Biomedical subjects
Publications and source records attributed to M K Chan.
Zygomycosis often occurs in patients with an underlying disease, e.g., diabetes mellitus, leukemia, and lymphoma, or an immunocompromised state. This report discusses a case of a 21-year-old woman with systemic lupus erythematosus complicated by uremia, acidosis, steroid therapy, prolonged antimicrobial therapy, and disseminated zygomycosis.
Renal response to a 60 g protein load was investigated in 33 normal subjects in terms of creatinine clearance and urinary protein excretion. The test was repeated in 10 of these subjects six months after donor nephrectomy. Creatinine clearance and urinary protein excretion increased significantly one and two hours after ingestion of the protein load (in the form of casein mixture); the change in urinary protein excretion correlated significantly with the change in creatinine clearance (p less than 0.0001). Plasma urea, calcium, and phosphate concentrations increased after protein ingestion, while plasma creatinine and uric acid decreased. Six months after donor nephrectomy the creatinine clearance had decreased but baseline protein excretion had increased. The pre-nephrectomy renal response to protein ingestion (i.e. increase in creatinine clearance and urinary protein excretion) did not predict creatinine clearance of the kidney after donor nephrectomy. After donor nephrectomy, the single kidney was able to increase creatinine clearance after a protein load, although qualitatively the response was different from that obtained with two kidneys in situ.
The clinical course and biopsy findings of twenty-one patients with IgA nephropathy, followed up for a mean period of 37.4 mth (range 24-54 mth) after diagnosis, were reviewed retrospectively to determine whether the clinical presentations, the laboratory findings or histopathologic changes have prognostic implications. An age of 24 yr or above and a serum creatinine of 0.18 mmol/l or above at diagnosis correlated significantly with renal insufficiency at the end of the follow-up (P = 0.023 & 0.03). Proteinuria of 1.5 g/d or more and hypertension (systolic greater than 150 mmHg or diastolic greater than 100 mmHg) when well controlled, were not found to be significant. Asymptomatic proteinuria and gross hematuria, on the other hand, correlated negatively with renal insufficiency at the end of the follow up (P = 0.034). With respect to histopathological changes, greater than 30% global glomerular sclerosis and moderate or marked tubular atrophy correlated significantly with renal insufficiency (P = 0.005 and 0.005). However, less than 10% glomerular crescents, small amounts of mesangial electron dense deposits or absent ultrastructural peripheral glomerular capillary wall abnormalities correlated negatively with renal insufficiency (P = 0.017, 0.03 & 0.03).
Hypoglycemia is frequently reported in hemodialysis patients on propranolol. The effects of beta-blockers on the glucose, alanine and free fatty acid responses to glucagon challenge (2 mg) in fourteen hemodialysis patients were studied. Patients on propranolol had impaired glycemic response while those on metoprolol had decreased response only before dialysis. There was a significant negative correlation between propranolol level (log-transformed) and glycemic responses, suggesting that propranolol has direct effect on the latter. Hemodialysis patients had fasting alanine levels comparable to those of normal subjects. After glucagon challenge, the decrements in alanine level had no consistent relationship to the impaired glycemic response. Thus suppression of gluconeogenesis is unlikely to be the prime cause of propranolol-induced hypoglycemia. The basal free fatty acid levels were significantly lower among hemodialysis patients on propranolol. This limited availability of free fatty acid as well as the inhibitory effect on hepatic glucagon-stimulated glucose output may contribute to the predisposition to hypoglycemia in dialysis patients given propranolol. The results suggest that metoprolol has less interference on energy substrate supply in hemodialysis patients under fasting conditions.
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We have investigated the effects of hyper- and hypothyroidism (clinical and subclinical) on lipid metabolism, with special emphasis on serum high-density lipoprotein cholesterol, post-heparin plasma hepatic lipase and lipoprotein lipase activities. In 16 patients with hyperthyroidism, increased post-heparin plasma hepatic lipase activity, decreased serum total cholesterol and serum high-density lipoprotein cholesterol were found while lipoprotein lipase activity and serum triglyceride were normal. In six patients with overt hypothyroidism serum total cholesterol and triglyceride were increased, post-heparin plasma hepatic lipase and lipoprotein lipase were decreased while serum high-density lipoprotein cholesterol was normal. In six patients with subclinical hypothyroidism, serum total cholesterol was increased, serum high-density lipoprotein cholesterol was decreased, while serum triglyceride, post-heparin plasma hepatic lipase and lipoprotein lipase were normal. When the three groups of patients became euthyroid, serum total cholesterol, serum triglyceride, post-heparin plasma hepatic lipase, lipoprotein lipase, and serum high-density lipoprotein cholesterol reverted to normal except for serum high-density lipoprotein cholesterol in the hyperthyroid group which showed no significant change with treatment. A positive correlation was found between serum T3 and post-heparin plasma hepatic lipase while negative correlations were found between serum total cholesterol and serum T3, post-heparin plasma hepatic lipase and serum total cholesterol, lipoprotein lipase and serum triglyceride respectively. Thus in these patients with thyroid dysfunction, significant reversible alterations in serum total cholesterol, triglyceride and high-density lipoprotein cholesterol were found and could be correlated with the observed changes in the activities of hepatic lipase and lipoprotein lipase.
