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Aim: To evaluate survival in patients undergoing palliative resection versus non-resection surgery for primary colorectal cancer in a retrospective analysis., Methods: Demographics, TNM status, operating details and survival were reviewed for 67 patients undergoing surgery for incurable colorectal cancer. Palliative resection of the primary tumor was performed in 46 cases in contrast to 21 patients with non-resection of the primary tumor and bypass surgery. Risk factors for postoperative mortality and poor survival were analyzed with univariate and multivariate analyses., Results: The two groups were comparable in terms of age, gender, preoperative presence of ileus and tumor stage. Multivariate analysis showed that median survival was significantly higher in patients with palliative resection surgery (544 vs 233 d). Differentiation of the tumor and tumor size were additional independent factors that were associated with a significantly poorer survival rate., Conclusion: Palliative resection surgery for primary colorectal cancer is associated with a higher median survival rate. Also, the presence of liver metastasis and tumor size are associated with poor survival. Therefore, resection of the primary tumor should be considered in patients with non-curable colon cancer.

Aim: To evaluate the mechanism underlying the effects of 5-Fluorouracil (5-FU) on adenoviral infection., Methods: Low and high Coxsackievirus-Adenovirus Receptor (CAR) expressing human colon carcinoma cell lines were treated with 5-FU and two E1-deleted adenoviral constructs, one transferring GFP (Ad/CMV-GFP) the other bax (Ad/CEA-bax). The number of infected cells were monitored by GFP expression. To evaluate the effects of 5-FU in a receptor free system, Ad/GFP were encapsulated in liposomes and treated with 5-FU. Ad/GFP release was estimated with PCR and infection of 293 cells with the supernatant. Electron microscopy of the Ad5-GFP-liposome complex was made to investigate morphological changes of the liposomes after 5-FU., Results: Infection rates of all cell lines increased from 50% to 98% with emerging 5-FU concentrations. The enhanced viral uptake was independent of the CAR expression. Additionally, 5-FU treated liposomes released 2-2.5 times more adenoviruses. Furthermore, 5-FU-treated liposomes appeared irregular and porous-like., Conclusion: Adenoviral uptake is enhanced in the presence of 5-FU irrespective of CAR and is associated with morphological changes in membranes making the combination of both a promising option in gene therapy.

Background: Crohn's disease (CD) patients with increased disease activity may reveal an increased risk for perioperative complications. The "Crohn's disease activity index" (CDAI) and the "Vienna classification" (VC) were developed for standardized disease activity estimations. The significance of these scores to predict extent, type and early outcome of surgery in CD patients was analyzed., Methods: In 179 surgically treated CD patients, the CDAI and VC were assessed from a prospective database. Relations of the scores with CD risk factors, type, number, location and complications of surgery were analyzed., Results: VC behavior and location subtypes were associated with distinct types of surgery (i.e. "strictureplasty" in "stricturing disease", "colon surgery" in "colon involvement"), but not with surgery type and extent or outcome. Surgery extent (i.e. with 5 vs. 3 "surgical sites" 425 +/- 25 vs. 223.3 +/- 25) and complications (357.1 +/- 36.9 (with) vs. 244.4 +/- 13 (without)) were associated with elevated CDAI levels; however, nicotine abuse remained the only significant risk factor for perioperative complications after multiple logistic regression., Conclusion: The significance of VC or CDAI for predicting the extent of surgery or complications is limited. None of the tested variables except preoperative nicotine abuse influenced the likelihood for perioperative complications., (Copyright (c) 2006 S. Karger AG, Basel.)

Background: Primary graft dysfunction due to ischemia and reperfusion injury represents a major problem in liver transplantation. The related cell stress may induce apoptosis, which can be suppressed by bcl-2. The purpose of the study was to investigate the effect of adenoviral bcl-2 gene transfer on early graft function and survival in rat liver transplantation., Methods: An adenoviral construct that transfers bcl-2 under the control of a tetracycline inducible promoter was generated (advTetOn bcl-2) and used with a second adenovirus that transfers the repressor protein (advCMV Rep). Forty-eight hours before explantation, donor rats were treated with advTetOn bcl-2/ advCMV Rep (n=7) and doxycyclin, with the control adenoviral construct advCMV GFP (n=8) or with doxycyclin alone (n=8). Liver transplantation was performed following 16 hours of cold storage (UW). Bcl-2 expression and intrahepatic apoptosis was assessed. Bile flow was monitored 90 min posttransplantation. The endpoint for survival was 7 days., Results: Bcl-2 was expressed in hepatocytes and sinusoidal lining cells. This was associated with a significant reduction of apoptotic sinusoidal lining cells and hepatocytes after 24 hours and 7 days. Bile production was significantly higher following bcl-2 pretreatment. Furthermore, bcl-2 transfer resulted in significantly improved survival (100% vs. 50% both control groups)., Conclusions: Adenoviral bcl-2 transfer results in protein expression in hepatocytes and sinusoidal lining cells resulting in early graft function and survival enhancement after prolonged ischemia and reperfusion injury. The inhibition of apoptosis in the context of liver transplantation might be a reasonable approach in the treatment of graft dysfunction.

