Biomedical subjects
Publications and source records attributed to G S Chiang.
In this paper, we describe a child with Henoch-Schonlein nephritis presenting with nephrotic syndrome and selective proteinuria. Renal biopsy showed ISKDC Class IIIA nephritis. He responded to steroid treatment and is currently well. The significance of renal involvement in Henoch-Schonlein Purpura is discussed.
The value of anorectal manometry as a diagnostic tool for Hirschsprung's disease (HD) was assessed in 50 children presenting with chronic constipation. Anorectal manometric studies and rectal biopsy were performed on all children. Biopsy specimens were stained with hematoxylin and eosin and serial sections were examined for ganglion cells. Forty-five children had concordant manometric and histologic results, 15 of whom were positive for HD and 30 negative. In five children, the results were discordant. Using histologic aganglionosis as the reference point for the final diagnosis of HD, the overall accuracy of anorectal manometry as a discriminative test was 90.0%. The sensitivity, specificity, and positive and negative predictive values of manometric studies for the diagnosis of HD were 0.79, 0.97, 0.94, and 0.88, respectively. Factors responsible for the inaccuracies of manometric studies are discussed.
Among 98 patients with IgA nephritis who had protein selectivity studies performed, 54% had nonselective proteinuria and the remaining 46% had selective proteinuria. Patients with nonselective proteinuria had a higher incidence of glomerulosclerosis. At the end of a 4-year follow-up period, patients with nonselective proteinuria had lower creatinine clearance, higher incidence of hypertension and chronic renal failure when compared to patients with selective proteinuria. Six out of eleven patients (55%) in the study who had the nephrotic syndrome had selective proteinuria. Among these 6 patients, 1 had spontaneous remission and 5 responded to steroid or cyclophosphamide therapy. The remaining 5 patients with nonselective proteinuria did not respond to therapy. In the patients who had selectivity studies repeated, the data showed that the selectivity index (SI) can fluctuate depending on the clinical course of the patients. SI can therefore be used to monitor the progress of patients on long-term follow-up. Protein selectivity appears to be a useful prognostic index in IgA nephritis. For patients with the nephrotic syndrome it may serve as a guide to therapy.
This study was aimed at determining the pattern of glomerulonephritis (GN) in Singapore children from a histopathological perspective. Fifty-seven consecutive children, aged between 10 weeks to 16 years, who underwent a renal biopsy at the Departments of Paediatrics, National University of Singapore and Singapore General Hospital over an 8 year period were studied. The main indications for biopsy were nephrotic syndrome (67%), recurrent gross haematuria (16%), nephritic syndrome (7%), and renal failure (10%). Primary GN occurred in 81%, while secondary GN was seen in 19%, the most common being lupus nephritis. Of the primary GN, minor abnormalities was the most common (22%), followed by focal global sclerosis (20%), focal segmental glomerulosclerosis (17%), diffuse mesangial proliferative GN (11%), focal mesangial proliferative GN (9%), membranous GN (7%), diffuse endocapillary GN (4%), diffuse sclerosing GN (4%), diffuse mesangial sclerosis (4%), and diffuse crescentic GN (2%). Immunofluorescent examination was performed in 50 children. IgA nephropathy was diagnosed in 17% of the patients with primary GN. Of the children with primary nephrotic syndrome due to minimal change disease or focal global sclerosis, about half had IgM mesangial deposits. Of 47 patients who were followed up, 9 developed chronic renal failure, of which 7 reached end-stage disease (4 have died, while 3 are on chronic dialysis). Three other patients died of other complications. The histopathological findings influenced the therapeutic decision in 49% of our patients. In summary, the pattern of GN in our cohort of patients tended to reflect more severe glomerular lesions, mainly due to our criteria of selection for renal biopsy.
This study examined the frequency of anti-vascular endothelial cell (VEC) antibodies (Ab) in 72 patients with IgA nephropathy (IgAN), and their possible relationship to clinical and histological parameters of the disease. An enzyme immunoassay was developed to measure the binding of sera to endothelial cells grown to a confluent monolayer. Thirty-two percent of IgAN patients had serum anti-VEC activity as compared to 4% of controls (P = 0.004) and 9% of patients with other primary glomerulonephritis (P = 0.017). This was shown to be due to anti-HLA class I Abs in 6 of the 23 IgAN patients, and in the 1 control positive for anti-VEC activity. Hence 17 IgAN patients had anti-VEC Abs, predominantly of the IgA subclass. Stimulation of the endothelial cells with interferon-gamma and interleukin 1 did not increase the binding of these Abs. There was no correlation with circulating immune complex (IC) levels, and removal of ICs in positive sera by ultracentrifugation did not decrease anti-VEC binding. Significant correlations were found between anti-VEC Abs and proteinuria greater than 1 g/day (P = 0.044), as well as IgA anti-VEC Abs and C3 or IgA deposition in renal arterioles (P = 0.048). These IgA Abs may be an important marker of pathogenetic activity in IgAN.
