Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

The potential impact of high-quality MRI of the biliary tree on ERCP workload.

BACKGROUND: Magnetic resonance cholangiography (MRC) is a non-invasive method of imaging the biliary tree with virtually no morbidity. Endoscopic retrograde cholangiopancreatography (ERCP) has a significant morbidity, mortality and failed imaging rate. Unlike MRC, ERCP is highly dependent on the clinical team for high-quality results and minimal morbidity. MRC requires high-quality image acquisition and appropriate reconstructions, with skilled reading of the images. OBJECTIVES: To assess the impact on ERCP workload of using MRC as the initial imaging modality for the biliary tree in selected patient groups, and to assess procedure-related morbidity and mortality. METHODS: An analysis of 1078 consecutive ERCP examinations performed at our institution over the six years to 1996 has been undertaken. Complications, imaging failure rates and ERCP findings have been analysed in the different referral categories to assess the potential impact of MRC on future ERCP workload and patient outcomes. RESULTS: At our institution, if MRC had been used as the first imaging investigation in patients with abdominal pain (n = 336, with or without abnormal liver function tests but without clinical jaundice) and those with present or past acute pancreatitis (n = 101), we estimate that 83 (19%) would have needed to go on to ERCP, but 354 (81%) would not have required further invasive investigation. In these categories, this would have resulted in five patients with stones missed at MRC, but 14 extra patients with stones would have been identified whose stones would have been missed at ERCP (failed examinations). There would be an overall 33% reduction in ERCP workload and 20 serious complications related to ERCP would have been avoided. Overall 7% of patients would be subjected to both investigations. CONCLUSIONS: In the interests of efficient use of resources, minimization of patient complications and accurate identification of those requiring therapeutic ERCP, MRC should be the preferred initial investigation in selected groups of patients presently being subjected to ERCP.

Subclinical esophageal peristaltic dysfunction during the early phase following a stroke.

Evaluation of swallowing following stroke has previously concentrated on the oropharyngeal phase. We have studied whether there is esophageal dysmotility during the early phase following stroke in patients with no clinical evidence of oropharyngeal dysfunction. Twenty-five patients with a clinical diagnosis of stroke, and CT scan confirmation, without swallowing abnormalities at bedside evaluation were studied. Each subject had two esophageal manometric studies, one between days 3-5 after the stroke and the second during the third week after the stroke. Mean percentage (+/-SE) of completed peristaltic events increased from 57.8 +/- 5.9 (days 3-5) to 77.3 +/- 3.9 (week 3) (P = 0.005). Mean propagation of peristalsis (+/-SE) between 10 and 5 cm above the lower esophageal sphincter increased from 2.9 +/- 0.2 cm/sec (days 3-5) to 3.7 +/- 0.3 cm/sec (week 3) (P = 0.003). We have demonstrated subclinical peristaltic dysfunction in the smooth muscle segment of the esophagus in stroke patients with relatively preserved oropharyngeal function.

Measurement of carbohydrate-deficient transferrin (CDT) in a general medical clinic: is this test useful in assessing alcohol consumption.

