Employment prospects for patients with intestinal stomas: the attitude of occupational physicians.

The attitude of 126 occupational physicians to the employment problems of patients with intestinal stomas were assessed by a postal questionnaire. Heavy work and work in hot places were commonly (65 and 49 per cent of respondents respectively) considered 'unsuitable'. Work as a food handler, handling toxic chemicals and driving duties was thought to be 'unsuitable' by 35, 14 and 10 per cent of respondents respectively and actually forbidden by a few physicians. Risk of spread of infection was perceived to be greater than normal for someone with a stoma by 28 per cent of respondents. This attitude was significantly more common (p less than 0.05 Chi square) among the associate members compared to full members of the Faculty of Occupational Medicine. Attitudes to people with either an ileostomy or a colostomy were similar. Most respondents (87 per cent) expected more sickness absences than normal for people with inflammatory bowel disease without a stoma but half appreciated that the creation of a stoma would result in normal amounts of sickness absence. The Occupational Physicians' views of which jobs within their industry were unsuitable for stoma patients were inconsistent. In practice most tasks can be performed normally by someone with a stoma so that each case should be assessed on an individual basis. There is a need for greater understanding and awareness by doctors of the good employment potential of people with intestinal stomas. The reasons for present attitudes are reviewed and new guidelines suggested.

Bacterial infections complicating liver disease.

Bacterial infection is a serious and often fatal complication of patients with liver disease and can prove fatal either directly or by precipitation of gastrointestinal bleeding, renal failure, or hepatic encephalopathy. At greatest risk are patients with alcoholic cirrhosis or decompensated chronic liver disease, or cases of acute liver disease who progress to fulminant hepatic failure or subacute hepatic necrosis. Infection appears to be unusual in patients with primary biliary cirrhosis. The site and type of infection is unrelated to the aetiology of the liver disease. Bacteraemia, pneumonia, urinary tract infection and spontaneous bacterial peritonitis are most common but infective endocarditis and meningitis, especially with pneumococci, are easily overlooked. Clinical suspicion of infection must be high as the only indication may be a general deterioration in the patients' clinical state, increasing encephalopathy or renal impairment. In the case of patients with fulminant hepatic failure, infection may precipitate the initial or recurrent encephalopathy and contributes to death in 10% of fatal cases. Spontaneous bacterial peritonitis is now recognized to occur in the absence of clinical features of peritonitis. The PMN content of the ascitic fluid may provide the only indication of infection and is the most readily available screening test. The most common types of organism responsible for all types of infection are Gram-negative enteric and streptococci, especially pneumococci, while infection with anaerobes is rare. Risk factors for infection include decompensated alcoholic liver disease, fulminant hepatic failure, gastrointestinal bleeding, invasive practical procedures and impaired host defence mechanisms against infection. Of the host defence mechanisms, impaired function of the reticuloendothelial system, complement, and PMNs represent the most common and serious defects. Defects of humoral immunity are present in ascitic fluid from patients with cirrhosis and are probably a major reason for development of spontaneous bacterial peritonitis. Diuresis improves these functions and reduces the risk of peritonitis. Treatment of infections even with the appropriate antibiotic is still associated with a high mortality but the use of adjuvant gut sterilization is promising, particularly in cases infected with Gram-negative enteric organisms. Infusions of fresh frozen plasma, blood and cryoprecipitate improve some systemic host defences and may be beneficial in the treatment and reduction of risk of infection.

Employment problems and prospects for patients with inflammatory bowel disease.

A random sample of 170 patients (88 men) with chronic inflammatory bowel disease (75 ulcerative colitis) were first interviewed in 1978 about their employment status, problems at work, and influence of surgery. Surgery had been carried out on 120 and 53 had an ileostomy. After six years 144 (92%) of the 156 survivors replied to a follow up postal questionnaire. Of the initial sample, 122 (72%) were working and there were only three (1%) registered unemployed. After six years a similar proportion were working and only seven (5%) were unemployed. Continuity of employment was good with 57% in the same job. Changes in work because of health had been made by 72 patients mainly caused by bowel disease. After surgery 10% completely changed and 22% modified their work while a few had to retrain or retire. Panproctocolectomy and ileostomy resulted in more changes and longer time off work after surgery than colectomy and ileorectal anastomosis, with 35% and 17% respectively off work after one year. Problems at work, in particular general malaise and arthritis were experienced by 34 (28%) patients. Fewer problems were experienced by patients with a stoma who also had less sickness absence than those without a stoma. Colleagues and employers were usually supportive although some patients encountered discrimination especially those with a stoma or working in the food industry. Few patients had been counselled on their work. In general employment prospects and time off work were good and employers should be encouraged to take an optimistic and supportive role. Doctors should consider that convalescence after surgery may be longer than they perceive and must provide better counselling for patients.

