Making and covering of surgical footprints.
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Abdomen↗
Biomedical subjects
L Holmdahl
Publications and source records attributed to L Holmdahl.
Treatment with hyperbaric oxygen affects endothelial cell fibrinolysis.
OBJECTIVE: To investigate the effect of hyperbaric oxygen treatment (HBO) on the thrombolytic properties of endothelial cells. SETTING: University hospital, Sweden. INTERVENTIONS: Human endothelial cells were derived from saphenous veins, and exposed to oxygen in a compression chamber at 2.5 atmospheres absolute (ATA, =250kPa). Cells exposed to 2.5 ATA with a gas mixture similar to air (HB Air), and unpressurised air-exposed cells served as controls. MAIN OUTCOME MEASURES: Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). RESULTS: Immediately after treatment there was a significant increase in t-PA protein in the medium in cultures treated with HBO compared with HB Air (p = 0.015, n = 6), and untreated controls (p = 0.015, n = 6). The PAI-1 concentration in media was also higher in the HBO-treated group compared with HB Air (p = 0.004, n = 6) and untreated controls (p = 0.004, n = 6). Six hours after treatment there was still a significant increase in PAI-1 in the HBO-treated group compared with untreated controls (p = 0.007, n = 6), but not with the pressure control. t-PA concentrations were similar. Specific mRNA for t-PA and PAI-1 was detectable immediately after treatment and six hours later in all experimental groups as assessed by reverse transcriptase polymerase chain reaction (RT-PCR). HBO increased the gene expression for both t-PA and PAI-1. CONCLUSIONS: HBO affects endothelial cell function and its fibrinolytic response. These findings may have clinical relevance in hyperbaric medicine and trauma care.
Adult↗
The role of cytokines, coagulation, and fibrinolysis in peritoneal tissue repair.
Peritoneal tissue repair is a distinct entity. Regardless of the type of injury, a common series of events follows, culminating in inflammation and restoration. Molecular actors interact in a series of events in which the balance of fibrin deposition and degradation is vital. Although the complexity of the repair is illustrated by the multitude of effects and the overlap of molecular mediators involved, a framework is emerging. In this context, the overall role of cytokines is to shift the balance of fibrin deposition and degradation in favour of fibrin residues. Coagulation, as well as generating fibrin, is probably of importance in stimulating remesothelialisation, and fibrinolysis is instrumental in the degradation of fibrin deposits. As far as wound healing in concerned, we propose that the ultimate goal may not be to prevent adhesions, but rather to control their formation. To attain this, site-specific modulation of the repair process is essential. The new insights in mediators and modulators reviewed in this paper may provide means for site-specific modulation of peritoneal tissue repair as well as constituting molecular markers of the repair process.
Cytokines↗
Polymers that reduce intraperitoneal adhesion formation.
BACKGROUND: Viscous macromolecules and phospholipids have been shown to reduce postoperative adhesion formation. The ideal agent, or combination of agents, still remains to be identified. METHODS: The effect of hydrophobically modified ethyl (hydroxyethyl) cellulose (HM-EHEC) and polyquarternium-24 (LM-200), two cellulose-derived polymers, and of sphingomyelin, was examined in an animal model. Adhesions were induced in the parietal peritoneum in a standardized manner and quantity, and the morphology of adhesion formation was evaluated after 7 days. RESULTS: A significant reduction in adhesion formation was seen in animals receiving LM-200 (P=0.013) and HM-EHEC (P=0.012) as a short-term treatment compared with controls given saline, but not in animals receiving sphingomyelin (P=0.733). Additional effects were seen in the animals receiving LM-200 as a prolonged treatment (P< 0.001) compared with controls. There was no difference in the magnitude of the inflammatory response between the groups. CONCLUSION: These results suggest that hydrophobically modified polymers are efficient in reducing adhesions, without affecting the inflammatory response.
Animals↗
Tissue markers as predictors of postoperative adhesions.
BACKGROUND: Postoperative adhesion formation has been associated with a decreased capacity to degrade intra-abdominally deposited fibrin. Adhesions, once lysed, have a high propensity for reformation. This study tested the hypothesis that patients with a high propensity for adhesion formation as well as adhesion tissue had a reduced fibrinolytic capacity. METHODS: Peritoneal biopsies were taken during abdominal surgery from 21 patients who had previously undergone operation; previously formed adhesion tissue was sampled from ten of these patients. Adhesion formation was scored. The fibrinolytic capacity of peritoneum was determined in tissue extracts. RESULTS: At the time of opening of the abdominal cavity, levels of plasminogen activator inhibitor (PAI) type 1 (P = 0.009) and tissue-type plasminogen activator (tPA)/PAI complex (P = 0.008) were increased in peritoneal samples from patients with severe adhesions compared with those in samples from patients with less severe adhesions. Adhesion tissue similarly had reduced fibrinolytic capacity as judged by a decrease in tPA activity (P = 0.005) and an increase in PAI-1 level (P = 0.01), reflected in an increased level of tPA/PAI complex (P = 0.008) compared with unaffected peritoneum. CONCLUSION: These observations demonstrate reduced fibrinolytic capacity in peritoneal tissue in patients with a greater propensity for development of adhesions and likewise in adhesion tissue. This suggests that components of the fibrinolytic system may be used as markers of an increased risk of adhesion development.
