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Biomedical subjects

S M Lim

Publications and source records attributed to S M Lim.

At least 55 records · Page 3Linked to original sources
PubMed1991

The pharmacology of immunosuppression.

In this paper, we review the pharmacological techniques by which graft rejection can be prevented from the early development of azathioprine to the current controversies surrounding FK 506. The basic chemistry of each drug is outlined, its source, mode of action, current uses and the clinical management are briefly documented. In addition to the more usual immunosuppressive agents, the current state of art of using monoclonal antibodies as immunosuppressives is addressed.

Adrenal Cortex Hormones↗
PubMed1991

Organ procurement in Singapore.

Kidney transplantation, an accepted therapeutic intervention for patients with end stage kidney failure, was pioneered in Singapore on 8 July 1970 by the University Departments of Surgery and Medicine, University of Singapore. Up to 1987, an average of 4.7 cadaveric kidney transplants were performed annually. The introduction of Sandimmune (cyclosporine) in 1985 significantly increased graft survival and consequently created a demand for more cadaveric kidneys for transplantation. The rate of cadaveric kidney transplants escalated to 31.3 kidney transplants annually for the period 1988 to 1990. This increase can be attributed both to the appointment of full time transplant coordinators beginning April 1986 and the implementation of the Human Organ Transplant Act in July 1987. The Human Organ Transplant Act accounted for more than half of all kidneys procured for transplantation (55/94) for the period 1988 to 1990.

Cadaver↗
PubMed1991

An in vitro assessment of human fetal pancreatic islets of Langerhans in culture.

The human fetal pancreas is a potential source of islets for transplantation into insulin-dependent diabetic patients. In this study, 35 human fetal pancreas obtained from prostaglandin-induced abortions (12-26 weeks gestation), were placed in culture to determine their capacity to secrete insulin over 30 days. Culture media were sampled twice weekly for insulin and histology was performed serially. Of the 35 pancreases cultured, six were lost due to bacterial contamination, five discarded due to undetectable levels of insulin in culture, nine are still under study, whilst 15 pancreases have been cultured for one month, and insulin studies completed. Three patterns of insulin release were observed: (a) progressive decline (n = 6), indicating non-viable tissue at the onset; (b) delayed decline, indicating significant tissue damage before organ culture (n = 5); and (c) insulin production in vitro over 30 days (n = 4), with viable islets detected histologically. Factors such as gestational age and cold ischaemia time did not correlate with the pattern of insulin secretion observed. This was probably due to a more important variable, not easily assessed, of the period of intrauterine (warm) ischemia. These data suggest: (1) that a small number of fetal pancreases procured from prostaglandin-induced abortuses do yield islets which remain viable in culture over 30 days, and (2) the functional status of islets can be monitored in vivo by measuring insulin secretion, thereby providing a means of identifying tissue suitable for transplantation.

Culture Techniques↗
PubMed1991

Fetal pig pancreas--a preliminary assessment of tissue for transplantation.

Porcine fetal pancreases (PFP) obtained from 4 pregnant sows were pooled, minced into 1 mm3 fragments and studied in organ culture for up to 30 days to determine tissue viability and insulin production in vitro. After 7-9 days in culture, some of these explants were transplanted into euglycemic, N:NIH-nu(s) nude recipient mice, and studied histologically over 69 days following grafting. Using RPMI 1640 supplemented with 5% fetal calf serum as the culture medium in 90% air/10% CO2, it was found that explants were viable with insulin production detected in vitro, which was maximal at day 7 (197 +/- 18.9 mU/L, n = 11), and gradually declined thereafter. By 22 days, insulin levels were less than 60.1 +/- 28.5 mU/L (n = 6). Histology of the explants showed viable tissue with evidence of mitoses present in insulin-positive cells at day 16 in vitro. Beyond this time, tissue viability diminished. Explants transplanted into euglycemic nude mice did not undergo rejection during the observation period of 69 days. Grafts remained viable with evidence of an increase in mitotic activity in the endocrine tissue on immunoperoxidase staining. These preliminary investigations confirm that pancreatic explants from porcine fetuses can be maintained in culture for up to 16 days. Such explants, when transplanted under the kidney capsule of euglycemic, nude mice, did not undergo necrosis, but remained viable, with evidence of mitoses in the islet tissue.

