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Biomedical subjects

A G Sheil

Publications and source records attributed to A G Sheil.

At least 199 records · Page 11Linked to original sources

Incidence of cancer in renal transplant recipients.

In summary, the susceptibility of transplant recipients to the development of cancer is dramatically revealed by the oncogenic effects of sunlight. Skin and other forms of carcinoma are aggressive and develop particularly in patients doing well from the immunological point of view post transplantation. Patients with cancer are less susceptible to rejection than those without. Patients with malignancy survive significantly better in the early post transplant years than do those without cancer, but fare much worse later on because of deaths caused by cancer and because of the need to withdraw immune suppressive therapy in those patients with proliferating cancer. Almost 40% of long survivors have cancer, an incidence which continues to increase. Cancer has become a major cause of mortality in long survivors. It seems that, with time, most carcinomas which occur in the general population will occur with increased frequency in renal transplant recipients.

Adenocarcinoma↗

Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs.

A collaborative study including centres in the United Kingdom, Australia, and New Zealand was instituted in 1970 to determine the incidence of cancer in patients treated for at least three months with azathioprine, cyclophosphamide, or chlorambucil. Follow-up of 3823 renal transplant recipients showed an almost 60-fold increase of non-Hodgkin's lymphoma together with an excess of squamous-cell skin cancer and mesenchymal tumours. A series of 1349 patients without transplants showed an excess of the same tumours, though to a less extent. These preliminary findings provide no clear evidence that immunosuppressive drugs produce the increased risk of most of the common cancers that might be expected from the simplest interpretation of impaired "immunosurveillance."

Adolescent↗

Arterial reconstruction with polytetrafluoroethylene: a preliminary report.

Early results of arterial reconstruction with reinforced expanded polytetrafluoroethylene (PTFE) in the lower extremity have been obtained by reviewing 55 patients undergoing 59 operations - 38 femoropopliteal bypasses and 21 long bypasses distal to the popliteal artery. The one-year accumulated patency rates were 73% for the femoropopliteal bypass group and 50% for the long bypass group. Early results suggest that PTFE is superior to Dacron and is an acceptable substitute for autogenous saphenous vein when the latter is unavailable or of inadequate calibre.

Adult↗

Cancer following renal transplantation.

Ninety-nine (21%) of 471 patients who survived with functioning grafts for at least six months following renal transplantation developed cancer. Of these 76 (77%) had skin malignancy, 29 (29%) had malignancy affecting other organs, and six had cancer of both skin and other organs. In patients with skin cancer squamous cell carcinoma (SCC) was three times as frequent as basal cell carcinoma (BCC). SCC tended to be multiple, recurrent and aggressive. Seven (12%) patients with SCC developed metastases of whom five died. Cancers other than skin included reticulum cell sarcoma (9), acute leukaemia (2) and cancers involving the gastrointestinal (5), genitourinary (11) and respiratory (2) systems. Incidence of cancer in patients surviving beyond one, five and nine years after operation was 98/428 (23%), 70/179 (39%) and 20/45 (44%) respectively. In 31 patients who died more than five years after transplantation cancer was the major cause in eight (26%). For the types of cancers recorded estimates show allograft recipients to be at increased risk when compared with the age-matched Australian population by factors which varied from 300 times for reticulum cell sarcoma to 1.8 times for invasive carcinoma of the cervix. The full extent of the threat of cancer in immune suppressed transplant recipients remains to be determined.

Adolescent↗

A comparison of flushing fluids for initial perfusion of kidneys for transplantation.

Four solutions for initial flushing of kidneys prior to transplantation were tested under conditions designed to resemble those of clinical cadaveric donor renal transplantation. The experimental model was the dog subjected to bilateral nephrectomy with renal autograft. Kidney grafts were subjected to 15 minutes' anoxia in vivo, 30 minutes' warm ischaemia at 37 degrees C ex vivo, and two hours' cold ischaemia before reimplantation. The four solutions used were Collins (C3), Perfudex (P), hyperosmolar citrate (HC), and a solution of bovine albumin containing dog red blood cells (BBA). Effects of the flushing fluids were compared by parameters relating to dog survival, renal function, and serum enzyme levels. With all parameters studied the best results occurred in HC perfused kidneys. Results with BBA perfusion were marginally worse, while C3 perfused kidneys were again inferior. P perfused kidneys clearly did least well. The results support the use of HC for clinical application.

