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Biomedical subjects

A C Wicks

Publications and source records attributed to A C Wicks.

At least 19 recordsLinked to original sources

Expression of the mucosal gamma delta T cell receptor V region repertoire in patients with IgA nephropathy.

IgA nephropathy (IgAN) is characterized by the deposition of IgA in the glomerular mesangium and often leads to progressive renal dysfunction and kidney failure. We have previously shown that the mesangial IgA is likely to derive from the bone marrow plasma cells, and suggested that a primary abnormality within the mucosal immune system may underly the pathogenesis of IgAN. This study has analyzed the T cell receptor (TCR) variable (V) region expression by gamma delta T cells in the intestinal mucosa of patients with IgAN. The V gamma and V delta usage of TCR transcripts was determined using a semiquantitative reverse transcriptase-PCR protocol. Primers specific for the four human V gamma and six V delta subfamilies were used each with a constant (C) gamma or C delta specific primer, and the PCR-amplified TCR transcripts were detected by Southern blotting and oligonucleotide hybridization. gamma delta TCR V region expression was determined in gut biopsies and peripheral blood of 11 patients with IgAN, and the TCR V gamma and V delta repertoires were compared to those in gut and peripheral blood of 11 control individuals. gamma delta T cells in normal blood predominantly expressed V gamma 2 (V gamma 9 gene) and V delta 2 gene segments whereas those in normal gut mainly expressed V gamma 3 and V delta 3. In IgAN patients, V delta 2 was also the predominant V delta gene utilized by peripheral blood gamma delta T cells, however, we observed a predominance of V gamma 3 and reduced V gamma 2 usage by these cells. gamma delta T cells in the gut of IgAN patients mainly used V gamma 3 and V delta 1. While the gamma and delta TCR V region repertoires did not differ significantly between the peripheral blood of patients and controls, there were significant differences in V gamma and V delta repertoire expression between IgAN and control gut biopsies. V gamma 3 gene expression was significantly decreased in IgAN gut compared to control gut (P = 0.023). In addition, there was a significant decrease in V delta 3 gene expression in IgAN gut compared to control gut (P = 0.043). These findings indicate that a subpopulation of gamma delta T cells, which represent the majority of gamma delta T cells in normal gut mucosa, are significantly diminished in the gut of patients with IgAN. This suggests that a "hole" in the mucosal gamma delta T cell repertoire may play a fundamental role in contributing to the pathogenesis of IgAN.

Adult

Near patient testing for Helicobacter pylori: a detailed evaluation of the Cortecs Helisal Rapid Blood test.

OBJECTIVE: To evaluate the Cortecs Helisal Rapid Blood test for accuracy overall and in specific subgroups by age and ethnic origin. Additionally, to assess readability of results, including inter-observer error, with consideration also given to usability and acceptability. DESIGN: A prospective evaluation using four reference tests. SETTING: A hospital endoscopy unit. METHODS: Two hundred patients attending for endoscopy were recruited for H. pylori testing with the Helisal test, plus antral biopsies for CLO test, culture and histology and serology using a commercial enzyme-linked immunosorbent assay (ELISA). The Helisal test was carried out and results read strictly according to the manufacturer's instructions. Two or more reference tests positive were taken as a gold standard positive; all results negative as negative and any remaining cases were regarded as equivocal. Performance figures were calculated twice, treating patients with equivocal status as either positive or negative. Results were in most cases double-read, blinded, by two observers and readings subsequently compared. RESULTS: The test was considered convenient, easy to use and acceptable to symptomatic patients, but a notable proportion (10%) of results were very difficult to read. Sensitivity was acceptable (91-92% overall, 95% confidence interval (CI) 82-97%), but specificity was poor overall (56-62%, 95% CI 45-72%), and particularly in patients aged 45 years or over (44-51%) and those of South Asian origin (42-50%). CONCLUSION: The test could be appropriate for testing younger symptomatic patients. Its usefulness was, however, found to be limited by poor readability of some results and poor specificity. Reading of some results as equivocal would be appropriate.

