[Hepatopulmonary syndrome. A consideration in patients with liver disease accompanied by dyspnoea and hypoxaemia]. / Het hepatopulmonaal syndroom.

BACKGROUND: Hepatopulmonary syndrome is a severe complication of liver disease, with greatly increased mortality. The syndrome is characterized by increased blood-flow, intrapulmonary vasodilatation and angiogenesis, leading to effects including the formation of shunts. This leads to a decrease in arterial oxygen pressure. Liver transplantation is the only effective treatment. CASE DESCRIPTION: A 74-year-old woman with cirrhosis of the liver attended the pulmonary outpatients' clinic with progressive dyspnoea, which worsened if she sat upright from a lying position (platypnoea). Contrast echocardiography confirmed the diagnosis 'hepatopulmonary syndrome'. The patient was not eligible for liver transplantation. She was given oxygen therapy and died from decompensated cirrhosis of the liver eighteen months later. CONCLUSION: Early recognition of hepatopulmonary syndrome is important, because patients may be given priority for liver transplantation. Contrast echocardiography is indicated in patients with liver disease and suffering from hypoxaemia for which there is no other explanation, to reveal the presence of intrapulmonary shunt.

Cirrhosis patients have a coagulopathy that is associated with decreased clot formation capacity.

BACKGROUND: The coagulopathy in cirrhosis is associated with thrombosis and bleeding. OBJECTIVES: To gain better insights into the coagulopathy in patients with cirrhosis, we evaluated plasma thrombin generation and whole blood clot formation in a cross-sectional study. METHODS: Blood was collected from 73 patients with all-cause cirrhosis (Child-Pugh-A n = 52, B n = 15, C n = 6) and 20 healthy controls. Activity of the coagulation pathways was measured with assays for factor (F) VIIa and FIXa-antithrombin and FXa-antithrombin complexes, respectively. Thrombin generation by calibrated automated thrombography was determined in platelet-poor plasma using a 1 or 5 pm tissue factor trigger with/without thrombomodulin. ROTEM measurements were performed in whole blood triggered with 35 pm tissue factor without/with 175 ng mL(-1) tissue plasminogen activator (the latter refered to as 'tPA-ROTEM'). RESULTS: We observed an increased generation of FVIIa and a moderately elevated amount of FIXa (in complex with antithrombin) without apparent increase in FX activation in patients with cirrhosis. In accordance with this prothrombotic state, markers of thrombin generation potential were also increased upon increasing severity of cirrhosis. In the whole blood clotting assay we observed delayed clot formation and decreased clot strength associated with increased severity of cirrhosis. No significant differences were found for tPA-ROTEM parameters of clot degradation. CONCLUSION: These results indicate that cirrhosis patients have an overall procoagulant plasma milieu but a decreased whole blood clot formation capacity with an apparently unaltered resistance to clot lysis.

Fatigue and health-related quality of life in inflammatory bowel disease: results from a population-based study in the Netherlands: the IBD-South Limburg cohort.

BACKGROUND: The importance of fatigue in chronic disease has been increasingly recognized; however, little is known about fatigue in inflammatory bowel disease (IBD). The aim of the present study was to investigate the prevalence and severity of fatigue and the impact on health-related quality of life (HRQoL) in patients included in a population-based IBD cohort in the Netherlands. METHODS: IBD patients, diagnosed between January 1st, 1991, and January 1st, 2003, were followed up for a median of 7.1 years. They completed a questionnaire, which included a disease activity score, the Multidimensional Fatigue Inventory (MFI-20), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the Short Form health survey (SF-36). Hemoglobin levels were recorded. RESULTS: Data were available in 304 Crohn's disease (CD), 368 ulcerative colitis (UC), and 35 indeterminate colitis (IC) patients. During quiescent disease, the prevalence of fatigue was nearly 40%. MFI-20 and HRQoL scores were significantly worse in IBD patients having active disease. In a multivariate analysis, disease activity was positively related with the level of fatigue in both CD and UC. In UC, anemia influenced the general fatigue score independently of disease activity. Disease activity as well as fatigue were independently associated with an impaired IBDQ. CONCLUSIONS: In IBD, even in remission, fatigue is an important feature. Both in CD and in UC, fatigue determined HRQoL independently of disease activity or anemia. This implies that in IBD patients physicians need to be aware of fatigue in order to better understand its impact and to improve the HRQoL.

Neuromuscular manifestations in hereditary haemochromatosis.

