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Biomedical subjects

A G Sheil

Publications and source records attributed to A G Sheil.

At least 163 records · Page 9Linked to original sources

Treatment of acute rejection episodes in dog renal allograft recipients receiving cyclosporin A:ATG vs prednisolone.

Prednisolone and antithymocyte globulin (ATG) were compared for their abilities to reverse acute rejection in cyclosporin A-treated canine graft recipients. Outbred dogs bearing kidney allografts were treated with a suboptimal dose of cyclosporin A (10 mg kg-1); at the onset of an acute rejection episode, animals received daily prednisolone (40 mg kg-1) or ATG (20 mg kg-1) until serum creatinine levels decreased. In seven untreated allograft recipients, rejection was first diagnosed at a mean 4.4 days post-transplant. In 23 dogs receiving cyclosporin A, rejection was first diagnosed in all dogs at a mean 43.6 days post-transplant. Compared to ATG, prednisolone was more successful in the reversal of primary acute rejection episodes (5/8 and 7/8 reversals, respectively) and produced a quicker return to normal renal function (mean 15.4 and 6.8 days, respectively). ATG therapy, however, resulted in fewer subsequent acute rejection episodes than prednisolone therapy (mean 1/5 and 6/7 developed secondary rejection episodes, respectively); the possible advantage of 'clonal depletion' following ATG therapy is discussed.

Acute Disease↗

Long-term survival of human fetal pancreatic tissue transplanted into an insulin-dependent diabetic patient.

The explants of two human fetal pancreases of 15 weeks gestational age were cultured for 6-7 days before being implanted in a 29-year-old insulin-dependent diabetic woman who had received a renal graft two months previously. One pancreas was placed in the flexor muscles of the forearm whilst the other was implanted in an omental pouch. To reduce the chances of rejection the tissue was cultured in vitro, the donor of the tissue placed in the forearm was DR antigen matched with the recipient and the patient remained on cyclosporin and prednisone therapy. At 3 months a mass developed in the forearm muscle at the site of transplantation, and continued to grow. Biopsy at 13 months showed a small area of original pancreas surrounded by a large collection of mature lymphocytes and fibrous tissue. A and D cells could be seen around pancreatic ducts but B cells and acinar tissue were absent. At no stage during follow-up was plasma C-peptide detected in the recipient.

Administration, Oral↗

Renal autotransplantation for severe loin-pain/haematuria syndrome.

Most forms of therapy for the loin-pain/haematuria syndrome are unsuccessful, though nerve-block procedures and renal denervation sometimes provide temporary relief. Three young patients, with pain so severe that they were dependent on narcotics, were treated for this syndrome. All three had been repeatedly admitted to hospital. Loin pain was unilateral in two patients and predominantly so in the third. Renal function, excretion urography, and angiography were normal, but renal biopsy specimens showed deposition of the third component of complement in the renal arterioles. All were treated with renal autotransplantation; the kidney causing pain (or the one causing the most pain) was completely excised and reimplanted in the iliac fossa. Two patients had complete relief of pain and the third almost complete relief, despite recurrence of haematuria in all three. It is too early to determine whether this major procedure is justified in the treatment of the loin-pain/haematuria syndrome, but the early results are encouraging.

Adolescent↗

Post-transplant acute renal failure in cadaver renal recipients treated with cyclosporine.

The outcome of patients with acute renal failure following cadaveric renal transplant has been evaluated in a prospective, controlled trial, comparing treatment with cyclosporine (CSA) to prednisone, azathioprine, and antilymphocyte globulin (AZA). There was a high incidence of acute post-transplant renal failure in both groups: 37 of 51 CSA and 31 of 45 AZA patients, due to the long exposure of kidneys to warm and cold ischemia. Onset of adequate renal function was delayed for three or more weeks in 27 (53%) CSA and only nine (20%) AZA patients, and the only predisposing factor found was donor hypotension. All nine AZA and 18 of the 27 CSA patients with prolonged oliguria subsequently had a spontaneous diuresis. Nine of the CSA patients were changed to azathioprine and prednisone because of suspected CSA toxicity, and eight of these kidneys began functioning within days, even though they had been oliguric for 21 to 83 days. Of these nine patients, five had adequate long-term function on AZA, three developed CMV infections that were fatal to two individuals, and two rejected their grafts. Plasma CSA levels fluctuated widely in all patients, but were not higher in any group, including those with prolonged oliguria. During the oliguric period, biopsy specimens proved rejection was more common in the nine patients who had their CSA stopped than in the other CSA patients, and seven of these nine developed a diffuse interstitial fibrosis that was thought to be a manifestation of CSA toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Effects of verapamil in the prevention of warm ischaemia induced acute renal failure in dogs.