A considerable amount of data indicates that transplanted patients are at increased risk for de novo and recurrent cancer. Treatment of this population is difficult. It remains unclear if the immunosuppressive therapy should be continued, tapered or even stopped or if immunosuppressive drugs with antiproliferative properties have beneficial effects in this situation. In various models, mTOR-inhibitors were shown to have immunosuppressive and anti-tumor effects. Here, we have reviewed the current literature trying to clarify if mTOR-inhibition brings advantages for the transplanted patients suffering from tumors.

Inhibition or destruction of Kupffer cells (KC) may protect against ischemia-reperfusion (IR) induced primary graft nonfunction (PNF) in liver transplantation. Besides KC activation, PNF is characterized by microvascular perfusion failure, intrahepatic leukocyte accumulation, cell death and hepatocellular dysfunction. KCs can be inactivated by different agents including gadolinium chloride (GdCl3), methyl palmitate (MP) and glycine. The effects of three KC inactivators on IR-injury after rat liver transplantation were compared in the present study. Lewis liver donors were treated with GdCl3, MP, glycine or saline (control). Liver grafts were transplanted following 24 h storage (UW solution). KC populations and IR damage were assessed by histologic analysis, quantitative real-time polymerase chain reaction (RT-PCR) and intravital microscopy. The number of hepatic ED-1 positive macrophages was diminished after GdCl3 (114.8+/-4.4/mm2 liver tissue) and MP treatment (176.0+/-5.0), versus the glycine (263.9+/-5.5) and control (272.1+/-5.6) groups. All three treatment modalities downregulated phagocytic activity for latex particles, paralleled by reduced microvascular injury (acinar perfusion index, GdCl3: 0.75+/-0.03; MP: 0.83+/-.03; glycine: 0.84+/-0.03; 0.63+/-0.03). Quantitative RT-PCR revealed elevated myeloperoxidase mRNA after glycine versus GdCl3 and MP pretreatment (3.2- and 3.4-fold, P=0.011, respectively), without difference to controls (2.9-fold of glycine). TNFalpha-mRNA was reduced after glycine- (5.2-fold), GdCl3- (19.7-fold), MP-treatment (39.5-fold) compared with controls. However, profound prevention of intrahepatic cell death and liver graft failure was solely achieved with glycine preconditioning. Different than GdCl3 and MP, glycine modulates rather than destroys KCs. Glycine appears to preserve cell viability and to TNFalpha/leukocyte dependent organ regeneration capacity, which is related to increase graft survival following liver transplantation.

Lactic acid accumulation is generally believed to be involved in muscle fatigue. However, one study reported that in rat soleus muscle (in vitro), with force depressed by high external K(+) concentrations a subsequent incubation with lactic acid restores force and thereby protects against fatigue. However, incubation with 20 mm lactic acid reduces the pH gradient across the sarcolemma, whereas the gradient is increased during muscle activity. Furthermore, unlike active muscle the Na(+)-K(+) pump is not activated. We therefore hypothesized that lactic acid does not protect against fatigue in active muscle. Three incubation solutions were used: 20 mM Na-lactate (which acidifies internal pH), 12 mM Na-lactate +8 mm lactic acid (which mimics the pH changes during muscle activity), and 20 mM lactic acid (which acidifies external pH more than internal pH). All three solutions improved force in K(+)-depressed rat soleus muscle. The pH regulation associated with lactate incubation accelerated the Na(+)-K(+) pump. To study whether the protective effect of lactate/lactic acid is a general mechanism, we stimulated muscles to fatigue with and without pre-incubation. None of the incubation solutions improved force development in repetitively stimulated muscle (Na-lactate had a negative effect). It is concluded that although lactate/lactic acid incubation regains force in K(+)-depressed resting muscle, a similar incubation has no or a negative effect on force development in active muscle. It is suggested that the difference between the two situations is that lactate/lactic acid removes the negative consequences of an unusual large depolarization in the K(+)-treated passive muscle, whereas the depolarization is less pronounced in active muscle.

