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Biomedical subjects

S M Chong

Publications and source records attributed to S M Chong.

At least 19 recordsLinked to original sources

The teaching of pathology.

A/Professor Chong Siew Meng relates the teaching of Pathology in the Medical School since 1905. The Pathology Department of the College of Medicine is closely associated with the Department of Pathology of the Government Medical Service. Pathologists in the Government Medical Service taught medical students till 1955 when the chair of Pathology was filled by Professor R Kirts. Undergraduates and postgraduate teaching and research in the department are described briefly.

Education, Medical↗

Lymphocytic gastritis-like T cell lymphoma: molecular evidence of an unusual recurrence.

This report describes a patient with a gastric biopsy specimen showing histomorphological and immunohistochemical appearances indistinguishable from those usually present in lymphocytic gastritis, a rare condition of unknown aetiology with a distinctive phenotype. The patient had a history of a biopsy confirmed T cell non-Hodgkin lymphoma at two anatomical sites (bladder and stomach), which was subsequently treated. Molecular analysis of the T cell receptor (TCR) gamma chain gene rearrangements showed a distinct monoclonal T cell population in the bladder and gastric biopsies. The same analysis in the lymphocytic gastritis-like biopsy sample showed a monoclonal population with identical base pair size to that identified in the other specimens. This report highlights the importance of TCR gene rearrangement analysis in the diagnosis of unusual gastric inflammation, and the use of capillary electrophoresis based polymerase chain reaction in the follow up of lymphoproliferative disorders.

Antigens, CD↗

The natural history of spontaneous osteonecrosis of the medial tibial plateau.

The natural history of spontaneous osteonecrosis of the medial tibial plateau remains controversial and incomplete. We have studied 21 patients (aged between 53 and 77 years) with clinical and scintigraphic features of spontaneous osteonecrosis of the medial tibial plateau who were observed prospectively for at least three years (37 months to 8.5 years). The mean duration of follow-up was 5.6 years. The mean duration of symptoms at presentation was 4.7 weeks (3 days to 12 weeks). Radiographs of the affected knee at the first visit were normal in 15 patients and mildly arthritic in six. The characteristic radiographic lesion of osteonecrosis was noted at presentation in five of the mildly arthritic knees and during the evolution of the disease in eight of the radiographically normal knees. During the follow-up, subchondral sclerosis of the affected medial tibial plateau was noted in 16 knees. There are three distinct patterns of outcome: 1) acute extensive collapse of the medial tibial plateau in two knees within three months of onset; 2) rapid progression to varying degrees of osteoarthritis in 12 knees, in eight within a year, in all within two years and deterioration of the pre-existing osteoarthritis in three; and 3) complete resolution in four knees, two of which were normal at presentation and two mildly osteoarthritic. The two patients with acute extensive collapse and three who had rapid progression to severe osteoarthritis required total knee arthroplasty. We conclude that osteonecrosis of the medial tibial plateau progresses in most cases to significant degenerative disease of the knee.

Acute Disease↗

The 3-week sulphasalazine syndrome strikes again.

A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called "3-week sulphasalazine syndrome", a rare, but often fatal, immunoallergic reaction to sulphasalazine.

Adult↗

A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: implication for the intense tumor infiltration by T lymphocytes and macrophages.

Nasopharyngeal carcinoma (NPC) is characterized by harboring Epstein-Barr virus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphocytes and macrophages. The mechanism of this intense infiltration has long been a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and macrophages, by an immunohistochemical approach. In biopsies obtained from nasopharynx of 17 NPC patients that contained tumor cells, expression of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, macrophage chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells, with MIP-1alpha and MCP-1 found in nearly all biopsies and the others relatively less frequently. Furthermore, expression of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in the 13 control biopsies that were either normal or with nonspecific inflammation, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1alpha and MCP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these chemokines, was also detected in the tumor-infiltrating cells. These data indicate that the intense tumor infiltration by T cells and macrophages is a result of active recruitment. It seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reactive T cells. T cells migrate into the tumor tissue in an antigen-specific mode, and IFN-gamma secreted from these pioneer T cells activates tissue macrophages to express CC chemokines, especially MIP-1alpha and MCP-1, which consequently recruit more T cells and macrophages into the tumor tissue.

Antibodies, Viral↗

Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis.

