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DNA Testing (dna + testing)
Kinds of DNA Testing Selected AbstractsEditorial: DNA Testing for Inherited Diseases in AnimalsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2004Julie A.L. Cavanagh BScAgr No abstract is available for this article. [source] HPV detection rate in discordant Pap tests between cytotechnologists and pathologistsDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2009David C. Chhieng M.D. Abstract When a Pap test is referred for pathologist review, it is accompanied by the cytotechnologist's provisional interpretation. Discordant interpretations between pathologists and cytotechnologists are sometimes noted. The objective is to correlate HPV detection rate with both estimated false-negative fraction (EFNF) and ASC to SIL ratio among discordant ASC cases. ThinPrep Pap tests in which the cytotechnologists' provisional interpretations were up- or down-graded by pathologists to ASC were retrieved between January and December 2006. HPV DNA testing was performed using hybrid capture technique. EFNFs and ASC to SIL ratio were estimated for cytotechnologists and pathologists, respectively. Overall, the EFNF ratio was 3.4% and the high-risk HPV DNA detection rates in cases that were "over-" or "under-" interpreted by technologists were 0.71 and 0.40, respectively. The overall ASC to SIL ratio was 1.41 and the high-risk HPV DNA detection rates in cases that were upgraded or downgraded to ASC were 0.40 and 0.71, respectively. In conclusion, our ASC to SIL ratios and EFNF were within acceptable range. We did not observe any association between ASC to SIL ratio and HPV detection rate in cases that were upgraded or downgraded to ASC by pathologists or between EFNF ratio and HPV detection rate in cases that were "over-interpreted" (or "under-interpreted") by cytotechnologists. The HPV detection rates for ASC cases that were originally "over-interpreted" by cytotechnologists were comparable to the HPV detection rates for LSIL, whereas those that were underinterpreted were comparable to the HPV detection rate for ASC. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Cytology of metastatic cervical squamous cell carcinoma in pleural fluid: Report of a case confirmed by human papillomavirus typingDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2009Roberto G. Gamez M.D. Abstract Cervical squamous cell carcinomas are rarely the cause of malignant effusions. Their identification can be relatively easy when keratinizing atypical squamous cells are present, but may be very difficult when only nonkeratinizing malignant cells are present. We present the case of a 47-year-old woman who presented with a large left pleural effusion after having recently completed chemoradiation therapy for stage IIB cervical squamous cell carcinoma. Cytologic examination of the fluid showed a uniform population of single atypical cells with finely vacuolated cytoplasm, ectoendoplasmic demarcation, cell-in-cell arrangements, and short rows of cells with intervening "windows," all features reminiscent of mesothelial cells. No keratinization or three-dimensional cell clusters were identified. A panel of immunohistochemical stains was performed on the cell block material, and the atypical cells were positive for cytokeratin 5/6, p63, and p16 but not for cytokeratin 7, calretinin, WT1, or Ber-EP4 or TTF1. These findings were consistent with metastatic squamous cell carcinoma. HPV DNA determination and typing by PCR confirmed the presence of HPV16 in an aliquot of pleural fluid. This is to our knowledge the first reported case of pleural fluid involved by metastatic squamous cell carcinoma where HPV DNA testing was used to confirm the origin of the metastasis. Despite its rarity, metastatic nonkeratinizing squamous cell carcinoma should be considered when a single cell population of large atypical cells is found in effusions. Immunoperoxidase stains and HPV testing can be performed to establish the diagnosis and confirm the origin from a cervical primary. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] ASC-US and high-risk HPV testing: Performance in daily clinical practiceDIAGNOSTIC CYTOPATHOLOGY, Issue 11 2006Suzanne M. Selvaggi M.D.Article first published online: 13 OCT 200 Abstract Data are beginning to accrue on high-risk HPV DNA testing in patients with ASC-US on cervical cytology. We report on our experience at the University of Wisconsin Hospital and Clinics. From February 2002 through December 31, 2005 (3 yr, 11 mo), the cytopathology laboratory processed 49,599 Pap Tests, of which 1,792 (3.6%) were diagnosed as ASC-US. Six hundred and seventy two (37.5%) of these cases were processed for high-risk HPV genotypes using the Digene Hybrid® Capture II method. Of these cases, 266 (39.6%) were positive for