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Among 151 patients with IgA nephritis, 18/151 (12%) had hypertension at presentation and 50/151 (33%) were hypertensive after an interval of 65 +/- 40 (Mean +/- SD) months. Hypertensive patients (n = 50) had a higher incidence of glomerulosclerosis, medial hypertrophy of blood vessels, tubular atrophy, poorly selective proteinuria and extension of immunodeposits to peripheral capillary walls compared to normotensive patients (n = 101). Chronic renal failure occurred more commonly among hypertensives compared to normotensive patients (42%) versus 14%. However, the time taken for patients to reach renal impairment or end stage renal failure was not significantly different. The cumulative renal survival for the hypertensive group was 78% after 8 years compared to 91% in the normotensive group (p less than 0.05). In the second part of the study, patients who were hypertensive at presentation (n = 18) were compared with those who developed hypertension on follow up (n = 32). Apart from a shorter duration of follow up for patients with hypertension and a higher incidence of glomerulosclerosis, there were no significant differences in their clinical presentation, laboratory indices or other histological parameters. The incidence of chronic renal failure and the time taken to reach end stage renal failure were not different. Uncontrolled hypertension was an important cause for rapid deterioration to end stage renal failure within 3 years, compared to 8 years when hypertension was controlled.
Forty-eight patients with IgA nephritis entered a 3 year controlled prospective trial using a combination regimen of cyclophosphamide for 6 months and dipyridamole and low dose warfarin for 36 months. Those in the treatment group (n = 27) had stable renal function and a significant decrease in proteinuria (p less than 0.01) but in the controlled group (n = 21) there was a significant fall in creatinine clearance (p less than 0.01) and rise in serum creatinine (p less than 0.02) with no change in proteinuria. The data suggested that the above treatment resulted in a significant reduction of proteinuria and more stable renal function. Eleven patients in the treatment group and 10 patients in the controlled group had repeat renal biopsies after the trial. Eight parameters were used in the evaluation of the renal biopsies: mesangial hypercellularity, crescents, tuft adhesion, segmental sclerosis, global sclerosis, tubular atrophy, interstitial fibrosis and vascular sclerosis. Each lesion was graded from 0 to 3 and a total scoring system used for evaluation of histological severity. In the treatment group there was no significant histological deterioration but in the controlled group there was progressive histological deterioration. Mean total histological score was 3.7 +/- 2.6 before the trial and 6.5 +/- 3.1 after the trial (p less than 0.05). This histological progression appeared to run parallel with the clinical course.
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Fifty-two pairs of patients with idiopathic diffuse mesangial proliferative glomerulonephritis entered a controlled 3-year prospective trial of a combination regimen of cyclophosphamide, dipyridamole and warfarin. In the treatment group proteinuria decreased significantly (p less than 0.01) and renal function remained stable, but in the control group there was no change in proteinuria and creatinine clearance (Ccr) decreased significantly (p less than 0.01). The time patients with renal impairment in the control group and those in the treatment group took to reach end stage renal failure was significantly different (6.1 years versus 8.9 years, p less than 0.02). Among the patients with IgA nephritis, those in the treatment group (n = 27) had stable renal function and a significant decrease in proteinuria (p less than 0.01) but in the control group (n = 21) there was a significant fall in Ccr (p less than 0.01) and rise in serum creatinine (p less than 0.02) with no change in proteinuria. Among 23 pairs of patients in the study who were matched for renal function and degree of glomerulosclerosis, those in the treatment group had stable renal function and decrease in proteinuria (p less than 0.01) whereas those in the control group had decreased Ccr (p less than 0.01) but no change in proteinuria.
The pattern of glomerulonephritis (GN) consisting of 1057 renal biopsies is presented. Primary GN accounted for 91% and secondary GN 9% of which the commonest is lupus nephritis. Asymptomatic haematuria and proteinuria was the commonest mode of presentation (41%), gross haematuria 9%, nephrotic syndrome 29% while 5.5% presented with renal impairment and 4.3% with hypertension. Mesangial proliferative GN is the commonest histopathological lesion forming 66% of all primary GN. Minimal Lesion, Focal Global Sclerosis and Focal Segmental Glomerulosclerosis accounted for 7% each. Membranous GN was uncommon (3%) while Mesangiocapillary GN, Diffuse Endocapillary GN and Crescentic GN were even rarer. If the presenting feature was asymptomatic haematuria and proteinuria the likely diagnosis was IgA nephritis, and, if nephrotic syndrome it was likely to be Idiopathic Mesangial Proliferative GN but with negative staining on immunofluorescence. The course and prognosis of the various forms of GN are next discussed. Nephrotic syndrome with Minimal Lesion has an excellent prognosis while Crescenteric GN usually carries a grim prognosis. Finally, factors affecting the progression of IgA nephritis, the commonest form of GN occurring in Singapore are examined. Patients who developed renal failure ran two different courses; one was a slowly progressive course over an average of 7.7 years before reaching end stage renal failure (ESRF), while the other was a more rapid decline to ESRF within an average of 3.3 years where severe uncontrolled hypertension seemed to be the major adverse factor. 9% had renal impairment at the end of a follow up of 50 + 1/2 - 34 months while 5% progressed to ESRF. The cumulative renal survival was 91% after 6 years with no further loss up to 14 years. Unfavourable long term prognostic indices were proteinuria of more than 2 gms, hypertension, crescents on renal biopsy, severe segmental sclerosis and medial hypertrophy of blood vessels.
