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Biomedical subjects

J H Duff

Publications and source records attributed to J H Duff.

At least 37 records · Page 2Linked to original sources

A simplified method for metabolic studies in conscious swine.

Reliable short-term blood access in conscious swine was provided by implanting multiple silastic catheters. Catheters were inserted into the aorta, hepatic vein, portal vein, and inferior vena cava through a midline laparotomy incision. Multiple catheters also were placed into the external jugular vein through a separate cervical incision. Catheter patency rates for blood withdrawal on the sixth post-operative day were: arterial 100%, hepatic 91%, portal 86%, inferior vena cava 71%. No animal had major wound or catheter infection on the seventh post-operative day. The methods described allow metabolic studies, including measurements of splanchnic blood flow, to be carried out either acutely or for up to at least 7 days post-operatively.

Animals↗

2,3-Dihydroxybenzoic acid. Effect on mortality rate in a septic rat model.

Neutrophil-derived oxygen-free radicals may play a role in organ dysfunction associated with generalized sepsis. A rat model was used to test the effects of two free radical scavengers, dimethyl sulfoxide (DMSO) and 2,3-dihydroxybenzoic acid (2,3-DHB), on mortality from intra-abdominal sepsis produced by cecal ligation and perforation. Being an iron-chelating agent, 2,3-DHB may have an additional bacteriostatic effect. Therapeutic regimens included no treatment; gentamicin sulfate (2 mg given intraperitoneally [IP] every eight hours); DMSO (2 g/24 hr given IP every eight hours in divided doses); 2,3-DHB (35 mg/kg given IP every eight hours); and combinations of gentamicin with each free radical scavenger. No statistically significant improvement in survival was obtained by therapeutic intervention with gentamicin alone, DMSO alone, 2,3-DHB alone, or gentamicin in combination with DMSO. When used in combination with gentamicin, 2,3-DHB yielded a statistically significant improvement in survival when compared with gentamicin alone or with no treatment. These results show that 2,3-DHB when used in combination with gentamicin has a beneficial effect on mortality following intra-abdominal sepsis in this model.

Abdomen↗

Esophagogastrectomy without thoracotomy for carcinoma of the cardia and lower part of the esophagus.

Between 1 October 1979 and 1 September 1983, 34 patients with 25 adenocarcinomas and nine squamous cell carcinomas of the cardia and lower part of the esophagus have been treated with resection of the celiac lymph nodes (metastasis in 83 per cent of the patients), the lesser curvature of the stomach, cardia and total esophagus without thoracotomy. There was transmural spread of the cancer in 88 per cent of the patients. The esophagus was replaced by a tube made from the greater curvature of the stomach, which was brought through the mediastinum and anastomosed to the cervical esophagus. There was a hospital mortality of 2.9 per cent and the median hospital stay was 15 days. Morbidity included seven anastomotic leaks which closed spontaneously, intrathoracic bleeding (one), secretion retention (six), transient hoarseness (12), persistent dysphagia (one) and transient dumping syndrome (four). No patient has complained of aspiration or reflux of gastric juices. Satisfactory long term relief of dysphagia was achieved in 94 per cent of the patients. There have been no recurrences of tumor at the site of the anastomosis. The one year survival rate is 70 per cent and the median survival time is 19 months.

Abdomen↗

Liver transplantation: the initial experience of a Canadian centre.

At the University Hospital in London, Ont., 19 patients have received 24 liver transplants. The commonest indications for transplantation were primary biliary cirrhosis and cirrhosis from chronic active hepatitis. The first three patients in the series died of infectious complications. Eleven of the subsequent 16 recipients are alive from 5 months to 2 1/2 years after transplantation. Eight patients who are alive more than 1 year after the operation have an excellent quality of life. Cyclosporine and steroids in combination are used for immunosuppression. With current surgical techniques, modern immunosuppression and good patient selection, the restoration of patients with advanced irreversible liver disease to good health by liver transplantation is a realistic goal. Much effort and considerable resources are required to run a liver transplant program.

Adolescent↗

Experimental low colorectal anastomosis.

