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Biomedical subjects

K W Chan

Publications and source records attributed to K W Chan.

At least 19 recordsLinked to original sources

Interferon treatment for hepatitis B-associated membranous glomerulonephritis in two Chinese children.

Two Chinese boys, aged 3.5 and 5 years, developed nephrotic syndrome and were chronic carriers of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg). Renal biopsy showed membranous glomerulonephritis and liver biopsy showed chronic persistent hepatitis. They were given interferon-alpha-2a at a dose of 5 MU/m2 on alternate days for 12 and 16 weeks after 2 years of persistent nephrotic syndrome. Patient 1 showed complete remission and resolution of hepatosplenomegaly, but his serum remained positive for HBsAg, HBeAg and hepatitis B virus DNA. Patient 2 showed only a transient clinical response and seroconversion from HBeAg to anti-HBe status. Although not always successful, interferon treatment should be considered in severe persistent nephrotic states, since there is at present no satisfactory treatment for this form of glomerulonephropathy.

Biopsy

Patterns of interchange in the dispensing of non-steroidal anti-inflammatory drugs.

Patterns of change in dispensings of non-steroidal anti-inflammatory drugs (NSAID) were evaluated from the pharmacy records of a health maintenance organization (HMO). Overall, 52.8% of NSAID prescriptions were followed by another NSAID prescription within 60 days. Among patients for whom NSAIDs were dispensed twice within 60 days, 15% received a different NSAID. Switching between NSAIDs was more frequent in younger age groups; there was no difference between males and females. Chronic and non-chronic indications for NSAID use were associated with similar probabilities of switches between drugs among repeat users. NSAIDs that were frequently switched to for lack of efficacy or for prior toxicity of other NSAIDs were not as a whole themselves associated with more frequent switches for the same reasons.

Adolescent

A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D.

We evaluated the effects of the intravenous administration of anti-D, an immune globulin directed at the D antigen on erythrocytes that is purified from plasma from sensitized persons, on patients with idiopathic thrombocytopenic purpura. To determine the most effective dose, the duration of response, and the side effects of this therapy in children, we performed a multicenter cohort study of escalating doses of intravenously administered anti-D in children aged 1 to 18 years with chronic idiopathic thrombocytopenic purpura, defined as idiopathic thrombocytopenic purpura persisting for more than 6 months with a platelet count of less than 50 x 10(9) cells/L. Twenty-five Rh-positive children received increasing doses of anti-D as follows: day 1, 25 micrograms/kg; day 2, 25 micrograms/kg; day 7, 35 micrograms/kg; day 14, 45 micrograms/kg; and day 21, 55 micrograms/kg. Administration of anti-D was stopped after day 21 or when the platelet count rose to greater than 150 x 10(9) cells/L or the hemoglobin level was 100 gm/L. Platelet count was less than 50 x 10(9) cells/L in all children before treatment. A response was defined as an increase in the platelet count to more than 50 x 10(9)/L and a doubling of the pretreatment platelet count. Of 25 children, 23 (92%) had responses by day 7 of the initial treatment protocol. Eighteen children (72%) had platelet counts greater than 150 x 10(9) cells/L by day 7 after two doses of anti-D. Median duration of response was 5 weeks (range 1 to 24 weeks). Average drop in hemoglobin level was 13.7 gm/L; in one child (a nonresponder) hemoglobin value fell to less than 100 gm/L. No other untoward side effects were seen. Of the 23 children who responded, 21 were retreated with one dose of anti-D when platelet counts returned to baseline values of less than 50 x 10(9) cells/L; all but three of the children who underwent retreatment showed a response the second time. Sixteen children continued to receive intermittent anti-D therapy after completion of the study, and all continued to have excellent responses. We conclude that anti-D is a safe, effective, and relatively inexpensive therapy for childhood chronic idiopathic thrombocytopenic purpura.

Adolescent

Early prediction of anthracycline cardiomyopathy using standard M-mode and digitized echocardiography.

