The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study.

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

A review of medial temporal lobe and caudate contributions to visual category learning.

Here we review recent functional neuroimaging, neuropsychological and behavioral studies examining the role of the medial temporal lobe (MTL) and the caudate in learning visual categories either by verbalizeable rules or without awareness. The MTL and caudate are found to play dissociable roles in different types of category learning with successful rule-based (RB) categorization depending selectively on the MTL and non-verbalizeable information-integration (II) category learning depending on the posterior caudate. These studies utilize a combination of experimental cognitive psychology, mathematical modeling (Decision Bound Theory (DBT)) and cognitive computational modeling (the COVIS model of Ashby et al. [1998. A neuropsychological theory of multiple systems in category learning. Psychological Review 105, 442-481]) to enhance the understanding of data obtained via functional magnetic resonance imaging (fMRI). The combination of approaches is used to both test hypotheses of the cognitive model and also to incorporate hypotheses about the strategies used by participants to direct analysis of fMRI data. Examination of the roles of the MTL and caudate in visual category learning holds the promise of bridging between abstract cognitive models of behavior, systems neuroscience, neuropsychology, and the underlying neurophysiology of these brain regions.

Action selection and refinement in subcortical loops through basal ganglia and cerebellum.

Subcortical loops through the basal ganglia and the cerebellum form computationally powerful distributed processing modules (DPMs). This paper relates the computational features of a DPM's loop through the basal ganglia to experimental results for two kinds of natural action selection. First, functional imaging during a serial order recall task was used to study human brain activity during the selection of sequential actions from working memory. Second, microelectrode recordings from monkeys trained in a step-tracking task were used to study the natural selection of corrective submovements. Our DPM-based model assisted in the interpretation of puzzling data from both of these experiments. We come to posit that the many loops through the basal ganglia each regulate the embodiment of pattern formation in a given area of cerebral cortex. This operation serves to instantiate different kinds of action (or thought) mediated by different areas of cerebral cortex. We then use our findings to formulate a model of the aetiology of schizophrenia.

Polytetrafluoroethylene and bovine mesenterial vein grafts for hemodialysis access: a comparative study.

PURPOSE: This study aimed to evaluate the safety and patency rate of bovine mesenterial vein grafts (BMVG) for vascular access (VA) in hemodialysis patients (HDP), compared to expanded polytetrafluorethylene (ePTFE grafts) over a mid- to long-term period. METHODS: Patency and complication rate of 23 consecutive HDP with BMVG for VA were compared to a control group consisting of 23 similar HDP with ePTFE grafts. In both groups, the graft was placed preferably in a forearm loop configuration. The same surgeon performed all procedures. All patients were followed over a period of 4 yrs. RESULTS: Graft placement was successful in all patients. Patency rates did not differ significantly in both groups. However, there were less severe complications in the BMVG group. CONCLUSION: The BMVG is a viable alternative for HD access in patients where autologous construction is not possible, and should be given priority in patients with a failed ePTFE graft or high risk for infection.

Neural correlates of rule-based and information-integration visual category learning.

An emerging theory of the neurobiology of category learning postulates that there are separate neural systems supporting the learning of categories based on verbalizeable rules (RB) or through implicit information integration (II). The medial temporal lobe (MTL) is thought to play a crucial role in successful RB categorization, whereas the posterior regions of the caudate are hypothesized to support II categorization. Functional neuroimaging was used to assess activity in these systems during category-learning tasks with category structures designed to afford either RB or II learning. Successful RB categorization was associated with relatively increased activity in the anterior MTL. Successful II categorization was associated with increased activity in the caudate body. The dissociation observed with neuroimaging is consistent with the roles of these systems in memory and dissociations reported in patient populations. Convergent evidence from these approaches consistently reinforces the idea of multiple neural systems supporting category learning.

Neural correlates of artificial grammar learning.

