L. W. Poll

Portal application of autologous CD133+ bone marrow cells to the liver : a novel concept to support hepatic regeneration

The liver has a large capacity for regeneration after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSCs) to participate in liver regeneration. Here we report on three patients subjected to intraportal administration of autologous CD133+ BMSCs subsequent to portal venous embolization of right liver segments, used to expand left lateral hepatic segments as FLRV. Computerized tomography scan volumetry revealed 2.5‐fold increased mean proliferation rates of left lateral segments compared with a group of three consecutive patients treated without application of BMSCs. This early experience with portovenous application of CD133+ BMSCs could suggest that this novel therapeutic approach bears the potential of enhancing and accelerating hepatic regeneration in a clinical setting.

Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

Abstract.Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021).

Evidence-based recommendations for monitoring bone disease and the response to enzyme replacement therapy in Gaucher patients

ABSTRACT Background: Bone disease is a serious complication of Gaucher disease. Untreated, it can result in pain, permanent bone damage and disability. Enzyme replacement therapy reverses many of the clinical signs of Gaucher bone disease but early assessment and treatment, and regular monitoring, are essential in optimising outcomes. Scope: In September 2005, a group of European experts met to review current knowledge and identify best practice and unmet needs in the monitoring of Gaucher bone disease and the response to enzyme replacement therapy. Methods: Medline searches of peer-reviewed literature (no date restrictions) were conducted and supplemented by additional information considered relevant by panellists to furthering discussions. Findings and conclusions: The groups recommendations included: currently used biochemical bone markers are not clinically practical or reliable; plain X‐rays should not be the sole method of assessing bone disease; MRI is the most sensitive method for monitoring bone marrow infiltration by Gaucher cells; semi-quantitative methods for assessing bone marrow infiltration in routine clinical practice should use readily available technology, include an assessment of Gaucher cell infiltration in the lumbar spine and femur, and be validated for inter-rater reliability and in comparison to other methods; a multidisciplinary approach is required for the treatment of Gaucher patients; all Gaucher patients should receive a comprehensive initial radiologic evaluation for bone disease and ongoing radiological monitoring at least once every 2 years.

Myocardial delayed contrast enhancement in patients with arterial hypertension: initial results of cardiac MRI

Purpose: In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. Methods and material: Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. Results: Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. Conclusion: In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

Myocardial delayed contrast enhancement in patients with arterial hypertension: initial results of cardiac MRI.

PURPOSE In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. MRI enables the detection of myocardial fibrosis, infarction and scar tissue by delayed enhancement (DE) after contrast media application. Aim of this study was to investigate patients with arterial hypertension but without known coronary disease or previous myocardial infarction to detect areas of DE. METHODS AND MATERIAL Twenty patients with arterial hypertension with clinical symptoms of myocardial ischemia, but without history of myocardial infarction and normal coronary arteries during coronary angiography were investigated on a 1.0 T superconducting magnet (Gyroscan T10-NT, Intera Release 8.0, Philips). Fast gradient-echo cine sequences and T2-weighted STIR-sequences were acquired. Fifteen minutes after injection of Gadobenate dimeglumine inversion recovery gradient-echo sequences were performed for detection of myocardial DE. Presence or absence of DE on MRI was correlated with clinical data and the results of echocardiography and electrocardiography, respectively. RESULTS Nine of 20 patients showed DE in the interventricular septum and the anteroseptal left ventricular wall. In 6 patients, DE was localized intramurally and in 3 patients subendocardially. There was a significant correlation between myocardial DE and ST-segment depressions during exercise and between DE and left-ventricular enddiastolic pressure. Patients with intermittent atrial fibrillation showed a myocardial DE more often than patients without atrial fibrillation. CONCLUSION In our series, 45% of patients with arterial hypertension showed DE on cardiac MRI. In this clinical setting, delayed enhancement may be due to coronary microangiopathy. The more intramurally localization of DE, however, rather indicates myocardial interstitial fibrosis.

