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Objective: To assess a new bloodless technique using radiofrequency energy for segmental liver resection of hepatic tumors., Summary Background Data: Liver resection remains a formidable surgical procedure; safe performance requires a high level of training and skill. Intraoperative blood loss during liver resection remains a major concern because it is associated with a higher rate of postoperative complications and shorter long-term survival., Methods: From January 2000 to June 2001, 15 patients with various hepatic tumors were operated on using radiofrequency energy to remove the tumor in its entirety. Radiofrequency energy was applied along the margins of the tumor to create "zones of necrosis" before resection with a scalpel., Results: No blood transfusions were required. The mean blood loss during resection was 30 +/- 10 mL. No mortality or morbidity was observed. The median postoperative stay was 8 days (range 5-9). No liver recurrence was detected in patients undergoing resection with this technique during follow-up periods ranging from 2 to 20 months., Conclusions: Segmental and wedge liver resection assisted by radiofrequency is safe. This novel technique offers a new method for transfusion-free resection.

Transfusion of blood or blood products peri- or postoperatively is often necessary in patients undergoing liver resections for hepatic or biliary tract neoplasms. In Jehovah's Witnesses this inevitably poses a difficult dilemma for clinicians. A 66-year-old female Jehovah's Witness with a T1b gallbladder cancer was referred to our specialist unit for further treatment after having had a routine laparoscopic cholecystectomy in another hospital. Although an abdominal computed tomography scan preoperatively showed a normal liver with no evidence of regional lymph node involvement, histologically the tumor was found in the posterior wall of the gallbladder adherent to the liver bed and had a full thickness involvement of the muscular layer, raising suspicion of a local invasion into the liver bed. The patient, having refused liver resection, was treated with a laparoscopic radiofrequency ablation under intraoperative ultrasound guidance using a newly developed "cooled-tip" needle and a 500-kHz radiofrequency generator. A "zone of necrosis" measuring 3.5 cm in diameter was created in the liver bed and adjacent tissues. The procedure lasted 90 min with no blood loss. Postoperatively, the patient was discharged on the third postoperative day and remained disease free at the 9-month follow-up. Although the follow-up in this case was too short to determine the long-term result of this approach, we believe that this is a single unique case posing a challenging problem to clinicians for which radiofrequency ablation may have a role in offering an alternative to major resections.

Background and Aims: E1B-deleted virus dl1520 (ONYX-015) has been previously used in clinical trials mainly for treatment of head and neck tumors, and has been shown to have beneficial effects independent of p53 status. The main aim of this investigation was to carry out a preclinical study for assessment of the use of dl1520 in in vitro and in vivo hepatocellular carcinoma (HCC) models with various p53 status (deleted, mutant, and wild type), and study the ultrastructural changes in the carcinoma cells during and following treatment with dl1520., Methods: dl1520 (ONYX-015) virus was used for treatment of three HCC cell lines in culture, then for treatment of developed xenografts in SCID mice. The effects of dl1520 on HCC cell growth and accompanied morphological changes were assessed by various techniques including transmission electron microscopy. dl1520 infection was confirmed using polymerase chain reaction and immunolabeling at transmission electron microscopy level., Results: dl1520 was effective in killing cells and inhibiting HCC cell growth both in vitro and in vivo. The cell killing was at higher levels in cells possessing abnormal p53. Survival rates in SCID mice treated with dl1520 were statistically significantly higher in HCC tumors with deleted and mutant p53, than in tumors with wild-type p53., Conclusions: The findings in this study suggest that dl1520 could be safely and effectively used for treatment of HCC dependent on the p53 status of the cells in vivo. Characteristic morphological changes that took place in the dl1520-treated HCC cells/tumors were distinct at transmission electron microscopy level and are the first of their kind to be reported.

Man-made vitreous fibers (MMVF) are classified within the European Union (EU) as carcinogenic category 3 (possibly carcinogenic), but criteria exist to exonerate fibers from this classification. The HT stone wool fiber type is a MMVF that fulfills European regulatory requirements for exoneration from classification as a carcinogen based on in vivo testing. The chemical composition of the fibers and the results of the in vivo and in vitro studies that defined the chemical compositional range for a CAS registry number for these fibers are presented and discussed. Results from in vitro dissolution measurements at pH 4.5 of 52 fiber compositions (9-23 wt% Al(2)O(3) and 32-47 wt% SiO(2)) ranging from traditional stone wool to the biosoluble HT fibers are presented. The results are evaluated as a function of the ratio Al/(Al+Si) in the glass network and as a function of the fraction of Si-O-Si linkages in the glass. It is suggested that the dissolution mechanism for these fibers relates to the density of the surface silica layer on dissolving fibers and that the fraction of Si-O-Si linkages influences this., ((c) 2002 Elsevier Science (USA).)

Although resection is currently the only curative approach for metastatic liver cancer, only a small number of cases are suitable for this procedure. In the past few years, gene therapy has emerged as an appealing treatment option for liver cancer. Phase I and II clinical trials have been conducted in patients with either primary or secondary liver cancer using a variety of genes including tumor-suppressor gene p53, suicide genes, immune genes, and replication-competent oncolytic adenoviruses. The results have shown that, although gene therapy has been well tolerated and toxicity has been low, the clinical benefit has so far been marginal. Gene therapy as a definitive treatment for liver metastases remains limited, at least for the time being, but it may be useful as an adjuvant treatment in combination with radiotherapy, chemotherapy, and/or surgery to achieve disease-free survival., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Radiohumeral stability to forced translation was experimentally analyzed in 8 osteocartilaginous joint preparations. The joints were dislocated in 8 centrifugal directions at 12 different combinations of joint flexion and rotation while a constant joint compression force of 23 N was applied. Stability was measured as the maximum resistance to translation. On average, the specimens could resist a transverse force of 16.4 N (range, 13.0-19.1 N). Stability was greater in some directions than in others. Rotating the joint changed the direction at which stability was greatest, whereas joint flexion did not. In supination, the greatest stability was observed for anteromedial dislocations, in neutral rotation for posteromedial dislocations, and in pronation for posterolateral dislocations. The findings from this study indicate systematic variations in wall height around the radial head concavity as well as individual variations in joint constraint. This may have implications for the treatment of conditions involving radiohumeral joint dislocation.

