poor prognosis (median survival < 6 months). A subgroup of these patients with no dissemination in other organs may benefit from surgery. Available data in the literature suggest that only in exceptional cases do these patients survive more than 2 years when given chemohormonal therapy or supportive care alone. We report the results of liver resection in patients with isolated hepatic metastases from breast cancer and evaluate the rate of long-term survival, prognostic factors, and the role of neoadjuvant high-dose chemotherapy. PATIENTS AND METHODS: Over the past decade, 17 women underwent hepatic metastectomy with curative intent for metastatic breast cancer. The follow-up was complete in each patient. The median age at the time breast cancer was diagnosed was 48 years. Neoadjuvant high-dose chemotherapy (HDC) with hematopoietic progenitor support was used in 10 patients before liver resection. Perioperative complications, long-term outcome, and prognostic factors were evaluated. RESULTS: Seven of the 17 patients are currently alive, with follow-up of up to 12 years. Four of these patients are free of tumors after 6 and 17 months and 6 and 12 years. The actuarial 5-year survival rate is 22%. One patient died postoperatively (mortality rate, 6%) of carmustine-induced fibrosing pneumonitis. There was no further major morbidity in the other patients. The liver was the primary site of recurrent disease after liver resection in 67% of the patients. Patients in whom liver metastases were found more than 1 year after resection of the primary breast cancer had a significantly better outcome than those with early (< 1 year) metastatic disease (P = .04). The type of liver resection, the lymph node status at the time of the primary breast cancer resection, and HDC had no significant impact on patient survival in this series. CONCLUSIONS: Favorable 22% long-term survival can be achieved with metastasectomy in this selected group of patients. Careful evaluation of pulmonary toxicity from carmustine and exclusion of patients with extrahepatic disease are critical. Improved survival might be achieved with better selection of patients and the use of liver-directed adjuvant therapy.

Actuarial Analysis↗
PubMed2000

Hand-assisted laparoscopic surgery (HALS) with the HandPort system: initial experience with 68 patients.

OBJECTIVE: To evaluate the feasibility and potential benefits of hand-assisted laparoscopic surgery with the HandPort System, a new device. SUMMARY BACKGROUND DATA: In hand-assisted laparoscopic surgery, the surgeon inserts a hand into the abdomen while pneumoperitoneum is maintained. The hand assists laparoscopic instruments and is helpful in complex laparoscopic cases. METHODS: A prospective nonrandomized study was initiated with the participation of 10 laparoscopic surgical centers. Surgeons were free to test the device in any situation where they expected a potential advantage over conventional laparoscopy. RESULTS: Sixty-eight patients were entered in the study. Operations included colorectal procedures (sigmoidectomy, right colectomy, resection rectopexy), splenectomy for splenomegaly, living-related donor nephrectomy, gastric banding for morbid obesity, partial gastrectomy, and various other procedures. Mean incision size for the HandPort was 7.4 cm. Most surgeons (78%) preferred to insert their nondominant hand into the abdomen. Pneumoperitoneum was generally maintained at 14 mmHg, and only one patient required conversion to open surgery as a result of an unmanageable air leak. Hand fatigue during surgery was noted in 20.6%. CONCLUSIONS: The hand-assisted technique appeared to be useful in minimally invasive colorectal surgery, splenectomy for splenomegaly, living-related donor nephrectomy, and procedures considered too complex for a laparoscopic approach. This approach provides excellent means to explore, to retract safely, and to apply immediate hemostasis when needed. Although the data presented here reflect the authors' initial experience, they compare favorably with series of similar procedures performed purely laparoscopically.

Abdomen↗
PubMed1999

Biliary secretion of extracorporeal porcine livers with single and dual vessel perfusion.

BACKGROUND: Hepatic support systems that provide detoxification without biliary secretion (i.e., isolated hepatocyte systems) are sufficient to improve encephalopathy and bridge patients to transplantation. However, biliary secretion may be critical when hepatic support attempts to restore function and regeneration of the host liver. The purpose of these studies was to optimize the support liver secretory response to bile acid by either single-vessel (portal vein; PV) or dual-vessel (hepatic artery [HA] + PV) perfusions during extracorporeal porcine liver perfusion. METHODS: Extracorporeal porcine liver perfusion of anesthetized pigs was developed using support porcine livers perfused through the PV (n=4) alone and through the HA + PV (n=4) via a venovenous circuit. Support livers were provoked with taurocholate (TC) to enhance bile aqueous and hydrophobic outputs. RESULTS: After cold preservation and reperfusion, both PV and HA + PV livers had initial 1-hr bile aqueous outputs < 15% of in vivo flow, with cholesterol (C) and phospholipid (PC) outputs <25% of in vivo flow. Bile flow was significantly greater for recovered HA + PV livers (3.0+/-0.01 ml/15 min) than PV livers (1.9+/-0.01 ml/15 min). Despite this, PC output was significantly greater for PV than HA + PV livers. The C/PC ratio of PV livers was twice that of HA + PV livers. TC infusion (48 micromol/kg/15 min) of HA + PV livers demonstrated significantly greater increments in bile flow, PC output, and C output than PV livers. CONCLUSION: In the unstimulated state, porcine support livers with dual-vessel perfusion generated greater aqueous and C outputs despite diminished PC output than in those with single-vessel perfusion. TC stimulation increased bile flow, PC output, and C output in dual-perfused livers more than in PV livers. HA + PV perfusion of support livers is the preferred technique for removing hydrophobic compounds that require PC transport for excretion or exist in the aqueous phase.

