Biomedical subjects

R Ricciardi

Publications and source records attributed to R Ricciardi.

At least 19 recordsLinked to original sources

PubMed2005

Causes of portal venous thrombosis in cirrhotic patients: the role of genetic and acquired factors.

OBJECTIVE AND METHODS: We compared frequencies of three common prothrombotic mutations (factor V Leiden, the G20210A mutation of the prothrombin gene, and homozygosity for C677T methylenetetrahydrofolate reductase) in 219 cirrhotic patients, 43 with and 176 without portal vein thrombosis (PVT). The following variables were related to PVT: prothrombin levels, platelet count, Child-Pugh classification, previous abdominal surgery, number of decompensation events, size of varices, red markers on varices, and sclerotherapy. All patients were followed up for a mean period of 18 months (range 10-30). RESULTS: Prothrombotic mutations were detected in 64 of the 219 cirrhotic patients (29.2%), at equal frequency in patients with or without PVT. At univariate analysis, PVT was associated with Child-Pugh classes B and C, signs of liver decompensation, large varices with red markings, sclerotherapy, and abdominal surgery. At multivariate analysis, PVT was associated with sclerotherapy [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.2-11] and previous surgery (OR 2.8, 95% CI 1.2-6.3). The combination of the two acquired factors increased the risk of PVT, whereas the combination of local with genetic defects did not. Only a single patient with genetic thrombophilia and without PVT at inclusion developed the complication during follow-up, concomitantly with the development of hepatocellular carcinoma. CONCLUSION: In cirrhotic patients prothrombotic mutations by themselves are not causative of PVT. Sclerotherapy and previous abdominal surgery favour the development of two-thirds of cases of PVT; in the remaining cases the pathogenesis remains elusive.

Adult↗

PubMed2004

Independent predictors of morbidity and mortality in blunt colon trauma.

We sought to determine the impact of (1) grade of the colon injury, (2) the formation of an ostomy, and (3) associated injuries on outcomes such as morbidity and mortality after blunt colon injuries. We retrospectively reviewed 16,814 cases of blunt abdominal trauma. Patients with colonic injuries were selected and charts reviewed for demographic, clinical, and outcomes data. Injuries were grouped by the Colon Injury Scale (grades I-V). Independent risk factors of morbidity included spine and lung injuries, as well as increased age. A higher grade of colon injury trended toward a significant association with intra-abdominal complications. Independent risk factors of mortality included liver, heart, and lung injuries, as well as intracerebral blood and female gender. The grade of colon injury, the formation of an ostomy, and management of the colon trauma did not independently predict increased intra-abdominal complications, morbidity, or mortality. These results indicate that patients afflicted with blunt colon trauma experience a high rate of morbidity and mortality from associated injuries and or increased age. Treatment regimens directed at these factors will be most helpful in reducing the high morbidity and mortality after blunt colon trauma. Factors such as ostomy formation and management strategy are not associated with increased morbidity or mortality after blunt colon trauma.

Adolescent↗

PubMed2002

Appropriateness of urea breath test: a prospective observational study based on Maastricht 2000 guidelines.

BACKGROUND: The urea breath test is routinely used for diagnosing or confirming the eradication of Helicobacter pylori. AIM: To evaluate the appropriateness of urea breath test referrals. METHODS: The age, sex, symptoms, endoscopic findings, use of non-steroidal anti-inflammatory drugs, family history of gastric cancer or H. pylori infection and concomitant diseases of patients referred for urea breath testing in a 1-year period were recorded. The appropriateness of urea breath test referrals was judged according to Maastricht guidelines. RESULTS: One thousand, three hundred and twenty subjects (47 +/- 16 years) were referred in 2001: 578 (43.8%) for the diagnosis and 742 (56.2%) for confirmation of the eradication of H. pylori. The urea breath test was considered to be appropriate in 836 (63.3%) patients, inappropriate in 192 (14.5%) and appropriate but avoidable in 292 (22.1%). The appropriateness ratios of urea breath test referrals were 4.6 and 9.0 (P < 0.0001) for general practitioners and gastroenterologists, respectively. Of the patients (n=230) with un investigated dyspepsia, who underwent urea breath testing according to a 'test and treat' strategy, 98 (42.6%) presented at least one risk factor for organic disease. CONCLUSIONS: In Italy, nearly 36% of urea breath test referrals are inappropriate or could be avoided if all dyspeptic patients with risk factors were referred for endoscopy or all dyspeptic patients undergoing endoscopy were tested for H. pylori infection with biopsy methods. Both general practitioners and, to a lesser extent, gastroenterologists require educational programmes to deal effectively with H. pylori.

Adult↗

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

FRAP-p70s6K signaling is required for pancreatic cancer cell proliferation.

