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Biomedical subjects

A Cuschieri

Publications and source records attributed to A Cuschieri.

At least 235 records · Page 13Linked to original sources

Microencapsulation of human cells: its effects on growth of normal and tumour cells in vitro.

The growth kinetics of established human colorectal tumour cell lines (HT29, HT115 and COLO 320DM) and human diploid fibroblasts (Flow 2002) were studied in conventional culture and in microcapsules formed from alginate-poly(L-lysine)-alginate membranes. The tumour lines grew rapidly in microcapsules but, in the case of the substrate-adherent lines HT29 and HT115, only after a prolonged lag phase. This phase was reduced by serial passage in microcapsules. The anchorage-independent line COLO 320DM showed no lengthening in lag phase. Microencapsulated fibroblasts underwent negligible growth but remained viable. Some evidence for functional differentiation (microvilli, cell-cell junctions) of the tumour line HT115 within the microcapsules was observed. We conclude that the use of microcapsules provides an alternative system with some advantages for the study of human cancer and its metastases in vitro.

Cell Adhesion↗

Pyridinium crosslinks as markers of bone resorption in patients with breast cancer.

Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone.

Adult↗

Safety of vessel ligation in laparoscopic surgery.

Laparoscopic ligaturing entails the use of the Roeder knot which is fashioned outside the abdomen, slipped along the ligature to the intended site and locked in place. The safety of the one-way Roeder slip knot in securing blood vessels and the tension a vessel ligature has to withstand were investigated ex vivo. Ligature tension was measured using perfused blood vessels in a test rig. From these data the ligature tension exerted by vessels up to 3 mm diameter at 150 mm Hg pressure was observed to be less than 5 grams. The relationship between ligature tension (T) and intravascular pressure (p), radius of the vessel (r) and radius of the vessel at the point of ligature (delta) is expressed by the formula: T = 3/2 pr delta. A good correlation between values for ligature tension derived from this formula and those observed in the test rig confirmed the validity of this equation for the calculation of approximate ligature tension. Catgut sutures tied with Roeder knots were subjected to strain gauge distraction under different conditions. The tension required to induce reverse slipping of the Roeder knot fashioned from 0/chromic catgut had a median value of 1125 (225-2700) grams weight. Thus in laparoscopic surgery the Roeder knot with dry chromic catgut has a substantial safety factor ratio of 55:1 in ligation of vessels up to 3 mm diameter.

Blood Pressure↗

Total pancreatectomy with preservation of the duodenum and pylorus for chronic pancreatitis.

In an effort to minimize the nutritional complications that follow resection of the pancreas for severe chronic pancreatitis, the authors have performed a duodenum-preserving total pancreatectomy in eight patients for severe unremitting pain requiring large doses of opiate analgesia. Good relief of pain was obtained in six patients (75%), in whom the quality of life was undoubtedly improved. There were no problems with the control of diabetes after this procedure in any of these patients, and no patient has suffered any hypoglycemic attacks requiring medical treatment. This improved control of the diabetic state is probably related to a more physiologic state of the upper digestive tract, enabling a normal food intake. The authors found the operation to be technically difficult, however, and although there were no post-operative deaths, major complications were encountered in four patients. These consisted of postoperative bleeding requiring reoperation (two patients), sepsis, and a duodenal fistula, which progressed to stenosis.

Adult↗

Laparoscopic cardiomyotomy for achalasia.

A technique of laparoscopic cardiomyotomy is described. The procedure has been performed in a patient with manometrically confirmed classical achalasia with complete relief of episodic total dysphagia and no untoward symptoms including reflux. The procedure was followed by minimal postoperative discomfort and the patient was discharged on the third postoperative day. Laparoscopic cardiomyotomy has the advantage of diminished surgical trauma with accelerated recovery, constitutes definitive therapy comparable to standard myotomy, and by being less disruptive of the lower oesophageal fixation it is prone to precipitate gastro-oesophageal reflux.

Adult↗

Local and systemic effects of repeated intraperitoneal epirubicin treatment.

