Objective assessment of the contribution of each diagnostic test and of the ordering sequence in jaundice caused by pancreatobiliary carcinoma.

BACKGROUND: Computer-assisted diagnostic systems are not substantially more accurate than the clinician in the differential diagnosis of jaundice but may help in optimal selection and sequencing of tests. The present study aimed to assess with an electronic diagnostic tool the pattern of ordering tests and the diagnostic contribution and related financial cost of each test in jaundiced patients with pancreatobiliary carcinoma, in an effort to make the clinician's diagnostic behaviour more efficient and economical. METHODS: Clinical and diagnostic test data were prospectively gathered from 356 jaundiced patients with pancreatobiliary carcinoma and entered in a Bayesian diagnostic programme. The test results were added to the existing diagnostic evidence, and the programme calculated the diagnostic contribution of each test. RESULTS: A total of 1804 diagnostic tests were ordered. Quantitative assessment of the diagnostic contribution of each test showed that percutaneous transhepatic cholangiography and computed tomography were associated with the highest provision of information. The most cost-effective tests were ultrasonography and liver function tests. CONCLUSIONS: It is possible to determine objectively the diagnostic contribution of each test in establishing the diagnosis of pancreatobiliary carcinoma. The observed physician behaviour in ordering the various diagnostic tests might be improved with regard to its efficacy and its cost-effectiveness profile.

Major clinical events, signs and severity assessment scores related to actual survival in patients who died from primary biliary cirrhosis. A long-term historical cohort study.

BACKGROUND/AIMS: One of the prognostic methods for survival in primary biliary cirrhosis (PBC) is the Mayo model, with a time-scale limited to 7 years. The aim of our study was to assess how major clinical events, signs, several severity assessment methods and Mayo survival probabilities fit in with actual patient survival, by using yearly observations until 0.5 years before patient death from PBC. METHODOLOGY: Data of 32 patients dying from PBC were collected prior to death at -0.5, -1, -2 etc. years (median: -5 years, range: -16 to -0.5 years). Major events registered were: first occurrence of ascites, upper gastrointestinal bleeding or manifest hepatic encephalopathy and signs, first observation of spider naevi or purpura. Severity assessment methods applied (all with scores and classes) were: Mayo (M), Child-Campbell (C), Pugh-Child (P), Pugh-Child-PBC (PP), 'Child-Pugh' (CP), and Ascites Nutritional State-Child (ANS). Fifty percent survival estimates were calculated from Mayo scores. Severity assessment method variables were: ascites (C, P, PP, CP, ANS), encephalopathy (C, P, PP, CP), nutritional state (C, ANS), edema (M), age (M), serum albumin (M, C, P, PP, CP), bilirubin (C, M, P, PP, CP), and prothrombin time (M, P, PP, CP). RESULTS: In 27 out of 32 patients a major event occurred, always between -6 and -0.5 years (median: -1 year) and, never between -16 and -7 years (p < 0.0001). A sign was first observed in 30/32 between -14 and -0.5 years (median: -2 years). Compared to the total population, a sign, and even more so, an event indicated a shorter survival (p = 0.004 and p = 0.0002, respectively). The median 50% estimated survival (predicted by the Mayo model) fitted the actual survival from -6 to -0.5 years (r = -0.7, p < 0.0001), but not from -16 to -7 years (r = -0.1, p = 0.4). All -6 to -0.5-year severity scores correlated (p < 0.0001) both with actual survival (M, C, P, PP, and CP r = 0.7; ANS r = 0.5) and with estimated M 50% survival (C, P, PP, CP r = -0.9; ANS r = -0.6; M score: -0.99), but none with actual survival from -16 to -7 years, except for M, slightly (r = -0.3, p = 0.04). A nomogram for mean C, CP, M and ANS scores related to actual survival was constructed for the -6 to -0.5-year period. The C and CP classes A, B, and C did not appear to distinguish sufficiently into actual survival, whereas the M classes did. CONCLUSIONS: The occurrence of a major event appeared to exclude survival over 6 years. In these final 6 years, Child-Campbell, Mayo and Pugh scores correlated equally well with actual survival and better than Ascites/Nutritional State score. In our PBC patients, Campbell was an excellent alternative for Pugh; for Pugh, the original Child-Turcotte variable limits were fully sufficient.