Capacity for work and employment record of patients with inflammatory bowel disease.

The literature on the vocational effects of inflammatory bowel disease is scanty. This paper describes the effects in a sample of 170 patients, supplemented with data obtained from the Ileostomy Association. Work capacity is affected by diarrhoea, urgency (including the problem of access to toilets), fatigue, and hospitalization. Rare complications, such as arthritis, represent special difficulties. The fashioning of an ileostomy has, as a general rule, a positive effect on the ability of the patient to work and, overall, inflammatory bowel disease should not prevent the vast majority of patients from successfully following a chosen career.

Polymorphonuclear leucocyte locomotion and aggregation in patients with alcoholic liver disease.

Defects in stimulated movement of polymorphonuclear (PMN) leucocytes was detected in 57% of patients with alcoholic liver disease. Serum from patients with the cellular defect had no effect on the function of normal PMN leucocytes. Aggregation responses of patients' PMN leucocytes suggest that the cellular defect may be related to specific abnormalities in the response to the C5a chemotactic factor. Defective serum attractant activity was found in 65% of the patients tested and the presence in the patients serum of humoral directed antagonists appeared to be responsible for the defect in majority of cases. Further analysis pointed to the presence of at least two distinct antagonists and the possible involvement of proteases in this serum abnormality. The activity of the serum antagonists or the severity of the cellular defect were unrelated to the presence of bacterial infection or elevations in serum IgA or IgG. The high frequency of cellular defects, possibly as a result of in vivo activation, in conjunction with serum abnormalities could account for the increased susceptibility of patients with alcoholic liver disease to bacterial infection.

Application of different counting systems in measuring localised retention the entero-hepatic circulation.

The use of labelled bile salt retention is likely to be a major new technique in assessing the function of the terminal ileum. Papers to date have described two techniques to measure both the 100% and the seven-day retention values. These use whole body counters or uncollimated gamma cameras. We have compared the use of simple probe systems with an uncollimated gamma camera for the retention measurements. There was no significant difference in the results obtained with any of these systems. It is concluded that simple probe measurements can provide a precise and highly reproducible assessment of bile salt retention which greatly increases the availability of this test.

Defects in serum attractant activity in different types of chronic liver disease.

Serum attractant activity, measured in 57 patients with chronic liver disease, was significantly reduced in 66% of the 27 patients with alcoholic liver disease and in 29% of the 17 patients with chronic active hepatitis, but was normal in 13 patients with primary biliary cirrhosis despite the presence of established cirrhosis in nearly half of them. In patients with alcoholic liver disease, but not in those with chronic active hepatitis, there was a correlation between the serum defect and severity of liver disease. The defect could not be related to the deficiency of key complement components, raised concentrations of IgA or G or the concurrent presence of bacterial infection. These findings suggest that the aetiology of liver disease may be an important factor in the development of serum attractant abnormalities.

Yeast opsonisation and complement in children with liver disease. Analysis of 69 cases.

Opsonisation of heat-killed bakers yeast and C3 and C4 concentrations were determined in sera from 69 children with liver disease and 39 controls as simple screening procedures for abnormalities in the complement system. Where significant defects in these moieties were encountered, the activity of the following was measured: total haemolytic complement, C4, C5, total alternative pathway, factor B and D activities were measured. Complement activation was detected by the presence of C3d in EDTA plasma samples. Yeast opsonisation, C3 and C4 concentrations and activities of all complement components measured were significantly (P less than 0.001) reduced in all of 10 children with fulminant hepatic failure (FHF) and six with chronic active hepatitis (CAH). There was no consistent relationship between complement deficiency and standard tests of liver function. C3 breakdown products were identified in plasma from five patients with CAH and complement deficiency but not in three patients with complement deficiencies associated with FHF. Complement concentration and activity improved in children recovering from FHF and in CAH treated by immunosuppressants. Yeast opsonisation index was raised significantly without parallel increase in C3 or C4 concentration in eight of nine children with biliary atresia before surgery and 11 of 13 with alpha-1-antitrypsin deficiency regardless of age or the presence of active liver disease. Yeast opsonisation indices became normal after successful surgery in patients with biliary atresia.

Impaired opsonization by serum from patients with chronic liver disease.