The local toxicity, general morbidity and mortality of repeated intraperitoneal administration of epirubicin (0.5 mg/kg in 100 ml isotonic saline) was investigated using a rat model. This dose is equivalent to that which would be used in the human. After six perfusions, the incidence of peritoneal inflammation was similar in the epirubicin group and saline controls. The vesicant properties of the drug were reflected in a significantly higher incidence of peritoneal fibrosis (P = 0.0015) but adhesions were more common in the controls (29%) than in the epirubicin perfused animals (4%). Animals from both groups showed inflammatory collections within the liver. There were no chronic hepatic lesions such as fibrosis/cirrhosis. This may be owing to portal bacteraemia caused by repeated cannulation of the peritoneal cavity. Evidence of microabscess formation in the hepatic parenchyma was observed in both animals. No histologically demonstrable toxicity was observed in the heart or gastrointestinal tract of the animals included in this study. The mortality of the epirubicin treated rats (2/146 perfusions) was similar to that of the saline controls (2/84 perfusions). These findings indicate that repeated intraperitoneal perfusion with epirubicin is not associated with significant toxicity. This anthracycline is therefore suitable for prolonged cyclical intraperitoneal chemotherapy.

Animals↗

Potential use of tumour marker CA 15-3 in the staging and prognosis of patients with breast cancer.

The tumour marker CA 15-3 has been assayed in 130 patients with breast cancer and correlated with stage of their disease at presentation. The median value of CA 15-3 (43 kU/l) in 26 patients with stage IV disease was significantly higher than the median for 97 patients classified as stage I or II (17 kU/l). Values were elevated in 18 of 21 (86%) patients with bone metastases at presentation. For the 41 patients with stage I or II disease presenting with levels of CA 15-3 of greater than 20 kU/l, the disease-free interval and survival were significantly less than for 56 patients presenting with levels of less than 20 kU/l. CA 15-3 provides additional information to conventional staging tests for patients presenting with breast cancer and may also have a role as a prognostic indicator. This may be particularly useful in the selection of patients for neoadjuvant therapy.

Adult↗

Effect of repeated intraperitoneal chemotherapy with epirubicin on the hepatic transport of bile acids and their enterohepatic circulation.

The effect of repeated intraperitoneal perfusion with epirubicin on the clearance of 14C-taurocholate by the liver and the enterohepatic circulation of the synthetic bile acid 75-SeHCAT were investigated using a rat model. After six treatments there was no significant difference in the transport rate constants (plasma to liver, liver to bile and liver to plasma) between and within the saline and epirubicin groups. Similarly, there were no differences detected between the groups for the parameters derived from these transport rate constants. Thus the initial plasma clearance after six perfusions was 39 +/- 9, and 36 +/- 11 ml/min/kg in the epirubicin and saline groups respectively. The excretory efficiency of the liver at this stage was identical: 67 +/- 10% in the epirubicin treated animals and 67 +/- 6% in the saline controls. A deterioration in the SeHCAT retention was observed after repeated intraperitoneal perfusion in both groups. This was significant only in the cytotoxic group, between the first and sixth epirubicin perfusion: 59 +/- 9% vs 48 +/- 9% at 24 h (P = 0.03), 31 +/- 8% vs 22 +/- 5% at 48 h (P = 0.019) and was not cumulative beyond this stage. These findings indicate that repeated intraperitoneal perfusion chemotherapy with epirubicin does not impair bile acid clearance by the hepatocyte. The decrease in the retention of SeHCAT is unlikely to be the result of epirubicin-induced ileal mucosal damage since the reduction was not cumulative beyond 48 h of administration of the compound.

Animals↗

Jejunal pouch reconstruction after total gastrectomy for cancer: experience in 29 patients.

The experience with interposed jejunal pouch after total gastrectomy for cancer in 29 patients is reviewed. There were two postoperative deaths (7 per cent) due, respectively, to myocardial infarction on day 5 and massive haemorrhage from the splenic vein on day 14. Anastomotic leaks, all from the proximal anastomosis, were encountered in three patients (11 per cent). These consisted of one minor clinical leak in a stapled anastomosis and two radiological leaks from hand-sutured anastomoses. Obstruction of the pouch or its conduit by recurrent tumour was not observed in any patient, including those who died from metastatic disease. There was one instance of benign stenosis of the distal anastomosis to the duodenum which required revisional surgery. The symptomatic assessment in the long-term surviving patients was good except for mild oesophagitis due to bile reflux in five patients. Body-weight was maintained and adverse nutritional consequences were not observed.