Diagnosis and therapy of Gaucher disease. Current recommendations of German therapy centers in the year 2000

BACKGROUND Gauchers disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multisystem disease, the prevalence of which is about 1:40,000 in central Europe and up to 1:2,000 in some other countries (e.g. Israel). The acute and chronic neuronopathic forms of the disease (formerly defined as Gaucher types 2 and 3) account for only 5 to 10% of all Gaucher patients in Central Europe and Germany and are thus less frequent than the non-neuronopathic disease (formerly defined as Gaucher type 1). Gauchers disease is usually associated with spleno- and hepatomegaly, fatigue, skeletal complications, and several corresponding hematological and laboratory abnormalities. In 5 to 10% of the patients there are also central nervous symptoms such as myoclonic seizures, oculomotoric apraxia and a slight mental retardation. METHODS Four specialized centers care for more than 2/3 of all German Gaucher patients today. These centers present their consensus recommendations for state-of-the-art diagnosis and treatment of Gauchers disease. RESULTS Recent epidemiological data indicate that only 10 to 20% of all Gaucher patients are correctly diagnosed (and treated) in Germany. The diagnosis today can be done in all patients by noninvasive methods, i.e. determination of the glucocerebrosidase activity in peripheral leukocytes and of the genetic defect. The current enzyme replacement therapy with glucocerebrosidase has proven effective to improve and often normalize hematological abnormalities, hepatosplenomegaly, skeletal complications and quality of life, provided that the therapy is started early and is given at adequate dosages. CONCLUSION In view of the availability of an effective therapy, efforts should be made to increase the awareness of Gauchers disease in differential diagnosis, to help to diagnose the disease with noninvasive techniques at early stages, and to provide practical guidelines for adequate treatment.ZusammenfassungHintergrund: Beim Morbus Gaucher handelt es sich um die häufigste Sphingolipidose, deren Vorkommen zwischen 1 : 40 000 (in Zentraleuropa) und 1 : 2 000 (in einigen außereuropäischen Ländern, zum Beispiel Israel) variiert. Zugrunde liegt dieser Speichererkrankung ein autosomal-rezessiv vererbter Defekt der Glucocerebrosidase, der zu einem verminderten Abbau der Sphingolipide führt. Die akuten und chronischen neuronopathischen Verlaufsformen (früher als Gaucher-Typen 2 und 3 bezeichnet) sind mit 5 bis 10% in Mitteleuropa und Deutschland seltener als die nicht neuronopathische Variante (früher als Gaucher-Typ 1 bezeichnet). Klinisch ist der Morbus Gaucher charakterisiert durch die Kernsymptome Hepatosplenomegalie, Abgeschlagenheit, Knochenbefall sowie hämatologische und laborchemische Veränderungen. Bei ungefähr 5 bis 10% der Fälle ist auch das Zentralnervensystem beteiligt, meist in Form einer myoklonischen Epilepsie, einer okulomotorischen Apraxie und einer leichten mentalen Retardierung. Methodik: Die Betreuung von mehr als zwei Drittel aller deutschen Patienten erfolgt aktuell in vier Therapiezentren, die in diesem Beitrag ihre Empfehlungen zur Diagnose und Therapie des Morbus Gaucher zusammenfassen. Ergebnisse: Nach epidemiologischen Daten ist die Erkrankung in Deutschland derzeit nur bei 10 bis 20% der Betroffenen korrekt diagnostiziert. Die Diagnose ist heute über die Analyse der verminderten Glucocerebrosidaseaktivität in Leukozyten und die Bestimmung des Gendefekts bei allen Patienten ohne invasive Techniken möglich. Die jetzt zur Verfügung stehende intravenöse Substitution des defekten Enzyms Glucocerebrosidase führt – bei frühzeitigem Beginn und adäquater Dosis – zur meist kompletten Rückbildung der viszeralen, ossären und laborchemischen Veränderungen bzw. Beschwerden und bewirkt eine erhebliche Besserung des Allgemeinzustands der Patienten. Schlussfolgerung: Wegen der jetzt verfügbaren wirksamen und nebenwirkungsarmen Therapie sollten die Bemühungen verstärkt werden, das Krankheitsbild des Morbus Gaucher in die differentialdiagnostischen Überlegungen mit einzubeziehen, rechtzeitig zu diagnostizieren und adäquat zu behandeln.AbstractBackground: Gauchers disease is the autosomally recessively inherited deficiency of the lysosomal enzyme glucocerebrosidase. Increasing storage of glucocerebrosides leads to a multisystem disease, the prevalence of which is about 1 : 40,000 in central Europe and up to 1 : 2,000 in some other countries (e. g. Israel). The acute and chronic neuronopathic forms of the disease (formerly defined as Gaucher types 2 and 3) account for only 5 to 10% of all Gaucher patients in Central Europe and Germany and are thus less frequent than the non-neuronopathic disease (formerly defined as Gaucher type 1). Gauchers disease is usually associated with spleno- and hepatomegaly, fatigue, skeletal complications, and several corresponding hematological and laboratory abnormalities. In 5 to 10% of the patients there are also central nervous symptoms such as myoclonic seizures, oculomotoric apraxia and a slight mental retardation. Methods: Four specialized centers care for more than 2/3 of all German Gaucher patients today. These centers present their consensus recommendations for state-of-the-art diagnosis and treatment of Gauchers disease. Results: Recent epidemiological data indicate that only 10 to 20% of all Gaucher patients are correctly diagnosed (and treated) in Germany. The diagnosis today can be done in all patients by noninvasive methods, i. e. determination of the glucocerebrosidase activity in peripheral leukocytes and of the genetic defect. The current enzyme replacement therapy with glucocerebrosidase has proven effective to improve and often normalize hematological abnormalities, hepatosplenomegaly, skeletal complications and quality of life, provided that the therapy is started early and is given at adequate dosages. Conclusion: In view of the availability of an effective therapy, efforts should be made to increase the awareness of Gauchers disease in differential diagnosis, to help to diagnose the disease with noninvasive techniques at early stages, and to provide practical guidelines for adequate treatment.