Acute renal failure in the immediate postoperative period remains a significant complication of renal transplantation. A major factor in the pathogenesis may be warm ischaemia (WI). Recent evidence implicates a calcium mediated mechanism as a final common pathway in certain models of acute renal failure. This study was undertaken to evaluate the effects of Verapamil, a calcium antagonist, in the prevention of warm ischaemia-induced acute renal failure following renal autotransplantation in the dog. Twenty-one mongrel dogs were randomly allocated to three groups. Group 1 (control, 8 dogs) received 20 ml normal saline before a standardized 60 min warm ischaemic insult to the left kidney. Group 2 (6 dogs) received Verapamil (0.3 mg/kg) by intravenous injection and Group 3 (7 dogs) received Verapamil (0.3 mg/kg) by intra-arterial injection into the left renal artery prior to the same ischaemic insult. The left kidney was heterotopically grafted to the right iliac fossa in the warm ischaemic period. Contralateral nephrectomy was performed. The dogs were followed up to 7 days after operation by serial creatinine estimation. Histological examination of some autografts was performed. Of the eight controls, six showed marked renal impairment (serum creatinine greater than 800, or death in renal failure). Three of the six dogs given intravenous Verapamil showed marked renal impairment. None of the seven dogs receiving intra-arterial Verapamil showed marked renal impairment (P = 0.013, chi 2 test). The mean rate of serum creatinine rise for each group was analysed by multivariate analyses of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Should polytetrafluoroethylene grafts be used in preference to saphenous vein for femoropopliteal arterial bypass?

Some surgeons have advocated using polytetrafluoroethylene (PTFE) as the graft material of choice for femoropopliteal arterial bypass so that the saphenous vein could be preserved for future cardiovascular surgery. We have examined our results to see if this approach could be justified in our patient population. PTFE was used for 101 femoropopliteal reconstructions in 96 patients (56 male and 40 female). Thirty-eight (40%) complained of debilitating claudication and 58 (60%) had limb-threatening ischaemia. There were 83 primary PTFE femoropopliteal reconstructions and 18 repetitive procedures after failure of an earlier ipsilateral bypass. Twenty-nine of the 101 PTFE grafts were anastomosed distally to the popliteal artery above knee and the remaining 72 below knee. At 5 years, the cumulative patency for all grafts was only 11%. The 4 year cumulative patency was better for claudicants (40%) than for those with threatened limb loss (11%) but two of the 38 claudicants required amputation when their grafts failed. Patency rates were not significantly affected by the site of the distal anastomosis or by a previous failed ipsilateral femoropopliteal bypass. Worthwhile limb salvage was achieved only by frequent re-operation. Our results with PTFE are not good enough to use it in preference to an adequate saphenous vein for femoropopliteal bypass.

Aged↗

A comparison of the effects of cyclosporin A and standard agents on primary wound healing in the rat.

Eighty-six Sprague-Dawley rats were randomly allocated to three treatment groups given tap water (control group), cyclosporin A (CSA group) and azathioprine and prednisone (AP group). Two incisions, one skin and one musculofascial, were made in each rat with a standardized technique. The healed incisions were subjected to tensiometery at days eight and 15 after operation. Histologic examination was undertaken on some wounds. The results indicate that cyclosporin A in clinical doses does not inhibit skin or musculofascial healing in the rat. Azathioprine and prednisone immunosuppression significantly retarded skin healing on day eight postoperatively although this had returned to control levels on day 15. Azathioprine and prednisone did not affect musculofascial healing at the administered dose. In the sections available for study, there were no qualitative histologic differences between groups at both days eight and 15 postoperatively.

Animals↗

Nonspecific immunological studies in kidney transplant recipients with and without skin cancer.

The immunocompetence of the following patient groups was compared using peripheral blood mononuclear cells in a variety of in vitro assays: controls (84); hemodialysis patients (32); kidney transplant recipients without cancer (172), and those with skin cancer (18). The in vitro functions assayed were blastogenic responsiveness to phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen, allogeneic lymphocytes, and two cocktails of bacterial, viral, and fungal antigens; cytotoxic functions assayed were spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Compared with control subjects, hemodialysis patients showed depressed responsiveness to one antigen cocktail only. Transplant patients with no cancer showed uniformly depressed responsiveness to PHA and allogeneic lymphocytes and reduced SCMC and ADCC activity up to 12 years after transplant; responsiveness in these patients to the two antigen cocktails, after initial depression, recovered by 3 years after transplant to exceed control values. The group of 18 transplant recipients with skin cancer, when compared with transplant recipients with no cancer at a comparable period after transplant, showed similar depression of SCMC and ADCC activity, but significantly greater depression of responsiveness to PHA (P less than 0.01), allogeneic lymphocytes (P less than 0.05), and the 2 antigen cocktails (P less than 0.05).

Antibody Formation↗