Aged↗

CA72-4: a new tumour marker for gastric cancer.

To date, tumour markers for gastric cancer have proved unreliable. In this study the value of a new serum marker, CA72-4, was compared with the serum activities of carcinoembryonic antigen (CEA) and CA19-9 in a consecutive series of patients with gastric cancer. The results show that the CA72-4 assay is significantly better at separating stage I and II disease from normal controls (P less than 0.01) than CEA (n.s.) or CA19-9 (n.s.). CA72-4 also gave better differentiation between patients with positive and negative nodes (P less than 0.01) and between those who were serosa positive and negative (P less than 0.01). CEA differentiated between patients with positive and negative nodes (P less than 0.05) but CA19-9 could not. CA19-9 and CEA could not discriminate between patients who were serosa positive and negative. In this study, at a specificity of 95 per cent, the sensitivities of CEA, CA19-9 and CA72-4 were 0.25, 0.41 and 0.94 respectively. These preliminary findings indicate that CA72-4 is a reliable tumour marker of disease stage and activity in gastric cancer. Further longitudinal studies are required for full evaluation of its clinical utility.

Adult↗

Laparoscopic repair/peritoneal toilet of perforated duodenal ulcer.

Laparoscopic techniques have been refined to the point where exposure, haemostasis and tissue approximation by suture approach those obtained at open access surgery. We report a patient with acute perforation of an ulcer in the first part of the duodenum who was successfully treated by laparoscopic oversewing and omental patching. The clinical indications for contemplating use of laparoscopic surgery for acute ulcer perforation, techniques employed and the areas for potential improvement of instruments, needles and sutures are discussed.

Adult↗

Non-surgical options for the management of gallstone disease: an overview.

The modalities for the non-surgical treatment of gallstones include oral dissolution by bile salts, local dissolution by methyl-tert-butyl-ether (MTBE), extracorporeal shockwave lithotripsy (ESWL) and percutaneous gallstone clearance. The results of oral bile salt therapy for cholesterol stones have been disappointing, and the only indication for this treatment is after ESWL. The high efficacy initially reported for MTBE has not been confirmed by subsequent experience in other centres: this therapy is toxic and best confined to specialized centres. ESWL, though effective in noncalcified stones, has limited overall applicability (approx. 15%) and is frequently followed by recurrence despite maintenance therapy with oral bile salts. Percutaneous gallstone clearance (radiologic or laparoscopic) has been superseded by laparoscopic cholecystectomy. This offers definitive treatment in a single session and has significant advantages over open cholecystectomy in terms of short hospital stay and accelerated recovery with early return to work or full activity. Destruction of the gallbladder by sclerosant agents (chemical cholecystectomy) requires further experimental evaluation before its introduction to clinical practice.

Chenodeoxycholic Acid↗

Rationalizing whole body disinfection.

As part of the preparation for a large prospective trial investigating the effect of preoperative whole body disinfection on the postoperative wound infection rate, this preliminary volunteer study was carried out to establish (a) the optimum number of preoperative washes required to achieve a maximum level of skin disinfection and (b) if showering or bathing is a more efficient method of skin disinfection. Ten healthy volunteers were recruited. The results show a significant decrease (p less than 0.005) in the skin flora after the first and second showers (a decrease of 93.55% and 77.49% respectively), but no further significant fall with subsequent showers. There was a significant fall (p less than 0.005) in skin flora after a single bath (a decrease of 70.98%) with subsequent baths producing no further significant reduction in skin flora. From these results it is recommended that three preoperative showers with 4% chlorhexidine detergent be used as an optimum preoperative whole body disinfection regimen. Three showers ensures against less thorough washing by the patients compared to the healthy volunteers in the study and fits easily into a preoperative regimen.

Adult↗