Biomedical subjects

S G Lim

Publications and source records attributed to S G Lim.

17 recordsLinked to original sources

PubMed2000

Triple therapy in the eradication of Helicobacter pylori in patients with duodenal ulcer disease: results of a multicentre study in South-East Asia. South-East Asia Multicenter Study Group.

BACKGROUND: The efficacy of proton pump inhibitor based triple therapy in patients from South-East Asia, where metronidazole resistance is reportedly high, has not been formally assessed in randomized, multicentre trials. AIM: To compare the eradication rates of Helicobacter pylori, ulcer healing rates and side-effects of three regimens of omeprazole triple therapy in patients with duodenal ulcer from South-East Asia and to study the impact of metronidazole resistance. METHODS: A single blind, randomized parallel group, comparative multicentre study. A total of 246 patients from 15 centres in four South-East Asian countries were randomized to receive OAC (omeprazole 20 mg b.d., amoxycillin 1 g b. d., clarithromycin 500 mg b.d.), OAM (omeprazole 20 mg b.d., amoxycillin 1 g b.d., metronidazole 400 mg b.d.) or OMC (omeprazole 20 mg b.d., metronidazole 400 mg b.d., clarithromycin 500 mg b.d.) for 7 days. After triple therapy, the patients were further randomized to receive either omeprazole or placebo for 7 days. Upper gastrointestinal endoscopy was performed before treatment and 4 weeks after treatment. Biopsies for culture and for histopathological examination for H. pylori were taken from corpus and antrum before treatment and 4 weeks after treatment. RESULTS: The eradication rates were intention-to-treat/per protocol (95% CI): OAC 87% (79-94%)/94% (89-100%); OAM 80% (70-89%)/91% (83-98%); OMC 85% (77-93%)/94% (88-100%). The difference in eradication rates between the three groups was not statistically significant (P=0.419). Pre-treatment metronidazole resistance, was found in 34% of isolates and was a significant prognostic factor in patients receiving OAM (odds ratio 5.26) but not in patients receiving OAC or OMC. CONCLUSIONS: All three treatment regimens were safe, well tolerated and highly effective for eradication of H. pylori and ulcer healing. Pre-treatment metronidazole resistance reduced the efficacy of OAM but did not affect the efficacy of OMC.

Adolescent↗

PubMed1998

Improving the success of culturing Helicobacter pylori from gastric biopsies.

Factors influencing the successful isolation of Helicobacter pylori from human gastric biopsies were studied. Within 24 h, each of the gastric biopsies was inoculated onto chocolate blood agar media and incubated for up to 2 weeks. Among 63 (70%) culture positive cases in 90 patients, 58 (64%) cases were culture positive for both specimens, while five (6%) cases were culture positive in only one biopsy. Of the 63 positive cultures, 51 H. pylori strains (81%) grew on both media with and without antibiotics. Eight strains (13%) grew only on medium without antibiotics, while four isolates (6%) were obtained only from medium with antibiotics. These results support the previous histological observation of patchy colonization of H. pylori in the stomach. The success rate for culture of H. pylori from gastric biopsies increased when two biopsies were taken and inoculated on chocolate blood agar media with and without antibiotics.

Helicobacter Infections↗

PubMed1996

Evaluation of cardiac sympathetic neuronal integrity in diabetic patients using iodine-123 metaiodobenzylguanidine.

Autonomic dysfunction is associated with increased mortality in diabetic patients. To evaluate the cardiac autonomic dysfunction in these patients, a prospective study was undertaken using iodine-123 metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET). The study groups consisted of ten diabetic patients with cardiac autonomic neuropathy (group I) and six without autonomic neuropathy (group II). Autonomic nervous function tests, thallium scan, radionuclide ventriculographic data including ejection fraction and wall motion study, and 24-h urine catecholamine levels were evaluated. 123I-MIBG SPET was performed at 30 min and 4h following injection of 3 mCi of 123I-MIBG in groups I and II and in normal subjects (n=4). On planar images, the heart to mediastinum (H/M) ratio was measured. Defect pattern and severity of MIBG uptake were qualitatively analysed on SPET. Compared with control subjects, diabetic patients had a reduced H/M ratio regardless of the presence of clinical autonomic neuropathy. There was no difference in H/M ratio between groups I and II. On SPET images, focal or diffuse defects were demonstrated in all patients in group I, and in five of the six patients in group II. The extent of defects tended to be more pronounced in group I than in group II. In conclusion, 123I-MIBG scan was found to be a more sensitive method than clinical autonomic nervous function tests for the detection of autonomic neuropathy in diabetes.