Artificial grammar learning (AGL) is a form of nondeclarative memory that involves the nonconscious acquisition of abstract rules. While data from amnesic patients indicate that AGL does not depend on the medial temporal lobe, the neural basis of this type of memory is unknown and was therefore examined using event-related fMRI. Prior to scanning, participants studied letter strings constructed according to an artificial grammar. Participants then made grammaticality judgments about novel grammatical and nongrammatical strings while fMRI data were collected. The participants successfully acquired knowledge of the grammar, as evidenced by correct identification of the grammatical letter strings (57.4% correct; SE 1.9). During grammaticality judgments, widespread increases in activity were observed throughout the occipital, posterior temporal, parietal, and prefrontal cortical areas, reflecting the cognitive demands of the task. More specific analyses contrasting grammatical and nongrammatical strings identified greater activity in left superior occipital cortex and the right fusiform gyrus for grammatical stimuli. Increased activity was also observed in the left superior occipital and left angular gyrus for correct responses compared to incorrect. Comparing activity during grammaticality judgments versus a matched recognition control task again identified greater activation in the left angular gyrus. The network of areas exhibiting increased activity for grammatical stimuli appears to have more in common with studies examining word-form processing or mental calculation than the fluency effects previously reported for nondeclarative memory tasks such as priming and visual categorization. These results suggest that a novel nondeclarative memory mechanism supporting AGL exists in the left superior occipital and inferior parietal cortex.

Influence of naloxone on gastric emptying of solid meals, myoelectrical gastric activity and blood hormone levels in young healthy volunteers.

There is considerable evidence that opioid mechanisms are involved in the mediation of pyloric motor responses that in turn regulate gastric emptying. The purpose of this randomized, placebo-controlled crossover study was to investigate the effect of naloxone on gastric emptying of a solid meal, gastric myoelectrical activity and the postprandial release of gastrointestinal peptides and neuropeptides in 20 healthy volunteers. Naloxone was administered as an intravenous bolus, followed by continuous infusion according to an intravenous dosing nomogram. Gastric emptying time was evaluated by scintigraphy and gastric myoelectrical activity was evaluated by cutaneous electrogastrography. Naloxone did not significantly alter gastric half-emptying time and postprandial dominant gastric electrical frequency compared with placebo. It also did not significantly change the plasma levels of several peptide hormones with the exception of neuropeptide Y, which was significantly increased (P = 0.001). In conclusion, in doses that influence human intestinal motility, naloxone had no effect on gastric motility and release of several peptide hormones in healthy male volunteers. The importance of the isolated increased neuropeptide Y plasma level needs further investigation.

Risk assessment in patients with ruptured abdominal aortic aneurysms.

OBJECTIVES: Surgery of ruptured abdominal aortic aneurysms is associated with a high mortality rate, mostly related to multi-organ-failure after a prolonged intensive care therapy. In a retrospective study attempts are made to identify individual organ-dysfunction risk profiles influencing the outcome. METHODS: Fifty seven patients (53 men, 4 women, mean age 71.8 +/- 8.8 years) with ruptured abdominal aortic aneurysms underwent graft replacement in a three year period. Fourty eight preoperative, 13 intraoperative and 34 postoperative variables were analyzed. A multi-organ dysfunction (MOD) score was used. RESULTS: The perioperative mortality rate was 31%. Significance of pre-existing risk factors at admission was identified only for cardiovascular diseases. Multiple linear regression analysis indicated that hemoglobin < 90 g/l, systolic blood pressure < 80 mmHg and ECG signs of ischemia at admission are highly significant risk factors. Patients, who died later than 48 hours postoperatively, deceased mainly from MOD (93%) and required intensive care significantly longer than surviving patients (p < 0.0005). All patients with a MOD score > or = 4 died (n = 7). These patients required 26% of all ICU-days and 72% of the ICU-days of the nonsurvivors. CONCLUSION: Patients with ruptured aortic aneurysms should not be excluded from treatment. However, a physiological scoring system after 48 h appears justifiable in order to decide on the appropriateness of continued ICU support.

Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?

BACKGROUND: In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. AIM: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. METHODS: In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. RESULTS: The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. CONCLUSIONS: Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.

[Incidence, classification and therapy of isolated pelvic artery aneurysm]. / Häufigkeit, Klassifikation und Therapie der isolierten Beckenarterienaneurysmen.

INTRODUCTION: Isolated iliac artery aneurysms (IAA) are rare. The rupture risk, however, is high and the diagnosis can be difficult. The aim of this study was to report the frequency, morphology and outcome of these lesions. METHODS: Retrospective analysis of the medical data of all patients treated for IAA from 1990 to 1999. RESULTS: Fifty-nine consecutive patients, 55 (93%) male and 4 (7%) female, were included in the study. The median age was 68 (48-86) years. During the same time period, 741 consecutive patients with aortoiliac aneurysms were treated; thus the frequency of IAA was 8%. The median diameter of the IAA was 7 (3-12) cm. Most patients had at least one risk factor. IAA were unilateral in 40 (68%) or bilateral in 19 (32%) patients and affected the common iliac artery in 25 (19%), the internal iliac artery in 11 (19%) and simultaneously the common and internal iliac artery in 21 (36%) patients. Additional involvement of the external iliac artery was noted in 2 (3%) patients. Thirty-six (61%) patients with IAA underwent elective treatment while 23 (39%) patients had to be treated on an emergency basis. Endovascular stent grafts were inserted in 2 patients. Overall mortality was 10% (n = 6), 2.8% (n = 1) in asymptomatic and 22% (n = 5) in symptomatic or ruptured IAA. Overall morbidity in this study was 30%. The median follow-up of the patients was 36 (2-120) months. DISCUSSION: Surgical therapy in patients with asymptomatic IAA can be performed with a reasonable mortality. However, mortality and morbidity in patients with symptomatic or ruptured IAA remains high. Postoperative long-term results are excellent. The value of endovascular therapy for IAA has yet to be determined.

[Results of surgical therapy and classification of non-ruptured abdominal aortic aneurysms]. / Standortbestimmung der chirurgischen Therapie und Klassifikation nicht rupturierter Bauchaortenaneurysmen.

INTRODUCTION: Surgery for symptomatic aortic abdominal aneurysms (sAAA) is associated with an increased mortality and morbidity compared to asymptomatic aortic aneurysms (aAAA). With the advent of endovascular therapy, an alternative therapeutic modality has become available. Endovascular therapy, however, depends on certain morphologic criteria, whereas open surgery can be performed on any type of AAA. The purpose of this study was to analyse our data of surgical treatment of non ruptured AAA and to identify the amount of patients in whom endovascular therapy would have been possible. METHODS: Retrospective analysis of the medical data of all patients operated upon non ruptured AAA in our department by 3 responsible vascular surgeons from 1995-1999. RESULTS: 225 consecutive patients with a median age of 65 (42-95) years were included in the study. There were 184 (82%) male and 41 (18%) female patients with 143 (63.5%) aAAA and 82 (36.5%) sAAA. Patients with sAAA underwent emergency aneurysm repair and had a significantly increased aneurysm diameter compared to the aAAA, who underwent elective surgical aneurysm repair (6.9 +/- 1.6 cm vs. 6 +/- 1.2 cm; p = 0.002). A total of 11 (4.9%) patients had an inflammatory AAA. Smoking was found to be the only significant increased preoperative risk factor in the group of sAAA compared to aAAA (91 vs. 35 patients; p = 0.008). Morbidity was significantly increased in the patients with sAAA compared to the aAAA (55% vs. 31.5%; p = 0.041) The mortality however did not differ significantly in the two groups (2 vs. 3 patients; p = 0.691). Considering morphological criteria of the AAA, endovascular therapy would have been possible in 59 (26%) patients. However, in 24 (11%) of the 59 patients, endovascular therapy was not feasible because of aortic kinking, heavy calcification of the aneurysm neck, a patent inferior mesenteric artery or atherosclerotic diseased iliac arteries. Consequently, only 35 (15%) patients would have qualified for an endovascular therapy. DISCUSSION: Surgical therapy can be performed in patients with asymptomatic and symptomatic AAA with an equal low mortality. This finding underlines the fact, that surgical therapy still remains the standard therapy for AAA. In addition, in our study only a relative small amount of patients would have qualified for an endovascular therapy.

