36 research outputs found
Field trial of three different Plasmodium vivax-detecting rapid diagnostic tests with and without evaporative cool box storage in Afghanistan
<p>Abstract</p> <p>Background</p> <p>Accurate parasitological diagnosis of malaria is essential for targeting treatment where more than one species coexist. In this study, three rapid diagnostic tests (RDTs) (AccessBio CareStart (CSPfPan), CareStart PfPv (CSPfPv) and Standard Diagnostics Bioline (SDBPfPv)) were evaluated for their ability to detect natural <it>Plasmodium vivax </it>infections in a basic clinic setting. The potential for locally made evaporative cooling boxes (ECB) to protect the tests from heat damage in high summer temperatures was also investigated.</p> <p>Methods</p> <p>Venous blood was drawn from <it>P. vivax </it>positive patients in Jalalabad, Afghanistan and tested against a panel of six RDTs. The panel comprised two of each test type; one group was stored at room temperature and the other in an ECB. RDT results were evaluated against a consensus gold standard based on two double-read reference slides and PCR. The sensitivity, specificity and a measure of global performance for each test were determined and stratified by parasitaemia level and storage condition.</p> <p>Results</p> <p>In total, 306 patients were recruited, of which 284 were positive for <it>P. vivax</it>, one for <it>Plasmodium malariae </it>and none for <it>Plasmodium falciparum</it>; 21 were negative. All three RDTs were specific for malaria. The sensitivity and global performance index for each test were as follows: CSPfPan [98.6%, 95.1%], CSPfPv [91.9%, 90.5%] and SDBPfPv [96.5%, 82.9%], respectively. CSPfPv was 16% less sensitive to a parasitaemia below 5,000/μL. Room temperature storage of SDBPfPv led to a high proportion of invalid results (17%), which reduced to 10% in the ECB. Throughout the testing period, the ECB maintained ~8°C reduction over ambient temperatures and never exceeded 30°C.</p> <p>Conclusions</p> <p>Of the three RDTs, the CSPfPan test was the most consistent and reliable, rendering it appropriate for this <it>P. vivax </it>predominant region. The CSPfPv test proved unsuitable owing to its reduced sensitivity at a parasitaemia below 5,000/μL (affecting 43% of study samples). Although the SDBPfPv device was more sensitive than the CSPfPv test, its invalid rate was unacceptably high. ECB storage reduced the proportion of invalid results for the SDBPfPv test, but surprisingly had no impact on RDT sensitivity at low parasitaemia.</p
Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.
Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development
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Relationship between primary Gleason pattern on needle biopsy and clinicopathologic outcomes among men with Gleason score 7 adenocarcinoma of the prostate
To examine the relationship among needle biopsy primary grade, prostatectomy grade, and postprostatectomy biochemical recurrence among men with Gleason score 7 disease.
We identified 320 men with Gleason score 7 tumors on prostate biopsy treated with radical prostatectomy between 1991 and 2001 by a single surgeon. None of these patients had received neoadjuvant or adjuvant hormonal therapy or radiotherapy. The chi-square test and Kaplan-Meier method were used to evaluate the correlation among biopsy Gleason score, prostatectomy Gleason score, and biochemical recurrence.
A total of 252 (79%) and 68 (21%) men had primary Gleason pattern 3 and 4 identified on needle biopsy, respectively. Of the patients with Gleason pattern 3 + 4 tumors on biopsy, 24% were upgraded to primary pattern 4 or more on final pathologic analysis. Of the patients with Gleason pattern 4 + 3 tumors on biopsy, 47% were downgraded to primary pattern 3 or less on final pathologic analysis. The actuarial risk of biochemical prostate-specific antigen recurrence was significantly lower among patients with Gleason pattern 4 + 3 on biopsy, if the prostatectomy Gleason score was downgraded to 3 + 4 or less (P = 0.03).
Approximately 47% of men with a diagnosis of Gleason pattern 4 + 3 on needle biopsy are downgraded at radical prostatectomy and will have biochemical prostate-specific antigen recurrence-free outcomes similar to patients originally diagnosed with Gleason pattern 3 + 4 adenocarcinoma. This group of patients may benefit from definitive treatment such as radical prostatectomy for management of their disease
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667: Pathological and Biochemical Outcomes after Radical Prostatectomy for Men with a Biopsy Gleason Score of 8 to 10
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Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative gleason sum of 8 to 10
Clinical Validation of an Epigenetic Assay to Predict Negative Histopathological Results in Repeat Prostate Biopsies
PURPOSE: The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. MATERIALS AND METHODS: We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation specific polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. RESULTS: The epigenetic assay resulted in a negative predictive value of 88% (95% CI 85–91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60–4.51). CONCLUSIONS: The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88% negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies