Home About us Contact
|
Home About us Contact | ||
|
|
||
Screening Protocol (screening + protocol)
Selected AbstractsCompetitive binding comparison of endocrine-disrupting compounds to recombinant androgen receptor from fathead minnow, rainbow trout, and humanENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2007Vickie S. Wilson Abstract Typically, in vitro hazard assessments for the identification of endocrine-disrupting compounds (EDCs), including those outlined in the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Tier 1 Screening protocols, utilize mammalian receptors. Evidence, however, exists that fish sex steroid hormone receptors differ from mammalian receptors both structurally and in their binding affinities for some steroids and environmental chemicals. Most of the binding studies to date have been conducted using cytosolic preparations from various tissues. In the present study, we compare competitive binding of a set of compounds to full-length recombinant rainbow trout androgen receptor , (rtAR), fathead minnow androgen receptor (fhAR), and human androgen receptor (hAR), each expressed in COS cells. Saturation binding and subsequent Scatchard analysis using [3H]R1881, a high-affinity synthetic androgen, revealed an equilibrium dissociation constant (Kd) of 0.11 nM for the rtAR, 1.8 nM for the fhAR, and 0.84 nM for the hAR. Compounds, including endogenous and synthetic steroids, known mammalian antiandrogens, and environmental compounds, were tested for competitive binding to each of the three receptors. Overall, agreement existed across receptors as to binding versus nonbinding for all compounds tested in this study. Minor differences, however, were found in the relative order of binding of the compounds to the individual receptors. Studies such as these will facilitate the identification of EDCs that may differentially affect specific species and aid in the development and support of future risk assessment protocols. [source] De novo malignancies following liver transplantation: Impact and recommendationsLIVER TRANSPLANTATION, Issue S2 2009J. Ignacio Herrero Key Points 1. De novo malignancy is one of the leading causes of late mortality after liver transplantation. 2. The risks of skin cancers and lymphoma are more than 10-fold greater than the risks in an age-matched and sex-matched general population. 3. Some types of neoplasia, such as lung, head and neck, and colorectal cancer, are more frequent in liver transplant recipients than in an age-matched and sex-matched population. The risks of other frequent malignancies, such as prostate and breast cancer, do not seem to be increased. 4. The most important risks for posttransplant malignancy are Epstein-Barr virus seronegativity (for lymphoma), sun exposure (for skin cancer), smoking, and increasing age. 5. Despite the absence of evidence, general recommendations (such as avoidance of overimmunosuppression, sunlight protection, and cessation of smoking) should be given. Screening protocols may help to detect neoplasia at an early stage of disease. Liver Transpl 15:S90,S94, 2009. © 2009 AASLD. [source] Screening for Adolescent Depression in a Pediatric Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 5 2006Emily Gale Scott MD Abstract Objectives: To describe the prevalence of depressive symptoms in adolescents presenting to the emergency department (ED) and to describe their demographics and outcomes compared with adolescents endorsing low levels of depressive symptoms. Methods: The Beck Depression Inventory,2nd edition (BDI-II) was used to screen all patients 13,19 years of age who presented to the ED during the period of study. The BDI-II is a 21-item self-report instrument used to measure the presence and severity of depressive symptoms in adolescents and adults. Demographics and clinical outcomes of screening-program participants were abstracted by chart review. Patients were categorized into one of four severity categories (minimal, mild, moderate, or severe) and one of three presenting complaint categories (medical, trauma, mental health). Results: Four hundred eighty-seven patients were approached, and 351(72%) completed the screening protocol. Participants endorsed minimal (n= 192, 55%), mild (n= 52, 15%), moderate (n= 41, 11%), or severe depressive symptoms (n= 66, 19%). Those with moderate or severe depressive symptoms were more likely to be hospitalized. Of patients completing the BDI-II, 72% with psychiatric, 12% with traumatic, and 19% with medical chief complaints endorsed either moderate or severe depressive symptoms. Conclusions: Depressive symptoms are prevalent in this screening sample, regardless of presenting complaint. A substantial proportion of patients with nonpsychiatric chief complaints endorsed moderate or severe depressive symptoms. A screening program might allow earlier identification and referral of patients at risk for depression. [source] Myocardial perfusion imaging and cardiac events in a cohort of asymptomatic patients with diabetes living in southern FranceDIABETIC MEDICINE, Issue 4 2006A. Sultan Abstract Aims, To assess the association between abnormal stress myocardial perfusion imaging (MPI) and cardiac events (CE) in asymptomatic patients with diabetes and with , 1 additional risk factor. Predictors of abnormal stress MPI were also evaluated. Methods, Four hundred and forty-seven consecutive patients who underwent stress MPI were prospectively followed for 2.1 [0.5,4.1] years for the subsequent occurrence of hard CE (myocardial infarction and sudden or coronary death) and soft CE (unstable angina and ischaemic heart failure requiring hospitalization). Re-vascularization