Adult

Ten years' experience of screening patients with Barrett's oesophagus in a university teaching hospital.

BACKGROUND: Barrett's metaplasia is a premalignant condition for which screening is recommended. AIMS/METHODS: Annual screening endoscopies have been performed on all subjects suitable for surgery for many years. To examine the benefits to patients of continuing this policy 10 years' experience of screening for Barrett's oesophagus was reviewed. RESULTS: Of the 29,374 endoscopies performed over this period, Barrett's metaplasia was present in 1.4%. There was an approximate equal sex distribution with the majority of cases being identified in patients over 50 years old. Thirty five per cent of these patients were suitable to enter a yearly screening programme. During screening, the length of oesophagus involved did not vary over time. As a result of 379 endoscopies performed for screening purposes, only one patient was identified as developing carcinoma solely as a result of the screening programme. Two further patients had carcinoma identified as a result of progressive dysphagia requiring additional endoscopies. All three patients who developed carcinoma while in the screening programme had "long segment" (> 8 cm) regions of Barrett's metaplasia with a stricture present at the initial endoscopy. CONCLUSIONS: The poor yield from this screening programme suggests that the policy should be reconsidered. Resources may be better spent on focusing on patients who present with ulceration or stricture in addition to Barrett's metaplasia.

Barrett Esophagus

Selection criteria for preoperative endoscopic retrograde cholangiopancreatography in the laparoscopic era.

BACKGROUND: Indicators for cholangiography were originally designed to select patients at risk for common bile duct (CBD) stones for intraoperative cholangiography. OBJECTIVE: To refine these criteria to apply to the much more invasive procedure of preoperative endoscopic retrograde cholangiopancreatography (ERCP). DESIGN: Retrospective review of selection criteria for ERCP in consecutive patients referred over 18 months following the introduction of laparoscopic cholecystectomy. SETTING: Two ERCP units in adjacent teaching hospitals. PATIENTS: Three hundred seventeen patients with gallstones and in situ gallbladders. INTERVENTION: Common bile duct imaging at ERCP. MAIN OUTCOME MEASURES: Abnormalities justifying ERCP. RESULTS: Abnormalities justifying ERCP were found in 66% of patients. This group differed significantly from those with normal ducts, with more being referred with abnormal results of all liver function tests (P < .001), jaundice (P < = .001), a dilated CBD on ultrasound (P < .001), or CBD stones on ultrasound (P < .001). On the other hand, patients with normal ducts were significantly more likely to have been referred with pancreatitis (P = .003) or elevated results of individual liver function tests (P < .001). A logistic regression model using age, presence of jaundice at ERCP, levels of alkaline phosphatase and albumin, and ultrasonography showing dilated ducts or visible CBD stones was found to have a specificity of 75% and a sensitivity of 89%. Past pancreatitis or elevated results of individual liver function tests were not predictive factors. CONCLUSION: The use of such a model rather than individual criteria would improve the selection of patients for preoperative ERCP, optimizing its role in the laparoscopic era.

Adult

No obvious advantages for thoracoscopic two-stage oesophagectomy.

Thoracoscopically assisted Ivor-Lewis oesophagectomy potentially combines the pulmonary advantages of transhiatal oesophageal dissection, with the visibility and control permitted by thoracotomy. This study reviewed 17 patients who underwent this procedure with an intrathoracic anastomosis. Five patients required conversion to thoracotomy, four because of technical difficulties with the anastomosis. After operation 13 patients had radiological evidence of atelectasis, six developed a left pleural effusion and five had clinically significant pneumonia. Three patients developed an anastomotic leak, two of whom died giving an in-hospital mortality rate of 12 per cent. Median postoperative hospital stay was 12 days. Four patients developed benign anastomotic strictures requiring dilatation. The 1- and 2-year survival rates were 73 per cent (11 of 15 patients) and 63 per cent (five of eight) respectively. The use of minimal access techniques in this context does not appear to reduce the postoperative incidence of either pulmonary or anastomotic complications.