In a recent study we have demonstrated that interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) serum levels correlate positively with the severity of acute pancreatitis (AP), induced by bile acid injected into the pancreatic duct of rabbits. In this article we describe the effect of an IL-10 analogue IT9302 and a monoclonal anti-IL-8 (mon. IL-8) antibody on the content of several pro-inflammatory cytokines in the serum of rabbits, after induction of AP. We found that the serum content of inflammatory cytokines IL-8, IL-1beta, TNF-alpha and monocyte chemoattractant protein 1 (MCP-1) are increased during AP. Injection of IT9302 or mon. IL-8 antibody, diminish the concentration of these cytokines in the serum, with the exception that mon. IL-8 antibody actually increased the circulating level of MCP-1. In addition, intravenous administration of IT9302 increased the serum levels of IRAP, an IL-1beta receptor antagonistic cytokine. Furthermore, intravenous injection of mon. IL-8 antibody increased serum levels of IL-4. It can be concluded that both the human IL-10 analogue IT9302 and mon. IL-8 antibody are able to alter the pro-inflammatory cytokine levels in rabbits suffering from experimentally induced AP., (Copyright 2002 Elsevier Science Ltd.)

A previous anatomic study has revealed that the lateral collateral ligament (LCL) complex of the elbow has a Y-shaped configuration, which consists of a superior, an anterior, and a posterior band. The LCL complex, including the annular ligament, functions as a 3-dimensional (3D) Y-shaped structure. On the basis of this concept, joint laxity after transection of the anterior band was studied in 5 normal, fresh-frozen cadaver elbows with a 3D kinematic testing apparatus. Cutting the anterior band produced significant laxity to varus torque with a mean 5.9 degree at 10 degree of elbow flexion and caused significant laxity to torque in external rotation with a mean 8.5 degree at 40 degree of flexion. No significant laxity was observed during application of valgus or internal rotational torque. Further transection of the posterior band resulted in gross instability with dislocation of the ulnohumeral joint. The laxity occurring after severance of the anterior band suggests that these fibers play a role in preservation of elbow stability against varus and external rotational torque. These results indicate that the LCL functions as a complex with a Y structure and not as an isolated linear ligament. A concept of conjoint point is hypothesized for the function of the LCL complex to restrain posterolateral rotatory instability.

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.

The antiphospholipid antibody syndrome is a multisystem disorder characterized by persistently elevated antiphospholipid antibodies and/or arterial or venous thrombosis, thrombocytopenia and recurrent spontaneous abortion. Anticardiolipin antibodies and the lupus anticoagulant are different classes of antiphospholipid antibodies associated with this disorder. Various hematologic, neurologic, obstetric and cutaneous abnormalities are manifest in this syndrome. This article reviews the characteristic features of the antiphospholipid antibody syndrome.

In this study the kinematics of partial and total ruptures of the medial collateral ligament of the elbow are investigated. After selective transection of the medial collateral ligament of 8 osteoligamentous intact elbow preparations was performed, 3-dimensional measurements of angular displacement, increase in medial joint opening, and translation of the radial head were examined during application of relevant stress. Increase in joint opening was significant only after complete transection of the anterior part of the medial collateral ligament was performed. The joint opening was detected during valgus and internal rotatory stress only. After partial transection of the anterior bundle of the medial collateral ligament was performed, there was an elbow laxity to valgus and internal rotatory force, which became significant after transection of 100% of the anterior bundle of the medial collateral ligament and was maximum between 70 degrees to 90 degrees of flexion. No radial head movement was seen after partial or total transection of the anterior bundle of the medial collateral ligament was performed. In conclusion, this study indicates that valgus or internal rotatory elbow instability should be evaluated at 70 degrees to 90 degrees of flexion. Detection of partial ruptures in the anterior bundle of the medial collateral ligament based on medial joint opening and increased valgus movement is impossible.

One century ago surgical gloves were introduced to practice as part of the new antiseptic technique and originally to protect the hands of the surgeon and his assistants from the harmful dermatologic effects of powerful antiseptics (e.g., carbolic acid) in use at that time. Since then, the wearing of gloves during surgery has been standard practice. Furthermore, the protection value of surgical gloves in preventing cross-infection has stood the test of time. Nevertheless, materials used in glove manufacturing have caused a succession of iatrogenic problems in surgical patients over the years. More recently, emergence of transmissible viruses, such as hepatitis B and C and human immunodeficiency virus, has led surgeons to consider their own safety with the frequent possibility of perforation of surgical gloves by sharp instruments. In this review we discuss the problems associated with surgical glove practice: glove powder-induced peritonitis and adhesions, latex rubber-associated hypersensitivity, and glove perforation.

The contribution of the radial head to elbow joint kinematics was studied in 7 osteoligamentous elbow preparations. During unloaded flexion and extension, radial head excision induced a maximum varus displacement of 1.6 degrees with 20 degrees of joint flexion and a maximum external rotation of 3.2 degrees at 110 degrees of flexion. With application of a 0.75-Nm load, radial head excision induced a maximum laxity of 3.3 degrees at 20 degrees of flexion in forced varus and a maximum laxity of 8.9 degrees at 10 degrees of flexion in forced external rotation. No laxity was observed in forced valgus or internal rotation. The results were independent of the rotation of the forearm. This study indicates that the radial head acts as stabilizer to the elbow joint in forced varus and in forced external rotation. The results suggest that fractures of the radial head cannot be treated by simple excision without altering the basic kinematics of the elbow joint.

Background: We recently demonstrated that laparoscopic cholecystectomy is followed by a much smaller hepatic catabolic stress response than conventional cholecystectomy. It is not known what is responsible for this difference., Methods: Thirty pigs were randomly allocated to the following five treatment groups: (1) laparotomy, (2) pneumoperitoneum, (3) pneumoperitoneum with insertion of four trocars, (4) laparotomy, (5) pneumoperitoneum. Groups 1-3 were operated on in an ambulatory setting, whereas groups 4 and 5 were operated on in a stationary setting. Urea synthesis, as quantified by functional hepatic nitrogen clearance, and the response of stress hormones and cytokines were assessed., Results: Laparotomy increased the functional hepatic nitrogen clearance by 195% (p < 0.001); pneumoperitoneum and trocars increased it by 145% (p < 0.001); and pneumoperitoneum alone increased it by 113% (p < 0. 001). The difference between laparotomy and both pneumoperitoneum groups was significant. If the stress factor of ambulatory surgery was eliminated, the increase in functional hepatic nitrogen clearance was reduced to 87% (p < 0.01) after laparotomy and 38% (NS) for animals subject to pneumoperitoneum. There were significant differences in concentrations of stress hormones, tumor necrosis factor alpha, and interleukin 8 among groups intra- and postoperatively., Conclusions: The magnitude of the postoperative hepatic stress response after laparotomy compared to pneumoperitoneum with and without insertion of trocars seems to be caused by the greater trauma to the abdominal wall. Furthermore, an ambulatory setting seems to be an important postoperative stress factor in itself.

