An older female patient with refractory anemia and hemochromatosis

CASE HISTORY AND CLINICAL FINDINGS: A 69-year-old woman was admitted because of a normocytic anemia. One year before an acute B19 parvovirus infection had been diagnosed, but the anemia was attributed to intestinal bleeding caused by a dysplastic colonic polyp. However, anemia persisted despite polypectomy. There was an excessive elevation of serum ferritin. ADDITIONAL EXAMINATIONS: A bone marrow biopsy and aspirate led to the diagnosis of a myelodysplastic syndrome (pure sideroblastic anemia). Ultrasound demonstrated advanced fibrosis of the liver. Fibrosis in association with severe parenchymatous siderosis was also demonstrated by histology. Analysis of the hemochromatosis gene (B-HFE, nt 845, G/A) was negative. DIAGNOSIS, THERAPY AND CLINICAL COURSE: The patient had secondary hemochromatosis due to a myelodysplastic syndrome. An acute infection with parvovirus B19 had been noted at the time of the first admission, one year before MDS was diagnosed. At that time, hemochromatosis had already caused fibrosis of the liver. However, complete regression of organ siderosis was achieved by deferoxamine administration. The myelodysplastic syndrome itself did not show any progression even 7 years after the diagnosis was established. CONCLUSION: Our case demonstrates the uncommon association between sideroblastic anemia and secondary hemochromatosis. Acute parvovirus infection may induce severe anemia in myelodysplastic syndromes. In acute B19 parvovirus infections an underlying hematologic disease should be excluded.     

Final results of a long-term,clinical follow-up in fatty liver patients

Objective. There is increasing focus on non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to conduct a long-term clinical follow-up of patients with biopsy-confirmed fatty liver without inflammation or significant fibrosis (pure fatty liver), to analyse for potential risk factors at the time of index liver biopsy important for survival and the development of cirrhosis and to describe the causes of death. Material and methods. Patients were linked through their personal identification number to the Danish National Registry of Patients and the Register of Causes of Death. All admissions, discharge diagnoses and causes of death during follow-up were collected. All surviving patients were invited to a clinical follow-up. Results. The follow-up period was 20.4 and 21.0 years, respectively, for the NAFLD and alcoholic fatty liver disease (AFLD) groups. Two NAFLD patients (1.2%) developed cirrhosis during the follow-up period versus 54 (22%) AFLD patients. Sixty-four percent of 178 surviving patients out of an original cohort of 417 patients attended the clinical follow-up. In NAFLD patients, none of the risk factors studied was significant in relation to the risk of death. Patients with AFLD died primarily from cirrhosis and other alcohol-related disorders, whereas in patients with NAFLD the main causes of death were cardiovascular disease and cancer. Conclusions. For patients with pure non-alcoholic fatty liver, survival was good and independent of the histological, clinical and biochemical characteristics at the time of biopsy; the main causes of death were cardiovascular disease and cancer.     

Das maligne epitheloide Hämangioendotheliom der Leber Ein sehr seltener Tumor im Kindesalter

We report on a 12-year old boy suffering from malignant epithelioid hemangioendothelioma of the liver, which is a very rare tumor in childhood. The tumor was detected by ultrasound examination at the age of 10 and appeared at that time as a solitary intrahepatic nodular lesion. During the following 2 years multiple nodular lesions developed in both hepatic lobes. There were neither any suspect anamnestic findings nor abnormal clinical or laboratory data. The tumor showed the typical histomorphological, immunohistochemical, and ultrastructural features of this entity, which is usually seen in older patients. We investigated proliferative activity, apoptotic regulation, and expression of VEGF and VEGF-receptor flk-1 by means of immunohistochemical techniques. According to the known slow growth activity of these tumors we found only a few Ki-67 positive tumor cells. We did not detect any apoptotic cells using TUNEL technique. The positive immunoreaction of the tumor cells with antibodies against VEGF and VEGF-receptor flk-1 may indicate the regulation of tumor growth by angiogenetic factors. We present our findings together with a summary of the most important publications of recent years concerning these tumors.     

Predicting deterioration in patients with lobar haemorrhages

OBJECTIVE: To study the clinical course and determine predictors of deterioration in patients with lobar haemorrhages). METHODS: A comprehensive review of 61 consecutive patients with lobar haemorrhages was performed. Neurological deterioration was defined as (1) decrease in Glasgow coma sum score by 2 points, (2) new neurological deficit, or (3) clinical signs of brain herniation. A univariate logistic regression was performed and expressed in odds ratios. RESULTS: Sixteen of 61 (26%) patients with lobar haemorrhages deteriorated after admission. In a univariate analysis, only a Glasgow coma score <14 predicted deterioration (75% of deteriorators v 24% who did not deteriorate; p<0.0001). Initial CT characteristics predictive of deterioration included haemorrhage volume >60 ml (63% v 16%, p< 0.0001), shift of the septum pellucidum (75% v 36%, p<0.01), effacement of the contralateral ambient cistern (33% v 0%, p<0.0001), and widening of the contralateral temporal horn (50% v 0%, p<0.0001). Patients presenting and deteriorating within 12 hours of ictus declined due to enlargement of the haemorrhage. Those who deteriorated more than 12 hours after initial neurological symptoms, showed increased mass effect secondary to oedema. CONCLUSION-Patients with lobar haemorrhages presenting immediately after ictus are at risk for deterioration from enlargement of the haemorrhage and predictors of deterioration may be absent. Patients with large volume lobar haemorrhages presenting to the emergency department with decreased level of consciousness and shift on CT are at risk for further deterioration from worsening oedema. These patients require close observation and early aggressive management may be warranted.     