Helicobacter pylori and ammonia concentrations of whole, parotid and submandibular/sublingual saliva.

The aim of this study was to determine the ammonia concentration in whole, parotid and submandibular/sublingual saliva of healthy volunteers using the indophenol direct method. It also investigated the hypothesis that higher saliva ammonia concentrations are associated with the presence of Helicobacter pylori (H. pylori) in the oral cavity. In healthy volunteers, the mean ammonia concentration of whole saliva (2574 mumol/l) was significantly higher (P < 0.0001) than the mean ammonia concentration of both parotid (238 mumol/l) and submandibular/sublingual (355 mumol/l) saliva. In whole saliva, no difference in ammonia concentration was found between healthy controls and dyspeptic patients (mean ammonia values 2574 and 2489 mumol/l respectively, P = 0.7). In addition, no significant differences were observed in the salivary ammonia concentration between dyspeptic patients with and without H. pylori carriage. It is concluded that the ammonia concentration in parotid and submandibular/sublingual saliva does not differ, but is significantly lower than the ammonia concentration of whole saliva. This difference is not due to carriage of H. pylori with its strong urease activity. Therefore, the determination of ammonia in whole saliva is an inappropriate screening test for patients being at risk for (chronic) gastritis and peptic ulcer disease.

Determination of ammonia in cerebrospinal fluid using the indophenol direct method.

We have determined ammonia in cerebrospinal fluid (CSF) with the indophenol direct method. The results were compared with an enzymatic method. The method is very simple, and precision (coefficient of variation 1.6%) and linearity (r = 0.9999, p < 0.001) of the method are excellent. The recoveries of the method are very good (within-sample recovery: range 88-93, median 93%; between-sample recovery: 88-93, median 91%). In a population of 23 neurological patients not suffering from liver disease, the reference values ranged from 8 to 26, median 18 microM. Males and females did not differ (p = 0.5). The values obtained with the indophenol method were equal to the enzymatic method (range 9-28, median 18 microM, p = 0.6). On storage in the deep freeze (-20 degrees C), there was no change in CSF ammonia concentration for at least 1 mo. When stored at 4 degrees C (refrigerator), ammonia determinations have to be performed within 2 d. CSF storage at room temperature results in artificially elevated ammonia levels and should be avoided.

Assessment of liver cirrhosis severity in 1015 patients of the Euricterus database with Campbell-Child, Pugh-Child and with ascites and ascites-nutritional state (ANS) related classifications. Euricterus Project Management Group.

BACKGROUND/AIMS: The assessment of disease stage in cirrhosis is important for the individual patient (prognosis, timing and risk for requiring surgical intervention) and also for population comparisons and trials. There are several established methods, and we have aimed at comparison of the methods within a large cirrhosis population. METHODOLOGY: In the European Union Euricterus database, there are 1015 patients with a "certain" diagnosis of cirrhosis, each of whom in one session had a protocol work-up of history, physical examination and all laboratory investigations needed for this study. The Child-Turcotte (CT), Campbell-Child (C) and Pugh-Child (P) classifications, as well as ascites/no ascites, ascites 1, 2, 3 (no, therapy responsive, nonresponsive) and ascites/nutritional state (ANS, 1-9) scores were used. CT and C have the same 5 variables, P has prothrombin time instead of nutritional state. CT, C and P variables score 1-3 each. C and P furthermore have variable range scores of 5-15. CT, C and P have classes A-C. The variables used were ascites, nutritional state, encephalopathy, bilirubin, albumin and prothrombin time. RESULTS: Only 53 patients (5%) fit within the CT criteria. C and P variable range scores (5-15) correlated strongly (r = 0.84). Cross-over calculation showed slightly different results in the P and C choice of variables, while the variable ranges (1-3) did not matter. Different selection of score ranges for the A-C classes in C and P resulted in 69% class C in P (35% in C) and 3% A in P (19% in C). The patients with ascites (70%) had worse bilirubin, albumin, nutritional states and C and P 5-15 scores (p < 0.0001). Patients with ascites 3 had all variables and also C, P 5-15 scores worse than those with ascites 2 (p < 0.02). ANS scoring showed wasting in 33% of the patients without ascites (ANS 3), 50% of the patients with ascites 2 (ANS 6) and 60% with ascites 3 (ANS 9) (p < 0.0003), and C and P scores were higher in the 3 ANS scores with wasting. CONCLUSIONS: Campbell and Pugh 5-15 scores correlated closely and can be used interachangeably. As C does not contain the more elaborate prothrombin time determination, it probably can be used anywhere in the world. Ascites (degree) and Ascites/Nutritional State (ANS) scoring only use history and physical examination and are, or remain, although less refined, clinically relevant.

Physician's working diagnosis compared to the Euricterus Real Life Data Diagnostic Tool Trial in three jaundice databases: Euricterus Dutch, independent prospective and independent retrospective.

BACKGROUND/AIMS: In the European Union Euricterus Project on (sub)Icterus proforma, the history and physical examination items were to be used for the physician's working diagnosis (PWD) and 'among others, for the development of the real life data electronic diagnostic tool, Trial. Trial delivers diagnosis probabilities based on Bayes' Theorem (B), completed by Trial Algorithm (TA). We wanted to compare the diagnostic accuracies (PWD and Trial probabilities as a percentage of the final diagnosis (FD) in a patient population) in 3 Dutch databases. METHODOLOGY: The inclusion criteria for both Euricterus and Trial were age > or = 16 and bilirubin > or = 20 mmol/l. Euricterus data gathering took place at the bedside on a proforma with (among other questions) 79 questions on history and physical examination as well as the diagnosis levels for the PWD (1 alternative possible) and FD (17 disease categories, dc). Trial was developed on the data of 7,104 Euricterus patients and its data-entry Demo has the same questions. It calculates the probability of each diagnosis of the 17 dc as a percentage, as each significant finding is encountered (BO, Bayesian Overall). It can simultaneously calculate the resemblance of the patient's signs and symptoms to each disease concomitantly (BV, Bayesian Vertical), and to any subset of a disease. Any probability is further tested for compatibility using TA, a subset of BV, delivering TA-PWD, TA-BO and TA-BV. The Trial test patients came from 3 databases: a Euricterus Dutch Patients Random Sample EDRS (n = 184, internal database) and 2 independent databases: prospective P (n = 80) and retrospective R (n = 152), totalling 416 patients. RESULTS: The accuracies of PWD and Trial showed no differences between the databases, and the results are therefore pooled (n = 416). With testing on the highest probability found, the PWD accuracy was 78%, TA-PWD 81%, TA-BO 74% and TA-BV 72%. The true FD's were mentioned (at any probability) in the PWD in 86%, TA-PWD in 92%, TA-BO in 94% and TA-BV in 91% of the patients. Testing only patients whose FD was "certain" or whose data were without omissions did not improve accuracy. Testing on probability > 95% improved BO and BV accuracy, but not TA-BO or TA-BV. CONCLUSIONS: The Physician's Working Diagnosis accuracy was approximately 80% and did not greatly improve after TA. The Trial TA-BO and TA-BV accuracies were only slightly less than the PWD. For well-trained physicians, Trial strengthens the physician's judgment, and for those less trained (or those to be trained), it delivers a (sub)icterus diagnostic disease probability at nearly consultant level.

Survival probabilities of Pugh-Child-PBC classified patients in the euricterus primary biliary cirrhosis population, based on the Mayo clinic prognostic model. Euricterus Project Management Group.

