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Biomedical subjects

D K Cooper

Publications and source records attributed to D K Cooper.

At least 271 records · Page 15Linked to original sources

Infectious complications after heart transplantation.

Infection has been the major cause of death and morbidity in patients undergoing cardiac transplantation at Groote Schuur Hospital. Twenty-two (55%) patients suffered at least one major episode of infection, which accounted for 10 (59%) of the deaths in the first year. The major site of origin of infection was the lung, though dissemination was not infrequent. Bacteria accounted for 22 (59%) infections; but viral, fungal and protozoal infections were not uncommon and in fact accounted for seven (64%) of the fatal infections. Several unusual causative microorganisms have been isolated in this group of immunocompromised subjects. There is a higher incidence of infection in patients over the age of 35 years and in patients who did not comply with instructions and advice.

Adult↗

Toxoplasmosis of donor and recipient hearts after heterotopic cardiac transplantation.

Toxoplasmosis of both donor and recipient hearts was diagnosed by means of endomyocardial biopsy specimens after heterotopic cardiac transplantation for dilated cardiomyopathy. Before transplantation, the donor had raised antibody titers to Toxoplasma, and the recipient was negative. When toxoplasmosis was diagnosed on the basis of endomyocardial biopsy specimen, the recipient had a greatly elevated antibody titer of 1:1,027. This suggests that the infection could have been transferred with the donor heart. The mononuclear cell response elicited by disrupted toxoplasmic cysts interferes with the diagnosis of rejection in graft biopsy specimens. Electron microscopy is valuable in confirming a light microscopic diagnosis of toxoplasmosis. Drug therapy eradicated the toxoplasmosis, but the patient died later of tuberculous meningitis.

Diagnosis, Differential↗

Medical, legal and administrative aspects of cadaveric organ donation in the RSA.

A shortage of donors remains the major limiting factor as regards the number of kidney and heart transplants performed in South Africa each year. The medical, legal and administrative aspects of cadaveric organ donation in this country are reviewed. The pathophysiology of brain death and the criteria necessary for a definite diagnosis are described, together with the criteria for the selection of cadaveric organ donors. The statutory requirements pertaining to the removal of human hearts and kidneys for the purposes of transplantation are detailed. The subsequent management of the brain-dead donor up to the time of excision of the required organ is described, and a note regarding the preservation and transportation of the donor organs is added.

Age Factors↗

The assessment and selection of patients for heterotopic heart transplantation.

In the 2-year period 1979-1980, 34 patients were assessed at Groote Schuur Hospital as candidates for heterotopic heart transplantation. Ischaemic heart disease was the most common underlying cause (19 patients), with cardiomyopathy (9), rheumatic heart disease (2), failed transplants (3), and endomyocardial fibrosis (1) as the other causes of myocardial disease. Five patients were not accepted into the transplant programme, 2 declined after being accepted, and in 3 the initial decision of acceptance was later reversed. Nine patients died while awaiting suitable donors, the mean survival time from the date of acceptance being only 26 days. Fifteen patients underwent heterotopic heart transplantation, 11 remaining alive at the end of the period of study; 8 had normally functioning donor hearts but 3 had suffered irreversible rejection and awaited a second transplant.

Adolescent↗

Twenty-four-hour preservation of the pig heart by a portable hypothermic perfusion system.

A portable hypothermic perfusion system for storage of hearts has been developed. The system uses the airlift pump principle, whereby the flow of gas maintains circulation of the perfusate through the heart; no other energy source is required. Performance on ex vivo functional testing of 10 pig hearts stored for 20 to 24 hr using this system (group 3) was compared with that of freshly excised hearts (group 1) and hearts stored simply in the perfusate under hypothermic conditions, but not perfused (group 2). Group 2 hearts performed less well on functional testing than those of groups 1 and 3 which showed little statistical difference, suggesting good preservation by hypothermic perfusion. This has been confirmed by orthotopic transplantation of similarly preserved baboon hearts with survival until rejection at a mean of 27 days. The importance of the various constituents of the perfusate and the significance of weight gain during the storage and reperfusion periods are discussed.

Animals↗

Technique, complications, and clinical value of endomyocardial biopsy in patients with heterotopic heart transplants.

A review of 157 consecutive biopsies of donor endomyocardium in patients with heterotopic heart transplants is reported. The technique of percutaneous transvenous endomyocardial biopsy after this operation is described; manipulation of the catheter and bioptome into the junction of the donor superior vena cava and right atrium can be difficult when this anastomotic junction is small, as a result either of operative surgical technique or of subsequent contraction. The complication rate was 4%, but one patient may have died from infection resulting from biopsy when the bioptome had to be introduced at the groin. The histopathological changes seen in the biopsy specimens have been graded according to a scoring system to give the clinician a guide to the severity of rejection. Histopathological assessment was of clinical value in 96% of cases, but was inaccurate on two occasions, once because an opinion was given on what was in retrospect an inadequate sample. In patients undergoing persistent low-grade acute or chronic rejection there was difficulty in detecting or appreciating the true extent of myocardial fibrosis; this led to inadequate immunosuppressive treatment in two patients. Attention is drawn to the fact that ischaemic fibrosis resulting from the vascular changes of chronic rejection may spare the endomyocardium, which is kept viable by intracavitary blood, and that this may lead to a misleading histopathological report.