The aim of this study was to measure serum carbohydrate-deficient transferrin (CDT) in consecutive patients attending a general medical clinic with a range of alcohol intakes to determine its value in assessing such intake. Eighty-one consecutive patients (42 male, 39 female) aged 20-85 years (median = 49.5 years) attending an out-patient clinic were selected for the study. Each patient completed an alcohol diary detailing the units of alcohol consumed in the previous week, a CAGE questionnaire and an alcohol history, and underwent conventional blood tests including mean corpuscular volume (MCV), liver function tests, and gamma-glutamyl transferase (GGT). CDT was estimated using an enzyme immunoassay (CDTect, Pharmacia). The group comprised of 17 teetotallers, 28 light (<100 g/week), 23 moderate (100-400 g/week), and 13 heavy (>400 g/week) drinkers. Median serum CDT for heavy drinkers (25.5 U/l) was significantly higher than for the rest (median = 17 U/l, Kruskal-Wallis test, P = 0.01). Serum CDT correlated significantly with the CAGE score (Mann-Whitney test, P = 0.01), but poorly with alcohol diary records (r = 0.1, P = 0.4). However the correlations between GGT and diary records (r = 0.43, P = 0.001) and MCV with diary records (r = 0.5, P < 0.001) were significant. Sensitivity, specificity, and positive predictive value for elevated serum CDT were 69, 81 and 41% respectively in detecting heavy drinking. The positive predictive values for the various parameters were 43% for elevated serum GGT, 41% for raised erythrocyte MCV, and 75% for a positive score on the CAGE questionnaire. When a combination of the markers CDT, GGT, and MCV was used, elevation in two of the three markers detected heavy drinking with sensitivity of 85%, specificity of 88%, and positive predictive value of 61%. We conclude that, in out-patients with a wide range of alcohol intakes conventional markers such as serum GGT and erythrocyte MCV were more suitable than serum CDT for assessing alcohol intake. Serum CDT when used in combination with serum GGT and erythrocyte MCV was useful in detecting heavy drinking. The importance of careful history-taking including a standardized questionnaire is emphasized.

Information for patients about inflammatory bowel disease.

In inflammatory bowel disease it is important that patients understand their condition since this helps to improve long-term management of the disease. The aim of this study was to assess the information given to patients with inflammatory bowel disease about their condition, its treatment and the National Association for Colitis and Crohn's disease. Two surveys were performed, using anonymous questionnaires. One was of all association members in north-east England, the other was a sample of patients attending medical outpatients. The surveys showed that more patients heard of the National Association for Colitis and Crohn's disease from the media than from medical sources. Of patients seen in medical clinics, 75% would welcome more information about their disease. In four of the six participating centres less than half the patients had been told about the existence of a patients' association. There was considerable variation in the instructions on what action to take in the event of a relapse. These findings suggest that the opportunity offered by out-patient clinics to educate and inform patients is often wasted. Clinicians often neglect to mention the National Association for Colitis and Crohn's disease, especially to patients with long-standing disease. A higher priority should be given to providing patients with appropriate information on inflammatory bowel disease. Three simple audit standards for the organisation of outpatient clinic information are proposed.

ERCP: present practice in a single region. Suggested standards for monitoring performance.

A survey of consecutive endoscopic retrograde cholangiopancreatography (ERCP) procedures has been undertaken for all the Units performing this procedure in the (old) Northern region of the UK. The process, imaging success, procedural success and complications have been analysed for 255 ERCP procedures. Overall, the results seem to be reassuring, with an imaging success rate of 88% (n = 297 ducts required), additional procedural success rate of 88% (n = 178) and with a serious complication rate of 6%. However, there are wide differences both in terms of practice (contrast agent used, antibody prophylaxis), imaging success (76-95%) and outcomes (procedure success 75-100%, serious complications 0-16%). This wide difference in practice seems difficult to justify. Individual Units should monitor their performance. Standards of practice are suggested for discussion and debate.

Case report: chronic mesenteric ischaemia as a cause of abnormal bowel uptake of labelled leucocytes.

Chronic mesenteric ischaemia is often difficult to diagnose. A high level of clinical suspicion is needed and further investigation requires invasive procedures. We present a case where weight loss and abdominal pain were dominant features and initial interpretation of a labelled leucocyte scan suggested inflammatory bowel disease. Subsequent investigations excluded this possibility and chronic ischaemia was confirmed at autopsy. Positive small bowel images using 99Tcm-HMPAO labelled leucocytes may indicate chronic ischaemia.

Acute dystonic drug reaction or tetanus? An unusual consequence of a 'Whizz' overdose.

The case history presented illustrates that, following an overdose of 'Whizz' and alcohol, a protracted dystonic syndrome can develop, clinically indistinguishable from tetanus. A prolonged period of ventilation may be necessary, but, in this case, complete recovery eventually occurred.

Improving information given to patients before endoscopy: a regional audit.

