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Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Introduction: We sought to identify correlates with psychological symptoms in long-term cardiac arrest (CA) survivors. Mindfulness, or nonjudgmental awareness of the present moment, is a modifiable protective factor against psychological symptoms in various clinical populations and could be a potential treatment target for CA survivors. Methods: We conducted a longitudinal survey study between 10-11/2019 (baseline) and 10-11/2020 (1-year follow-up) with long-term CA survivor members of the Sudden Cardiac Arrest Foundation. We collected demographic and CA characteristics at baseline. At both timepoints, we assessed posttraumatic stress symptoms (PTS) through the PTSD Checklist-5 (PCL-5) and depression and anxiety symptoms through the Patient Health Questionnaire-4 (PHQ-4). At follow-up, we assessed mindfulness through the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R). We used adjusted linear regression to predict 1-year PCL-5 and PHQ-4 scores, with particular consideration of the CAMS-R as a cross-sectional correlate of outcome. Results: We included 129 CA survivors (mean age: 52 years, 52% male, 98% white). At 1-year follow-up, in adjusted models, CAMS-R (β: -0.35, p Conclusion: Mindfulness was inversely associated with psychological symptoms in long-term CA survivors. Future studies should examine the longitudinal relationship of mindfulness and psychological symptoms after CA.

High-throughput sequencing is increasingly favoured to assay the presence and abundance of micro RNAs (miRNAs) in biological samples, even from low RNA amounts, and a number of commercial vendors now offer kits that allow miRNA sequencing from sub-nanogram (ng) inputs. However, although biases introduced during library preparation have been documented, the relative performance of current reagent kits has not been investigated in detail. Here, six commercial kits capable of handling

OBJECTIVE: Despite their promise for increasing treatment precision, Personalized Trials (i.e., N-of-1 trials) have not been widely adopted. We aimed to ascertain patient preferences for Personalized Trials. STUDY DESIGN AND SETTING: We recruited 501 adults with ≥2 common chronic conditions from Harris Poll Online. We used Sawtooth Software to generate 45 plausible Personalized Trial designs comprised of combinations of 8 key attributes (treatment selection, treatment type, clinician involvement, blinding, time commitment, self-monitoring frequency, duration, cost) at different levels. Conditional logistic regression was used to assess relative importance of different attributes using a random utility maximization model. RESULTS: Overall, participants preferred Personalized Trials with no costs vs. $100 cost (utility difference 1.52 [standard error 0.07], p

Importance: Guidelines lack consensus about the optimal approach to measuring office blood pressure (BP) when screening for hypertension. Objective: To compare the accuracy provided by different office BP measurement approaches that differ based on number of office BP readings within a visit, number of visits, and assessment method. Design: Cross-sectional Setting: Primary care. Participants: 707 employees without prior diagnosis of hypertension or cardiovascular disease and with screening BP Measures: Six standardized BP readings were taken during each of 3 office visits at least 1 week apart, using 2 assessment methods (mercury sphygmomanometer and BpTRU oscillometric device) for a total of 12,645 readings. Confirmatory factor analysis was used to develop a model from which estimates of the probability of correctly classifying an individual’s office BP status using differing numbers and types of office BP readings were generated. Results: A single systolic BP reading correctly classified an individual as having BP above or below the cutpoint for elevated office BP (i.e. 140 mmHg) when the reading was 155 mmHg, respectively. Averaging three systolic BP readings across two visits correctly classified an individual 95% of the time if the averaged reading was 148 mmHg. There was more confidence gained by increasing the number of visits than the number of readings within a visit. There was no clinically significant confidence gained by dropping the first reading versus averaging all readings, nor by measuring with a manual mercury device versus with an automated oscillometric device. Limitations: Only evaluated research quality BP readings. Similar probabilities may not apply to BP measured in routine clinical practice. Conclusions and Relevance: Averaging BP readings across two or more office visits might best balance increased confidence in BP status with efficiency of BP measurement, though the preferred measurement strategy may vary with the clinical context. Patients with average readings modestly below the 140/90 mmHg cutpoint (e.g., 134-139 mmHg) might be appropriate for referral to out-of-office BP testing as one cannot gain strong confidence that their “true” office BP is below goal.

