Budd-Chiari syndrome: combination of genetic defects and the use of oral contraceptives leading to hypercoagulability.

A young female, who had been in excellent health and had used third-generation oral contraceptives, was admitted to hospital because of abdominal pain and ascites. Budd-Chiari syndrome (BCS) was diagnosed by radiographic and histological examination. Tests for myeloproliferative disease, deficiency of coagulation inhibitors and paroxysmal nocturnal haemoglobinuria were negative. DNA investigation showed a double heterozygous defect: the Arg506Gln mutation in the factor V gene (factor V Leiden) and G20210A nucleotide substitution in the prothrombin gene. This double defect was also found in the patient's father, who had never experienced an episode of venous thromboembolism. Genetic and acquired thrombogenic risk factors are being detected increasingly in patients with BCS. With the discovery of new genetic defects leading to hypercoagulabiulity an increasing number of patients with serious thrombotic manifestations, such as BCS, will exhibit concurrence of hereditary and acquired risk factors for thrombosis.

A patient with neurofibromatosis type 1 and watery diarrhoea syndrome due to a VIP-producing adrenal phaeochromocytoma.

A patient with neurofibromatosis type 1 and watery diarrhoea syndrome due to a VIP-producing adrenal phaeochromocytoma (Case Report). J Intern Med 1999; 246: 231-234. A 43-year-old patient with neurofibromatosis type 1 suffered from watery diarrhoea syndrome induced by excessive production of vasoactive intestinal polypeptide (VIP) in an adrenal phaeochromocytoma. This case report emphasizes that patients with neurofibromatosis are prone to develop more than one disease induced by tumours originating from the neural crest. Since excessive VIP production in a phaeochromocytoma may mask the symptoms of catecholamine overproduction, and in view of the therapeutic consequences, neurofibromatosis patients with hyperVIP-aemia must be checked for the presence of a phaeochromocytoma.

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.

Computer assistance in the practice of internal medicine.

An overview is given of the possibilities of electronic support in the practice of internal medicine and of the preferred electronic environment in the hospital. For efficient exchange of information, mutual cooperation between all departments and medical specialists in the hospital is of great importance. The development of a sufficient hospital information system has to start with the composition of an information design, based on the concept of an open hospital database with connections to subsystems of the different departments and medical specialisms. Within this design basic, organizational, management and (medical) knowledge-providing programs can be applied. General, medical, scientific and organizational aspects of electronic support in internal medicine are discussed with some practical examples. A brief comment is made on the necessity of using code numbers for diagnoses.

Preference and significance of HBeAg and anti-HBe, determined by enzyme immunoassay, in patients with acute, chronic and resolved hepatitis B.

HBeAg and anti-HBe were determined by enzyme immunoassay in a prospective longitudinal study of 50 patients with hepatitis B, 43 of whom recovered completely. Followup studies were possible in 37 of the recovered patients and in all 7 non-recovering patients for a median of 5 years. Five of the non-recovering patients could be followed up from the initial acute stage of the disease. HBeAg was present in 17 of 18 recovering patients from whom serum was still available from the early stage of disease (i.e. before peak SGPT levels were reached). The presence of HBeAg was transitory for a median period of one week before the peak SGPT level until it was actually attained. All HBeAg-positive serums contained HBsAg and IgM-anti-HB core as well. 39 of the 43 recovering patients developed anti-HBe, first present after a median period of 2 weeks after peak SGPT. After 5 years 25 of 30 tested patients were still anti-HBe positive, all were HBeAg (and HBsAg) negative. Of the non-recovering patients 2 remained HBeAg-positive for at least 4 years, 4 seroconverted to anti-HBe between 0.5 and 2.5 years after the acute stage of the disease, without apparent correlation with the biochemical activity or the histological diagnosis, and 1 patient already had anti-HBe in the acute stage of the disease. Thus HBeAg is as a rule transiently present in acute hepatitis B, during early stages of the disease. HBeAg has been regarded commonly as a viral constituent. The conversion from HBeAg to anti-HBe in the patients with chronic hepatitis B, however, may cast doubt on this assumption in favour of the hypothesis that the HBe/anti-HBe system is of host origin. Anti-HBe, when present without markers of virus replication, may serve as a sign of previous, completely resolved hepatitis B.

Anti-HBc titers and anti-HBc immunoglobulin (M/G) classes in acute, chronic and resolved hepatitis B.