BACKGROUND/AIMS: Estimation of prognosis becomes increasingly important in primary biliary cirrhosis (PBC) with advancing disease and also with regard to patient management. The ubiquitous used Pugh scoring for severity of disease is simple while the Mayo model which has been validated for survival estimates is more sophisticated. We wanted to investigate whether Pugh and Mayo scores correlate (they have 3 of 5 variables in common) and if so whether a survival probability based on Mayo data could be affixed on Pugh classes and scores obtained in the same patients. METHODOLOGY: All variables used for Mayo Clinic Prognostic Model (Mayo) scoring and Pugh-Child-PBC (Pugh) scoring were available in 143 PBC patients of the Pan European database Euricterus. Pugh scores P5-P15 and has classes A (P5-6), B (P7-9) and C (P10-15). We subdivided P5 in P5A (patients with albumin > 40 g/l plus prothrombin time < or = 12 secs) and P5B (the other patients in P5). We designed a category Pugh Early (PE) for patients with P5A characteristics and bilirubin < 17 mmol/l. Mayo scores R0-R15-with 1-7 years survival probabilities S-and has risk classes Low (L), Intermediate (Int), High (H) and Very High (VH). RESULTS: The estimated survival probabilities of the 143 patients ranged from 88% at 7 years to 0% at 1 year, median 14% at 5 years. The Pugh and Mayo scores correlated r = 0.87 (p < 0.0001) and except age with P, all Mayo and Pugh variables correlated with both R and P at p < 0.0001. Survival in Pugh class A was median 43% at 7 years and was not different from survival in Mayo L+Int (p 0.58). In Pugh class B 7 years survival was 2%, not different from Mayo H (p 0.25). Survival in Pugh C was median 24% at 1 years and better than Mayo VH (p 0.02). Between P5A (survival 78% at 7 yr) and R 3-4; P5B-6 (40% at 7 yr) and R5; P7 (22% at 7 yr) and R6; P8-11 (12% at 5 yr) and R7-8; and P12-14 (5% at 1 yr) and R9-10 no significant differences were found. From P8 upward there was a steep increase in death rate. PE has a 7 year survival of at least 89%. Charts of projected survival estimates for Pugh scores and classes are presented. CONCLUSION: It was possible (affixing Mayo to Pugh) to define 1-7 years survival probabilities to Pugh classes and scores for the last 7 years of the disease, i.e. the most important period for therapeutic decisions. These results need to be validated in other PBC populations.

Primary biliary cirrhosis: an electronic diagnostic tool trial based on symptoms, (past) history and signs only, using the European database euricterus. The Euricterus PMG.

BACKGROUND/AIMS: Primary Biliary Cirrhosis (PBC) is a relatively rare chronic progressive disease in which a working diagnosis of PBC easily leads to a final diagnosis by testing for anti-mitochondrial antibodies. Liver transplantation is the only effective treatment. The aim of this study was to test an electronic diagnostic tool (tool) for it's ability to include PBC in the working differential diagnosis. METHODOLOGY: In the European Union Euricterus project a large number of (sub)icteric patients in 17 discrete disease categories, PBC being one of them, were gathered prospectively. A tool was developed-using Bayes (B) and Trial Algorithm (TA) pattern-recognition and based on items related to the history, symptoms and signs of all Euricterus patients. We have tested the diagnostic tool on 143 PBC Euricterus patients. RESULTS: PBC was mentioned by the tool in 86% (B) and 91% (TA) of the 143 patients. These figures were higher for patients under 60 and (TA only) females. Females under 60 (n = 89) scored 92% B and 96% TA. A sole diagnosis of PBC was made in 31% (B) and 66% (TA). In the other patients with a PBC probability, 7 other (first) diagnoses were presented by the tool of which non-alcoholic active liver disease and pancreatic or biliary carcinoma were the leaders. These 7 diseases appeared evenly distributed along the percentual probabilities of PBC given by the tool (B) and also along Pugh and Mayo scores (B and TA). PBC was mentioned by the tool in all patients with a Pugh score 10 or higher (advanced disease, class C). In the patients in whom the tool did not mention PBC, the primary diagnoses came from 9 other disease categories. CONCLUSION: This electronic tool has been able to identify PBC as one of the differential diagnostic modalities in the large majority of a present population of PBC patients.