Biomarkers↗
Depression of peritoneal fibrinolysis during operation is a local response to trauma.
BACKGROUND: Peritoneal fibrinolytic capacity decreases during abdominal operation. This may be a local effect or a part of a generalized response to the procedure. METHODS: Plasma and paired peritoneal biopsy specimens were taken at intervals during abdominal operation, and fibrinolytic components were assayed in plasma and tissue extracts. Values are given as median [interquartile range]. RESULTS: In peritoneal tissue there was a gradual decrease of tissue-type plasminogen activator (tPA) activity, and at 90 minutes of the operation differed significantly from that of the initial sample (1.0 [1.0] ng/mg protein, and 5.1 [6.5] ng/mg protein, respectively, p < 0.05). The tPA activity levels at the wound were significantly lower (1.0 [1.0] ng/mg protein) at 90 minutes compared with a remote peritoneal site (1.8 [1.9] ng/mg protein, p < 0.05). At the wound, the tPA activity correlated significantly with time (r = -0.48, n = 26, p < 0.01). tPA activity and antigen peaked in plasma at 30 minutes (p < 0.05) and 60 minutes (p < 0.05), respectively. Plasminogen activator inhibitor type 1 activity increased in plasma during operation (p < 0.05), but was not detectable in peritoneal samples. CONCLUSIONS: The intraoperative changes in tissue tPA activity were not consistently reflected in plasma samples. These findings suggest that the reduction in peritoneal fibrinolysis during abdominal operation is a local response to trauma.
Aged↗
Characterization and fibrinolytic properties of mesothelial cells isolated from peritoneal lavage.
Human peritoneal mesothelial cells were harvested from patients undergoing open or laparoscopic surgery for non-septic conditions using three different approaches: (1) from a peritoneal biopsy, (2) from peritoneal fluid, and (3) from lavage fluid collected from peritoneal cavity. When these different methods were compared, cells derived from peritoneal fluid or lavage were more likely to result in established cultures than those obtained from biopsies. The cells displayed morphological, immunohistochemical and ultrastructural characteristics of mesothelial cells. The cultured mesothelial cells produced tissue type plasminogen activator (t-PA), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor type-1 and type-2 (PAI-1 and PAI-2) during unstimulated conditions. Treatment with the proinflammatory mediators LPS and TNF-alpha resulted in an overall decreased fibrinolytic capacity with a decrease in the release of t-PA and an increase in plasminogen activator inhibitors PAI-1 and PAI-2. TNF-alpha had a more profound effect than LPS, especially on the release of t-PA. This may be an important mechanism by which inflammatory mediators disrupt the fibrin degradation. In conclusion, peritoneal lavage is a convenient and reproducible source of mesothelial cells for culture.
Cell Division↗
Plasminogen activators and inhibitors in peritoneal tissue.
Serosal trauma elicits an inflammatory response which leads to the deposition of fibrin at injured sites, the residuals of which appear to be essential in excessive tissue repair and formation of intraabdominal adhesions. Local plasminogen activity may modulate this early phase of tissue repair. The present study was undertaken to investigate the distribution and cellular expression of plasminogen activators and their inhibitors in human peritoneal normal and inflamed tissue. Tissue-type plasminogen activator (t-PA) was expressed in subserosal capillary walls, and in normal mesothelium, but not in inflammation. Immunoreactivity for the plasminogen activator inhibitor type 1 (PAI-1) was present in normal mesothelium, and substantially increased in inflammation, where, in addition, immunoreactivity was found throughout the submesothelial tissue. This PAI-1 was partly co-localized with macrophages, as was the urokinase plasminogen activator (u-PA), suggesting an involvement of these cells in peritoneal tissue fibrinolysis. Inflammation or abrasion of the mesothelium during surgery is likely to cause a depletion of the local t-PA source and expose the potentially PAI-1-containing submesothelial tissue, thus promoting persistence of fibrin and formation of adhesions.
Epithelium↗
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.
Blood Vessels↗
Endotoxin and particulate matter on surgical gloves.