Adenocarcinoma

Three simple methods of detecting malnutrition on medical wards.

Malnutrition in hospital is often unrecognized. A nutrition team aims to teach simple methods of detecting malnutrition. On a single day all medical in-patients underwent a nutritional assessment. Eighty-four patients (43 men), median age 71 years (range 28-97), were assessed. The most common diagnoses were cardiac disease (26), stroke/dementia (12), non-malignant lung disease (9) and malignancy (6). A weight loss of more than 10% (%WL) was found in 17/65 (26%) and a body mass index (BMI) of less than 19 kg/m2 in 13/69 (19%). A mid-arm muscle circumference (MAMC) less than the fifth percentile occurred in 16/83 (19%) patients. Percentage weight loss alone detected seven patients of whom four were overweight (BMI > 25 kg/m2), BMI alone detected three patients, and MAMC alone eight patients of whom three could not be weighed and three had fluid retention. There was fluid retention in 35/84 (42%) patients of whom nine were malnourished (six detected by BMI and/or %WL, and three by MAMC alone). All three measurements were made in 64 patients, six (9%) of whom were detected as malnourished by all three methods. Combining the three measurements 29/84 (35%) of patients were malnourished and only 28% of these patients had been assessed by a dietitian. BMI and %WL detect most patients but fluid retention may limit their accuracy. MAMC is useful in those who cannot be weighed or who have fluid retention.

Adult

Laparoscopic Heller's cardiomyotomy without an antireflux procedure.

The treatment of achalasia by laparoscopic Heller's cardiomyotomy may combine the minimally invasive advantages of pneumatic dilatation with the success rate and low risk of perforation of conventional surgery. The requirement for an antireflux procedure remains a contentious issue, as in conventional surgery. Nine patients underwent laparoscopic cardiomyotomy; excellent symptomatic relief was obtained in eight at follow-up between 12 and 21 months after operation. Four of these patients agreed to 24-h pH monitoring and showed no evidence of acid reflux. One patient, however, developed recurrent symptoms associated with significant acidity on monitoring. Laparoscopic Heller's cardiomyotomy without an antireflux procedure produced effective symptomatic relief in this small group of patients.

Adult

Colorectal cancer screening in asymptomatic populations.

Colorectal cancer is the second commonest cause of cancer death in the UK. An effective national screening programme is urgently required to reduce the substantial morbidity and mortality from the disease. The success of any screening programme will depend on the screening test detecting early Dukes's A carcinomas and adenomatous polyps. Prognosis is directly related to tumour staging and a proportion of carcinomas are thought to arise from polyps. Two screening methods exist--faecal occult blood testing and sigmoidoscopy. Large trials of faecal occult blood testing show that it detects more early lesions than in patients presenting with symptoms, but whether this reduces mortality is not yet confirmed and lack of sensitivity for cancers and polyps may ultimately limits its usefulness. The role of sigmoidoscopy in screening, particularly flexible sigmoidoscopy, has not been fully investigated. Flexible sigmoidoscopy has a greater sensitivity for distal lesions than stool testing and a randomised controlled trial of its efficacy is planned in Britain. Compliance with screening is essential to ensure its cost effectiveness in both health and economic terms. Large trials of faecal occult blood testing conducted over several years achieved compliance rates in excess of 60%, although in smaller studies these are often much less. Women frequently participate more than men. There are many reasons for non-compliance including lack of appreciation of the concept of asymptomatic illness and fear of the screening tests and cancer itself. Colorectal cancer screening is relatively cheap compared with breast and cervical cancer screening. Provisional cost estimates suggest that the amount spent to detect or prevent cancer by screening is similar to the amount required to treat a symptomatic patient.

Adenoma

Screening for colorectal cancer: reasons for refusal of faecal occult blood testing in a general practice in England.