Primary biliary cirrhosis: Dutch application of the Mayo Model before and after orthotopic liver transplantation.

BACKGROUND/AIMS: A retrospective study of primary biliary cirrhosis (PBC) was performed to study the Original Mayo Model for predicting survival by a Dutch data-set of patients, presentation of disease progression; assessment of liver transplantation, prediction of post-transplantation survival; and the addition of two laboratory variables to the Original Mayo Model. MATERIALS AND METHODS: Survival of 83 patients, 37 of whom underwent transplantation, were studied. Mean follow-up was 6.0 +/- 0.45 SEM years. Risk score at diagnosis, platelet count, and serum sodium were analyzed in a Cox model. RESULTS: The Original Mayo Model estimated survival for low-, medium-, and high-risk groups accurately and it also presented disease progression. Baseline Mayo risk score in a Cox model had a regression coefficient of 1.01, indicating an excellent predictor p < 0.0001. Platelet count was a predictor of survival (p < 0.002), whereas serum sodium did not (p = 0.67). A new model combined of the Original Mayo risk score and platelet count predicted survival in high-risk patients somewhat better compared to the Original Mayo Model. With both models, liver transplantation had a significant beneficial effect on survival (p < 0.001). The scores revealed no significant influence (p = 0.47) for overall post-transplantation survival. CONCLUSIONS: The Original Mayo Model remains the model of choice for patients with PBC for prognostication from 3-8 years, is a useful tool in the assessment of liver transplantation but not an indicator of post-transplantation survival. Platelet count showed to have additional prognostic value. A new model combined of platelet count and the Original Mayo risk score did predict survival in high-risk groups slightly better compared to the Original Mayo Model.

Whole blood and plasma water in health and disease: longitudinal and transverse observations and correlations with several different hematological and clinicochemical parameters.

In a healthy reference population, hemoglobin (Hgb) and hematocrit (Hct) have been proposed as surrogate markers for whole blood water (WBW). We have extended this study under different physiological and pathological conditions in two longitudinal series, viz. (1) acute hyper- and hypohydration experiments in a healthy individual and (2) three athletes running 5 km each, and in three transverse series, viz. (3) a young reference population (n = 97, 49 females), (4) an old reference population (n = 37, nine females) consisting of inhabitants of a nursing home and (5) cardiac, hematological and renal patients including severe anaemia, polycythaemia and abnormal protein levels (n = 50, 25 females) with suspected hydration disturbances. The only sex difference found was a lower WBW in males in the young reference group. The percentage change of PW was less than that of WBW. In all five groups together (n = 293) WBW correlated closely (P < 0.0001) with Hgb and Hct (both r = -0.95) and with erythrocyte count (r = -0.85), whereas PW correlated with total protein (Tprot) (r = -0.84). In the longitudinally studied groups (1) and (2) WBW also correlated (P < 0.0001) with cholesterol, Ca, Tprot, albumin, platelets, globulin and white blood cells (r +/- 0.98-0.37), while PW correlated (P < 0.0001) not only with the same clinicochemical parameters but also with Hct, Hgb and red blood cells (r +/- 0.98-0.44). The homeostasis of PW is more narrowly regulated than that of WBW. Hgb, Hct and erythrocyte count reflect WBW and Tprot reflects PW also under disease conditions. WBW (mass%) can be calculated from Hgb and Hct using the formulae: -0.09 x Hgb (g/l) + 91.7 and -28.6 x Hct (v/v) + 91.8 and PW (mass%) from Tprot using the formula: -0.09 x Tprot (g/l) + 97.6. Other correlations were observed only in a longitudinal setting and presumably are due to concentration and dilution.