Chronic radiation enteritis (RE) has been reported in up to 20% of patients receiving pelvic radiotherapy and can lead to intestinal failure (IF), accounting for 3.9% of new registrants for home parenteral nutrition (HPN) in the UK annually. Our aim is to report nutritional and survival outcomes for patients with RE referred to a national IF unit. A retrospective study of all new admissions over a 13-year period at the Intestinal Failure Centre, Manchester, UK. Data are presented as median (range). Twenty-three (3.8%) of 611 patients were admitted with IF secondary to RE. The primary site of malignancy was genitourinary in 17 (74%) patients. Radiotherapy was administered 9.5 (1–42) years previously. Patients underwent 2 (1–5) laparotomies prior to intestinal failure unit (IFU) admission. Twelve (52%) patients were admitted with intestinal obstruction and 11 (48%) with intractable weight loss and/or high output fistulae/stomas. Additional conditions contributing to IF were noted in 11 (48%) patients. Twenty-two (96%) patients had 2 (1–5) laparotomies prior to IFU referral. At discharge, 5 (22%) patients resumed oral diet without the need for artificial nutrition support, 3 (13%) required enteral feeding and 13 (56%) commenced HPN. The 10-year survival of the patient cohort was 48.2%. Surgical intervention is infrequently required, whereas the majority of patients with IF secondary to RE require long-term HPN. The judicious use of surgery in selected patients, coupled with an aggressive medical strategy to detect and treat contributing factors, and optimal enteral feeding may allow a modest proportion of patients with IF secondary to RE to achieve independence from PN.

Background In 1996 two transplantation centres in the UK were commissioned by the National Specialist Commissioning Advisory Group for England and Wales to assess small intestinal transplantation in adults. The joint experience of the two centres is presented. Methods Patients with irreversible small intestinal failure and complications of parenteral nutrition, and those with abdominal disease requiring extensive visceral resection, were assessed as candidates and where appropriate listed for surgery. Results Thirty-six patients were assessed for small intestinal transplantation and, of these, 14 underwent surgery. Twelve patients survived the transplantation procedure. Of these, seven patients were alive at 1 year, five at 3 years and three at 5 years. Three patients remain alive. Patient and graft survival improved with experience; the 1-year survival rate improved in the last 4 years of this experience from 43 to 57 per cent, and the 3-year survival rate from 29 to 43 per cent. Conclusion Small intestinal transplantation is associated with a high mortality rate but may benefit carefully selected patients in whom conservative management is likely to carry a greater mortality rate.

Contains fulltext : 165702.pdf (Publisher’s version ) (Closed access) Intestinal failure (IF) is the consequence of a reduction of gut function below the minimum necessary for the absorption of nutrients from the gastrointestinal tract. Types I and II comprise acute intestinal failure (AIF). Although its prevalence is relatively low, type II AIF is serious and requires specialist multidisciplinary care, often for prolonged periods before its resolution. The key aspects are: sepsis control, fluid and electrolyte resuscitation, optimization of nutritional status, wound care, appropriate surgery and active rehabilitation. The ESPEN Acute Intestinal Failure Special Interest Group (AIF SIG) has devised this position paper to provide a state-of-the-art overview of the management of type II AIF and to point out areas for future research.

Background: Perioperative oral supplementation has been shown to reduce post-operative complications. However, the use of preoperative standard oral supplements in a cohort of colorectal cancer patients has not been evaluated. The present study examined whether preoperative supplements are beneficial in this group. Methods: In a randomised controlled trial, patients were assigned to receive 400 mL of oral supplement and dietary advice or dietary advice alone. Primary outcome was the number of post-operative complications. One hundred and twenty-five patients were recruited (59 randomised to the intervention group and 66 to the control group) and nine were excluded. Results: In the intervention group, 24 (44%) patients had a complication compared to 26 (42%) in the control group (P = 0.780). In the intervention and control groups, there were eight (15%) and 16 (25%) surgical site infections, respectively (P = 0.140) and seven (13%) and 11 (17%) chest infections, respectively (P = 0.470). Subgroup analysis for hypothesis generation included 83 (71%) weight-losing patients, where there was a significant reduction in surgical site infections using the Buzby definition (P = 0.034), although this was not the case for the Centre for Disease Control definition (P = 0.052). Conclusions: There was no evidence that preoperative supplements were beneficial in reducing the number of complications, although there may be some benefit for surgical site infections in selected weight-losing preoperative

Background: The present study aimed to determine the extent of malnutrition in preoperative colorectal cancer patients. Malnutrition has been shown to affect post-operative outcome, so it would be beneficial to identify those who are malnourished or who are at risk of becoming so preoperatively. We examine whether weight loss is related to the length of stay or changes in fat free mass. Methods: Patients were enrolled consecutively from outpatients 2?4 weeks prior to surgery. Assessments included body mass index, percentage weight loss, dynamometry, Malnutrition Universal Screening Tool, Subjective Global Assessment and bioelectrical impedance. Cancer staging and hospital length of stay were recorded. Results: One hundred and thirty-two patients were eligible and 87 enrolled. Sixty-seven patients were weight losing and 20% had lost >10% of their usual body weight. Handgrip strength was lower in malnourished patients compared to those who had not lost weight (mean 19.4 and 27.3 kg, respectively, P = 0.013). Mean (SD) fat free mass in patients with a weight loss >10% was 39.7 (13.5) kg and, in those with

This is an introduction to the Gut tutorial “A patient with impaired gastric motility” hosted on BMJ Learning—the best available learning website for medical professionals from the BMJ Group. The functional as opposed to inflammatory effects of gastrointestinal pathology are often neglected by clinicians. Helicobacter pylori infection may impair gastric function either due to …

SUMMARY Malnutrition is common and undiagnosed in the majority of affected hospital patients; it is associated with impaired organ function, morbidity, and increased length of hospital stay. Artifical nutritional support in malnourished patients leads to improvement in nutritional status and clinical outcome. Nutritional support is required in malnourished patients, patients who are unable to take normal diet and patients with intestinal failure. Gastroenterologists are required to supervise patients with intestinal failure, to insert endoscopic feeding devices, and increasingly to participate in, or lead, nutritional support teams. Major developments in nutrient delivery have included percutaneous endoscopic feeding devices, the recognition that enteral feeding is possible in patients with gastric stasis, and that nutrient needs can be met by peripheral parenteral nutrition. There is much interest in the use of new substrates, or substrates delivered in pharmacological doses such as glutamine and arginine, to manipulate the response to disease. Many hospitals lack an organized approach to artificial nutritional support. Patients continue to suffer from a lack of treatment or the consequences of inappropriate or inadequate treatment. This article reviews the current status of artificial nutritional support and provides guidelines for patient managment.

The development of intravenous fat emulsion (IVFE) is the culmination of physiological, biochemical, nutritional, and medical scientific advancements. IVFEs have the ability to deliver critical nutritional substrates to the patient. Recent literature purports that they may also play roles in modulation of immune functionality and pulmonary physiology, but data supporting these potential benefits are limited. While soybean-based IVFEs have comprised the dominant fat in U.S. markets, a number of other novel IVFEs may prove to optimize the care of children and adults in both hospitalized and home settings. The October 2013 U.S. Food and Drug Administration (FDA)/American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Public Workshop brought together scientists, researchers, and clinical experts to present updated clinical perspectives of IVFEs, including historical development, current state of usage throughout the world, and considerations for the regulatory approval of new IVFEs in the United States.

Summary Five patients with primary antibody deficiency were investigated because of intermittent but persistent diarrhoea of several years duration despite immunoglobulin replacement therapy. We found no evidence of Giardia lambia or other intestinal pathogens to explain their gastrointestinal symptoms. All five had definite radiological evidence of small bowel Crohn's disease and three had histological specimens available with abnormalities consistent with Crohn's disease. One patient had a non-caseating granuloma in an oral ulcer. A second patient with stricturing disease in the small bowel had a mucosal inflammatory infiltrate with non-caseating granulomas. A third had transmural inflammation but no granulomas. All five patents were diagnosed as having Crohn's disease and have responded symptomatically to steroid therapy.

