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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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

"Venous" ulceration is usually ascribed to deep venous insufficiency. We record the cases of 20 patients with 23 ulcers without a history suggestive of deep vein disease who were found to have a normal deep venous system when evaluated by Doppler ultrasound, ambulatory venous pressures, and photoplethysmography. All had gross varicose veins present for many years (mean 24 years; range 10 to 35 years), and only 14 limbs had incompetent calf perforating veins. Effective treatment is facilitated by recognition of the relationship of varicose ulcer to superficial venous disease, usually incompetence of the saphenofemoral junction, with or without the presence of incompetent calf perforating veins.

Although urine volume (and, less frequently, concentration) is often measured in the perioperative period, little attempt has been made to separate temporal phases of the intra- and postoperative response to surgery. In 7 patients undergoing standard severe single trauma and managed by a conventional regimen which included intraoperative Hartmann's solution, we have investigated the hourly pattern of urine solute and electrolyte excretion over the first 48 h. Contrary to expectation, in the first 5 h Na+ excretion increases in association with overall solute excretion, and thereafter progressively diminishes. K+ excretion increases 4 h postoperatively and remains elevated for 24 h, after which it returns to normal, even though Na+ excretion remains low. Free water excretion is negative for the first 24 h, though urine osmolality does not suggest a maximal antidiuretic response by the kidney--the highest concentration achieved being just below 800 mosmol/kg. In order to distinguish between the physiological adaptive changes due to starvation and those due to injury, the hourly pattern of urine solute and electrolyte excretion was further investigated in 12 healthy volunteers mimicking postoperative conditions. Apart from the early postoperative period, the hourly pattern of Na+, K+ and osmolar excretion shows no discernible difference from the operated group. These results show that, particularly in relation to Na+, the changes seen in the post-injury patient, even after major uncomplicated surgery, are largely adaptive, and this is especially striking at 24 h after surgery.

Growth of skin bacteria on the infraclavicular region was studied in two series of male volunteers. In the first, Op Site, a polyurethane adhesive film dressing, was compared with an occlusive polyvinyl chloride (PVC) dressing, on povidone iodine (PVI) prepared skin in 10 volunteers. Bacteria were sampled, using perspex cylinders and buffered Triton X-100 detergent, at 2, 4, 7 and 14 days, cultured aerobically and anaerobically, and colonies counted at 24 and 48 h respectively. Colony counts under Op Site were less than for undressed (control) skin and under PVC, at all days sampled, the difference being statistically significant at 2 and 14 days for controls and 4 days for PVC. In the second, four regimens of skin preparation, with Op Site dressings were compared in 12 volunteers, skin being sampled 4, 7 and 14 days. Chlorhexidine (CHD) and PVI were compared with and without defatting. Defatting significantly reduced colony counts at 4 and 7 days, whereas no differences were demonstrated between CHD and PVI. The combination of defatting and CHD resulted in colony counts consistently less than 10(3) organisms at 4 and 7 days. Op Site does not potentiate the growth of skin bacteria and is preferable to an occlusive PVC adhesive dressing. Op Site may be left intact on the chest for up to 7 days, colony counts remaining within acceptable limits.

Severe sepsis leads to depression of the reticulo-endothelial system (RES) with delayed bloodstream clearance of particulate matter and bacteria. Splenectomy results in increased susceptibility to infection with encapsulated organisms but its effect on the resistance to postoperative Gram-negative infection has been little studied. We have investigated the effect of splenectomy on RES function by measurement of plasma fibronectin concentrations and bacterial clearance in the presence and absence of sepsis. In experiment 1, rabbits underwent splenectomy (n = 8) or laparotomy only (n = 8) 4 weeks before a second laparotomy. In experiment 2, animals had either splenectomy (n = 8) or laparotomy only (n = 8) followed 4 weeks later by devascularization of the appendix (sepsis). Plasma fibronectin concentrations and the blood clearance and organ distribution of an intravenous injection of 75Se-labelled viable Escherichia coli (2-3 X 10(8) colony forming units (c.f.u.] were measured 24 h after the second operation. Splenectomy resulted in: (1) a persistent reduction in plasma fibronectin concentration in the presence and absence of sepsis, and (2) a delay in the bloodstream clearance with reduced hepatic (Kupffer cell) uptake of E. coli which was exaggerated in the septic splenectomized animal. It is concluded that the spleen may be important for Gram-negative bacterial clearance, possibly related to its influence on plasma fibronectin concentration and Kupffer cell function.

