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Biomedical subjects

F T Lam

Publications and source records attributed to F T Lam.

At least 19 recordsLinked to original sources
PubMed2004

Acute rejection after renal transplantation is reduced by approximately 50% by prior therapeutic blood transfusions, even in tacrolimus-treated patients.

BACKGROUND: The authors investigated the relationship between therapeutic blood transfusion before renal transplantation and rejection rates in cyclosporine- and tacrolimus-treated patients. METHODS: In one center, 265 consecutive recipients were studied. Protocol induction was with azathioprine, prednisolone, and cyclosporine or tacrolimus; 37% had biopsy-proven acute rejection in the first 6 months and 46% had received zero to two units of blood before transplantation. RESULTS: Lower risk of rejection was associated with tacrolimus induction (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.29-0.95; P=0.049), prior transfusion of three or more units of blood (OR, 0.54; 95% CI, 0.33-0.90; P=0.024), and older age at transplantation (mean, 44.23 +/- 12.56 [+/- SD] years vs. 38.96 +/- 12.37 years; P=0.001). Multiple logistic regression modeling showed the effect of three or more prior transfusions on acute rejection was as follows: OR, 0.49; 95% CI, 0.29 to 0.83; P=0.008. CONCLUSIONS: Induction immunosuppression should take account of the higher risk of rejection in patients coming to transplantation who have previously received zero to two units of blood.

Acute Disease↗
PubMed2000

Conversion from tacrolimus to cyclosporin in stable renal transplant patients: safety, metabolic changes, and pharmacokinetic comparison.

BACKGROUND: Conversion from tacrolimus to cyclosporin has not previously been reported as routine clinical practice, but only as indicated by rejection or adverse effects. METHODS: The safety and metabolic outcome of elective conversion from tacrolimus to cyclosporin was examined in 19 recipients of cadaver renal transplants. Conversion was performed in stable patients at 3-6 months after transplantation. RESULTS: Patient and graft survival was 100% at 3 months after conversion, with no rejection episodes. Three patients have been subsequently converted back to tacrolimus, two for rejection and one for hirsutism. There were no significant changes in creatinine, urate, or blood sugar levels after conversion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82 (0.65-1) mmol/liter (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4-6.8) to 5.5 (3.8-7.6) mmol/liter (P=0.033). Pharmacokinetic profiles were measured before and after conversion, and showed that cyclosporin (Neoral) exhibited significantly less interpatient and intrapatient variability than tacrolimus, for area under the curve (AUC), maximum concentration postdose (Cmax), minimum concentration postdose (Cmin), time to maximum concentration (Tmax). CONCLUSION: This is the first study that has examined the outcome of conversion from tacrolimus- to cyclosporin-based immunosuppression in stable patients after renal transplantation. This conversion was performed without early immunological hazard, but there was a small rise in blood cholesterol levels after conversion. Pharmacokinetic studies showed cyclosporin in the form of Neoral showed less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.

Adult↗
PubMed2000

Conversion from tacrolimus to cyclosporine in stable renal transplant patients: safety, metabolic changes, and pharmacokinetic comparison.

BACKGROUND: Although conversion between tacrolimus and cyclosporine has been performed when indicated for rejection or adverse effects, the safety and metabolic outcome of elective conversion from tacrolimus to cyclosporine has not previously been examined. METHODS: Conversion from tacrolimus to cyclosporine was performed in 19 recipients of cadaver renal transplants at 3-6 months after transplantation. Pharmacokinetic profiles and biochemical studies were performed three times, in steady state, before, and after conversion. RESULTS: Patient and graft survival was 100% at 3 months after conversion, with no rejection episodes. Three patients have been subsequently converted back to tacrolimus, two for rejection and one for hirsutism. There were no significant changes in creatinine, urate, or blood sugar levels after conversion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82 (0.65-1) mmol/L (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4-6.8) to 5.5 (3.8-7.6) mmol/L (P=0.033). Pharmacokinetic profiles were measured before and after conversion, and showed that cyclosporine (Neoral) exhibited significantly less interpatient and intrapatient variability than tacrolimus, for area under the curve (AUC), maximum concentration after dose (Cmax), minimum concentration after dose (Cmin), and time to maximum concentration (Tmax). CONCLUSION: This is the first study that has examined the outcome of conversion from tacrolimus- to cyclosporine-based immunosuppression in stable patients after renal transplantation. This conversion was performed without early immunological hazard, but there was a small rise in blood cholesterol levels after conversion. Pharmacokinetic studies showed that cyclosporine in the form of Neoral exhibited less inter- and intrapatient variability than tacrolimus, although this is of uncertain clinical significance.