3-Iodobenzylguanidine↗

PubMed1995

Small bowel bacterial overgrowth in systemic sclerosis: detection using direct and indirect methods and treatment outcome.

Twenty-four patients with proven systemic sclerosis and with symptoms suggestive of malabsorption (i.e. chronic diarrhoea and weight loss) were investigated for small bowel bacterial overgrowth. Of the patients selected, six were suffering from the diffuse form of the disease. Jejunal aspiration was performed in all patients, and in nine normal volunteers. A specially designed double-lumen sterile catheter was used for this purpose and was introduced via a gastroscope. Twenty of these patients underwent a glucose hydrogen breath test. Eight patients (33%) had significant bacterial counts: > 10(5) colony forming units per ml (cfu/ml) of jejunal fluid. Less than 10(2) cfu/ml were found in the jejunal fluid from the nine control subjects. Glucose hydrogen breath testing was positive in seven patients, all of whom had significant jejunal bacterial growth. Diarrhoea rather than weight loss was shown to be the symptom which correlated best with the presence of bacterial overgrowth. Ciprofloxacin was used in six patients whose diarrhoeal symptoms ceased dramatically within 48 h of commencing the antibiotic. Trimethoprim produced a partial response despite bacterial sensitivity. A disadvantage of the hydrogen breath test is that subsequent antibacterial therapy cannot be specific, as bacterial species, antibiotic sensitivity and resistance are unknown. Systemic sclerosis involving the small intestine in the past has been said to more prevalent in patients with diffuse disease, whereas this study showed a preponderance of patients with long-standing limited cutaneous systemic sclerosis and small bowel involvement.

Adult↗

PubMed1995

Intestinal disaccharidase activity in human immunodeficiency virus disease.

BACKGROUND: The relationship between disaccharidase activity, progression of human immunodeficiency virus (HIV) disease, and diarrhoea and weight loss was investigated. METHODS: Forty-six HIV-positive patients ingested a solution of lactose, palatinose, sucrose, and lactulose after 24 h of dietary exclusion and overnight fasting, after which urine was collected for 10 h. Urinary disaccharide (activity) ratios-lactose/lactulose (L/LL), palatinose/lactulose (P/LL), and sucrose/lactulose (S/LL)-were measured by thin-layer chromatography. RESULTS: There was a significant decrease in disaccharidase activity (L/LL, P/LL, and S/LL) with advancing clinical stage of HIV disease (p < 0.05, Wilcoxon rank sum test) as well as decreasing CD4 count (p < 0.05, Spearman correlation). Patients with weight loss/diarrhoea also had significantly (p < 0.05) decreased disaccharidase activity compared with control but not as compared with AIDS patients. Anti-retroviral therapy did not influence disaccharidase activity. CONCLUSION: Impairment of disaccharidase activity occurs with advancing HIV disease, but its role in HIV patients with weight loss and diarrhoea remains to be determined.

Adult↗

PubMed1994

Ischaemia of the small intestine in patients with systemic sclerosis: Raynaud's phenomenon or chronic vasculopathy?

We investigated duodenal and gastric mucosal blood flow by endoscopic laser Doppler flowmetry (LDF) in ten patients with systemic sclerosis (SSc) and in ten healthy volunteers. In addition, we tested for the presence of small bowel bacterial overgrowth by jejunal aspiration. Jejunal aspiration and LDF were done consecutively, via a gastroscope, using a flexible catheter and laser Doppler probe. Following these procedures, two duodenal biopsies were obtained for light and electron microscopy. Mean duodenal and gastric blood flow were significantly lower in patients with SSc than in normal subjects (516 flux units vs. 240, 521 vs. 202, both p < 0.001). There was no correlation between age and blood flow in patients or volunteers. Four of the ten patients had evidence of significant bacterial overgrowth on jejunal aspiration (> 10(5) colony-forming units/ml). These findings support the hypothesis that within the small intestine of patients with SSc, factors independent of bacterial overgrowth may be responsible for malabsorption. The observed reduction in small-intestine mucosal blood flow may play an important contributory role. Further studies are required to determine whether this represents reversible or chronic progressive ischaemia, and its effect on nutrient absorption.