Unlabelled: Apoptosis represents a crucial mechanism of ischemia-reperfusion injury after liver transplantation. Bcl-2 may inhibit apoptosis. This study investigates the effect on ischemia/reperfusion injury and survival after rat liver transplantation of adenoviral bcl-2 transfer into donor livers., Methods: A nonreplicative adenovirus, expressing bcl-2 under control of a tetracyclin-inducible promoter (adv TetOn bcl-2) was used to treat male Lewis rats in combination with a second adenovirus transferring the TetOn repressor protein under control of a cytomegalovirus promoter (advCMVRep). Virus induction was achieved by addition of doxycyclin to the drinking water. Controls were pretreated with a control adenovirus (advCMV GFP) or with doxycycline. Liver transplantations were performed after 16-hour graft storage. Bcl-2 expression was evaluated by Western blot and immunohistology. Survival was monitored for 7 days, and tissue specimens were collected at 24 hours and 7 days post reperfusion., Results: After pretreatment with advTetOn bcl-2/adv CMVRep, intrahepatic bcl-2 expression was evident at 24 hours and 7 days but was absent among controls. Bcl-2 expression was detected in hepatocytes and, to a high degree, in sinusoidal lining cells. TUNEL-positive sinusoidal lining cells were strikingly reduced after bcl-2 transfer (0.1 +/- 0.3 cells/hpf, mean +/- SD) compared to control virus (4.8 +/- 2.3) or doxycyclin-treated grafts (1.3 +/- 0.2); P < .05. After bcl-2 treatment, survival after transplantation was 100%, whereas it was 50% in both control groups (P = .035)., Conclusion: The study shows the feasibility of transient, doxycyclin-controlled adenoviral gene transfer in a transplantation model. Bcl-2 expression increased survival after ischemia/reperfusion in rat liver transplantation, potentially through protection of sinusoidal lining cells.

Background: Apoptosis plays a crucial role after ischemia-reperfusion in organ transplantation. It is executed by caspases and influenced by the rheostat of pro- and anti-apoptotic proteins of the bcl-2 family. This study investigated the effect of specific inhibition of caspases 3 and 7 on graft function, survival, and hepatic bcl-2 levels after liver transplantation., Methods: Lewis rats underwent syngeneic orthotopic liver transplantation after 16 hr of cold graft storage (in University of Wisconsin solution). Livers of donor animals treated with D(OMe)E(OMe)VD(OMe)-fluoromethylketone (specific inhibitor of apoptosis executor caspases 3 and 7), and appropriate control groups, were investigated. Early graft injury was quantified by measurement of bile flow and determination of microvascular graft injury by using in vivo fluorescence microscopy. Apoptosis and its regulation were examined by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining and Western blot analysis of cell death effectors, respectively., Results: After specific in vivo caspase inhibition, Western blot analysis revealed inhibition of caspase-induced cleavage of poly-ADP-ribose-polymerase. Inhibition of caspases 3 and 7 resulted in a significantly decreased number of apoptotic endothelial cells and improved microvascular perfusion. A cell protective effect was also suggested by an increase of bcl-2 levels at 7 days. Most important, specific caspase blockade resulted in improved rat survival after liver transplantation., Conclusion: Specific inhibition of apoptosis executor caspases effectively reduces graft ischemia-reperfusion injury and improves survival in liver transplantation. Better tissue preservation after caspase inhibition correlates with reduced apoptosis execution, improved microvascular perfusion, and bcl-2 up-regulation. Therefore, specific caspase inhibition represents a promising regimen for clinical use in liver transplantation.

