Epithelioid cellular chordoma of the sacrum: a potential diagnostic problem

We describe a sacral chordoma composed of solid nests of epithelioid cells. The tumor originated in the presacral area. Extensive clinical workup did not reveal any other lesion in the patient. In contrast to typical chordomas, this tumor contained only rare physaliferous cells, had no myxoid stroma, and was immunohistochemically unreactive with the antibody to S-100. The diagnosis of chordoma was supported by electron microscopy, which showed that the tumor cells contained numerous mitochondria surrounded by profiles of rough endoplasmic reticulum. The abundance of mitochondria, the narrow intercellular spaces, combined with a lack of glycogen, and a lack of extracellular myxoid material accounted for the epithelioid appearance of the tumor. We report this case to point out that the cellular chordomas can appear epithelioid in the sacrum and they may resemble metastatic squamous or transitional cell carcinomas.     

Molecular cytogenetic analysis of chromosomes 1 and 19 in glioma cell lines

Deletions of chromosome 1p and 19q arms are frequent genetic abnormalities in primary human gliomas and are especially common in oligodendrogliomas. However, the chromosome 1p and 19q status of many glioma cell lines has not been established. Using homozygosity mapping, fluorescence in situ hybridization (FISH), and comparative genomic hybridization to arrayed BAC (CGHa), we screened 17 glioma cell lines for chromosome 1 and 19 deletions. Sequence tagged site polymorphisms were used to evaluate the cell lines for regions of chromosome 1p and 19q homozygosity. Cell lines A172, U251, TP265, U118, SW1088, U87, SW1783, and D32 contained significant regions of 19q homozygosity. In addition, A172, U87, TP483, D37, U118, MO67, and TP265 contained significant regions of 1p homozygosity. FISH probes localized to 1p36.32 and 19q13.33 as well as CGHa were used to determine which cell lines had deletions of 1p and/or 19q. Cell lines A172, U87, TP483, TP265, H4, U251, and D37 were deleted for portions of 1p. CGHa and homozygosity mapping of these cell lines define a 700-kilobase (Kb) common deletion region that is encompassed by a larger deletion region previously mapped in sporadic gliomas. This common deletion region is localized at 1p36.31 and includes CHD5, a putative tumor suppressor gene. Cell line A172 was observed to have a deletion between 19q13.33 and 19q13.41, while U87 was observed to have a smaller deletion of 19q13.33. Cell lines A172 and U87 contain 1p and 19q deletions similar to those found in sporadic gliomas and will be useful cellular reagents for evaluating the function of putative 1p and 19q glioma tumor suppressor genes.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

Typing and subtyping of Clostridium difficile isolates by using multiple-locus variable-number tandem-repeat analysis

Using the genomic sequence of Clostridium difficile strain 630, we developed multiple-locus variable-number tandem-repeat analysis (MLVA) with automated fragment analysis and multicolored capillary electrophoresis as a typing method for C. difficile. All reference strains, representing 31 serogroups, 25 toxinotypes, and 7 known subtypes of PCR ribotype 001, could be discriminated from each other. Application of MLVA to 28 isolates from 7 outbreaks due to the emerging hypervirulent PCR ribotype 027-pulsed-field gel electrophoresis type NAP1 resulted in recognition of 13 clusters. Additionally, 29 toxin A-negative, toxin B-positive isolates belonging to PCR ribotype 017 from eight different countries revealed eight country-specific clusters. MLVA is a highly discriminatory genotyping method and a new tool for subtyping of newly emerging variants of C. difficile.     

A randomized comparison of medical abortion and surgical vacuum aspiration at 10-13 weeks gestation.

BACKGROUND: Since 1991, mifepristone in combination with a prostaglandin analogue has been licensed for termination of pregnancy in the UK at up to 9 weeks amenorrhoea, and since 1995, beyond 13 weeks. Surgical methods are used almost exclusively at 10-13 weeks amenorrhoea. METHODS: A patient-centred, partially randomized, controlled trial was carried out. Those who expressed a strong preference for either medical (n = 15) or surgical (n = 62) abortion were allocated to that method. The remainder agreed to be randomized. The medical method (n = 188) was mifepristone 200 mg followed by misoprostol up to 3 doses, and surgery (n = 180) was by vacuum aspiration under general anaesthesia. Outcome measures included efficacy rates, medical complications within 8 weeks of the procedure, patient preferences and acceptability. RESULTS: Among women who underwent medical abortion, 5.4% required a second procedure compared with 2.1% who had surgery, although this difference was not statistically significant. Side effects experienced were higher in women who underwent medical abortion compared with those who underwent surgery. There were no significant differences in the rates of major complications up to 8 weeks. Prior to termination, 80% of women had a preference for a method, with 72% preferring medical and 28% preferring surgical abortion. Following abortion, 70% of those who underwent medical termination and 79% who underwent surgery would opt for the same method in the future. CONCLUSION: Medical abortion is safe and effective at 10-13 weeks gestation and should be considered an option for those women who wish to avoid surgery and anaesthesia.     

