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Biomedical subjects

C H Lim

Publications and source records attributed to C H Lim.

At least 19 recordsLinked to original sources

The role of glutathione in the acute nephrotoxicity of sodium dichromate.

Ascorbate treatment 30 min prior to sodium dichromate (20 or 30 mg/kg, s.c.) shows higher potency than that of glutathione (GSH) in protecting against both the metabolic disturbance and nephrotoxicity induced by dichromate. However, ascorbate treatment after 2 h of dichromate intoxication had no effect on dichromate-induced blood urea nitrogen (BUN) elevation 3 days after intoxication. In contrast, dichromate-induced glucosuria, which reached maximum levels at 3 days after treatment, was significantly decreased by GSH or N-acetyl cysteine (NAC) treatment, even if its administration was after 24 h of dichromate intoxication. Pretreatment with GSH depletors such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) had no effect on dichromate-induced nephrotoxicity. GSH levels in the liver and kidney were not affected at 3 h after dichromate treatment. However, dichromate significantly increased tissue GSH levels with a marked increase in liver per kidney GSH ratio at 24 h after treatment, if food was withheld subsequent to dichromate treatment, indicating that GSH biosynthesis resulted from the accelerated protein breakdown. These results suggest that GSH-mediated dichromate reduction is not a kinetically favorable pathway in vivo; however, GSH plays an important role in protection against dichromate-induced nephrotoxicity. In addition, the cellular metabolism of dichromate in the early period after treatment is important in the pathogenesis of its nephrotoxicity.

Animals

Cytomegalovirus infection in renal transplant patients with hepatitis B--case report.

Cytomegalovirus (CMV) infection in Hepatitis B carrier renal transplant patients who are immunosuppressed can be easily overlooked especially in those presenting with jaundice and liver failure. Recognising hepatitis due to CMV in renal transplant patients who are also hepatitis B carriers is important therapeutically as measures for the treatment and prevention of CMV infection are already available. This is especially so as Hepatitis B has a moderately high prevalence in this part of the world. We describe our clinical experience of cytomegalovirus infection in two renal transplant patients who are also asymptomatic hepatitis B carriers.

Adult

The impact of HLA match transfusions and presensitization on renal transplantation in the cyclosporine era.

The successful engraftment of a renal transplant is dependent on multiple factors, immunological factors being of major importance. Specifically, histocompatibility, lymphocytotoxic antibodies and pretransplant blood transfusions have been shown to play a major role in determining graft outcome in renal transplant recipients receiving Azathioprine-Prednisolone immunosuppression. The impact of the immunosuppressive drug, Cyclosporine on graft outcome in relation to established risk factors were examined among 116 cadaveric and 34 living related renal allograft recipients from our center. Histoincompatibility and pretransplant blood transfusions did not significantly affect graft survival among cadaveric transplant recipients. Similarly, graft survival was not significantly different between two haplotype-matched and less well-matched living-related graft recipients (75% versus 96.5% respectively). On the other hand, lymphocytotoxic antibodies remained a major risk factor for immunologically mediated graft loss among cadaveric graft recipients (48.0% versus 92.2% four year graft survival among those with and without antibodies respectively). These results suggest that Cyclosporine has abrogated some immunological risk factors in renal transplantation.

Adult

Pharmacokinetics and nephrotoxicity of cyclosporine.

Cyclosporine (CsA) is a potent immunosuppressive agent which has dramatically improved graft and patient survivals in clinical solid organ transplantation. However, CsA nephrotoxicity (NTX) is the most frequent and serious side effect of CsA therapy and occurs in a significant proportion of patients. The clinical presentation of NTX is that of reduced creatinine clearance, elevation of serum creatinine and a disproportionate rise in blood urea. The clinical picture occurs as three syndromes, namely acute, subacute and chronic CsA NTX. Regardless of the clinical syndrome, the pathoaetiology of NTX is related to decline in renal blood flow and increase in renal vascular resistance probably due to CsA induced changes in renal haemodynamics. Unfortunately, the dose that yields an optimal therapeutic index, namely maximal efficacy with minimal toxicity has yet to be defined. Optimal dosing is confounded by not only inter and intraindividual variabilities in drug absorption, distribution and metabolism, but also by the lack of a clear relationship between drug efficacy and trough CsA level monitoring. This paper describes the pharmacokinetics and nephrotoxicity of CsA and evaluates various strategies to overcome this toxicity.