Animals↗

False-negative saralasin responses in renovascular hypertension.

Blood pressure responses to the infusion of saralasin and plasma renin levels were measured in 31 hypertensive patients following preparation with frusemide. Five patients had unilateral renal artery stenosis, with renal vein ratios lateralising strongly to the affected side. Saralasin produced depressor responses in 3 of these but failed to evoke significant effects in the other 2, despite the fact that in both cases hypertension was subsequently alleviated by renal bypass surgery. A further period of more severe sodium depletion increased plasma renin levels and the depressor effect of saralasin, but did not help to differentiate renal artery stenosis from other forms of hypertension.

Adult↗

Allograft vein arterial bypass.

Untreated allograft saphenous veins used for arterial bypass failed in ten of 11 cases. The precise cause of failure was uncertain, but immune reactions of the recipient against the allograft seemed to be related to failure.

Arteriovenous Shunt, Surgical↗

Distal lower limb arterial reconstruction with modified allograft saphenous veins.

Cadaveric donor saphenous veins subjected to proteolytic enzymatic digestion, crossbonding and heparin bonding were used for arterial reconstruction in the legs of 13 patients threatened with amputation and without suitable autogenous saphenous veins. Distal anastomoses were to the tibial and peroneal vessels. Twelve patients (92 per cent) were discharged from hospital with functioning grafts; 9 grafts (69 per cent) continue to function 2-16 (average 8) months after operation. Amputation was avoided in 11 patients (85 per cent). Although early results are encouraging, late results are yet to be determined.

Aged↗

Small arterial reconstruction using modified cadaveric saphenous veins.

Human saphenous veins removed from cadaver donors were subjected to proteolytic enzymatic digestion, cross bonding, and heparin bonding. They were tested as small arterial substitutes in dogs. Eight of eleven were successful, persisting without development of stenosis or aneurysm, the longest for eighteen months. In humans, similarly prepared veins were used as arterial bypasses to revascularize ischemic limbs in eleven patients and aneurysmal degeneration of an earlier unmodified allograft bypass in one patient. Distal arterial anastomoses were to the tibial and peroneal arteries. Nine patients who had not undergone previous reconstructive surgery involving the vessel used for distal anastomosis were treated successfully; all remain with healed limbs between three and twelve months after surgery, eight with functioning bypasses. In three patients who had undergone previous operations on the same artery used for distal anastomosis, long bypasses failed, although amputation was avoided in one patient by additional bypass with modified vein to the profunda femoris artery. We conclude that modified saphenous vein allografts are suitable small arterial substitutes. It remains to be seen whether veins will maintain patency for long periods without development of complications.

Aged↗

Autogenous veins and velour dacron in femoropopliteal arterial bypass.

Sixty-five patients treated by femoropopliteal bypass in 1974 were surveyed; the mean follow-up time was 10.4 months. The one year cumulative patency rate for velour Dacron was 50 percent; this was less successful than were the results from a comparable group in which vein grafts were used (79 percent). These poor results were due principally to the high failure rate of velour Dacron in patients suffering from clinically severe ischemia. In these only one in four grafts remained patent. If a less than perfect arteriographic runoff was obtained, only one in three still functioned. These results occurred despite high intraoperative graft flows. It appears that velour Dacron may be acceptable in patients treated for claudication if no adequate vein is available. This prosthesis gives an unacceptably high failure rate in patients with severe ischemia.

Adolescent↗

E-rosette forming cell numbers in the blood of human renal allograft recipients.