To improve the information given to patients before endoscopy an audit was performed in 16 of 18 endoscopy units in Northern region. Details of current endoscopy information leaflets provided by the 16 respondents were discussed by nurses and consultants from the participating units, and a standard, including 12 separate items, was agreed. Each unit was provided with a comparison of its current leaflet with the standard, which highlighted areas for potential improvement. Six months later the participating units were again asked to provide details of the information; 13 replied, 11 of which had produced new leaflets and two which were in the process of doing so. In the initial survey only 35% (range 8-67%) of the items in the standard were included in the leaflets. Particular omissions were an indication of risks of procedures (three units), notification of follow up procedures (two), details for obtaining the results of the endoscopy (five), advice for people with diabetes (two) and providing a contact number for the endoscopy unit (four). In the repeat audit all 11 units had made changes to their leaflets and, overall, 80% of the items were included. Through this simple audit the range of information given to patients attending for endoscopy in the region has improved.

Caffeine clearance by enzyme multiplied immunoassay technique: a simple, inexpensive, and useful indicator of liver function.

The clinical value and sensitivity of serum caffeine clearance measurement has been evaluated as an indicator of hepatic disease. After a 17 hour caffeine exclusion period, 300 mg of caffeine citrate was administered orally to the study subjects. Serum samples were taken four and 16 hours later. Serum caffeine concentrations were measured using an enzyme multiplied immunoassay technique (EMIT) and a clearance value derived. Conventional liver function tests were measured at the same time. A total of 103 subjects attending the medical unit in a district general hospital were studied. Twenty one had alcoholic liver disease, 11 non-alcoholic cirrhosis, nine non-cirrhotic liver disease, 21 suspected liver disease, six hepatic tumours, and 35 were hospital and normal control subjects. Caffeine clearance values were lowest in subjects with alcoholic liver disease (median 0.19 ml/min/kg, range 0.04-0.61 ml/min/kg) and significantly reduced in all subjects with liver disease (median 0.32 ml/min/kg, range 0.04-2.68 ml/min/kg) compared with control subjects (median 1.27 ml/min/kg, p less than 0.001). In subjects with suspected liver disease subsequently shown to have another explanation for abnormal liver function test results, caffeine clearance values were normal (median 1.31 ml/min/kg, range 0.23-2.64 ml/min/kg) and significantly different, p less than 0.001, from those of subjects with liver disease. Serum albumen values were not different for these latter two groups. Using a cut off value of 0.86 ml/min/kg, caffeine clearance measurement was 100% sensitive for alcoholic liver disease and 89% sensitive for all liver disease. The respective sensitivities for conventional liver function test measurement were 76% and 83%. In the suspected liver disease group, caffeine clearance was abnormal in only 24%, conventional liver function tests were abnormal in 95%. The respective specificities for caffeine clearance and liver function test measurement in control subjects were 93% and 100%. Caffeine clearance determined by EMIT is a simple inexpensive hepatic metabolic function test. This study indicates that it is a more sensitive indicator of structural liver disease than conventional liver function tests, especially for alcoholic liver disease. The test could be widely introduced as a useful, repeatable assessment of hepatic function.

Chronic active hepatitis: a sixteen year survey at a district general hospital.

Over a period of 16 years (1971-87) all cases of chronic active hepatitis (CAH) diagnosed following liver biopsy have been reviewed to assess incidence, aetiology, outcome and response to treatment. North Tees District serves a population of 210,000 and 26 cases were identified (20 female) age range 9-73 years (median 56 years). Incidence remained constant at 1:100,000/year. Twenty cases (77%) had an immune aetiology. Other aetiologies were hepatitis B virus (HBV) infection, alpha-1AT deficiency, non-A non-B hepatitis and a complex multisystem disease. The median follow-up period was 50 months. There were 7 deaths, three unrelated to liver disease. Survival analysis gives an 86% 5-year survival and 56% 10-year survival. Twenty four patients were treated with steroids (and 6 additionally with azathioprine); 15 (63%) were steroid responsive and 9 were non-responsive. In five patients steroids were successfully discontinued but in 10 patients severe symptomatic relapse occurred on steroid reduction below 7.5-10 mg/day. Steroid non-responders were not typical CAH, 5 with predominantly a rise in alkaline phosphatase, one multisystem disease and one HBV positive. Steroid discontinuation was only possible in one third of the patients responding. Eighteen subjects (69%) were cirrhotic at initial biopsy; 9 had follow-up biopsies, 6 were unchanged but three had progressed to cirrhosis despite apparent steroid responsiveness.