Background: There is a high incidence of postoperative complications and late recurrences after operative therapy of a pilonidal sinus. The optimal treatment strategy is still matter of discussion. We studied the long-term results after excision of a pilonidal sinus and primary midline closure compared with the open surgical procedure., Materials and Methods: A total of 73 patients (62 male and 11 female, mean age 26.6 years) underwent a total of 79 operations between 1992 and 2001. Thirty patients (38%) were previously operated on because of a pilonidal sinus.Twenty-four were treated in our institution by an open procedure (five after simple abscess incision, 19 after sinus excision) and 52 by primary midline closure. Another three patients received skin flap procedures., Results: Follow-up was possible for 65 patients (82%) for a median of 50 months.Recurrent pilonidal sinus occurred in 22 cases: 18 after primary midline closure (42%) and four after open procedure (21%, P=0.4). We found no relapse following the three skin flap procedures. There was a significantly higher relapse rate in patients operated with recurrent disease (12/25 vs 10/40; P<0.05)., Conclusions: Despite of numerous previously operated patients (38%), there was a high recurrence rate (42%) after excision of a pilonidal sinus and primary midline closure. Alternative operative techniques creating a lateral wound or the various skin flap procedures may be promising alternatives. We are in the process of changing our treatment strategy for patients suffering from a pilonidal sinus.

Objective: The presence of working memory deficits suggests abnormalities of prefrontal cortex (PFC) in schizophrenia. Although much is known about spatial working memory deficits in schizophrenia, including its potential as a phenotypic marker, it is unclear whether object working memory is similarly affected. Our goal was to examine nonspatial, object working memory function in relation to clinical symptoms., Methods: We assessed object working memory and clinical symptoms in 28 schizophrenia patients during acute psychotic episode and 4 months later during partial remission. Delayed-matching-to-sample tasks for familiar object (DMTS-F) and novel shapes (DMTS-N) were used. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). 33 age-matched normal subjects were also tested over the same time period., Results: Acutely psychotic patients showed deficits in both DMTS-F and DMTS-N. Four months later, their DMTS-F performance improved significantly but deficits in DMTS-N were still present. During acute psychosis, symptoms correlated with DMTS-F but not with the DMTS-N. Four months later, negative symptoms correlated with both tasks., Conclusions: Object working memory as measured by DMTS-N was impaired in schizophrenia patients during both acute and chronic states. When schizophrenia patients were in partial remission, object working memory was associated with negative symptoms., (Copyright 2002 Elsevier Science B.V.)

Background: Attentional abnormalities may lie at the core of cognitive symptoms in schizophrenia, but it is unclear how they relate to symptoms. The major aim of our study was to understand the relation between spatial attention and clinical symptoms from acute to chronic state., Methods: Thirty-six acutely psychotic schizophrenia patients and 42 matched control subjects were assessed on three spatial attention measures: target location detection, interference (concurrent inhibition of distractor), and negative priming (subsequent inhibition of distractor). Symptoms were assessed by the Positive and Negative Syndrome Assessment Scale. Four months later, the same subjects were re-tested, and symptoms were re-assessed., Results: Symptoms were significantly reduced at the follow-up. Schizophrenia patients were slower at detecting target location than control subjects, but they improved significantly over time. Schizophrenia patients and control subjects did not differ on the interference task. Negative priming was abolished during acute psychosis, but 4 months later it was restored. Positive symptoms were correlated with reduced negative priming but not with interference, nor with target detection. Negative priming during acute psychosis was significantly correlated with the clinical symptoms at the follow-up., Conclusions: These results suggest that reduced negative priming may be associated with increased clinical, symptoms especially the positive symptoms.

Purpose: Standard diagnostic proctologic procedures in the assessment of pelvic floor disorders include clinical evaluation and endoscopy. Particular aspects of combined pelvic floor disorders, especially those involving more than one pelvic compartment, may remain undetected without additional technical diagnostic procedures such as videoproctoscopy, cinedefecography, or colpocystodefecography. The aim of the study was to review the potentials of dynamic magnetic resonance imaging defecography to elucidate the underlying anatomic and pathophysiologic background of pelvic floor disorders in proctologic patients., Patients and Methods: Dynamic magnetic resonance imaging defecography was performed in 20 Patients (13 females) with main diagnoses such as rectal prolapse or intussusception, rectocele, descending perineum, fecal incontinence, outlet obstruction, and dyskinetic puborectalis muscle after clinical evaluation. The investigation was performed on a 1.5 T-magnetic resonance imaging machine in supine position. The rectum was filled with Gd-DTPA enriched ultrasound gel. First a T1/T2 weighted investigation of the pelvis was performed, followed by defecography with evacuation of the rectum. Images were obtained in a sagittal plane in a frequency of 1 image/second (true FISP) at rest and during straining. The obtained magnetic resonance imaging video tapes were analyzed off-line with cinematographic evaluation of bladder base, uterus, and anal canal position in relation to the pubococcygeal line by a blinded radiologist. Investigation time was 20 minutes., Results: In dynamic magnetic resonance imaging defecography of the pelvic floor, 12 patients with descending perineum, 10 rectoceles (10 females), 6 cystoceles (6 females), 4 enteroceles (4 females), 8 intussusceptions (5 females), and a dyskinetic puborectalis muscle in 3 males were detected. In 11 females and 3 males multifocal disorders were found, involving more than one compartment in females, whereas in males complex defects were restricted to the posterior compartment. Magnetic resonance imaging defecography revealed diagnoses consistent with clinical results in 77.3 percent and defects in addition to clinical diagnoses in combined pelvic floor disorders in 34 percent., Conclusions: In complex pelvic floor disorders, involving more than a single defect, dynamic magnetic resonance imaging represents a convenient diagnostic procedure in females and to a lesser extent in males, in particular in terms of dynamic imaging of pelvic floor organs during defecation. In addition to the clinical assessment, dynamic magnetic resonance imaging had clinical impact in proctologic and interdisciplinary treatment.

