PubMed Health⌕ Search

Biomedical subjects

A G Lim

Publications and source records attributed to A G Lim.

At least 19 recordsLinked to original sources
PubMed2006

Exonic STK11 deletions are not a rare cause of Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant cancer predisposition syndrome characterised by oro-facial pigmentation and hamartomatous polyposis of the gastrointestinal tract. A causal germline mutation in STK11 can be identified in 30% to 80% of PJS patients. METHODS: Here we report the comprehensive mutational analysis of STK11 in 38 PJS probands applying conventional PCR based mutation detection methods and the recently introduced MLPA (multiplex ligation dependent probe amplification) technique developed for the identification of exonic deletions/duplications. RESULTS: Nineteen of 38 probands (50%) had detectable point mutations or small scale deletions/insertions and six probands (16%) had genomic deletions encompassing one or more STK11 exons. CONCLUSIONS: These findings demonstrate that exonic STK11 deletions are a common cause of PJS and provide a strong rationale for conducting a primary screen for such mutations in patients.

AMP-Activated Protein Kinase Kinases↗
PubMed2003

Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome.

Germline mutations in the LKB1/STK11 tumour suppressor gene cause Peutz-Jeghers syndrome (PJS), a rare dominant disorder. In addition to typical hamartomatous gastrointestinal polyps and pigmented perioral lesions, PJS is associated with an increased risk of tumours at multiple sites. Follow-up information on carriers is limited and genetic heterogeneity makes counselling and management in PJS difficult. Here we report the analysis of the LKB1/STK11 locus in a series of 33 PJS families, and estimation of cancer risks in carriers and noncarriers. Germline mutations of LKB1/STK11 were identified in 52% of cases. This observation reinforces the hypothesis of a second PJS locus. In carriers of LKB1/STK11 mutations, the risk of cancer was markedly elevated. The risk of developing any cancer in carriers by age 65 years was 47% (95% CI: 27-73%) with elevated risks of both gastrointestinal and breast cancer. PJS with germline mutations in LKB1/STK11 are at a very high relative and absolute risk of multiple gastrointestinal and nongastrointestinal cancers. To obtain precise estimates of risk associated with PJS requires further studies of genotype-phenotype especially with respect to LKB1/STK11 negative cases, as this group is likely to be heterogeneous.

AMP-Activated Protein Kinase Kinases↗
PubMed2001

It could only happen to a doctor--Haemophilus aphrophilus septicaemia complicated by a prevertebral infection after dental work.

A 53 year old man presented with severe neck pain and a flu-like illness; he had recently returned from Sri Lanka and had had dental treatment six days before illness onset. Blood culture showed infection by Haemophilus aphrophilus. Magnetic resonance imaging was performed and exploratory surgery undertaken. The prevertebral cervical fascia was inflamed but no abscess identified. He was treated with antibiotics and made an uneventful recovery.

Dental Care↗
PubMed1999

Diversion colitis: a trigger for ulcerative colitis in the in-stream colon?

The aetiology of ulcerative colitis is unknown. Two patients without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest that diversion colitis may be a risk factor for ulcerative colitis in predisposed individuals and that ulcerative colitis can be triggered by anatomically discontinuous inflammation elsewhere in the large intestine.

Adolescent↗
PubMed1998

Trends in prescribing H2-receptor antagonists and proton pump inhibitors in primary care.

BACKGROUND: H2-receptor antagonists and proton pump inhibitors account for approximately 15% of primary care prescribing costs in the UK. AIM: To examine the use of antisecretory drugs in primary care between October 1991 and September 1996. METHOD: Analysis of prescribing data from an ongoing postal survey performed every 3 months on a rolling quota of 250 UK general practitioners (GPs), identified from a representative sampling frame of 1000 GPs. RESULTS: There were 8811 new courses of proton pump inhibitors and 11,948 new courses of H2-receptor antagonists during this study. The number of new prescriptions for proton pump inhibitors increased by 174.5%, but decreased for H2-receptor antagonists by 12.5%. Proton pump inhibitors were mostly prescribed for reflux disease (52.7%) and H2-receptor antagonists for non-specific dyspepsia (43.6%). Proton pump inhibitors (14.1%) were less likely to be stopped than H2-receptor antagonists (35.3%) overall, and they were less likely to be stopped because of perceived ineffectiveness (5.3%) than H2-receptor antagonists (23.8%). The rate of stopping treatment because of side-effects was about 3% for both classes of drug. CONCLUSIONS: Prescribing of proton pump inhibitors has increased sharply each year since 1991. One reason may be that GPs perceive proton pump inhibitors to be more effective than H2-receptor antagonists.