Lactate and ammonia concentration in blood and sweat during incremental cycle ergometer exercise.

It is known that the concentrations of ammonia and lactate in blood increase during incremental exercise. Sweat also contains lactate and ammonia. The aim of the present study was to investigate the physiological response of lactate and ammonia in plasma and sweat during a stepwise incremental cycle ergometer exercise test in ten subjects. During this test lactate and ammonia were measured in blood obtained from the earlobe and in sweat collected in a bag attached to the back of the subject. At the end of each interval this bag was emptied for measuring lactate and ammonia. A disproportional increase in the concentration of lactate and ammonia in blood was found, in sweat a disproportional decrease. The lactate concentrations in sweat were higher than those in blood. We hypothesise that lactate in sweat is produced from glycogen granules of the clear cell of the eccrine gland. This lactate production results in acidification of sweat, which facilitates the diffusion of ammonia from eccrine duct cell to duct lumen. It is uncertain how far duct cell ammonia originates from plasma, the duct cell itself might produce ammonia. Part of the ammonia in sweat could come from the breakdown of urea by skin bacteria.

Primary biliary cirrhosis in The Netherlands. An analysis of associated diseases, cardiovascular risk, and malignancies on the basis of mortality figures.

BACKGROUND/METHODS: In 1979 death rate registration for primary biliary cirrhosis (PBC) became available in The Netherlands. In the 14-year period 1979-92, 417 persons died of and 179 with PBC. We investigated secondary causes of death using standardized mortality ratios (SMR) (1.0 as reference, P < 0.001 regarded as significant). RESULTS: Median age was 70-74 (35 to > 85) years. Secondary causes of death originated from the circulatory, digestive, and respiratory tracts and malignancies. Younger persons (< 60 years), dying of PBC, more often died with "toxicity related to immunosuppression' than older persons (P < 0.01). Younger persons (< 60) dying with PBC, more often died of hepatocellular carcinoma (HCC) than older ones (P < 0.05). In patients with PBC the frequency of HCC (SMR, 25.5; P < 0.0001) and diseases of the musculoskeletal system/connective tissue (SMR, 5.1; P < 0.0001) was higher than in the general population. Malignancies in general (SMR, 0.7), pancreatic carcinoma (SMR, 2.5), breast cancer (SMR, 0.1) and diseases of the circulatory system (SMR, 0.8) differed but not significantly (P < 0.05 - < 0.01). No difference existed in the localization of malignancies in patients dying of as compared with those dying with PBC. CONCLUSIONS: Deaths occurred predominantly in the older age classes, with an age-related difference in some associated disorders. Patients with PBC showed an increased risk of HCC and diseases of the musculoskeletal system. Similar studies from different countries are needed.

Clinical presentation of (subclinical) jaundice--the Euricterus project in The Netherlands. United Dutch Hospitals and Euricterus Project Management Group.

BACKGROUND: From a primary clinical database, we wanted to obtain insight in disease distribution and clinical presentation of adult jaundiced patients in a Western country. MATERIALS AND METHODS: As part of the Euricterus project, 24 Dutch general and academic hospitals in a period of 2 years gathered prospectively 702 patients on a standard proforma. Patient aged 16 years or more (median 61) and with a serum bilirubin of 20 mmol/l or more (median 83) were included. The final diagnosis was established within 3 months. RESULTS: Pancreatic or biliary carcinoma (20%), gallstone disease (13%) and alcoholic liver cirrhosis (10%) were the 3 most frequent diagnoses. Imaging (79%), clinical course (63%) and chemistry/serology (57%) were the most used ascertaining methods. Pancreatic or biliary carcinoma and gallstone disease were more common and age higher in general hospitals (p = 0.0001), and 'immunological' liver disease, non-alcoholic cirrhosis and hepatocellular carcinoma (HCC) more common in academic hospitals (p = 0.001). Patients aged 90 years or older (13%) had pancreatic or biliary carcinoma, liver metastases or heart failure and patients with age less than 20 (0.9%) had acute viral hepatitis, nonalcoholic active liver disease or HCC. Risk factors were more apparent (p < 0.02) in those aged less than 61 years. Feeling unwell (78%), dark urine (67%) and anorexia (57%) were the 3 most frequent symptoms; the 3 most frequent signs were liver enlarged (39%), looking ill (29%) and appearing wasted (23%). CONCLUSIONS: Through Euricterus, fresh clinical knowledge has emerged of symptomatology, age stratification and hospital preponderance of (sub)clinical jaundice in this country. This is important both for teaching and in preparing clinical studies.

