Validating the prediction of lower urinary tract infection in primary care: sensitivity and specificity of urinary dipsticks and clinical scores in women.

BACKGROUND: Dipsticks are one of the most commonly used near-patient tests in primary care, but few clinical or dipstick algorithms have been rigorously developed. AIM: To confirm whether previously documented clinical and dipstick variables and algorithms predict laboratory diagnosis of urinary tract infection (UTI). DESIGN OF STUDY: Validation study. SETTING: Primary care. METHOD: A total of 434 adult females with suspected lower UTI had bacteriuria assessed using the European Urinalysis Guidelines. RESULTS: Sixty-six per cent of patients had confirmed UTI. The predictive values of nitrite, leucocyte esterase (+ or greater), and blood (haemolysed trace or greater) were confirmed (independent multivariate odds ratios = 5.6, 3.5, and 2.1 respectively). The previously developed dipstick rule--based on presence of nitrite, or both leucocytes and blood-- was moderately sensitive (75%) but less specific (66%; positive predictive value [PPV] 81%, negative predictive value [NPV] 57%). Predictive values were improved by varying the cut-off point: NPV was 76% for all three dipstick results being negative; the PPV was 92% for having nitrite and either blood or leucocyte esterase. Urine offensive smell was not found to be predictive in this sample; for a clinical score using the remaining three predictive clinical features (urine cloudiness, dysuria, and nocturia), NPV was 67% for none of the features, and PPV was 82% for three features. CONCLUSION: A clinical score is of limited value in increasing diagnostic precision. Dipstick results can modestly improve diagnostic precision but poorly rule out infection. Clinicians need strategies to take account of poor NPVs.

The surgical management of acute upper gastrointestinal bleeding: a 12-year experience.

INTRODUCTION: Acute upper gastrointestinal bleeding (AUGIB) is a common reason for admission to gastroenterologists, with only 2% of patients requiring surgical intervention. The aim of this study was to review the surgical management of patients with non-variceal AUGIB in a single institution over a 12-year period and compare practice with recognised regional and national standards. MATERIALS AND METHODS: Data was collected retrospectively for all patients undergoing surgery for AUGIB between September 1995 and September 2007. Audit standards included the local hospital protocol, British Society of Gastroenterology Endoscopy Committee guidelines and the UK Comparative Audit of AUGIB and the Use of Blood. RESULTS: 53 patients were identified, of which 41 case notes were available. Mean (range) age of the patients was 75.8 (45-92) years. 56% had pre-existing cardiorespiratory comorbidity and 63% were taking anti-inflammatory drugs. Pre-operative Rockall score was >or=7 in 46% and ASA score was >or=3 in 65% of patients. 56% of operations were performed by the registrar, compared with 20% reported nationally. All cases after 2004 were performed by the consultant. No operations were performed after midnight beyond 1999. 23 (56%) patients suffered post-operative complications compared with 55% reported nationally; cardiorespiratory (n = 16), wound infection (n = 7) and rebleed (n = 6). 37% required intensive care support and median length of hospital stay was 13 days. In-hospital mortality rate was 10%, compared with 30% reported nationally and this increased with rising Rockall, Blatchford, APACHE-2, P-POSSUM and Charlson scores. CONCLUSIONS: These findings highlight the high rate of morbidity and mortality associated with surgical treatment for AUGIB. The small volume of cases and reduction in registrar operating raises training issues. An integrated approach with greater use of interventional radiology is likely to play a greater role in the future.

Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: observational study.

OBJECTIVE: To assess the natural course and the important predictors of severe symptoms in urinary tract infection and the effect of antibiotics and antibiotic resistance. DESIGN: Observational study. SETTING: Primary care. PARTICIPANTS: 839 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection. MAIN OUTCOME MEASURE: Duration and severity of symptoms. RESULTS: 684 women provided some information on symptoms; 511 had both laboratory results and complete symptom diaries. For women with infections sensitive to antibiotics, severe symptoms, rated as a moderately bad problem or worse, lasted 3.32 days on average. After adjustment for other predictors, moderately bad symptoms lasted 56% longer (incidence rate ratio 1.56, 95% confidence interval 1.22 to 1.99, P<0.001) in women with resistant infections; 62% longer (1.62, 1.13 to 2.31, P=0.008) when no antibiotics prescribed; and 33% longer (1.33, 1.14 to 1.56, P<0.001) in women with urethral syndrome. The duration of symptoms was shorter if the doctor was perceived to be positive about diagnosis and prognosis (continuous 7 point scale: 0.91, 0.84 to 0.99; P=0.021) and longer when the woman had frequent somatic symptoms (1.03, 1.01 to 1.05, P=0.002; for each symptom), a history of cystitis, urinary frequency, and more severe symptoms at baseline. CONCLUSION: Antibiotic resistance and not prescribing antibiotics are associated with a greater than 50% increase in the duration of more severe symptoms in women with uncomplicated urinary tract infection. Women with a history of cystitis, frequent somatic symptoms (high somatisation), and severe symptoms at baseline can be given realistic advice that they are likely to have severe symptoms lasting longer than three days.

Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial.

OBJECTIVE: To assess the impact of different management strategies in urinary tract infections. DESIGN: Randomised controlled trial. SETTING: Primary care. PARTICIPANTS: 309 non-pregnant women aged 18-70 presenting with suspected urinary tract infection. INTERVENTION: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed (by 48 hours) antibiotics; or targeted antibiotics based on a symptom score (two or more of urine cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or both leucocytes and blood), or a positive result on midstream urine analysis. Self help advice was controlled in each group. MAIN OUTCOME MEASURES: Symptom severity (days 2 to 4) and duration, and use of antibiotics. RESULTS: Patients had 3.5 days of moderately bad symptoms if they took antibiotics immediately. There were no significant differences in duration or severity of symptoms (mean frequency of symptoms on a 0 to 6 scale: immediate antibiotics 2.15, midstream urine 2.08, dipstick 1.74, symptom score 1.77, delayed antibiotics 2.11; likelihood ratio test for the five groups P=0.177). There were differences in antibiotic use (immediate antibiotics 97%, midstream urine 81%, dipstick 80%, symptom score 90%, delayed antibiotics 77%; P=0.011) and in sending midstream urine samples (immediate antibiotics 23%, midstream urine 89%, dipstick 36%, symptom score 33%, delayed antibiotics 15%; P<0.001). Patients who waited at least 48 hours to start taking antibiotics reconsulted less (hazard ratio 0.57 (95% confidence interval 0.36 to 0.89), P=0.014) but on average had symptoms for 37% longer than those taking immediate antibiotics (incident rate ratio 1.37 (1.11 to 1.68), P=0.003), particularly the midstream urine group (73% longer, 22% to 140%; none of the other groups had more than 22% longer duration). CONCLUSION: All management strategies achieve similar symptom control. There is no advantage in routinely sending midstream urine samples for testing, and antibiotics targeted with dipstick tests with a delayed prescription as backup, or empirical delayed prescription, can help to reduce antibiotic use. STUDY REGISTRATION: National Research Register N0484094184 ISRCTN: 03525333.

Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.