Certain neurochemical and connectional characteristics common to extended amygdala and the nucleus accumbens shell suggest that the two represent a single functional-anatomical continuum. If this is so, it follows that the outputs of the two structures should be substantially similar. To address this, projections from the caudomedial shell and central nucleus of the amygdala, a key extended amygdala structure, were demonstrated in Sprague-Dawley rats with different anterograde axonal tracers processed separately to exhibit distinguishable brown and blue-black precipitates. The caudomedial shell projection is strong in the ventral pallidum and along the medial forebrain bundle through the lateral preopticohypothalamic continuum into the ventral tegmental area, distal to which it thins abruptly. The central nucleus projects strongly to the bed nucleus of the stria terminalis and the sublenticular extended amygdala, but substantially to the lateral hypothalamus only at levels behind the rostral part of the entopeduncular nucleus. Innervation of the ventral tegmental area by the central amygdala is minimal, but the lateral one-third of the substantia nigra, pars compacta and an adjacent lateral part of the retrorubral field receive substantial central amygdala input. Central amygdaloid projections are robust in caudal brainstem sites, such as the reticular formation, parabrachial nucleus, nucleus of the solitary tract and dorsal vagal complex, all of which receive little input from the accumbens. The substantial differences in the output systems of the caudomedial shell of accumbens and central amygdala suggest that the two represent distinct functional-anatomical systems.

Objective: To establish and monitor a rabbit model of graded severity of acute pancreatitis to test the hypothesis that interleukin-8 (IL-8) and the adhesion molecule complex CD11b/CD18 are involved in the development of systemic complications in severe acute pancreatitis., Methods: Acute pancreatitis induction in rabbits by duct ligation with or without infusion of 5.0% or 0.5% chenodeoxycholic acid or 0.9% saline. Control animals underwent laparotomy. The animals were monitored biochemically, histologically and immunohistochemically., Result: Increased serum levels of IL-8, tumour necrosis factor alpha (TNF-alpha), amylase and lipase were found in the chenodeoxycholic acid groups when compared with the saline, duct-ligated or control groups. Leukopenia, hypocalcaemia, and hyperglycaemia were marked in the 5.0% chenodeoxycholic acid group as compared to the saline, duct-ligated and control groups. Histologically, the 5.0% chenodeoxycholic acid group manifested a significant degree of pancreatic necrosis and neutrophil infiltration. The lungs of these animals showed acute lung injury and a significant up-regulation of CD11b/CD18. IL-8 was produced in pancreatic acinar and ductal cells. A significantly large output of ascitic fluid was seen in the 5.0% chenodeoxycholic acid group., Conclusion: The rabbit models of acute pancreatitis are reliable in that enzymatic and histological evidence of acute pancreatitis with or without systemic complications developed. IL-8 is produced locally in pancreatic acinar and ductal cells and significantly increased in peripheral blood during severe but not mild pancreatitis. The expression of the adhesion molecule complex CD11b/CB18 is significantly increased in lung tissue during severe acute pancreatitis with acute lung injury. IL-8 and CD11b/CB18 are involved in the pathogenesis of severe acute pancreatitis but not of mild oedematous pancreatitis.

Background: As impaired immune function observed in cirrhotic patients is known to increase the risk of postoperative complications, the immunological response to surgery was investigated., Methods: Twenty-eight patients with postnecrotic liver cirrhosis or chronic hepatitis C and symptomatic gallstone disease were randomly allocated to laparoscopic (LC) or open cholecystectomy (OC). Changes in concentrations of cytokines (TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10) were followed and the effect of surgical trauma on the distribution of lymphocyte subpopulations (CD3, CD4, CD8, CD16 and CD19) and NK cell cytotoxicity were measured., Results: After OC a decrease in circulating CD3 (p < 0.05) and CD4 (p < 0.05) and an increase in CD19 (p < 0.05) cells were detected in contrast to LC after which only CD16 cells decreased (p = 0.05). The number of CD3 cells was higher after LC than after OC (p < 0.01), whereas the number of CD19 cells was higher after OC than after LC (p < 0.01). NK cell cytotoxicity was reduced after LC (p < 0.05). In cirrhotic patients circulating cytokines were unaffected by OC, whereas TNF-alpha (p < 0.05) and IL-1beta (p < 0.05) were reduced after LC. In chronic hepatitis IL-1beta decreased after OC (p = 0.05) and IL-10 was significantly higher after LC than following OC (p < 0.05)., Conclusion: The immune response is less pronounced after a laparoscopic procedure compared to a conventional approach in patients with chronic liver disease.

Background: Proinflammatory cytokines like TNF-alpha and IL-8 have been thought to play a pivotal role in the propagation of severe acute pancreatitis (AP) and the development of its systemic complications, particularly acute lung injury., Objective: To investigate the effects of pretreatment with hydrocortisone on the production of cytokines and the occurrence of acute lung injury in rabbits with AP., Methods: AP was induced in 17 rabbits by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ductal ligation. The rabbits were allocated to pretreatment with subcutaneous and intravenous hydrocortisone (25 mg/kg, respectively; n = 7) or 0.9% saline (n = 10) 30 min before induction of AP. Rabbits were observed for 12 h. Serum amylase, lipase, TNF-alpha, IL-8, glucose, calcium and leukocyte count were measured every 3 h. At the end of the experimental period, ascitic fluid was collected and tissue specimens from the pancreas, lungs and kidney were obtained., Results: Hydrocortisone pretreatment improved survival from 40 to 100%. Serum TNF-alpha and IL-8 were lower in the hydrocortisone group than in the control group at 6 h (p = 0.006 and p < 0.001, respectively). Hydrocortisone abolished leukopenia (p < 0. 001), hyperamylasemia (p = 0.05), the occurrence of acute lung injury and reduced the volume of ascites., Conclusions: Our findings suggest a role for TNF-alpha and IL-8 in mediating the progress of AP from a local disease into a systemic illness. Hydrocortisone should be tested experimentally after the induction of AP and clinically as a prophylactic measure to avoid severe AP induced by endoscopic retrograde cholangiopancreaticography.