Anti-Ulcer Agents↗
PubMed1998

Serum IgA antibodies to human gut luminal aspirates and human liver in alcoholic liver disease.

BACKGROUND: Elevation of serum IgA is a characteristic feature of alcoholic liver disease. It has been proposed that this occurs partly as an antigenic response to gut-derived proteins or acetaldehyde-modified liver proteins, but the principal antigens responsible remain unknown. AIMS: The goal of this study was to determine if serum IgA antibodies were present against human gut luminal antigens or liver antigens in alcoholic liver disease. PATIENTS AND METHODS: Twenty-nine patients with alcoholic liver disease, 10 with primary biliary cirrhosis, 12 with "other" liver diseases, 8 alcoholics, and 20 healthy subjects were studied. Western blotting was used to examine the reactivity of sera from these groups against human small and large bowel aspirates and liver tissue from alcoholic liver disease patients. RESULTS: Serum IgA antibodies to a 140 kDa colonic luminal protein were found in 22 (76%) patients in the alcoholic liver disease group (p < 0.0001), and 7 (24%) patients had serum IgA antibodies to a 40 kDa colonic luminal protein (p = 0.04). These responses were confined to colonic aspirates and not observed in other disease groups, alcoholics or healthy subjects. There was no significant serum IgA response to human liver proteins in alcoholic liver disease. CONCLUSIONS: Serum IgA antibodies to a human 140 kDa colonic luminal protein are frequently found in alcoholic liver disease. This novel antigen may contribute to the increased levels of circulating IgA in alcoholic liver disease.

Adult↗
PubMed1997

Serum intercellular adhesion molecule-1 in alcoholic liver disease and its relationship with histological disease severity.

BACKGROUND: Infiltration of the liver by leukocytes is a histological feature of alcoholic liver disease. Intercellular adhesion molecule-1 (ICAM-1) mediates the migration of lymphocytes from the circulation to target sites of inflammation. It has been demonstrated in the liver of alcoholic liver disease subjects and as a circulating soluble form (sICAM-1). The origin of sICAM-1 and its relationship to disease severity is unknown, although it has been postulated that it may arise from activated T lymphocytes and is an inflammatory marker. AIMS: The aim of the study was to determine the relationship of sICAM-1 to clinical and histological severity of alcoholic liver disease and to serum T-cell (soluble interleukin-2 receptor (sIL-2R), beta 2-microglobulin) and monocyte (neopterin) immune activation markers. METHODS: Serum from 48 outpatients with biopsy proven alcoholic liver disease (steatosis = 9, cirrhosis = 28, hepatitis +/- cirrhosis = 11), 31 with primary biliary cirrhosis and 27 normals was assayed for sICAM-1, sIL-2R, beta 2-microglobulin, and neopterin. RESULTS: sICAM-1 was significantly elevated, p = 0.0001, in alcoholic liver disease and primary biliary cirrhosis patients compared to normals. Circulating sIL-2R (p = 0.0001) and beta 2-microgloblin (p = 0.0034) were significantly elevated in alcoholic liver disease compared to controls. There was a highly significant correlation between levels of sICAM-1 and histological grade of disease, Rs = 0.80 (p = 0.0001), but no significant correlation with clinical correlates of disease severity or circulating immune activation markers. CONCLUSIONS: sICAM-1 is elevated in alcoholic liver disease, is a marker of histological severity of disease and does not appear to originate from activated T lymphocytes. Measurements of sICAM-1 may be useful in assessing histological severity of alcoholic liver disease.

Adult↗
PubMed1997

Helicobacter pylori eradication using a 7-day regimen of low-dose clarithromycin, lansoprazole and amoxycillin.

AIM: To evaluate the efficacy of a 7-day regimen of clarithromycin 250 mg b.d., amoxycillin 1 g b.d., and lansoprazole 30 mg b.d. as a treatment for Helicobacter pylori infection. METHODS: H. pylori status of dyspeptic patients was assessed by 13C-urea breath test and at endoscopy by histology, culture and rapid urease testing of gastric biopsies. Fifty-one H. pylori-positive patients were treated with the above regimen. H. pylori status was reassessed by 13C-urea breath test not less than 28 days after completing treatment. Adverse events and compliance were evaluated. RESULTS: On an intention-to-treat basis. H. pylori infection was cured in 77% (95% CI: 65-88%) of patients. Minor side-effects including diarrhoea, nausea and taste disturbance were reported by 64% of patients. Ninety-five per cent of patients consumed > 95% of tablets. Metronidazole resistance was 29% but all cultures were sensitive to amoxycillin and clarithromycin. CONCLUSION: This 7-day treatment with low-dose clarithromycin was moderately effective in curing H. pylori infection. Although compliance was excellent, there was a high frequency of minor adverse events.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Helicobacter pylori serology and the management of young dyspeptics: a UK survey of gastroenterologists and general practitioners with an interest in gastroenterology.

