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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.

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.

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.

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, 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.

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.

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.

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 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 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.

Few doctors routinely examine the epitrochlear glands as part of their physical examination of a patient. No palpable epitrochlear nodes were detected in 140 healthy subjects, but palpable epitrochlear nodes were present in 27% of 184 patients with diseases in which lymphadenopathy occurs. Whilst epitrochlear nodes are commonly enlarged in specific acute, subacute, and chronic infections, they are not enlarged in the mild, transient, non-specific febrile illnesses with cervical lymphadenopathy of children and young adults. Enlarged epitrochlear glands provide a useful discriminatory sign in the diagnosis of glandular fever. Enlargement of these nodes is common in most of the lymphoproliferative disorders except Hodgkin's disease. In rheumatoid arthritis their palpability indicates activity of hand joints. The examination of epitrochlear nodes should form part of the routine physical assessment of any ill patient.

From 1973 to 1987, 71 patients (age greater than or equal to 16 years) with stage IA supradiaphragmatic Hodgkin's disease were treated with radiotherapy alone. 23 patients (20, clinical stage; 3, pathological stage) had disease localised to the suprahyoid region of the neck (upper deep cervical, 11; submandibular, 6; submandibular and upper deep cervical, 5; submental, 1). The age range was 17 to 64 (median 33). The male to female ratio was 2.8:1. The histological types were: lymphocyte predominant, 11; nodular sclerosis grade I, 8; mixed cellularity, 4. The 5 and 10 year cause-specific survival was 100% with a disease-free survival of 90% at 5 and 10 years. The proportion of patients with suprahyoid Hodgkin's disease IA was constant over the 15-year period. This only became apparent when the histology of patients with suprahyoid non-Hodgkin's lymphoma stage IA was reviewed.

Splenic function was assessed in subjects aged 70 years or over by counting pits in erythrocytes viewed under differential interference contrast microscopy. An increased percentage of pitted cells has previously been described after splenectomy and in medical hyposplenism. The mean percentage of erythrocytes with one or more pits was significantly higher in 40 elderly patients (3.4%) than in 40 younger patients (1.6%), confirming the results of a previous study on a Brazilian population. There was greater variability of splenic function in the elderly subjects with a subgroup with a greatly increased percentage of pitted erythrocytes. Impaired splenic function may predispose elderly patients to pneumococcal infection. This relationship deserves further study.

A 30 year old man with von Hippel-Lindau syndrome presented with obstructive jaundice caused by a carcinoid tumour of the mid- and upper common bile duct. This association is probably causally related in view of the propensity for patients with von Hippel-Lindau syndrome to develop neuroendocrine tumours.

The case histories of two sisters with Hodgkin's disease are reported. Although the disease developed at different ages, the clinical presentation was similar and the histological classification of biopsy material was identical in the two cases. The relative importance of genetic and environmental factors in the aetiology of the disease is discussed.

One hundred and twenty patients who were members of the Nottinghamshire Coeliac Group completed a questionnaire about the occurrence of coeliac disease, ulcerative colitis and Crohn's disease amongst first-degree relatives. Siblings were at a 20-fold risk of developing coeliac disease and a 15-fold risk of developing ulcerative colitis, and significantly increased risks for these two conditions were also seen in other family members. The relatives of patients with coeliac disease are at increased risk not only of developing coeliac disease but also ulcerative colitis. This provides further support for a possible role of a dietary allergen in the development of ulcerative colitis.

An Irish family with an unusual periodic syndrome is described. Attacks consist of fever with localized myalgia and painful erythema. Other features include abdominal pain and pleurisy, with leucocytosis and a high ESR. The syndrome resembles classical familial Mediterranean fever (FMF) but differs from it in its prompt response to steroids and its autosomal dominant pattern of inheritance. The disease appears to have a benign course and no patient has developed amyloid.

Two cases of type III glycogen storage disease are reported in adults; the occurrence of cirrhosis in one case illustrates the potential development of chronic liver disease in this condition. The other was the oldest patient with this condition found in a review of published reports. Electron microscopy of peripheral blood leucocytes to demonstrate excess glycogen was found to be a quick and useful aid to diagnosis. Histology of these adult cases showed a distribution of hepatocyte vacuolation which has not been previously recorded.