Background: Disturbances of coagulation and fibrinolysis are well-known systemic effects of acute necrotising pancreatitis (ANP). The purpose of this experimental study was to evaluate the initial events in the haemostatic activation during ANP in an animal model with relevance to the human situation., Methods: ANP was introduced in 7 rabbits by infusion of chenodeoxycholic acid in the pancreatic duct. Seven rabbits served as sham-operated controls. Serial measurements of coagulation variables (prothrombin time, activated partial thromboplastin time, FVII activity, fibrinogen, tissue factor activity), anticoagulant proteins (protein C, antithrombin) and fibrinolytic factors (tissue plasminogen activator, plasminogen activator inhibitor-1) were performed for 5 h., Results: ANP was confirmed by elevated serum amylase, development of ascites, and histological changes of the pancreas. A moderate activation of the coagulation system was found in both study groups. A significant decrease in protein C concentration from 1 h after the induction of ANP was found, whereas the response of antithrombin and the inhibition of the fibrinolytic system were similar in the 2 study groups. Microthrombosis of the lungs or kidneys was found in 2 rabbits with ANP., Conclusion: An immediate activation of protein C is a specific characteristic of the haemostatic activation in ANP in rabbits. This activation has not been described previously and the possible therapeutic implications ought to be studied.

Background: New therapies designed to downregulate the aberrant immune response associated with severe acute necrotizing pancreatitis (ANP) are being increasingly investigated in different experimental models of ANP. The aim of this study was to test the potential effects of sodium fusidate on the course of severe ANP in rabbits., Methods: ANP was induced in 20 rabbits by retrograde injection of 5 per cent chenodeoxycholic acid into the pancreatic duct followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiological saline or sodium fusidate 80 mg/kg 30 min before the induction of ANP. Levels of serum amylase, lipase, tumour necrosis factor (TNF) alpha, interleukin (IL) 8, glucose and calcium, and leucocyte count were measured every 3 h for a total of 12 h. At the end of the experiment, ascitic fluid was collected and the pancreatic, lung and kidney tissues were obtained for histological examination., Results: Pretreatment with sodium fusidate reduced the mortality rate from six of ten to three of ten (P < 005) and reduced the output of ascitic fluid from 5 2 to 2.0 ml/h (P < 0001). Serum levels of TNF-alpha and IL-8 were reduced significantly in the treated group from 5 min up to 9 h after induction of ANP. The leucopenia observed after 3 h in the untreated group was not significantly improved in the group treated with sodium fusidate (P = 0.055). By contrast, both treated and untreated rabbits had similar biochemical changes including levels of amylase, lipase, glucose and calcium as well as similar histological changes in the pancreas and lungs., Conclusion: Pretreatment with sodium fusidate resulted in a considerable reduction in mortality rate and ascitic fluid output in rabbits with bile-induced ANP, probably by lowering the TNF-alpha and IL-8 blood levels. However, pretreatment with sodium fusidate did not alter the local or systemic manifestations of ANP. Thus, cytokines other than TNF-alpha and IL-8 are likely to mediate the local and systemic symptoms of ANP.

The aim of this study was to evaluate the anti-inflammatory effect of tirilazad mesylate on edema and interleukin-1 (IL-1) levels in serum following standardized surgical procedures. Four groups, each containing eight rats, were randomized for treatment as follows: A) no medication, B) low-dose tirilazad, C) high-dose tirilazad, and D) corticosteroids. The animals were examined by nuclear magnetic resonance imaging (NMRI) 24 and 72 hours after surgery and the NMRI data were used in the determination of soft tissue edema. In addition, serum was obtained for analysis of IL-1 levels. Four other groups of animals were subjected to the same treatment regimen as groups A-D), respectively, and 24 hours after surgery the animals were killed, whereafter serum was obtained for analysis of IL-1 levels. The present study demonstrated that low-dose tirilazad significantly reduces soft tissue edema compared with all other treatment regimens 24 hours postoperatively. At 72 hours postoperatively significant reduction of soft tissue edema was achieved at low-dose tirilazad when compared to high-dose tirilazad and steroids. In addition, a significant suppression of the expression of IL-1 was observed at 24 and 72 hours when comparing low-dose tirilazad and the control group.

We compared the stress-strain distributions obtained from isolated segments of the guinea pig duodenum, jejunum, and distal ileum, and the relation between the elastic properties and the collagen content. The segments were immersed in Krebs-Ringer solution containing 10(-2) M MgCl2 to abolish contractile activity. Stepwise inflation of an intraluminal balloon in which the cross-sectional area (CSA) was measured provided the luminal pressure-loading stimulus. The wall thickness was measured by means of 20-MHz A-mode ultrasound. The stress-strain and the incremental elastic modulus-strain distributions were derived from the steady-state values of wall thickness, internal radius, and applied pressure. The CSA-pressure relations and the wall thickness-pressure relations were nonlinear and both differed between the segments (P < 0.01). The stress-strain distributions showed an exponential behavior that fitted well to the equation Y = a x Exp(b x X) (r2 = 0.97 +/- 0.01). The intercept with they axis (a) and the slope of the curves (b) differed between the segments (P < 0.01 and P < 0.05). The collagen contents were 3.99 +/- 0.18 microg/mg, 2.51 +/- 0.13 microg/mg, and 2.10 +/- 0.11 microg/mg in the duodenum, jejunum, and distal ileum, respectively. This difference was significant among all three locations (P > 0.05). An association was found between the collagen content and the incremental elastic modulus (stiffness) at a stress level of 70 kPa (P < 0.05).

