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Biomedical subjects

R J Finley

Publications and source records attributed to R J Finley.

At least 37 records · Page 2Linked to original sources

The results of esophagogastrectomy without thoracotomy for adenocarcinoma of the esophagogastric junction.

Between 1980 and 1988, 98 patients with adenocarcinoma of the esophagogastric junction were seen at the University of Western Ontario. Eighty-two patients underwent resection of the celiac lymph nodes, lesser curve and cardia of the stomach, and thoracic esophagus through abdominal and neck incisions avoiding thoracotomy. The esophagus was replaced by a stomach tube in 80 patients or by a colon tube in two patients. Two of 82 patients died while hospitalized. Early postoperative morbidity included anastomotic leaks that closed spontaneously (13), transient hoarseness (10), myocardial infarction (2), pulmonary embolus (6), and atelectasis or pneumonia (13). Late postoperative complications included delayed gastric emptying (4), symptomatic reflux (4), diarrhea (10), and anastomotic strictures (17). The 2-year survival of 30% was significantly affected by the stage of disease (p = 0.003), depth of tumor penetration (p = 0.02), lymph node metastasis (p = 0.001), tumor differentiation (p = 0.008), and tumor DNA ploidy (p = 0.02). Local recurrences appeared initially in 20 patients: anastomotic (3), peritoneal (14), mediastinal (3); distant metastasis occurred in 27 patients: bone (15), liver (5), brain (2), and multiple organs (5). Swallowing was restored and maintained in 75 patients. Esophagogastrectomy without thoracotomy provides a safe, effective method of restoring swallowing in patients with adenocarcinoma of the esophagogastric junction. This technique provides acceptable survival and local recurrence rates.

Adenocarcinoma↗

Multiorgan failure in critically ill patients.

Of 1136 patients admitted consecutively to two medical-surgical intensive care units, 100 were found to have multiorgan failure, defined as failure of more than two organ systems. The average duration of stay in the intensive care units was 13.4 days. The overall death rate was 78% compared with 12.8% for patients without multiorgan failure. The most common initiating illnesses or insults were sepsis, surgery, accidental trauma and cardiogenic shock. Of potential risk factors studied, shock, sepsis, surgery, pre-existing organ disease and age over 65 years were the most common. Although sepsis occurred before or during the course of multiorgan failure in 78 patients, in only 34 was sepsis judged to be the prime insult leading to multiorgan failure. Surgery during the course of multiorgan failure had neither an adverse nor beneficial effect on outcome. The mean number of organ systems failing was 4.36 for survivors and 5.03 for nonsurvivors. The most common systems to fail were central nervous, cardiovascular and respiratory.

Adolescent↗

Effect of antibiotic and fluid resuscitation upon survival time in experimental intestinal ischemia.

Acute massive intestinal ischemia is an abdominal catastrophe. Prompt diagnosis and restoration of blood flow is essential; otherwise, massive intestinal resection occurs, leading to death or, in the survivors, intestinal cripples. In this study, the time of warm reversible ischemia in the canine intestine was explored. After this time was established, fluids and antibiotics were administered to note change in survival times. Massive intestinal ischemia (superior mesenteric artery was clamped) was tolerated without death for five hours (20 dogs in each group). With six hours of ischemia, a 10 per cent mortality rate occurred; with seven hours of ischemia, a 90 per cent mortality rate occurred. These dogs had a maintenance of 75 milliliters of fluid administered per hour. Using this group of dogs as the control (that is, the group with seven hour clamping time of the superior mesenteric artery with maintenance intravenously administered replacement), fluids were given to dogs in the experimental group to keep the pulmonary artery wedge pressure at a normal value (average of 300 milliliters per hour). This group of dogs had an increased survival rate of 40 per cent (ten dogs). Antibiotics were given to the dogs in the experimental group both before and after clamping, increasing the over-all survival rate to more than 80 per cent (46 dogs). Aggressive fluid replacement and antibiotic coverage may lengthen the so-called golden period in which intestinal ischemia may be reversed by revascularization.

Animals↗

Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man.

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.

Aged↗

Insulin decreases muscle protein loss after operative trauma in man.

Seventy-two hours after major operative trauma, nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acid/m2/day) showed a negative nitrogen balance, increased muscle catabolism, as measured by 3-methylhistidine excretion, increased amino acid efflux from muscle, and decreased circulating levels of insulin. When 5 U of insulin/hr were added to the infusate, arterial insulin levels rose significantly from 39.7 +/- 4.1 microU/ml to approximately the pretrauma levels (74.6 +/- 7.7 microU/ml). Despite this normalization of insulin levels, excretion of nitrogen and 3-methylhistidine and the efflux of amino acids from forearm muscle fell but did not return to pretraumatic levels, suggesting some insulin resistance. Visceral gluconeogenesis from amino acids appeared to decrease, since insulin infusion decreased the efflux of alanine from skeletal muscle with no change in its arterial level. Insulin also significantly reduced the efflux of isoleucine, tyrosine, phenylalanine, glutamine, and total amino acid nitrogen from forearm muscle. These findings, along with the partial reduction in the excretion of 3-methylhistidine and nitrogen, suggest that insulin, in combination with infused calories and protein, decreases the loss of muscle protein after trauma.