Purpose: Evaluation of magnetic resonance defecography in the diagnosis of pelvic floor disorders were examined prospectively. MRI was performed on a 1.5 T scanner. The rectum was opacified with 200 ml of ultrasound transmission gel. A sagittal single section T2-weighted gradient echo sequence with a temporal resolution of 1.1 second was performed. Changes of the anorectal angle and the position of the pelvic organs in relation to the pubococcygeal line were registered at rest, during straining, and during evacuation of the rectum., Results: Patients with obstructed defecation (n = 15) showed prolapse of the rectal mucosa (n = 5), anterior rectocele (n = 8), pelvic floor descent (n = 5), enterocele (n = 2), and anorectal dyscoordination (n = 3). Individuals with stool incontinence (n = 15) had an anterior rectocele (n = 10), pelvic floor descent (n = 11), enterocele (n = 2), prolapse of rectal mucosa (n = 1), and a puborectal insufficiency (n = 1). Urine incontinence was associated with cystocele (n = 10) or normal findings (n = 4). In patients with unspecific symptoms (n = 6), anorectal dyscoordination (n = 4) and prolapse of the rectal mucosa (n = 2) were found. MRI was superior for the detection of enteroceles, cystoceles and pelvic floor descent compared with clinical investigation., Conclusion: Dynamic MR imaging supplies complex information in anorectal disease and thus improves proctoscopy.

Purpose: The aim of this review is to describe the most frequent and important coloproctologic pelvic floor disorders. Relevant diagnostic procedures of the pelvic floor will be presented., Material and Methods: A host of diagnoses and symptoms such as the descending perineum syndrome, rectocele, cystocele, enterocele, uterine and vaginal descensus, anal and rectal prolapse, outlet obstruction, anismus, inertia recti and intussusception are included under the heading "pelvic floor disorders". Although symptoms are often varied, problems concerning urinary and/or faecal continence commonly lead to primary consultation of a physician., Results: Quite often, apparently divergent symptoms such as constipation and incontinence are simultaneously mentioned. A clear gender disposition is observed with female patients inflicted nine-fold in comparison to male patients. The primary consultant may belong to a variety of specialities such as urology, proctology, gynaecology or dermatology, depending upon the predominant symptom. A feeling of trust is essential for the treatment of a disorder involving highly intimate regions of the body., Discussion: An exact medical history and standardized proctologic evaluation consisting of inspection, palpation, rectoscopy and proctoscopy may be augmented by investigations such as anorectal manometry or endosonography. Conventional defecography has been replaced more and more by dynamic MRI of the pelvic floor in specialized institutions, enabling additional gynaecologic and urologic investigations avoiding ionizing radiation.

Because of its unknown etiology the treatment of Crohn's disease is of a symptomatic nature. Therapeutic decisions mostly revolve around hour one can obtain the best quality of life for the patient. An active inflammatory flare-up is normally treated with steroids; there is no known remission maintenance therapy thereafter. In all other cases a surgical treatment option has to be considered, in particular with steroid dependency, refractory disease and the presence of complications. Deficiencies after surgery must be assessed. 5-Aminosalicylic acid helps in maintaining postoperative remission maintenance.