Involvement of peripheral nerves and skeletal muscles has been reported in the course of hereditary haemochromatosis (HH) but a systematic study is lacking. However, patients with HH report symptoms suggesting a possible polyneuropathy or myopathy. In this study patients with DNA proven HH were recruited from a large general teaching hospital. First, all patients were clinically examined using a structured interview and neurological exam. After reviewing these data an expert panel reached consensus about the presence of a possible neuropathy or myopathy and made recommendations for ancillary investigations (nerve conduction studies, electromyography, thermal threshold tests, laboratory tests). After a second meeting consensus was reached about the final diagnosis. Patients who had a neuropathy or myopathy of which the origin was still unclear were referred to an independent neurologist for further evaluation. Ultimately, of 46 patients included, 25 had no myopathy or neuropathy, 5 an axonal sensory motor polyneuropathy of which the cause was found (diabetes in 2, combination of diabetes and chemotherapy in 1, Charcot Marie Tooth type 2 in 1, Morbus Sjögren in 1), 9 an idiopathic axonal sensory motor polyneuropathy, 3 an idiopathic small fiber polyneuropathy and 4 a carpal tunnel syndrome. There were no cases of proven myopathy. We conclude that an idiopathic polyneuropathy was diagnosed in a relative large number of patients with HH (26%), but the causal relationship needs to be confirmed in larger (case-control) series.

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

OBJECTIVES: Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group. METHODS: IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were calculated as outcome parameters. RESULTS: In total, 476 Crohn's disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective. CONCLUSIONS: This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Changing aspects of HFE-related hereditary haemochromatosis and endeavours to early diagnosis.

HFE-related hereditary haemochromatosis (HH) is an iron overload disease attributed to the highly prevalent homozygosity for the C282Y mutation in the HFE gene. The pathophysiology of this error in iron metabolism is not completely elucidated yet, although deficiency of the iron regulatory hormone hepcidin appears to play a role. Ways of diagnosing iron overload include measurement of the serum iron parameters, i.e. serum transferrin saturation and serum ferritin, by a liver biopsy or by calculating the amount of mobilisable body iron withdrawn by phlebotomies. Clinical signs attributed to HFE-related HH include liver failure, arthralgia, chronic fatigue, diabetes mellitus and congestive heart failure. organ failure can be prevented by phlebotomies starting before irreversible damage has occurred. Therefore, screening to facilitate early diagnosis is desirable in individuals at risk of developing HFE-related iron overload. over time it appeared that the clinical penetrance of the HFE mutations was much lower than had previously been thought. This changed the opinion about a suitable screening modality from case detection, via population screening, to family screening as the most appropriate method to prevent HFE-related disease. However, before the implementation of family screening it is vital to have thorough information on the relevance of the specific health problem involved, on the clinical penetrance of C282Y homozygosity and on the effectiveness of the screening approach.

Morbidity and mortality in first-degree relatives of C282Y homozygous probands with clinically detected haemochromatosis compared with the general population: the HEmochromatosis FAmily Study (HEFAS).

BACKGROUND: Family screening has been suggested as a sophisticated model for the early detection of HFE-related hereditary haemochromatosis (HH). However, until now, controlled studies on the morbidity and mortality in families with HH are lacking. METHODS: Data on iron parameters, morbidity and mortality were collected from 224 dutch C282Y-homozygous probands with clinically overt HH and 735 of their first-degree family members, all participating in the HEmochromatosis fAmily study (HEfAs). These data were compared with results obtained from an age- and gender-matched normal population. HEfAs and controls filled in similar questionnaires on demographics, lifestyle factors, health, morbidity and mortality. RESULTS: A significantly higher proportion of the HEfAs first-degree family members reported to be diagnosed with haemochromatosis-related diseases: 45.7 vs 19.4% of the matched normal population (McNemar p<0.001). Mortality among siblings, children and parents in the HEFAS population was similar to that in the relatives of matched control. CONCLUSION: In this study we show that, morbidity among first-degree family members of C282Y-homozygous probands previously diagnosed with clinically proven HH is higher than that in an age- and gender-matched normal population. Further studies are needed to definitely connect these increase morbidity figures to increase prevalenc of the C282Y mutated HFE-gene and elevated serum iron indices.

[Diagnostic image (74) A woman with stomach cramps and vomiting]. / Diagnose in beeld (74). Een vrouw met buikkrampen en braken. Hernia van Spigelius.

In a 53-year-old woman with abdominal pain, nausea and vomitus lasting for a month and leading to weight loss, abdominal CT showed abdominal spigelian hernia.

Iron saturation of serum ferritin in patients with adult onset Still's disease.