STUDY OBJECTIVE: To ascertain reasons for non-compliance with faecal occult blood tests in colorectal cancer screening programmes. DESIGN: A standard interview by a trained nurse of a random sample of those who declined screening. SETTING: The Leicestershire town of Market Harborough, where most of the 25,000 population are served by a single general practice of 10 partners. PARTICIPANTS: Altogether 4185 residents aged 51 to 70 years were invited to receive a free faecal occult blood test (Haemoccult). Eighty one subjects from a sample of 351 who wrote declining the offer were interviewed. MAIN RESULTS: Non-compliers were divided into those who did not request a test kit and those who returned an unused kit. In the former group the commonest reasons given were intercurrent illness (39%), fear of further tests and surgery (24%), and feeling well (22%). For those who returned unused kits the commonest reasons were the unpleasantness of the stool collection procedure (65%), feeling well (30%), intercurrent illness (23%), and fear of further tests and surgery (20%). In both groups the main concern of those who did not comply were fear of further diagnostic tests and surgery rather than concern at the lack of effective treatment for cancer. CONCLUSIONS: To increase compliance, education and publicity must explain the concept of asymptomatic illness and allay people's fear of hospital investigation and treatment. The benefits of screening should be particularly emphasised to those who return kits so they may overcome their reservations.

Aged

Factors predicting outcome after selective ERCP in the laparoscopic era.

This study assessed the outcome of 342 patients with in situ gallbladders undergoing ERCP for suspected choledocholithiasis. The result of ERCP was found to play a significant role (P < 0.0001) in determining whether patients were subsequently managed conservatively (n = 152) or underwent either laparoscopic (n = 110) or open (n = 80) surgery. Those undergoing laparoscopic surgery were noted to be younger (P = 0.0001) and were less likely to be jaundiced (P = 0.0015) or have CBD stones at ERCP (P = 0.0295). In 28 patients with CBD stones remaining after ERCP, pre- rather than postoperative timing of ERCP prevented a potential second operation. The current success rate of 85% in clearing CBD stones at ERCP cannot support a routine policy of intraoperative cholangiography followed by postoperative ERCP.

Adolescent

Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy.

Glomerular IgA in IgA nephropathy (IgAN) is at least in part polymeric, and is thought to derive from the mucosal IgA system in view of the association between mucosal infection and haematuria in this condition. To investigate this hypothesis, an in situ hybridization (ISH) technique was developed for the detection of J chain mRNA, the expression of which has been correlated with the secretion of high level polymeric immunoglobulin (pIg). Endoscopic duodenal biopsies from ten patients and matched controls were examined by: (i) two color immunofluorescence (IF); (ii) ISH; and (iii) combined ISH and IF, to permit simultaneous identification of plasma cell type. IF revealed a reduction in the percentage of IgA plasma cells (P < 0.02) and increased absolute numbers of IgG cells (P < 0.02) in patient biopsies. ISH demonstrated fewer J chain mRNA expressing plasma cells (P < 0.005) with lower signal intensity (P < 0.002) in patients' biopsies compared with controls. Combined ISH and IF confirmed a reduction in J chain mRNA-positive IgA plasma cells in the patient biopsies (P < 0.02). The reduction in J chain mRNA expression in duodenal IgA plasma cells in IgAN argues against the gastrointestinal lamina propria as the source of glomerular pIgA.

Adult

Butterfat absorption--a valuable screening test in malabsorption.

