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Biomedical subjects

J D Maxwell

Publications and source records attributed to J D Maxwell.

At least 19 recordsLinked to original sources
PubMed1999

Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver function tests and prolongs survival in primary biliary cirrhosis (PBC). The dose of 10- 15 mg/kg/day used in the large trials has largely been based on that used for gallstone dissolution. The only dose-response study of UDCA in PBC suggested that a dose of 8 mg/kg/day was the most efficacious. However, disease stage of the patients was not known, higher doses of UDCA were not tried and there was no 'washout period' between the different doses. The aim of this study was to determine the optimum dose of UDCA in early-stage PBC (stage 1 and 2). METHODS: Twenty-four biopsy-proven early-stage PBC patients (one male, 23 female) received five doses of UDCA (0, 300, 600, 900, 1200 mg/day) each for 8 weeks with 4-week washout periods between doses. Symptoms (pruritus, fatigue, diarrhoea) were assessed on a four-point scale (none, mild, moderate, severe). Liver function tests (LFTs) were performed using conventional methods, and serum bile acids were measured using gas liquid chromatography. RESULTS: The dose of 900 mg/day produced the greatest enrichment of UDCA in serum bile acids; although there was no difference in the enrichment of UDCA between the different doses. There was a trend towards normalization of the abnormal LFTs in a dose-dependent manner (for y-glutamyl transferase (yGT), alkaline phosphatase (ALP), alanine transaminase (ALT) and IgM). Multi-factorial analysis showed that UDCA treatment, irrespective of dose, was significantly better than placebo for all the variables. The 900 and 1200 mg doses were better than both 300 and 600 mg using yGT and total bilirubin as variables, better than 300 mg using ALP and IgM as variables, and better than 600 mg using albumin as a variable. No variables showed a significant difference between 900 and 1200 mg. CONCLUSION: The optimum dose of UDCA is 900 mg/day (equivalent to 13.5 mg/kg/day).

Adult↗
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

A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in terminal galactose and N-acetylglucosamine.

Serum IgG from rheumatoid arthritis patients contains a decreased number of oligosaccharide structures ending in galactose and thus there is an increase in N-acetylglucosamine as the terminal sugar, compared with healthy individuals. The relationship between these two sugars varies depending on the disease examined: IgG from patients with rheumatoid arthritis, juvenile onset chronic arthritis and Crohn's disease are at one extreme, and exhibit a reciprocal galactose:N-acetylglucosamine relationship, while Sjögren's syndrome and osteoarthritis IgG are at the other extreme, exhibiting a parallel increase in the expression of both galactose and N-acetylglucosamine. These results may occur as a consequence of more than one glycosylation site which is differentially glycosylated, but more likely by changes in the level of bisecting N-acetylglucosamine.

Acetylglucosamine↗
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

Is there an irritable bladder in the irritable bowel syndrome?

In this prospective case controlled study 16 premenopausal women with documented irritable bowel syndrome were recruited from the gastroenterology clinic and 16 premenopausal controls without symptoms of irritable bowel syndrome were recruited from the gynaecology clinic. All women answered a standardised bowel and urinary symptom questionnaire and underwent twin channel subtracted cystometry. Women with irritable bowel syndrome also underwent oesophageal balloon distension studies for perception and pain. Oesophageal and bladder sensory thresholds were compared. Urinary frequency and urgency and the urodynamic finding of detrusor instability were significantly more common in women with irritable bowel syndrome (P < 0.05). We were unable to demonstrate a relationship between first sensation of bladder fullness and oesophageal perception or between maximum bladder capacity and oesophageal pain thresholds. These findings suggest that there is an irritable bladder in the irritable bowel syndrome and support the concept that irritable bowel syndrome is part of a generalised disorder of smooth muscle.

Adult↗
PubMed1996

Review article: quantitative leucocyte scanning in the assessment of inflammatory bowel disease activity and its response to therapy.