Pancreatic function testing: serum PABA measurement is a reliable and accurate measurement of exocrine function.

A comparison between the NBT-PABA/14C-PABA test (NBT-PABA, n-benzoyl-tyrosyl para-aminobenzoic acid) using the PABA excretion index (PEI) and serum PABA estimation at 90 minutes has been made in 42 consecutive subjects attending for investigation of possible pancreatic disease to a District General Hospital (DGH). The PEI was unobtainable or incorrect on 38% of occasions compared with 9% for the serum test. Sensitivity, specificity, and efficiency for the PEI (n = 33 valid results) were 71%, 88%, and 79% respectively and for the serum PABA (n = 41 valid results), 95%, 90%, and 93% respectively. These results confirm that measurement of serum PABA is a simpler, more reliable, and a more accurate method of assessing pancreatic function.

Colonic inflammation and nonsteroidal anti-inflammatory drug administration. An assessment of the frequency of the problem.

Over an 18-month period at a single clinic, 43 new cases of colonic inflammation have been diagnosed (19 proctitis only). Crohn's colitis has been excluded from this analysis. In all these subjects a careful drug history has been taken in a prospective manner and in 4 of these 43 patients colonic inflammation appeared to be directly related to non-steroidal anti-inflammatory drug (NSAID) administration (mefenamic acid, 2; piroxicam, 2). In all 4 patients there was a time interval (mean 3 months) between initiation of treatment with NSAID and presentation with diarrhoea and weight loss. Pathological findings were minor and biochemical changes insignificant, in contrast to the protracted troublesome symptoms. Resolution of symptoms was very rapid on discontinuation of NSAID medication but 2 patients experienced immediate return of symptoms following inadvertent rechallenge. Approximately 10% of newly diagnosed colitis may be related to NSAID administration. Subjects taking NSAID medications appear to be five times more likely to develop colonic inflammation than the general population.

Autonomic neuropathy in an alcoholic population.

Autonomic nervous system integrity has been assessed in 30 alcoholic subjects and 30 age-sex matched controls using five simple tests of cardiovascular responses. There was evidence of parasympathetic neuropathy alone in five of the alcoholic subjects (16%) and of combined parasympathetic and sympathetic neuropathy in an additional six (20%). None of the controls showed any abnormality. Within the alcoholic group, those with autonomic neuropathy were older, were more likely to be female and to have established alcoholic liver disease. Symptoms were a poor guide to the presence or absence of autonomic neuropathy.

Depressed selenium and vitamin E levels in an alcoholic population. Possible relationship to hepatic injury through increased lipid peroxidation.

Serum selenium and vitamin E levels have been measured in subjects with established alcoholic liver disease, in alcoholics within the community, and in appropriate controls. Both serum selenium and vitamin E levels were shown to be significantly depressed (P less than 0.01) in the alcoholic study groups and serum selenium was more markedly depressed in subjects with established liver disease (controls, serum selenium 108 +/- 13 micrograms/liter, vitamin E 27.6 +/- 7.2 mumol/liter; community alcoholics, serum selenium 94 +/- 19 micrograms/liter, vitamin E 15.3 +/- 3.4 mumol/liter; alcoholic liver disease, serum selenium 78 +/- 15 micrograms/liter, vitamin E 14.7 +/- 5.6 mumol/liter). Depressed serum selenium levels correlated closely with poor nutritional status (r = 0.91). There were no changes in serum glutathione peroxidase activity. Liver disease activity, as judged by transaminase (AST), was more markedly abnormal in subjects with combined vitamin E and selenium deficiency compared to those with normal levels or isolated deficiencies (no deficiency, AST 48 +/- 19 units, combined deficiency, AST 75 +/- 21 units, P less than 0.03). Serum lipid peroxides were elevated in those with combined deficiency and the values correlated significantly with serum transaminases (r = 0.40, P = 0.03).