AIM: To survey the current use of Helicobacter pylori serology for pre-endoscopy screening and management of young dyspeptics amongst gastroenterologists and general practitioners with an interest in gastroenterology in the United Kingdom. METHODS: A postal questionnaire was sent to 536 members of the British Society of Gastroenterology and 164 members of the Primary Care Society in Gastroenterology. RESULTS: Of those who responded (66%), 25% of general practitioners and 17% of gastroenterologists were using H. pylori serology as a screening test for young dyspeptics. General practitioners and gastroenterologists differed in their use of serology to guide management strategies (P < 0.0003): general practitioners eradicate infection from sero-positive patients prior to endoscopy (92%), whilst the majority of gastroenterologists endoscope sero-positive patients before treatment (55%). More gastroenterologists (89%) would re-test all or selected patients to assess eradication compared to general practitioners (45%). 106 different drug regimes were being used as first line treatment. CONCLUSIONS: H. pylori serology as a pre-endoscopy screening test for young dyspeptic patients was used by only a fifth of respondents. There were wide variations in attitudes and practice in the way H. pylori serology was used in the management of young dyspeptics. Trials comparing clinical outcome and cost-effectiveness of different serology-based strategies are needed.

Adult↗
PubMed1997

Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: effect of ursodeoxycholic acid and immunosuppressive therapy.

OBJECTIVES: Soluble intercellular adhesion molecule-1 (sICAM-1) is thought to be released by a variety of cells at sites of inflammation, and their serum levels have been used as markers of inflammatory and immune activity. Our aim was to determine the effect of therapy with ursodeoxycholic acid alone and in combination with azathioprine and prednisone on serum sICAM-1 levels in primary biliary cirrhosis. DESIGN/METHODS: Twenty-four patients with primary biliary cirrhosis and 17 healthy subjects were studied. Primary biliary cirrhosis patients received ursodeoxycholic acid for 12 months and were then randomized in a double-blind fashion to receive prednisone and azathioprine, or placebo in addition to ursodeoxycholic acid. RESULTS: sICAM-1 levels were significantly higher in primary biliary cirrhosis patients than healthy subjects and fell by a median of 20% after 12 months' therapy with ursodeoxycholic acid (P<0.0004). Addition of azathioprine and prednisone to ursodeoxycholic acid resulted in a further reduction of sICAM-1 levels by a median of 25% (P< 0.01). Reductions in sICAM-1 were accompanied by improvement in liver function tests but not in the lymphocyte activation marker, soluble interleukin-2 receptor. CONCLUSION: sICAM-1 levels in primary biliary cirrhosis are reduced by ursodeoxycholic acid. Further reductions were achieved by adding prednisone and azathioprine. These reductions probably reflect an improvement in hepatobiliary excretion and a reduction in cellular production of sICAM-1.

Adult↗
PubMed1995

Soluble E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in primary biliary cirrhosis.

BACKGROUND/AIMS: E-selectin and vascular cell adhesion molecule-1, important in leucocyte adhesion, have recently been detected in soluble form in the circulation. However, their clinical significance remains unclear. Our aims were to determine whether the levels of these molecules are increased in primary biliary cirrhosis, and to relate these to histological disease stage, biochemical measures of liver damage and to lymphocyte activation. METHODS: We studied 42 patients with primary biliary cirrhosis, nine with primary sclerosing cholangitis, 14 with alcoholic liver disease and 17 healthy subjects. Circulating E-selectin and vascular cell adhesion molecule-1 levels were measured by enzyme-linked immunosorbent assay. In subgroups of patients with primary biliary cirrhosis, hepatic bile acid uptake and excretory rates and T-cell activation were also determined. RESULTS: Soluble E-selectin and vascular cell adhesion molecule-1 levels were significantly elevated in primary biliary cirrhosis compared to healthy controls. However, there was no difference between primary biliary cirrhosis and other liver disease groups. In primary biliary cirrhosis, both adhesion molecules correlated with disease stage, but differed in their relationships with specific liver function tests. They did not correlate with either hepatic bile acid uptake or excretion, or lymphocyte activation. CONCLUSIONS: We conclude that soluble E-selectin and vascular cell adhesion molecule-1 are elevated in chronic liver diseases. In primary biliary cirrhosis, they reflect the stage of disease and may reflect the degree of leucocyte adhesion and migration.

Adult↗