E. Eriksson

Aneurysm Sac Hygroma: A Cause of Endotension

Purpose: To describe a new pathophysiological mechanism for endotension. Case Reports: Four patients developed aneurysm sac expansion after repair of abdominal aortic aneurysms, one with a conventional polytetrafluoroethylene (PTFE) graft and the others with a variety of commercially made endografts (2 PTFE, 1 Dacron). Pressures within the sacs were nonpulsatile and approximately half the systemic blood pressure. Attenuation on computed tomography (CT) was significantly less in the sac than in the graft in 3 of the patients. A clear, highly viscous fluid was aspirated from all 4 sacs, supporting the diagnosis of aneurysm sac hygroma. Prominent local hyperfibrinolysis in the sac was combined with signs of local coagulation activation. Conclusions: A new mechanism for continued sac expansion based on aneurysm sac hygroma is proposed. Measurement of attenuation may be of diagnostic value. It is further proposed that local hyperfibrinolysis/coagulation may promote rebleeding, liquefaction, and continued expansion analogous to the chronic subdural hematoma.

Expression and kinetics of fibrinolytic components in plasma and peritoneum during abdominal surgery

Summary Objective: A reduced peritoneal tissue fibrinolytic capacity is thought to be pathogenetic in intra-abdominal adhesion formation. Therefore, the aim of this study was to characterize the expression of fibrinolytic components in peritoneal tissue and peripheral blood at the beginning and end of abdominal surgery. Design: Peripheral blood and peritoneal tissue were sampled simultaneously from consecutive patients operated for non-septic causes (Group 1, n = 27) or for intra-abdominal infections (Group 2, n = 10). Setting: Surgical department, University hospital. Subjects: Thirty-seven surgical patients. Interventions: Abdominal surgery. Main outcome measures: Tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type-1 (PAI-1) and the inactive complex formation between t-PA and PAI-1 were assayed in plasma and peritoneal tissue extracts sampled at the beginning and end of surgery. Results: The expression of fibrinolytic components in plasma was similar in the two groups when surgery commenced. However, the intraoperative response was partly different. In Group 1, significant increases in t-PA antigen, PAI-1 antigen and t-PA/PAI complex were observed during surgery as opposed to Group 2. When surgery started, Group 2 displayed a reduced fibrinolytic capacity in peritoneal tissue compared with Group 1. In the latter, there was a rapid decline in t-PA activity, followed by an increase in uPA, PAI-1 and t-PA-PAI complex. The changes in Group 2 were similar, but attenuated. There was no correlation in concentrations of fibrinolytic parameters between peritoneal and blood samples. Conclusion: These observations provide novel insights into the early systemic and tissue response to surgery and may lead to new therapeutic strategies.

Measurement of fibrinolytic components in human tissue

The fibrinolytic system is involved in the resolution of thrombi and in tissue repair. Quantitation of the activators and inhibitors of this system at tissue level is crucial to further characterise these processes. Hitherto, there have been difficulties in measuring the individual components of the plasmin system in human vascular and peritoneal tissue. The aim of this study was to develop a protocol allowing quantitation of activators and inhibitors of plasmin generation at the tissue level. Following a strict protocol in the processing of tissue, the efficiency of extraction in tissue homogenisates was compared using buffers containing acetic acid, 1% Triton X-100 and thiocyanate. The influence of different modalities of normalisation was investigated by normalising to wet weight, total protein content, protein content in supernatant or DNA. Using the protocol, all buffers extracted components of the plasmin system sufficiently for detection. The acetic acid buffer yielded the greatest amount of protein, and in extracting plasminogen activators was comparable to the thiocyanate buffer and significantly more efficient than the Triton buffer (p < 0.05). The relationship between the individual components was unaltered by different means of normalisation. The protocol described, using an acetic acid buffer and normalising to wet weight, seems to be a simple and efficient technique for measuring components of the fibrinolytic system, at least in the tissues investigated.

Complex intracellular signal transduction regulates tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) synthesis in cultured human umbilical vein endothelium.

Endothelial cells are central in fibrinolysis because of their high production of both activators (t-PA, uPA) and inhibitors (PAI-1). The t-PA and PAI-1 synthesis could be regulated by signals transduction at several cellular levels. The purpose of this in vitro study, on cultured endothelial cells, was to explore the receptor/second messenger regulation of the t-PA and PAI-1 synthesis. Quiescent confluent human umbilical vein endothelial cells, cultured in passage 1, were exposed to different test substances. Samples from the conditioned medium were collected after 16 and 24 h and analysed for t-PA and PAI-1 antigen. All data presented were related to the data from control dishes (= 100%), in the same experiment. The results from the present study (mean +/- 95% confidence interval) demonstrated the following. (1) Forskolin, with a documented direct cAMP-inducing effect, decreased the basal PAI-1 production to 61 +/- 15%, and Na-nitroprusside, with a documented cGMP-inducing effect, increased the basal PAI-1 production to 141 +/- 38% without affecting the basal t-PA production. The surface receptor agonists isoprenalin or ephedrine, which indirectly affect adenylate cyclase, had no effect on t-PA or PAI-1 production. (2) Phorbolester (PMA), which directly activates proteinkinase C (PKC), increased the basal t-PA and PAI-1 production to 350 +/- 71%, and 163 +/- 35% respectively. (3) Thrombin, but not endothelin-1 (ET-1), increased the basal t-PA and PAI-1 production to 195 +/- 34% and 136 +/- 18%, respectively, indicating an PKC-mediated thrombin effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Inter-rater reliability in a resource-oriented physiotherapeutic examination