Background: Proinflammatory cytokines (eg, tumor necrosis factor [TNF]-alpha, interleukin [IL]-1 and Il- 8) are believed to play an important role in the pathogenesis of acute necrotizing pancreatitis (ANP) and its systemic complications. Recently, IL-10 has emerged as a major anti-inflammatory cytokine, inhibiting the secretion and activities of inflammatory cytokines. Further, a protective effect of IL-10 has recently been shown in experimental acute pancreatitis. The purpose of this study was to test the potential role of a newly developed IL-10 agonist, IT 9302, in a model of ANP in rabbits., Methods: ANP was induced in 18 rabbits by retrograde injection of 5% chenodeoxycholic acid in the pancreatic duct, followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiologic saline solution or IT 9302 (200 micrograms/kg) 30 minutes before the induction of ANP., Results: Injection of IT 9302 resulted in a significant reduction in the blood levels of TNF-alpha and IL-8 from 3 to 6 hours. IT 9302 also reduced the amount of ascitic fluid and significantly inhibited neutrophil infiltration and margination, as well as the number of CD11b- and CD18-positive cells in the lung tissues. By contrast, the local pancreatic necrosis, as well as the biochemical changes such as serum amylase, lipase, and calcium, was sever and similar in both groups. Survival was improved significantly after treatment with IT 9302., Conclusions: As expected, IT 9302 cannot change the degree of ANP induced by 5% bile acid but does reduce mortality rates and the development of acute lung injury, probably through the inhibition of circulating levels of TNF-alpha, IL-8, and the expression of the adhesion molecule complex CD11b/CD18.

Background: Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis., Aims: To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis., Methods: Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis., Results: Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor alpha (TNF-alpha) from three to six hours after induction of acute pancreatitis (p = 0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-alpha, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose., Conclusion: WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-alpha, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.

Parasitic diseases of the biliary tract occur frequently in tropical and subtropical areas and cause high morbidity and mortality. In general, neither the clinical presentation nor the general laboratory findings are sufficiently unique to raise the possibility of a parasitic biliary infestation in the mind of the surgeon. Once considered, however, the presence of a parasitic biliary infestation is easily confirmed. Most commonly this is accomplished by the identification of the parasite in stools or duodenal contents. Ultrasonography, CT and MRI are not only important in the diagnosis of parasitic biliary diseases but also in the follow-up and surveillance. ERCP is an excellent diagnostic tool for demonstrating the presence of parasites in the biliary tree. Furthermore, ERCP is also used in the therapy of biliary parasitic infestations and carries less morbidity and mortality than the surgical approach. Surgery is only indicated in complicated cases. Mechanisms that may be effective against parasites include: antibodies; cytotoxic T cells; T-cell-induced activated macrophages; natural killer cells, and a variety of cells that mediate antibody-dependent cell-mediated cytotoxicity and modulators of the immune system such as cytokines. Future research has to focus on the importance of these mechanisms for the immune evasion by parasites.

Interleukin 10 (IL-10) is a recently described natural endogenous immunosuppressive cytokine that has been identified in human, murine, and other organisms. Human IL-10 (hIL-10) has high homology with murine IL-10 (mIL-10) as well as with an Epstein-Barr virus genome product BCRFI. This viral IL-10 (vIL-10) shares a number of activities with hIL-10. IL-10 significantly affects chemokine biology, because human IL-10 inhibits chemokine production and is a specific chemotactic factor for CD8+ T cells. It suppresses the ability of CD4+ T cells, but not CD8+ T cells, to migrate in response to IL-8. A nonapeptide (IT9302) with complete homology to a sequence of hIL-10 located in the C-terminal portion (residues 152-160) of the cytokine was found to possess activities that mimic some of those of hIL-10. These are: (i) inhibition of IL-1beta-induced IL-8 production by peripheral blood mononuclear cell, (ii) inhibition of spontaneous IL-8 production by cultured human monocytes, (iii) induction of IL-1 receptor antagonistic protein production by human monocytes, (iv) induction of chemotactic migration of CD8+ human T lymphocytes in vitro, (v) desensitization of human CD8+ T cells resulting in an unresponsiveness toward rhIL-10-induced chemotaxis, (vi) suppression of the chemotactic response of CD4+ T human lymphocytes toward IL-8, (vii) induction of IL-4 production by cultured normal human CD4+ T cells, (viii) down-regulation of tumor necrosis factor-alpha production by CD8+ T cells, and (ix) inhibition of class II major histocompatibility complex antigen expression on IFN-gamma-stimulated human monocytes. Another nonapeptide (IT9403) close to the NH2-terminal part of hIL-10 did not reveal cytokine synthesis inhibitory properties, but proved to be a regulator of mast cell proliferation. In conclusion, we have identified two functional domains of IL-10 exerting different IL-10 like activities, an observation that suggests that relatively small segments of these signal proteins are responsible for particular biological functions.

MCAF (MCP-1) a member of the chemokine-beta-family known to be chemotactic for monocytes is believed to play a significant role in several inflammatory processes, both immuno-pathological disorders, such as atherosclerosis, psoriasis, chronic inflammatory diseases of the liver and lungs, and during the normal immune response against microorganisms. This chemokine is produced spontaneously by monocytes, and in the present article we also demonstrate that MCAF induces its own production in monocytes. The methods used are two dimensional SDS-PAGE gel electrophoresis. Western-blotting and ELISA quantification of supernatant from monocyte cultures stimulated with MCAF (1, 10, 100 ng ml). Also, we found that this process is regulated by IL-10 (100 ng ml). Our results suggest that monocytes migrating to a site of inflammation due to the local production of the chemokine MCAF/MCP-1 further enhance the focal accumulation of monocytes by producing and releasing bioactive MCAF MCP-1.

Objective: To investigate if double gloving can reduce the rate of perforation of glove barriers during abdominal surgery., Design: Randomised controlled trial., Setting: County hospital, Denmark., Subjects: 400 glove barriers from principal surgeons and first assistants used at consecutive abdominal operations., Intervention: Each participant was randomised to wear either a pair of single or double gloves., Main Outcome Measures: The number of perforated glove barriers in the two study groups., Results: 40 single glove barriers perforated (20%) and in 8 of the double glove group both gloves perforated (4%) (p < 0.001). Glove barriers on non-dominant hands were more often perforated than those on dominant hands, and both the duration of the operation and the seniority of the doctor were associated with increased rates of perforation., Conclusion: Double gloving reduces the rate of perforation of glove barriers during abdominal surgery and thereby the number of episodes in which transmission of disease from patient to surgeon would be possible.