Inflammatory bowel disease (IBD) symptoms may be due not only to the effects of bowel inflammation, but also can result from many non-inflammatory consequences of the disease. Clinical scores and health questionnaire ratings produce a global assessment which is useful in the overall evaluation of the impact of the illness on the patient, and the effect of treatment. However many studies have failed to recognize the need to separately assess changes in the degree of bowel inflammation, in addition to a global clinical response. Radiolabelled white cell scanning using 111-indium has been shown to provide an accurate, quantitative and non-invasive method for assessing the degree of bowel inflammation in IBD and its response to therapy, using faecal collection or total body counts of radioactivity. More recently 99mTc hexamethyl propylene amine oxime (HMPAO) labelled white cell scanning has been introduced, which has advantages over the 111-indium method, including reduced radiation dosimetry and enhanced image quality. 99mTc-HMPAO scanning using three-dimensional white cell scanning (single photon emission computerized tomography; SPECT) allows visualization of the entire bowel separate from overlying structures. 99mTc-HMPAO white cell scanning with SPECT has now been computerized and automated to permit measurement of segmental and total bowel radiolabelled white cell infiltrate. This method could potentially provide the gold standard for objective assessment of the response of disease activity in Crohn's disease and ulcerative colitis, and merits application in clinical trials of novel therapies for IBD.

Acute-Phase Proteins↗
PubMed1996

Seasonality of tuberculosis: the reverse of other respiratory diseases in the UK.

BACKGROUND: In Western societies there is a winter peak in mortality, largely accounted for by respiratory and cardiovascular deaths. In view of the known seasonal variation in vitamin D, and of the postulated link between tuberculosis and vitamin D deficiency, a study was undertaken to examine whether the presentation of tuberculosis had the same seasonal rhythm as other pulmonary infections. METHODS: Using cosinor analysis the presence or absence of seasonality was determined for 57,313 tuberculosis notifications for England and Wales. OPCS data in four weekly notifications over a 10 year period (1983-92) were examined as two quinquential sets (1983-7 and 1988-92). These were compared with two groups of acute respiratory illness: 138,992 notifications to OPCS of pneumonia deaths for 1988-92 and all admissions to Scottish hospitals with respiratory disease (252,163 cases) during 1980-4. RESULTS: Analysis of notifications of tuberculosis revealed a summer peak with an amplitude of 10%. This pattern differs markedly from other respiratory disorders in which a winter peak and summer trough is observed. CONCLUSIONS: The unusual seasonality of tuberculosis is currently unexplained. One possibility is that low post-winter trough levels of vitamin D (which are known to affect macrophage function and cell mediated immunity) might result in impaired cellular immunity leading, after a latent period, to reactivation of dormant mycobacterial infection.

Humans↗
PubMed1995

Prospective screening of dyspeptic patients by Helicobacter pylori serology.

Helicobacter pylori infection is associated with 95% of duodenal ulcers and more than 80% of gastric ulcers. Several reports have indicated that screening for H pylori may avoid subsequent endoscopic examination. We screened 183 dyspeptic patients, aged under 45, by taking a history of sinister symptoms and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), together with serological testing for H pylori. Endoscopy was performed on 113 patients, of whom 90 (49%) were seropositive, 14 (8%) had sinister symptoms, and 9 (5%) had used NSAIDs regularly. In 34 (19%) patients we detected peptic ulceration. The remaining 70 (38%) patients who were H pylori seronegative, had no sinister symptoms, and had not taken NSAIDs (screen-negative), did not undergo endoscopy but were returned to their primary care physician for treatment of symptoms. At subsequent reassessment (of the non-endoscoped group), symptom severity (p = 0.002), interference with life events (p = 0.01), and medication (p = 0.0002) were all significantly lower in the 6 months after screening than in the 6 month period before screening. Only three screen-negative patients were re-referred after screening but their endoscopic findings were normal. Thus, 67 (36%) endoscopies were avoided. When the non-endoscoped screen-negative patients were compared with a cohort of endoscoped screen-negative patients, the groups did not differ in terms of symptom severity (odds ratio 1.12, 95% CI 0.53-2.35, p = 0.77) or interference with life events (0.82, 0.38-1.76, p-0.61). However, medication use was significantly less (0.37, 0.17-0.80, p = 0.01) in those who did not have an endoscopy. Our study indicates that colonisation screening based on H pylori serology, a history of sinister symptoms, or a history of NSAID use was worthwhile in dyspeptic patients. We avoided 37% of endoscopies and reduced drug usage without disadvantaging those not endoscoped.