The diagnosis of intestinal malabsorption is difficult to make without the use of specific tests such as endoscopic retrograde cholangiopancreatography (ERCP) or duodenal biopsy which are invasive and potentially hazardous. Faecal fat estimation or C14 Triolein breath tests have limitations as screening tools are time consuming and expensive. The butterfat absorption test (BFAT) is, in contrast, a simple, quick and cheap test for fat malabsorption. We have assessed the performance of this test in a blinded retrospective study of all such procedures performed in a teaching hospital over an 8 year period. One hundred and fourteen cases of suspected malabsorption had one or more butterfat tests. These were divided into absorbers and malabsorbers without knowledge of the butterfat test results. We found the butterfat test to have a sensitivity of 88% and a specificity of 94% using a cut-off of 20 light-scattering intensity units to discriminate normal from abnormal tests. At this level, predictive values are 91% for a positive result and 92% for a negative. These results are similar to those reported with the C14 Triolein breath test and adjusted faecal fats. We conclude that the butterfat test is a simple, cheap and effective screening test in the diagnosis of malabsorption.

Adolescent

National industry's interest in colorectal cancer screening programmes.

The interest of the largest 200 British industries in developing and financing colorectal screening services for employees was determined. A standard questionnaire asked if the company would advertise screening supply names of employees to local hospitals and finance faecal occult blood testing. The reasons for rejection were noted. Eighty-six companies returned the questionnaire (43% response rate) of which 78 firms (39% of the total mailed) were prepared to advertise screening programmes at the workplace. A quarter of the companies were prepared to both advertise and release employee details. Companies willing to participate employed significantly more people (mean of 17,000 employees) than those rejecting screening (mean of 6100 employees, Mann-Whitney U test = 7, P < 0.05). Fifty-nine industries would consider financing screening, although only five made a definite decision to do so. All companies rejecting (36/36) were concerned about releasing employee information to hospitals. If screening does reduce mortality and community programmes are developed industry could and is prepared to advertise such programmes. If a partnership between hospitals and industry is developed, concerns about employee confidentiality needs to be addressed.

Advertising

A nationwide survey of liver biopsy--is there a need to increase resources, manpower and training?

A postal questionnaire survey was conducted to establish the pattern of current practice of liver biopsy, to estimate the frequency of adverse events and their possible associations, and to compare respondents' personal preferences with what they offer patients. Three hundred and sixty-four members of the British Society of Gastroenterology (BSG) were questioned. There were 296 returns, of which 278 were appropriate, giving an overall response rate of 81.3%. Over the previous 2 years complications were reported in 80 patients who required blood transfusion, 11 who needed laparotomy (including 1 for pain), 13 with septicemic shock, 29 who had peritonitis, and 1 with a subphrenic collection; 53 had pulmonary complications (hemoptysis, pneumothorax and 1 hemothorax), and there were 19 deaths. The overall complication rate was 5.6 per 1,000, and the mortality rate 5.2 per 10,000. The complication rate gradually decreased with increasing number of biopsies performed until the number reached 20 per month, after which there was a significant increase in complications (chi 2 = 42.98, p < 0.001). Although 50% of the respondents were themselves prepared to have a liver biopsy on a day case basis, only 11% do it routinely on patients, and 72% do not offer it at all (chi 2 = 76.8, p < 0.001). There were no differences in complication and death rates between the above groups, but those who do occasional (< 50%) day case biopsies have a significantly higher complication rate (chi 2 = 24.3, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle

Mortality in patients with ulcerative colitis in Leicestershire, 1972-1989. An epidemiological study.

The mortality in 1014 patients with ulcerative proctocolitis diagnosed while resident in Leicestershire identified in a population-based study from 1972 to 1989 was assessed. Ninety-two Europeans and one South Asian died. The standardized mortality ratio (SMR) in South Asians was 26 (95% confidence interval 0-147). In Europeans the overall mortality was not increased, the SMR was 93 (95% confidence interval 75-114). The SMR did not differ between established disease extents, but was highest in those patients in whom the extent was undefined (SMR = 237, 95% confidence interval 130-397). Comparison of SMRs and survival curves showed no difference in mortality in patients diagnosed from 1972 to 1980 and from 1981 to 1989. Mortality was similar in patients who had colectomy and those who had not (SMR = 130, 95% confidence interval 71-219, chi 2(1) = 1.2, NS). Mortality did not change during the study. These findings should be made available to patients and their families.

Adult