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Biomedical subjects

D M Scott-Coombes

Publications and source records attributed to D M Scott-Coombes.

At least 19 recordsLinked to original sources

Abdominal complications from crack cocaine.

Not only is cocaine a powerfully addictive and dangerous drug of abuse, the use of the purified cocaine derivative crack has also reached epidemic proportions. Apart from causing fatal cardiorespiratory complications, crack cocaine is capable of producing surgical emergencies, which may or may not be associated with the pharmacology of cocaine itself. This is a report of crack-induced pneumoperitoneum, the mechanism of which seemed to be related to the prolonged Valsalva manoeuvre during crack smoking. Other differential diagnoses of crack related pneumoperitoneum are also discussed.

Adult↗

Comparison of immunologic and physiologic effects of CO2 pneumoperitoneum at room and body temperatures.

BACKGROUND: Prolonged and complex laparoscopic procedures expose patients to large volumes of cool insufflation gas. The aim of this study was to compare the effects of a conventional room temperature carbon dioxide (CO2) pneumoperitoneum with those of a body temperature pneumoperitoneum. METHODS: Patients were randomized to undergo laparoscopic cholecystectomy with a CO2 pneumoperitoneum warmed to either body temperature (n = 15) or room temperature (n = 15). The physiologic and immunologic effects of warming the gas were examined by measuring peroperative core and intraperitoneal temperatures, peritoneal fluid cytokine concentrations, and postoperative pain. RESULTS: The mean duration of surgery was 32 min in both groups. Core temperature was reduced in the room temperature group (mean, 0.42 degrees C; p < 0.05). No reduction in temperature occurred when the gas was warmed. Greater levels of cytokines were detected in peritoneal fluid from the room temperature insufflation group tumor necrosis factor alpha (TNF-alpha): mean, 10.9 pg/ml vs. 0.42, p < 0.05; interleukin 1 beta (IL-1beta): mean, 44.8 pg/ml vs. 15.5, p < 0.05; and IL-6: mean, 60.4 ng/ml vs. 47.2. There was no difference in postoperative pain scores or analgesia consumption between the two groups. CONCLUSIONS: The authors conclude that intraoperative cooling can be prevented by warming the insufflation gas, even in short laparoscopic procedures. In addition, warming the insufflation gas leads to a reduced postoperative intraperitoneal cytokine response.

Ascitic Fluid↗

The role of fibrinolytic system proteins in cholesterol gallstone formation.

BACKGROUND: Accelerated nucleation, supersaturation of bile, and biliary stasis are known to be key factors in cholesterol gallstone formation. The mechanisms through which these factors interact to form stones are still incompletely understood. Among the proteins now known to be present in bile are several components of the fibrinolytic system: tissue plasminogen activator, urokinase-like plasminogen activator, and plasminogen activator inhibitors 1 and 2. The concentrations of plasminogen activator inhibitors 1 and 2 in gallbladder bile are increased in patients with gallstones. The aim of this study was to determine whether these fibrinolytic system proteins act as pro-nucleating agents for cholesterol gallstone formation. METHODS: Nucleation assays were done on gallbladder bile from eight cholesterol stone patients and eight control patients. The effects of tissue plasminogen activator, urokinase-like plasminogen activator, and plasminogen activator inhibitors I and 2 on cholesterol crystal appearance time (CCAT) were tested, by direct observation using polarizing microscopy, after measurement of biliary lipids and calculation of cholesterol saturation indices. RESULTS: There was no significant difference in cholesterol saturation indices between bile that nucleated and bile that did not (mean, 2.0 +/- 1.5 versus 1.8 +/- 0.5). When all samples in which nucleation occurred were compared, tissue plasminogen activator significantly shortened CCAT median from 4.75 days (range, 2-21) to 3.5 days (2.5-18) (P < 0.05). This was similar to the effect of fibronectin (3.75 days; range, 2-20), a known pro-nucleator used as a nucleation accelerating control (P < 0.05). None of the other fibrinolytic system proteins significantly accelerated CCAT. CONCLUSIONS: The results of this study suggest that tissue plasminogen activator may act as a pro-nucleating agent for cholesterol gallstone formation in gallbladder bile.

Adult↗

Fibrinolysis and the biliary tree.