Azygos continuation syndrome with aneurysm of the azygos vein: CT and MR appearances.

We present a case of azygos vein continuation with aneurysm of the azygos vein simulating a tumor in the right upper mediastinum. The dynamic CT examination initially showed a structure of malignant appearance during the early arterial phase. Further dynamic CT revealed marked enhancement of the mass during the late venous phase, suggesting a vascular structure. Confirmation of diagnosis was made by MRI using a fast gradient echo imaging technique in cine mode, showing turbulent flow in the azygos aneurysm, and contrast-enhanced MR angiography, demonstrating a dilated azygos vein. Dynamic CT has a potential pitfall in the diagnosis of vascular structures.

Type I Gaucher disease: extraosseous extension of skeletal disease

Abstract  Objective. To investigate the frequency and morphology of extraosseous extension in patients with Gaucher disease type I. Design and patients. MRI examinations of the lower extremities were analyzed in 70 patients with Gaucher disease type I. Additionally, the thoracic spine and the midface were investigated on MRI in two patients. Results. Four cases are presented in which patients with Gaucher disease type I and severe skeletal involvement developed destruction or protrusion of the cortex with extraosseous extension into soft tissues. In one patient, Gaucher cell deposits destroyed the cortex of the mandible and extended into the masseter muscle. In the second patient, multiple paravertebral masses with localized destruction of the cortex were apparent in the thoracic spine. In the third and fourth patient, cortical destruction with extraosseous tissue extending into soft tissues was seen in the lower limbs. Conclusions. Extraosseous extension is a rare manifestation of Gaucher bone disease. While an increased risk of cancer, especially hematopoietic in origin, is known in patients with Gaucher disease, these extraosseous benign manifestations that may mimic malignant processes should be considered in the differential diagnosis of extraosseous extension into soft tissues. A narrow neck of tissue was apparent in all cases connecting bone and extraosseous extensions.

Gaucher disease of the spleen: CT and MR findings.

We present a 26-year-old male patient with Gaucher disease who presented with epigastric pain and a palpable mass in the left abdomen. Ultrasound, abdominal computed tomography, and magnetic resonance imaging showed massive splenomegaly with multiple splenic nodules up to 7 cm in diameter. Splenic nodules should be included in the differential diagnosis of splenic masses. Follow-up is necessary because of the increased incidence of hematologic malignancies in Gaucher disease.

A rapid and reliable semiautomated method for measurement of total abdominal fat volumes using magnetic resonance imaging

The aim of this study was the development of a reliable and fast method to estimate total abdominal fat volumes (TAF) in diabetic subjects on the basis of T1-weighted MR images. Thirty-seven patients with diabetes were examined (age 48 +/- 13 y mean +/- SD). A semiautomated computer assisted software program was developed to quantify intraabdominal (IAF), subcutaneous (SCF), and total abdominal fat volumes (TAF). The variability of image analysis for fat measurements between two observers and within observers was assessed. Mean volumes (+/- SD) for IAF, SCF and TAF were 10.5 1 (+/- 5.0 1), 15.1 1 (+/-7.3 1) and 25.7 1 (+/-11.5 1), respectively. Inter- and intraobserver reliability was excellent (r = 0.999 to r = 1.0). Per patient, the analysis required nine minutes in addition to a scan duration of seven minutes. As this analytic method using T1-weighted MR images allows a fast and reliable quantification of TAF, IAF and SCF, it may serve as a valuable tool for respective studies in diabetic subjects.