Biopsy↗

Emergency open-heart surgery. Experience with 100 consecutive cases.

One thousand two hundred and three open-heart operations were performed at Papworth Hospital between January 1973 and December 1978 with an early (30 day) operative mortality of 5.3%. One hundred patients were treated on an emergency basis. This is defined as an operation necessarily performed within 24 hours of referral to a surgeon. The early mortality in this group was 24 (24 per cent) and accounted for one third of the early deaths during the period under review. The main clinical conditions requiring emergency surgery included ischaemic heart disease (36 patients, early mortality 22.2%); critical valve disease (24 patients, 12.5%); bacterial endocarditis (14 patients, 28.5%); acute aortic dissection (11 patients, 36%) and complications associated with valve substitutes (11 patients, 36%). Almost all the deaths in the ischaemic heart disease group occurred in those undergoing operation for the complications of infarction. Many factors contribute to the higher risk of emergency open-heart surgery. Of these, dysfunction of other organ systems secondary to low cardiac output and the state of the left ventricle are the most important. Earlier referral for operation of patients with critical valve disease should help to reduce mortality.

Adult↗

Changes in indications for heart transplantation. An additional argument for the preservation of the recipient's own heart.

The 1 year survival rate after heart transplantation since 1967 from +/-30% to +/-70%, and the 5 year survival rate is now +/-50%. This improvement has brought renewed interest in this procedure, now done in about twenty centers in eight countries, and increased confidence has widened the indication to patients who are less than terminally ill, to restore quality of life. This trend is illustrated by the Cape Town series, which can be divided into two parts: 10 patients treated by orthotopic heart transplantation (OHT), from 1967 to 1973, and 40 patients treated by heterotopic heart transplantation (HHT), from 1974 to 1981. The HHT group was younger (mean 37 +/- 10 years versus 51 +/- 9 years, p less than 0.001), had been ill for a shorter length of time (mean 3.6 +/- 0.7 years versus 6.6 +/- 1.4 years, p less than 0.091), and were in a lower New York Heart Association (NYHA) class (mean 3.45 +/- 0.11 versus 3.9 +/- 1.0, p less than 0.006). The improved survival is linked to patient selection, progress in management, and switch to HHT, but not to progress in matching between donor and recipient. Since there is no means to predict tolerance of the donor heart, HHT limits the risks from unforseeable mismatch. The recipient's heart is a built-in assist device, maintaining life when the donor heart fails acutely at operation or during acute [three cases] or chronic [two cases] rejection. Had these patients undergone OHT they would have died. Comparing the 10 oldest HHT patients with the OHT series, no difference in pretransplant parameters was found. However, survival of HHT recipients was longer during the critical post-HHT period: at 3 months, p less than 0.011; at 6 months, p less than 0.05. Larger series will separate the effects of progress in management from the intrinsic advantages of HHT. Retaining the recipient's heart is logical and has brought few complications. Survival rate of 40 HHT patients was 73% at 6, 65% at 12, and 51% at 36 months; 85% of survivors are in NYHA Class I. In patients in less than desperate condition, but who refuse to remain cripples, HHT eliminates the growing ethical problem of removing a recipient's heart that may still support the patient.

Adolescent↗

Orthotopic transplantation of the baboon heart after 20 to 24 hours' preservation by continuous hypothermic perfusion with an oxygenated hyperosmolar solution.

Baboon hearts were rapidly excised after being flushed with 500 ml of cardioplegic solution at 4 degrees C and then immersed in cold 4 degrees C saline or cardioplegic solution for 2 minutes. The hearts were then perfused at 8 to 10 cm H2O pressure for 20 to 24 hours under refrigeration with a hyperosmolar clear fluid maintain perfusate at 6 to 8 degrees C, through which 95% oxygen and 5% carbon dioxide were continually bubbled to maintain the perfusate pH between 7.2 and 7.4. Myocardial temperature remained at approximately 6 to 8 degrees C. The hearts were then orthotopically transplanted into recipient baboons matched for size and AB blood group. Two groups (A and B) were studied, differing significantly only with respect to the constitution of the cardioplegic solution and perfusate used. The cardioplegic agent used in Group B contained a higher concentration of magnesium than that used in Group A and included the calcium antagonist verapamil. Perfusate B had higher osmolality than perfusate A, largely due to the inclusion of sucrose. A preliminary group of 10 baboons in Group A received no immunosuppression. Five of the remaining six immunosuppressed baboons in this group survived more than 48 hours to rejection or until killed at 2 to 29 days. All six of the baboons in Group B survived to rejection between 6 and 33 days, with mean survival 19.5 days. Cardiac catheterization was performed in six surviving baboons (Group A, four; Group B, two) between postoperative days 6 and 10 and showed good hemodynamic function. Histologic examination of hearts after death has shown only minor ischemic changes in those hearts which functioned well.