high-risk HPV genotypes, 11 (1.6%) were equivocal, and 395 (58.8%) were negative. Biopsy follow-up was available for 127 (47.7%) of the 266 cases, of which 66 (52%) were negative, 46 (36.2%) showed CIN I, 9 (7.1%) were CIN II, and 6 (4.7%) were CIN III. Of the remaining 139 (52.3%) cases, 86 (62%) had follow-up Pap Tests, of which 57 (66.3%) were negative, 15 (17.4%) were ASC-US, 12 (15%) were low-grade squamous intraepithelial lesions, and 2 (2.3%) were high-grade squamous intraepithelial lesions; 53 (38.1%) were lost to follow-up. In combination, 90 (42.25%) of the 213 cases with follow-up showed atypia or above after a diagnosis of ASC-US; of which 58 (64%) were low-grade lesions and 17 (19%) were high-grade lesions. Our laboratory's reported high-risk HPV positivity is comparable to recent reports in the literature on its use in daily clinical practice. In addition, cervical abnormalities were found in a significant proportion of the cases. Diagn. Cytopathol. 2006;34: 731,733. © 2006 Wiley-Liss, Inc. [source] Anal cytology: Is there a role for reflex HPV DNA testing?DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005A.E. Walts M.D. Abstract There is an increased incidence of anal squamous carcinoma and its precursor lesions (anal intraepithelial neoplasia [AIN]) among persons who engage in anal-receptive sex. Analogous to cervical cancer screening, anal Papanicplaou (Pap) smears currently are used to screen these high-risk populations. Human papilloma virus (HPV) has been implicated in anal carcinoma pathogenesis and this study was performed to assess the potential role of HPV DNA testing as an adjunct to anal cytology. We correlated cytological diagnoses and HPV DNA (Digene Hybrid Capture [HC II] assay) in anal specimens collected in SurePath liquid medium from 118 patients; 54.8% of cases diagnosed as atypical squamous cells of undetermined significance (ASC-US) and 87.8% diagnosed as low-grade squamous intraepithelial lesion (LSIL) or above tested positive for high- risk HPV DNA (B+). High-grade SIL (HSIL) was present in 31 of the 51 patients with follow-up. Although a cytological diagnosis of ASC-US or above was a reliable indicator for AIN, cytology frequently did not accurately predict the grade of SIL in subsequent biopsy. Our findings suggest that reflex HPV DNA testing would be helpful in triaging patients diagnosed with ASC-US. However, patients diagnosed with LSIL or above should go directly to ansocopic biopsy. Diagn. Cytopathol. 2005;33:152,156. © 2005 Wiley-Liss, Inc. [source] Pseudomigraine With Lymphocytic Pleocytosis: A Calcium Channelopathy?HEADACHE, Issue 8 2003Clinical Description of 10 Cases, Genetic Analysis of the Familial Hemiplegic Migraine Gene CACNA1A Objective.,To report the clinical findings of 10 patients diagnosed with pseudomigraine with lymphocytic pleocytosis and the results of mutational analysis of the CACNA1A gene in 8 of these patients. Background.,Pseudomigraine with lymphocytic pleocytosis, also referred to as headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL), is characterized by episodic transient neurologic dysfunction associated with moderate to severe headache and cerebrospinal fluid lymphocytic pleocytosis. Episodes are recurrent and the condition is self-limiting. The etiology of this sporadic condition remains unknown, but the episodic nature and its ability to be triggered by angiography is somewhat reminiscent of the phenotypic features of familial hemiplegic migraine, a condition caused by mutations in the CACNA1A gene. Design/Methods.,Utilizing retrospective chart review, we describe the clinical features of pseudomigraine with lymphocytic pleocytosis in 10 patients. Whole blood was taken from 8 patients (2 were lost to follow-up) and used for DNA testing. The CACNA1A gene was screened for mutations using heteroduplex analysis and direct DNA sequencing. Results.,Clinical features of pseudomigraine with lymphocytic pleocytosis included transient episodes of weakness, sensory and visual symptoms, aphasia, and confusion lasting minutes up to 4 hours. Sensory symptoms, typically affecting the face and arm, were the most common presentation. Localization of symptoms did not conform to vascular territories. Headache was typically throbbing and most often bilateral. Genetic analysis did not identify any mutations in the CACNA1A gene. Conclusions.,Similarities between familial hemiplegic migraine and pseudomigraine with lymphocytic pleocytosis include recurrent headache with reversible neurologic deficit, cerebrospinal fluid lymphocytic pleocytosis, and triggers such as angiography. Even so, heteroduplex analysis and DNA sequencing failed to identify any sporadic mutations or shared polymorphisms in the exons or the intron/exon boundaries of the CACNA1A gene. These results do not support a role