Whole-body [18F]-FDG-PET/MRI for staging of pediatric non-Hodgkin lymphoma: first results from a single-center evaluation.

AIM: In 2015, the revised International Pediatric Non-Hodgkin Lymphoma Staging System was published. It mentions [18F]-FDG-PET/MRI as the latest method to perform whole-body imaging. However, supporting data are pending. Our aim was to investigate the performance of whole-body [18F]-FDG-PET/MRI in pediatric non-Hodgkin lymphoma patients by using a limited number of MRI sequences. MATERIALS AND METHODS: Ten pediatric patients with histologically proven non-Hodgkin lymphoma underwent whole-body [18F]-FDG-PET/MRI at staging. The retrospective analysis included three steps: First, [18F]-FDG-PET and MR scans were evaluated separately by a nuclear medicine physician and a pediatric radiologist. Nineteen nodal and two extranodal regions as well as six organs were checked for involvement. Second, discrepant findings were reviewed together in order to reach consensus. Third, [18F]-FDG-PET/MRI findings were correlated with the results of other clinical investigations. RESULTS: Of the 190 lymph node regions evaluated, four were rated controversial. Consensus was reached by considering metabolic, functional and morphologic information combined. Concordantly, [18F]-FDG-PET and MRI detected Waldeyer's ring involvement in two patients whose Waldeyer's ring was negative on clinical assessment. In four patients MRI showed pleural effusion. However, in only two of them an increased glucose metabolism as a reliable sign of pleural involvement was detectable. In six patients [18F]-FDG-PET and MRI detected skeletal lesions although bone marrow biopsy was positive in only one of them. CONCLUSION: Despite the small number of cases evaluated, whole-body [18F]-FDG-PET turned out to be a valuable tool for staging of pediatric non-Hodgkin lymphoma.

[Differential diagnosis of cystic abdominal masses in children]. / Differenzialdiagnosen zystischer abdominaler Raumforderungen im Kindesalter.

BACKGROUND: Cystic abdominal masses are a common main or incidental finding in daily radiological practice; however, differentiation is not always trivial. OBJECTIVES: In children, cystic abdominal masses represent a special feature compared to adults, since the spectrum of congenital lesions must be taken into consideration. The article gives a structured overview of the most common entities. MATERIALS AND METHODS: The standard methods in abdominal imaging in pediatric radiology are ultrasound and MRI. Based on a literature review, the most important differential diagnoses with their characteristics in ultrasound and MRI were compiled. RESULTS AND DISCUSSION: With anatomical classification, presence or absence of solid components as well as the contrast agent behavior in the MRI, the cystic masses can be well differentiated and classified into three groups: congenital and acquired cysts as well as neoplasms.

[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

[Accident or maltreatment? Radiographic X­ray patterns in non­accidental trauma : The concept of sentinel injuries]. / Unfall oder Misshandlung? Radiologische Befunde beim nichtakzidentiellen Trauma : Das Konzept der "sentinel injuries".

The focus of this review article is on child abuse and the radiographic pattern of X­ray findings. The radiologist should be able to recognize typical injuries resulting from child abuse. In some cases the findings are highly specific for abuse and these include metaphyseal corner fractures of the long bones in children aged up to 24 months. In other cases the fractures are not specific but highly indicative of child abuse: rib fractures, for example can be associated with child abuse in more than 50 % of the cases; however, maltreatment is difficult to diagnose without taking the entire pattern of skeletal findings into consideration so that a radiological screening of the entire skeleton is often necessary. The concept of sentinel injuries might be helpful for deciding in which cases a complete skeletal screening should be performed. In the age group up to 24 months old a complete skeletal status (with some exceptions) is recommended if one of the three sentinel injuries of rib fractures, intracranial bleeding and abdominal trauma is present.

Striated Nephrogram as an Incidental Finding in MRI Examination of Children.