Arterial ammonia with Blood Ammonia Checker II and with indophenol reaction to assess presence of hepatic encephalopathy.

Hepatic encephalopathy (HE) is associated with elevated arterial ammonia levels. The relationship is variable, in part due to ammonia methodology. One method, based on the indophenol reaction (IPh), is interfered with a number of amino acids including all aromatic amino acids. We have determined arterial ammonia simultaneously with the Blood Ammonia Checker II (BAC) as reference method and with the IPh method. The difference BAC-IPh, mumol/l, was assumed to express the interference in the indophenol method (IFI) by amino acids. It may be positive or negative. The aim was to establish the value of BAC in comparison with IPh in the diagnosis of liver disease and overt HE and to assess any added value of IFI. Of two reference groups without disturbances, A (n = 39) had not and B (n = 13) had encephalopathy. Group C consisted of 125 liver patients (34 no cirrhosis, 91 cirrhosis) of which 55 had no manifest HE (C:HE-) and 70 had HE (C:HE+). Median BAC ammonia nitrogen (NH3-N), mumol/l: A 21, B 35, C 80, C:HE - 57 and C:HE+ 98 (A < B < C and A < B < C:HE - < C:HE +, P < 0.001). Median IPh NH3-N, mumol/l: A 27, B 30, C 30, C:HE - 25 and C:HE + 35 mumol/l (A = B = C and C:HE - < C:HE+, P < 0.01). IFI medians: A -6, B 3, C 40, C:HE - 29 and C:HE + 58 mumol/l (A < B (P < 0.05) < C (P < 0.0001); A, B < C:HE - and C:HE+; C:HE- < C:HE + (all P < 0.0001)). While BAC correlated weakly with IPh in the (sub)groups C, C:HE-, C:HE+ (r = 0.3, 0.3, 0.4, P < 0.05), it correlated strongly with IFI (r = 0.9, 0.9, 0.8, P < 0.0001). There was no correlation between IPh and IFI. BAC, as well as IFI, could discriminate all liver patients (C) from both reference groups A and B with 100% positive likelihoods. BAC, IPh and IFI could discriminate between HE- and HE+. To differentiate cirrhosis from non-cirrhosis the specificity of IPh was uniformly high and the sensitivity satisfactory, whereas BAC had a high sensitivity but an insufficient specificity. In conclusion, in blood, BAC is the ammonia determination of choice. It differentiates between reference groups (encephalopathic or not) and liver disease and the more so HE. The combination of BAC and IPh (indicating IFI) may eventually be shown useful to rapidly assess the severity of underlying liver disease in HE patients. In other biological fluids, IPh is excellent when the inhibiting influence of non-protein nitrogen substances is absent or can be eliminated.

Primary biliary cirrhosis (PBC) in an European country--a description of death rates in The Netherlands (1979-1992).