of the CACNA1A gene in the etiology of pseudomigraine with lymphocytic pleocytosis. [source] Occult hepatitis B virus infection in a North American adult hemodialysis patient populationHEPATOLOGY, Issue 5 2004Gerald Y. Minuk Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units. A possible contributing factor is the presence of occult HBV (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty-one adult hemodialysis patients were screened for occult HBV. HBV DNA testing was performed by real-time polymerase chain reaction (PCR) with 2 independent primer sets (core promoter and surface). Two (0.8%) of the 241 patients were HBsAg positive. Of the remaining 239 HBsAg-negative patients, 9 (3.8%) were HBV DNA positive. Viral loads in these individuals were low (102 -104 viral copies/mL). Seven of the 9 (78%) were nt 587 mutation (sG145R mutant) positive. Demographic, biochemical, and HBV serological testing did not help to identify those with occult HBV. In conclusion, the prevalence of occult HBV in adult hemodialysis patients in this North American urban center is approximately 4 to 5 times higher than standard HBsAg testing would suggest. The majority of these infections are associated with low viral loads and a high prevalence of the sG145R mutant. Finally, the demographic, biochemical, and/or serological features of HBV DNA,positive subjects do not distinguish these individuals from the remainder of the dialysis patient population. (HEPATOLOGY 2004; 40:1072,1077.) [source] The health and economic effects of HPV DNA screening in The Netherlands,INTERNATIONAL JOURNAL OF CANCER, Issue 9 2010Johannes Berkhof Abstract We studied the health and economic effects of human papillomavirus (HPV) DNA testing in cervical screening using a simulation model. The key data source was a Dutch longitudinal screening trial. We compared cytological testing with repeat cytology (for borderline/mildly abnormal smears) to HPV testing with cytology triage (for HPV-positive smears), combination testing (combined HPV and cytology) and cytological testing with HPV triage (for borderline/mildly abnormal smears). We varied the screening interval from 5 to 10 years. The main outcome measures were the number of cervical cancer cases, the number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The base-case estimates were accompanied with ranges across 118 calibrated parameter settings (calibration criteria: cervical intraepithelial neoplasia 2/3, cancer and mortality rates). In comparison to 5-yearly cytology, 5-yearly HPV testing with cytology triage gave a reduction in the number of cancer cases of 23% (range, 9,27%). The reduction was 26% (range, 10,29%) for combination testing and 3% (range, ,1 to 8%) for cytology with HPV triage. For strategies with primary HPV testing, the model also estimated a reduction in cancer cases when the screening interval was extended to 7.5 years. Five-yearly cytology with HPV triage and 5 to 7.5-yearly HPV testing with cytology triage were cost effective for the base-case settings and the majority of calibrated parameter settings (ICER below Dutch willingness-to-pay threshold of ,20,000/QALY). Our model indicates that HPV testing with cytology triage is likely to be cost effective. An extension of the screening interval may be considered to control costs. [source] Cervical cancer screening program integrating Pap smear and HPV DNA testing: A population-based studyINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Angel Chao Abstract We conducted a population-based cohort study to evaluate the complementary value of HPV testing to Papanicolaou (Pap) smear and the prevalence and genotype distribution of HPV in Taiwan. In this report, we described the design of the whole study and analyzed the cross-sectional results. Female residents (age , 30 years) of Taoyuan, Taiwan were invited. After signing informed consent, every participant had a Pap smear and a HPV testing. Patients with Pap , atypical squamous cell of undetermined significance (Group I) or those with HPV-positive but normal cytology (Group II) were referred for a colposcopic examination. A total of 10,014 women were eligible. The overall HPV prevalence was 10.8% (95% confidence interval 10.5%,11.4%) in the study population. A total of 37 types of HPV were identified and the leading three were HPV-52, -18 and -58. There was a significant positive correlation of HPV prevalence with older age, postmenopausal status, current-user of oral contraceptives and never-user of hormone replacement therapy. Past users of oral contraceptives and never users of Pap were associated with higher risk of abnormal Pap, while age 40,49 strata had lower risk. Fifty-nine cases of cervical intraepithelial neoplasia (CIN) 2 from Group I and additional 11 from Group II were identified. The improvement of sensitivity