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Biomedical subjects

J D Cooper

Publications and source records attributed to J D Cooper.

At least 253 records · Page 14Linked to original sources

Ten-year experience with extracorporeal membrane oxygenation for severe respiratory failure.

In the last ten years, 17 patients with respiratory failure refractory to standard ventilator therapy have been treated with extracorporeal membrane oxygenation (ECMO) at the Toronto General Hospital. One patient was treated with ECMO twice. Four perfusions were veno-arterial, the remainder veno-venous. Perfusions ranged from 1 1/2 to 19 days, with a mean of six days. Ten patients died during treatment or soon after it was discontinued. Eight patients improved enough to allow resumption of standard ventilation, and four patients recovered sufficiently to have normal arterial blood gas levels on room air. Three are long-term survivors. Multiple surgical procedures have been performed successfully during use of ECMO including lung lavage, open lung biopsy and three lung transplants. Major complications include hemorrhagic diatheses and sepsis. The technique involves a substantial commitment of time and personnel but remains a tenable option for presumed reversible life-threatening respiratory failure.

Adolescent↗

Accurate counting of neurons in frozen sections: some necessary precautions.

In 30 microns frozen sections of rat midbrain the retrograde axonal transport of diamidino yellow, a fluorescent tracer, was used to demonstrate a population of neurons in the substantia nigra. However, when visualisation was carried out using the routine Nissl method a significant proportion of neurons failed to stain. As the presence of the retrograde tracer did not affect Nissl staining of such cells, such incomplete staining, with consequent underestimation of neuronal populations, is probably a common error in similar material. Further investigation revealed that the proportion of such unstained neurons was greater when the staining time was short, when stain concentration was low, or when section thickness was increased. Some stains were worse in this respect than others. Cresyl fast violet resulted in the highest proportion of unstained neurons, thionin resulted in the lowest proportion. It was concluded that the rate of diffusion of the stain into the section was the main factor limiting the staining of neurons present. Staining with pure thionin at 0.1% concentration for at least 3 minutes and with sections no thicker than 30 microns is one regime which would avoid this problem.

Animals↗

Captopril--a potential free radical scavenger: inhibition of PMN NADPH oxidase.

We postulated that Captopril may be capable of acting as a scavenger of free radicals, and performed in vitro studies using harvested human neutrophils. We studied the effect of Captopril on the reduction of Fe3+ cytochrome c by stimulated PMN's. Captopril acts as a reducing agent in this system, and is capable of reducing Fe3+ cytochrome c by itself. NADPH oxidase was harvested from PMA-stimulated human PMN's. Captopril inhibited the activity of this enzyme as assessed by the disappearance of NADPH determined spectrophotometrically. Since similar inhibition could be demonstrated with the superoxide scavenger superoxide dismutase, further studies were conducted using a DTNB assay of the terminal sulfhydryl group of Captopril, in the presence of a biochemical generator of superoxide (hypoxanthine/xanthine oxidase). We were unable to demonstrate disappearance of the thiol group in this system, suggesting that reaction of the SH group with 02- is unlikely under our conditions. We conclude that Captopril may interfere with human PMN NADPH oxidase in vitro.

Captopril↗

A new model for assessment of lung preservation.

No completely satisfactory experimental model exists to compare different techniques of preservation currently used in the distant procurement of a lung allograft. A canine model of left lung transplantation is described in which an inflatable cuff is placed around each pulmonary artery. Each cuff is connected to a subcutaneous reservoir, which allows alternate occlusion of either pulmonary artery. Functional assessment of lung function is made during ventilation of both lungs and after a 10-minute period of perfusion to the native lung alone and then to the transplanted lung alone. Systemic and pulmonary artery pressures are recorded continuously, and measurement of arterial blood gases and oxygen uptake are made immediately after the operation and again at 3 days. The animal is then put to death and the lungs are excised and weighed. Five dogs underwent transplantation of the donor lung immediately after excision (mean ischemic time = 55 +/- 7 minutes). Similar values for oxygen tension and oxygen uptake were obtained postoperatively for the right lung (oxygen tension = 420 mm Hg, oxygen uptake = 101 ml/min) and the left lung (oxygen tension = 368 mm Hg, oxygen uptake = 108 ml/min). However, carbon dioxide tension was elevated (right lung = 41 mm Hg, left lung = 52 mm Hg). Mean pulmonary artery pressure increased during allograft perfusion (right lung = 14 mm Hg, left lung = 24 mm Hg), although systemic blood pressure was unchanged. Similar results were observed at 3 days. The mean weight of the native lung was 101 +/- 2 gm and that of the transplanted lung, 128 +/- 6 gm. This model achieves consistent survival and allows serial observations of the functional adequacy of an allograft compared with a normal contralateral lung.

