Pediatric Burkitt's lymphoma and diffuse B-cell lymphoma: are surveillance scans required?

Outcomes in pediatric B-Non-Hodgkin Lymphoma (B NHL) have improved with intensive chemotherapy protocols, with long-term survival now over 80%. However, long-term adverse effects of therapy and poor outcomes for patients who relapse remain challenges. In this study, we aimed to evaluate the potential risks and benefits of routine relapse surveillance imaging after the completion of therapy. We reviewed 44 B NHL patients diagnosed and treated at Texas Children's Cancer Center in the period between 2000 to 2011. All cross-sectional diagnostic imaging examinations performed for disease assessment after completion of chemotherapy were reviewed and cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. Only 3 patients of the 44 relapsed (6.8%), though none of the relapses were initially diagnosed by computed tomography (CT) or fludeoxyglucose positron emission tomography (FDG-PET) scans. Median effective dose of ionizing radiation per patient was 40.3 mSv with an average of 49.1 mSv (range 0-276 mSv). This single-institution study highlights the low relapse rate in pediatric B-NHL with complete response at the end of therapy, the low sensitivity of early detection of relapse with surveillance CT or FDG-PET imaging, and the costs and potential increased risk of secondary malignancies from cumulative radiation exposure from surveillance imaging. We propose that routine surveillance CT or FDG-PET scans for these patients may not be necessary.

Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors.

Understanding the heterogeneous genetic mechanisms of tumor initiation in lymphoid leukemias (LL) will lead to improvements in prognostic classification and treatment regimens. In previous studies of mouse leukemias, we showed that retroviral insertion at the ecotropic viral insertion site 32 locus leads to increased expression of Prdm14, a pluripotency gene implicated in the self-renewal capacity of embryonic stem cells and the early stages of breast cancer. Here, we show that PRDM14 is also overexpressed in ∼25% of human lymphoid neoplasms, with increased frequencies in T-cell acute LL and hyperdiploid precursor B-cell acute LL. To test if Prdm14 overexpression could initiate leukemia, mice were transduced with bone marrow cells transfected with a Prdm14 expression vector. LLs developed in 96% of female mice and 42% of male mice. Before the onset of leukemia, differentiation of transduced cells was biased up to 1000-fold toward cells with features of common lymphoid progenitors (CLPs), and lymphoid differentiation showed a relative block at the pro-B stage. Microarray gene expression analysis of expanded CLP-like cells before the onset of leukemia demonstrated upregulation of genes involved in pluripotency, tumor initiation, early B-lineage commitment, Wnt/Ras signaling and the epithelial-to-mesenchymal transition. Among the dysregulated genes were imprinted genes and non-coding RNAs including Dlk1 and Meg3, which are also key pluripotency mediators. Heightened expression of the estrogen-dependent oncogene, Myb, in tumors suggests a basis for the increased frequency of cancer in female mice. These data provide the first direct evidence for the association of Prdm14 with cancer initiation in an in vivo mouse model and in human lymphoid malignancies, while suggesting mechanisms for Prdm14's mode of action.

Cloning and expression of human HBP1, a high mobility group protein that enhances myeloperoxidase (MPO) promoter activity.

Factors which regulate transcription in immature myeloid cells are of great current interest for the light they may shed upon myeloid differentiation. In the course of screening for transcription factors which interact with the human myeloperoxidase (MPO) promoter we, for the first time, identified and cloned the cDNA and genomic DNA for human HBP1 (HMG-Box containing protein 1), a member of the high mobility group of non-histone chromosomal proteins. HBP1 cDNA was initially cloned from rat brain in 1994, but its presence in human cells or in myeloid tissue had not been described previously. The sequence of human HBP1 cDNA shows 84% overall homology with the rat HBP1 cDNA sequence. We have subsequently cloned the gene, which is present as a single copy, 25 kbp in length. Northern blotting reveals a single 2.6 kb mRNA transcript which is expressed at higher levels in human myeloid and B lymphoid cell lines than in T cell lines tested and is present in several non-myeloid human cell lines. Comparison of the mRNA and genomic sequences reveals the gene to contain 10 exons and 9 introns. The sequence of human HBP1 mRNA contains a single open reading frame, which codes for a protein 514 amino acids in length. The amino acid sequence specified by the coding region shows 95% homology with the rat HBP1 protein. The human protein sequence exhibits a putative DNA-binding domain similar to that seen in rat HBP1 and shows homology with the activation and repressor domains previously demonstrated in the rat protein. We have expressed human HBP1 protein both in vitro and in prokaryotic and eukaryotic cells. The expressed fusion protein binds to a sequence in a functionally important region within the basal human MPO promoter. In transient co-transfection experiments HBP1 enhances MPO promoter activity. Human HBP1 appears to be a novel transcription factor which is likely to play an important role in regulating transcription in developing myeloid cells.

[Antibiotic resistance in Staphylococcus aureus mastitis in sheep, sheep milk and its products]. / Rezistencia na antibiotiká u Staphylococcus aureus pri mastitídach oviec, v ovcom mlieku a výrobkoch z neho.