The prevalence of coronary artery disease (CAD) among South Asians (SAs) significantly exceeds that of Caucasians. South Asians also suffer from more premature, clinically aggressive and angiographically extensive (3-vessel) disease. The role of conventional CAD risk factors (CCRFs) remains controversial.We sought to determine if the CCRF burdens of SA immigrants differed from Caucasians. We also sought to determine whether angiographic CAD was more extensive among SAs and whether SA ethnicity was an independent predictor of 3-vessel disease.We reviewed the CCRFs and angiograms of 520 SAs and 219 Caucasians consecutively referred with stable angina pectoris or acute coronary syndrome.Three-vessel CAD was significantly more common among SAs than Caucasians (32.5% vs 22.4%; P = .006). Diabetes mellitus (DM), age and male sex independently predicted 3-vessel disease. South Asian ethnicity showed a trend toward predicting 3-vessel disease (P = .06). The frequency of DM (55% vs 31.1%; P.001), hypertension (77.5% vs 68.5%; P = .01), obesity (63.1% vs 44.3%; P.001) and dyslipidemia (75.6% vs 61.6%; P.001) were significantly greater among SAs; however, smoking was significantly more common among Caucasians (44.3% vs 21.3%; P.001). Compared to Caucasians, SAs were significantly younger at the time of presentation for coronary angiography (58.5 vs 61.1 yrs; P = .001).SAs referred for coronary angiography with stable angina and acute coronary syndromes are younger, have significantly higher rates of 3-vessel disease, as well as higher rates of DM, hypertension, obesity and dyslipidemia than Caucasians. Aggressive screening, prevention and treatment may be warranted in this population.

The prevalence of coronary artery disease (CAD) among migrant Indian populations exceeds that of Caucasians. Migrant Indians also suffer from more premature, clinically aggressive and angiographically extensive, (i.e., 3-vessel disease). It is not known whether the extent of angiographic CAD or the conventional CAD risk factors of Indo-Guyanese (IG) immigrants differs from that of Caucasians.We reviewed the conventional CAD risk factors and angiographic findings of 198 IG and 191 Caucasians who were consecutively referred for cardiac catheterization with a diagnosis of stable angina pectoris or acute coronary syndrome.Three-vessel CAD was approximately 1.5 times more common among IG than Caucasians (34.8% vs. 24.0%; P = .02). Age (P = .01), male sex (P = .03) and diabetes mellitus (P = .05) were independently associated with an increased likelihood of 3-vessel CAD and there was a trend towards IG ethnicity predicting 3-vessel disease (P = .13). The frequency of diabetes mellitus (51.5% vs. 30.9%; P.001), hypertension (82.3% vs. 67.0%; P.001) and dyslipidemia (75.5% vs. 60.2%; P = .001) were significantly greater among IG, however, that of smoking was not. While IG were significantly leaner than Caucasians (27.7 kg/m2 vs. 30.0 kg/m2 ; P.001), their mean body mass index fell within the ethnic-specific range for obesity.We conclude that IG immigrants presenting for coronary angiography have significantly higher rates of 3-vessel CAD as well as higher rates of diabetes mellitus, hypertension and dyslipidemia than Caucasians. Aggressive screening, prevention and treatment may be warranted in this cohort.

which is associated with increased risk of complications, morbidity and mortality. Adequate nutrition is essential in thecare of the hip fracture patients in order to achieve recovery without complications. The aim of this pilot was to investigate the effects ofan improved care intervention in relation to nutritional status. Following patient consent, Mid Arm Circumference (MAC) and Hand GripStrength were measured on admission and discharge and length of stay recorded (Table 1).From January 2008 to June 2008, a total of 81 patients over the age of 75 years with a fractured femur were seen by the NutritionSupport Team (NST). Seventy six patients (94%) were screened by the NST on admission using the Malnutrition Universal ScreeningTool (MUST); 43 (57%) of patients were assessed as medium or high risk. Due to cognitive impairment only 31 and 21 patientsrespectively consented to MAC and grip strength being measured on admission and discharge