BACKGROUND: Haptoglobin knockout (Hp-/-) mice are more sensitive to phenylhydrazine-induced hemolysis than Hp+/+ mice. METHODS: Hemolysis was induced in Hp-/- and Hp+/+ mice using phenylhydrazine. Relative renal tissue damage and function were then assessed. RESULTS: Hp-/- mice had higher basal levels of renal lipid peroxidation, as evidenced by levels of malonaldehyde and 4-hydroxy-2(E)-nonenal (MDA/HNE). After the administration of phenylhydrazine, levels of 8-hydroxyguanine (but not other products of oxidative DNA damage) were significantly elevated in the renal DNA. There was also increased induction of heme oxygenase-1. The more severe renal damage in Hp-/- mice was also evident in the delayed erythropoietin gene expression and poorer renal clearance of 3H-inulin. This reduction in glomerular filtration function in Hp+/+ and Hp-/- mice could be restored to baseline by vasodilators (prazosin or diazoxide), implicating renal vasoconstriction as a major mechanism of acute renal failure during induced hemolysis. Precipitation of hemoglobin in the kidney was not increased in Hp-/- mice. CONCLUSIONS: Haptoglobin appears to play an important physiological role as an antioxidant, particularly during hemolysis.

Acute-Phase Reaction↗

Increased production of interferon-gamma by tumour infiltrating T lymphocytes in nasopharyngeal carcinoma: indicative of an activated status.

Undifferentiated nasopharyngeal carcinomas (UNPC) are characterised by an association with Epstein-Barr virus and an abundant lymphoid stroma. We studied the functional status of the infiltrating T cells in ten UNPC biopsies using an immunohistochemical approach. Twelve non-NPC biopsies were included as controls. Tumour cells of UNPC were positive for HLA class I (10/10) and II (8/10), LMP1 (3/10), and CD86 (6/10). Tumour infiltrating T cells (TILs) were detected with antibodies directed at CD3, CD4, and CD8, and shown to be comparable to that in the control biopsies. Although expression of CD28 was shown to be decreased in TILs, expression of CD25 and IFN-gamma at a relatively high percentage could be consistently detected in the UNPC biopsies. These data suggest that TILs in UNPC are in an activated status, and this T cell response is possibly directed at the tumour cells.

Antigens, CD↗

Small cell neuroendocrine carcinoma of the cervix with involvement of multiple pelvic nodes--A successfully treated case by multimodal approach.

Small cell neuroendocrine carcinoma of the cervix is very rare and is usually associated with dismal prognosis if treated by conventional surgery and radiotherapy even in early stage disease. This tumor is characterized by early lymphatic and hematogenous spread. Only one successfully treated case of small cell neuroendocrine carcinoma of the cervix with dissemination to the pelvic nodes had been reported before in the literature. We are reporting a case of small cell neuroendocrine carcinoma of the cervix with multiple pelvic nodal metastases including the common iliac nodes, which had been successfully treated with a multimodal approach including radical hysterectomy, pelvic/para-aortic lymphadenectomy, and postoperative chemotherapy using cisplatin-etoposide combinations and pelvic irradiation.

Adult↗

X-chromosome inactivation analysis of isolated Reed-Sternberg cells in nodular sclerosing Hodgkin's disease.

In spite of several studies of immunoglobulin (Ig) gene rearrangements in whole Hodgkin's disease (HD) tissues and in isolated single Reed-Sternberg (RS) cells, the issue of clonality of the RS cell in HD remains incompletely resolved. Analysis of X-chromosome inactivation patterns (XCIPs) can be used to determine whether cell populations are clonal in origin. By PCR amplification of the human androgen receptor (HUMARA) loci using nested primers, we have studied XCIPs in six cases of HD of the nodular sclerosing (NS) subtype in which individual RS cells were isolated by micromanipulation from formalin-fixed, paraffin-embedded tissue sections immunostained with CD30 or CD15. In order to assess whether a clonal population of RS cells might be present in NSHD tissues, we compared the XCIPs obtained from whole NSHD tissues with those obtained from single RS cells harvested from the same tissues. Whole tissues from all six cases of NSHD showed balanced HUMARA allelic patterns, whereas an average of 83% (range 77-91%) of single RS cells from each of the six tissues expressed the same high- or low-molecular weight allele, suggesting that a clonal population of RS cells was likely to be present in each case. These data are consistent with the presence of a clonal population of RS cells in NSHD tissues.