Because of the continual need to protect of health care workers, gloves are increasingly used. Most gloves purchased are powdered. Besides having deleterious effects on wound healing, glove powder can act as a vehicle for latex allergens, endotoxin, and possibly bacteria. Few tested gloves had undetectable levels of endotoxin, and only one was free from particulate matter. Since powder particles can become airborne and are thus easily spread, concerns for health care professionals and patients arise. To reduce risks for exposure, glove-selection criteria must include low or undetectable levels of latex allergens, endotoxin, and particulate matter.
Endotoxins↗
Causes and consequences of trauma in Swedish county 1989-1992.
OBJECTIVE: To document the occurrence, causes, severity and consequences of accidental injuries over a time period May 1989-May 1992. DESIGN: Prospective study. SETTING: County of Alingsås, Sweden. SUBJECTS: 33,000 inhabitants. MAIN OUTCOME MEASURES: Incidence, age, sex, activity preceding accident, mechanism of trauma, type of injury and injury severity score (ISS). RESULTS: The yearly incidence was 14.7% (n = 4,867), and a third of them occurred within the home. The largest percentage (36%) happened during spare time activities, followed by sports (18%), and on the road (11%). Only 34 (0.7%) were severe injuries (ISS > 12). Most injuries (67%) occurred in people below the age of 40. The risk of getting injured was the same for elderly (> 75) as for young people, and 9% of all those who were injured were admitted to hospital. CONCLUSIONS: Injuries were a common reason for seeking medical attention, but only 1 in 10 needed admission to hospital. Most injuries occurred at home during spare time activities. Serious injuries were rare.
Accidents↗
The role of fibrinolysis in adhesion formation.
Postsurgical abdominal adhesions and their sequelae continue to present major clinical and medicoeconomic problems. A complex network of mediators and responses affecting at least five interrelated biological systems, including the fibrinolytic system, are involved in the pathogenesis of postsurgical adhesions. The fibrinolytic system degrades fibrin through the action of the enzyme plasmin, which is stored as the inactive substrate plasminogen. Fibrinolysis, by mediating fibrin degradation, appears to play a pivotal role in adhesiogenesis. Tissue-type plasminogen activator (tPA) is the chief plasminogen activator in the blood, but its activity is restricted by plasminogen activating inhibitors type 1 (PAI-1) and type 2 (PAI-2). Inadequate peritoneal fibrinolysis may result from decreased tPA, increased PAI-1 and PAI-2, or both. The causal relationship between a reduction in fibrinolytic capacity and the formation of adhesions has been demonstrated in animals. In human studies, plasminogen activator activity (PAA) was significantly reduced in peritoneal biopsies from patients with peritonitis compared with those from normal patients. During surgery, PAA declined significantly in both normal and inflamed peritoneum. tPA was responsible for about 95% of PAA. Reduced fibrinolysis in human peritoneum associated with peritonitis and abdominal surgery correlates with increased adhesion formation and may thus be an important early biochemical event leading to adhesion formation. The regulation of plasmin-mediated fibrin degradation in the peritoneal cavity is poorly understood. However, new insights in the cellular distribution of fibrinolytic components in peritoneal tissue suggest that the mesothelium appears to have a principal role in fibrin regulation in the peritoneal cavity and in the early formation of adhesions.
Animals↗
Adhesions: pathogenesis and prevention-panel discussion and summary.
This article summarizes the discussions of the faculty and chairpersons on four major topics on postsurgical adhesions examined at the symposium, "Adhesions: Pathogenesis and Prevention". These topics are: 1) clinical significance; 2) pathogenesis; 3) research status and directions; and 4) recommendations for reduction or prevention. Abdominal postsurgical adhesions develop following trauma to the mesothelium, which is damaged often by surgical handling and instrument contact, foreign materials such as sutures and glove dusting powder, desiccation, and overheating. Postoperative adhesions occur after most surgical procedures and can result in serious complications, including intestinal obstruction, infertility, and pain. A long-term and unpredictable problem, postoperative adhesions impact the surgical workload and hospital resources, resulting in considerable health care expenditures. Although understanding of the pathogenesis of adhesions has improved recently, the molecular mechanisms involved continue to be delineated. Adhesions result from the normal peritoneal wound healing response and develop in the first five to seven days after injury. Adhesion formation and adhesion-free re-epithelialization are alternative pathways, both of which begin with coagulation which initiates a cascade of events resulting in the buildup of fibrin gel matrix. If not removed, the fibrin gel matrix serves as the progenitor to adhesions by forming a band or bridge when two peritoneal surfaces coated with it are apposed. The band or bridge becomes the basis for the organization of an adhesion. Protective fibrinolytic enzyme systems of the peritoneum, such as the plasmin system, can remove the fibrin gel matrix. However, surgery dramatically diminishes fibrinolytic activity. The pivotal events determining whether the pathway taken is adhesion formation or re-epithelialization are therefore the apposition of two damaged