In all of 12 patients with chronic liver disease, whose platelet dynamics were investigated by the 51Cr-labelling technique in association with surface counting, platelet survival was reduced and in 11 the splenic platelet pool was increased. Surface counting showed high initial spleen liver ratios in eight patients, and in four there was evidence of progressive destruction of platelets in the spleen. In one patient, subsequently shown to have a hepatoma, progressive accumulation of platelets was noted at the tumour site.

A series of 4 cases of free perforation of the gallbladder into the peritoneal cavity associated with peritonitis are reported. Two were diagnosed at laparotomy and 2 at post-mortem. The 3 patients who died were men who were either elderly or had serous concomitant diseases, including diabetes, atherosclerosis or alcoholism. The sole survivor was a fit young woman.

A patient developed cholestatic jaundice following therapy with co-trimoxazole. Inadvertent re-challenge with the drug resulted in further clinical and biochemical deterioration, but complete recovery ensued on stopping this drug.

Problems of communication with patients with acute leukaemia and their families were explored by interviewing the next of kin of 26 patients, six of whom were still alive. In all but two cases the diagnosis had been disclosed to the relatives before the patient, but almost one-third of the relatives were not entirely satisfied with the way in which the diagnosis was presented. Medical prognostications at these initial interviews were, on the whole, regarded as being realistic by the relatives. Nine patients learnt of their diagnosis at an early stage, but relatives were undecided whether patients should be told of the diagnosis in explicit terms. Patients often established complete dependence on the hospital and its staff and had difficulties in relating to their own general practitioners while at home during their illness. Social chats were preferred by the relatives rather than regular progress reports from the doctors.

A monoclonal antibody, RL23/36, reacting preferentially with a determinant expressed on normal human hepatocytes is described. Use of an immunohistochemical technique on frozen sections from a range of 75 human liver biopsy specimens revealed that the determinant detected by RL23/36 was not expressed on hepatocytes from a number of patients with biopsy-proven liver disease. Although a normal staining pattern was observed in 28 of 29 biopsy specimens from patients with no evidence of liver disease, the antibody did not bind to hepatocytes in some cases of chronic active hepatitis (2/13), alcoholic liver disease (2/9), haemochromatosis (1/1), cirrhosis (1/2) and liver metastases (2/8). Furthermore, as in a previous study undertaken in the rat, the antibody failed to bind to tumour cells in the single human hepatoma observed in this study. These results suggest that further studies using RL23/36 may shed light on the pathogenesis of a number of liver diseases, including primary hepatocellular carcinoma.

The clinical and pathological features of a fourth patient with progressive encephalomyelitis with rigidity are reported and compared with those previously described. It is suggested that the muscular rigidity, abnormal postures, painful muscular spasms, and myoclonus are a product of excessive and abnormal discharges of alpha motor neurones caused by their release from control by spinal internuncial neurones. A count of neuronal perikarya in the ventral horns confirmed that the disease selectively destroyed small and medium sized neurones, most of which were spinal internuncial neurones. Experimental, clinical, and pathological evidence concerning spinal internuncial neurones is reviewed and found to conform to this theory. The pathogenesis of opsoclonus may be similar.

Twelve patients with cryptogenic hepatic abscess were admitted to hospital in Nottingham between 1977 and 1984. Two patients died and those that recovered were variously treated with open surgical drainage, aspiration and antibiotics.

The haematological role of the spleen has been investigated in a series of 22 patients with active chronic hepatitis. Severe pancytopenia occurred in one patient after three years of steroid therapy and this episode was associated with an increase in spleen size and a high splenic index of red cell destruction. Although the spleen was usually enlarged in the remainder of treated and untreated patients no others showed increased splenic haemolysis. The red cell survival was slightly reduced in most patients but splenic pooling of red cells and expansion of the plasma volume did not significantly reduce the haematocrit level. No consistent haematological differences were detected between the untreated and the treated patients.

Pleomorphic T-cell leukaemia occurring in an adult Caucasian patient is described. The leukaemia cells expressed both antigenic determinants (T4 and T8) normally detected separately on either helper or suppressor cells. They functioned as helper cells and there was evidence of unbridled antibody production. It is possible that a distinctive subtype of pleomorphic T-cell leukaemia occurs in Caucasian patients.

In four cases of biopsy proven amyloidosis there was evidence of impaired splenic function. All had absent or grossly reduced splenic uptake on colloid isotope scans and three had haematological changes consistent with hyposplenism. Poor splenic function with a normal sized or enlarged spleen may be a clue to underlying amyloid.