Aged↗

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↗

Management of adenocarcinoma in a columnar-lined esophagus.

Of 89 patients diagnosed between 1973 and 1983 as having at least 3 cm of columnar-lined esophagus, 22 were found to have adenocarcinoma. There was no difference in sex ratio, smoking, or the use of alcohol between the benign and adenocarcinoma groups. The patients with adenocarcinoma were older (63 years versus 57 years) and had a higher frequency of dysphagia (64% versus 46%), gastrointestinal bleeding (36% versus 24%), extended columnar-lined esophagus (94% versus 28%), and epithelial dysplasia (68% versus 10%). Heartburn was less frequent in the adenocarcinoma group (59% versus 79%), but when it occurred, it was of longer duration (mean, 18.8 years versus 10.9 years). In 2 patients, progression from benign columnar-lined esophagus to early adenocarcinoma was observed. Of the patients with adenocarcinoma, 2 received palliative treatment without resection and died four and nine months later. Six underwent partial esophagogastrectomy with 1 postoperative death. Four had residual columnar-lined esophagus at the resection margins. In one of them, stricture developed and in one, anastomotic recurrence of adenocarcinoma; 1-year survival was 50%. Fourteen patients underwent total thoracic esophagectomy with no operative deaths, strictures, or anastomotic recurrences; 1-year survival was 5 of 6. Surgical staging revealed that 63% had transmural spread and 55%, lymph node involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

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↗

Renal and cardiovascular response to nonhypotensive sepsis in a large animal model with peritonitis.

We studied the functional effects of intraperitoneal sepsis on systemic hemodynamics in general, and on renal function in particular, in sheep in whom bacterial peritonitis was induced by cecal perforation. In the first group of seven sheep (group 1) fluid was administered throughout the period of sepsis to maintain pulmonary capillary wedge pressure as close to presepsis values as possible. These sheep exhibited hemodynamic changes known to be associated with sepsis in man: increased cardiac output and decreased systemic vascular resistance. In a second group of seven sheep (group 2) fluid intake was restricted; compared with group 1, these sheep demonstrated a smaller increase in cardiac output that did not persist and that was associated with an increase in the systemic vascular resistance during the septic period. Plasma renin levels increased fivefold in group 2 but were unchanged in group 1. Serial renal biopsies during the septic period revealed that all sheep had evidence of tubular cell damage on electron microscopy: cell swelling, loss of the microvillous brush border, and cell necrosis. Both groups of sheep also demonstrated marked tubular proteinuria similar to that found in humans with generalized sepsis. Despite this, sheep in group 1 exhibited no functional renal changes: creatinine clearance levels rose slightly from control values, urine concentrating ability was unimpaired, and fractional excretion of sodium increased appropriately in response to a sodium load. In contrast, group 2 sheep exhibited a fall in creatinine clearance levels but fractional sodium excretion did not fall as would have been expected were renal function entirely normal. The results suggest that generalized "hyperdynamic" sepsis induces tubular cell damage and tubular proteinuria by an unknown mechanism. However, this does not necessarily produce renal impairment since the glomerular filtration rate does not fall unless volume contraction is also allowed to occur.

Animals↗

Empyema: analysis of treatment techniques.

Empyema is associated with a high mortality. To study the factors responsible for the failure of treatment, the authors reviewed 90 cases of nontuberculous thoracic empyema seen at the University of Western Ontario in London, between 1970 and 1980. The most common causes of empyema were bronchopulmonary infections (63%), complications of pulmonary surgery (14%) and secondary infections of hydrothoraces or hemothoraces (13%). In 51 patients (57%) the condition was acquired in hospital or was related to previous medical therapy. Nine cases were recognized only at autopsy. The treatment of empyema was assessed in 81 patients, who received an average of 2.2 antibiotics during the course of treatment. Five patients received antibiotics as the only therapy; one died. Seventy-two patients were treated by surgical drainage; 35 (49%) were cured and 18 (25%) subsequently died. Twelve of 18 decortication procedures were successful including 4 performed as a primary procedure and 8 as a secondary procedure. Five of seven patients who underwent thoracoplasty were cured. The overall mortality in the series was 23%. Prevention and early recognition of empyema may reduce the mortality. Patients who do not improve promptly with surgical drainage may benefit from early decortication.

Adolescent↗

The effect of an infusion of zymosan-activated plasma on hemodynamic and pulmonary function in sheep.