Animals↗
PubMed1999

Injury to aberrant bile ducts during cholecystectomy: a common cause of diagnostic error and treatment delay.

OBJECTIVE: The purpose of this study was to determine the prevalence of injured aberrant bile ducts in a population with complications after cholecystectomy and to determine whether such injury resulted in significant delay in the diagnosis and treatment of bile duct injuries. MATERIALS AND METHODS: The cholangiograms of 82 patients who sustained bile duct injury during cholecystectomy were reviewed. Prevalence of aberrant bile duct anatomy in the injured ducts was noted. The time periods from injury to diagnosis and treatment of bile duct leaks in patients with aberrant bile duct anatomy were compared with those in patients with normal anatomy. RESULTS: Seventeen percent (14/82) of the patients were found to have aberrant bile duct anatomy. Fifteen percent (12/82) were found to have had an aberrant bile duct involved in the injury. Eleven of the patients had an aberrant bile duct leak, and one patient had an aberrant bile duct clipping injury. The time period required for diagnosis and treatment of a leaking aberrant bile duct was significantly longer (p < .005) than that required for a bile leak in an anatomically normal bile duct. CONCLUSION: Aberrant bile ducts are present in a significant number of patients who sustain bile duct injuries during cholecystectomy. Diagnosis of an aberrant bile duct leak may be delayed because of nonfilling of the bile duct during standard cholangiographic techniques. Careful examination of cholangiograms for nonfilling segments and contrast material injection of biloma drains and T tubes may shorten the time to definitive treatment for this group of patients.

Adult↗
PubMed1999

Laparoscopic gastrectomy in the porcine model: our initial experience with a new hand-assist device.

Many advanced laparoscopic cases remain technically difficult and are less widely accepted. To a great extent, advanced laparoscopic surgery is handicapped by the loss of a surgeon's tactile sense. The concept of introducing the surgeon's hand as an aid to minimally invasive surgery has been described. We report a new hand-assist device designed to allow the introduction of the surgeon's hand, wrist, and forearm through a small incision in the abdomen to assist laparoscopic surgery with pneumoperitoneum. Important factors in the hand-assist design are ease of use, reliable maintenance of pneumoperitoneum, and minimal hand/arm fatigue, which were met with this device.

Animals↗
PubMed1998

Hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is one of the world's most common malignancies. The aims of the present paper are to review data on (1) epidemiology and screening programmes for the early detection of the tumour and (2) advances in the diagnostic imaging and management. METHODS: Relevant English language articles, published between January 1985 and December 1997, were reviewed. Articles were identified through Medline search, using the key words 'hepatocellular carcinoma'. Articles cited in the bibliographies of these articles were searched manually. RESULTS: Hepatocellular carcinoma has a heterogeneous geographical distribution. Although its risk factors have been identified, the efficacy of screening programmes remains uncertain. Imaging has improved substantially with the recent application of dual-phase helical computed tomography and magnetic resonance imaging employing specific contrast agents. The comparative efficacy of conservative therapy and surgical resection is uncertain, since well controlled trials are lacking. CONCLUSION: Hepatocellular carcinoma is commonly a problem of two diseases, the malignancy itself and cirrhosis. This renders treatment rarely curative, even when surgical resection can be applied in a technically successful sense. Liver transplantation could be a definitive treatment but this is plagued by limited donor resources.

Carcinoma, Hepatocellular↗
PubMed1998

Laparoscopic surgery and the systemic immune response.

OBJECTIVE: The authors review studies relating to the immune responses evoked by laparoscopic surgery. SUMMARY BACKGROUND DATA: Laparoscopic surgery has gained rapid acceptance based on clinical grounds. Patients benefit from faster recovery, decreased pain, and quicker return to normal activities. Only more recently have attempts been made to identify the metabolic and immune responses that may underlie this clinical success. The immune responses to laparoscopy are now being evaluated in relation to the present knowledge of immune responses to traditional laparotomy and surgery in general. METHODS: A review of the published literature of the immune and metabolic responses to laparoscopy was performed. Laparoscopic surgery is compared with the traditional laparotomy on the basis of local and systemic immune responses and patterns of tumor growth. The impact of pneumoperitoneum and insufflation gases on the immune response is also reviewed. CONCLUSIONS: The systemic immune responses for surgery in general may not apply to laparoscopic surgery. The body's response to laparoscopy is one of lesser immune activation as opposed to immunosuppression.

Carbon Dioxide↗