OBJECTIVES: To estimate clinical and dipstick predictors of infection and develop and test clinical scores; to compare management using clinical and dipstick scores with commonly used alternative strategies; to estimate the cost-effectiveness of each strategy; and to understand the natural history of urinary tract infection (UTI) and women's concerns about its presentation and management. DESIGN: There were six studies: (1) validation development for diagnostic clinical and dipstick scores; (2) validation of the scores developed; (3) observation of the natural history of UTI; (4) randomised controlled trial (RCT) of scores developed in study 1; (5) economic analysis of the RCT; (6) qualitative study of patients in the RCT. SETTING: Primary care. PARTICIPANTS: Women aged 17-70 with suspected UTI. INTERVENTIONS: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed antibiotics; target antibiotics based on a higher symptom score; target antibiotics based on dipstick results; or target antibiotics based on a positive mid-stream specimen of urine (MSU). MAIN OUTCOME MEASURES: Antibiotic use, use of MSUs, rates of reconsultation and duration, and severity of symptoms. RESULTS: (1) 62.5% of women had confirmed UTI. Only nitrite, leucocyte esterase and blood independently predicted diagnosis of UTI. A dipstick rule--based on having nitrite or both leucocytes and blood--was moderately sensitive (77%) and specific (70%) [positive predictive value (PPV) 81%, negative predictive value (NPV) 65%]. A clinical rule--based on having two of urine cloudiness, offensive smell, reported moderately severe dysuria, moderately severe nocturia--was less sensitive (65%) (specificity 69%, PPV 77%, NPV 54%). (2) 66% of women had confirmed UTI. The predictive values of nitrite, leucocyte esterase and blood were confirmed. The dipstick rule was moderately sensitive (75%) but less specific (66%) (PPV 81%, NPV 57%). (3) Symptoms rated as moderately bad or worse lasted 3.25 days on average for infections sensitive to antibiotics; resistant infections lasted 56% longer, infections not treated with antibiotics 62% longer and symptoms associated with urethral syndrome 33% longer. Symptom duration was shorter if the doctor was perceived to be positive about prognosis, and longer with frequent somatic symptoms, previous history of cystitis, urinary frequency and more severe symptoms at baseline. (4) 66% of the MSU group had laboratory-confirmed UTI. Women suffered 3.5 days of moderately bad symptoms if they took antibiotics immediately but 4.8 days if they delayed taking antibiotics for 48 hours. Taking bicarbonate or cranberry juice had no effect. (5) The MSU group was more costly over 1 month but not over 1 year. Cost-effectiveness acceptability curves showed that for a value per day of moderately bad symptoms of over 10 pounds, the dipstick strategy is most likely to be cost-effective. (6) Fear of spread to the kidneys, blood in the urine, and the impact of symptoms on vocational and leisure activities were important triggers for seeking help. When patients are asked to delay taking antibiotics the uncomfortable and worrying journey from 'person to patient' needs to be acknowledged and the rationale behind delaying the antibiotics made clear. CONCLUSIONS: To achieve good symptom control and reduce antibiotic use clinicians should either offer a 48-hour delayed antibiotic prescription to be used at the patient's discretion or target antibiotic treatment by dipsticks (positive nitrite or positive leucocytes and blood) with the offer of a delayed prescription if dipstick results are negative.

Developing clinical rules to predict urinary tract infection in primary care settings: sensitivity and specificity of near patient tests (dipsticks) and clinical scores.

BACKGROUND: Suspected urinary tract infection (UTI) is one of the most common presentations in primary care. Systematic reviews have not documented any adequately powered studies in primary care that assess independent predictors of laboratory diagnosis. AIM: To estimate independent clinical and dipstick predictors of infection and to develop clinical decision rules. DESIGN OF STUDY: Validation study of clinical and dipstick findings compared with laboratory testing. SETTING: General practices in the south of England. METHOD: Laboratory diagnosis of 427 women with suspected UTI was assessed using European urinalysis guidelines. Independent clinical and dipstick predictors of diagnosis were estimated. RESULTS: UTI was confirmed in 62.5% of women with suspected UTI. Only nitrite, leucocyte esterase (+ or greater), and blood (haemolysed trace or greater) independently predicted diagnosis (adjusted odds ratios 6.36, 4.52, 2.23 respectively). A dipstick decision rule, based on having nitrite, or both leucocytes and blood, was moderately sensitive (77%) and specific (70%); positive predictive value (PPV) was 81% and negative predictive value (NPV) was 65%. Predictive values were improved by varying the cut-off point: NPV was 73% for all three dipstick results being negative, and PPV was 92% for having nitrite and either blood or leucocyte esterase. A clinical decision rule, based on having two of the following: urine cloudiness, offensive smell, and dysuria and/or nocturia of moderate severity, was less sensitive (65%) (specificity 69%; PPV 77%, NPV 54%). NPV was 71% for none of the four clinical features, and the PPV was 84% for three or more features. CONCLUSIONS: Simple decision rules could improve targeting of investigation and treatment. Strategies to use such rules need to take into account limited negative predictive value, which is lower than expected from previous research.

Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum beta-lactamases in the UK.