AIMS: To investigate the fibrinolytic activity of normal and calculous human bile. METHODS: Fibrinolytic properties of the biliary tract were studied in patients with gall bladder stones (n = 7) compared with acalculous gall bladders (n = 8). RESULTS: Bile plasminogen activating activity was detected in a wide range in both groups (calculous bile median 0.35 IU/ml; range: 0.06-6.59, versus normal bile 0.70 IU/ml; 0.19-3.56). There was no difference in the bile concentration of tissue plasminogen activator between the two groups (calculous bile median 21.5 ng/ml versus normal bile 9.5 ng/ml), which was present in much greater concentrations than urokinase (calculous bile median 0.10 ng/ml versus normal bile 0.36 ng/ml). Both plasminogen activators were detected in low concentrations in gall bladder mucosa. Plasminogen activator inhibitors-1 and 2 were detected in bile in significantly greater concentrations in patients with gall bladder stones (plasminogen activator inhibitor-1: calculous bile median 15 ng/ml versus normal bile < 2 ng/ml, plasminogen activator inhibitor-2: 157 ng/ml versus < 6 ng/ml, p < 0.05). CONCLUSIONS: Human bile possesses fibrinolytic activity and the principal plasminogen activator in bile seems to be tissue plasminogen activator. Plasminogen activator inhibitors were present in greater concentrations in stone bile and may be a factor in the pathogenesis of gall stone formation.

Adult↗

Surgical management of gastrointestinal endocrine tumours.

The surgical management of gastrointestinal endocrine tumours must involve a multidisciplinary approach. The importance of accurate diagnosis, rendering the patient safe, and, in our opinion, localizing the tumour(s) before embarking on surgery cannot be overemphasized. Surgery is the only available treatment for cure. Occult primary tumours are now rarely a problem with novel imaging techniques, which can also improve detection and hence clearance of local spread. Surgical management in extensive metastatic or multicentric disease is less rigidly defined, and is dependent on the endocrine syndrome. A better understanding of tumour pathology, for example in MEN 1, has not always simplified matters. An appreciation of the benefit of chemotherapy, use of somatostatin analogues and hepatic artery embolization are vital to target appropriate palliative surgery. Hepatic transplantation may have an increasing role in the future. Surgical strategies must adapt to new medical treatments. If therapeutically relevant, advances in tumour biology (for example somatostatin receptor subtypes and growth factors) will influence surgical strategies in the future.

Diagnostic Imaging↗

The operative peritoneal fibrinolytic response to abdominal operation.

OBJECTIVE: To measure changes in the fibrinolytic properties of human peritoneum during operation. DESIGN: Open study. SETTING: University hospital, UK. SUBJECTS: 20 patients undergoing elective operations for non-inflammatory disease. INTERVENTIONS: Peritoneum was biopsied at the beginning and end of operation. MAIN OUTCOME MEASURES: Peritoneal plasminogen activating activity (PAA) and the concentrations of tissue plasminogen activator (t-PA), urokinase, and plasminogen activator inhibitors 1 and 2 were measured at both time points. RESULTS: Peritoneal PAA was reduced over the time of the operation (p < 0.05) as was the concentration of t-PA (p < 0.05). The urokinase concentration rose significantly (p < 0.05), but plasminogen activator inhibitors 1 and 2 were not detected. CONCLUSIONS: Elective abdominal operation caused an immediate reduction in peritoneal PAA which seemed to be secondary to a reduced concentration of t-PA. Such a reduction in peritoneal fibrinolytic activity allows the early deposition of fibrinous deposits within the peritoneal cavity.

Abdomen↗

Tumour necrosis factor-mediated release of plasminogen activator inhibitor 1 by human peritoneal mesothelial cells.

Human mesothelial cells synthesize plasminogen activator inhibitor (PAI) 1 in inflamed peritoneal tissue. The role of tumour necrosis factor (TNF) in the mediation of this response was studied. Postoperative peritoneal drain fluid contained both TNF and PAI-1. Peak levels of TNF at 4 h (median 271 pg/ml) preceded a rise in PAI-1 concentration, which peaked at 18 h (median 943.1 ng/ml). Thus TNF may mediate increased PAI-1 release in inflamed peritoneum. TNF significantly increased the mean(s.e.m.) release of PAI-1 by human peritoneal mesothelial cells in vitro at 4 h (control 1.84(0.17) ng/micrograms versus TNF 2.37(0.17) ng/micrograms, P < 0.05), 6 h (2.53(0.09) versus 3.88(0.46) ng/micrograms, P < 0.05), 18 h (0.50(0.02) versus 1.04(0.11) ng/micrograms, P < 0.05) and 24 h (0.87(0.05) versus 1.35(0.11) ng/micrograms, P < 0.05). TNF may be an important mediator of PAI-1 production by human mesothelial cells during peritoneal inflammation.

Ascitic Fluid↗

Surgical treatment of primary duodenal carcinoma: a personal series.

In a personal series, 22 patients (11 men, 11 women) of median age 60 (range 25-81) years with primary duodenal adenocarcinoma underwent operation between 1979 and 1993. Tumours arising from bile duct, ampullary or pancreatic tissue were excluded. Principal presenting symptoms were jaundice (12 patients), pain (seven), anaemia (six) and vomiting (six). A pre-existing villous adenoma was seen in 11 patients and adjacent duodenal dysplasia in 13. Sites of origin were mostly the second part of the duodenum (18 patients) but also the third and fourth parts (two each). Seventeen patients underwent 'curative' resection with one hospital death at 25 days; the 5-year survival rate thereafter was 40 per cent. Five patients who received palliative surgery survived for a median of 7 months. Primary duodenal carcinoma is a distinct entity with a better prognosis than pancreatic cancer after radical resection. It favours the descending duodenum and is closely linked with villous adenoma and epithelial dysplasia.