Serum opsonization of two organisms, E. coli and yeasts (S. cerivisiae), was examined in 68 patients with chronic liver disease (CLD). Impaired opsonization for yeasts was found in seven (29%) of 24 patients with chronic active hepatitis, six (27%) of 22 with alcoholic cirrhosis and five (23%) of 22 with primary biliary cirrhosis. Opsonization for E. coli was normal in patients with primary biliary cirrhosis but impaired in seven (29%) patients with chronic active hepatitis and three (14%) of those with alcoholic cirrhosis. The defect of opsonization in chronic active hepatitis was found mainly in patients with histological evidence of active disease. A deficiency, rather than antagonism or inhibition, of normal opsonization factors was responsible, but could not be related to reduced levels of serum complement factors of either the classical or the alternative pathway present in 45% of the patients with chronic active hepatitis, 71% with alcoholic cirrhosis and 18% of those with primary biliary cirrhosis. Serum from two of 11 patients with impaired opsonization antagonised the function of normal polymorphonuclear leucocytes, and polymorphonuclear leucocytes from six of seven patients had slightly reduced phagocytosis/killing of E. coli opsonized in normal serum. Defects of serum opsonization, complement activity and polymorphonuclear leucocyte function may be causes of the increased susceptibility to bacterial infection in patients with CLD.

Bacterial and fungal infection in children with fulminant hepatic failure: possible role of opsonisation and complement deficiency.

Serious bacterial infection, including eight episodes of bacteraemia, developed in seven of 15 (47%) children with fulminant hepatic failure. Those with infections had a slightly higher leucocyte response than those who did not. Serum immunoglobulin concentrations were normal or raised in all patients. Opsonisation of heat-killed baker's yeast, functionally measured total haemolytic complement, C4, C5, total alternative pathway activity, factor B and D activity, and C3 concentrations were all significantly (p less than 0.005) reduced at presentation but returned to normal in those who survived. The severity of defects in yeast opsonisation, C4, and factor B activity at presentation were significantly correlated with the subsequent development of infection. In five patients bacteraemia occurred at a time when opsonisation and complement components were defective. Plasma infusions in vivo improved opsonisation in vitro and only one bacterial isolate was obtained within four days of such an infusion. Those patients who developed infection had received significantly (p less than 0.05) fewer plasma infusions than those who did not. Our findings suggest that both alternative and classical pathways of complement are defective in children with severe liver disease and may contribute to the susceptibility of such patients to infections. Plasma infusions might be useful in reducing the incidence of bacterial infection in such conditions.

Serum stimulatory activity and polymorphonuclear leucocyte movement in patients with fulminant hepatic failure.

Serum from 27 patients with fulminant hepatic failure and grade IV encephalopathy had reduced ability to stimulate the movement in vitro of normal polymorphonuclear leucocytes. All patients had a deficiency of serum complement factors C3 and C5 and there was a significant positive correlation between C5 and serum stimulatory activity. However, in addition to this complement defect, serum from 22% of patients contained an antagonist to normal serum stimulatory factors. This antagonism was attributed to at least two different substances in the serum on the basis of differences in heat lability, dialysability and action on complement factor C5a. Polymorphonuclear leucocytes from eight of 13 patients had reduced movement toward serum, but serum from only one patient contained an antagonist acting on the cells; this was probably related to an underlying carcinoma of the breast. During the early stages of clinical recovery, serum stimulatory and complement activity returned to normal. These serum and cellular defects have not been reported previously in patients with fulminant hepatic failure and represent major defects in the body's defenses against bacterial infection.

Defects of serum chemoattraction and polymorphonuclear leucocyte movement in patients with primary hepatocellular carcinoma.

Movement of polymorphonuclear leucocytes to the site of tumour cells may be an important stage in host defences against tumours in a variety of organs. In this study, sera from 29 of 30 patients with primary hepatocellular carcinoma had reduced ability to stimulate the movement in vitro of normal polymorphonuclear leucocytes. The serum defect was more severe in 11 patients with underlying cirrhosis but was not related to abnormalities of tests of liver function, levels of serum alphafetoprotein, or deficiency of complement factors C3 and C5. Serial studies showed that the defect was persistent and progressive in patients in whom the tumour did not respond to treatment. In 35% of patients, mainly those with cirrhosis, the sera contained antagonists to normal serum chemotactic factors which were heat stable and dialysable, but could be distinguished by their effect on complement factor C5a. A heat labile dialysable antagonist(s) was found in sera from 28% of the patients (mainly those without cirrhosis) which antagonized the movement of normal polymorphonuclear leucocytes (cell directed antagonism). In addition to these serum defects, polymorphonuclear leucocytes from two of seven patients studied had reduced movement which was not related to the presence in the serum of cell directed antagonists. These serum and cellular defects have not been reported previously in patients with primary hepatocellular carcinoma, and could compromise the body's defences against the tumour.

Defective yeast opsonisation and functional deficiency of complement in sickle cell disease.