Animals↗

Experimental and clinical double lung transplantation.

We have previously demonstrated the technical feasibility of an en bloc double lung transplantation in acute canine experiments. We have now conducted survival experiments in cynomolgus monkeys. Profound hypothermia and circulatory arrest were used to avoid the need for cardiopulmonary bypass in these very small animals. Because of the complexities of this technique, few long-term survivals resulted, but these experiments did confirm excellent lung function and satisfactory tracheal healing. On the basis of these experiments, we have performed our first clinical double lung transplantation on a 42-year-old woman with end-stage emphysema caused by alpha 2-antitrypsin deficiency. The patient has returned to normal activities with excellent lung function.

Adult↗

Esophagectomy for complex benign esophageal disease.

We evaluated the use of total thoracic esophagectomy and replacement with stomach in a group of 21 patients between 1976 and 1986 who had undergone multiple unsuccessful esophageal operations. All patients had between one and four unsuccessful operations for benign esophageal disorders. Sixteen patients had primary motor disorders: achalasia in nine and esophageal spasm in seven. Of these patients, 11 also had recurrent gastroesophageal reflux and peptic esophagitis. Complicated reflux disease characterized by severe esophagitis, stricture, and impaired peristalsis without primary motor disorder occurred in five patients. In one patient a functionally impaired long-segment colon interposition was removed and replaced with stomach. Total thoracic esophagectomy and cervical esophagogastric reconstruction was done in all patients. The transhiatal approach was chosen for resection in 16 patients and thoracotomy was used in the other five. There was one perioperative death (5%), from massive aspiration 4 days after transhiatal esophagectomy. Other complications included transient anastomotic leak (three patients), tracheoesophageal fistula (one), recurrent nerve palsy (one), and transient hoarseness (two). Follow-up is complete between 1 and 10 years and reveals the following functional results: 12 patients good to excellent, seven fair, one poor. In this patient group in which multiple prior procedures have failed to improve severe incapacitating symptoms, we believe further attempts at hiatal reconstruction are unlikely to succeed. For this circumstance, we recommend total thoracic esophagectomy with the use of stomach as the replacement organ of choice.

Adult↗

Significance of metastatic disease in subaortic lymph nodes.

Thirty-five patients underwent resection of primary bronchogenic carcinoma of the left upper lobe or left main bronchus in the presence of metastatic disease in subaortic lymph nodes. No patient had metastatic disease in other mediastinal node stations. There was 1 postoperative death. Complete follow-up is available on 34 patients. Three-year and five-year actuarial survival for the entire group is 44% and 28%, respectively. For 23 patients undergoing complete resection, five-year actuarial survival is 42%. Resection of primary bronchogenic carcinoma in the presence of subaortic nodal metastases is associated with improved survival relative to reports of survival following resection of metastatic disease in other mediastinal node stations. Resection should be undertaken in these patients especially when it is judged that the resection is likely to be complete.

Adult↗

Peptic ulcer in acquired columnar-lined esophagus: results of surgical treatment.