surfaces and the extent of fibrinolysis. Research in postsurgical adhesion formation and prevention abounds in a variety of avenues of investigation, including: 1) identification on a molecular level of the components involved in adhesiogenesis and their interactions; 2) clarification of the role of fibrin and fibrinolysis in adhesion formation; 3) standardization of design in preclinical and clinical studies of adhesion formation and prevention; 4) delineation of the relationship between adhesion formation and adhesive complications; and 5) elucidation of efficient, site-specific methods of prophylactic drug delivery. Currently, it seems logical to focus preventive research on development of barriers, fibrinolytic drugs, and selected agents such as phospholipids. The major strategies for adhesion prevention or reduction are adjusting surgical practice and applying adjuvants. Surgeons should adjust their major practices by: 1) becoming aware of the potential adhesive complications of a procedure; 2) minimizing the invasiveness of surgery; and 3) minimizing surgical trauma, ischemia, exposure to intestinal contents, introduction of foreign material into the body, and the use of talc- or starch-containing gloves. Available adjuvants include a newly developed by hyaluronic acid-phosphate-buffered saline solution applied intraoperatively to protect peritoneal surfaces from indirect surgical trauma and three mechanical barriers. One of these, a bioresorbable membrane consisting of hyaluronic acid and carboxymethylcellulose, has demonstrated efficacy and safety in both general and gynecological surgery. The other two barriers, one made of expanded polytetrafluoroethylene and one developed from oxidized regenerated cellulose, are indicated only for use in gynecological surgery.
Humans↗
Adhesions: prevention and complications in general surgery.
OBJECTIVE: To document the incidence of adhesion-related problems and the current concepts on the prevention of adhesions among Swedish surgeons. DESIGN: Postal questionnaire during 1992. SETTING: Sweden. MATERIAL: All surgical units performing abdominal surgery. MAIN OUTCOME MEASURES: Number of patients admitted with or operated on for adhesive small bowel obstruction, methods in use to prevent the formation of adhesions, and costs of adhesion-related complications in abdominal surgery. RESULTS: At least 4700 patients were admitted annually with symptoms of adhesive small bowel obstruction. Of these, 2200 were operated on to relieve the obstruction. No consistent methods were in use to minimise formation of adhesions. Surgical gloves were not washed before operation by 49 of the 84 units that replied and of those only 12 always used powder-free gloves, which gives a likelihood of starch contamination in 70%-82% of all operations. Only 13 (16%) of the units consistently avoided suturing the peritoneum separately. Yearly, at least 1500 laparotomies were complicated by previously formed adhesions. The annual medical expenditure for adhesive small bowel obstruction was more than US $6 million. CONCLUSIONS: Postoperative adhesion formation created substantial morbidity and workload in surgical units. Efforts to reduce the formation of adhesions must be instituted. To start this process, the suturing of peritoneum and the use of powdered gloves could be omitted from clinical practice.
Data Collection↗
Mechanisms of adhesion development and effects on wound healing.
This paper reviews the evidence that glove powder plays an important role in adhesion formation and has adverse effects on the healing of abdominal incisional wounds. The underlying mechanisms leading to these adverse effects are beginning to be revealed. By affecting the mesothelial cell function, powder contamination disrupts the delicate balance of fibrin deposition and degradation, provoking adhesion formation, and interfering with wound healing. Studies are described showing that starch impairs incisional wound healing by its effect on the T cell-mediated immune system. Furthermore starch powder may act as a vector for endotoxin. This paper concludes that starch powder is harmful and its use in a hospital setting can no longer be supported.
Abdomen↗
Cost of bowel obstruction resulting from adhesions.
OBJECTIVE: To assess the direct costs associated with bowel obstruction resulting from adhesions. DESIGN: Prospective study. SETTING: University Hospital, Sweden. SUBJECTS: 57 patients aged 16 years or older who fulfilled the clinical and radiological criteria of bowel obstruction. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Course of, and direct costs associated with, the illness. RESULTS: In 34 of the 57 patients (60%) bowel obstruction was caused by adhesions, and in all 34 the small bowel was obstructed (85% of all cases of small bowel obstruction). 22 of the 42 patients who required a hospital stay of more than 24 hours (52%) had adhesive obstruction, and 10 of these (45%) had to be operated on, 2 of them twice. Major complications occurred in 6 (60%) and one died. In a national perspective, adhesive bowel obstruction may cause 2330 hospital admissions annually, which is associated with an estimated direct cost of about US$13 million. CONCLUSIONS: Adhesions are a serious, common, and costly complication of surgery. Efforts have to be undertaken to control their formation.
Adult↗
[Trauma grading for quality assurance of health care].
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Humans↗
[A special emergency unit for severe cases of trauma established. Organization and experiences from Ostra hospital in Gothenburg].
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Air Ambulances↗