The incidence of circulating T lymphocytes (ET-RFC) and a sub-population of T lymphocytes (EE-RFC) were monitored in the blood of seventy-one cadaver renal allograft recipients for the first 2 months after transplantation. In patients with uneventful post-operative courses, the incidence of both ET-RFC and EE-RFC fell promptly upon initiation of immunosuppression returning approximately to pre-operative levels 3-5 weeks after operation; the fall in cell numbers was greatest in those patients receiving adjunct ALG therapy. With the onset of an acute rejection episode, the EE-RFC level rose quickly eventually exceeding the pre-operative level; in 88% (thirty episodes) of cases this rise occurred 1-6 days before clinical diagnosis of rejection and in 12% of cases on the same day as clinical diagnosis. The incidence of ET-RFC rose in conjunction with some cases of acute rejection but remained unchanged in other cases. It is suggested that measurement of the incidence of EE-RFC in blood is valuable in predicting the onset of acute rejection and for the differential diagnosis of acute rejection and ischaemic renal damage.

Creatinine↗

Occlusive arterial disease in uraemic and haemodialysis patients and renal transplant recipients. A study of the incidence of arterial disease and of the prevalence of risk factors implicated in the pathogenesis of arteriosclerosis.

The prevalence of clinical and sub-clinical occlusive arterial disease and of risk factors implicated in the pathogenesis of arteriosclerosis was assessed in 21 patients with chronic renal failure, 27 on maintenance haemodialysis and 51 renal allograft recipients. Clinical occlusive arterial disease was present in 27 patients, and sub-clinical arterial disease in 34. Myocardial infarction, cerebral thrombosis and lower limb arterial thrombosis had occurred only in the transplant recipients; these patients had, however, been followed for a longer period of time than the other two groups. In the allograft recipients, the cumulative incidence of any occlusive arterial disease was 416 per 1000, and that of coronary heart disease was 267 per 1000 at six years. Hypertension was present in 76 per cent of patients prior to renal replacement therapy. Following institution of definitive therapy, hypertension was of shorter duration and less common in haemodialysis patients than in renal transplant recipients. Uraemic and haemodialysis patients with occlusive arterial disease had required antihypertensive medication for significantly longer than those free of arterial disease. Transplant recipients with hypertension had a greater mean serum creatinine, were receiving a larger maintenance dosage of corticosteroids and less frequently had undergone prior bilateral nephrectomy than those transplant patients without hypertension. Serum lipid levels were elevated in 62 per cent of patients. In the uraemic and haemodialysis patients hypertriglyceridaemia was the predominant abnormality while in the transplant recipients combined hypertriglyceridaemia/hypercholesterolaemia was more frequent. Despite regular aluminium hydroxide therapy 81 per cent of uraemic and haemodialysis patients had a calcium X phosphate product higher than normal. Arterial and/or soft tissue calcification as demonstrable in 20-38 per cent of patients within each group, but could not be related to the calcium X phosphate product of radiographic evidence of hyperparathyroidism. Glucose intolerance was present in 71 per cent of the uraemic and haemodialysis patients and 33 per cent of the transplant recipients. Hyperuricaemia, cigarette smoking, obesity and a sedentary existence were also prevalent. The majority of patients had several risk factors implicated in the pathogenesis of arteriosclerosis. Occlusive arterial disease is a major problem in patients with end stage renal disease, being no less common after transplantation than with long-term maintenance dialysis. The aetiology is multifactorial.

Adult↗

Cancer in renal allograft recipients in Australia and New Zealand.