Adult↗

School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls.

BACKGROUND: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world. OBJECTIVE: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia. DESIGN: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B were randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation. RESULTS: By the end of the study, 2% of the girls had dropped out and > 96% had taken > or = 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment. CONCLUSION: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls.

Adolescent↗

Splenic actinomycosis.

We report a rare case of abdominal actinomycosis occurring in the spleen and review the literature on abdominal actinomycosis.

Actinomycosis↗

Increased susceptibility in Hp knockout mice during acute hemolysis.

Haptoglobin, a conserved plasma glycoprotein, forms very stable soluble complexes with free plasma hemoglobin. Hemoglobin binding by haptoglobin is thought to be important in the rapid hepatic clearance of hemoglobin from the plasma and in the inhibition of glomerular filtration of hemoglobin. To evaluate these functions, Haptoglobin knockout (-/-) mice were created. These mice were viable but had a small, significant reduction in postnatal viability. Contrary to popular belief, the lack of haptoglobin did not impair clearance of free plasma hemoglobin in -/- mice. Induction of severe hemolysis by phenylhydrazine caused extensive hemoglobin precipitation in the renal tubular cells of both -/- and +/+ mice, with death occurring in 55% of -/- mice and in 18% of +/+ mice. In general, phenylhydrazine-treated -/- mice suffered greater tissue damage, as evidenced by the induction of hepatic acute phase response resulting in increased plasma alpha 1-acid glycoprotein (AGP) levels. Among -/- and +/+ mice that survived, -/- mice tend to suffer greater oxidative damage and failed to repair or regenerate damaged renal tissues, as indicated by their higher plasma malonaldehyde (MDA) and 4-hydroxy-2(E)-nonenal (HNE) levels and lower mitotic indices in their kidneys, respectively. This study suggested that a physiologically important role of hemoglobin-haptoglobin complex formation is the amelioration of tissue damages by hemoglobin-driven lipid peroxidation.

Acute-Phase Reaction↗

Characteristics and prognosis of KI-1 positive anaplastic large cell lymphoma in Asians.

BACKGROUND: Ki-1 positive anaplastic large cell lymphoma is a rare type of non-Hodgkin's lymphoma (NHL), and has not been extensively described in Asian patients. AIM: To evaluate the clinical characteristics, prognostic factors and treatment outcome of Ki-1 positive lymphoma in an Asian community. METHODS: A retrospective analysis of all patients with CD30 antigen positive anaplastic large cell lymphoma from 1987 to 1996 in a single institution. RESULTS: Of 218 patients with NHL, ten (5%) were identified with Ki-1 positive anaplastic large cell lymphoma. Eight were Chinese, two Indians. The male:female ratio was 1.5:1, and the median age was 32 years. Seven patients presented with B-symptoms, and five had stage III/IV disease. The majority (seven of ten) was low- or low-intermediate risk according to the International Prognostic Index (IPI). Four out of five cases immunophenotyped showed a T-cell origin. Five out of eight patients who received first-line combination chemotherapy achieved a complete remission. Two relapsed, with one being re-induced into a durable second remission. One patient with recurrent cutaneous lymphoma received solely radiotherapy and was disease-free at 20+ years from diagnosis. At analysis, two patients had died, five were disease-free at four, 27, 78, 89 months and 20 years respectively, and three were alive with disease. The IPI appears to have prognostic significance. CONCLUSION: Incidence and clinical characteristics in our Asian patients were similar to those described in Western populations. The IPI appears to have prognostic relevance. In approximately one-third of patients, long term survival can be achieved with standard treatment.

Adolescent↗

Malignant ovarian germ cell tumours: experience in the National University Hospital of Singapore.