Objective: To investigate the occurrence of compartment syndrome and the results of fasciotomy in vascular surgical patients., Design: Retrospective study of case records from 1980-1994., Materials: Fifty-seven limbs in 53 patients had fasciotomies following surgical revascularisation. Fifty-three (93%) limbs were acutely ischaemic, while four (7%) had undergone elective vascular surgery. Forty-four (77%) limbs had signs of compartment syndrome, while 13 (23%) fasciotomies were prophylactic., Methods: The fasciotomies were done as subcutaneous procedures (n = 40), as double-incision fasciotomies (n = 11), or by an unknown method (n = 6). The skin incisions were closed primarily in 26 (46%) cases, delayed primarily in 11 (19%) cases, and by skin grafting in eight cases (14%)., Results: Five (13%) subcutaneous fasciotomies required revision. Surgical debridement was required in four (7%) limbs. At discharge, 36 (68%) patients had kept their limbs, 11 (21%) patients were amputated, and six (11%) had died. No complications relating to the fasciotomies were observed., Conclusions: Compartment syndrome is usually related to acute ischaemia and rarely following elective vascular surgery. Subcutaneous fasciotomy does not always ensure sufficient decompression of all four lower leg compartments. Complications related to fasciotomy are rare.

We wished to study the effects of intravenous glucose/ insulin infusion to brain-dead pigs on the hepatic glycogen content. Four groups of 40-kg pigs were studied: brain-dead and control pigs given isotonic saline or glucose/insulin (7.5 mg glucose/kg/min, 1.25 mU insulin/kg/ min) (n = 5 to 10 in each group). Brain death was induced by inflating a balloon placed in the epidural space. In brain-dead pigs given saline, liver glycogen decreased from 45 +/- 11 mmol/g DNA (mean +/- SEM) to 7 +/- 3 mmol/ g DNA after 6 hours. Thereafter, it increased to 28 +/- 9 mmol/g DNA after 9 hours (P = .05 compared with the 6-hour measurement). These changes were accompanied by transient increases in plasma adrenaline, glucose, free fatty acids (FFA), and glucagon. Following glucose/ insulin infusion, hepatic glycogen increased steadily and was approximately double after 12 hours (P < .01) in both brain-dead and in non-brain-dead pigs. In brain-dead pigs, the increases in the aforementioned blood measurements were smaller following glucose/insulin infusion than following saline infusion. However, studies of longer duration will be needed to examine these effects on a time scale that is relevant to human organ donors. In conclusion, the decrease in hepatic glycogen content after brain death could be prevented by intravenous glucose/insulin infusion probably because of a reduction of the adrenaline response to the induction of brain death.

The effect of the type of venous drainage of the graft on its endocrine function was studied in two groups of pigs after segmental pancrease autotransplantation. Group 1 comprised 10 pigs with portal venous drainage (PVD) and group 2 comprised 10 pigs with systemic venous drainage (SVD). The graft consisted of body and tail of the pancreas. The pigs were totally pancreatectomized. The pancreatic duct was occluded by neoprene injected into the duct. One week before and 1 and 3 months after transplantation, intravenous glucose tolerance (IVGTT) and meal stimulation tests (MST) were performed. Plasma glucose (PG), insulin (INS), C-peptide, glucagon (GLU),and pancreatic polypeptide (PP) were measured during the tests. All pigs had normal fasting PG, 1 and 3 months after PanTx, although MST disclosed significantly higher PG (P<0.05) during the test after transplantation. In the PVD group, a decrease in INS level during both test was recorded after PanTx (P<0.05), while in the SVD group a nonsignificant rise in INS level was recorded compared with before transplant. A significant difference (P<0.05) in INS levels were present both 1 and 3 mon. after PanTx between the two groups. Pigs with PVD showed a higher (P<0.05) C-peptide level than pigs with SVD during IVGTT. The initial significant rise in PP during MST and the initial fall in PP during IVGTT recorded in all pigs before transplantation were totally lost after transplantation in both groups. During the tests, PP remained steady and significantly lower than the pretransplantation levels in both groups. A significantly higher GLU level during both IVGTT and MST was observed in SVD compared with PVD 1 month after PanTx (P<0.05), being more pronounced during MST. This accentuated GLU concentration decreased by 3 months after transplantation, although it was still significantly greater than pretransplantation levels. We concluded that the unnatural mode of delivery of pancreas endocrine secretion to systemic rather than to portal circulation leads to derangements in pancreatic endocrine function in order to maintain glucose homeostasis. This may cause earlier exhaustion of islet cells. Segmental rather than whole organ and duct occlusion rather than exocrine drainage may further contribute to this, shortening the effective life of the graft.

Interleukin-8 (IL-8), a neutrophil-activating cytokine, also activates certain T cell functions such as chemotaxis. We additionally find (n = 6) that recombinant (rIL-8; 1-100 ng/ml), when added to 24 h culture of human CD4+ T cells, suppressed the spontaneous production of IL-4 (50-85%). Steady state production of Il-4 was typically around 30 pg/ml, determined by use of a solid- phase immunoabsorbant assay. De novo synthesis of IL-4 from CD4+ T cells cultured for 3 days was also evaluated by use of detection of [35S]methionine incorporation, as visualized by autoradiography of 2-D gels, and showed that IL-8 suppressed IL-4 production. This suppression of IL-4 production was confirmed in the cytosol fraction by use of Western blotting. The effect of IL-8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon-gamma, both strongly suppressing IL-4 production. The regulatory effect of IL-8 on IL-4 production was also indicated by the fact that addition of a neutralizing monoclonal anti-IL-8 antibody (WS.4) enhanced the spontaneous IL-4 production when added to the culture of CD4+ T cells, thereby probably inactivating the effect of IL-8 originating from the cultured T cells. Also, we observed that IL-4 mRNA expression was down-regulated when the CD4+ T cells were cultured for 12 h in the presence of 100 ng/ml IL-8. The suppression of IL-4 mRNA expression could be prevented by adding anti-IL-8 (20 microgram/ml) or IL-10 (100 ng/ml) l h before adding rIL-8. Thus, IL-8 may be an important regulator of CD4+ T cell-derived IL-4, thereby possibly regulating the balance between humoral and cellular T cell-dependent responses.