The primary aim of the study was to examine inter-rater reliability of the resource-oriented body examination method, which includes a physical examination of body posture, respiration, body function, and muscle palpation. A secondary aim was to determine the relationship between percentage of agreement and reliability as assessed by kappa coefficient. Two independent evaluators examined 19 apparently healthy persons, simultaneously and without the knowledge of one anothers results. Inter-rater reliability was expressed as kappa coefficient and as percentage of agreement between raters. The median kappa findings for posture, respiration, body function, and muscle palpation, were 0.55, 0.54, 0.42, and 0.27, respectively. The percentage of median agreement for posture, respiration, body function, and muscle palpation were 74%, 82%, 84%, and 72% respectively. Significance of the kappa coefficients was seen for posture in 77%, for respiration in 75%, and for body function and muscle palpation in 45% of the items when tested. There was a positive correlation between significant kappa coefficient and percentage of agreement, rs =. 96, P <. 001, where a kappa coefficient of 0.50 responded to about 74% agreement.

Kinetics of transperitoneal tissue-type plasminogen activator absorption*

Summary Peritoneal hypofibrinolysis has been suggested to be a central denominator in the formation of postoperative adhesions. Topical application of tissue-type plasminogen activator (t-PA) has been demonstrated to reduce adhesion formation, but the absorption of t-PA is not known. The aim of the present study was to determine the absorptive kinetics of t-PA by injecting varying doses of t-PA in intraperitoneally (i.p.) in rats. Plasma elimination was investigated in another set of experiments, where the same doses were injected intravenously (i.v.). The concentrations of t-PA in plasma were dose-dependent after both administrations, and at three and six hours the t-PA concentration in plasma was significantly higher after i.p. [64 (12.8) ng/mL (40 μg dose)] and [297.6 (6.7) (400 μg dose)] then after i.v. [27.9 (15.8) (40 μg dose)] and [127.0 (35.0) (400 μg dose)] ( P

Thrombin signal transduction of the fibrinolytic system in human adult venous endothelium in vitro

Thrombin can regulate the-fibrinolytic system by increasing the endothelial production of both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). The thrombin receptor transducts signals through the GTP-binding protein system, the classical pathway being the Galpha q-protein. The purpose of the present study was to examine the roles of Galpha i-protein and tyrosine kinases in the thrombin signal transduction of t-PA and PAI-1 production from human adult vein endothelial cells (HAVEC). t-PA and PAI-1 antigen were analysed in conditioned medium from cultured HAVEC after 16 h incubation. Data are expressed as percentages of basal release (100%), means +/- 95% confidence intervals. Thrombin increased t-PA and PAI-1 production (234 +/- 42% and 211 +/- 42%, respectively). Pertussis toxin (PTX) (inhibiting Galpha i-pathway) reduced basal PAI-1 (66 +/- 8%), but had only a weak influence on basal t-PA production. Pertussis toxin and genistein (inhibiting tyrosine kinase) significantly reduced the thrombin induction of both t-PA and PAI-1 (PTX: 142 +/- 23% and 146 +/- 19%, respectively, genistein: 156 +/- 42% and 76 +/- 24%, respectively). The present study demonstrated that thrombin can increase the production of t-PA and PAI-1 by transducting signals through the Galpha i and tyrosine kinase pathway, in addition to the Galpha q/protein kinase C pathway as has been found previously.

Aspects of the non-pharmacological treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most commonly diagnosed gastrointestinal conditions. It represents a significant healthcare burden and remains a clinical challenge. Over the years IBS has been described from a variety of different perspectives; from a strict illness of the gastrointestinal tract (medical model) to a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial/psychosomatic model). In this article we present aspects of the pathophysiology and the non-pharmacological treatment of IBS based on current knowledge. Effects of conditioned stress and/or traumatic influences on the emotional system (top-down) as well as effects on the intestine through stressors, infection, inflammation, food and dysbiosis (bottom-up) can affect brain-gut communication and result in dysregulation of the autonomic nervous system (ANS), playing an important role in the pathophysiology of IBS. Conditioned stress together with dysregulation of the autonomic nervous system and the emotional system may involve reactions in which the distress inside the body is not recognized due to low body awareness. This may explain why patients have difficulty identifying their symptoms despite dysfunction in muscle tension, movement patterns, and posture and biochemical functions in addition to gastrointestinal symptoms. IBS shares many features with other idiopathic conditions, such as fibromyalgia, chronic fatigue syndrome and somatoform disorders. The key to effective treatment is a thorough examination, including a gastroenterological examination to exclude other diseases along with an assessment of body awareness by a body-mind therapist. The literature suggests that early interdisciplinary diagnostic co-operation between gastroenterologists and body-mind therapists is necessary. Re-establishing balance in the ANS is an important component of IBS treatment. This article discusses the current knowledge of body-mind treatment, addressing the topic from a practical point of view.

Non-Pharmacological Approach to Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a commonly diagnosed gastrointestinal condition. It represents a significant healthcare burden and still remains a real challenge. Over the years, IBS has been described as a strict illness of the gastrointestinal tract (medical model) or as a more complex multi-symptomatic disorder of the brain-gut axis (biopsychosocial or psychosomatic model). The reason why IBS has been such a challenge and is so difficult to handle might be related to different approaches. These differences in the view of the syndrome have affected the assessment, treatment and handling of the IBS patient. Patients with IBS, where the symptoms from the gastrointestinal tract are one part of a multi-symptom palette sometimes hidden in the body or mind, need a more holistic outlook. The key to an effective treatment approach is a gastroenterological examination to exclude other diseases along with an assessment of the whole body and its awareness by a body-mind therapist. This chapter discusses the view of the patient together with patient evaluations and body-mind treatment from a practical point of view.