with additional HPV testing was 15.3%. Besides, no specific subgroup was found to most benefit from the combined strategy. The value of adding HPV test to conventional Pap smear has to be evaluated after longer-term follow-up of this population-based cohort. © 2008 Wiley-Liss, Inc. [source] Cost-effectiveness of primary cytology and HPV DNA cervical screeningINTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Peter Bistoletti Abstract Because cost-effectiveness of different cervical cytology screening strategies with and without human papillomavirus (HPV) DNA testing is unclear, we used a Markov model to estimate life expectancy and health care cost per woman during the remaining lifetime for 4 screening strategies: (i) cervical cytology screening at age 32, 35, 38, 41, 44, 47, 50, 55 and 60, (ii) same strategy with addition of testing for HPV DNA persistence at age 32, (iii) screening with combined cytology and testing for HPV DNA persistence at age 32, 41 and 50, iv) no screening. Input data were derived from population-based screening registries, health-service costs and from a population-based HPV screening trial. Impact of parameter uncertainty was addressed using probabilistic multivariate sensitivity analysis. Cytology screening between 32 and 60 years of age in 3,5 year intervals increased life expectancy and life-time costs were reduced from 533 to 248 US Dollars per woman compared to no screening. Addition of HPV DNA testing, at age 32 increased costs from 248 to 284 US Dollars without benefit on life expectancy. Screening with both cytology and HPV DNA testing, at ages 32, 41 and 50 reduced costs from 248 to 210 US Dollars with slightly increased life expectancy. In conclusion, population-based, organized cervical cytology screening between ages 32 to 60 is highly cost-efficient for cervical cancer prevention. If screening intervals are increased to at least 9 years, combined cytology and HPV DNA screening appeared to be still more effective and less costly. © 2007 Wiley-Liss, Inc. [source] Faecal screening of colorectal cancerINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2008A. Loganayagam Summary Aims:, Screening and prevention of colorectal cancer (CRC) is a public health priority. Recent progress in understanding the biology of CRC has lead to possible new approaches to screening. In particular, assay of faecal molecular markers represents a promising non-invasive approach to screening, with improved safety, accuracy and patient compliance. Methods:, MEDLINE/PubMed searches were used to identify key articles relating to faecal-based screening with secondary review of cited publications. Results:, Faecal markers of CRC can be broadly divided into DNA based and non-DNA based. Conclusions:, Faecal occult blood testing for CRC screening has been advocated for decades for its non-invasiveness and low cost. It has exhibited a 15,33% decrease in mortality, despite drawbacks with sensitivity and compliance. Other non-DNA markers have the adequate sensitivity for inflammatory lesions but do not have the required specificity for screening average-risk populations. Faecal DNA testing has the potential to enhance the performance characteristics of stool testing. Because of molecular heterogeneity of cancer, no single DNA marker has yielded adequate sensitivity. Analysis of several combinations of markers in studies have produced high detection rates of both CRC and advanced adenomas in selected patient groups. However, the currently available markers, both non-DNA and DNA, have not yet been validated in large-scale studies screening average -risk population nor have they so far shown the necessary sensitivity and specificity required for large-scale screening programmes. Another major drawback with the DNA-based markers is the cost-effectiveness. Issues regarding implementation and compliance remain unanswered. These critical problems have to be rectified before these techniques can be recommended for large-scale CRC screening. [source] Multiple endocrine neoplasia type 2BINTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2001Seiji Nakata Abstract We report a case of multiple endocrine neoplasia type 2B (MEN 2B) in a 30-year-old woman. There was no family history of MEN 2B in her family. DNA testing was carried out and a point mutation was found in exon 16, codon 918 (ATG to ACG) in the RET proto-oncogene. The woman died of medullary thyroid carcinoma, 13 years after a total thyroidectomy. [source] Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish WomenJOURNAL OF MEDICAL VIROLOGY, Issue 4 2002Ola Forslund Abstract Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32,38 years were analyzed using a general HPV primer (GP5+/6+) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2,7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy. J. Med. Virol. 