Adult↗

PubMed1993

Short report: the absorption of fluconazole and itraconazole under conditions of low intragastric acidity.

The study investigated the oral absorption of two antifungal agents, fluconazole and itraconazole, under conditions of low intragastric acidity. Twelve healthy male volunteers received each of 4 dosing regimens: 200 mg itraconazole alone, 200 mg itraconazole and famotidine, 100 mg fluconazole alone, and 100 mg fluconazole and famotidine. Two oral doses of 40 mg famotidine were used to induce hypochlorhydria. Serum drug concentrations were measured (by high pressure liquid chromatography) for 48 h after a single dose of each anti-fungal agent. When dosed with famotidine, there was a significant 52.9% decrease of the peak intraconazole concentration (P < 0.011), and a significant 51.1% decrease of the 48-h integrated serum intraconazole concentration (P = 0.005). Famotidine-induced hypochlorhydria did not affect the absorption of fluconazole.

Adult↗

PubMed1993

Mucosal macrophage subsets of the gut in HIV: decrease in antigen-presenting cell phenotype.

The effect of HIV infection on intestinal lamina propria macrophage subsets was investigated in 41 patients at various stages of HIV infection (asymptomatic HIV infection, n = 17; AIDS, n = 24). Duodenal biopsies taken from HIV patients at endoscopy were snap frozen and cryostat sections cut for immunohistochemical staining. MoAbs CD68 (EBM11, pan-macrophage marker), RFD1 (antigen-presenting cells) and RFD7 (mature phagocytic macrophages) were used to identify cell subsets using indirect immunoperoxidase or alkaline phosphatase. Double immunofluorescence using MoAbs to HIV proteins (p24, p17 and gp120) and RFD1 were used to identify HIV-infected antigen-presenting cells. Double immunofluorescence was also used to identify macrophages that expressed both RFD1 and RFD7 ('suppressor' macrophages). Intensity of HLA-DR expression in lamina propria cells was investigated using a MoAb to HLA-DR directly conjugated to glucose oxidase. The results show that there was no difference in overall density of macrophages, but there was a significant decrease in dendritic cells (RFD1+) in all clinical stages of HIV. There was no difference in the density of RFD7+ macrophages, nor was there a difference intensity of HLA-DR expression in lamina propria cells. Only four HIV-infected cells were positively identified in the 41 patients. This result suggests that the antigen-presenting arm of mucosal immune defences may be seriously compromised in HIV infection, and represents a further insult to mucosal immunity already impaired as a result of loss of CD4+ T lymphocytes. This may contribute to development of opportunist infection in the gut.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Loss of mucosal CD4 lymphocytes is an early feature of HIV infection.

T cell subsets in the gut mucosa are distinct populations and their imbalance in HIV has specific implications in infection. Alterations in T cell subsets in duodenal biopsies were investigated in 17 asymptomatic HIV patients, 24 AIDS patients and 10 controls with non-ulcer dyspepsia. Immunohistochemistry and immunofluorescence using MoAbs to CD3, CD4, CD8, CD68, CD45RA, CD45RO and gp120 were performed on frozen sections. In the lamina propria, there was a significant depletion of CD4+ cells at all stages of HIV, but the density of CD8 lamina propria cells was increased. Intraepithelial lymphocytes were decreased in AIDS patients. There was a significant correlation between cellular density and mucosal CD3+ lymphocytes, and between mucosal CD3+ and CD8+ lymphocytes. Although mucosal CD4,CD45RO+ 'memory' cells were decreased, CD8,CD45RO+ 'memory' cells were increased. Mucosal CD4+ lymphocyte depletion occurred early in HIV, and thus their role in mucosal protection against opportunistic infection should be revised. Mucosal CD8+ lymphocytes initially increased, but decreased when CD4 blood counts were depleted, perhaps contributing to loss of host protection against infection. Intraepithelial lymphocyte depletion may also contribute to opportunistic infection.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Audit of endoscopic surveillance biopsy specimens in HIV positive patients with gastrointestinal symptoms.