OBJECTIVES: During 2003, the Health Protection Agency's Antibiotic Resistance Monitoring and Reference Laboratory began to receive isolates of Escherichia coli for confirmation of extended-spectrum beta-lactamase production with a phenotype implying a CTX-M-type beta-lactamase, i.e. MICs of cefotaxime > or = 8-fold higher than MICs of ceftazidime. Many were referred as being from community patients. We examined 291 CTX-M-producing isolates from the UK and investigated the genetic basis of their phenotype. METHODS: PCR was used to detect alleles encoding CTX-M enzymes and to assign these to their blaCTX-M phylogenetic groups. Selected alleles were sequenced. Producers were compared by analysis of banding patterns generated by pulsed-field gel electrophoresis of XbaI-digested genomic DNA. MICs were determined by an agar dilution method or by Etest. RESULTS: Of 291 CTX-M-producing E. coli isolates studied from 42 UK centres, 70 (24%) were reportedly from community patients, many of whom had only limited recent hospital contact. Community isolates were referred by 12 centres. Two hundred and seventy-nine (95.9%) producers contained genes encoding group 1 CTX-M enzymes and 12 contained blaCTX-M-9-like alleles. An epidemic CTX-M-15-producing strain was identified, with 110 community and inpatient isolates referred from six centres. Representatives of four other major strains also produced CTX-M-15, as did several sporadic isolates examined. Most producers were multi-resistant to fluoroquinolones, trimethoprim, tetracycline and aminoglycosides as well as to non-carbapenem beta-lactams. CONCLUSIONS: CTX-M-producing E. coli are a rapidly developing problem in the UK, with CTX-M-15 particularly common. The diversity of producers and geographical scatter of referring laboratories indicates wide dissemination of blaCTX-M genes. Because of the public health implications, including for the treatment of community-acquired urinary tract infections, the spread of these strains--and CTX-M-15 beta-lactamase in particular--merits close monitoring.

Interferon plus amantadine versus interferon alone in the treatment of naïve patients with chronic hepatitis C: a UK multicentre study.

BACKGROUND/AIMS: The antiviral agent amantadine may have activity against the hepatitis C virus. To determine whether the combination of interferon-alpha plus amantadine was more effective than interferon monotherapy we conducted a multicentre clinical trial in untreated patients with chronic hepatitis C infection. METHODS: We performed a pilot study in two centres (36 patients) to determine the number needed for a statistically significant clinical trial and then conducted a multicentre, randomized controlled clinical trial involving 14 centres and 143 patients. RESULTS: There was no significant difference in sustained response rates in patients receiving interferon and amantadine compared to those receiving interferon alone. The on treatment response rate at 3 months was 65% on combination vs. 49% on interferon alone (P = 0.05) while the sustained response was 18 and 15%, respectively. CONCLUSIONS: Combination therapy with interferon plus amantadine does not lead to a significant increase in sustained response rates when compared to interferon monotherapy.

Surgery for active culture-positive endocarditis: determinants of early and late outcome.

BACKGROUND: The purpose of this study was to describe a single unit experience in the surgical treatment of active culture-positive endocarditis and identify determinants of early and late outcome. PATIENTS AND METHODS: One hundred eighteen consecutive patients with positive blood culture up to 3 weeks before operation (or positive valve culture) and macroscopic evidence of lesions typical for endocarditis, undergoing operation between January 1973 and December 1996 in Southampton, were evaluated. The aortic valve was infected in 53 (48.9%), the mitral in 46 (39%), both aortic and mitral in 12 (10.1%), the tricuspid in 4 (3.9%), and the pulmonary valve in 3 (2.5%). Native valve endocarditis was present in 83 (70.3%) and prosthetic valve endocarditis in 35 (29.7%). Streptococci and staphylococci were the most common pathogens. Mean follow-up was 5.6 years (range, 0 to 25 years). RESULTS: Operative mortality was 7.6% (9 patients). Endocarditis recurred in 8 (6.7%). A reoperation was required in 12 (10.2%). There was 24 late deaths, 17 of them cardiac. Actuarial freedom from recurrent endocarditis, reoperation, late cardiac death, and long-term survival at 10 years were 85.9%, 87.2%, 85.2%, and 73.1%, respectively. On multiple regression analysis the following were independent adverse predictors: pulmonary edema (p = 0.007) and impaired left ventricular function (p = 0.02) for operative mortality; prosthetic valve endocarditis (p = 0.01) for recurrent infection; myocardial invasion by the infection (p = 0.01) and reoperation (p = 0.04) for late cardiac death; and coagulase-negative staphylococcus (p = 0.02), annular abscess (p = 0.02), and longer intensive care unit stay (p = 0.02) for long-term survival. CONCLUSIONS: Operation for active culture-positive endocarditis carries an acceptable mortality. Freedom from recurrent infection, reoperation, and long-term survival are satisfactory. In our data, patients' hemodynamic status at operation was the major determinant of operative mortality. Prosthetic valve endocarditis, coagulase-negative staphylococcus, and annular or myocardial infectious invasion were the critical adverse determinants of late outcome.