The clinical and histological features of 151 patient with IgA nephritis were analyzed to determine the prognostic features of the disease. The mean duration of follow up examinations was 50 +/- 34 months (range 6 to 168 months). The majority of the patients were young males and showed no signs of IgA nephritis. The disease was detected by routine screening before induction into national service. The plot of the reciprocals of serum creatinine against time in the patients with progressive disease showed that the patients ran two different courses when they developed renal impairment; one was a slow progressive course over an average of 7.7 years before reaching end stage renal failure (ESRF), while the other was a more rapid decline to ESRF within an average of 3.3 years in which severe uncontrolled hypertension seemed to be the major adverse factor. Hypertension was present in 23% of patients. Nine percent had renal impairment at the end of the follow up period while 5% progressed to ESRF. The cumulative renal survival was 91% after 6 years with no further development of renal failure up to 14 years. Unfavorable long term prognostic indices were proteinuria of more than 2 gm, hypertension and presence of crescents on renal biopsy.
Eight cases of pulmonary sarcoidosis with a mean age of 27.8 years were seen in our Department since May 1974. There were 5 males and 3 females and 5 of our patients were Chinese. 75% of cases were symptomatic at initial presentation. Extra pulmonary manifestation was seen in only one patient who had a right facial palsy. Hilar adenopathy was the principal radiological finding. (Bilateral hilar adenopathy was present in 6 and unilateral hilar adenopathy was seen in 1 patient) 50% of our patients had x-ray evidence of pulmonary parenchymal involvement and received steroid therapy. Though sarcoidosis is rare among Asians especially among Chinese, we feel an increase in prevalence can be expected in future.
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Malignant tumours with teratoid or blastomatous features are exceptionally rare in the upper respiratory tract with only 8 documented cases, including the 3 in this report. The tumours occurred in adults aged 27 to 62 yr, and the sites of origin were the ethmoid sinus (4 cases), ethmoid and other paranasal sinuses (2 cases), unspecified sinuses (1 case) and nasopharynx (1 case). The disease was rapidly fatal in 3 cases in which treatment was restricted to surgery and was associated with longer survivals in those given supportive radiotherapy. The tumours are locally aggressive and may invade soft tissues, bone, orbit and cranial cavity. Histologically, the tumours are characterized by a mixture of epithelial and mesenchymal components including cellular elements with immature or embryonal characteristics. These tumours, variously termed malignant teratoma, blastoma, teratocarcinoma or teratoid carcinosarcoma, probably comprise a homogeneous group of neoplasms since their histological and biological features are essentially similar. It is postulated that the tumours develop from primitive embryonic tissues or pluripotential cells that have remained sequestered in the sinonasal tract.
The renal biopsies of 100 patients presenting with the Nephrotic Syndrome were analysed. Eighty-seven percent were due to primary glomerulonephritis and the other 13% due to secondary glomerulonephritis of which Systemic Lupus Erythematosus was the commonest. Diffuse mesangial proliferative glomerulonephritis (DPGN) formed the largest group (60%). Minimal lesion occurred in 15% of patients and only 5% had Membranous Glomerulonephritis. 63% of patients with DPGN had negative staining on immunofluorescence. Even though Mesangial IgA Nephritis is prevalent in Singapore, it accounted for only 4% of glomerulonephritis causing the Nephrotic Syndrome.
The nephrotic syndrome complicating malignancy is an unusual occurrence. We report here four cases of nephrotic syndrome associated with malignant tumours. Three cases were associated with bronchogenic carcinoma and one with adenocarcinoma of colon. One of the four cases developed nephrotic syndrome before the discovery of bronchogenic carcinoma. All patients had renal biopsies with light microscopy, immunofluorescence and electron microscopy. The findings suggest an immune-complex disease complicating malignancy. The true incidence of nephrotic syndrome associated with malignant tumours is unknown. However it is clinically prudent to screen for malignancy in older patients presenting with nephrotic syndrome.