Adult↗
PubMed1995

Extracellular cation sensing by the enterocyte: prediction of a novel divalent cation "receptor".

We report that the divalent cation Ni2+ elicits elevations in the cytosolic free Ca2+ concentration ([Ca2+]) in cultured enterocytes. These elevations were monophasic, each response consisting of a rapid initial transient rise of cytosolic [Ca2+] to a peak value followed by an exponential decline. The magnitude of the cytosolic [Ca2+] elevation varied with the concentration of applied Ni2+. In some cells, a single application of Ni2+ induced oscillatory changes in cytosolic [Ca2+]. There was also evidence for use-dependent inactivation: a conditioning application of Ni2+ substantially attenuated the response resulting from its subsequent application. Our findings thus demonstrate the existence of a divalent cation-sensing "receptor" on the enterocyte. This putative receptor may play a role in regulating mineral absorption across the enterocyte membrane.

Calcium↗
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↗
PubMed1995

Direct assessment of the mechanism for a raised serum bile acid level in chronic liver disease.

BACKGROUND: Impaired hepatic uptake is the major cause of raised serum bile acid levels in liver disease, but confirmation in humans by direct measurement is lacking. The synthetic gamma-labelled bile acid 75Se-homocholic acid taurine (75SeHCAT) provides a tool for the direct measurement of hepatic bile acid handling. OBJECTIVE: To determine the interrelationships among hepatic handling of 75SeHCAT, the kinetics of its disappearance from plasma and serum bile acid levels in patients with chronic liver disease. DESIGN: We studied 12 patients with primary biliary cirrhosis and 14 with cirrhosis arising from other causes. Fasting serum bile acid levels were measured enzymatically. After intravenous administration of 75SeHCAT, we determined plasma disappearance rates (initial K1, late K2) from serial blood samples and hepatic uptake and excretory rates directly from dynamic abdominal gamma-camera scanning. Both scanning and sampling were carried out over a period of 90 min. RESULTS: Serum bile acid concentrations correlated with K1 and with hepatic uptake (Rs = -0.53, P < 0.01; Rs = -0.47, P < 0.02, respectively) but neither with K2 nor with the excretory rate. K1 and uptake were reduced (P < 0.05) in patients with high serum bile acid levels and in those with varices. Serum bile acid levels were higher in patients with varices (P < 0.05), which might suggest that portosystemic shunting occurred. However, this is unlikely because the varices were not independent of liver function. CONCLUSION: Hepatic bile acid uptake and excretion are independent processes. Hepatic uptake is related to initial, whereas hepatic excretion is related to late, plasma disappearance. Impaired hepatic uptake is a major determinant of the rise in serum bile acid levels in chronic liver disease.

Adult↗
PubMed1995

Quantification of inflammatory bowel disease activity using technetium-99m HMPAO labelled leucocyte single photon emission computerised tomography (SPECT).

Technetium-99m HMPAO labelled white cell bowel uptake was quantified in 23 patients with suspected colitis by means of the novel technique of single photon emission computerised tomography (SPECT) using a standard gamma-camera. Uptake in colon segments was quantified on transaxial images and expressed as a fraction of marrow uptake (SPECT score). Segmental histological disease activity was assessed at colonoscopy (20) or at surgery (3). Segmental histology score correlated with SPECT score r = 0.79 (p < 0.001). Overall SPECT score for all affected segments correlated with Crohn's disease activity index (CDAI) r = 0.66, p = 0.001 and with laboratory activity indices; erythrocyte sedimentation rate r = 0.44, p = 0.03, C reactive protein r = 0.38, p = 0.05, and albumin r = -0.46, p = 0.03. Small bowel SPECT score in 13 patients correlated with CDAI r = 0.65, p < 0.01 but not with erythrocyte sedimentation rate or C reactive protein. Five patients with positive small bowel white cell uptake had normal C reactive protein and erythrocyte sedimentation rate. Overall SPECT score for disease at all sites correlated with both CDAI and with laboratory indices of inflammation. 99mTc HMPAO SPECT provides non-invasive and accurate quantification of inflammatory bowel disease activity in both large and small bowel and may be useful in the objective evaluation of treatment for inflammatory bowel disease.