OBJECTIVE: Patients with Still's disease show a prominent acute phase reaction. Our hypothesis is that under these circumstances the iron uptake of ferritin will not keep pace with its synthesis, and is therefore not a valid reflection of the iron status in these patients. METHODS: Previously we developed a method to measure the iron content of ferritin; we investigated the usefulness of this method to establish the iron status of patients with anemia of inflammation. RESULTS: In 9 patients with adult onset Still's disease (AOSD) we observed high ferritin concentrations and measured the iron saturation of ferritin. The mean value of saturation was 9.1%, while saturation in the healthy control group was 17.8%, a statistically significant difference (p < 0.005). Soluble transferrin receptor concentrations indicated a functional iron deficiency. CONCLUSION: We conclude that the acute phase ferritin in patients with AOSD contains less iron in comparison to ferritin in healthy controls. We suggest that soluble transferrin receptor is the method of choice in estimating the iron status of patients with an acute phase reaction.

Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: effects on antioxidant status and fatty acid profile.

In patients with Crohn's disease (CD), malnutrition is frequently observed and is generally accepted to be an important issue. The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants (AO) or n-3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue, respectively, in patients with long-standing CD currently in remission. In a randomized, double-blind placebo-controlled study, CD patients received either placebo, AO, or n-3 fatty acids plus AO for 3 months in addition to their regular diet. In all, 25/37 CD patients completed the study. AO status was assessed by blood biochemical parameters. A statistical per-protocol analysis was performed. Serum concentrations of selenium, vitamin C, and vitamin E, the activity of superoxide dismutase and total antioxidant status were significantly (p < 0.05) increased after AO supplementation. Furthermore, compared with controls, serum concentrations of beta-carotene, selenium, and vitamin C and the activity of glutathione peroxidase (GPx) were significantly (p < 0.05) lower before supplementation; however, after AO supplementation these levels were not significantly different from controls (except for GPx). N-3 fatty acids plus AO supplementation significantly (p < 0.05) decreased the proportion of arachidonic acid, and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue. Supplementation with antioxidants improved antioxidant status in patients with CD in remission. In addition, supplementation with n-3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile, which may lead to the production of eicosanoids with attenuated proinflammatory activity. This study indicates that an immunomodulating formula containing n-3 fatty acids and/or AO may have the potential to play a role in the treatment of CD.

Iron saturation of ferritin in the course of phlebotomy treatment in patients with haemochromatosis.

This paper describes the iron saturation of ferritin in haemochromatosis patients during phlebotomy therapy. The iron saturation of ferritin does not change during therapy and cannot be used as a parameter to follow therapy. Furthermore, the iron saturation seems to be a constant characteristic of a given person. It does not vary with the body iron stores in patients with haemochromatosis.

Familial aggregation of inflammatory bowel disease: a population-based study in South Limburg, The Netherlands. The South Limburg IBD Study Group.

BACKGROUND: The aim of our study was to investigate the prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in first-degree relatives of IBD patients living in a well-defined area. METHODS: IBD patients known at the IBD Registration South Limburg as well as population controls were asked about the occurrence of IBD in their first-degree relatives. RESULTS: IBD was reported and confirmed in 16 (out of 1554) relatives by 11 (out of 245) patients. Prevalence of IBD was highest for siblings (1.5%) and children (1.3%), while only 0.2% of the parents were affected with IBD. Among relatives of the control subjects, IBD was observed in 0.8% (versus 4.5% in IBD patients), resulting in an odds ratio of 5.7 (95% CI: 2.0-16.7). CONCLUSIONS: The observed risk of IBD for first-degree relatives of IBD patients was higher than in controls. However, the risk in our population is lower than has been reported by other centres, possibly because of the population-based character of our study.

The iron content of serum ferritin: physiological importance and diagnostic value.

In this paper we present a method for determining the iron saturation of ferritin as a possible independent predictor of iron stores. Serum ferritin was purified by immunochemical precipitation, and could be completely recovered from serum without any contamination from transferrin. The iron content of the precipitated ferritin was determined by flameless atomic absorption spectrophotometry (FAAS) and the ferritin-iron saturation was calculated using the original serum ferritin concentration. The intra- and inter-assay variation coefficients were 4.2% and 13.4% respectively. The first results with this assay indicate that serum ferritin contains a considerable amount of iron. Furthermore the results show that the iron saturation of ferritin in patients with acute phase response is significantly lower than the saturation found in healthy volunteers (19.3% and 24.3% respectively). These results suggest a possible role for the ferritin-iron saturation in the assessment of iron stores in patients suffering from acute phase response. In addition, the considerable amount of iron in ferritin suggests the need to revise the physiological role of this substance in relation to the serum iron homeostasis.

"Downhill" oesophagus varices: a clue to a serious disease.

Downhill oesophagus varices are rarely observed. In this report a patient is described with downhill oesophagus varices in the absence of the vena cava superior syndrome. The observation of these varices was the clue to the diagnosis of a serious disease: a malignant thymoma.