Experimental adhesion prophylaxis with recombinant tissue plasminogen activator.

The deposition of fibrin in the peritoneal cavity leads to fibrous adhesion formation. Recombinant tissue plasminogen activator (rtPA), delivered locally, was investigated as a method of preventing adhesion formation. Six standardised areas of peritoneal ischaemia were formed in each of 36 male Wistar rats randomised to three intraperitoneal treatments: (A) no treatment control; (B) carboxymethylcellulose gel; (C) rtPA-carboxymethylcellulose gel combination. At 1 week all animals underwent relaparotomy and the number of ischaemic sites with an adhesion counted by an independent observer. rtPA-treated animals formed fewer adhesions compared with gel alone or controls (median number of adhesions 1.5 versus 2.5 versus 5, P < 0.001, ANOVA). Intraperitoneal rtPA in a slow-release formulation is able to reduce adhesion formation significantly in an animal model and may prove to have clinical benefit.

Effect of experimental peritonitis and ischaemia on peritoneal fibrinolytic activity.

OBJECTIVE: Measurement of the fibrinolytic response of the peritoneum to experimental peritonitis and ischaemia. DESIGN: Controlled study SETTING: Academic surgical unit, UK MATERIAL: Male Wistar rats INTERVENTIONS: Peritoneal injuries were caused in four groups of male Wistar rats (n = 35 in each group): (1) control group ("open and close" laparotomy); (2) bacterial peritonitis (mixed faecal flora); (3) chemical peritonitis (10 mg/ml tetracycline) and; (4) ischaemic peritoneum (ligated peritoneal buttons). Peritoneal biopsy specimens were taken from five animals in each group at seven time intervals and plasminogen activating activity (PAA) measured by fibrin plate assay. RESULTS: Compared with the control group the three peritoneal injuries produced a uniform reduction in PAA during the first 6 and 12 hours: at 6 hours the median PAA was 0.029 IU/cm2 for bacterial peritonitis, 0.021 IU/cm2 for chemical peritonitis, and 0.05 IU/cm2 for ischaemic peritoneum compared with 0.112 IU/cm2 for the control group; p < 0.001, ANOVA. At 12 hours the median PAA was 0.024 IU/cm2 for bacterial peritonitis, < or = 0.014 IU/cm2 for chemical peritonitis, and 0.05 IU/cm2 for ischaemic peritoneum compared with 0.112 IU/cm2 for the control group; p < 0.001, ANOVA. There then followed a rebound peak in all groups, maximal at 4-7 days, before a return to baseline values at two weeks. CONCLUSION: Peritoneal fibrinolysis was appreciably inhibited after three different standardised peritoneal injuries. The data support the hypothesis that there is a single pathophysiological mechanism of adhesion formation.

Targeting of microdiscs in white cells to tibial abscesses in rabbits.

The ability to deliver drugs to specific foci of infection is a sought-after goal. One solution is to use microparticles as drug carriers. This approach is limited by detection of microparticles by the reticuloendothelial system (RES). In order to reduce RES uptake of such particles, we investigated the possibility of "hiding" microparticles within white cells prior to targeting them to experimental tibial abscesses. We used radioactive silicone microdiscs, supplied by the Royal Signals & Radar Establishment. Twelve rabbits with abscesses in the right tibia were used: six control animals received radioactive opsonised microdiscs intravenously, and six animals received the same dose of microdiscs following incubation of the microdiscs with white cells. Each animal's liver, spleen, lungs, and both tibiae were removed, weighed, and homogenised. Radioactivity counts were obtained from each tissue, and the ratio of counts per gram of tissue for the right/left tibiae was calculated for the two groups of animals. The ratio of counts in the control group was 1.66 (+/- 0.57 SD), and the mean ratio of counts from the rabbits who had microdisc incubated with white cells was 3.32 (+/- 0.52 SD). This difference was statistically significant at p = 0.02 (Mann-Whitney U test).

Haemodynamic significance of incompetent calf perforating veins.

A total of 149 consecutive unselected patients (221 limbs) who presented with signs and symptoms of chronic venous problems (varicose veins with or without ankle oedema, skin changes and leg ulcers) have been studied by clinical examination, ascending deep to superficial venography, Doppler ultrasound and ambulatory venous pressure measurements. Of the limbs, 180 (82 per cent) had varicose veins without obstruction in the deep veins or reflux in the popliteal or femoral veins while 41 (18 per cent) had deep venous disease. Of the 180 limbs with 'primary' varicose veins 110 (60 per cent) did not have incompetent calf perforating veins (group A) while 70 (40 per cent) did (group B). On the basis of the ambulatory venous pressure after calf muscle exercise and the refilling time, the incompetent calf perforating veins of limbs in group B belonged to three subgroups of different haemodynamic significance. In 20 limbs (30 per cent) they were found to be of no haemodynamic significance, in 25 (35 per cent) of moderate haemodynamic significance and in 25 (35 per cent) of major haemodynamic significance. The last were, on clinical examination, indistinguishable from limbs with deep venous disease although they had patent deep veins with competent popliteal valves.