A study of current resistance to antibiotics was conducted in 500 strains of Staphylococcus aureus isolated from ewes with clinical and latent mastitis, from sheep milk and products made from it (sheep lumpy cheese, bryndza cheese). A diffusion disk method was used to assay 14 kinds of antibiotics (AMP, BAC, CEF, ERY, GEN, CMP, KAN, LIN, OXA, PEN, RIF, SPI, VAN, TET) and one chemotherapeutic drug (COT). The highest resistance was observed in the cases of clinical mastitis (from 8% and 10% in COT and KAN to 68% and 69% in PEN and TET). Resistance significantly decreased in 13 kinds of antibiotics in the group of cases with latent mastitis (from 3% in SPI to 30% in PEN), it increased in KAN (13%) and COT (12%) only. Resistance also decreased in bulk samples of sheep milk; it was the highest in PEN (27%) and AMP (17%) and the lowest in CEF, RIF and SPI (5%). Sheep lumpy cheese and bryndza cheese are mostly made from unpasteurized milk. Resistance continued to decrease even in these dairy products. It ranged from 2% in CEF to 16% in OXA in sheep lumpy sugar, while it varied from 0% in SPI to 14% in TET in bryndza cheese. The results demonstrate that sheep milk and products made from it are not any important sources of antibiotic resistance of S. aureus in Central Slovakia.

[Salmonellosis in breeds of pigs with latent infections and in salmonellosis foci]. / Salmonely v chovoch osípaných s latentnými infekciami a v ohniskách salmonelóz.

The occurrence of salmonellae in pigs in Slovakia is described for the period from 1971 to 1980. On the whole, 1430 strains (11 serological types) of salmonellae were isolated in stocks with latent infections. The proportions of the serological types were as follows: S. agona 0.69%, S. anatum 0.14%, S. arizona 0.07%, S. bareilly 0.14%, S. decatur 0.07%, S. enteritidis 1.12%, S. give 0.28%, S. heidelberg 0.07%, S. choleraesuis 93.71%, S. panama 0.07% and S. typhimurium 2.45%. In 1315 salmonellosis foci 1333 strains (six serological types) of salmonellae were isolated. The proportions of the serological types were as follows: S. agona 0.37%, S. anatum 0.07%, S. bareilly 0.22%, S. enteritidis 1.20%, S. choleraesuis 90.59% and S. typhimurium 5.30%. The annual pattern of the occurrence of the most frequent serological types is described.

[Incidence of salmonellae in domestic fowl in Slovakia from 1971 to 1980]. / Výskyt salmonel u kúr domácich na Slovensku v rokoch 1971-1980.

In flocks with latent infections, 2724 strains of salmonellae (19 serotypes) were isolated from the birds. The following species were represented as follows: S. gallinarum-pullorum (65.08%), S. typhimurium (9.10%), S. bareilly (6.90%), S. enteritidis (2.38%) and S. agona (1.98%). In the foci of salmonelloses 893 strains of salmonellae (19 serotypes) were isolated. The highest representation was found in the S. gallinarum-pullorum (54.20%), S. typhimurium (24.53%), S. bareilly (7.72%), S. choleraesuis (2.29%), S. enteritidis (1.68%), S. infantis (1.54%) and S. anatum (1.23%). Post-mortem examination resulted in recording 15 887 strains of salmonellae (41 serotypes). The following were represented by the largest proportions: S. gallinarum-pullorum (26.62%), S. typhimurium (25.20%), S. bareilly (18.93%), S. infantis (7.20%), S. enteritidis (4.62%), S. agona (3.51%), S. choleraesuis (3.17%), S. anatum (2.19%), S. lille (1.54%) and S. bredeney (1.16%).

Prevention, diagnosis and treatment of carbon monoxide poisoning in an East-Slovakian ironworks.

The development of industry brings an increase in number of industrial poisonings by carbon monoxide. To treat these the East-Slovakian Ironworks has organised preventive measures. Instructive cases are illustrated. Measurement of carbon monoxide--haemoglobin in the laboratory gives an objective index for the degree of poisoning and the progress of treatment. The authors used cobaltous nitrate (0.13 mol/l) for control of the method. The best treatment was found to be hyperbaric oxygen in combination with multi-vitamin treatment. In some cases cardiorespiratory and antibiotic treatment is also necessary.

[Voice changes during hormonal contraception]. / Príspevok kstúdiu zmien hlasu pri hormonálnej antikoncepcii.

PIP: Hormonal contraception may be accompanied by voice disorders. The authors examined a woman who suffered from symptoms of virilization (enlarged larynx with male-sounding voice), after having taken the preparation Biogest. It may thus be advisable to monitor women taking hormonal contraceptives to observe possible changes in their voices. As soon as such changes occur, a phoniatrist should be consulted. Increased attention should be paid to women whose vocal organ is subjected to increased requirements. (Authors' modified)^ieng