66:535,541, 2002. © 2002 Wiley-Liss, Inc. [source] A Review of the Evidence Comparing the Human Papillomavirus Vaccine Versus Condoms in the Prevention of Human Papillomavirus InfectionsJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 3 2008Shelley Miksis ABSTRACT Objective:, To examine the evidence related to the efficacy of condom use versus the human papillomavirus vaccine in the prevention of human papillomavirus infections. Data sources:, Cochrane, CINHAL, PubMed, and Clinical Evidence. Various combinations of the keywords HPV, vaccine, and condoms were used for the search. Study selection:, Randomized, double-blinded placebo-controlled trials were reviewed for evaluation of the human papillomavirus vaccine. Several longitudinal studies and a meta-analysis were used for review of condom efficacy related to human papillomavirus transmission. Data extraction and synthesis:, Studies evaluating the use of either condoms or the human papillomavirus vaccine and its impact on human papillomavirus transmission rates, detected through either human papillomavirus DNA testing or clinical disease. Conclusions:, The evidence indicates that the greatest degree of protection from specific types of human papillomavirus infection is provided by the vaccine. However, the use of condoms in addition to the human papillomavirus vaccine provides the greatest protection from the untoward effects of human papillomavirus infection and may also provide protection against human papillomavirus types not in the vaccine and other sexually transmitted infections. [source] As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasiaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2008M. PAREKH Summary Background, Colorectal cancer screening and treatment are rapidly evolving. Aims, To reappraise stool-based colorectal cancer screening in light of changing test performance characteristics, lower test cost and increasing colorectal cancer care costs. Methods, Using a Markov model, we compared faecal DNA testing every 3 years, annual faecal occult blood testing or immunochemical testing, and colonoscopy every 10 years. Results, In the base case, faecal occult blood testing and faecal immunochemical testing gained life-years/person and cost less than no screening. Faecal DNA testing version 1.1 at $300 (the current PreGen Plus test) gained 5323 life-years/100 000 persons at $16 900/life-year gained and faecal DNA testing version 2 (enhanced test) gained 5795 life-years/100 000 persons at $15 700/life-year gained vs. no screening. In the base case and most sensitivity analyses, faecal occult blood testing and faecal immunochemical testing were preferred to faecal DNA testing. Faecal DNA testing version 2 cost $100 000/life-year gained vs. faecal immunochemical testing when per-cycle adherence with faecal immunochemical testing was 22%. Faecal immunochemical testing with excellent adherence was superior to colonoscopy every 10 years. Conclusions, As novel biological therapies increase colorectal cancer treatment costs, faecal occult blood testing and faecal immunochemical testing could become cost-saving. The cost-effectiveness of faecal DNA testing compared with no screening has improved, but faecal occult blood testing and faecal immunochemical testing are preferred to faecal DNA testing when patient adherence is high. Faecal immunochemical testing may be comparable to colonoscopy every 10 years in persons adhering to yearly testing. [source] Photodynamic therapy of cervical intraepithelial neoplasia with hexaminolevulinate,LASERS IN SURGERY AND MEDICINE, Issue 9 2008Philipp Soergel MD Abstract Background and Objective CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries. Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non-invasive alternative with minimal side effects. This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection. Study Design/Materials and Methods Twenty four patients with a CIN 2 or 3 or a persistent CIN 1 and a positive high-risk HPV-DNA test were included. Each patient had gynaecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Ten milliliters of HAL-thermogel (10 mM) were topically applied to the cervix for 3,5 hours, followed by 1,000 seconds of illumination of both ecto- and endocervical canal with red coherent light (wave length 633 nm) using a PDT laser and a special light catheter. Follow-up examinations were carried out after 3 (cytology, colposcopy, HPV DNA testing, and if needed re-PDT) and 6 months. Results Seven, 10, and 7 patients had a CIN 1, 2, or 3, respectively. Treatment could be accomplished in all cases and no severe side effects were encountered. Fifteen out of the 24 patients had a complete response (15/24,=,63%) and a HPV remission 6 months after 1,3 treatments. The remission rates were 71%, 