Objectives. To examine the outcome in patients with SSc requiring parenteral nutrition (PN), and to compare their clinical characteristics with those of other SSc patients and of patients requiring PN/home parenteral nutrition (HPN) for other conditions. Methods. Retrospective review of SSc and Intestinal Failure Unit databases at a tertiary referral centre for SSc/national unit for intestinal failure over a 13-yr period. Results. Eight patients with SSc requiring PN during the study period were identified (2 males, 6 females: median age at commencement of PN 51 yrs, range 42–56 yrs). All patients commencing PN had bacterial overgrowth and malabsorption not responding to antibiotic therapy. The median duration of PN therapy in the eight patients was 40 months (range 0.8–192 months). Between them the eight patients had a total of 13851 catheter-use days and only two line infections (0.14/1000 catheter days), a lower rate of line infection than in other HPN-treated patients at Hope Hospital (0.52/1000 catheter days). Three patients died during the 13-yr period, none of causes related to their PN. Six were unable to manage their HPN regime themselves, mainly because of problems with hand function. Conclusions. Although patient numbers were small, our findings suggest that HPN can be safely and successfully used long-term in patients with SSc and should be considered for patients unable to maintain their nutritional status because of severe gastrointestinal involvement. Impaired hand function should not preclude SSc patients from receiving HPN: family members or community nurses may be trained in the care of the HPN line. Background Approximately 90% of patients with the multisystem connective tissue disease SSc develop gastrointestinal involvement of their disease, although many are asymptomatic [1, 2]. Gastrointestinal problems occur in both the lcSSc and dcSSc disease subtypes [3]. Any part of the gastrointestinal tract may become involved and an autopsy study showed that approximately half of the patients have histological involvement of their small bowel [4]. A small minority of patients develop intestinal failure. The usual scenario in this minority is that small intestinal involvement, with impaired peristalsis, results in bowel dilatation and stasis that in turn lead to bacterial overgrowth, malabsorption, and sometimes pseudoobstruction. Gastrointestinal involvement in SSc can therefore be life-threatening: of 264 patients with dcSSc from 29 centres, with an average duration of follow-up of 5.2 yrs, 13 (5%) died of gastrointestinal disease, representing 15% of deaths definitely related to SSc [5]. When a patient is unable to maintain his/her nutritional status, as in SSc-related intestinal failure, parenteral nutrition (PN) may be required to prevent, or correct, malnutrition. Other forms of artificial feeding, including oral supplementation, naso-jejunal feeding and feeding via percutaneous enterogastrostomy (PEG)/ percutaneous jejunostomy tubes may be tried before introducing PN. Complications of PN administration include central venous catheter infections, occlusions and fractures of the central line, hepatic disease and osteoporosis. If the indication for PN suggests that long-term treatment will be required, as in SSc, home parenteral nutrition (HPN) may be considered. PN is a potentially life-saving treatment but training the patient as carer for the central line for HPN may pose particular problems in SSc because of concomitant problems including impaired hand function and cardiorespiratory disease. The aim of this retrospective study was to examine the outcome in patients with SSc requiring PN, and to compare their clinical characteristics with those of other SSc patients and of patients requiring PN/HPN for other conditions.

Background Intestinal failure is the outcome of a number of gastrointestinal diseases and characterized by significant reduction in functional gut mass. If not resolved patients often face long-term nutritional support. This study gathered information about how patients referred with intestinal failure are managed in specialised European centres. Methods A questionnaire was circulated in 7 European countries via representatives of the ESPEN-HAN working group to seek information about experience in treating patients with intestinal failure. We asked about clinical outcome, information about structure and organisation of the department, referral criteria, treatment procedures and guidelines. Results 17 centres in 6 European countries completed the questionnaire: UK, n = 6, France, n = 4, Spain, n = 3, Denmark, n = 2, Italy, n = 1, Poland, n = 1. The experience of the centres in treating patients was in the range 12–30 years. The total number of patients on HPN in all centres was 590. The number of patients referred to centres with intestinal failure during the period January to December 2000 was n = 882: UK, n = 375 (range 2–175), France, n = 308 (range 24–182), Italy and Spain, n = 43 (range 9–52), Denmark n = 51 (range 14–37), the centre in Poland included 53 patients. Comparing all centres the following distribution among patients (median % (range%)) with regard to the endpoints were reported: Oral nutrition 32% (23–50%), enteral/tube feeding 11% (4–23%), HPN 36% (15–57%), lost to follow up 10% (0–35%), dead 9% (5–18%). No patients had an intestinal transplant. Conclusion The study provides information about how patients with intestinal failure are managed across Europe and the data indicates that treatment practice varies between countries.