procedures performed as a result of the screening protocol were not included in the analysis. Results, Follow-up was successful in 419 of 447 patients (94%), of whom 71 had abnormal MPI at baseline. Medical therapy was intensified in all subjects and especially in those with abnormal MPI. Twenty-three patients with abnormal MPI underwent a re-vascularization procedure. CEs occurred in 14 patients, including six of 71 patients (8.5%) with abnormal MPI and eight of 348 patients (2.3%) with normal MPI (P < 0.005). Only two patients developed a hard CE and 12 a soft CE. In multivariate analysis, abnormal MPI was the strongest predictor for CEs [odds ratio (OR) (95% CI) = 5.6 (1.7,18.5)]. Low-density lipoprotein cholesterol , 3.35 mmol/l [OR (95% CI) = 7.3; 1.5,34.7] and age > median [OR (95% CI) = 6.0 (1.2,28.6)] were additional independent predictors for CE. The independent predictors for abnormal MPI were male gender, plasma triglycerides , 1.70 mmol/l, creatinine clearance < 60 ml/min and HbA1c > 8%, with male gender the strongest [OR (95% CI) = 4.0 (1.8,8.8)]. Conclusions, Asymptomatic patients with diabetes in this study had a very low hard cardiac event rate over an intermediate period. This could be explained by the effects of intervention or by the low event rate in the background population. Randomized studies of cardiac heart disease screening are required in asymptomatic subjects with diabetes to determine the effectiveness of this intervention. Diabet. Med. (2006) [source] Utility of a juvenile fathead minnow screening assay for detecting (anti-)estrogenic substancesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2002Grace H. Panter Abstract The European Chemical Industry's aquatic research program for endocrine disrupters includes the development of an in vivo juvenile fathead minnow (Pimephales promelas) screening assay.Working within the Organization for Economic Cooperation and Development's (OECD, Paris, France) tiered approach to endocrine disrupter evaluation in fish, the juvenile fish screening protocol was adapted from the OECD test guideline 204. Six chemicals, with different (anti-)estrogenic potencies, were used to develop the in vivo juvenile fish screening protocol: diethylstilbestrol, 17,-ethynylestradiol, genistein, methoxychlor, 4- tert -pentylphenol, and ZM189,154 (a novel pharmaceutical antiestrogen). Mixed-sex juvenile fathead minnows were exposed to individual chemicals (with chemical analyzes) and sampled after 4, 7, 14, and 21 d of exposure. Wet weight, total length, condition factor, and whole-body homogenate concentrations of vitellogenin (VTG) were determined. Estrogens and antiestrogens were detected in this screen by virtue of the VTG response (an elevation or suppression, respectively) after 14 d. The study showed that the use of VTG concentrations in mixed-sex juvenile fish provides a sensitive and robust assay for the detection of both estrogenic and antiestrogenic chemicals, with widely divergent potencies. [source] Screening Strategies for Group B Streptococcus in the Third Trimester of PregnancyJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 12 2002APRN-BC, FAANP, Lorna Schumann PhD Purpose To identify the best screening protocol to prevent neonatal group B streptococcal (GBS) sepsis through literature review. Data Sources Selected research articles, texts, and Internet sources. Conclusions Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics (AAP), American College of Obstetricians and Gynecologists (ACOG), and American College of Nurse Midwives (ACNM) have issued guidelines describing methods to identify pregnant women at risk of intrapartum transmission of GBS to their babies. Studies have been conducted to discover the superiority of one prevention method over the other but no consensus has been reached. Implications for Practice Before widely used prevention methods, approximately 8,000 babies each year became infected with GBS; of those, 400 died and many survivors suffered life-long sequelae. Adoption of an appropriate protocol can prevent transmission of GBS from a colonized mother to her infant. Clinicians should implement either universal culture-based or risk factor-based screening guidelines for prenatal diagnosis and intrapartum prophylaxis of GBS disease. [source] The impact of cold temperatures during grain maturation on selected quality parameters of wheatJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2007Maryke Craven Abstract The influence of sudden cold spells during grain filling of wheat on the quality traits of three South African hard red wheat cultivars (Gariep, Elands and Tugela-DN) was studied, with the emphasis on Hagberg falling number (HFN). Four treatments were used (,1 °C at soft dough stage, , 1 °C at late milk stage, , 4 °C at soft dough stage and , 4 °C at late milk stage) and were administered for one night only. From the results it was concluded that, although limited in duration, such frost conditions did have an effect on the quality of the wheat cultivars. Cultivars differed in their response to the various treatments but also as to what quality traits were affected the most. The , 4 °C at late milk stage resulted in significantly reduced HFN being measured for both Elands and Tugela-DN. A similar effect was observed for Gariep, but was not statistically significant. Although the response was limited to the main tillers only, the conclusion was made that it is probable that the reduced HFN would be visible in the pooled sample of head and side tillers. A screening protocol was suggested that would allow classification of cultivars for frost tolerance. Copyright © 2007 Society of Chemical