PURPOSE: A highly striated contrast pattern of the kidneys occasionally appears in abdominal MRI examinations of children following the administration of gadolinium. As this phenomenon is well known but has not yet been explicitly described in literature, we investigated how frequently and in which clinical context this occurred. MATERIAL AND METHODS: 855 abdominal MRI examinations with contrast media of 362 children between 2006 and 2014 were analysed retrospectively. RESULTS: A striated renal parenchyma was found in a total of nine children and eleven examinations (1.3 % of examinations) and did only occur at a field strength of 3 Tesla. Of these children, seven had previously had tumors and chemotherapy. In two children there was no evidence of a previously serious condition with medications or a kidney disease. All of them had a normal renal function. CONCLUSION: A noticeably striated nephrogram in the later phase of an MRI examination following administration of gadolinium may appear as an incidental finding in examinations at 3 Tesla without pathological relevance. KEY POINTS: • striated nephrograms may appear at a field strength of 3 Tesla. • incidental finding without pathological relevance.

Significance of MR angiography in the diagnosis of aberrant renal arteries as the cause of ureteropelvic junction obstruction in children.

PURPOSE: To determine the importance of MRI with contrast-enhanced MRA for the detection or exclusion of aberrant or obstructing renal arteries in ureteropelvic junction obstruction in children. MATERIALS AND METHODS: Key word-based search in RIS database (ureteropelvic junction obstruction/ MRI) and retrospective comparison of arterial findings from preoperative contrast -enhanced MRA and intra-operative inspection. From 2007 to 2013, 19 children with ureteropelvic junction obstruction underwent contrast-enhanced MRA. Based on the results of the MRI scan and MAG3 scintigraphy, the children were referred to surgery (Anderson-Hynes-pyeloplasty). RESULTS: An aberrant renal artery was diagnosed with MRI in 14 of 19 children, and intra-operative inspection confirmed 13 of those 14. In the remaining 5 children, no aberrant vessel could be observed in MRI and this was confirmed intra-operatively in 3 of the 5 cases, while in the remaining 2, an aberrant vessel was found. Of the 14 children with aberrant vessels, 12 underwent surgery due to assumed ureteral obstruction, which was confirmed by surgery in 11 cases. In one case, an aberrant artery was found intra-operatively, but obstruction could not be confirmed. In one of the 14 children, the vessel was found in MRI, but its obstructing character was negated via MRA, which was confirmed intra-operatively. In the diagnosis of aberrant and obstructing renal arteries, contrast-enhanced MRA presents 85% sensitivity and 80% specificity, with a positive predictive value of 0.8. CONCLUSION: MRI with contrast-enhanced MRA is suitable to detect aberrant and obstructing renal arteries. An obstructive effect of the aberrant vessel is to be assumed if the vessel has a close relationship to the ureteropelvic junction and if it is linearly stretched. KEY POINTS: • MRI with contrast-enhanced MRA is a sure method for the detection of aberrant renal arteries in children with ureteropelvic junction obstruction. • The obstructive effect of the aberrant vessel can be derived from the close proximity of the vessel to the ureteropelvic junction and from the streched course of the vessel.

Demonstration of estrogen and progesterone receptors as well as Ki-67 and p-145 antigens in single tumor cells from blood and pleural effusions using a slide assay.

We describe a slide assay that allows the demonstration of antigens localized in the nucleus from isolated white blood cells as well as from single tumor cells derived from malignant effusions. With the antibodies Ki-67 and anti-p-145 an increased rate of nuclear and nucleolar staining resulted in cells from highly malignant lymphomas. An almost identical reaction was obtained when tumor cells from malignant effusions were tested. Cells isolated from the blood of patients with leukemic spread of lymphomas of low malignancy yielded a weak staining comparable to that of normal mesothelial cells from non-tumorous cavity fluids. The detection of estrogen and progesterone receptors (ER and PR) localized in the cell nucleus can be achieved by the same assay. The reaction is enhanced by incubation of the tumor cells for 30 min at 37 degrees C prior to fixation. Pleural effusions from 20 patients with breast cancer were tested. ER was positive in 13 and PR was positive in 12 of the 20 samples. In 5 cases there was a divergent reaction with ER and PR antibody. The hormone receptors of the primary tumor were known in 15 (ER) and 14 (PR) patients, respectively. In each cohort there was only one case with a negative reaction of the primary tumor and a positive reaction with the isolated tumor cells from the pleural effusions. These results indicate that the demonstration of hormone receptor proteins in cells from malignant effusions is possible and that there is a correlation with the status of the primary site of cancer.