Adenocarcinoma↗

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.

Administration, Topical↗

Plasminogen activator inhibitor 2 reduces peritoneal fibrinolytic activity in inflammation.

Fibrinolysis in peritoneal tissue may play a role in the development of intra-abdominal adhesions. The plasminogen-activating capacity of human peritoneum results largely from the presence of tissue plasminogen activator (tPA). Inflammation reduces peritoneal plasminogen-activating activity and leads to the appearance of plasminogen activator inhibitor (PAI) type 1. The role of PAI-2 in the inhibition of peritoneal fibrinolysis during inflammation was investigated in this study. The plasminogen-activating activity of peritoneal biopsy homogenates (seven inflamed, seven normal), measured using a fibrin plate technique, was reduced in inflamed compared with normal tissue (median < 0.07 versus 13.9 units/cm2, P < 0.01); tPA antigen levels were not significantly different (median 1.02 versus 1.34 ng/ml). PAI-1 and PAI-2 antigens were not detected in normal human peritoneum but were present in inflamed peritoneum (median concentration 8.8 ng/ml for PAI-1, 26.7 ng/ml for PAI-2). These inhibitors may be important factors in adhesion formation by contributing to the abolition of peritoneal plasminogen-activating activity.

Fibrinolysis↗

Fibrinolytic activity of ascites caused by alcoholic cirrhosis and peritoneal malignancy.

Coagulopathy is a well recognised complication of peritoneovenous shunting for ascites. The relative contributions of primary fibrinolysis and disseminated intravascular coagulation remain controversial. Plasminogen activating activity was significantly lower in malignant ascites (n = 10, median < 0.02 (range < 0.02-1.26) IU/ml) than in alcoholic ascites (n = 10, 1.07 (0.30-1.49) IU/ml) (p < 0.05). Fibrinolytic activity was determined by a balance between tissue plasminogen activator and plasminogen activator inhibitor-1. There was no significant difference between the two groups in the concentration of tissue plasminogen activator (34 (12-64) ng/ml in malignant ascites v 29 (12-43) ng/ml in alcoholic ascites), but the concentration of plasminogen activator inhibitor-1 was significantly higher in malignant ascites (736 (213-1651) ng/ml) than in alcohol ascites (29 (12-43) ng/ml) (p < 0.05). Malignant ascites contained significantly higher concentrations of urokinase (0.7 (< 0.1-1.3) ng/ml v 0.2 (< 0.1-0.6) ng/ml in alcoholic ascites) and plasminogen activator inhibitor-2 (33 (< 6-140) ng/ml v 9 (< 6-28) ng/ml alcoholic ascites). The plasminogen activating activity of alcohol ascites may lead to primary fibrinolysis after peritoneovenous shunting. The considerably lower activity found in malignant ascites may explain why coagulopathy after shunting is less pronounced in this group of patients.

Adult↗

General surgeons' attitudes to the treatment and prevention of abdominal adhesions.

A questionnaire survey of general surgeons was undertaken to estimate the incidence of abdominal adhesions as a clinical problem and to establish current attitudes to the treatment of adhesional bowel obstruction and the prevention of adhesion formation. Replies were received from 362 of 416 surgeons (response rate 87%). In all, 76% (95% confidence limits, 72%-80%) of surgeons operate upon at least two patients each year with adhesional small bowel obstruction and 31% (26-36) operate upon more than five patients. More than five patients are admitted each year with suspected adhesional bowel obstruction by 64% (59-69) of surgeons and 35% (30-40) of surgeons found adhesions to be a problem during a non-adhesion-related laparotomy in more than five patients each year. This represents an estimated annual incidence of between 12,000 and 14,000 adhesion-related clinical problems in the United Kingdom. A number of preventive measures, such as the wearing of starch-free gloves (78% of surgeons; 95% CL 74%-82%), peritoneal lavage (68%; 63-73) and placement of the omentum beneath the wound closure (90%; 87-93) are generally accepted, whereas routine wetting of swabs (39%; 34-44) and the role of non-essential adhesiolysis (49%; 44-54) are controversial. Routine small bowel plication (1%; 0-2) and intubation (2%; 0-5) are rarely used. This survey gives an indication of the large burden on patients and the health services caused by abdominal adhesions, and demonstrates surgeons' wide variety of approaches to both the treatment and prevention of adhesion formation.

Attitude of Health Personnel↗