This quantitative in vivo fluorescence microscopy study investigated the impact of warm versus cold Ringer's lactate (RL) graft rinse on various microvascular manifestations of ischemia-reperfusion injury after liver transplantation in the rat. Syngeneic orthotopic liver transplantation, including arterial revascularization, was performed in male Lewis rats following 24 h of cold storage in University of Wisconsin (UW) solution. In one group (n = 8) liver grafts were rinsed with 4 degrees C (cold) RL, whereas in the other group (n = 8) grafts were rinsed with 37 degrees C (warm) RL immediately prior to revascularization. Hepatic microvascular perfusion, leukocyteendothelium interaction, and Kupffer cell activation were quantified 30-90 min after graft reperfusion by direct visualization with intravital fluorescence microscopy. Moreover, biliary excretory graft function was analyzed by determination of bile flow and bile salt excretion during the first 90 min after reperfusion. Compared to grafts rinsed with cold RL, acinar and sinusoidal perfusion were found to be significantly increased after rinsing the grafts with warm RL. The amount of nonperfused acini declined from 18.1% +/- 4.0% to 7.4% +/- 1.6% (P < 0.05), and the total percentage of perfused sinusoids increased from 80.1 +/- 1.4 to 88.4 +/- 1.2 (P < 0.001) after cold and warm rinse, respectively. After rinsing the graft with warm RL, WBC adherence in sinusoids and especially in postsinusoidal venules decreased significantly by 28% (P < 0.001) and 33% (P < 0.001), respectively. Kupffer cell activation was markedly reduced after rinsing with RL at 37 degrees C, as indicated by a decelerated adherence of latex particles injected 80 min after reperfusion. Excretory graft function was dramatically increased following warm RL rinse during the 90-min observation period. Bile flow was enhanced from 1.04 +/- 0.5 to 3.9 +/- 0.8 ml/100 g liver per 90 min (P < 0.01), with a parallel rise in bile salt excretion from 24.3 +/- 5.8 to 128.0 +/- 19.8 mmol/ 100 g liver per 90 min (P < 0.05) when compared to cold RL. These data strongly suggest that rinsing liver grafts with warm RL prior to reperfusion represents a simple and inexpensive way to reduce the incidence of primary graft failure secondary to ischemia and reperfusion injury in liver transplantation.

Objective: This study analyzed the pathophysiologic sequela of different modes of graft reperfusion in liver transplantation., Summary Background Data: The grafted liver may be reperfused either immediately after completion of portal anastomosis followed by delayed arterial reconstruction or simultaneously by portal and arterial blood if all vascular anastomoses are completed during the anhepatic period., Methods: Delayed arterialization, that is, arterial reperfusion 8 minutes after portal revascularization (n = 12), was compared with simultaneous arterialization (n = 8) using the model of syngeneic orthotopic liver transplantation in male Lewis rats. After cold storage for 24 hours in University of Wisconsin (UW) solution, intravital fluorescence microscopy was employed 30 to 90 minutes after reperfusion to assess hepatic microvascular perfusion, leukocyte accumulation, and phagocytic activity of Kupffer cells., Results: Compared with delayed arterialization, the number of both nonperfused acini and nonperfused sinusoids was reduced after simultaneous reperfusion by 71% (p = 0.008) and 78% (p < 0.001), respectively. Leukocyte accumulation in sinusoids and postsinusoidal venules after simultaneous arterialization decreased by 17% (p = 0.01) and 64% (P < 0.001), respectively. In addition, simultaneous revascularization was able to attenuate Kupffer cell activation, indicated by significantly slower adherence of latex beads injected 80 minutes after reperfusion. Improved hepatocellular excretory function after simultaneous arterialization was demonstrated by increased bile flow during the observation period of 90 minutes after reperfusion (2.24 +/- 0.7 vs. 0.95 +/- 0.4 mL/100 g liver [mean +/- SEM], p < 0.05)., Conclusions: Timing of arterial reperfusion in liver transplantation may be of critical importance in the prevention of various manifestations of reperfusion injury.

Recently, it has been demonstrated that the use of both cold Carolina rinse (CR, 4 degrees C) as well as warm Ringer's lactate (RL, 37 degrees C) attenuates microvascular perfusion failure and leukocyte (WBC) accumulation in liver grafts. The aim of this study was to analyse in vivo whether warming of CR can also lead to a reduction in microvascular reperfusion injury in rat liver transplantation. Syngeneic orthotopic liver transplantation, including arterial reconstruction, was performed in male Lewis rats (180-300 g). Livers were stored in University of Wisconsin (UW) solution for 24 h and rinsed with 15 ml CR which was either cold 4 degrees C (n = 7) or warm 37 degrees C (n = 8) prior to reperfusion. Hepatic microcirculation and WBC accumulation were assessed by intravital fluorescence microscopy, and graft function was determined by analysis of bile flow during the 90-min reperfusion period. Warm CR yielded significantly (P < 0.01) improved sinusoidal perfusion when compared with cold CR; however, the extent of WBC adherence in both sinusoids and postsinusoidal venules did not vary between the groups. In addition, bile flow was slightly increased after warm CR. We conclude that after 24 h of cold storage in UW solution, warming of CR may offer additional benefit in the prevention of microcirculatory reperfusion injury without affecting WBC accumulation.