The authors evaluated a side-to-end colorectal anastomosis carried out by the abdominoperineal approach, in which opening of the mucosal layer of the colon, and therefore the lumen, is delayed for 4 days. This technique was compared to transabdominal end-to-end anastomosis performed as low as possible, using the circular stapler and hand-sewing with a one-layer technique. Experimental end-to-end stapled and hand-sewn anastomoses were performed randomly in 24 female mongrel dogs. The operating time was similar for each group. Anastomoses were examined for leaks at 7 to 10 days digitally and by roentgenography after barium enema. At sacrifice 14 days after anastomosis, measurements were made of bursting strength and the distance of anastomoses from the anus. The degree of inflammation was evaluated histologically. There were three leaks in the hand-sewn anastomoses and none in the experimental end-to-end stapled anastomoses. The mean bursting strength was similar for all three techniques. The mean distance from the anus was lowest for the experimental anastomoses. Inflammatory changes were least in the end-to-end stapled anastomoses. Two dogs in this group and one in the experimental group were incontinent postoperatively. The experimental anastomosis compares favourably to end-to-end stapled and hand-sewn anastomoses and may have some advantages for low anastomosis in man.

Animals↗

Metabolism of branched-chain amino acids in dogs with Escherichia coli endotoxin shock.

The arterial-femoral venous difference of phenylalanine concentration is proportional to net proteolysis in the leg. In ten fasting dogs receiving Escherichia coli endotoxin (2 mg/kg) intravenously, the mean systolic blood pressure decreased from 141.1 +/- 25 to 71.5 +/- 17 mm Hg. The absolute net release from the leg of valine, isoleucine, and leucine and their net release relative to net proteolysis (arterial-femoral venous difference in concentration of each branched-chain amino acid relative to that of phenylalanine) were decreased, indicating increased transamination of these amino acids in skeletal muscle. However, the net release of the branched-chain alpha-keto acids formed by transamination, relative to net proteolysis (arterial-venous difference in concentration of each alpha-keto acid relative to that of phenylalanine), was not increased. The findings indicate that in dogs with E. coli endotoxin shock, there is increased oxidative decarboxylation in muscle of the alpha-keto acids derived from valine, isoleucine, and leucine.

Amino Acids, Branched-Chain↗

Amino acid metabolism in patients with severe burns.

In this study we set out to determine, if relative to net catabolism of skeletal muscle protein as measured by phenylalanine release, the transamination of branched-chain amino acids (valine, isoleucine, and leucine) was greater in nonseptic burn patients than in controls. Arterial and femoral venous amino acid concentrations and circulating liver enzyme levels were measured. When the ratio of the arterial-femoral venous difference in concentration of each branched-chain amino acid to that of phenylalanine was determined, transamination of the branched chain amino acids, relative to net proteolysis, was not occurring at a greater rate in the burn patients. The net release of alanine relative to that of phenylalanine was not significantly greater in the burn patients, consistent with the conclusion that relative to the net rat of proteolysis, transamination of branched-chain amino acids in skeletal muscle is not increased in burn patients. This finding differs from that in septic dogs and septic humans. The mean arterial-femoral venous differences in concentration of alanine, valine, isoleucine, leucine, and phenylalanine were greater in the burn patients (P less than 0.03), indicating increased proteolysis in this group.

Adult↗

Abdominal sepsis managed by leaving abdomen open.

Intra-abdominal sepsis and necrotizing infection of the abdominal wall are usually fatal unless adequate drainage and wide debridement are possible. To follow these principles, we managed 18 seriously ill patients with abdominal sepsis by leaving the abdomen completely open. All except two of the patients had severe intra-abdominal sepsis. Eight patients had full-thickness wound infections and intra-abdominal infections refractory to the usual surgical drainage techniques. Two had necrotizing wound infections only. In 12 an upper abdominal incision was managed open, and in six the open incision was lower. As part of the initiating illness, there were eight small bowel and six colon fistulas. They were managed by colostomy in five patients and ileostomy in two. More than one organism was cultured in all patients and 12 of 18 had a positive blood culture. Respiratory failure made mechanical ventilation necessary in 13 patients for an average of 44 days. Previous adhesions, usually present, or an intact greater omentum, were necessary to prevent bowel evisceration, but three patients required paralysis and mechanical ventilation until adhesions became strong enough to prevent evisceration. There were seven deaths (39%), six caused by continuing sepsis and one from hemorrhage. In those surviving, granulation tissue grew over omentum or bowel loops to eventually seal the abdominal cavity. The late management was split-skin grafting in five and secondary closure in two. Four healed by second intention. We conclude that leaving the abdomen completely open facilitates the widest possible drainage, uncompromising debridement of the abdominal wall, and is compatible with good recovery. The ultimate result in survivors is acceptable. This technique is preferable to closing an abdominal wall of questionable viability in the face of intraperitoneal sepsis.