Gram-negative septicemia is an increasingly common problem, and various suggestions have been made about the cause. One not often considered is that it may be the result of failure of hepatic removal of organisms which have crossed the intestinal mucosal barrier from the large bowel lumen to the portal blood stream. Splanchnic hypoperfusion both increases mucosal permeability and reduces the ability of the hepatic reticuloendothelial system (RES) to remove particulate matter from the blood. If RES funciton is reduced further by blockade with colloidal carbon, then any tnedency for bacteremia to occur in shock might be enhanced. Splenectomized greyhounds, who had received a portal perfusion of either colloidal carbon or saline, were subjected to a period of hypovolemia and then were resucitated. Peripheral blood cultures were sterile at all times in the control animals and before bleeding in the dogs that recived carbon. However, all the RE-blockaded animals developed bacteremia during shock, It was condluded that hepatic RES funciton was essential in the prevention of bacteremia in the hypovolemic dog and that investigation should be directed toward studies of RES function in man with a view to determining the importance or otherwise of the RES in relation to gram-negative bacteremia.

A policy of immediate investigation of patients with haematemesis or melaena or both led to the diagnosis of the Mallory-Weiss syndrome in 16 out of 121 patients admitted to a combined medical-surgical unit over three and a half years. A typical history suggestive of the diagnosis was obtainable in only nine of the 16 patients, though recent alcohol intake was high in another four. All patients survived the episode. Establishment of the diagnosis by oesophagogastroscopy was of special benefit when surgery was needed for control of continuing blood loss, but it also simplified the subsequent medical management of those patients in whom bleeding stopped spontaneously. The incidence of 13.2% in this series suggests that the Mallory-Weiss syndrome may be a relatively common cause of upper gastrointestinal bleeding.

The blood levels of thyrotrophin (TSH), thyroxine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were measured in a group of patients undergoing cholecystectomy and receiving 2000 kcal of glucose daily throughout the study. TSH changes suggested a peroperative peak followed by a fall and subsequent rise. T4 showed no significant changes. T3 fell and rT3 rose postoperatively, with a highly significant fall in the T3/rT3 ratio (p less than 0.001). Surgery and carbohydrate deprivation separately result in similar changes. However, the demonstration of the changes after injury despite adequate carbohydrate intake strongly suggests that they are a primary response to surgery and not a secondary response to the normal consequential fall in caloric and carbohydrate intake. The changes could be an appropriate adaptation to the changed metabolic requirements.

To investigate the possibility of increased tissue exposure to estrogen in breast cancer patients, plasma levels of estrogens and the percentage of unbound estradiol were measured in postmenopausal women with benign or malignant breast disease and compared with levels in normal postmenopausal women. The percentage of unbound estradiol in breast cancer patients [1.85 +/- 0.35% (S.D.)] was significantly higher (p less than 0.001) than in normal postmenopausal women [1.52 +/- 0.33%] and was still significantly higher when patients were matched with control subjects for weight (p less than 0.001) or ideal body weight (p less than 0.001). The binding capacity of sex hormone binding globulin was similar in both groups of women. No significant differences in the plasma levels of estrone, estradiol, or estrone sulfate were detected between breast cancer and normal subjects. It is concluded that, given similar concentrations of estradiol in plasma of normal and breast cancer subjects, the significant increase found in the unbound estradiol fraction may result in a very small increment in tissue exposure to estrogens in breast cancer subjects. However, even such a small increase in tissue exposure to estradiol may be significant, given the length of time required for breast tumor development.

