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 clinical value of rapid C-reactive protein measurement in cerebro-spinal fluid.

C-Reactive protein (CRP) has been measured in 90 consecutive CSF specimens using both latex agglutination and an immunoradiometric assay (IRMA). In the 60 CSF specimens otherwise normal by standard biochemical and microbiological criteria, the median CRP level was 32 micrograms/l (95% confidence limits, 0-108 micrograms/l) and in the remaining abnormal specimens the median level was 176 micrograms/l (95% confidence limits, 110-325 micrograms/l, p = 0.001). C-Reactive protein was detected by a commercial latex agglutination kit at a level of approximately 120 micrograms/l and all significant CNS bacterial infections were positive (7 bacterial meningitis, 2 infected shunts). In addition, viral encephalitis, extensive intracranial malignancy and subarachnoid haemorrhage gave positive agglutinations, but not in every case. A further nine specimens with a minor elevation of CRP level were detected by IRMA (median 76 micrograms/l), but this was of little practical significance. We have shown that normal CSF C-reactive protein levels are very low and we conclude that latex agglutination set at a sensitivity of 120 micrograms/l, although only semi-quantitative, is a rapid and useful method to assess CSF C-reactive protein in routine clinical practice and, when positive, is strong supporting evidence for bacterial infection.

Aminoterminal procollagen III peptide elevation in alcoholics who are selenium and vitamin E deficient.

Serum aminoterminal procollagen III peptide (PIIIP) was measured in 36 alcoholic subjects. There was a significant elevation of PIIIP in subjects with proven liver disease (median 17.5 ng/ml, n = 24) compared to those without liver disease (median 4.7 ng/ml, n = 12). Those subjects with raised serum transaminase values (AST) had elevated PIIIP values (median 13.7 ng/ml, n = 22) compared to those with normal transaminase values (median 3.7 ng/ml, n = 14). In those alcoholic subjects who were deficient in both selenium and vitamin E there was a significant elevation (p less than 0.01) of PIIIP values (median 26.4 ng/ml, n = 7) compared to subjects with normal levels (median 7 ng/ml, n = 11). Subjects deficient in selenium alone had PIIIP values in an intermediate range. Selenium and vitamin E, as important free radical scavengers, may protect the liver in alcoholic subjects from oxidative damage leading to hepatic fibrosis.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug influences on rat hepatic macrophage enzyme production and release in vitro.

Drug influences on hepatic macrophage enzyme release have been investigated using a rat model of macrophage recruitment and activation. N-acetyl-glucosaminidase (NAG), a lysosomal enzyme, and plasminogen activator (PA), a cytosolic enzyme, have been measured in both cell lysates and supernatants after 24 h in culture. 6-mercaptopurine (6-MP) and azathioprine significantly decreased (P less than 0.03) the enhanced production of NAG by recruited macrophages following stimulation in vitro (total NAG activity, nmol substrate hydrolysed/microgram cell protein; recruited macrophages exposed to endotoxin, no drug exposure 0.63 +/- 0.08, azathioprine 0.44 +/- 0.08, 6MP 0.36 +/- 0.06). Prednisolone, azathioprine and 6MP significantly reduced (P less than 0.05) the supernatant release of PA in response to endotoxin exposure in vitro by both cell types (supernatant PA values after 24 h in culture, recruited macrophages exposed to endotoxin, no drug 26.0 +/- 2.9 units, prednisolone 18.5 +/- 1.7 units, levamisole 27.3 +/- 4.7 units, azathioprine 18.1 +/- 2.3 units, 6MP 17.3 +/- 1.5 units). The results from this study indicate that certain drugs used in human liver disease are able to modify the secretory activity of rat hepatic macrophages.

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.

Primary sarcoma of the liver. Report of a case with excellent response to hepatic artery ligation and infusion chemotherapy.

A case of primary undifferentiated sarcoma of the liver in a 66-year-old woman is reported. The similarity of the presenting symptoms to those of a hepatic abscess is emphasized. The patient's response to palliative treatment by means of hepatic artery ligation and chemotherapy was excellent. We believe that this is the first report of such a response in a sarcoma localized to the liver. This therapy may well be useful in symptomatic patients in whom partial hepatectomy is not feasible.

The influence of endotoxin in vitro on hepatic macrophage lysosomal enzyme release in different rat models of hepatic injury.