Management of acute abdominal pain: decision making in the accident and emergency department.

In the management of patients who present to the accident and emergency department with acute abdominal pain the casualty officer has three options: to treat and discharge, to refer to the out-patient department or to refer for urgent admission. The early management of 512 adults presenting to one accident and emergency department with acute abdominal pain has been prospectively studied to determine the accuracy of the casualty officers' decisions as opposed to diagnostic accuracy. Of the 512 patients, 333 (65%) were discharged home with no further hospital follow-up having been arranged; of these 18 (5%) returned with persistent symptoms and five (2%) were admitted. Of 132 patients referred for urgent admission 113 (85.6%) were either admitted or further investigated and were followed up as out-patients. This study demonstrates a high accuracy of decision making by relatively junior hospital staff in the management of acute abdominal pain.

Questionnaire identification of surgical patients at risk of HIV infection.

The prevalence of human immunodeficiency virus (HIV) infection is increasing. Risks of hospital transmission, though small, will consequently also increase. Precautions taken during invasive procedures, particularly surgery, and in the handling of specimens from patients diminish this risk. As HIV antibody screening is not permissible, we have assessed the possible efficacy of a routine questionnaire to identify high-risk groups. Of 525 questionnaires given to routine surgical patients, 506 (96%) were completed. Twenty-eight (5.5%) indicated that they were in a high-risk group. High-risk patients were more likely to present with anorectal disease, to be male and to be young compared with patients from the remainder of the sample. The questionnaire was acceptable to 97% of patients although to a significantly smaller number (82%) of high-risk patients. Routine HIV antibody testing would be acceptable to 88% of low-risk patients but to only 60% of high-risk patients. Questionnaire assessment is an acceptable and perhaps more reliable method of assessing HIV risk status than the other currently available options. It has to be accepted that it will never result in complete identification but we recommend this method as one approach to the problem faced by the surgical team.

Extending the use of clinical audit data: a resource planning model.

OBJECTIVE: To create a means by which we can examine and understand the interrelations among the fundamental elements of hospital inpatient care (patients, beds, theatre time, and staff). DESIGN: Predictive study of resource utilisation based on a computerised clinical information system of five years' audit data from a surgical management system. SETTING: One surgical firm (of one consultant, one registrar, and one preregistration houseman) in a district general hospital. PATIENTS: 5267 Patients whose admission records were part of the five years' audit of surgical management. MAIN OUTCOME MEASURES: Mean length of stay; number of occupied beds; turnover interval; throughput (patients/bed); percentage elective theatre occupancy; waiting time for elective admissions; and theatre, hotel, and total costs. RESULTS: Predicted outcome was analysed in the model, taking the actual outcomes in 1988-9 as baseline values, for four clinical scenarios: an increase in accident and emergency admissions, a reduction in beds, a reduced length of stay, and creation of a new firm. Baseline values showed a mean stay of just over five days in 15 beds and with a theatre occupancy of 94%; the total cost was 812,000 pounds (hotel costs 597,000 pounds). Increasing the accident and emergency admissions to 460/year (19%), based on projected trends from 1984 to 1988, resulted in increased hotel costs (55,000 pounds) and reducing bed numbers (by halving admissions) in decreased use of theatres to 71%, decreased throughput, and increased waiting time, from 20 to 92 weeks, at a saving of 99,000 pounds (12%). Reducing stay marginally reduced bed occupancy (8%) and hotel costs (14%), and creating a new surgical team considerably reduced bed occupancy (14%) and waiting time for elective operations (by 20%). The minimum number of beds for referrals, accident and emergency admissions, and planned admissions was 9.0; that for urgent elective admissions was 3.3 and for non-urgent admissions was 2.4. CONCLUSION: A well designed clinical information system with the routine collection of data can provide the necessary output data to enable resource modelling. IMPLICATION: Use of such a model will allow clinicians to participate in resource planning on the basis of what is actually happening within the hospital.

Prediction of the delayed complications of intestinal and mesenteric injuries following experimental blunt abdominal trauma.

Injuries to the intestine and mesentery are often found in patients undergoing laparotomy for blunt abdominal trauma. Although treatment of perforations is relatively straightforward, the same is not true for contusions. Few guidelines exist at present to aid the surgeon in deciding which injuries require resection in order to avoid the complications of delayed perforation and late stricture formation. The natural history of these non-perforating intestinal and mesenteric injuries has been examined in an experimental model to identify possible criteria on which future management can be based. In the immediate postinjury period peristalsis and local mesenteric pulsation were absent in the majority of injuries which went on to full recovery and these observations are thus of little predictive value in predicting outcome. The initial size of contusion (length of contusion along longitudinal axis of bowel) relative to bowel wall circumference (BWC) was related to complications as follows: contusion less than BWC (n = 47)--one complication; contusion greater than BWC (n = 8)--three complications (P = 0.02). Similarly, six mesenteric injuries which produced an initial ischaemia (assessed by fluorescein) less than twice the BWC did not result in any complications, compared with four complications which occurred in ten cases when the initial ischaemia was greater than twice the BWC. These results go some way towards providing a better understanding of these injuries and in turn may help the emergency surgeon in deciding which injuries require resection.