An audit of upper gastrointestinal endoscopy in HIV infected patients with gastrointestinal symptoms assessed the frequency of disease detected by endoscopy and routine laboratory analysis of surveillance biopsy specimens. Sixty nine consecutive endoscopies were performed in 59 HIV infected patients. Endoscopic biopsy specimens were taken from the lower oesophagus, gastric antrum, and third part of the duodenum for virology, histopathology, parasitology, bacteriology, and mycobacterial culture. Endoscopic appearances detected disease in 25/59 (42.4%) patients (oesophageal candida, 14; oesophageal ulcer, 3; Kaposi's sarcoma, 4; others, 4), but only 4/43 (9.3%) specimens showed evidence of disease in the absence of endoscopic abnormality. Virology for cytomegalovirus (detection of early antigenic fluorescent foci and culture) was positive in 6/59 (10.2%) patients, but parasitology and mycobacterial culture were negative in all cases. Histopathology was abnormal in 11/52 (21%) oesophageal biopsy specimens, 13/47 (28%) gastric biopsy specimens, and 4/65 (6%) duodenal biopsy specimens. Abnormal findings were found predominantly in those with advanced HIV disease (CDC Stage IV) (21/33 patients (64%)) compared with those with early HIV disease (CDC Stage II) (5/26 (19%)). In conclusion, upper gastrointestinal endoscopy detects macroscopic disease in AIDS patients and those with low CD4 counts, but routine surveillance biopsy specimens of apparently normal bowel in early HIV disease (or where CD4 counts are greater than 0.2 x 10(9)/1) are of little value.

Adolescent↗

PubMed1993

Intestinal permeability and function in patients infected with human immunodeficiency virus. A comparison with coeliac disease.

The relationships among intestinal permeability, advancing human immunodeficiency virus (HIV) infection, and the presence of diarrhoea or weight loss were investigated in 51 HIV patients and 20 healthy controls. Ten patients with untreated coeliac disease were also investigated for comparison. Fasting subjects drank an isosmolar test solution containing D-xylose, lactulose (LL), L-rhamnose (R) and 3-O-methyl-D-glucose. Urine was collected for 5 h, test sugar content being subsequently measured by thin-layer chromatography for the dosing sugars. Intestinal permeability (LL/R excretion ratio) and recovery of D-xylose and 3-O-methyl-D-glucose in urine were abnormal in patients with HIV disease, and especially those with diarrhoea, as they were in coeliac disease. Patients with coeliac disease and HIV disease, especially when diarrhoea and/or weight loss were present, had significantly reduced 5-h excretion of L-rhamnose, D-xylose, and 3-O-methyl-D-glucose. These data indicate that abnormal permeability and reduced intestinal absorption capacity are common in HIV patients, occur at all stages of HIV disease, especially in the presence of diarrhoea, and, with the exception of lactulose permeation, are relatively similar to the alterations seen in coeliac disease.

3-O-Methylglucose↗

PubMed1992

Antibodies to platelet glycoproteins in haemophiliacs infected with HIV.

The techniques of Western blotting and the monoclonal antibody specific immobilization of platelet antigen (MAIPA) assay were used to detect antibodies to platelet glycoproteins in 43 samples of serum from 23 anti-HIV positive haemophiliacs (8 with severe thrombocytopenia, 6 with moderate thrombocytopenia, and 9 with a normal platelet count), six anti-HIV negative haemophiliacs and ten controls. Antibodies were present in the majority of anti-HIV positive patients' sera even before the onset of thrombocytopenia. Thrombocytopenia was associated with an increase in the incidence of antibodies to GPIIIa and GPIb, whereas the antigen most frequently recognized in patients without thrombocytopenia was GPIIb. Anti-GPIIb and/or GPIIIa reactivity was also seen in three out of the six anti-HIV negative patients. There was no correlation between the absolute platelet count and the detection of antibodies in either assay. Effective therapy for thrombocytopenia with zidovudine, interferon or splenectomy did not influence the presence of antibody. Eight of nine patients with AIDS were negative in the MAIPA assay, consistent with their depressed immune status. It is concluded that the production of antibodies to platelet membrane glycoprotein in anti-HIV positive haemophiliacs is influenced by factors other than HIV. The presence of such antibodies is independent of the platelet count and is therefore unlikely to play a causative role in HIV-related thrombocytopenia.

Antibodies, Monoclonal↗

PubMed1991

Fluconazole for oropharyngeal candidiasis in anti-HIV positive haemophiliacs.