50%, and 71% for CIN 1, 2 and 3. Conclusion HAL PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects which can be easily performed on outpatient basis. Lesers Surg. Med. 40:611,615, 2008. © 2008 Wiley-Liss, Inc. [source] Ethics and Genetic Selection in Purebred DogsREPRODUCTION IN DOMESTIC ANIMALS, Issue 1 2003VN Meyers-Wallen Contents There is an ongoing revolution in medicine that is changing the way that veterinarians will be counselling clients regarding inherited disorders. Clinical applications will emerge rapidly in veterinary medicine as we obtain new information from canine and comparative genome projects (Meyers-Wallen 2001: Relevance of the canine genome project to veterinary medical practice. International Veterinary Information Service, New York). The canine genome project is described by three events: mapping markers on canine chromosomes, mapping gene locations on canine chromosomes (Breen et al. 2001: Genome Res. 11, 1784,1795), and obtaining the nucleotide sequence of the entire canine genome. Information from such research has provided a few DNA tests for single gene mutations [Aguirre 2000: DNA testing for inherited canine diseases. In: Bonagura, J (ed), Current Veterinary Therapy XIII. Philadelphia WB Saunders Co, 909,913]. Eventually it will lead to testing of thousands of genes at a time and production of DNA profiles on individual animals. The DNA profile of each dog could be screened for all known genetic disease and will be useful in counselling breeders. As part of the pre-breeding examination, DNA profiles of prospective parents could be compared, and the probability of offspring being affected with genetic disorders or inheriting desirable traits could be calculated. Once we can examine thousands of genes of individuals easily, we have powerful tools to reduce the frequency of, or eliminate, deleterious genes from a population. When we understand polygenic inheritance, we can potentially eliminate whole groups of deleterious genes from populations. The effect of such selection on a widespread basis within a breed could rapidly improve health within a few generations. However, until we have enough information on gene interaction, we will not know whether some of these genes have other functions that we wish to retain. And, other population effects should not be ignored. At least initially it may be best to use this new genetic information to avoid mating combinations that we know will produce affected animals, rather than to eliminate whole groups of genes from a population. This is particularly important for breeds with small gene pools, where it is difficult to maintain genetic diversity. Finally, we will eventually have enough information about canine gene function to select for specific genes encoding desirable traits and increase their frequencies in a population. This is similar to breeding practices that have been applied to animals for hundreds of years. The difference is that we will have a large pool of objective data that we can use rapidly on many individuals at a time. This has great potential to improve the health of the dog population as a whole. However, if we or our breeder clients make an error, we can inadvertently cause harm through massive, rapid selection. Therefore, we should probably not be advising clients on polygenic traits or recommend large scale changes in gene frequencies in populations until much more knowledge of gene interaction is obtained. By then it is likely that computer modelling will be available to predict the effect of changing one or several gene frequencies in a dog population over time. And as new mutations are likely to arise in the future, these tools will be needed indefinitely to detect, treat and eliminate genetic disorders from dog populations. Information available from genetic research will only be useful in improving canine health if veterinarians have the knowledge and skills to use it ethically and responsibly. There is not only a great potential to improve overall canine health through genetic selection, but also the potential to do harm if we fail to maintain genetic diversity. Our profession must be in a position to correctly advise clients on the application of this information to individual dogs as well as to populations of dogs, and particularly purebred dogs. [source] Comparison of three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: A three-year experience in an Iranian university hospitalAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Fariba YARANDI Background: A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5,10% of women with ASCUS harbour serious cervical disease. Methods: We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies. Results: Mean age was 44.09 ± 