Animals↗
PubMed1991

Accessory heart graft as a surgical model in studies of transplantation immunology.

The heterotopic heart graft was examined as a surgical model for in vivo studies of transplantation immunology. Two innovations previously described distinguish it from an orthotopic heart transplant; its heterotopic, superficial position in the neck, and the use of portex cuffs to facilitate anastomoses of donor aorta and pulmonary artery to recipient common carotid artery and external jugular vein respectively. In this study, few modifications to the original technique were required. However, to ensure a high technical success rate exceeding 95%, it was found that the use of small donors (less than 200 g) and large recipient rats (greater than 230 g) was required. The former minimised the risk of kinking of the venous anastomoses, and the latter ensured an adequate luminal diameter of the carotid artery to facilitate the cuff anastomosis. With the vena cava and pulmonary veins ligated, the transplant served purely as an indicator graft with rhythmic contractions discernible by inspection or palpation. This simplified monitoring of the graft, with no requirement for ECG or biochemical studies. The direction of blood flow was established by angiography as via the aorta to the coronary vessels, returned to the right atrium and ventricle and out through the pulmonary artery to the recipient circulation. As the accessory heart did not provide any life-sustaining function, it could be removed for histological studies once rejection had occurred without compromising the survival of the recipient animal. This allowed the use of the recipient for further studies on its immunological status, including the performance of second grafts.

Animals↗
PubMed1991

Induction of tolerance to vascularised skin allografts using cyclosporin A--an experimental study on rats.

This study investigates the induction of tolerance to vascularised skin allografts in a low responder rodent strain combination. Pedicle skin grafts based on the epigastric vessels were grafted between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rats (n = 24). An extended treatment protocol of high dose cyclosporin A (CyA) (25 mg/kg) spanning nine weeks was used. The mean survival time of epigastric skin grafts in the no treatment control group was 7.6 days (n = 10). With high dose CyA (25 mg/kg), 5/14 animals died during CyA treatment with intact skin grafts. The remaining nine animals enjoyed prolonged graft survival throughout the treatment period. Between one and four weeks following cessation of CyA, rejection occurred in six of nine animals which could not be reversed by pulse CyA treatment. Long term graft survival greater than 200 days was achieved in three animals, but two animals went on to reject their grafts at 231 and 238 days post transplant. Only one animal became tolerant, as confirmed by the retention of a fresh donor-specific free skin graft, without the need for further CyA. This study confirms the difficulty of tolerance induction to vascularised skin grafts, despite using a dose schedule of CyA far in excess of that required to achieve tolerance to other solid organ grafts such as hearts.

Animals↗
PubMed1991

A study of the xenogeneic response in an isolated liver perfusion circuit--preliminary observations.

An isolated liver perfusion circuit was developed to study the xenogeneic reaction of human blood to porcine liver, and investigate the feasibility of using such a system for liver dialysis in fulminant hepatic failure. Three experimental groups were studied: a control group where pooled porcine blood was perfused through pig liver (n = 12), a xenogeneic group where banked human blood was perfused through porcine liver (n = 23), and a modified xenogeneic group where decomplemented human blood was perfused through porcine liver (n = 4). The following parameters of liver function were assessed: liver function tests, serum electrolytes, bile and ascites production. In addition, liver histology was assessed at the start and completion of each perfusion experiment. Control experiments established that the use of low perfusion pressures (mean inlet pressure of 29.5 +/- 7.4 mmHg), and low haematocrit of 20.5 +/- 8.9% (n = 14), enabled five hour perfusions to be consistently achieved with maintenance of normal acid base and electrolyte balance. Bile production over 5 hours was 18.8 +/- 8.0 ml in controls (n = 5) and 17.0 +/- 6.7 ml in the xenogeneic (human-pig) circuit (n = 11) (NS). Ascites production was 235.8 +/- 157.3 ml/hr in controls (n = 5) and 205 +/- 142.0 ml/hr in the xenogeneic circuit (n = 7) (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Techniques of ureteric reimplantation in kidney transplantation and its related urological complications.

Two common techniques of ureteric reimplantation for kidney transplantation, the Politano-Leadbetter and the extravesical ureteroneocystostomy are described in detail. Correct techniques of donor ureter harvesting, appropriate method of reimplantation and judicious use of double J stent are also emphasised so as to reduce the urological complications which occurred in about 7% to 15% in most series. More than 90% of urological complications are due to urinary fistulae and ureteric obstruction which carry a significant morbidity and mortality. The causation, diagnosis and management of these complications are reviewed. Early diagnosis and early aggressive surgical treatment is the key to a successful outcome.