The systemic inflammatory response syndrome as a predictor of bacteraemia and outcome from sepsis.

Criteria defining the systemic inflammatory response syndrome (SIRS) were used to assess prospectively 270 clinical episodes in which blood cultures were taken from patients in general medicine. SIRS, severe sepsis and septic shock occurred in 149 (55%), 13 (5%) and 9 (3%) episodes, respectively. However, evidence of organ hypoperfusion indicating severe sepsis was recorded as sought in only 26% of episodes of SIRS. Crude mortality at 28 days increased sequentially as more SIRS criteria were met, rising from 12% in non-SIRS blood culture episodes, to 36% when all four criteria were met. Mortality from severe sepsis and septic shock was 38% and 56%, respectively. In 61/64 (95%) episodes of clinically important bacteraemia, patients fulfilled SIRS criteria when the blood culture was taken. However, the positive predictive value of SIRS for predicting bacteraemia was only 7%. Patients who did not fulfil SIRS criteria when blood cultures were taken were at low risk of bacteraemia and comprised 45% (121/270) of the study population. Three patients in this low-risk group had bacteraemia. Mortality in bacteraemic patients with severe sepsis or septic shock who were initially treated with ineffective antibiotics for up to 48 h was 80%, compared to 42% in those always treated appropriately.

High osmolality feedings do not increase the incidence of thrombophlebitis during peripheral i.v. nutrition.

BACKGROUND: Peripheral i.v. nutrition has been advocated for patients who require short-term i.v. nutrition support to avoid the complications and expense of central venous catheterization. Feeding formulas for peripheral administration have usually been modified by increasing the proportion of lipid, because increasing osmolality is reported to cause thrombophlebitis. The aim of this study was to determine whether standard feeding formulas can be given via the peripheral route and also to establish whether increasing osmolality does increase the incidence of thrombophlebitis under these conditions. METHODS: Thirty-six patients requiring parenteral nutrition were randomized to receive either a "high" (1700 mOsmol/L) or "standard" (1200 mOsmol/L) osmolality feeding containing 2000 kcal and 12 g nitrogen via a peripheral line. RESULTS: Twenty patients (mean age 55.6 years, range 16 to 78) received standard osmolality feedings using 20 peripheral feeding lines for a mean duration of 6.8 days (range 2 to 16) with 10 line failures (8 thrombophlebitis, 2 occlusion). Nineteen patients (mean age 56.1 years, range 27 to 83) received high osmolality feedings via 20 lines for a mean of 6.3 days (range 0 to 18) with five line failures (4 thrombophlebitis, 1 occlusion), one failed insertion, one line removed at the patient's request, and four lines that fell out. Forty lines were inserted overall of which 19 (47.5%) were removed electively, 12 (30%) developed thrombophlebitis, 3 (7.5%) occluded, 4 (10%) fell out, 1 (2.5%) was a failed insertion, and 1 (2.5%) was removed for nonmedical reasons. CONCLUSIONS: Increasing osmolality of total parenteral nutrition did not increase episodes of thrombophlebitis in this trial and did not affect the success rate of the lines. We conclude that standard total parenteral nutrition formulas of higher osmolality than previously thought can be safely given via the peripheral route for short-term feeding and do not increase the risk of thrombophlebitis.

An atypical case of Corynebacterium diphtheriae endocarditis and subsequent outbreak control measures.

An atypical case of Corynebacterium diphtheriae endocarditis with severe rhabdomyolysis and cerebral emboli is presented. The patient underwent successful mitral and aortic valve replacements and is only the third reported case with a successful outcome following surgery. Outbreak control measures were complicated by an equivocal result from guinea pig toxin tests.

Polymerase chain reaction detection of small round-structured viruses from two related hospital outbreaks of gastroenteritis using inosine-containing primers.