Absorption

Maintenance haemodialysis in Singapore.

The chronic haemodialysis programme of the Singapore General Hospital started in 1968 as a hospital-based fully nurse-assisted programme. This has since expanded to include Self Dialysis and Home Dialysis programmes. Data of 425 patients who entered the dialysis programmes was analysed retrospectively. The major cause of end stage renal failure was chronic glomerulonephritis (52%). Almost half of the patients in the haemodialysis programme were patients on self-dialysis (49%). There were 157 withdrawals and 116 deaths. Survival has improved tremendously with the use of treated water for dialysis from 1981. The 5 year survival in an earlier group of patients dialysed with untreated water was 48% compared with 81% in a late group dialysed with treated water (p less than 0.001). The pattern of complications has also changed with a lower incidence of dialysis osteomalacia, hypertension, hepatitis and eradication of dialysis dementia.

Acute Kidney Injury

Pattern of proteinuria in IgA nephritis by SDS-PAGE: clinical significance.

Of sixty patients with IgA nephritis, none had CRF at first examination, 13 developed CRF with creatinine above 1.6 mg/dl within 6 years. Among these patients who had analysis of proteinuria by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), 31 patients had middle molecular weight (MMW) proteinuria alone (pattern 1), 10 had MMW and Low MW (LMW) or tubular proteinuria (pattern 2), 10 had high MW (HMW) and MMW proteinuria (Pattern 3) and 9 had HMW, MMW and LMW proteinuria (Pattern 4). At the end of a follow up period of 6 years (1983-1989) patients with mixed proteinuria had a higher incidence of chronic renal failure (CRF), 11/29 (38%) compared to those with pattern 1 proteinuria, 2/31 (6%) (chi 2 = 8.7, p less than 0.005). Based on the glomerular selectivity index (GSI), 19 patients had nonselective proteinuria but they did not have a higher incidence of CRF. By the selectivity index (SI), 18 patients had nonselective proteinuria and they showed a significantly higher incidence of CRF. Compared to the 41 patients who did not have LMW proteinuria, 19 patients with LMW proteinuria had more severe proteinuria. After a follow-up period of 6 years, patients with LMW proteinuria had a higher incidence of CRF (10% versus 47%, p less than 0.001). The presence of LMW proteinuria indicates a less favourable outcome and the pattern of proteinuria as assessed by the SDS-PAGE appears to be a better prognostic index in IgA nephritis than the SI and the GSI.

Adult

Acute renal failure prognostic indices in hospital inpatients referred for haemodialysis.

Forty-eight patients with acute renal failure (ARF) who were referred to the Department of Renal Medicine, Singapore General Hospital for acute dialysis between August 1985 and August 1989 were studied retrospectively to identify risk factors associated with ARF that serve as prognostic indicators. There was no difference in the mean age of survivors and non-survivors (49.5 +/- 17.5 years vs 53.5 +/- 18 years, p greater than 0.05). The overall mortality rate was 52%. ARF as a result of surgical complication had a higher mortality rate in comparison to ARF from medical complications (66% vs 50%, p greater than 0.05). Septicaemia was the most common cause of ARF requiring dialysis. Hepatobiliary sepsis was the most frequent cause of septicaemia. Pre-dialysis serum urea and creatinine levels, and the number of dialysis treatments did not affect the outcome. Poor prognostic indicators included oliguria or anuria, fluid overload and coma. Patients tended to have a worse outcome if they had more than three risk factors taken from the following list:-decreased renal perfusion, assisted ventilation, coma, gastrointestinal dysfunction, recent surgery, sepsis, congestive heart failure, hepatobiliary dysfunction, malignancy, diabetes mellitus, chronic renal insufficiency and poor nutritional status. Early referral of patients with septicaemia due in particular to hepatobiliary infection may improve the prognosis.