Neutrophil count and luminol-dependent chemiluminescence were measured pre-operatively and on the second, sixth and ninth days after operation in nine patients undergoing major, elective gastrointestinal surgery. The aim of the study was to test the hypothesis that elective surgery as a form of injury has no prolonged deleterious effect on neutrophil activity in non-septic patients. A significant increase in neutrophil count was demonstrated in all patients at Day 2 (P less than 0.01) and Day 9 (P less than 0.01). Neutrophil chemiluminescence increased on Day 2 and Day 6, the increase on Day 6 being significant (P less than 0.02). In the first 9 days after elective gastrointestinal surgery, a biphasic neutrophilia occurs and the metabolic response of neutrophils to an opsonized particle is not impaired. These data would support the hypothesis that major elective surgery has no deleterious effects on neutrophil activity, and indeed that neutrophil activity may be enhanced.

Plasma fibronectin and a fragment of the third component of complement (C3b) are both opsonins of the reticulo-endothelial system. Twenty patients undergoing uncomplicated gastro-intestinal surgery were studied. There was a significant reduction in plasma fibronectin and total haemolytic complement, but not C3, in the early postoperative period (days 1 to 3). In six surgical patients critically ill with severe sepsis both plasma fibronectin concentrations and C3 concentration were reduced significantly when compared with the early postoperative period of uncomplicated surgery. In addition, in the critically ill patients, direct evidence of complement activation was demonstrated. These studies show a transient reduction of humoral host defence mechanisms following surgery which may be permissive to bacteraemia and complement activation.

Early weight gain by starving patients managed with total parenteral nutrition has been regarded as spurious - that is, merely an increase in body water. We designed an experiment to mimic the starved state in which glycogen stores are depleted and sodium intake is very low. The subjects were then repleted with a sodium-free, high carbohydrate intake. All subjects who received potassium gained weight and switched to a respiratory exchange ratio which suggested mainly carbohydrate oxidation. From changes in weight and total body water the weight gain was calculated to be the consequence of glycogen storage with 1 g of glycogen obligating 3.21 +/- 0.57 g water. Two patients with total dysphagia showed a similar pattern. Two subjects who did not receive potassium showed a rise in respiratory exchange ratio but failed to store glycogen. Early weight gain in patients who received high-carbohydrate feeding after starvation is a normal phenomenon and represents a return to a more hydrated state consequent upon glycogen repletion.

To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and 75selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.

When patients are admitted to hospital with acute abdominal pain, clinicians, irrespective of a specific diagnosis, intuitively select three diagnostic classes: operation definitely required (Group A); operation definitely not required (Group B); need for operation uncertain (Group C). The last is followed either by a precautionary laparotomy or a variable period of observation/investigation. We have studied prospectively the influence of laparoscopy on the distribution between these classes and particularly on outcome in group C. One hundred and twenty-five consecutive patients with abdominal pain severe enough for emergency admission have been classified by one of two admitting surgeons (SHO/registrar), who also expressed in group C a view on how they would proceed--operation or observation. Group C were then laparoscoped. The procedure confirmed a provisional view that laparotomy was needed in 11 of 15 patients. In the 'observation' sub-group the provisional decision was confirmed in 14 of 16 and early discharge followed in most. Six inappropriate decisions were thus avoided. Seven management decisions in group A and 4 in group B proved incorrect (11/94: 12 per cent). The majority were potentially recognizable by laparoscopy. Though relatively high rates of successful decision making are achieved with conventional clinical techniques, they can be further improved by laparoscopy. This procedure is particularly applicable in the management of patients with acute abdominal pain without a definite diagnosis, or when appendicitis is regarded as an established diagnosis.