IgM-anti-HBc and IgG-anti-HBc serum titers were determined by indirect immunofluorescence in a prospective longitudinal study of 50 patients with hepatitis B, 43 of whom recovered completely. 37 of the recovered patients and all 7 non-recovering patients were followed up for a median of 5 years. Five of the non-recovering patients were followed up from the initial acute stage of the disease. IgM-anti-HBc was present in the acute stage in 39/43 of the recovery patients. The median maximal titer, 1:1000, was reached during the week before peak SGPT. It always disappeared in recovering patients within a median period of 5 weeks after peak SGPT. IgG-anti-HBc was present in all 43 recovering patients in the acute stage of disease with a median maximal titer of 1:1000, maintained for at least 10 weeks. After 5 years, 28 of 37 recovered patients were still IgG-anti-HBc positive with a median titer of 1:200. All non-recovering patients showed persistent IgM as well as IgG-anti-HBc positivity. In the acute stage the medians of the maximal titers were 1:100 for IgM-anti-HBc and 1:1000 for Igg-anti-HBc. After 5 years they were 1:100 for IgM and 1:10000 for IgG-anti-HBc. The presence of IgM-anti-HBc in a preceding study was considered to be a marker of hepatitis B virus replication. From this study no evidence can be obtained to support the view that the titer level of anti-HBc is reliable in the differentiation between infectious anti-HBc positive blood, as there was no difference (p = 0.4) between the number of patients with an anti-HBc level of 1:1000 after at least five years, who had recovered (9/28) and who had not recovered (3/7).

Immunoglobulin classes of smooth muscle antibody in the course of acute hepatitis B: prognostic significance.

A prospective longitudinal study was performed in 48 patients with acute hepatitis B (AHB) of whom 38 were previously healthy (PH) and 10 drug addicted (DA). Smooth muscle antibody was present in 23/38 PH and in 8/10 DA patients for a median of 4 weeks; other autoantibodies were not found. In the PH patients SMA was of IgM class in 23/23 and 8/23 of the IgG class as well. In the 8 DA patients 2 had IgM-SMA only, 3 (IgM+IgG)-SMA and 3IgG-SMA only. IgG-SMA presence could not be related to the duration or titer height of SMA nor to the type of fluorescence patterns. In SMA-negative patients IgM-anti-HBc was cleared within 6 weeks and in IgM-SMA positive patients within 32 weeks (medians 4 and 5 weeks) after maximal S-GPT. IgM-anti-HBc persisted for years in 3/3 IgG-SMA positive and in 2/11 IgG-IgM positive patients. In the remaining 9 IgG-IgM SMA positive patients it disappeared within 15 (median 9) weeks after maximal S-GPT. All 34 patients without SMA or with IgM-SMA only recovered completely. The 3 patients with IgG-SMA and 2 of the 11 patients with IgG+IgM SMA developed chronicity. Determination of SMA and of its immunoglobulin classes, at maximal SGPT may in acute hepatitis B be of help in predicting the outcome of disease.

Natural history of acute hepatitis B in previously healthy patients: A prospective study.

A prospective study of the natural history of acute hepatitis B was performed in 38 patients. Fatigue started median 4 weeks, abdominal symptoms median 3 weeks and signs of cholestasis median 2.5 weeks before peak SGPT values were reached. Extrahepatic manifestations occurred throughout the prodromal stage, the presence of arthropathy, urticaria or skin rashes was not related to the biochemical severity of liver disease. The higher the the maximal values of serum bilirubin and/or the older the patient, the longer the period of bilirubin elevation; a maximal bilirubin elevation less than 20 X the upper limit of normal was associated with normalisation of serum bilirubin within 6 weeks. No such correlations were found between the height of serum glutamic pyruvic transaminase, alkaline phosphatase, thymol turbidity and cholesterol levels and the subsequent duration of their abnormality. The elevation of alkaline phosphatase as well as the abdominal complaints might partly be caused by gastro-intestinal involvement. Immobilisation before peak SGPT was attained was associated with normalisation of serum glutamic pyruvic transaminase levels within 8 weeks after peak levels. 37 patients recovered completely. In one HBs-antigenemia and slight SGPT elevation persisted. Long term follow up was possible in 33 patients for 4 to 7 years, median 5 years.

A longitudinal study on the occurrence of autoantibodies in the course of acute hepatitis B.

The presence or absence of autoantibodies in acute hepatitis B was investigated longitudinally in a prospective study of 38 patients, 37 of whom recovered completely. Antibodies to nuclei, bile canaliculi or mitochondria were not found in any of the 354 investigated sera. Smooth muscle antibody (SMA) was present in 23 patients for median 4 weeks and from (median) -1 to +3 weeks from peak SGPT. Titers reached from 1:10 to 1:400, with a median of 1:50. In the patient with persistent HBs-antigenemia, SMA - present in low titer (1:10) - persisted as well. Besides smooth muscle cells, other localisations were: glomerular (15 patients), around hepatocytes ('polygonal' 11 pts), around renal tubuli (10) and in the gastric mucosal layer (8). These fluorescence patterns, the presence of which was not correlated to the SMA titer height, disappeared either earlier than or simultaneously with smooth muscle cellular fluorescence. A maximal titer greater than 1:50 was associated with a thymol turbidity ten times the upper limit of normal or more (i.e. greater than 25 S-H U) and with the peak serumgammaglobulin about simultaneously with peak SGPT. The presence of SMA was not correlated with extrahepatic manifestations nor with the peak values attained for ESR, SGPT, alkaline phosphatase or bilirubin.