'Relapse' of chronic active hepatitis--not always what it seems.

Immune chronic active hepatitis is a disease notorious for its unpredictability. In a patient with chronic hepatitis who has already suffered relapses a search for a second cause of jaundice is not usually necessary. This report emphasises the essential role of liver biopsy.

Neurological complications of celiac disease: a rare but continuing problem.

Neurological complications are a recognized but unusual manifestation of celiac disease. We present here our experiences with four current cases. Age of patients at presentation with neurological signs varied from 7 to 67 yr. In one patient, the neurological disability developed before the diagnosis of celiac disease, whereas, in the other three, it occurred from months to 16 yr after the diagnosis had been established. One patient died of rapidly progressive neuromyopathy. The other three patients had combinations of cerebellar and posterior and lateral column abnormalities. All four patients developed neurological complications despite a strict gluten-free diet. In three of four patients, there was no improvement in duodenal histology on this diet. Treatment with vitamin B12, folic acid, or vitamin D failed to reverse the changes. No other nutritional deficiencies were found. Vitamin E levels were normal in two of three patients. One patient had no response to treatment with immunosuppressive drugs. The mechanisms responsible for these neurological complications are poorly understood, although patients whose duodenal histology fails to improve on a gluten-free diet may be at greater risk. There have been no real advances in the understanding of this condition since the original description nearly 30 yr ago.

Primary gastric lymphoma in clinical practice 1973-1992.

This study assessed the presentation, treatment, and prognosis of primary gastric lymphoma in general hospital practice and its relation to infection with Helicobacter pylori. The number of patients that would on the current recommendations have been suitable for H pylori eradication therapy was also examined. All lymphomas were graded according to a standard classification of gut lymphoma into high and low grade disease. Forty five patients (mean age 65 years) were identified. The overall five year survival was 40% with a trend in favour of an improved prognosis for low grade and stage I disease. H pylori was present in 80%. Only one of 18 patients with a low grade mucosa associated lymphoid tissue tumour had mucosal disease alone, which responded to omeprazole and amoxycillin. All other patients had bulk disease. These patients were treated by surgery, chemotherapy or radiotherapy or a combination of these treatments. In district hospital practice, most cases of primary gastric lymphoma have bulk disease at presentation. Even in patients with low grade gastric lymphoma on histological examination, many on the current evidence would not be suitable for anti-H pylori therapy alone.

Functional hyposplenism following allogeneic bone marrow transplantation.

AIMS: To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS: Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS: Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION: These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT.

Functional hyposplenism in alcoholic liver disease: a toxic effect of alcohol?

Functional hyposplenism, seen in some patients with alcoholic liver disease, may contribute to the increased susceptibility to infections. As hyposplenism does not complicate non-alcohol related chronic liver disease, it is probably secondary to a toxic effect of alcohol. Over a two year period the case notes of 82 patients with alcoholic liver disease, whose splenic function had been assessed by the counting of pitted erythrocytes using differential interference microscopy, were reviewed to monitor mortality and the effects of hyposplenism. Thirteen patients (seven with hyposplenism) had serial measurements of pitted erythrocyte count made to assess the effect of abstinence from alcohol on splenic function. Thirty one of the 82 alcoholic patients had pitted erythrocyte counts greater than 2%. Eighteen of 82 (16%) patients died over the two years and 11 of these had been unable to stop drinking. Only one patient died of sepsis. Five patients (6%) had pitted erythrocyte counts comparable with those in splenectomised patients. In 12 of 13 patients who had abstained from alcohol for two months, the pitted erythrocyte count fell from a median of 3 to 1.3% (mean: 8.1 to 2.6%. p = 0.01). The pitted red cell count in two patients increased. One had abstained, the other had continued to drink heavily. Short term mortality in alcoholics is high, particularly if they continue to drink heavily. Only a few of these deaths are secondary to infection. Splenic function, as assessed by these methods, improves in most patients with abstinence, suggesting that the functional hyposplenism may be a result of a direct toxic effect of alcohol on the spleen.

Non-Hodgkin's lymphoma in elderly patients: a phase II study of MCOP chemotherapy in patients aged 70 years or over with intermediate- or high-grade histology.