In this study, we attempted to identify echocardiographic findings that can be used as early predictors of left ventricular dysfunction due to anthracyclines in 26 pediatric oncology patients. Retrospective review identified six patients (group 1 mean anthracycline dose = 337 +/- 123 mg/m2) who developed clinical evidence of cardiomyopathy and 20 consecutive patients followed prospectively (group 2 mean anthracycline dose = 298 +/- 102 mg/m2) who did not. All of the patients had serial m-mode echocardiography before and at approximately every 50 mg/m2 of anthracycline treatment depending on the dosage schedule. The following measurements were recorded: left ventricular dimensions and wall thickness, indices of left ventricular function, including systolic time intervals, shortening fraction, and ejection fraction. Using digitized echocardiography, the following parameters were recorded: peak and normalized systolic and diastolic velocities of the left ventricular chamber, posterior and septal wall velocities, and percent of posterior wall thickening. Variations from established normal longitudinal bounds and actual changes from pre-anthracycline values were compared for the two groups throughout the course of therapy. At 70 mg/m2 of anthracycline, group 1 showed significant deterioration in shortening fraction (mean change = 8.8 versus 2.5, p = .03), left ventricular velocity in diastole (2.9 versus 0.21, p = .04), left ventricular normalized velocity in systole (.65 versus 0.03, p = .02), and left ventricular normalized velocity in diastole (1.15 versus 0.002, p = .04) compared to group 2. These values were mostly compensated by 125 mg/m2, but they slowly deteriorated again at higher doses of anthracycline, leading to the appearance of clinical evidence of cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Wolman's disease: a review of treatment with bone marrow transplantation and considerations for the future.

Wolman's disease is a fatal disorder characterized by absence of acid lipase and accumulation of cholesterol esters. Inanition due to malabsorption and intractable diarrhea has been the most prominent cause of early demise within the first year. Further complications have included cirrhosis and pulmonary failure due to cholesterol ester storage in respective cells. Although sustained caloric balance can be maintained by total parenteral nutrition, this has not altered the eventual course of disease. The acid lipase deficiency in leucocytes in Wolman's disease can be corrected subsequent to bone marrow transplantation. This has proven to be the case in two patients so transplanted. In two other patients, engraftment was not obtained following bone marrow transplantation. The concept of treatment of Wolman's disease by providing normalization of the acid lipase activity by allogeneic bone marrow transplantation remains valid. However, improvement of bone marrow transplant procedure needs to be implemented since pre-existing morbid pathology enhances toxicity and may prevent engraftment. Alternative modifications for accomplishing sustained engraftment without toxicity need to be examined. Other potential therapies need to be inspected in treatment of patients with Wolman's disease. The capability of reducing cellular cholesterol synthesis by use of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, is now available. In the future, isolation and purification of acid lipase will allow for direct infusion of missing enzyme. The molecular biology now known concerning acid lipase gene holds promise for the future for recombinant manufacturing of acid lipase. And, gene therapy with its use of autologous bone marrow transplantation will be tried in future.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation

Autologous blood transfusion for pediatric bone marrow donors.

Nine normal bone marrow donors aged 7-166 months (median 69 months) received autologous red cells which had been removed from their marrow harvest after collection. The median volume of marrow removed from the donors was 18.6 ml/kg which was equivalent to a median blood volume loss of 23.3%. Three infant donors were transfused with autologous red blood cells intraoperatively. These cells had been salvaged from the initial marrow aliquot and were transfused while bone marrow harvesting continued. No donors required homologous blood transfusion. This technique is useful for marrow donors in the pediatric age group when preharvest autologous blood collection is not feasible or available.

Adolescent

Focal sclerosing glomerulopathy. Risk factors of progression and optimal mode of treatment.