Adult↗
PubMed1995

Serology for Helicobacter pylori compared with symptom questionnaires in screening before direct access endoscopy.

This prospective study aimed to compare serology for Helicobacter pylori with two, symptom questionnaires in screening patients before direct access endoscopy. Methods were compared in terms of the number of endoscopies saved and pathology missed in 315 patients referred to a gastroenterology unit by 65 local GPs. The serology used was based on an acid glycine extract of H pylori. One in-house questionnaire was based on the Glasgow dyspepsia (GLADYS) system and the other questionnaire was that reported by Holdstock et al. A cut off point of 6.3 U/ml for H pylori serology was selected for screening patients (97% sensitive and 75% specific). Serology was combined with a history of NSAID usage in determining who should have endoscopy. For the in-house questionnaire, a cut off score of more than 8 out of a possible maximum of 18 was chosen, after prior evaluation in 118 patients referred for direct access endoscopy (the sensitivity for detection of peptic ulcer was 88%, specificity 61%). A cut off score of more than 412 was used for the Holdstock questionnaire. In patients under 45 years, serology detected more peptic ulcers than the in-house questionnaire and the Holdstock questionnaire (27/28 v 24/28, NS and v 20/28, p < 0.05 respectively). The Holdstock questionnaire saved significantly more endoscopies than the other two methods (76/149 v 57/149 for the in-house questionnaire, p = 0.05 and 59/149 for serology, p = 0.05). In all age groups combined, serology was significantly better than the in-house and Holdstock questionnaires at detecting peptic ulcers and gastric cancer (61/63, 52/63, p<0.02, and 50/63, p<0.01 respectively). But serology saved significantly fewer endoscopies (89/315, 135/315, p<0.005, and 119/315, p<0.05 respectively). Serology was inferior to the Holdstock questionnaire at detecting severe oesophagitis. It is concluded that serology is the method of choice in screening before direct access upper gastrointestinal endoscopy in those under 45 years. It best combines a high sensitivity for peptic ulcer disease with a large reduction in unnecessary negative endoscopies.

Adolescent↗
PubMed1995

Comparison of 99m technetium hexamethylpropylene-amine oxime labelled leucocyte with 111-indium tropolonate labelled granulocyte scanning and ultrasound in the diagnosis of intra-abdominal abscess.

Fifty patients with suspected intra-abdominal abscess were investigated prospectively with ultrasound and with 99mTc-hexamethylpropylene-amine oxime (HMPAO) isotope labelled mixed leucocytes, using 111-In tropolonate granulocyte scanning as the reference standard. Twenty five patients had inflammatory bowel disease (three were postoperative): 21 of these had Crohn's disease and four had ulcerative colitis. The remainder comprised nine with postoperative fever and 16 with fever and abdominal pain. An abscess was diagnosed when focal activity on serial 111-In tropolonate and 99m-Tc-HMPOA images at one, three, and 24 hours resulted in activity at least equal to liver activity at 24 hours. Thirteen abscesses were diagnosed using each type of white cell scanning, resulting in 100% sensitivity for 99m-Tc-HMPAO compared with 111-In tropolonate. Bowel inflammation was easily distinguished from abscess on serial images. Eight of these 13 abscesses were detected by ultrasound. Altogether 17 abscesses were found. Ultrasound detected 12, including four liver abscesses which were not purulent and had not been detected by white cell scanning. Ultrasound had a sensitivity of 71% (12 of 17) and a specificity of 87% (33 of 38) using all confirmed abscesses as the reference standard. White cell scanning showed a sensitivity of 76% (13 of 17: as a result of the four non-purulent liver abscesses) and a specificity of 100%. 99m-Tc-HMPAO scanning is as accurate as 111-In tropolonate scanning, and has several advantages including simplicity, availability, superior image quality, and reduced radiation dose. Both methods are more sensitive and specific than ultrasound for intra-abdominal abscess detection but ultrasound is advisable if a neutrophil infiltrate is not suspected.

Abdominal Abscess↗