Management of thirteen cases of malignant ovarian germ cell tumours was reported. Of these, 5 (38%) were immature teratoma, 3 (23%) were endodermal sinus tumour, 1 (8%) was dysgerminoma and 4 (31%) were mixed germ cell tumour. Eight (61%) had stage I, 1 (8%) had stage II and 4 (31%) had stage III diseases. Six had unilateral salpingo-oophorectomy, 6 had total abdominal hysterectomy and bilateral salpingo-oophorectomy and 1 had bilateral oophorectomy. Ten (77%) had adjuvant chemotherapy predominantly with bleomycin/etoposide/cisplatin combination. All patients with stage I and stage II tumours were alive with no evidence of disease at 1/2 year to 5 years followup. Of the 4 patients with stage IIIC diseases, 2 with optimal debulking surgery were alive and disease free at 4 and 7 years after surgery. The other 2 patients with stage IIIC tumours had multiple bulky residual tumours. One of them with a combination of endodermal sinus tumour and embryonal carcinoma died of progressive disease despite chemotherapy 6 months after surgery and the other with mixed endodermal sinus tumour and dysgerminoma was alive with disease at 6 months. Alpha-fetoprotein levels were raised in all 6 patients with endodermal sinus tumour, either pure or combined with other tumours. Regression of alpha-fetoprotein levels was of important prognostic significance in endodermal sinus tumour.

Adult↗

Pre and intraoperative diagnosis of ovarian tumours: how accurate are we?

In the assessment of malignant potential of ovarian tumours, frozen section has been found to be accurate in 97.1% (168 of 173) of cases. The positive predictive value of frozen section in the diagnosis of a malignant lesion was 100% (34 of 34). Errors were mainly made in the diagnosis of borderline tumours with a predictive value of 87.5% (7 of 8). The negative predictive value was 98.4% (127 of 129). Frozen section however, was less accurate in the diagnosis of specific histological type with an accuracy rate of 91.9% (159 of 173). Macroscopic features were found to be useful in the intraoperative prediction of malignant potential. Completely cystic tumours were benign in 96.4% (108 of 167) of cases. Solid/cystic tumors were malignant in 69% (27 of 38) of cases. Completely solid tumours were malignant in 56% (9 of 16) of cases. Frozen section in completely cystic tumours only marginally improved the clinical macroscopic diagnosis of malignancy. The sensitivity and specificity of ultrasound scan in the diagnosis of malignant/borderline tumours were 82% and 86% respectively. The false negative rate of 7% makes laparoscopic excision of unsuspected malignant ovarian cyst a significant possibility. The predictive value of ultrasound scan in the diagnosis of malignant ovarian tumour was 62% (26 of 42). In the preoperative assessment of malignant potential of ovarian tumours, this study shows that ultrasound scan has a high false positive and a significant false negative rate. Careful intraoperative assessment of gross features and the use of frozen section especially in those with solid/cystic and solid tumours will help achieve a high accuracy rate in the assessment of ovarian tumours.

Female↗

Plasma macrophage colony-stimulating factor and P-selectin levels in malaria-associated thrombocytopenia.

Thrombocytopenia is a common finding in malaria. In clinical trials, recombinant macrophage colony-stimulating factor (M-CSF) causes a reversible, dose-dependent thrombocytopenia, and high M-CSF has been reported in autoimmune thrombocytopenias. P-selectin, which is secreted into the plasma following platelet/endothelial activation or damage, is elevated in certain consumptive thrombocytopenic disorders. The relationships between thrombocytopenia, M-CSF and P-selectin were analysed in 63 patients with severe (n = 13) or uncomplicated (n = 26) P. falciparum (PF) or P. vivax (PV) malaria (n = 24). On admission, 69% of PF patients and 75% of PV patients were thrombocytopenic (platelets < 150 x 10(9)/l). M-CSF was elevated in PF (3021 +/- 1844 pg/ml) and PV (2602 +/- 1668 pg/ml) patients, compared to controls (589 +/- 200 pg/ml). The platelet count was inversely correlated with M-CSF in PF (r = -0.681), and in PV malaria (r = -0.548). Elevated P-selectin was found in severe PF malaria, but not in PV malaria. Severe PF malaria was associated with marked thrombocytopenia, very high M-CSF, elevated P-selectin and compelling evidence of disseminated intravascular coagulopathy (DIC). Platelet counts, M-CSF and P-selectin returned to control values in 7-14 days. These data suggest that elevated M-CSF in malaria, by enhancing macrophage activity, may result in increased macrophage-mediated platelet destruction. Further, platelet/endothelial activation or damage, as measured by P-selectin, or DIC could intensify thrombocytopenia in severe PF malaria, but does not appear to contribute to thrombocytopenia in uncomplicated PF or PV malaria.

Acute Disease↗