Adult↗
PubMed1999

Metastases from a regressed malignant melanoma as a cause of haemoperitoneum.

We report a case of metastasis from a regressed cutaneous melanoma presenting as an acute abdomen. The patient presented with peritonitis, which at operation was found to be due to intraperitoneal haemorrhage from a bleeding metastatic melanoma lesion in the ileum. Surgical resection was performed and the patient remained well 2 years later.

Adult↗
PubMed1998

Serial flow cytometric analysis of T-cell surface markers can be useful in differential diagnosis of renal allograft dysfunction.

We examined changes in the circulating T-cell subsets and their activation to see if consistent changes occur following renal transplantation, during acute rejection episodes (ARE), cytomegalovirus (CMV) infection, and cyclosporine (CsA) nephrotoxicity. Serial blood samples were taken from 28 patients on standard triple immunosuppresion therapy. Using two-colour flow cytometric analysis, the percentages of CD3+, CD4+, and CD8+ T-cells were determined, and coexpression of CD25, HLA/DR, and CD45 isoforms used to define their activation status. During ARE and CMV infection, increased levels of circulating CD4+ CD25+, CD8+ HLA/DR+, CD4+ CD45RO+, CD8+ CD45RO+ were observed. The increased levels of CD45RO+ T-cells were associated with a significant decrease in the percentages of CD45RA+ of both CD4+ and CD8+ T-cells. No significant changes were seen during CsA nephrotoxicity. The pattern of marker expression seen during ARE and CMV infection was similar to that seen in Con-A stimulated T-lymphocytes from 22 normal controls. We conclude that, the increase in the levels of these surface markers do not differentiate between lymphocyte activation indicative of rejection or infection, but clearly distinguish episodes of CsA nephrotoxicity. These results could be useful in the differential diagnosis of renal allograft dysfunction.

Acute Kidney Injury↗
PubMed1998

Organ transplantation from donor who died of cyanide poisoning: a case report.

Shortage of donor organs has become on of the most important limiting factors in the field of transplantation. Suitability of organs from patients dying from poisoning is an unexplored area. This is because of the suspicion that the organs, in particular the liver and the kidneys, might have been irreversibly damaged by the poison. We report a case of cyanide poisoning in which the kidneys and corneas were harvested after the level of poison fell to below lethal concentration. These organs were later transplanted without any evidence of adverse effects at follow-up.

Adult↗
PubMed1997

Clinical significance of selective decline of donor-reactive IL-2-producing T lymphocytes after renal transplantation.

Limiting dilution analysis technique was used to enumerate the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) in 28 renal allograft recipients before (pre-tx) and at three intervals (T1: 60-90 days, T2: 120-180 days, T3: 360-1620 days) after transplantation (post-tx). Two patterns of responses were identified, in group 1 (n = 12), a five to 31-fold reduction of donor-reactive HTLpf (ranging from 1/19231-1/62500) occurred within 90-1620 days post-tx, while in group 2(n = 16), no significant changes of donor-reactive HTLpf were seen. In both groups, the third-party-reactive HTLpf in most of these patients remained largely unchanged throughout the study period. The number of HLA-DR mismatches, total number of rejection episodes, serum creatinine levels, and biopsy findings at T3 were compared in both groups using Fisher's exact probability, and the Mann-Whitney test. We found that 11 patients (92%) in group 1 were HLA-DR compatible with donors, while nine (56%) patients in group 2 were HLA-DR compatible with donors, p = 0.04. In group 1 eight rejection episodes occurred in five (41.6%) patients during the study period, compared to 33 in 13 (81%) patients in group 2, p = 0.03. Group 1 had a significantly lower serum creatinine level (at T3); median: 136 vs 165 mumol/l for group 2, p = 0.03. Biopsy indicated no rejection (at T3) in eight (66%) patients in group 1 as compared to three (18%) patients in group 2, p = 0.03. Taken together, these results indicate that the frequency of circulating HTLpf correlate with the clinical status of the graft. Therefore monitoring of HTLpf in the peripheral blood could be useful in predicting graft outcome and selecting patients for reducing immunosuppression.

Adolescent↗
PubMed1997

Steroid withdrawal and donor-specific hyporeactivity after cadaveric renal allotransplantation on maintenance triple therapy.