Since bacterial endotoxin is known to be involved in the pathogenesis of hepatic injury, the influence of endotoxin on lysosomal enzyme production by hepatic macrophages has been investigated. Macrophages have been isolated from the livers of normal rats, from the livers of rats given stilboestrol subcutaneously 4 days previously and from the livers of rats given Corynebacterium parvum intravenously 6 days previously. Following isolation and overnight culture, the macrophages have been maintained in in vitro culture for a further 24 h and the production of N-acetyl-beta-glucosaminidase (NAG) has been measured. Histological assessment has shown that in stilboestrol model an approximate doubling of sinusoidal cell numbers occurs and in the C. parvum model a heavy mononuclear cell infiltrate is present, together with granuloma formation. These changes are reflected in the numbers of macrophages isolated from the respective models. Levels of NAG production by resident macrophages from normal livers are low (0.25 +/- 0.05 nmol substrate hydrolysed/microgram cell protein/h) and unchanged following endotoxin exposure (0.25 +/- 0.05 units). Macrophages isolated from the stilboestrol model show levels of NAG production similar to normal (0.34 +/- 0.06 units), but this increases significantly following exposure to endotoxin (0.42 +/- 0.07 units). Macrophages from the C. parvum model demonstrate markedly enhanced production (0.61 +/- 0.09 units), but this does not increase significantly following endotoxin exposure (0.65 +/- 0.09 units). In contrast to macrophages from normal rat livers, macrophages recently recruited in the stilboestrol model demonstrate enhanced lysosomal enzyme production following endotoxin exposure. It is suggested that endotoxin, as well as other mediators of macrophage activation, may promote hepatic damage through this influence on newly recruited macrophages.

Monocyte lysosomal enzyme release in response to naturally occurring circulating immune complexes.

To investigate the influence of naturally occurring immune complexes (ICs) on monocyte lysosomal enzyme release, blood monocytes have been isolated from normal human volunteers, purified, and maintained in culture for 5 days. These cells have been exposed in vitro to sera containing ICs and to the same sera depleted of ICs with 2% polyethylene glycol (PEG). IC-containing sera have been shown to result in increased lysosomal enzyme release (N-acetyl-beta-glucosaminidase (NAG) and beta-glucuronidase) sustained for up to 5 days even after brief (24-h) exposure (NAG activity at 120 h, nmol substrate hydrolysed ml-1 culture supernatant: control, 98 +/- 27; 2% PEG control, 70 +/- 10; IC serum exposure for 120 h, 305 +/- 73; IC serum exposure for 24 h, 330 +/- 95; exposure to IC-depleted sera 120 h, 158 +/- 93). Further analysis showed no relationship between the total IC concentration and enzyme release, nor was there any relationship between the complement component (C3) composition of the complexes and degree of enzyme release. These results confirm the potential importance of circulating IC on monocyte activation in man and indicate that this could result in changes in macrophage activity at the sites of inflammation.

Effect of long-term corticosteroid therapy on monocyte chemotaxis in man.

The influence of prednisolone on monocyte chemotactic activity in vitro at prednisolone concentrations comparable with those achieved in man following oral dosage has been investigated. Chemotactic activity of monocytes from each of sixteen normal subjects was suppressed by concentrations of prednisolone as low as 25 ng/ml (suppression of chemotaxis, 20%). Maximal suppression occurred at 100 ng/ml (suppression of chemotaxis, 48%) and no significant increase in suppression was produced by increasing the concentration to 200 ng/ml (suppression of chemotaxis, 53%). In contrast, monocytes isolated from ten patients receiving corticosteroid therapy showed no significant suppression of chemotactic activity when exposed to these concentrations of prednisolone, even though they exhibited a normal ability to respond to a chemotactic stimulus. The lack of suppression of monocyte chemotaxis in patients receiving corticosteroid therapy is unexplained, but may represent a change in the circulating monocyte or lymphocyte populations.

Serum prednisolone levels in Crohn's disease and coeliac disease following oral prednisolone administration.

Serum prednisolone levels have been measured following the oral administration of 20 mg prednisolone in 10 normal subjects, in 9 patients with Crohn's disease and in 6 with coeliac disease. Serum prednisolone levels showed more variation in patients with Crohn's disease when compared to normal subjects. In those patients with Crohn's disease who failed to respond to corticosteroid therapy, adequate serum levels of prednisolone were achieved. Patients with coeliac disease had levels similar to normal. Serum protein binding of prednisolone was not significantly different between the groups. We conclude that, even in the presence of mucosal damage, patients with coeliac disease and Crohn's disease achieve therapeutic serum prednisolone levels.