BACKGROUND: FRAP-p70s6K signaling regulates mitogenic responses to growth factors in eukaryotic cells. Constitutive p70s6K activation occurs in some human malignancies and may contribute to dysregulated cell growth. We examined whether inhibition of this pathway affects mitogen-induced proliferation and cell cycle progression of human pancreatic cancer cells in vitro. METHODS: Quiescent BxPC3 and Panc-1 human pancreatic cancer cells treated with or without 20 ng/mL rapamycin (FRAP inhibitor) were repleted with 10% FCS to induce cell cycle entry. Proliferation was measured with MTT assay. Cell cycle and apoptosis were determined by FACS analysis. Phosphorylation of p70s6K, Akt, and cdc2 was evaluated by Western blot. Statistical analysis was by two-tailed t test (P < 0.05). RESULTS: Rapamycin (Rapa) inhibited the phosphorylation of p70s6K while inducing G(1) cell cycle arrest (P < 0.005). In both cell lines, Rapa inhibited serum-induced proliferation (P < 0.05) without affecting apoptosis. Cdc2 phosphorylation was inhibited by 15 min with Rapa (not shown), consistent with cell cycle arrest. Akt phosphorylation was not affected, indicating FRAP specificity of Rapa. CONCLUSIONS: FRAP-p70s6K signaling appears to be necessary for G(1)-to-S phase progression and proliferation in pancreatic cancer cells. This supports earlier work demonstrating a similar regulatory role for PI-3' kinase, an upstream activator of FRAP-p70s6K.

Adenocarcinoma↗

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

Heat shock protein 27 inhibits apoptosis in human neutrophils.

BACKGROUND: Prolonged neutrophil(PMN) survival has been implicated in tissue injury following sepsis. A variety of bacterial products have been identified which inhibit PMN apoptosis including lipopolysaccharide(LPS). Extracellular heat shock proteins(Hsp) have recently been identified as potent regulatory signals for the innate immune system during the inflammatory response. We hypothesized that Hsp 27 can affect PMN phenotype with respect to apoptosis and cytokine profile. MATERIALS AND METHODS: PMN were isolated from the peripheral blood of healthy human volunteers by red blood cell sedimentation and gradient centrifugation. Cells were placed in media and cultured for 18 h with and without recombinant human Hsp 27 at various concentrations. In parallel experiments, PMN were stimulated with LPS, a known inhibitor of PMN apoptosis, for comparison. Apoptosis was quantified using annexin V and propidium iodide staining with flow cytometric analysis. Culture supernatants were assayed for secretion of TNF-alpha, IL-10, and IL-12. RESULTS: Hsp 27 significantly inhibits PMN apoptosis [control; 81.8 +/- 3.6%, vs Hsp 27, 60.4 +/- 4.1% p < 0.05]. The reduction is similar to that signaled by LPS, alone. Together their effect is not synergistic. The Hsp 27 response is dose-dependent. Hsp 27 does not induce secretion of TNF-alpha, IL-10, or IL-12, whereas LPS does signal IL-12 and TNF-alpha secretion. CONCLUSION: These data demonstrate that exogenous Hsp 27 may play a role in neutrophil-mediated tissue injury during trauma and sepsis via its ability to inhibit neutrophil apoptosis. However, Hsp 27 does not significantly alter neutrophil phenotype with respect to cytokine production profile.

Apoptosis↗

PubMed2001

Activator protein 1 activation following hypoosmotic stress in HepG2 cells is actin cytoskeleton dependent.

BACKGROUND: Following hypoosmotic stress-induced cell volume change, the actin cytoskeleton reorganizes itself. The role of this reorganization in the activation of the phosphatidylinositol 3-OH-kinase/protein kinase B/activator protein 1 (PI-3-K/PKB/AP-1) proliferative signaling cascade is unknown. Focal adhesion kinase (FAK) participates in the cytoskeleton-based activation of PI-3-K. We hypothesized that hypoosmotic stress-induced activation of PKB and AP-1 in HepG2 cells is dependent on an intact actin cytoskeleton and subsequent FAK phosphorylation. METHODS: HepG2 cells were incubated for 1 h with or without 20 microM cytochalasin D, an actin disrupter, and were then exposed for up to 30 min to hypoosmotic medium (200 mOsm/L) to induce swelling. Tumor necrosis factor alpha (1.4 nM) and medium alone served as positive and negative controls, respectively. Western blots measured cytoplasmic phosphorylated or total FAK and PKB. EMSAs measured nuclear AP-1. All experiments were performed in triplicate. RESULTS: Exposure to hypoosmotic stress resulted in activation of the following signaling messengers in a sequential fashion: (1) phosphorylation of FAK occurred by 2 min, (2) phosphorylation of PKB occurred by 10 min, (3) nuclear translocation of AP-1 occurred by 30 min. All three signaling events were abolished when these cells were pretreated with cytochalasin D. CONCLUSION: Actin reorganization following hypoosmotic stress is essential for the FAK-mediated activation of the PI-3-K/PKB/AP-1 proliferative cascade. These data delineate a possible mechanism by which the cell swelling-induced cytoskeletal changes can initiate proliferative signal transduction in human liver cancer.