Total incidence and outcome of cancer in all renal allograft recipients in one geographic area are known: 126 (7%) of 1884 patients developed cancer during an 11-year period. Proportions with cancer 1 and 5 years following successful transplantation were 11% and 24%, respectively. Numbers, proportion of malignancies, and average time of diagnosis post transplantation were as follows: reticulum cell sarcoma (RCS) 15 (11%), 18 months; adenocarcinoma 8 (6%), 21/2 years; cancer of cervix 6 (5%), 41/2 years; leukemia 2 (2%), 5 years. All were highly malignant except cancer of the cervix, 2 localized forms of RCS, and 4 cases of cerebral RCS that responded to radiotherapy. Skin malignancy (SM) occurred in 97 patients (77% of cancers). The frequency increased with time, and after 4 years 18% of survivors had this cancer. In patients with SM 17% had multiple lesions when first diagnosed; further cancers or recurrences of the same type developed in 23%; another form of SM developed in 15%; metastases occurred 9 times (9%), 4 fatally. Six (6%) patients with SM developed other forms of malignancy, as compared to 33 (2%) of 1786 patients without SM. Ooulook for patients with SM with regard to survival and graft function was greatly improved at 5 years, as compared to that for patients without SM. Thereafter the outlook for patients with SM worsened rapidly because of additional effects of malignancy.

Adenocarcinoma↗

Preparation and testing of goat anti--thymocyte globulin.

This study details methods of production, purification and testing of large volumes of uniformly potent, non-toxic, anti-human thymocyte globulin (ATG). Plasma from 70 goats immunised with human thymic lymphocytes was fractionated by ammonium sulphate precipitation to its IgG component. Contaminating antibodies were removed by absorption methods. After fractionation and absorption, ATG retained its ability to inhibit the formation of rosettes by human lymphocytes with sheep red blood cells. Antibodies to human glomerular basement membrane were not detected in any tested preparation. Tests performed on monkeys, mice and rabbits revealed low toxicity.

Absorption↗

Diazoxide-induced renin release in diagnosis of remediable renovascular hypertension.

In hypertensive patients with unilateral renal artery stenosis, intravenous diazoide increased renal vein renin activity more on the involved side than on the contralateral side, whereas, in a group with predominantly unilateral renal parenchymal disease, the increase in renal vein was similar for both kidneys. In patients with bilateral renal artery stenosis, the use of diazoxide was helpful in lateralizing the dominant ischaemic lesion. Diazoide administration appears to be a safe, rapid and convenient method of increasing the sensitivity of the renal vein renin test used in predicting the outcome of surgical treatment of renovascular hypertension. Bilateral renal vein renin determination of established value in the diagnosis of functional renal ischaemia. 1-4 However, in the use of this procedure to predict the efficacy of corrective surgery, false positive and false negative results still occur. Thus, various manoeuvres which stimulate renin release have been employed to improve the sensitivity of the test. 5-7 We report a new application the practical approach to of this procedure in the diagnosis of renal hypertension, which both basal and stimulated levels of renal venous renin activitity can be measured during a brief period of bilateral renal vein catherization.

Adolescent↗

Reversal of renal failure and control of hypertension in patients with occlusion of the renal artery.

Results of arteriographic investigation of patients with deteriorating renal function or poorly controlled hypertension have revealed that thrombosis of the renal artery is not an uncommon exacerbating factor. Seventeen patients with one or more occluded renal arteries had an operation to improve renal function or to control hypertension. Stenosis of the contralateral renal artery was present in addition to the occlusion in four patients. Reconstructive arterial procedures were performed in 15 patients and nephrectomy was performed in two. Eight patients with renal failure had marked improvement in renal function after revascularization of the occluded renal arteries. The group had a mean preoperative serum creatinine value of 7.95+/-1.81 (S.E.) milligrams per cent which fell postoperatively to 3.91+/-1.21 (S.E.) milligrams per cent at a mean follow-up period 20 months. Preoperative control of hypertension was difficult in 16 of the 17 patients. Postoperatively, the blood pressure fell to normal levels in six patients, and in an additional eight patients, it did so with the administration of antihypertension therapy. The hypertension was unchanged in two patients. Plasma renin activity was measured in 14 of the patients with hypertension. It was elevated in 13 patients and normal in one patient. Postoperatively, the blood pressure was unchanged in the patient with normal plasma renin activity, but in 12 of the 13 patients with elevated plasma renin activity, the blood pressure returned to normal levels. It is concluded that patients with occluded renal arteries should be treated surgically. The major benefits of an aggressive approach to this condition are reversal of renal failure and control of hypertension.

Acute Kidney Injury↗