Abdominal Muscles↗

Acute and chronic benign ulcers of the rectum.

In managing 21 patients with benign ulcers of the rectum, there were seven patients with acute bleeding ulcers and two with acute rectal necrosis. Acute, bleeding ulcers of the rectum are associated with serious illness or injury, similar to those thought to cause stress ulcers of the stomach and duodenum. Rectal prolapse, complete or incomplete, is the condition most commonly associated with chronic, benign ulcers of the rectum. Repair of the rectal prolapse was successful treatment. Two patients had a tight muscular stenosis at the anorectal ring. This appeared to be a causative factor as complete healing occurred after myotomy.

Acute Disease↗

Necrotizing anaerobic infections.

Severe necrotizing anaerobic infections carry a high mortality. From a retrospective review of 17 cases of gas gangrene, necrotizing fasciitis and nonclostridial myonecrosis seen at the Victoria and University hospitals in London, Ontario, between Jan. 1, 1975 and Dec. 31, 1977, the most common antecedent was found to be minor trauma. Location of the infection varied; the scrotum and perineum were most commonly involved. Local findings were most frequently edema, skin tenderness and induration. Mixed infections predominated with a pure growth of Clostridium sp. occurring in only three cases. The overall mortality was 29%. The mainstay of treatment after initial administration of fluids followed by broad-spectrum antibiotics is early aggressive surgical debridement of all necrotic tissue.

Anaerobiosis↗

Total exchangeable potassium in patients receiving total parenteral nutrition.

Total exchangeable potassium (Ke) measurements were done on 13 patients who received total parenteral nutrition (TPN) at 25% dextrose and 2.5% amino acids (AA) (a hypertonic dextrose solution) by central vein, and 12 patients who received TPN as 10% dextrose, 10% fat emulsion (Intralipid), and 2.5% AA with lipid supplying about 60% of the nonprotein calories. There were 13 patients with benign diseases, three with carcinoma resected for cure, four with sepsis, three with severe burns, and two receiving chemotherapy for cancer. All but four of the septic and three of the burned patients had lost more than 10% of their normal body weight. A tracer dose of 150 to 300 microCi of K42 was injected intravenously during the first few days of the TPN therapy and a 48-hour urine collection and 24-, 36-, and 48-hour urine spot samples were obtained. Measurement of Ke was repeated after 7, 14, or 21 days of TPN therapy. Calories per kilogram per day, delta K per day, and percent delta K per day were determined for each patient and the data entered into a Textronics graphics computer for selection of curves of best fit. Similar curves of calories per kilogram per day versus delta K per day were obtained for the central and peripheral TPN groups. Intercepts where the body cell mass was maintained were at 32 calories/kg/day for the central TPN group and 34 calories/kd/day for the peripheral TPN group. Patients in both groups received a minimum of 0.6 gm protein/kg/day and the majority received from 0.8 to 1.2 gm protein/kg/day. Protein intake correlated with delta K per kilogram per day in the central but not the peripheral TPN group. We conclude that in nonseptic malnourished patients, an Intralipid calorie is as efficient as a dextrose calorie and that delta K is related to caloric rather than protein intake. None of the septic or burned patients maintained his body cell mass. However, they all received less than 30 calories/kg/day for a number of reasons.

Amino Acids↗

Bile reflux gastritis and esophagitis.

The authors reviewed 39 patients in whom bile reflux gastritis and esophagitis were diagnosed and treated. All had epigastric pain not relieved by antacids, 26 had heart burn, 13 dysphagia and 7 hematemesis. On endoscopic examination, all had reflux of bile into the stomach with gastritis, 14 had bile in the esophagus and 21 had esophagitis. Results of biopsy in 15 patients were consistent with gastritis or esophagitis. All but one patient had a history of peptic ulcer disease-gastric or duodenal-and 35 had undergone 48 gastric operationns. Treatment was medical but those refractory to medical management underwent operation. A Roux-en-Y diversion of bile was the most successful operative treatment, benefiting 9 of 12 patients. An adequate length of the efferent limb was found to be important as two patients were not improved until this length was increased to 45 cm. Successful treatment depends on the ability to distinguish this syndrome from recurrent acid peptic disease and esophageal reflux due to sphincteric incompetence.