Candidiasis of the oropharynx and oesophagus is one of the most common problems encountered in patients with HIV disease. Fluconazole is a bis-triazole antifungal agent with a long serum half-life. Sixteen anti-HIV positive patients (15 haemophiliacs and one blood transfusion recipient) with a clinical diagnosis of oropharyngeal candidiasis were treated with 50 mg fluconazole daily for 14-28 days and then either 150 mg fluconazole or placebo weekly for 6 months in a prophylactic phase. Clinical cure occurred in all patients, and mycological cure occurred in 13/16 (81%) patients. In the prophylactic phase, there were 2/5 (40%) relapses in the placebo arm compared with 1/8 (12.5%) in the fluconazole arm, but this was not statistically significant by Fisher's one-sided exact test (P = 0.31). It is concluded that fluconazole is an effective treatment of oropharyngeal candidiasis and has potential for prophylactic use.

Adolescent↗

PubMed1991

Hepatitis C antibody assay in a longitudinal study of haemophiliacs.

Stored sera from 28 patients with inherited coagulation disorders who had developed non-A non-B hepatitis (NANBH) following a first exposure to clotting factor concentrates and 15 similar, but unmatched, patients who had received blood products but had normal transaminases on sequential testing were tested using the Ortho enzyme-linked immunosorbent assay (ELISA) anti-HCV assay. Twenty-seven of the 28 patients with NANBH were anti-HCV positive after exposure. In 10 of those in whom dates of first exposure and seroconversion were well-defined, the median time interval to NANBH was 4 weeks (range 1-7) and to anti-HCV seroconversion was 11 weeks (range 7.5-14.5). None of the 15 patients without NANBH developed anti-HCV. This first generation Ortho ELISA anti-HCV assay showed 96% sensitivity and 100% specificity and has potential use as an adjunct in the surveillance of new clotting factor products.

Adolescent↗

PubMed1990

The treatment of HIV associated thrombocytopenia in haemophiliacs.

HIV associated thrombocytopenia occurs in 5-10% of asymptomatic individuals, and 25-45% of people with AIDS. A variety of treatments are available but the inherited bleeding disorder in addition to the thrombocytopenia makes management in haemophiliacs a special problem. The management of this double coagulopathy is described in seven patients. IV gammaglobulin and steroids were useful only in the short term; zidovudine produced a good response, could be taken orally, had anti-HIV activity and was well tolerated in asymptomatic HIV positive patients. Interferon was an alternative when zidovudine was ineffective or produced intolerable side-effects. Splenectomy was considered only after failure of other treatments because of the increased risks of bleeding.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Zidovudine treatment for anti-HIV positive haemophiliacs.

Twenty haemophiliacs (17 CDC group IV and 3 CDC group II) were treated with zidovudine for a median of 37 weeks (range 10-66). Eight (40%) tolerated zidovudine without a dose change. Two patients died and five patients (29%) developed opportunist infections. Haematological toxicity occurred in ten CDC IV patients (59%) but only one case of sepsis occurred in 101 episodes of documented granulocytopenia. Thrombocytopenia responded to treatment with zidovudine in four of five patients. It is concluded that zidovudine is beneficial for symptomatic haemophiliacs and although the haematological toxicity is high, it is mostly asymptomatic, reversible and well tolerated. Two of the three CDC II patients treated with zidovudine progressed to CDC IV, but had low initial T4 lymphocyte counts and were P24 antigen positive.

Acquired Immunodeficiency Syndrome↗

PubMed1987

High dose intravenous gammaglobulin in immune haematological disease.

High dose intravenous gammaglobulin (0.4 g/kg/day) for five days, causes a rapid rise in the platelet count in immune thrombocytopenic purpura (ITP). The response in chronic ITP is transient making it useful in emergency situations. Efficacy in immune mediated neutropenia and warm antibody haemolytic anaemia has been reported but in limited numbers. We have used this therapy in twenty-three adults with ITP, one patient with immune neutropenia, four patients with warm antibody autoimmune haemolytic anaemia and one case of thrombotic thrombocytopenic purpura (TTP). In ITP only four of the twenty patients failed to respond to gammaglobulin and of these, three had a positive antinuclear factor but no other signs of systemic lupus erythematosis. The sole patient with neutropenia treated with IgG failed to show any response. In three patients with haemolytic anaemia parameters of haemolysis improved during therapy. The patient with TTP suffered a cerebrovascular accident during therapy prior to a documented response. High dose intravenous immunoglobulin rapidly elevates the platelet count in acute and chronic ITP. Its use in other immune mediated haematological conditions has yet to be fully evaluated.

Acute Disease↗