To assess the integrated cardiopulmonary response to acute microvascular lung injury, we infused zymosan-activated plasma (ZAP) into mature, awake sheep. ZAP infusion resulted in an immediate increase in the mean pulmonary artery pressure (PAP) from 17.5 +/- 4.5 mm Hg to a maximum of 33.0 +/- 5.4 mm Hg by 5 min (p less than 0.01) of a 90-min infusion. The pulmonary artery hypertension (PAH) was sustained throughout ZAP infusion, and for up to 30 min after infusion was completed (p less than 0.05). Lung lymph flow increased immediately, but lymph to plasma total protein ([L/P]) ratios remained unchanged, suggesting increased pulmonary microvascular permeability. The PaO2 fell to a minimum by 5 min (106.9 +/- 17 to 88.3 +/- 14 mm Hg; p less than 0.01), but recovered toward preinfusion values in the final 60 minutes of ZAP infusion. The cardiac index (CI) and stroke volume index (SVI) also fell significantly for 15 minutes (p less than 0.01), and then recovered to levels not different from baseline by 30 min. In parallel with all of these changes, the polymorphonuclear leukocyte count (PMN) in arterial blood fell immediately [baseline to 5 min, delta 4.9 +/- 2.5 (X 10(3))/mm3; (p less than 0.01)] due to sequestration within the pulmonary microvasculature, since a baseline PMNs were being released from the lung, -6.0 +/- 19%, while by 15 min the PMNs were being sequestered, +58.4 +/- 31% (p less than 0.01). Therefore, ZAP infusion reproduced the clinical picture of acute microvascular lung injury in humans, specifically acute PAH and increased pulmonary microvascular permeability. These two changes were due to a cascade of events associated with the pulmonary microvascular trapping of PMNs.

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↗

The management of nonmalignant intrathoracic esophageal perforations.

Eight patients with nonmalignant intrathoracic esophageal perforations recognized more than 48 hours (48 hours to 14 days) after rupture were treated at Toronto General Hospital between 1973 and 1978. Perforation was due to postemetic rupture in 7 patients and to instrumentation in 1. The patients were seen with pain (8), vomiting (7), fever (7), shock (4), respiratory insufficiency (5), pleural effusion (7), pulmonary infiltrates (7), and leukocytosis (6). All patients were managed with thoracotomy. Direct suture closure of the perforation was carried out in 4 patients with midesophageal perforations. Postoperative localized leaks developed in 2 of these patients but healed with conservative management. Cervical esophagostomy and esophageal diversion were used in 1 patient in whom a severe empyema developed in the postoperative period. Direct suture closure, reinforced with a gastric patch, was used to close three lower esophageal perforations. None of these patients had a postoperative leak but all developed subsequent reflux esophagitis. All 8 patients survived. In patients with delayed recognition of a nonmalignant intrathoracic esophageal perforation, elimination of continued chemical and bacterial contamination can be achieved by a clear definition and closure of the esophageal mucosal margins. The obliteration of potential pleural spaces by good tube drainage, lung decortication, and the elective use of mechanical ventilation with positive end-expiratory pressure decreases the incidence of uncontrolled intrapleural sepsis.

Adult↗

The effects of glucagon on protein metabolism in normal man.

Plasma glucagon rises after major injury and could act to increase gluconeogenesis and ureagenesis in the post-traumatic state. This study documents the effect of prolonged glucagon infusion on ureagenesis and nitrogen excretion, as well as possible sources of the increased ureagenesis, in normal man. Four healthy men fasted for 6 days during intravenous infusion of glucose (750 gmday), establishing a steady state of minimal ureagenesis. Glucagon (1 mg/day) then was added to the infusion for 5 days. Glucose alone was given for the final 2 days. Forearm muscle flux of metabolites was determined by standard arterial-deep venous sampling and capacitance plethysmography. Glucagon concentration was suppressed during glucose infusion (11 +/- 13 pg/ml) and rose to levels seen in subjects with major trauma during glucagon infusion (669 +/- 138 pg/ml). Glucose infusion stabilized urine nitrogen excretion at 1.54 +/- 0.42 gm of N/sq m/day. Nitrogen excretion increased to 2.40 +/- 0.53 gm of N/sq m/day with glucagon infusion, with urea accounting for the increased excretion. Excretion of 3-methylhistidine was unchanged. Plasma amino acid concentration was strikingly reduced on the first day of glucagon infusion, where it stabilized. Forearm flux showed a slight net release of amino acid nitrogen during glucose infusion. Addition of glucagon to the glucose infusion resulted in a net uptake of nitrogen by forearm skeletal muscle. These evidences strong suggest that glucagon infusion in normal man increases ureagenesis, not only at the expense of the free amino acid pool, but by the hydrolysis of visceral protein as well, with muscle protein being maintained.

Amino Acids↗

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↗