Ischaemia/reperfusion contributes to colonic injury following experimental aortic surgery.

OBJECTIVES: ischaemia of the colon is an important complication of abdominal aortic aneurysm (AAA) repair. The aim of this animal study was to investigate the effect of sequential ischaemia and reperfusion on sigmoid mucosal pO2 and its association with local ET-1 release. MATERIAL AND METHODS: twelve pigs underwent colonic ischaemia followed by complete reperfusion. Six other animals were sham controls. A Clark-type microcatheter was used for continuous mucosal pO2 measurements. Serial systemic and inferior mesenteric vein blood samples were obtained for determination of ET-1 concentration. Neutrophil extravasation was assessed by tissue myeloperoxidase (MPO) activity. RESULTS: arterial occlusion was associated with a gradual decrease of mucosal pO2 and local release of ET-1. After restoration of blood flow, mucosal pO2 returned to near baseline values, whereas ET-1 reached its maximum concentration during the reperfusion period. MPO activity was significantly increased. CONCLUSIONS: colonic ischaemia and reperfusion causes neutrophil extravasation and local ET-1.

[Assessment of intraoperative duplex sonography during carotid endarterectomy]. / Wertigkeit der intraoperativen Duplexsonographie bei der Carotisendarterektomie.

INTRODUCTION: Carotid endarterectomy (CEA) for prevention of strokes mandates a high amount of experience and a meticulous surgical technique. Intraoperative morphologic as well as hemodynamic monitoring of the endarterectomized arteries is rarely performed. The purpose of this study was to determine the value of intraoperative colour-coded-duplex-sonography to recognize eventual intraoperative technical problems that might result in serious cerebral damage. METHODS: Prospective analysis of the medical data of all patients who underwent CEA for treatment of high-grade carotid stenosis between 1996 and 1999. Adequacy of the repair was assessed intraoperatively by duplexsonography. RESULTS: Of 142 consecutive patients with a median age of 68 (43-84) years, 104 (73 %) were men and 38 (27 %) were women. 9 patients (6 %) had bilateral CEAs. Intraoperative duplexsonography revealed abnormalities during 11 (7 %) of 151 CEAs. 4 (3 %) were considered major and underwent immediate revision. There was one (0.7 %) temporary neurologic deficit (hyperperfusion syndrome) and 2 (1.3 %) cases of fatal intracerebral hemorrhage. 6 (4 %) postoperative surgical complications occurred, i. e. 3 cases of major wound hematoma (with revision) and 3 cases of temporary cranial nerve palsy. Median length of follow-up was 11 (3-35) months. No late neurologic event occurred during follow-up. 5 (3 %) patients developed asymptomatic restenosis. DISCUSSION: Routine intraoperative duplexsonography is a valuable and reliable diagnostic tool to detect correctable technical problems during CEA that subsequently may lead to neurological deficits, fatal stroke or a high incidence of restenosis.

[Rare, but severe complication of varicose vein surgery. Compartment syndrome]. / Seltene, aber folgenschwere Komplikation der Varizenchirurgie. Das Kompartment-Syndrom.

The compartment syndrome is an extremely rare complication after varicose vein surgery. If the early symptoms are not recognized and a treatment is not performed immediately most patients lose sensomotory function. Three cases with compartment syndrome after varicose vein stripping were the reason to point out the anatomy and pathophysiology of this complication and to explain the surgical technique.