[Effectiveness and side effects of recombinant alpha-2a interferon in patients with metastatic hypernephroma]. / Wirksamkeit und Nebenwirkungen von rekombiniertem Interferon alpha-2a bei Patienten mit metastasierendem Hypernephrom.

Eighteen patients with advanced renal cell carcinoma were treated with recombinant interferon alpha-2a (18 million IU s.c. three times a week). 9 patients had received prior hormonal therapy (tamoxifen). On entering the therapeutic schedule with recombinant interferon alpha-2a, all patients had progressive disease with multiple metastases. Flu-like symptoms occurred in general; they were severe in 9 cases. An impairment of the liver was shown by a rise of SGOT/SGPT and alkaline phosphatase in 2 patients, the gamma-GT was raised in 7 patients. The kidney function worsened in 3 cases. A fall in blood cell counts was seen in 8 cases. Five patients developed a transient stomatitis. Five patients (5/18) showed stable disease with the longest response duration of 17 months. One patient showed a complete remission 5 months after starting therapy for a duration of 7 months until now. Both the limited benefit from this treatment as well as some severe side effects indicate the need for further special evaluation and possible improvements of this therapeutic approach.

Serum antibodies to a normal cellular protein (P-65) in patients with Hodgkin's disease.

Samples from the L-428 Hodgkin's cell line and from several other lymphoma cell lines were lysed and the soluble proteins were subjected to one- or two-dimensional gel electrophoresis. The separated proteins were transferred to nitrocellulose by the Western Blot technique; antibody reactivity was detected by an immunoperoxidase reaction. Of 152 sera from patients with Hodgkin's disease (HD) 26 (17%) reacted with protein P-65 whereas in the control group, consisting of 35 healthy persons and 20 patients with other malignant diseases only 1 serum was reactive. Thus, the difference between the two groups was highly significant (P less than 0.01). These antibodies were most common in stage III HD. Splenectomy had no effect on the incidence of these antibodies, and there seemed to be no correlation with B-symptoms or with the histological subtype.

[Infection of the CNS caused by Listeria monocytogenes]. / Infektion des ZNS durch Listeria monocytogenes.

This report examines two cases of infection of the central nervous system by Listeria monocytogenes (L.m.). Both cases show that listeriosis is not only a differential diagnosis of purulent meningitis, but can also be the cause of an isolated brain stem syndrome with normal cerebrospinal fluid cell count. The prognosis depends crucially on the early antibiotic therapy (ampicillin). The first patient was a chronic alcoholic. He died of fulminant septic shock and meningitis with brain stem encephalitis (cell count of cerebrospinal fluid: 10500/microliters). L.m. was isolated from blood cultures and from cerebrospinal fluid. The second patient had no indications of preexisting immunological disorder. Two days after perianal injections for haemorrhoids, symptoms of a progredient brain stem syndrome developed. The cell count of cerebrospinal fluid was only 10/mu, but L.m. was isolated from blood cultures. The patient died of circulatory failure. At autopsy, a brain stem encephalitis and cerebellitis with inflammation of the surrounding leptomeninx was identified.

Characterization of the Epstein-Barr virus-induced early polypeptide complex p50/58 EA-D using rabbit antisera, a monoclonal antibody, and human antibodies.

A polypeptide complex (p52) belonging to the D-subspecificity of the EBV-induced early antigens (EA-D) was purified from chemically induced P3HR-1 cells. Rabbit antisera raised against the isolated polypeptides reacted with components of EA-D as could be shown by indirect immunofluorescence and immunoperoxidase staining of IdU-induced EA positive Raji cells, ELISA, and immunoblotting. In one-dimensional immunoblots the rabbit antisera detected a predominant polypeptide complex of 52 kDa. Two-dimensional immunoblots prepared with proteins from IdU-induced Raji cells showed that the rabbit sera detect three series of polypeptides of 52 kDa (pl 8.5-6.2), 55-58 kDa (pl 6.2-4.5), and 48-50 kDa (pl 6.0-4.5). These three groups of polypeptides could also be identified by 50 high titered anti-EA-D positive human sera and a specific monoclonal antibody (R3) as being the main components of EA-D in Raji and B95-8 cells. All polypeptides of the p50/58 complex showed DNA binding properties either by themselves or by an interaction with other proteins. When TPA or IdU-induced Raji cells were labeled with 2Pi, two phosphorylated polypeptides pp50 and pp58 could be immunoprecipitated with the rabbit sera and a high anti-EA titered human serum. The time course of the synthesis of polypeptides associated with the EA-D complex was studied by 2-D immunoblots: EA polypeptides of 52 kDa appeared as early as 6 hr after the addition of IdU to Raji cells in culture, polypeptides of 55-58 and 48-50 kDa after 18 and 25 hr, respectively. The coordinated appearance of these groups of polypeptides and their similar size and reactivity with human sera and rabbit antisera produced against the isolated p52 as well as with a monoclonal antibody (R3) suggested that most of these polypeptides are derived from post-translational modifications of one or a few initially synthesized polypeptides, possibly p52. Phosphorylation seems to be at least one possibility of post-translational modification.