Incidence,molecular epidemiology and clinical presentations of human metapneumovirus; assessment of its importance as a diagnostic screening target

BackgroundHuman metapneumovirus (HMPV) is a recently discovered human paramyxovirus associated with a spectrum of respiratory symptoms from the common cold to pneumonia and bronchiolitis.ObjectivesTo assess the clinical significance and epidemiology of HMPV, standardized comparison of frequencies of infection, age profiles and disease associations were made with other respiratory viruses in Scotland.Study design7091 respiratory samples collected in Scotland between 1 July 2006 and 30 June 2008 from 4282 individuals were screened by multiplex RT-PCR for respiratory syncytial virus (HRSV), adenovirus (AdV), parainfluenzaviruses 1–3 (PIV-1, -2 and -3), influenza A and B and by nested RT-PCR for HMPV.ResultsHMPV was the fifth most prevalent virus (2.0% of samples), found predominantly in young children in winter months. In the 2006–2007 respiratory season, 70% of HMPV isolates were genotype A, but a switch to predominantly type B infections occurred next winter. For samples with information on clinical presentations, 26% of HMPV infections were from subjects with lower respiratory tract presentations, lower than recorded for HRSV, but similar to adenovirus, parainfluenza viruses and influenza viruses A and B. Around 13% of HMPV infections were associated with upper respiratory tract symptoms or disease, comparable with other respiratory virus infections.ConclusionsNumerically and through its association with respiratory disease, HMPV represents a diagnostically significant target that should be included in PCR-based routine screening of respiratory samples. Understanding the biological basis of observed rapid turnover of HMPV variants, including the observed HMPV genotype change between respiratory seasons requires further longitudinal studies.     

How effective is patient-controlled analgesia? A randomized comparison of two protocols for pain relief during oocyte recovery

Although the conventional method of pain relief during outpatient oocyte recovery involves physician-administered drugs, patient- controlled analgesia (PCA) offers an alternative technique with the potential to give women more control over peroperative analgesia. We conducted a prospective randomized study to compare the effect of fentanyl administered either through a PCA delivery system or by a physician. Thirty-nine women were randomized to PCA during egg collection while 42 were allocated to receive intermittent doses administered by a physician. Pain was evaluated by means of a 100 mm linear analogue scale. The mean (SD) pain score in the PCA group was 38.5 (19.8) while in the other group it was 46.1 (21.3) (P = 0.1). In the PCA group, 64% of women felt very satisfied with their analgesia as compared with 57% in the non-PCA group (P = 0.6). Among the PCA users, 39% of demands were successful. Significantly more fentanyl (97.5 microg) was used in the PCA group than in the other group (84.6 microg) (P = 0.03). Though intraoperative PCA with fentanyl is an effective alternative to physician-administered techniques, many women still feel the need for more analgesia during the procedure.      

Effects of retinol and hepatocyte-conditioned medium on cultured rat hepatic stellate cells

Hepatic stellate cells (HSC) become activated in liver injury, proliferating and secreting components of connective tissue. Activated HSC lose their native retinol and fat storing capacity. Signals from hepatocytes and/or Kupffer cells injured (eg, by iron overload) may contribute to the so-called activated HSC phenotype. Primary rat HSC cultures were treated with retinol to determine if this could produce a quiescent cell for controlled in vitro studies of activation. Retinol resulted in suppressed DNA synthesis in proliferating HSC, a reorganization of actin filaments, and a return of fat storage. However, it did not suppress the expression of fibrogenic genes such as those for collagens type I and IV, and TGF-beta1. Furthermore, retinol-treated cells may increase expression of these genes in response to conditioned medium from hepatocyte cultures. The effect is especially apparent for collagen type I mRNA, and with conditioned medium from iron-loaded hepatocytes. Thus, retinol may be a two-edged sword in iron overload, potentially suppressing HSC proliferation on the one hand, and sensitizing a fibrogenic pattern of gene expression on the other. Factors influencing this balance merit further study.