Opsonisation of heat-killed baker's yeast, functional activity of the total alternative pathway of complement, and factor B detected functionally and immunochemically were significantly reduced in 72 children with sickle cell disease compared with 40 age-matched black control children. There was significant correlation between functional activity of the total alternative pathway and functionally measured factor B, but not between factor B measured functionally and immunochemically. The opsonisation defect could be corrected in vitro by normal serum, and factor B-depleted serum, and was qualitatively similar to that seen in patients with primary yeast opsonisation deficiency. Serial studies showed that these serum defects were persistent. Reduction in the activity of components of the alternative pathway of complement and opsonisation was found in 4 patients who had recovered from pneumococcal meningitis and in one who developed osteomyelitis. Defects of yeast opsonisation and complement which are common in patients with sickle cell disease, may partly explain the children's increased susceptibility to infection, and might help to identify individuals especially at risk.

Bacteraemia in patients with fulminant hepatic failure.

Among 103 patients with fulminant hepatic failure due to viral hepatitis, paracetamol overdose, or halothane anaesthesia, treated over a 2-year period, 23 had bacteraemia. Gram-positive organisms, mainly streptococci and Staphylococcus aureus, were isolated from 61% of patients. Escherichia coli, the main type of gram-negative organism isolated, was found in 26% of patients and was associated with a fatal outcome more often than gram-positive bacteria. The type of organism isolated was not related to the aetiology of the hepatic necrosis, the presence of renal failure, or the clinical outcome. In the 23 patients with bacteraemia the same organism was isolated from other sites of infection, including sputum in four, urine in two, and the central venous catheter and arteriovenous shunt in one. Bacteraemia usually occurred 3 days after admission or on average 2 days after clinical deterioration to grade IV encephalopathy had begun. In 11 patients, the infection had an adverse effect on their clinical course, in three patients being implicated as a cause of the encephalopathy. Although in four patients the development of infection after all signs of encephalopathy had cleared may have been a major factor in their death, two of these patients had evidence of severe sepsis, pneumococcal peritonitis, and renal abscesses from which Candida albicans was cultured. An awareness of infection as a complication both of the acute stage of the illness and during recovery is essential if early detection and treatment are to be effective.

Mechanism of the serum defect in yeast opsonization in children with fulminant hepatic failure (FHF).

Defective opsonization of heat-killed baker's yeast was found in all 14 children with fulminant hepatic failure (FHF) but returned to normal in two who recovered and was normal in six mothers of patients. Yeast opsonization was significantly correlated with factor B activity of FHF serum but not with other components of classical or alternative pathways of complement. Reconstitution and family studies suggested that defective yeast opsonization in FHF is secondary and, although dependent on factor B activity, is qualitatively and quantitatively similar to that of primary yeast opsonization deficiency. These findings suggest that the factors responsible for opsonization of yeasts, or their regulation, are synthesized or controlled by the liver.

Circulating immune complexes in patients with fulminant hepatic failure.

Circulating immune complexes were found in 15 of 16 patients with fulminant hepatic failure due to viral hepatitis and all of six patients who had had halothane anaesthesia; however, they were found in only five of 32 patients with paracetamol-induced hepatic necrosis. The levels of circulating immune complexes were not related to the severity of the clinical course, development of renal failure, final outcome, or severity of hypocomplementaemia. All the patients had depressed reticuloendothelial function as assessed by the clearance of 125I microaggregated albumin. These findings show that circulating immune complexes in fulminant hepatic failure are not simply a reflection of an immune response to liver antigens released as a result of the hepatic necrosis; nor are they a reflection of the failure of the reticuloendothelial system. This supports the view that circulating immune complexes are associated with immune mediated liver injury and may contribute to the process.

Improved survival after orthotopic liver grafting.

A total of 108 orthotopic liver transplants have been carried out in the Cambridge/King's College Hospital series. Over 13 years, changes in patient selection, immunosuppression, and surgical and anaesthetic techniques have led to a steady improvement in results. Results obtained in the last 22 patients indicated that over half survive for one year. Although at considerable risk during the operation, patients with non-malignant cirrhotic diseases who survive one year have a good long-term chance of survival

Clinical aspects of non-A, non-B hepatitis infection.

Although non-A, non-B hepatitis is usually a mild subclinical illness, 40% of cases of fulminant viral hepatitis are attributed to infection by this agent. The administration of coagulation factor IX concentrates before liver biopsy in 17 patients with chronic liver disease was followed by the development of hepatitis in four, which proved fatal in three cases. The diagnosis was confirmed by transmission in chimpanzees, and further studies demonstrated the existence of two types of non-A, non-B hepatitis with different incubation periods and specific ultrastructural changes in the hepatocytes. The progression of 40% of cases of acute viral hepatitis to chronic liver disease and the development of chronic liver disease in renal and hepatic transplant recipients is very disturbing. It is likely that this type of hepatitis is an aetiological factor in some cases of hepatitis B surface antigen-negative chronic active hepatitis.