Animals↗

Ex vivo functional evaluation of pig hearts subjected to 24 hours' preservation by hypothermic perfusion.

A system has been developed for the ex vivo functional testing of isolated hearts. Three groups, each of 10 pig hearts, have been studied: group 1--freshly excised hearts; group 2--heart hypothermically perfused for 20 - 24 hours with Krebs-Henseleit solution; group 3--hearts similarly perfused with a clear fluid hyperosmolar solution. Group 2 hearts performed poorly on functional testing and would clearly have been unsuitable for transplantation. Haemodynamic observations on group 3 hearts showed little statistical difference from those of group 1, suggesting good preservation. The value of the ex vivo testing system as a reliable means of assessing myocardial function is discussed, and has been confirmed by subsequent successful orthotopic transplantation of baboon hearts stored under identical conditions.

Animals↗

The incidence of postoperative infection and the role of antibiotic prophylaxis in pulmonary surgery. A review of 221 consecutive patients undergoing thoracotomy.

A study was made of the organisms cultured from the respiratory tract at or before operation and of the incidence of postoperative bronchopleural fistula, pneumonectomy space infection or chest infection in 221 consecutive patients undergoing thoracotomy. Patients receive either no antibiotics or one of three variations of an ampicillin/flucloxacillin mixture. Prophylactic systemic antibiotics significantly reduced the number of pneumonectomy space and chest infections; application of penicillin plus streptomycin powder to the bronchial stump had no effect. Systemic antibiotics given preoperatively reduced the incidence of bronchopleural fistula. The type of bacteria present in the preoperative sputum or bronchial lumen at operation was no help in predicting the effect therapy of postoperative infection.

Ampicillin↗

An investigation of the immunosuppressive effects of niridazole and metronidazole in rat and baboon heterotopic cardiac allograft models.

Niridazole alone (at 50 mg/kg/day) and particularly in combination with azathioprine and prednisolone showed potent immunosuppressive activity, far surpassing that produced by conventional agents, in the rat heterotopic cardiac allograft model. Benzoylmetronidazole or metronidazole (at 50 mg/kg/day) either alone or in combination with azathioprine and prednisolone demonstrated little immunosuppressive activity. The potent immunosuppression obtained with niridazole in the rat could not be reproduced in the baboon heterotopic cardiac allograft model in the doses used; niridazole at 50 mg/kg/day seems to be toxic in this animal.

Animals↗

Management of oesophageal perforation associated with benign stricture and hiatus hernia by oesophagoplasty and fundoplication.

The operation of oesophagoplasty and Nissen fundoplication has proved valuable in the management of intractable peptic stricture of the oesophagus. This report concerns its use in perforation of the oesophagus in an 81-year-old woman with benign peptic stricture in whom perforation occurred during instrumentation. She made an uneventful recovery from operation and remained well and able to swallow without difficulty at three-month follow-up.

Aged↗

The present status of heterotopic cardiac transplantation.

In the period November, 1974 to May, 1980, 30 patients underwent heterotopic heart transplantation at Groote Schuur Hospital. One patient subsequently underwent retransplantation for rejection. There were no operative deaths. Fifteen patients are alive 4 months to almost 5 1/2 years after transplantation. The 1 year survival rate has been 61%. Three of six patients have survived for more than 4 years. Eight of nine patients whose initial transplant operation was performed during the past 18 months remain alive. Seven patients died from infection, five from rejection, and three from other causes. The advantages of heterotopic over orthotopic heart transplantation, in particular in allowing patients survival even after graft destruction by irreversible rejection, are discussed.

Adult↗

Clinical transplantation of the heart: a review of 13 years' personal experience.

The results of the heart transplantation operations performed personally by one surgeon (CNB) at Groote Schuur Hospital between 1967 and 1980 are reviewed. Of 9 orthotopic transplants performed between 1967 and 1973, 4 survived for more than one year and 2 remain alive today twelve and ten years later. Of 11 heterotopic transplants performed since 1974, one-year patient survival has been 82%, though one patient survived on his own heart after irreversible graft rejection. Three of the original 4 patients remain alive over five years later. These results are rather better than the overall results of our unit, where a total of 37 heterotopic transplants has been performed; the possible reasons for this are discussed. One patient, previously unreported, who underwent transplantation of the heart and both lungs in 1971, died after 23 days from pulmonary complications. Heterotopic transplantation using a xenograft (baboon or chimpanzee heart) has been performed on two occasions as a means of temporary circulatory support in patients with acutely failing hearts when no human donor was available. The chimpanzee heart supported the circulation satisfactorily for four days.

Adolescent↗