Peritoneal fibrinolytic activity and intra-abdominal adhesions.

The mechanisms leading to reduction of peritoneal fibrinolytic activity in conditions that are associated with the formation of intra-abdominal adhesions were studied. Tissue plasminogen activator was found, by antibody inhibition techniques, to be the activator of fibrinolysis in homogenates of control peritoneum (n = 6). Homogenates of control (n = 10) and inflamed peritoneum (n = 10) were analysed. Plasminogen activating activity was much lower in inflamed peritoneum (median 0.07 IU/cm2) than in control tissue (median 12.0 IU/cm2) (p less than 0.001). Levels of tissue plasminogen activator and alpha 2-antiplasmin were similar in both control and inflamed tissue. Plasminogen activator inhibitor-1, not detectable in control peritoneum, was present in inflamed tissue and might be the reason for the reduction in functional fibrinolytic activity.

Effect of acute starvation on plasma fibronectin response to sepsis.

There is evidence that undernutrition may contribute to the reduction in plasma fibronectin concentration and the depression of the reticuloendothelial (RE) system associated with severe sepsis. We have investigated the effects of fasting, surgical trauma and sepsis on plasma fibronectin concentrations and RE function. In experiment 1, plasma fibronectin was measured in rabbits (n = 14) before and 48 h after fasting. In experiment 2, sepsis was induced by devascularization of the appendix in animals on a normal diet (sepsis group, n = 7). A third group of animals underwent only a laparotomy (laparotomy only group, n = 7). Plasma fibronectin concentrations and the blood clearance and organ distribution of 99mtechnetium tin colloid (TTC) were measured 24 h after operation. Compared with pooled reference plasma, fasting in experiment 1 resulted in a reduction in mean(s.e.m.) plasma fibronectin concentration from 98(1.5) per cent to 86(3.7) per cent (T = 2, P less than 0.005). Mean(s.e.m.) plasma fibronectin concentration was raised in the sepsis group to 117(4.6) per cent, compared with 97(2.5) per cent in the laparotomy only group (U = 5, P less than 0.02), but there was no such increase in the fasting and sepsis group. There was a delay in the blood clearance and reduced hepatic uptake of TTC in both sepsis groups. The dissociation between fibronectin concentrations and RE function in animal models of sepsis casts doubt on the importance of fibronectin in RE function.

Evaluation of fine catheter aspiration cytology of the peritoneum as an adjunct to decision making in the acute abdomen.

Fine catheter aspiration cytology of the peritoneal cavity was performed successfully in 61 patients admitted with acute abdominal pain. Aspirates were examined microscopically and the percentage of neutrophils in the specimen counted. In patients in whom the clinical need for operation was certain (n = 25) all patients required surgery and the peritoneal neutrophil count was greater than 50 per cent. In patients in whom the clinical need for operation was uncertain (n = 36) 19 patients required operation: the peritoneal neutrophil count was greater than 50 per cent in 18 and in one patient with ectopic pregnancy fresh blood was aspirated. Of the 17 patients not requiring operation the peritoneal neutrophil count was less than 10 per cent in 15 and greater than 50 per cent in two patients (both had acute pelvic inflammatory disease). This study confirms peritoneal cytology as a useful adjunct to decision making in those patients with acute abdominal pain in whom the decision to operate is in doubt.

Clinical decision making and laparoscopy versus computer prediction in the management of the acute abdomen.

A prospective study has been undertaken of 321 patients with acute abdominal pain admitted to hospital under one surgical firm over a period of 21 months. During the first 10 months patients were classified on admission according to the perceived need for operation, with laparoscopy being performed on all those in whom the need for operation was uncertain. In addition, all women with suspected appendicitis underwent laparoscopy because previous studies by us and others have demonstrated a high error rate in this group. During the second 11 months of the study a similar system of classification and procedure was used but the patient's initial assessment was entered on a structured data sheet. After the patient had been discharged home this information was entered into a computer-aided diagnosis program. Hypothetical retrospective computer-aided decisions were then made about patient management. The final management error rate (correct decision to operate or not) was compared with the actual error rate using the clinical system. The final overall error rate in the first 10 months was 11 out of 163 patients and this was improved to 3 out of 158 in the second 11 months of the study by the addition of the structured data sheet to selective laparoscopy. A management policy based entirely on diagnostic probabilities taken from the computer-aided diagnosis program would have produced an error rate of 26 out of 158. We conclude that in the management of the acute abdomen a policy based on clinical decision combined with selective laparoscopy may be superior to one based on diagnostic probabilities alone. Further improvement in results follows the introduction of a structured data sheet for initial data collection.