Primary retroperitoneal germ cell tumours: excision via a thoracoabdominal extraperitoneal approach

BACKGROUND: Primary retroperitoneal germ cell tumours usually present as a large abdominal mass in young men. The testes are normal on examination and ultrasonography but there are usually raised serum levels of human chorionic gonadotrophin and/or alpha-fetoprotein. METHODS: Fourteen men (median age 33 years) with primary retroperitoneal germ cell tumours were treated by chemotherapy followed by surgical resection of the primary tumour and metastases via a thoracoabdominal extraperitoneal approach. RESULTS: There was minimal morbidity. The survival rate was 13 of 14 and the disease-free survival rate was 11 of 14 after a median follow-up of 15 months. CONCLUSION: The thoracoabdominal extraperitoneal approach for the removal of retroperitoneal germ cell tumours and their metastases after chemotherapy improves tumour clearance, morbidity and recovery time compared with the transperitoneal anterior approach.     

Patterns of prehistoric human mobility in polynesia indicated by mtDNA from the Pacific rat

Human settlement of Polynesia was a major event in world prehistory. Despite the vastness of the distances covered, research suggests that prehistoric Polynesian populations maintained spheres of continuing interaction for at least some period of time in some regions. A low level of genetic variation in ancestral Polynesian populations, genetic admixture (both prehistoric and post-European contact), and severe population crashes resulting from introduction of European diseases make it difficult to trace prehistoric human mobility in the region by using only human genetic and morphological markers. We focus instead on an animal that accompanied the ancestral Polynesians on their voyages. DNA phylogenies derived from mitochondrial control-region sequences of Pacific rats (Rattus exulans) from east Polynesia are presented. A range of specific hypotheses regarding the degree of interaction within Polynesia are tested. These include the issues of multiple contacts between central east Polynesia and the geographically distinct archipelagos of New Zealand and Hawaii. Results are inconsistent with models of Pacific settlement involving substantial isolation after colonization and confirm the value of genetic studies on commensal species for elucidating the history of human settlement.     

Dose uniformity of ferromagnetic seed implants in tissue with discrete vasculature: a numerical study on the impact of seed characteristics and implantation techniques

There is evidence of a two-way interaction between gastric acid secretion and H. pylori-associated gastritis. Gastric acid secretion influences the density of H. pylori colonisation, its distribution within the stomach and the severity of the mucosal inflammatory response to the infection. In addition, H. pylori gastritis alters gastric acid secretion. In subjects with a predominant antral gastritis, it increases acid secretion predisposing to duodenal ulcer, whereas in others with predominant body gastritis, acid secretion is impaired and the subjects have an increased risk of gastric cancer. The two-way interaction between acid secretion and H. pylori gastritis is observed when H. pylori-positive subjects are treated with proton pump inhibitor agents. The inhibition of acid secretion induces a body gastritis and this inflammation of the body mucosa inhibits acid secretion thus augmenting the anti-secretory effect of the drug. In this article, we discuss the interaction between gastric acid secretion and H. pylori gastritis and its importance in determining disease outcome.     

Maternal and fetal plasma concentrations of endothelin, lipidhydroperoxides, glutathione peroxidase and fibronectin in relation to abnormal umbilical artery velocimetry

The topoisomerase II alpha (topo II alpha) enzyme is the target for several chemotherapeutic agents, including etoposide, teniposide, mitoxantrone, and doxorubicin (topo II poisons). The enzyme also is a marker of cell proliferation. Most cases of Hodgkin's disease (HD) are responsive to combination chemotherapy regimes that include topo II poisons such as doxorubicin. Immunoperoxidase methods for detection of the topo II alpha isoenzyme are now available for use in formalin-fixed, paraffin-embedded tissues, which may provide information about the proliferative capacity and possible sensitivity of tumors to drugs that target topo II. We used a specific antibody to analyze subsets of HD for topo II alpha staining patterns. Formalin-fixed blocks from 49 cases of HD, including 20 nodular sclerosis (NS), 14 mixed-cellularity (MC), and 15 lymphocyte-predominant (LP) subtypes, were analyzed by dual staining for topo II in combination with monoclonal antibodies against Reed-Sternberg (RS) cells consisting of CD15 for the NS and MC subtypes and CD20 for LP lymphocytic and histiocytic (L & H) cells. The number of morphologically appropriate cells coexpressing the RS or L & H marker and topo II alpha was quantitated. Positive nuclear staining for topo II alpha in RS or L & H cells was seen in 100% of cases, irrespective of subtype. Coexpression of CD15 and topo II alpha was seen in 58.4% of the RS cells or mononuclear variants in NSHD cases and 68.4% in MCHD cases. No significant difference in the percentage of neoplastic cells expressing topo II alpha was found between NS and MC subtypes. Cases of LPHD showed coexpression of CD20 and topo II alpha in 84.4% of the L & H cells, a significant increase over the level of tumor cell coexpression seen in NSHD and MCHD (P < .001). Only one case was found to have a low (< 25% of tumor cell coexpression) level of topo II alpha expression. Immunohistochemical detection of a high level of topo II alpha expression in HD, irrespective of subtype, suggests a molecular explanation for the excellent response of most HD to standard combination chemotherapy, which can include topo II poisons. The LP subtype has a higher expression of topo II alpha in the neoplastic cell population than do NS or MC subtypes, perhaps indicating increased sensitivity of these tumors to topo II poisons. It may be possible to identify subsets of HD that are more or less sensitive to conventional chemotherapeutic regimes, which would help in the selection of appropriate treatment.     

A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements

The control of mRNA stability is crucial to the regulation of cytokine expression. We describe here a novel, potent destabilizing element found in the 3' untranslated region of granulocyte colony-stimulating factor mRNA. This element, which appears to require at least one stem-loop structure, we term the stem-loop destabilizing element (SLDE). Functionally equivalent elements appear to also exist in the interleukin 2 and interleukin 6 mRNAs. The SLDE is functionally distinct from the A+U-rich elements, which are also present in these and other cytokine mRNAs, because it destabilizes a chimeric mRNA in a tumor cell line in which A+U-rich elements do not function. In addition, the effect of the SLDE is insensitive to calcium ionophore and is therefore regulated independently of A+U destabilizing elements. The existence of two distinct mRNA-destabilizing elements provides an additional mechanism for the differential regulation of cytokine expression.     

Assessment of uterine arterial notching as a screening test for adverse pregnancy outcome

Recombinant papillomavirus-like particles have recently been shown to be highly effective for the prevention of papillomavirus infections and associated tumors, and a virus-like particle-based vaccine against the most prevalent HPV causing genital infection in humans will be developed in the near future. Another use of these virus-like particles may lie in gene therapy and DNA immunization. We report here that human papillomavirus-like particles composed of the major capsid protein (L1) of HPV-16 are able to package unrelated plasmid DNA in vitro and then to deliver this foreign DNA to eukaryotic cells with the subsequent expression of the encoded gene. The results indicate higher gene transfer than with DNA alone or with liposome. Virus-like particles are a very promising vehicle for delivering genetic material into target cells. Moreover, the preparation of the gene transfer vehicle is relatively easy.