Cystostomy↗
PubMed1991

The immunology of xenotransplantation.

The transplantation of organs between species (xenografting) has long been considered impracticable due to the immunological barriers allegedly induced by the antigenic disparity of distantly related species. This paper challenges the long held dogma's on the immunology of xenografting. We present evidence that T-cells are not necessarily involved in the rejection of organs transplanted between closely related species and that antibody is not necessarily involved in the rejection of grafts between distantly related species.

Animals↗
PubMed1990

Cyclosporin A-induced tolerance is not amplified by the addition of a steroid therapy.

The effect of adding steroids to a cyclosporin A (CyA) schedule designed to induce tolerance to heart allografts in rats was investigated. CyA treatment alone, at a dose of 15 mg/kg per day for 2 weeks, resulted in the successful induction of tolerance (graft survival greater than 100 days) in 70% of the rats. The inclusion of 5 mg/kg of steroids (Solumedrone), administered IM for 40 or 60 days, not only failed to improve this long-term survival (LTS) rate achieved with CyA alone but reduced it from 70% to 50% after 40 days of steroid treatment and to 30% after 60 days of steroid treatment. The administration of 5 mg/kg and 40 mg/kg of steroids during the "high-risk" period for graft rejection (days 30-50 or 40-60) was shown to delay but not prevent subsequent rejections from occurring. Steroid treatment alone (5 mg/kg per day) was found to be ony weakly immunosuppressive. Thus, we have demonstrated that the addition of steroids to a CyA tolerizing schedule was detrimental to the induction of tolerance.

Animals↗
PubMed1990

The pathological differences of rejection in the heart allografts which are transplanted alone or with synchronous skin grafts in rats.

The morphological patterns of rejection of the heart allografts which were combinedly transplanted with skin grafts was examined to determine whether it was different from that of the heart grafts transplanted alone. The results showed that there were distinct differences in the pathology of the rejection between the two groups because in the single heart grafts mononuclear cells concentrated in almost all layers of myocardium but in the combinedly transplanted heart grafts not only concentration of them but also severe hemorrhage and edema were observed in it, and it suggests that skin graft has effects on rejection process of heart grafts. As we used an outbred strain of rats some survived heart grafts were observed and their pathology was characteristic in the interstitial accumulation of hypertrophic mast cells, most of which were degranulating.

Animals↗
PubMed1990

Current issues in heart transplantation.

Dramatic advances in heart transplantation have been made in the last decade. It is now a standard treatment option for end stage cardiac disease. There is tremendous potential for research and advances in the areas of heart transplantation, heart-lung transplantation, mechanical assist devices and the artificial heart. A few issues of current interest in heart transplantation are selected for discussion.

Follow-Up Studies↗
PubMed1990

Liver transplantation in cancer--a review.

Whilst liver transplantation is an accepted therapeutic modality for end stage cirrhosis, its application for hepatic malignancy has remained a controversial issue. This is due to the early experience in several centres of tumour recurrence within the first year. More recently, stringent patient selection criteria have been established to decrease the risk of tumour recurrence. Pre-operative assessment including liver biopsy, computerised axial tomography (CT) of both the thorax and abdomen, bone scans and pre-transplant laparotomy are routinely performed to exclude extrahepatic spread. Of the primary tumours, the most common groups are the hepatocellular carcinomas (HCC) and cholangiocarcinomas. A hierarchy of tumours favourable for transplantation exists, with HCC giving the best results, followed by central bile duct carcinoma, cholangiocellular carcinoma (peripheral), and secondaries, in descending order of suitability. With better patient selection based on adequate staging, and the confinement of liver grafting to lymph node negative stages, there has been a marked improvement in survival in otherwise unresectable and mainly untreatable tumours. The improved results support the application of liver grafting for malignancy, and suggest that the often discussed danger of tumour growth enhancement because of immunosuppression may not significantly be present. Despite the risk of tumour recurrence, liver transplantation gives worthwhile survival with the chance of cure for some and in others, considerable palliation with prolonged survival.

Humans↗