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We have examined the effects of anti-inflammatory and anti-rheumatic drugs on membrane-bound and purified Na+/K+-ATPase activity in vitro. Only the gold-containing compounds (gold sodium thiomalate and auranofin) were found to inhibit the enzyme activity in a dose-dependent manner. Sodium thiomalate and triethylphosphine, the ligand compounds for gold sodium thiomalate and auranofin, respectively, had no effect on ATPase activity. The antagonistic properties was abolished by preincubation of the gold compounds with dithiothreitol. Lineweaver-Burke analysis of the inhibitions of purified ATPase by the gold compounds was found to follow uncompetitive kinetics. Inhibition of ATPase by gold may cause disruption of transmembrane cation transport and thus result in impairment of several metabolic processes and cellular functions.
Effects of oral administration of equipotent antihypertensive doses of propranolol and nadolol on renal function were examined in 20 hypertensive patients with moderately impaired renal function. Creatinine clearance increased, and serum beta 2-microglobulin concentrations decreased, when patients were switched from propranolol to nadolol therapy (creatinine clearance = 46.7 +/- 4.9 ml min-1 on propranolol and 52.7 +/- 5.9 on nadolol; beta 2-microglobulin = 6.14 +/- 0.66 mg l-1 on propranolol and 5.62 +/- 0.62 on nadolol). When patients were put back on propranolol, their creatinine clearances (45.9 +/- 5.0 ml min-1) and serum beta 2-microglobulin concentrations (6.51 +/- 0.67 mg l-1) returned to values comparable to those obtained before the change to nadolol was made. Serum beta 2-microglobulin concentrations correlated significantly with creatinine clearance (r = -0.819, P less than 0.001).
The clinical course of a woman with systemic lupus erythematosus demonstrated that renal involvement in this disease can change, both in the predominant site of renal injury and in the pattern of glomerular lesions. Over 50 months she had first tubulo-interstitial lupus nephritis with no glomerular change, then a membranous nephropathy with disappearance of tubulo-interstitial inflammation, and finally crescentic glomerulonephritis. This case emphasizes the need for close follow-up of all lupus patients regardless of their initial renal manifestations and pathology.
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Pharmacokinetics of cefuroxime was studied in patients on continuous ambulatory or intermittent peritoneal dialysis. A single intravenous bolus (15 mg/kg) of cefuroxime provided a mean serum concentration of 86 mg/litre 5 min, 40 mg/litre 1 h, 163 mg/litre 24 h after the injection. The peritoneal clearance of cefuroxime varied widely among different individuals, ranging from 1.45 to 6.17 ml/min with a mean of 3.59 ml/min during 4-hour exchanges, and from 0,52 to 11.3 ml/min during 2-hour exchanges. A single injection (15 mg/kg) of the antibiotic could not provide satisfactory antibiotic concentrations in peritoneal effluent during peritoneal lavage. When cefuroxime had been added to peritoneal dialysis solution before the solution was instilled into the peritoneal cavity, a significant decrease in cefuroxime concentration occurred in the peritoneal effluent even after a short equilibration time. Furthermore, cefuroxime concentrations measured in residual dialysis solutions in the plastic bags ranged from 44.3 to 1,351% of the concentration of cefuroxime calculated from the added doses, indicating that despite great care, mixing of the antibiotic with dialysis solutions in plastic bags was far from uniform.
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An epidemiological survey of filariasis and malaria in Banggi Island and Upper Kinabatangan, Sabah, revealed microfilarial rates of 7.2% and 8.6% respectively and malaria prevalence of 9.7% and 16.9% respectively. Wuchereria bancrofti was a rural nocturnally periodic type with a periodicity index of 137.2 and average peak hour at 01.32 hrs; 9.2% of microfilaremic carriers as compared to 2.4% amicrofilaremic subjects had clinical filariasis. The Plasmodium falciparum: P. vivax: P. malariae ratios were 1:1:0.17 and 1.4:1:0.12 for Banggi and Upper Kinabatangan respectively. Anopheles flavirostris was incriminated as a new malaria vector in Banggi where the well-known primary malaria vector is An. balabacensis. The latter was also found for the first time to be a vector of rural W. bancrofti in Upper Kinabatangan. Experimental feeding also showed that L3 larvae of W. bancrofti were recovered at low rates from An. balabacensis. Aedes togoi appeared to be a suitable laboratory vector for W. bancrofti.
In a retrospective study of 196 hospital admissions for systemic lupus erythematosus (SLE) over five years acute deterioration in renal function occurred in 36 admissions (18.4 per cent) and was the commonest mode of deterioration of renal function in SLE patients. Active lupus accounted for the majority of cases, with crescentic WHO IV lupus glomerulonephritis (greater than or equal to 50 per cent crescents) the commonest underlying pathology. In 19 per cent of these 36 admissions, it was most likely that concurrent infections at onset precipitated the episodes. Central nervous system lupus and infections were the major causes of death. Recovery of renal function was, however, achieved in 76 per cent using mainly pulse methylprednisolone and immunosuppressives as well as elimination of provoking factors especially infections.
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