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (, CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%. Conclusions: Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results. [source] Autofluorescence spectroscopy for the diagnosis of cervical intraepithelial neoplasiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2002Helmut Weingandt Objective To assess the feasibility of autofluorescence spectroscopy in the diagnosis of cervical intraepithelial neoplasia (CIN) using broadband light excitation. Design Feasibility study. Setting Colposcopy clinic of an university hospital. Population Sixty-eight patients at risk for CIN. Methods After excitation with a broadband light between 375 and 440 nm, spectral distribution of native tissue fluorescence (autofluorescence) was acquired from 685 cervical sites for the localisation and differentiation of CIN, and compared with colposcopically directed biopsy and human papillomavirus (HPV) DNA testing. Main outcome measure Detection of CIN. Results The evaluation of spectral measurements revealed significantly lower autofluorescence values for CIN 3 lesions compared with normal tissue (P < 0.001), and compared with CIN 1 or CIN 2 (P < 0.002). High grade CIN lesions (CIN 2/3) presented with a significant reduced autofluorescence compared with CIN 1 (P < 0.002). Patients with a positive HPV DNA testing showed a significantly lower autofluorescence than patients tested negative for HPV DNA (P < 0.05). Severe inflammation such as chronic cervicitis may lead to false positive results. Conclusions Autofluorescence spectroscopy represents an interesting approach for the detection of cervical neoplasia. Using an excitation wavelength band between 375 and 440 nm, significant differences between normal and precancerous lesions of the cervix can be seen. [source] The occurrence of dominant spinocerebellar ataxias among 251 Finnish ataxia patients and the role of predisposing large normal alleles in a genetically isolated populationACTA NEUROLOGICA SCANDINAVICA, Issue 3 2005V. Juvonen Objectives,,, Frequency and distribution of dominant ataxias caused by dynamic mutations may vary in different populations, which has been explained on the basis of relative frequency of predisposing normal alleles. The aim of the study was to evaluate the occurrence of spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA) in Finland, and to investigate the role of predisposing normal alleles in a genetically homogenous population. Material and methods,,, Mutation analyses for SCA1, 2, 3, 6, 7, 8, 10, 12, 17, and DRPLA and frataxin genes were performed for 251 unrelated Finnish patients who presented with progressive ataxia disorder. Results,,, Expansions of SCA1, SCA2, SCA6, SCA7, SCA8, and SCA17 genes were detected in 2, 1, 1, 7, 22, and 1 patients, respectively. Altogether, 39 and 7% of dominant and sporadic SCA patients, respectively, harboured expansions at some of the investigated loci. Normal variation, collected from 477 to 502 chromosomes at each disease loci, revealed that Finns were different from the Japanese but largely similar to other Caucasians. Conclusions,,, Lack of SCA3 and excess of SCA8 are characteristic to the Finnish population. Homozygosity for the SCA8 expansion increases penetrance. Frequencies of large normal alleles at the SCA loci predict poorly prevalence of the respective diseases in Finland. Prioritization in DNA testing, based on ethnic origin and geographical location, is recommendable in Finland, and analogous approach may be applied to other countries as well. [source] Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramificationsCLINICAL GENETICS, Issue 1 2009HT Lynch More than one million patients will manifest colorectal cancer (CRC) this year of which, conservatively, approximately 3% (,30,700 cases) will have Lynch syndrome (LS), the most common hereditary CRC predisposing syndrome. Each case belongs to a family with clinical needs that require genetic counseling, DNA testing for mismatch repair genes (most frequently MLH1 or MSH2) and screening for CRC. Colonoscopy is mandated, given CRC's proximal occurrence (70,80% proximal to the splenic flexure). Due to its early age of onset (average 45 years of age), colonoscopy needs to start by age 25, and because of its accelerated carcinogenesis, it should be repeated every 1 to 2 years through age 40 and then annually thereafter. Should CRC occur, subtotal colectomy may be necessary, given the marked frequency of synchronous and metachronous CRC. Because 40,60% of female patients will manifest endometrial cancer, tailored management is essential. Additional extracolonic cancers include ovary, stomach, small bowel, pancreas, hepatobiliary tract, upper uroepithelial tract, brain (Turcot variant) and sebaceous adenomas/carcinomas (Muir-Torre variant). LS explains only 10,25% of familial CRC. [source] | |||||||||||||||||||||||||