Overexpression of the nm23H1 gene has been associated with the suppression of metastasis in several solid tumors. However, in colorectal carcinoma and neuroblastoma, increased levels of nm23 H1 nucleoside diphosphate kinase A (NDPKA) mRNA are associated with tumorigenesis. To determine the role of nm23 H1/NDPKA in the prostate, normal and/or malignant tissue samples from 29 consecutive patients were studied. Levels of nm23 H1/NDPKA mRNA and nm23 H1/NDPKA mRNA protein were determined in tissue from 18 and 27 patients, respectively. In all, 16 of the 18 tumor samples expressed increased levels of nm23 H1/NDPKA mRNA as compared with those measured in normal tissue. The level of nm23 H1/NDPKA mRNA was > 10-fold higher in a metastatic lymph node than in normal prostate tissue. All cancer specimens and areas of prostatic intraepithelial neoplasia showed immunoreactivity with the nm23 H1/NDPKA antibody; however, normal prostatic tissue was unreactive. These findings suggest that overexpression of the nm23 H1/NDPKA gene occurs frequently in adeno-carcinomas of the prostate and may be an early event in prostate cancer tumorigenesis.

The aim was to develop a method for the quantification of the stress-strain distribution of tubular organs in vivo using the porcine duodenum as an experimental model. We placed four electrodes for impedance planimetry and a 20 MHz ultrasound transducer inside an inflatable balloon mounted on a 6 mm-diameter probe for intraluminal use. By means of the ultrasound transducer and the impedance planimetric system, we measured the wall thickness and luminal cross-sectional area of the duodenum. We calculated the luminal radius on the basis of the latter. We validated ultrasonic measurements of wall thicknesses by comparing the former to microscopic measurements of the wall thickness of unstrained duodenal specimens in vitro. Also, we tested whether the magnitude of the applied balloon pressure affected ultrasonic measurements in vitro. The luminal and the outer radius increased non-linearly by a factor of three, rising steeply at low balloon pressures, moderately at higher pressures. The wall thickness decreased as an almost linear function of the applied balloon pressure, resulting in a 50% decrease. The stress-strain distribution calculated on the basis of the balloon pressures, the wall thicknesses and the luminal radii were non-linear. The wall reached a maximum circumferential strain of 1.71 at 6 kPa, corresponding to a stress of 64.8 kPa. Our system enabled us to quantify the stress-strain distribution of the porcine duodenum in vivo, and it may become a valuable tool for future biomechanical investigations of tubular organs in health and disease.

The neutrophil and T cell chemotactic factor interleukin 8 (IL-8) is believed to play a pathophysiological role in the development of various inflammatory disorders. So far no other effects of IL-8 on T cells have been observed. We observed that purified CD4+ T cells in particular, but also CD8+ T cells, spontaneously synthesize IL-8 mRNA and secrete IL-8 protein. The culture supernatants of CD4+ T cells contained T cell chemotactic activity as well as IL-8 protein. In addition, we confirmed the ability of CD4+ T cells to produce IL-8 by double immunofluorescence staining and by the demonstration of IL-8 mRNA expression. Further, IL-8 induced its own production in CD4+ T cells, while its synthesis by CD8+ T cells was low and not always auto-stimulatory. Both the spontaneous, as well as the IL-8 induced IL-8 production, could be inhibited in the presence of human interleukin 10 (100 ng/ml). This observation suggests that IL-10 plays a homeostatic role in regulating the IL-8 circuit in CD4+ T cells.

The aim was to study and compare the passive biomechanical wall properties in the isolated duodenum and distal ileum of the guinea pig in vitro. The organ bath contained a Krebs-Ringer solution with 10(-2) M MgCl2 to abolish smooth muscle contractile activity. Stepwise inflation of an intraluminal balloon, in which the cross-sectional area (CSA) was measured, provided the distension stimulus. The circumferential wall tension-strain distributions and wall stiffness-strain relations were computed from steady-state values of these measurements in order to evaluate the passive elastic properties. The CSA always reached equilibrium within the 2-min distension period. The CSAs obtained in the distal ileum were higher than those in the duodenum (P < 0.001). The basal CSA was 17.31 +/- 1.14 mm2 and 12.96 +/- 0.42 mm2 for the distal ileum and the duodenum, respectively (P < 0.01). At a maximum pressure of 6 kPa, the CSA of the ileum was 56.63 +/- 1.81 mm2 and 36.86 +/- 1.76 mm2 for the duodenum (P < 0.01). The circumferential wall tension-strain distributions showed an exponential behavior that accorded well with the equation Y = exp(a+bX) with determination coefficients of 0.96 +/- 0.01 and 0.99 +/- 0.00 in the duodenal segments in the distal ileal segments, respectively. The values of a (intercept with the y-axis) were 0.54 +/- 0.11 and -0.35 +/- 0.19 for the duodenal and ileal segments, respectively (P < 0.001). The slope of the curves (b values) were 4.34 +/- 0.35 in the duodenal and 5.23 +/- 0.37 in the ileal segments (0.1 > P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: Surgery results in a catabolic state of postoperative stress, where the efficiency of the liver to convert amino acids to urea is increased. This study measured the metabolic consequences of the less traumatic laparoscopic surgery in elective cholecystectomy compared with traditional open surgery technique., Summary Background Data: The authors previously have shown that open cholecystectomy doubles the urea synthesis measured by the means of the functional hepatic nitrogen clearance. Glucagon and cortisol increased by 50% (p < 0.05) and 75% (p < 0.05), respectively, after open cholecystectomy., Methods: Patients undergoing uncomplicated elective laparoscopic cholecystectomies were included. Preoperatively and on the first postoperative day, blood and urine samples were drawn every hour under basal conditions and during amino acid infusion. The urea synthesis rate was calculated from the urea excreted in urine and accumulated in total body water. Functional hepatic nitrogen clearance was quantified as the slope of the linear relation between blood amino-N concentration and the urea synthesis rate. The results were compared with an historic matched group of patients who underwent open cholecystectomies and were studied by the same protocol., Results: The laparoscopic cholecystectomy increased the functional hepatic nitrogen clearance by only 25% (from 8.7 +/- 0.9 to 11.1 +/- 1.5 mL/sec [mean +/- SEM; p < 0.05]), compared with a doubling after open cholecystectomy (from 9.4 +/- 0.9 to 17.6 +/- 3.3 mL/sec [p < 0.05]). The difference between the groups was significant (p < 0.05). Neither glucagon nor cortisol increased significantly after laparoscopic cholecystectomy., Conclusions: The laparoscopic technique results in a much smaller postoperative hepatic catabolic stress response and probably reduced tissue loss of amino-N. This may be important for the more rapid convalescence and reduced postoperative fatigue.