Acute Kidney Injury

Effects of triple therapy in IgA nephritis: a follow-up study 5 years later.

This study is a 5-year post trial assessment of patients with IgA nephritis who entered a 3-year prospective controlled trial of cyclophosphamide, dipyridamole (D) and low-dose warfarin (W). Patients entered the trial from 1979 to 1981 and the trial ended in 1984 with those in the treatment group having more stable renal function and less proteinuria compared to the control group. Present reassessment of the patients in 1989 showed no difference in the renal function between those in the treatment group (n = 27) and the control group (n = 21). 6 patients in the treatment group and 7 in the control group were in ESRF. At the conclusion of the trial in 1984, among the 27 patients in the original treatment group, 13 patients elected to continue with D + W while the other 14 patients chose to cease therapy and therefore served as the new control group. 5 years later, renal function in the new treatment group (n = 13) was significantly stable compared to the new control group (n = 14), (serum creatinine 1.4 +/- 0.7 versus 4.4 +/- 3.2 mg/dl, p less than 0.01). Furthermore, all the 6 patients with ESRF in the original treatment group of 27 patients were from the new control group (n = 14) where treatment with D + W had been ceased. None of the patients still on D + W are in ESRF.

Adult

beta-Adrenergic blocking action of halonitrophenethanolamines.

A series of phenethanolamines with N-isopropyl and N-tertbutyl substituents and ring-substituted with nitro- and halogen groups has been prepared. Using guinea-pig isolated atrial and tracheal preparations, the influence of the nitro-group on the beta 1- and beta 2-antagonist actions of the mono-halogen compounds was determined, and the antagonist and partial agonist effects of the halo-nitro-compounds on beta-adrenoceptors in these tissues measured to help elucidate structure-activity relations in this series. The halonitro compounds did not show enhanced activity compared with the mono-halogen substituted analogues. Several of the new compounds showed slight but significant beta 2-antagonist selectivity of action, and one compound was significantly beta 1-selective.

2-Hydroxyphenethylamine

Corneal nerve access in monkeys.

Electron microscopical examination of corneal nerves in rhesus and cynomolgous monkeys revealed that limbal, subepithelial nerves gained direct access to the corneal epithelium. Epithelial axons occurred singly and infrequently and they were confined to the basal layer of cells. All nerves of the stroma terminated within the layer and rami perforans were not found. The apparent barrier to nerve passage presented by Bowman's layer in monkeys was discussed in relation to primates in general. The isolation of stromal and epithelial nerve fibres confirms that terminals occur in both layers and their respective potential for excitation was briefly discussed.

Animals

2-Methoxyphenylethanolamines, potential beta-adrenergic blocking agents.

The effect of the introduction of a 2-methoxy substituent on the beta-adrenergic antagonistic properties of a series of 3- and 4-substituted phenylethanolamines (1) was studied. Both the series of bromo- and methyl-substituted compounds behaved similarly, indicating that electronic forces are not significant in determining beta-adrenergic antagonist activity. When compared with the corresponding phenylethanolamines without a 2-methoxy substitutent, the 2-methoxy-4-substituted derivatives (3a and 3d) had enhanced potency and selectivity but the 2,3- (3b and 3e) and the 2,5-disubstitution patterns (3c and 3f) showed a loss of activity. The inconsistent changes in activity prevented any firm conclusions being made about the effect of the ether oxygen and the beta-adrenoceptor antagonistic activity of phenoxypropanolamines.

Adrenergic beta-Antagonists