Increased incidence of IgA antibodies to the Epstein-Barr virus-associated viral capsid antigen and early antigens in patients with chronic lymphocytic leukemia.

Antibody titers to Epstein-Barr virus (EBV)-associated early antigens (EA) and the viral capsid antigen (VCA) were determined by ELISA on 263 sera obtained from healthy donors, patients with Hodgkin's disease (HD), non-Hodgkin lymphomas (NHL), infectious mononucleosis (IM), Burkitt's lymphoma (BL), and nasopharyngeal carcinoma (NPC). As expected, most lymphoma patients showed markedly elevated anti-VCA IgG and anti-EA IgG antibody titers. Only one patient in the NHL group (n = 56) consisting of patients with lymphomas other than chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), and 3 patients with HCL (n = 19) had high antibody titers of the IgA class to VCA and EA. Seventeen out of 48 patients (36%) with CLL had high IgA anti-VCA titers and 10 of these sera (21%) also contained IgA anti-EA. The geometric mean titer (GMT) of IgA anti-VCA was 2,510, the GMT of IgA anti-EA was 780. These antibody titers were about 10 times lower than the corresponding GMT of the NPC patients investigated in this study. The elevated IgG and IgA antibody titers to VCA and EA in CLL and HCL patients seem to reflect an immunodeficiency secondary to the malignant disease leading to reactivation of latent EBV infection. The possibility that at least some of these B-cell lymphomas are associated with EBV cannot be excluded.

[Primary orthostatic hypotension]. / Primäre orthostatische Hypotonie. Ein Fallbericht.

We studied a 25-year-old man suffering from primary orthostatic hypotension whose blood pressure decreased to 65/45 mm Hg during orthostasis and to 95/70 mm Hg during ergometric exercise (50 and 100 watt), and whose heart rate responses were inadequate. Resting catecholamine levels were within the normal range and did not show any significant increase related to orthostasis or to ergometric exercise. Hypersensitivity was observed to low doses of intravenous noradrenaline and isoproterenol. Specific binding of 3H-Yohimbine to intact platelets revealed a normal number of alpha-2-adrenoreceptors in agreement with the adrenaline-induced platelet aggregation in vitro, which was, however, in contrast to hypersensitivity to noradrenaline. Specific 3H-Dihydroalprenolol binding to intact polymorphonuclear leucocytes revealed an increased beta-2-adrenoreceptor density in agreement with hypersensitivity to Isoproterenol. Prescription of Fludrocortison improved orthostatic hypotension.

Purification of a polypeptide complex (p52) belonging to the D-subspecificites of Epstein-Barr virus-induced early antigens.