Focal sclerosing glomerulopathy and especially focal segmental glomerulosclerosis (FSGS) have been recognized as a distinct clinical entity, however, there still exist controversies in terms of prognostic risk factors of progression and optimal mode of treatment. A total of 32 patients (2 with focal global sclerosis; FGS, the remainder with FSGS) were followed up for a mean period of 82 months (3-240 months). Fourteen presented with nephrotic syndrome and 18 had proteinuria with or without hypertension. Thirteen patients, all of whom except 1 were nephrotic, received steroid treatment with or without other immunosuppressive agents (cyclophosphamide/cyclosporin A/azathioprine). Three of the steroid-treated remained stable in complete remission; 5 nephrotic non-responders had renal death. The mean slope of 1/creatinine versus time for steroid-treated and non-treated groups was -0.23 and -0.043, respectively (p = 0.04), suggesting that nephrotic range proteinuria might be prognostically important. However, for the population of FSGS/FGS as a whole, only the initial serum creatinine predicted renal survival (p = 0.001 by Cox's regression model). Hypertension and hypercholesterolaemia were not important variables by themselves. Nevertheless, we found that the 9 patients treated with antihyperlipidaemics (gemfibrozil/probucol/cholestyramine/maxEPA) fared better, mean slope being -0.023 versus -0.103 for non-treated, though not reaching statistical significance (p = 0.96). Controlled prospective study involving a larger number of patients might be worthwhile.

Adolescent

Amelioration of gentamicin nephrotoxicity by phospholipids.

The effect of phospholipids on gentamicin-induced nephrotoxicity was studied in Sprague-Dawley rats. Group 1a (5 rats) were given daily intraperitoneal injections of 100 mg/kg of gentamicin and sacrificed on day 7. Group 1b (10 rats) were similarly treated but were sacrificed on day 14. Group 2a (5 rats) were given 30 mg/kg of phospholipids for 6 days and sacrificed on day 7, serving as phospholipid controls. Group 2b (5 rats) were similarly treated, and from day 7 onwards daily intraperitoneal injections of 100 mg/kg of gentamicin were given while oral phospholipids were continued until the rats were sacrificed 7 days after gentamicin treatment. Group 2c (10 rats) were treated in the same manner as group 2b but the animals were sacrificed on day 28 after gentamicin treatment. Group 3 (10 rats) were given 30 mg/kg of phospholipids concurrently with intraperitoneal gentamicin injections and were sacrificed on day 28. Protein concentrations, N-acetyl-beta-glucosaminidase (NAG) activities and creatinine were measured in 24-h urine samples. Serum creatinine concentrations were measured in blood samples and 24-h creatinine clearance calculated. Gentamicin concentrations were determined in kidney tissues from which sections were also taken for light- and electron-microscopy. Results showed that gentamicin induced a marked increase in NAG and protein excretion, and a marked decrease in creatinine clearance with six rats succumbing to uraemia. Phospholipid treatment, whether started before or concurrently with gentamicin injections, reduced gentamicin-induced nephrotoxicity. The rats did not lose weight. Urinary excretion of NAG and protein was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase

Crescentic IgA glomerulonephritis following interleukin-2 therapy for hepatocellular carcinoma of the liver.

A patient who developed crescentic IgA nephropathy following treatment with recombinant interleukin-2 (rIL2) and lymphokine-activated killer (LAK) cell therapy for hepatocellular carcinoma was reported. Cessation of rIL2 and LAK cell treatment plus plasmapheresis and steroid therapy was successful in achieving partial improvement and stabilization of renal function. This is the first case report of biopsy-documented glomerulonephritis developing after IL2 and LAK cell therapy. This provides indirect in vivo evidence for the role of IL2 in mediating glomerular injury in IgA nephropathy.

Biopsy

A patient with focal segmental glomerulosclerosis and acute renal failure due to crescentic membranoproliferative glomerulonephritis.

We report a patient with relapsing nephrotic syndrome since the age of 4. Initial renal biopsy showed minimal change disease then focal segmental glomerulosclerosis. At the age of 21, he developed pulmonary tuberculosis, was treated with intermittent combination chemotherapy including rifampin and had oliguric acute or chronic renal failure 5 months later. Biopsy revealed crescentic membranoproliferative glomerulonephritis. The cause of the sequential glomerulonephritis is discussed.

Acute Kidney Injury