Measurements of rates of dissolution of typical insulation wool fibers (glasswool and basalt based stonewool) and an experimental fiber were made using a flow-through equipment. The liquids used were a modified Gamble's solution, adjusted to pH 4.8 and 7.7 +/- 0.2, respectively. The dissolution of SiO2 and CaO was determined over periods of up to three months. The rate of dissolution of stonewool fibers was lower than that of glasswool fibers at pH 7.7, whereas the opposite was true at pH 4.8. The stonewool fibers dissolve congruently, but glasswool fibers tend to dissolve with leaching. The rates of dissolution of fibers of different compositions, including insulation wool (glasswool, basalt-based stonewool, slagwool) and experimental fibers were screened using a stationary set-up. Both the chemical composition and pH influenced the rates of dissolution. At pH 7.7 alumina was a determining component and at pH 4.8 the content of SiO2 and CaO was determinant. One experimental fiber with a high content of alumina was an exception having a fairly high rate of dissolution both at pH 4.8 and 7.7.

The attitude of the Danish population towards organ transplantation was examined by means of an interview study, executed by the Gallup Institute. From a sample population of 1391 persons above 18 years of age, 798 persons (70%) were interviewed, in the period April 24th to May 3rd 1992. When asked what they thought the general attitude toward transplantation was amongst the population, 65% answered "positive" or "very positive". The attitudes to three situations, namely to organ donation after the death of a parent, spouse or child was examined subsequently. Amongst those who had an opinion, 75% (72-76%) were positive and 25% (24-27%) were negative. The younger the interviewed person, the more positive the attitude. According to the Danish law the relatives can decide for or against organ donation if the deceased has not expressed her view on organ donation. In view of the general positive attitude of the population it is proposed that we introduce a system where every adult person is asked concerning his/her attitude, e.g. in connection with the yearly income tax form or renewal of the health insurance certificate.

The first human pregnancies reported in Denmark following in vitro fertilization and embryo transfer of frozen and thawn embryos are presented. A total of nine embryo transfers, with a mean of one point eight embryos per transfer, were carried out, resulting in three singleton pregnancies. The benefits for the infertile couple, the ethics and technical aspects are discussed with respect to Danish legislation.

Gastrointestinal motility is a major field of research today; however, despite there being a huge amount of available data in the literature, its exact role as a diagnostic tool has yet to be defined. The purpose of this paper is to describe some of the existing experimental models and methods for conducting motility studies.

The transabdominal chorionic villus sampling method was compared with the transcervical route and second trimester amniocentesis in a 3-winged randomised trial. Examination of 45 epidemiological variables showed the three procedure groups to be comparable at enrollment. In 3079 women at low genetic risk, we compared transabdominal with transcervical chorionic villus sampling and amniocentesis. The total fetal loss was 10.9%, 6.3% and 6.4% in the transcervical, transabdominal chorionic villus sampling groups and the amniocentesis group, respectively (p < 0.001). The two CVS procedures were compared in 2882 low and high genetic risk women with cytogenetically normal fetuses. Rates of unintended post-procedure loss were 3.7% and 7.7% for transabdominal CVS and transcervical CVS, respectively (p < 0.001), difference in rates 4.0%, 95% C.I. +2.3% to +5.8%. By a priori ultrasound scanning, more transcervical than transabdominal procedures (p < 0.001) were considered to be inaccessible for sampling. Our data indicate that transabdominal allows freer access to the placental site than transcervical sampling and is easier to adapt to than transcervical CVS. Women run comparable risks with transabdominal CVS and amniocentesis. Given the results of our study, transabdominal procedures remain the first choice for prenatal diagnosis and, since in our hands transcervical sampling entails an increased fetal risk, we have abandoned transcervical CVS in our two study centres.

The aims of the study were to evaluate characteristics of spontaneous motility and of the ascending excitatory peristaltic reflex (AEPR) and intraluminal cross-sectional area in the isolated perfused porcine duodenum. The parameters were measured by an intraluminal catheter by use of the perfused side-hole technique and impedance planimetry. Respiratory parameters such as pH and oxygen consumption and the arterial perfusion pressure were monitored and did not vary significantly throughout the study time. Spontaneous motility was intense at the beginning but declined and disappeared within 45-90 min. It was abolished by atropine, epinephrine, and UK-14,304 (an alpha 2-adrenoceptor agonist). Secondary motility was evoked by intraluminal balloon distensions by raising the balloon pressure to 1.5 kPa for 1-min periods. Reproducible results regarding the AEPR, external balloon diameters to elicit the AEPR, and intraluminal cross-sectional area were obtained. The order of potency (pD2 values) for inhibition of the AEPR was the selective M3-receptor antagonist 4-DAMP greater than atropine greater than the selective M2-receptor antagonist AFDX-116 greater than the selective M1-receptor antagonist pirenzepine greater than hexamethonium. 4-DAMP was 16 and 29 times more potent than AFDX-116 (P less than 0.02) and pirenzepine (P less than 0.02). None of the drugs altered the intraluminal cross-sectional area during the balloon distensions. The model provides the opportunity for physiological and pharmacological studies of duodenal motility and duodenal cross-sectional area devoid of extrinsic neural and endocrine effects. The abolishment of the AEPR by atropine is caused by blockade of the M3-receptor in the porcine duodenum.

The influence of neurotransmitters on gastrointestinal motility is different in different segments of the gastrointestinal tract. To clarify the regulation of duodenal motility, the aim of the present study was to investigate the effects of alpha-adrenoceptor agonism and blockade and of galanin on duodenal motility. The study was undertaken in the isolated perfused porcine pancreatico-duodenal block. The agents under investigation were administered arterially. Duodenal motility was measured by means of a low-compliance perfusion system using an intraluminal catheter. In addition the concentration of galanin was measured in the portal effluent. We found that spontaneous motility was abolished by noradrenaline by an effect that was counteracted by the alpha 2-adrenoceptor antagonist idazoxan. In contrast, the selective alpha 1-adrenoceptor antagonist prazosin did not influence the effect of noradrenaline. Galanin, like noradrenaline, abolished duodenal motility. Furthermore, the concentration of galanin in the portal effluent was decreased by noradrenaline by an alpha 2-adrenoceptor mediated mechanism. We conclude that alpha 2-adrenoceptor activation and galanin inhibit duodenal motility and that the release of galanin from the pancreatico-duodenal preparation is reduced by alpha 2-adrenoceptors.