This quantitative in vivo fluorescence microscopy study investigated the relative impact of an optimized rinse solution (warm Carolina rinse) and that of an established storage solution (University of Wisconsin solution) on various pathomechanisms of hepatic reperfusion injury after cold storage. Syngeneic orthotopic, arterialized liver transplantation was performed in male Lewis rats after 24 hr of cold ischemia (n = 24). The four experimental groups differed according to the type of preservation/rinse solution used: University of Wisconsin solution/albumin rinse (group 1), autologous blood (just external cooling)/albumin rinse (group 2), blood/Carolina rinse (group 3) and University of Wisconsin solution/Carolina rinse (group 4). Hepatic microvascular perfusion, leukocyte accumulation and phagocytic activity of Kupffer cells were assessed by means of intravital fluorescence microscopy 30 to 90 min after reperfusion. Disturbances of microvascular perfusion were most pronounced in group 2, markedly reduced by University of Wisconsin solution (group 1) and Carolina rinse (group 3) and minimized by combined use of University of Wisconsin solution and Carolina rinse in group 4. Intrahepatic leukocyte-endothelium interaction in sinusoids and postsinusoidal venules was found to depend on the application of Carolina rinse before reperfusion rather than the use of University of Wisconsin solution during cold storage. Activation of phagocytosis by Kupffer cells was most pronounced in group 1, intermediate in groups 2 and 3 and not noticeable in group 4. Hepatocellular excretory function as assessed on the basis of total bile flow and excretion of bile acids during the first 90 min after reperfusion was found to be improved by application of Carolina rinse, both after storage in blood or in University of Wisconsin solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Flushing hepatic grafts immediately before revascularization with a specially designed rinse solution such as "Carolina rinse" has been reported to improve survival after liver transplantation in the rat. This study investigated the influence of Carolina rinse and adenosine rinse on early graft function, microcirculation, and leukocyte (WBC)-endothelial cell interaction of arterialized syngeneic orthotopic liver transplants in Lewis rats. Livers were preserved for 24 hr in University of Wisconsin solution and flushed immediately before reperfusion with either Ringer's lactate (group A: n = 7), Ringer's lactate + 0.2 mmol/liter adenosine (group B: n = 6), or Carolina rinse (group C: n = 7). Microvascular perfusion and WBC accumulation were assessed by intravital fluorescence microscopy. In group C, acinar perfusion was significantly improved, accompanied by a lower percentage of nonperfused sinusoids 1 hr after reperfusion (mean +/- SEM: 26 +/- 2% [group A], 21 +/- 2% [B], 11 +/- 1% [C], P < 0.01 for C vs. A or B). In addition, Carolina rinse and, to a lesser extent, adenosine rinse reduced the number of WBC sticking in sinusoids and postsinusoidal venules. Better graft function in group C was indicated by increased bile flow during the observation period of 90 min after reperfusion (0.5 +/- 0.3 ml/100 g liver [group A], 1.5 +/- 0.7 [B], 3.7 +/- 0.6 [C], P < 0.01 for C vs. A or B). We conclude that Carolina rinse is able to improve early excretory hepatocellular function, microvascular perfusion, and intrahepatic WBC accumulation after prolonged cold ischemia and reperfusion, but adenosine is unlikely to be the key component of this rinse solution.