Ulcerative peptic esophagitis may lead to the progressive replacement of squamous by columnar epithelium in the distal esophagus. A typical peptic ulcer (Barrett's ulcer) may develop in the columnar-lined segment, although this is a rare occurrence. Between 1975 and 1985 at Toronto General Hospital we treated 11 patients with penetrating peptic ulcer and acquired, columnar-lined esophagus. Presenting symptoms related to the ulcer were precordial and lower dorsal back pain in 4 patients, dysphagia in 6, and massive hemorrhage of the upper gastrointestinal tract in 4. None of the ulcers healed following a trial of medical therapy, and ultimately all 11 patients underwent antireflux procedures (gastroplasty and partial fundoplication). There was one operative death. Complete healing of the ulcer was observed in the 8 patients who underwent follow-up endoscopy between two and five months after operation. There has been no recurrence of symptoms resulting from ulcer in subsequent follow-up, which extends from 1 to 11 years (mean, 5 years). Adenocarcinoma developed in the columnar-lined segment in 2 of the 11 patients, which was diagnosed at 32 and 91 months following operation, respectively.

Adult↗

Extensive pharyngo-oesophageal reconstruction using multiple jejunal loops.

Two patients underwent subtotal pharyngo-oesophageal reconstruction using jejunum transferred by means of microvascular anastomosis. In both cases, two sets of vascular anastomoses were required, one in the lower neck and the other at the mid-sternal level. In the first patient, a continuous length of jejunum was employed but this led to great redundancy of the bowel on account of coiling as a result of its mesenteric attachment. In the second case, two isolated loops were employed with minimal redundancy. An anatomical study on three fresh cadavers indicated that the maximum defect which can be bridged by a single loop of jejunum lies between 15 and 20 cm. No particular part of the jejunum or ileum seems particularly advantageous in terms of its ability to span large defects.

Adult↗

Gastroplasty and fundoplication for complex reflux problems. Long-term results.

Between 1964 and 1984, 430 patients with complex reflux problems were managed by a modified Collis gastroplasty and partial fundoplication. The indications for selecting the addition of gastroplasty were as follows: (1) obvious acquired shortening due to peptic esophagitis and stricture, and (2) subtler degrees of acquired shortening frequently encountered in cases that required reoperation and in patients with massive sliding hiatal hernia. The addition of gastroplasty in this second group obviates the risk of even minimal tension on the repair. Follow-up is complete in 382 patients (90%), and extends 1-20 years. Two hundred fifty patients have been followed up for 5 or more years and 101 patients for more than 10 years. Results were classified as follows: good: asymptomatic, or inconsequential symptoms requiring no therapy; fair: improved, but with symptoms and/or endoscopic findings requiring intermittent therapy; poor: unimproved or worse. Patients are divided into four categories, and the results are tabulated below (see Table 2). The best results are obtained in patients with acquired shortening due to esophagitis with and without stricture who have had no prior antireflux surgery and have no associated primary motor disorder. The proportion of unsatisfactory results is almost tripled (20% fair or poor) after reoperation after one or more failed antireflux procedures. When reflux esophagitis and stricture are associated with a primary motor disorder, only half of the patients have a good result sustained throughout long-term follow-up.

Adenocarcinoma↗

Technique of successful lung transplantation in humans.

We have performed five single lung transplantations for end-stage pulmonary fibrosis, with four long-term survivors. Two patients underwent right lung transplantation and two underwent left lung transplantation. The procedure is performed with one lung anesthesia, although cardiopulmonary bypass is available on standby if required. Donor and recipient procedures are performed in adjacent operating rooms. On the basis of laboratory studies, a pedicle of omentum is wrapped around the bronchial anastomosis after its completion to restore bronchial artery circulation and protect the anastomosis. The four patients were discharge from the hospital within 4 to 6 weeks and three returned to normal employment at 3 months. Success in these cases is attributed to careful patient selection, use of cyclosporine, and use of an omental pedicle to protect and improve healing of the bronchial anastomosis.

Cyclosporins↗

Transplantation of the lungs.

After years of disrepute, single-lung transplant now seems to be a suitable form of treatment for a carefully selected group of patients with end-stage pulmonary fibrosis. In addition, there is the prospect of treating a wider range of pulmonary diseases in the near future, with the appropriate use of double-lung and heart-lung transplants.

Forecasting↗