Adult↗

Canadian surgery measured by British standards.

From a visit to 10 centres in England, Scotland and Ireland, the author assesses Canadian surgery by British standards. Canadian manpower and British manpower in general surgery are similar in number when British registrars are included. However, in Britain, manpower is distributed uniformly as hospital-based firms, vertically structured from houseman to registrar to consultant. Apart from teaching centres, the structure in Canada is horizontal. Most general surgeons are not hospital-based. They work independently and have no help from interns or residents. Canadians training is of short duration, highly co-ordinated and noncompetitive, and learning is focused to a large extent by a tough final examination. In contrast British training is long, not co-ordinated, competitive, and learning is focused by clinical experience and research as there is no final examination. Research in general surgery in Canada seems to be more difficult to generate and support than in Britain. Factors that stimulate research in Britain and do not exist in Canada are the professorial unit concept, the longer training and competition for positions, and possibly greater funding by government and private industry.

Canada↗

Arterial plasma amino acids during the first week following femoral shaft fracture.

In ten patients with a femoral shaft fracture, arterial plasma amino acids and glucagon, blood glucose, and serum insulin were measured after an overnight fast on the third, fifth, and seventh days following injury. Ten normal subjects were controls. On all days, concentrations of the key glucogenic amino acid, alanine, were the same in both groups, but levels of another glucogenic amino acid, glycine, were significantly less in the fracture patients. Other amino acid changes following injury were maximal at 7 days, with significant elevations of phenylalanine, methionine, tyrosine, ornithine, lysine, arginine, valine, isoleucine, and leucine. Increased levels of insulin, glucose, valine, isoleucine, and leucine on the fifth and seventh days after injury implied insulin resistance. Plasma glucagon was elevated on the third (p less than 0.05) and seventh (p less than 0.01) days after injury, but the concentrations measured are insufficient to explain the impaired carbohydrate tolerance following a fracture.

Alanine↗

Amino acid metabolism in dogs with E. coli bacteremic shock.

In 10 fasting dogs receiving 10(9) viable E. coli bacteria per kilogram intravenously, mean systolic blood pressure decreased from 120.6 +/- 15.1 to 82.2 +/- 12.8 mm Hg. The association of hypoglycemia and increased arterial alanine and glycine with elevated plasma glucagon implied impaired gluconeogenesis. A rapid elevation of blood urea concentration, indicating increased ureagenesis, a fall of blood glucose, and an increase of net urea synthesis relative to that of glucose suggested that an increased proportion of the carbon residues derived from glucogenic amino acids is catabolized via pathways other than gluconeogenesis. In the bacteremic dogs the absolute net release from the leg of valine, isoleucine, and leucine and their net release relative to the net rate of proteolysis were decreased, suggesting increased oxidation of these amino acids in skeletal muscle. An increased net release of alanine relative to the net rate of protein catabolism in muscle was in agreement with this contention.

Alanine↗

Femoral arteriovenous amino acid differences in septic patients.

Femoral arteriovenous differences and flux of amino acids across the leg were measured in seven septic patients and compared with those of six nonseptic patients on days 1 and 3 following major surgery. The septic patients were seriously ill and judged clinically to be catabolic. The postoperative patients, although not septic, were expected to have a maximal catabolic response to operation during the first 3 days after operation. Both groups had increased release of phenylalanine from the leg, an index of muscle proteolysis. Septic patients had decreased femoral arteriovenous differences (--20 vs --74 and --60 mumoles/liter) and decreased flux (34 vs 169 and 128 nm/100 gm of calf muscle) of the branched-chain amino acids as compared with the nonseptic postoperative patients on days 1 and 3. The arterial plasmal levels of the branched-chain amino acids and alanine were not different, but phenylalanine was elevated in the septic patients (88 vs 49 and 55 mumoles/liter). The insulin:glucagon molar ratio was lower in the septic patients (2.4 vs 4.4 and 5.5). These findings suggest that in the catabolism of sepsis there is greater oxidation of branched-chain amino acids in muscle than in the catabolism associated with uncomplicated surgery.

Abscess↗