Review of software for space-time disease surveillance

March 11th, 2010
Disease surveillance makes use of information technology at almost every stage of the process, from data collection and collation, through to analysis and dissemination. Automated data collection systems enable near-real time analysis of incoming data. This context places a heavy burden on software used for space-time surveillance. In this paper, we review software programs capable of space-time disease surveillance analysis, and outline some of their salient features, shortcomings, and usability. Programs with space-time methods were selected for inclusion, limiting our review to ClusterSeer, SaTScan, GeoSurveillance and the Surveillance package for R. We structure the review around stages of analysis: preprocessing, analysis, technical issues, and output. Simulated data were used to review each of the software packages. SaTScan was found to be the best equipped package for use in an automated surveillance system. ClusterSeer is more suited to data exploration, and learning about the different methods of statistical surveillance.

Low prevalence of Human Papillomavirus in oral cavity carcinomas

March 11th, 2010
Background: Increasing evidence shows that Human Papillomavirus (HPV) is preferentially associated with some head and neck squamous cell carcinomas (HNSCCs), with variable infection rates reported. Methods: We assessed HPV involvement in HNSCC using the Roche Linear Array HPV Genotyping Test, which can detect 37 different HPV types. We examined the prevalence of HPV infection in 92 HNSCCs (oropharynx, oral cavity, and other HNSCC sites). Results: HPV was frequently detected in oropharyngeal cancers (OPCs) (16/22, 73%), but was uncommon in oral cavity cancers (2/53, 4%), and in other HNSCC subsites (1/17, 6%). HPV positive tumors were associated with patients that were 40-60 years old (p=0.02), and node positive (p=<0.0001). HPV 16 was the most prevalent type, but other types detected included 6, 18, 33, 35, 45, and 52/58. Conclusion: Our results show that in contrast to oropharyngeal cancers, oral cancers and other HNSCCs infrequently harbor HPV.

Chronic presentation of Boerhaave’s syndrome

March 11th, 2010
Background: Spontaneous rupture of the esophagus (Boerhaave's syndrome) is a rare, well-defined clinical syndrome caused by a longitudinal perforation of the esophagus. It is a life-threatening condition that necessitates rapid diagnosis and treatment. Patients typically present acutely with a history of vomiting followed by chest or abdominal pain. However, the diagnosis may be difficult or missed when patients present with chronic symptoms that mimic other conditions.Case PresentationIn this report, we present a unique case of Boerhaave's syndrome in a 53-year-old male patient. In contrast to the more common acute presentation, our patient developed non-specific symptoms in association with an intrathoracic cyst. In this report, we will also review the usual presenting signs, symptoms, and treatment of Boerhaave's syndrome. Conclusion: Our emphasis in this paper will be on the importance of recognizing and diagnosing Boerhaave's syndrome in an acute as well as a chronic state.

Development of a new ultra sensitive real-time PCR assay (ultra sensitive RTQ-PCR) for the quantification of HBV-DNA

March 11th, 2010
Background: Improved sensitivity of HBV-DNA tests is of critical importance for the management of HBV infection. Our aim was to develop and assess a new ultra sensitive in-house real-time PCR assay for HBV-DNA quantification (ultra sensitive RTQ-PCR). Results: Previously used HBV-DNA standards were calibrated against the WHO 1st International Standard for HBV-DNA (OptiQuant(R) HBV-DNA Quantification Panel, Accrometrix Europe B.V.). The 95% and 50% HBV-DNA detection end-point of the assay were 22.2 and 8.4 IU/mL. According to the calibration results, 1 IU/mL equals 2.8 copies/mL. Importantly the clinical performance of the ultra sensitive real-time PCR was tested similar (67%) to the Procleix Ultrio discriminatory HBV test (dHBV) (70%) in low-titer samples from patients with occult Hepatitis B. Finally, in the comparison of ultra sensitive RTQ-PCR with the commercially available COBAS TaqMan HBV Test, the in-house assay identified 94.7% of the 94 specimens as positive versus 90.4% identified by TaqMan, while the quantitative results that were positive by both assay were strongly correlated (r=0.979). Conclusions: We report a new ultra sensitive real time PCR molecular beacon based assay with remarkable analytical and clinical sensitivity, calibrated against the WHO 1st International standard.

A new Purkinje cell antibody (anti-Ca) associated with subacute cerebellar ataxia: immunological characterization

March 11th, 2010
We report on a newly discovered serum and cerebrospinal fluid (CSF) reactivity to Purkinje cells (PCs) associated with subacute inflammatory cerebellar ataxia. The patient, a previously healthy 33-year-old lady, presented with severe limb and gait ataxia, dysarthria, and diplopia two weeks after she had recovered from a common cold. Immunohistochemical studies on mouse, rat, and monkey brain sections revealed binding of a high-titer (up to 1:10,000) IgG antibody to the cerebellar molecular layer, Purkinje cell (PC) layer, and white matter. The antibody is highly specific for PCs and binds to the cytoplasm as well as to the inner side of the membrane of PC somata, dendrites and axons. It is produced by B cell clones within the CNS, belongs to the IgG1 subclass, and activates complement in vitro. Western blotting of primate cerebellum extract revealed binding of CSF and serum IgG to an 80-97 kDa protein. Extensive control studies were performed to rule out a broad panel of previously described paraneoplastic and non-paraneoplastic antibodies known to be associated with cerebellar ataxia. Screening of more than 9000 human full length proteins by means of a protein array and additional confirmatory experiments revealed Rho GTPase activating protein 26 (ARHGAP26, GRAF, oligophrenin-1-like protein) as the target antigen. Preadsorption of the patient's serum with human ARHGAP26 but not preadsorption with other proteins resulted in complete loss of PC staining. Our findings suggest a role of autoimmunity against ARHGAP26 in the pathogenesis of subacute inflammatory cerebellar ataxia, and extend the panel of diagnostic markers for this devastating disease.