BACKGROUND/AIMS: In 1979, separate liver transplantation (LT) and primary biliary cirrhosis (PBC) death rate registration became available in The Netherlands (15 million inhabitants). The objective of this study was to investigate death rates from 1979-1992 and analyse the impact of LT. PATIENTS AND METHODS: PBC was either a primary or secondary cause of death. Rates were expressed as absolute numbers or per million inhabitants in the corresponding age category. Age classes of 5 years were used. The Netherlands was divided in four regions, North, South, East and West. Standardized mortality ratios (SMR) were used for calculation of regional differences. RESULTS: In the 14 year period between 1979-1992, 417 persons died from and 179 persons died with PBC, totaling 596 PBC patients (6.3 per million inhabitants > or = 35 years). No person younger than 35 died. Eighty-two percent were female, with a corresponding female/male ratio of 4.2 per million females/males inhabitants. In region South there were significantly fewer deaths (SMR 66%, p < 0.001) and in region North significantly more (SMR 141%, p < 0.05). The median age class at death was 70-74 (males and females alike). At age 35-59, death from PBC in 1992 per million was 1.2, and for > or = 65 years 15.7. In age class 80-84, the highest death rate from or with PBC was found with 28 deaths per million inhabitants and with a female/male ratio of 3.6. In 1992, with two deaths only, LT appeared to have nearly eliminated death from PBC in the age category 35-59 years. CONCLUSION: Death from PBC mainly occurs in the old and very old, who may never seek a specialized center. This indicates a more specific management and therapy for this particular group is needed.

Determination of ammonia in ear-lobe capillary blood is an alternative to arterial blood ammonia.

Blood ammonia determination is a laboratory test to diagnose hepatic encephalopathy. Arterial blood is superior to peripheral venous blood ammonia because of ammonia metabolism in muscle. We have compared capillary with arterial whole blood ammonia as capillary sampling is an attractive alternative. Ear-lobe capillary blood ammonia (ECA) was determined in all 173 persons studied, fingertip capillary blood ammonia (FCA) in 46 of these and arterial blood ammonia (AA) in 113. Of the 173, 60 were healthy (H), 64 were patients, not liver diseased (NLD) and 49 had liver disease (LD). Reference values, median and ranges, mumol NH3-N/l: AA, NLD, n = 64: 17 (7-42); ECA, H = NLD (P = 0.9), n = 124: 20 (7-45); FCA, H = NLD (P = 0.8), n = 33: 70 (29-151). Within the NLD group (n = 64) AA values (range 7-42) were little but significantly lower than the ECA values (range 7-45, P = 0.002). FCA NLD > AA NLD (n = 14, P < 0.0001); FCA H+NLD > ECA (n = 33, P < 0.0001). AA correlated very well with ECA, r = 0.87 (n = 113, P < 0.0001) and less well with FCA, r = 0.56 (n = 27, P < 0.01). ECA correlated with FCA, r = 0.51 (n = 46, P < 0.001). Ear-lobe capillary blood ammonia thus accurately reflects arterial ammonia and is an attractive alternative. The higher fingertip ammonia may be due to contamination with ammonia-rich sweat from finger grooves, regardless of the precautions taken.

[Current estimate of the number of patients for liver transplantation with Dutch mortality figures]. / Actuele raming van het aantal patiënten voor levertransplantatie, met Nederlandse sterftecijfers.

OBJECTIVE: To estimate the number of liver transplantations needed in the Netherlands, using death rates of the two periods 1979-1981 and 1989-1991. METHOD: Death rates of different liver diseases were divided into: generally accepted indications (transplantable liver diseases, TLD), alcoholic liver cirrhosis, ALC and primary liver cell carcinoma, PLC. The death rates in the two periods, 1979-1981 and 1989-1991, were compared, and the impact of liver transplantation was determined. Subsequently an estimate of the maximum number of patients for liver transplantation in the Netherlands was made, based on death rates. RESULTS: Mortality of TLD and PLC rose 14% and 7% respectively, while it dropped 13% for ALC. In the period 1989-1991 liver transplantation appeared to have had a quantitative effect on mortality, especially in the youngest age groups. In the age group 0-59 the maximum number of patients for liver transplantation per year was estimated to be 147, nearly 10 per million inhabitants, excluding ALC and PLC. CONCLUSION: In the period 1989-1991 21% of deceased TLD patients up to age 60 received liver transplantation in the Netherlands.