During the period 1 January 1988 to 31 July 1991, 74 patients were seen with intermediate- or high-grade non-Hodgkin's lymphoma who were aged 70 years or over. Of these 74 patients, 20 were treated with radiotherapy alone, and 46 were judged as suitable for treatment with the chemotherapy regime MCOP (mitoxantrone, cyclophosphamide, vincristine and prednisolone). Involved field radiotherapy (35-40 Gy in 20 fractions over 4 weeks) was given to 14 of the 21 patients with stage IA and IIA disease, and 6 of the 25 patients with stage III and IV disease after completion of chemotherapy. The complete response rate was 63% at the completion of all treatment (6 months), and 39% at 12 months. There were no treatment-related deaths, and the 3-year cause-specific survival was 26% (overall survival 21%). For patients aged 70-75 years, the 3-year cause-specific survival was 34% in comparison to 17% for those patients aged 76-93 years. The chemotherapy was well tolerated by those patients aged 70 years and over, 70% of the patients did not vomit and no patients had significant vincristine neuropathy. There were only four infections associated with neutropenia. All patients completing six cycles had moderate, patchy alopecia. This MCOP regime is suitable for patients aged 70 years and over with intermediate- and high-grade non-Hodgkin's lymphoma. The survival of patients is comparable to that obtained with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with less apparent toxicity.

Acquired C1 inhibitor deficiency with lymphoma causing recurrent angioedema.

A 52 year old man who developed recurrent, massive and generalized angioedema for the first time during adult life was found to have an acquired deficiency of C1q esterase inhibitor (C1 INH) in association with a B cell lymphoma producing a paraprotein. He had low levels of C4 and C1 INH during the attacks which returned to normal after the successful treatment of lymphoma. An underlying lymphoproliferative disease should always be considered in adult patients with this immunological profile, recurrent angioedema and a negative family history.

Splenic function in inflammatory bowel disease: assessment by differential interference microscopy and splenic ultrasound.

The role of the spleen in patients with ulcerative colitis and Crohn's disease was assessed by counting pitted erythrocytes with differential interference microscopy and by splenic ultrasound. The findings were compared with those from age- and sex-matched controls and a group of splenectomized patients. The incidence of hyposplenism was lower than previously reported, being found in six of 29 patients with ulcerative colitis (of whom five had relapsed pancolitis and one had quiescent pancolitis) and two of 21 patients with Crohn's disease. Pitted erythrocyte counts were significantly higher in patients with ulcerative colitis compared with age- and sex-matched controls (p < 0.001), but there was no difference in counts between patients with Crohn's disease and controls. Patients with relapsed but not quiescent ulcerative colitis had significantly smaller spleens than controls. Patients with the highest pitted erythrocyte counts had the smallest spleens on ultrasound. More effective medical and surgical therapy may account for the lower incidence of functional hyposplenism observed in this study. Nonetheless, patients may show marked hyposplenism and remain at risk of overwhelming infection and operative complications. Differential interference microscopy is a simple technique that can be used to assess splenic function in patients thought to be susceptible to infection.

Splenic function, assessed by quantification of erythrocyte membrane pits, is normal in chronic active hepatitis and primary biliary cirrhosis.

Splenic hypofunction has been described in a number of diseases in which autoimmune mechanisms are believed to play a part. It has been reported in association with chronic active hepatitis although this relationship has not been systematically investigated. Twenty patients with chronic active hepatitis and 22 patients with primary biliary cirrhosis, together with an equal number of age-matched controls for each group, were studied. Splenic function was assessed by counting pits on erythrocytes viewed under differential interference contrast microscopy. There was no difference between splenic function in either chronic active hepatitis, or primary biliary cirrhosis, and normal controls. In both groups of patients splenic hypofunction was significantly related to age.

Splenic function in alcoholic liver disease.

Splenic function was assessed in 42 patients with alcoholic liver disease by counting the percentage of erythrocytes with indentations or pits, seen by differential interference contrast microscopy. These pits represent cellular debris normally removed by the spleen. The findings were compared with 42 age and sex matched controls. Mean (SEM) pitted red cell counts in the patients was 2.7 (0.4)% and in the controls 0.7 (0.07)% (p < 0.001). In all of the eight reformed drinkers (five with biopsy proven cirrhosis), cell counts were normal. Six patients with alcoholic liver disease had had serious infections within the past year. Of these, one had had a recent pneumococcal pneumonia and another of the patients died from overwhelming pneumococcal septicaemia. Both of these patients had evidence of functional hyposplenism as judged by high pitted erythrocyte counts. A total of 18 patients were considered to have pitted red cell counts above the normal, and 11 of these had proven cirrhosis and/or gross ascites. This study is the first to show the presence of functional hyposplenism in alcoholic liver disease and provides further evidence of the predisposition that these patients have to infection. At present, it is unclear whether the hyposplenism is a direct toxic effect of alcohol or the result of cirrhosis; further studies are warranted.