This study investigated the influence of hepatic arterialization on early graft function, microcirculation, and leukocyte-endothelial interaction after syngeneic orthotopic liver transplantation in Lewis rats. Livers were preserved for 17 hr in UW solution and transplanted without rearterialization (group 1: n = 10) or with immediate arterial reconstruction (group 2: n = 10). Graft function was analyzed by bile flow; microcirculation was assessed by laser Doppler flowmetry (LDF) and intravital microscopy (IVM). In addition, flow behavior of leukocytes was quantified by IVM after i.v. injection of the WBC marker acridine orange. Improved graft function in group 2 was indicated by increased bile production during the observation period of 90 min after reperfusion (7.18 +/- 0.62 vs. 3.63 +/- 0.63 ml/100 g liver [mean +/- SEM] P < 0.001). In arterialized grafts LDF values increased by 22.9 +/- 3.8% upon reperfusion of the hepatic artery (P = 0.004). Arterialization increased WBC velocities in sinusoids (group 1: 0.29 +/- 0.02 mm/sec, group 2: 0.34 +/- 0.01 mm/sec, P < 0.001) and postsinusoidal venules (0.43 +/- 0.05 vs. 0.64 +/- 0.05 mm/sec, P = 0.029). In addition, the number of nonperfused midzonal sinusoids decreased significantly (8.5 +/- 2.2% of all sinusoids analyzed vs. 4.2 +/- 1.3%, P = 0.048). However, the marked sinusoidal and venular WBC adherence observed 1 hr after reperfusion was not altered by arterialization. It is concluded that arterial reconstruction in rat liver transplantation improves microvascular perfusion and graft function but this improvement does not relate to WBC accumulation within the graft. We propose that studies on hepatic preservation and postischemic reperfusion in the rat should be based on the physiological model of dual vascularization.

Phagocytic activity of sinusoidal lining cells was studied in 32 livers of male Lewis rats by in vivo fluorescence microscopy with epiillumination. Normal livers (group 1, n = 8) were compared with orthotopic syngeneic liver grafts 90 min after reperfusion after a period of cold storage in University of Wisconsin solution for 17 hr (group 2, n = 10) or 24 hr (group 3, n = 14). After bolus injection of fluorescence-labeled latex particles (3 x 10(8)/kg; diameter = 1.1 micron), zonal distribution and kinetics of adherence of latex beads were quantified by off-line video analysis. Hepatocellular function was estimated by the rate of bile production and biliary concentrations of bile acids. In normal livers 50%, 37% and 13% of injected latex beads adhered in zones 1, 2 and 3, respectively, whereas in transplanted livers a more homogeneous distribution was found (group 2: 37%, 41%, 22%; group 3: 37%, 39%, 24%; p less than 0.01 vs. controls by analysis of variance). Kinetic analysis of phagocytic activity showed no significant difference between group 1 (88% adherence of visible latex beads 3 min after injection) and group 2 (90% adherence). However, after long-term preservation in group 3, sinusoidal adherence was significantly faster (96.4% adherence; p less than 0.001). Bile secretion in group 2 was lower than in controls and severely depressed in group 3 (group 1: 1.1 +/- 0.07 microliter/min/gm liver [mean +/- S.E.M.]; group 2: 0.8 +/- 0.07; group 3: 0.1 +/- 0.04; p less than 0.001) without significant changes in bile acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

In 38 patients with malignant melanoma 44 radioimmunoscintigraphies (RIS) with 99mTc labeled F(ab')2 fragments of an anti-melanoma monoclonal antibody (225.28S, Tecnemab-K, Sorin Biomedica) have been performed. No side effects have been observed even in the patients with repeated RIS. Overall 81% (35/43) of all lesions were detected by imaging and 9 lesions have been previously unknown. Sensitivity and specificity was highest for lymphnode metastases with 100% each. Poor imaging was observed in lung and mediastinal metastases (2/7) as well as small skin metastases. RIS has to be studied for its clinical value in staging of lymphnode metastases preoperatively in patients undergoing regional lymphnode dissection.

In 71 patients with malignant melanoma 85 radioimmunoscintigraphies (RIS) with 99mTc-radiolabeled F(ab')2 fragments of a murine monoclonal antibody have been performed. The antibody is specific for an epitope of the HMW-MAA glycoprotein complex which is present in 90% of melanoma tissue samples. Sensitivity for RIS was 79% (73 metastatic sites out of a total of 92). 20 previously unknown lesions were found and there were also 2 false positives. Conventional staging procedures alone revealed 78% of the metastatic sites (72 of 92). No side effects were observed. RIS was especially useful for detection of lymph node metastases not found by conventional methods and is therefore considered complementary to conventional preoperative staging procedures.

Glial cells release a factor into their culture medium that induces a high degree of morphological differentiation in neuroblastoma cells under normal growth conditions. This phenomenon is not correlated with a change in intracellular adenosine 3':5'-cyclic monophosphate or in the rate of cell growth. Media from other cell lines tested induce less morphological differentiation or have no effect.