BACKGROUND: Even in low doses, long-term steroid immunosuppression is known to cause serious complications. However, the safety of steroid withdrawal has not been proven in randomized clinical trials. This study examines donor-specific hyporesponsive transplant recipients before and after steroid withdrawal, to see if reduction in immunosuppression was associated with consistent changes in antidonor immunological reactivity. METHODS: Using limiting dilution assays, the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) were determined in 21 consecutive cadaveric renal allograft recipients on standard triple therapy, before (pre-tx) and at different time points after transplantation (post-tx). Patients were selected for steroid withdrawal by clinical criteria (stable graft function and no or only one very mild rejection episode). RESULTS: Of 21 patients studied, steroids were successfully withdrawn in nine (steroid withdrawn group, SWG) for at least 187 days (mean: 380 +/- 168.5), and were not withdrawn in 12 patients (steroid continued group, SCG). In the SWG seven of nine patients developed at least fivefold reduction of post-tx donor-reactive HTLpf (range 5-17), relative to pre-tx, as compared to two of twelve patients in the SCG, P = 0.01. In both groups, the third-party-reactive HTLpf in most of these patients remained largely unchanged throughout the study period. In the SWG, no significant difference of serum creatinine level was found before and at 6 months after steroid withdrawal (mean: 138 +/- 24 versus 132 +/- 40, P = 0.45). CONCLUSION: Patients who developed donor-specific hyporeactivity as evidenced by low donor-reactive HTLpf had stable graft function and stable HTLpf levels after complete steroid withdrawal.

Adult↗
PubMed1993

The reflush effect--a prospective analysis of late perfusion.

This prospective randomized trial examines the effect of a "reflush" with preservation solution immediately prior to renal allograft implantation, using hyperosmolar citrate (HOC, n = 10) or phosphate-buffered sucrose (PBS140, n = 10) versus no reflush (n = 10). All kidneys had been stored in HOC. The HOC reflush did not alter the postpreservation intra- or extracellular electrolyte milieu, whereas the PBS140 reflush resulted in an apparent overall loss of both sodium and potassium from the kidney (P < 0.0005). A small amount of calcium was released into the venous effluent in both reflush groups. A similar amount of lactic acid was released into the venous effluent of the two reflush groups, reflected by a lower pH (P < 0.0005), and there was a similar loss of lactate dehydrogenase and creatine phosphokinase. An analysis of procoagulant activity in the first urine produced was performed as a marker of reperfusion injury. The median value was higher in the No Reflush group at 457.5 units, compared with 263.0 and 209.0 units for the PBS140 and HOC Reflush groups, respectively (P = 0.06). Reflushing the kidneys reduced the postoperative dialysis requirement (from 40% to 15%), but by the end of the first posttransplant week there was no significant difference between the renal functional analyses of the three groups, and there was no difference at one year. The proposed mechanism for the early renal functional improvement is a reduction in the calcium paradox and free radical formation, by release of calcium and ATP breakdown products into the venous effluent prior to implantation.

Adolescent↗
PubMed1990

Ranolazine--a new drug with beneficial effects on renal preservation.

Ranolazine is a new drug with a novel mode of action as a metabolic modulator and membrane stabilizer. In this prospective randomized double-blind trial, a porcine model of renal autotransplantation was used to assess the effects of this drug during preservation and reperfusion of kidneys cold-stored for 24 hr in phosphate-buffered sucrose (PBS140). Three groups of 10 animals were compared: a Placebo group (placebo given intravenously to the animal before nephrectomy, added to the preservation solution, and given again to the animal during reperfusion); a Storage group (Ranolazine before and during storage, placebo during reperfusion); and a Reperfusion group (placebo before and during storage, Ranolazine during reperfusion). Detailed analysis of posttransplant renal function was carried out over a 14-day follow-up period. There were 7 deaths with primary nonfunction: 2 Placebo, 1 Storage, 4 Reperfusion. Analysis of the whole group and separate analysis of the survivors demonstrated significantly improved glomerular (P less than 0.05), tubular (P less than 0.05), and loop of Henle (P less than 0.05) function in the Storage group. The results of this study clearly demonstrate the beneficial effects of Ranolazine during the storage phase of porcine renal preservation, and further investigation of this drug is warranted.

Acetanilides↗
PubMed1989

Improved 72-hour renal preservation with phosphate-buffered sucrose.

The result of this study shows that a simple phosphate buffered sucrose solution (PBS) is better than hyperosmolar citrate (HOC) solution in the flush perfusion and hypothermic storage of canine kidneys for 72 hr prior to autotransplantation with immediate contralateral nephrectomy. The peroperative measurement of postreperfusion renal blood flow revealed a significant reduction after 60 min in kidneys preserved with HOC solution. All grafts and animals in the PBS group (5/5) survived with primary renal function compared with one in the HOC group (1/5), which functioned after a period of oliguria. The early serum creatinine and urea levels were significantly lower in the PBS group, with a return to normal range within two weeks. This is reflected in higher inulin clearances and a more rapid recovery of proximal tubular function in the PBS animals, which also demonstrated a more rapid return of loop function and the ability to concentrate urine.

Animals↗