OBJECTIVE: To quantify the impact of infliximab therapy on health care resource utilization in the UK. METHODS: A retrospective audit was undertaken at seven centres in the UK, which reviewed patient notes for a period of 6 months before and 6 months after an initial infliximab infusion. Details of hospital admissions, outpatient visits, operations, diagnostic procedures, drug usage, and overall efficacy were collected. Results were compared for the two 6 month study periods. RESULTS: A total of 205 patients (62% female, median age 33 years) with moderate/severe Crohn's disease were audited. The majority of patients had chronic active disease (62%) and most received one infusion initially (72%). Clinicians rated 74% of responses as good to excellent and patients 72%. Most patients had concomitant immunosuppression (pre: 75%, post: 75%). Approximately half of the patients (45%) stopped taking steroids, with a further 34% having a dosage reduction. A fall of 1093 inpatient days was seen (1435 vs. 342) in the 6 months following infliximab administration. There were seven fewer operations, 33 fewer examinations under anaesthetic, and 99 fewer diagnostic procedures. Outpatient visits were similar pre- versus post- (555 vs. 534). The total reduction in direct costs amounted to an estimated pounds 591,006. Three hundred and fifty-three infliximab infusions were administered at an estimated cost of pounds 562,719. Thus, there was a net reduction of pounds 28,287 or pounds 137.98 per patient. CONCLUSIONS: Infliximab appears to be a potentially cost effective treatment for selected patients based on the reduced number of inpatient stays, examinations under anaesthetic, and diagnostic procedures over a 6 month period.

Over the last 10 years, the Nutrition Unit at Hope Hospital has trained and looked after 76 patients on home parenteral nutrition for a total of 100 patient years. Although 40 per cent of patients have required home parenteral nutrition for 6 months or less one patient has been on treatment for 7 years. The quality of life measured on a 4 point scale was good for the majority of patients. Sepsis and superior vena caval thrombosis are the main problems encountered. Overall mortality rate was 18 per cent and the sepsis rate was 0·14 episodes per patient per year. Home parenteral nutrition is an effective and safe treatment of intestinal failure.

Summary A women with β-thalassemia intermedia, and iron overload following many years’ treatment with oral iron, was treated with subcutaneous desferrioxamine. During the course of this treatment she developed tinnitus, which was considered to be a rare complication of the use of this chelating agent. The mechanism of this effect is not understood.

Blood concentrations of promethazine and promethazine sulphoxide have been measured following oral and intravenous administration of promethazine to seven healthy male volunteers. Promethazine disposition is characterised by a large volume of distribution (1970 1) and a high blood clearance (1.141 min-1). Less than 1% of the dose is excreted unchanged in the urine, therefore total body clearance is essentially metabolic clearance. In accord with this high clearance the oral availability of promethazine is only 25%. The absorption of promethazine from the gastrointestinal tract exceeds 80% in most subjects. Minimal metabolism by the gastrointestinal mucosa is implicated. Promethazine sulphoxide pharmacokinetics are consistent with a pronounced first pass effect. Although the area under the curve for this metabolite is not route dependent, there is a marked alteration in the shape of the metabolite curve when oral and intravenous data are compared. Evidence is presented to support the hypothesis that S-oxidation of promethazine is predominantly an hepatic event. The conclusions of previous investigators with regard to the role of the gut mucosa in S-oxidation of phenothiazines is critically assessed.

The pharmacokinetics of metronidazole were studied after oral and intravenous administration to seven patients with Crohn's disease and five patients with ulcerative colitis. The oral/intravenous availability ratio was 0.97 +/- 0.2 in the Crohn's patients and 0.90 +/- 0.1 in the colitics (mean +/- s.e. mean). Plasma clearance was 3.24 +/- 0.2 l h-1 and 4.1 +/- 0.5 l h-1, respectively. These differences were not statistically significant. Ten of the patients on long term sulphasalazine were studied to observe the effect of 2 weeks metronidazole therapy on plasma sulphapyridine concentration. The sulphapyridine concentration changed from 22.1 +/- 2.0 micrograms ml-1 to 15.95 +/- 4.5 micrograms ml-1 in the Crohn's patients and 26.0 +/- 6.0 micrograms ml-1 to 36.4 +/- 8.5 micrograms ml-1 in the colitis group, pre- and post-metronidazole. These differences were not statistically significant. These results suggest that metronidazole does not interfere with diazo-link splitting of sulphasalazine and that patients with Crohn's disease handle metronidazole in a similar manner to patients with colitis.

We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn's disease by carrying out a trial of treatment with antimycobacterial drugs. Twenty seven patients with Crohn's disease took part in a two year randomised double blind, crossover, controlled trial of rifampicin plus ethambutol against placebo. Fourteen patients completed the trial; four required an operation; five were withdrawn as poor compliers, and four because of adverse effects. There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn's disease activity index or any clinical indicator of disease activity. There was no suggestion that any subgroup of patients - for example, different regions of bowel affected or previous operation - were favourably affected by the drugs. There was no consistent pattern of change in prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period. A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy. The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn's disease.