Actins↗

PubMed2001

Extended thymectomy in myasthenia gravis: a team-work of neurologist, thoracic surgeon and anaesthesist may improve the outcome.

OBJECTIVE: We reviewed our overall experience on 163 patients, affected by myasthenia gravis, who underwent thymectomy between 1976 and 1998. A comparison between the oldest series of 72 patients (January 1976-December 1992), referred by various neurologists and operated on through different approaches, and the last 91 patients (January 1993-December 1998), taking part in a strict diagnostic-therapeutical programme, was made. METHODS: Anagraphic data, duration of symptoms, the surgical approach, necessity of respiratory assistance, the hospital stay, histopathological findings, preoperative and postoperative Osserman classification, as well as medications, were globally analyzed and then compared in the two groups. RESULTS: Significant differences in the length of hospitalization (8.7 days vs. 4.2 days; P=0.00001) and in the prolonged intubation rate (18 vs. 0; P<0.000001) were observed in the most recent series. Patients in the pre-operative Osserman stage I and operated on in the second period had a higher complete remission rate at the univariate analysis (P<0.001 and P<0.0001, respectively). At the multivariate analysis the only parameter which affected the outcome was to be operated on in the second period (P<0.01). CONCLUSIONS: Our experience confirms the role of the extended thymectomy in the treatment of myasthenia gravis. Whenever an extended thymectomy was performed through a complete sternotomy it was a quick procedure, with short hospitalization and acceptable cosmetic results. A careful pharmacological control of the myasthenic symptoms and the presence of team-work among neurologist, thoracic surgeon and anaesthesist in the peri-operative setting reduce the incidence of complications and might increase the efficacy of the thymectomy.

Adolescent↗

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

Increased frequency of euthyroid ophthalmopathy in patients with Graves' disease associated with myasthenia gravis.

We previously showed that myasthenia gravis (MG) has a mild clinical expression when associated with autoimmune thyroid diseases (AITD). In the present study we have investigated the frequency of thyroid-associated ophthalmopathy (TAO) in patients with Graves' disease (GD) associated with MG as compared with GD patients without MG. A total of 418 patients with GD were studied, 31 with MG and 387 without MG. TAO was evaluated by physical examination, exophthalmometry, computerized tomography, and computerized visual fields assessment. The overall prevalence of TAO was similar in GD patients with MG (61.2%) and in those without MG (56.4%). When the analysis was restricted to GD patients with ocular MG, a greater frequency of TAO was found (84.6%), compared with GD patients without MG or with GD patients with generalized MG, although the differences did not reach the statistical significance. GD patients with MG had a significantly greater prevalence (12.9%) of euthyroid ophthalmopathy (clinically overt ophthalmopathy without previous and/or current hyperthyroidism) than those without MG (3.1%; p = 0.003). The results suggest a preferential association between the ocular manifestations of GD and MG, which may be due to immunological cross-reactivity against common autoimmune targets in the eye muscle as well as to a common genetic background.

Adult↗

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↗

PubMed2000

First pelvic examination in the adolescent.

The first pelvic examination is often an emotionally charged and stressful event in the adolescent patient. The female adolescent patient has many unique health care needs, which if not met, can negatively impact future gynecologic health. History taking and physical examination techniques specific to the adolescent female patient are discussed. Indications for pelvic examination along with practice tips in communicating with the adolescent female patient are reviewed. Methods of reducing patient anxiety and empowering the adolescent to take charge of her health are discussed.

Adolescent↗

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

T-cell tumor necrosis factor-alpha receptor binding in myasthenic patients.

Myasthenia gravis (MG) is a T-cell-dependent and antibody-mediated autoimmune disease of the neuromuscular junction, in which the cytokine network may be deranged. Specific receptors for tumor necrosis factor (TNF)-alpha, a cytokine with several effects on the neuroimmune system, were found on human lymphocytes. In the present study, we assayed TNF-alpha binding on peripheral blood T-cells from MG patients, finding that T-cells from patients have significantly more TNF-alpha receptors than those from controls (Bmax: 654 +/- 12 vs. 133 +/- 4 (mean +/- SEM) receptors/cell). Such TNF-alpha binding sites are of the same type in patients and healthy subjects (Kd: 68.7 +/- 4.3 vs. 70.1 +/- 4.8 (mean +/- SEM) pM). The enhanced T-cell TNF-alpha binding is due to an increased number of TNF-alpha receptors on T-helper lymphocytes. These results are discussed in terms of MG immunopathogenesis, since it has been reported that activated T-cells have increased amounts of TNF-alpha receptors.

Adolescent↗