A two-dimensional immunoblot analysis of chemically induced EBV DNA carrying Burkitt's lymphoma cell lines shows besides a large number of minor components at least two major groups of polypeptides: the most prominent group of polypeptides is observed in the range of 48 to 58 kDa (pI 4.5 to 8.5) and another group at 38/36 kDa (pI 4.4). A polypeptide complex (p52) belonging to the Epstein-Barr virus (EBV)-induced early antigen complex (EA) has been isolated from IdU-induced Raji and B95-8 cells as well as from n-butyrate-induced P3HR-1 cells. The p52 polypeptides have been purified by chromatography on Blue-, DEAE-, CM-, and Phenyl-Sepharose. The purification of these components of the EA complex was monitored by ELISA and by two-dimensional immunoblots using a well-characterized high anti-EBV positive human serum. The isolated polypeptides have an apparent mol wt of about 52,000 Da as determined under nondenaturing conditions by gel filtration chromatography on Sephacryl S-300. One- and two-dimensional immunoblots show a major group of polypeptides of 52 kDa (pI 8.5 to 5.5) with EA activity and some minor components with smaller size up to 40 kDa. The latter seem to be generated by limited proteolysis of p52 polypeptides. The EA activity of the isolated polypeptides could be confirmed by their reaction with IgG anti-EA positive as well as IgA anti-EA positive sera by ELISA. The purified polypeptide complex did not react with anti-EA-D negative, anti-EA-R positive sera obtained from patients with African Burkitt's lymphoma, suggesting that these polypeptides belong to the EA-D complex. The monoclonal antibody R3 reacted with the isolated 52 kDa components of EA suggesting a common epitope present on these polypeptides, the same result was obtained with three rabbit sera produced against the isolated polypeptide complex.

Human adult T-cell leukaemia virus is distinct from a similar isolate of Japanese monkeys.

We have compared the structural polypeptides of an adult T-cell leukaemia (ATL) virus (ATLV) isolate from a Japanese patient with ATL with those of a similar virus derived from a Japanese macaque monkey. Both are distinct but related entities. Their core polypeptides p19 could not be distinguished, but p24, another core polypeptide, and their envelope glycopolypeptides differ. The human virus directs the synthesis of a single intracellular glycopolypeptide, gp68, while the macaque virus specifies two such glycopolypeptides, gp57 and gp50. Furthermore, the glycopolypeptides of both viruses are serologically distinct. Thus, these viruses represent subtypes of the ATLV family and the macaque virus is apparently not involved in human ATL.

[Demonstration of IgG- and IgA-antibodies against Epstein-Barr virus-associated antigens with a microtiter enzyme immunoassay system. The determination of serum antibodies against the viral capsid antigen and the early antigen complex in the sera of tumor and infectious mononucleosis patients]. / Nachweis von IgG- und IgA-Antikörpern gegen Epstein-Barr-Virus-assoziierte Antigene mit einem Enzymimmunoassay im Mikrotitersystem. Bestimmung der Serumantikörper gegen das Viruskapsidantigen und den Frühantigenkomplex in Seren von Tumorpatienten und Patienten mit infektiöser Mononukleose.

An enzyme-linked immunosorbent assay (ELISA) using micro-titre plates has been established for determination of IgG and IgA antibodies to the Epstein-Barr virus (EBV)-associated early antigen complex (EA) and the viral capsid antigen (VCA). The results obtained correlated well with the antibody titre determinations by the standard immunofluorescence technique. The ELISA was found to be about 15 to 30 times more sensitive than the immunofluorescence assay. Because of its high sensitivity, specificity and rapid performance the enzyme-immunoassay is a useful tool for large scale epidemiological studies of EBV-associated diseases as well as for the early diagnosis and monitoring of patients with EBV-associated tumours: Burkitt's lymphoma and nasopharyngeal carcinoma. IgG and IgA antibody titres to EA and VCA were determined in sera obtained from healthy controls, patients with EBV-associated tumours, infectious mononucleosis and various diseases known to be associated with EBV-reactivation, i.e. lymphomas and leukaemias. Except in sera of patients with nasopharyngeal carcinoma, IgA antibodies to VCA and EA could only be detected at a rather high frequency (36% IgA anti-VCA+, 21% IgA anti-EA+) and in substantial titres in sera obtained from patients with chronic lymphatic leukaemia.

Immunoglobulin light chains in chronic lymphocytic leukemia and related diseases.

The combination of two-dimensional mini gel electrophoresis with the 'western blot' technique proves to be a powerful tool in characterizing lymphoid cells. By testing for kappa and lambda immunoglobulin light chains we were able to differentiate between mono-, oligo-, and polyclonal B-cell diseases. The distribution of the lambda isotypes of 24 cases with chronic lymphocytic B-cell leukemia (B-CLL) tested was not random when compared to the distribution of the lambda light chains in B-lymphocytes of normal persons. This might implicate a genetic link between the lambda loci (chromosome 22) and the development of the lambda-CLL.