Observer variability in the evaluation of dual-isotope Tl-201/Tc-99m sestamibi rest/stress myocardial perfusion SPECT in men and women with known or suspected stable angina pectoris

BACKGROUND: Observer variability of dual-isotope myocardial perfusion imaging (MPI) with single photon emission computed tomography has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. METHODS AND RESULTS: We report on 507 patients with known or suspected stable angina who were studied before coronary angiography. A 1-day thallium 201/technetium 99m sestamibi rest/stress MPI protocol was used. MPI was interpreted by 2 independent observers without knowledge of clinical data, using a 20-segment scoring model. By consensus, the overall rate of abnormal MPI was 49% (59% in men and 34% in women). The interobserver agreement for the whole group (kappa = 0.85) and for men and women separately (kappa = 0.86 and 0.82, respectively) was excellent with regard to the overall diagnosis (normal, reversible, or fixed defects) as well as left anterior descending and left circumflex artery vascular territories (kappa = 0.85 and 0.82, respectively). However, in the right coronary artery territory, agreement was excellent in men (kappa = 0.83) but moderate in women (kappa = 0.57). CONCLUSIONS: In a relatively large group of men and women with stable angina pectoris, interpretive reproducibility (overall and individual vessel diagnosis) was excellent, except in the right coronary artery territory of women, in which it was moderate.     

Digital movement analysis,a new objective method of measuring tardive dyskinesia and drug-induced parkinsonian tremor: acceptability,reliability and validity

Digital movment analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS).The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal relibility of the apparatus was high, with correlation coefficients of 0.80–0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48–0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism.It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

K-ras mutations in the bile of patients with primary sclerosing cholangitis

BACKGROUND AND AIMS: The development of cholangiocarcinoma (CCC) is a complication of primary sclerosing cholangitis (PSC). To date, no reliable factors have been described which can define those PSC patients at high risk for the development of CCC and the clinical diagnosis of CCC in PSC patients is difficult. Therefore, molecular markers of cholangiocarcinogenesis, such as K-ras mutations, may improve the early diagnosis of CCC or the timing of liver transplantation. METHODS: K-ras mutations were analysed by enriched polymerase chain reaction/restriction fragment length polymorphism in the bile fluid of 56 PSC patients and 20 patients with other cholestatic diseases. To assess the value of K-ras mutations as a risk factor for cholangiocarcinogenesis, patients were prospectively investigated over a mean period of 31.5 months. RESULTS: In contrast with the control group, 17 (30%) patients with PSC revealed K-ras mutations in bile fluid. The mean Mayo score was not significantly different between PSC patients with (mean score 0.70) and without (mean score 0.13; p=0.2) K-ras mutations. In contrast with the group of PSC patients without K-ras mutations, four CCCs and two dysplasia were diagnosed in the group of patients with K-ras mutations during the follow up investigation (p<0.001). CONCLUSIONS: Our results indicate that K-ras mutations in bile fluid of PSC patients represent frequent early events during cholangiocarcinogenesis. However, most of the PSC patients with K-ras mutations remained tumour free after a long follow up investigation which is in agreement with the fact that these mutations are not specific for malignancy but may also occur in normal bile duct mucosa or in dysplasias. Therefore, analysis of K-ras mutations in bile should not be used for diagnosis of CCC in PSC patients. However, the results of our prospective follow up investigation indicate that K-ras mutations in bile fluid of PSC patients have to be considered as risk factors for the development of CCC which may have implications for the timing of liver transplantation.     

Acute effects of smoking on left ventricular function and neuro-humoral responses in patients with known or suspected ischaemic heart disease

Systolic left ventricular function was examined by radionuclide ventriculography in 12 habitual smokers with known or suspected ischaemic heart disease, aged 33-69 years, before, during, and after smoking of two cigarettes in a row and was repeated on a non-smoking control day. Plasma concentrations of adrenaline, noradrenaline, renin, and angiotensin II were determined on the smoking day, before and immediately after smoking. During smoking, there were significant increases in heart rate (+27%), rate-pressure product (+23%), and cardiac output (+14%) in the face of a significant increase in left ventricular end-systolic volume (+5%) and significant decreases in ejection fraction (-6%) and stroke volume (-8%). Blood pressure was virtually unchanged, and total peripheral resistance remained constant. Plasma adrenaline increased by 100%, renin decreased by 21%, and noradrenaline and angiotensin II did not change. The humoral changes were not correlated to changes in any of the haemodynamic variables. Areas of myocardial hypokinesis emerged or widened during smoking in 11 of 12 patients. Thus, in patients with known or suspected ischaemic heart disease, smoking was associated with an acute decrease in systolic ventricular function and development of widespread hypokinesis despite adrenaline stimulation.