Two outbreaks of gastroenteritis in the UK which occurred nine days apart at Lymington and Southampton hospitals were investigated. The clinical and epidemiological features of both outbreaks were characteristic of small round-structured virus (SRSV) infection with rapid onset of diarrhoea and/or nausea and vomiting and propagation of the outbreaks by secondary spread. SRSV particles were observed by immune electron microscopy (EM) in 60% of faecal samples from both outbreaks and no other pathogens were detected. The index case for the second outbreak was a patient who was admitted with diarrhoea and vomiting after being discharged from Lymington hospital during the first outbreak. The possibility that the two outbreaks were caused by the same strain of SRSV was investigated by the polymerase chain reaction (PCR). New inosine-containing PCR primers were designed to amplify the RNA polymerase region of SRSV cDNA from genetic groups I and II. The PCR using the group II primers achieved a higher detection rate for SRSVs in faecal samples (68% of samples positive from both outbreaks) than immune EM. SRSVs were not detected using the group I primers or using conventional degenerate PCR primers. The nucleotide sequences of PCR amplicons from both outbreaks were identical providing molecular epidemiological evidence for the involvement of a single SRSV strain. Comparison of the RNA polymerase region of this virus with the equivalent regions of genetic group I (69.4-75.0% amino acid identify) and genetic group II (88.9-100% amino acid and 77.1-88.1% nucleotide identity) SRSVs revealed that the causative SRSV was a distinct member of genetic group II.

Recovery despite impaired cerebral perfusion in fulminant hepatic failure.

We report 4 patients with fulminant hepatic failure who developed prolonged intracranial hypertension (> 35 mm Hg for 24-38 h) that was refractory to standard therapy and associated with impaired cerebral perfusion pressure (< 50 mm Hg for 2-72 h). All survived with complete neurological recovery. Refractory elevation of intracranial pressure and reduced cerebral perfusion pressure are generally thought to contra-indicate liver transplantation in hepatic failure and are indications to withdraw support. Our observations challenge this concept.

Chronic rejection of the liver allograft.

Chronic rejection remains one of the major problems in the management of liver transplant recipients. Histologic diagnosis is central to the management of this condition. It remains difficult to predict cases that will progress toward irreversible rejection, because there are no early diagnostic features. Furthermore, the determination that irreversible rejection has occurred and retransplantation is required also is difficult. There remain many unanswered questions about the cause and pathogenesis of this process. The bile duct loss and arteriopathy parallel changes seen in chronic rejection of other organs. The extent to which this process is specific to the liver or is common to the other transplanted organs and mediated by an immune attack on the vascular bed is unknown. The precise position of HLA matching or mismatching as a risk factor for subsequent chronic rejection remains to be answered but in hepatic transplantation does not seem to be a major factor. The relation between the immunologic trigger of a graft and an aggressive arteriosclerosis is a major challenge, and a greater understanding of this process should provide some new therapeutic options in preventing the disease.

Antibodies to Mycobacterium paratuberculosis and nine species of environmental mycobacteria in Crohn's disease and control subjects.

Cultural and serological studies have provided limited, often conflicting, evidence of a role for mycobacteria in the pathogenesis of Crohn's disease. Interest has focussed on Mycobacterium paratuberculosis, previously considered to be common in the environment with no major role as a human pathogen. Whether a specific serum antibody response to mycobacteria occurs in Crohn's disease or ulcerative colitis was investigated. Sera from patients with Crohn's disease (n = 38), ulcerative colitis (n = 15), and a healthy control population (n = 30) were assayed in an enzyme linked immunosorbent assay (ELISA) using eight filtered sonicate mycobacterial preparations and a purified protein derivative made from the bovine tubercle bacillus. In addition, IgG, IgM, and IgA levels to M paratuberculosis were determined in sera from patients with active (n = 24) or inactive (n = 29) Crohn's disease and the control populations. There was strong evidence of contact with environmental mycobacteria in all patients and control populations, with the greatest responses to preparations of M avium, M tuberculosis, and M kansasii. A large proportion of patients with Crohn's disease had antibodies that bound most antigens tested but there were no statistical differences between these values and those of the control population. Similarly, there were no differences in antibody levels to M paratuberculosis in patient and control groups. Although a subset of patients with active Crohn's disease (25%) had IgG concentrations that exceeded the control mean by more than 2 SD, this phenomenon may not be specific to Crohn's disease: 20% of a small group of patients with coeliac disease had similarly raised IgG levels to M paratuberculosis. These findings do not provide serological evidence of a role for this organism in the pathogenesis of Crohn's disease.