Industry [source] Which contingent sequential screening protocol?PRENATAL DIAGNOSIS, Issue 6 2005Dave Wright No abstract is available for this article. [source] Which prenatal screening protocol?PRENATAL DIAGNOSIS, Issue 10 2004M. A. Ferguson-Smith No abstract is available for this article. [source] Preparation of monoclonal antibody bank against whole water-soluble proteins from rapid-growing bamboo shootsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 22 2006Yu-Jen Wu Abstract An antibody bank against the whole proteins in a proteome is a useful tool for biological research. Using the standard cell fusion method, and a modified screening protocol, we produced an mAb bank against the total water-soluble proteins extracted from the rapid-growing green bamboo shoots. An improved two-stage strategy was employed to enrich those poor immunogenic or lower expressed proteins. Totally, we obtained a bank of 192 mAb which were identified as distinctive to each other by 2-DE and immunostaining. [source] Recruitment of African American Women to a Walking Program: Eligibility, Ineligibility, and Attrition During Screening,RESEARCH IN NURSING & HEALTH, Issue 3 2006JoEllen Wilbur Abstract The purposes of this study were to identify strategies successful in the recruitment of African American (AA) women to a home-based walking program and to examine factors that contribute to attrition, eligibility, and ineligibility during the recruitment screening protocol. Of the 696 women who contacted the researchers, 281 (40.4%) women enrolled in the study, 227 (32.6%) were lost to attrition, and 188 (27%) were ineligible. Those not enrolled due to attrition during screening or ineligibility reported more family risk for cardiovascular disease (CVD) and lived in neighborhoods with higher poverty. Although our recruitment strategies may have been successful in attracting low-income AA women, we were not as successful in preventing their attrition during the screening protocol, particularly for those living in poorer neighborhoods. © 2006 Wiley Periodicals, Inc. Res Nurs Health 29:176,189, 2006 [source] Outcomes and Efficacy of Newborn Hearing Screening: Strengths and Weaknesses (Success or Failure?),THE LARYNGOSCOPE, Issue 7 2008S. Korres MD Abstract Objective: To assess the outcomes of neonatal hearing screening with regard to the final diagnosis in a very large number of newborns and investigate related strengths and weaknesses of the program. Subjects: In this study, 76,560 newborns were assessed. Method: All neonates were assessed using transient evoked otoacoustic emissions (TEOAEs). Results: From the 76,560 neonates screened, 1,564 (2%) failed the test. According to the screening protocol, all parents of failed neonates were asked to bring their children 1 month following discharge to repeat the test. Of the 541 (34.6%) newborns who repeated the test, 303 (56%) were found normal and 238 (44%) again failed TEOAE. The latter children were referred to two special public centers for full audiology evaluation. In addition, 124 neonates were also referred due to other reasons revealed in the screening process (family history, high levels of bilirubin, etc.). Of the 362 children who were referred to the two special audiology centers, 113 (31.2%) were evaluated by these two centers. In addition, 42 children who had failed initial screening and did not show up for a follow-up appointment to repeat TEOAE were also assessed in the same centers. Of the 155 children who had a special audiologic evaluation, 56 (36.1%) were found to have hearing loss (HL) and 99 (63.9%) normal hearing. In detail, 28 had bilateral sensorineural HL greater than 40 dB, 10 had unilateral sensorineural HL greater than 40 dB, and 18 had otitis media with effusion or other conductive HL. Conclusions: Derived from the present study: 1) repeated testing of "failed" newborns in the maternity hospital and before discharge leads to an acceptable referral rate of 2%; 2) the 1-month follow-up of "failed" newborns further limits the false positive results but leads to high rate of newborns lost to follow-up; 3) a dedicated secretariat system should be implemented to follow-up each "failed" newborn and remind parents about their follow-up appointments; and 4) additional measures such as detailed educational material and parental friendly approach should also be implemented. [source] Clinical Burden of Screening Asymptomatic Patients for Coronary Artery Disease Prior to Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009D. Filě The aim of this study is to assess the clinical burden of silent coronary artery disease (CAD) in cirrhotic candidates for liver transplantation (LT), and to evaluate the usefulness of a CAD screening approach. Between July 1999 and January 2006, we evaluated 627 LT candidates. All of them underwent a detailed clinical history. Sixteen had a previous diagnosis of CAD or symptoms suggestive (2.5%). The remaining 611 underwent further tests according to a predefined protocol, including EKG, echocardiogram and, on the basis of CAD risk factors, heart stress tests. Selective coronary angiography (SCA) was performed in the 30 patients with positive heart stress test: in only 2 did SCA show any CAD, and in both it was subcritical disease requiring neither intervention nor contraindicating LT. The 611 screened patients continued their follow-up until study closure or death. No coronary events occurred in the study population in a mean follow-up of 32.50 months (+/, 23.67 DS). No perioperative mortality related to CAD occurred in the 233 transplanted patients. In conclusion, no prognostic advantage was achieved by following a strict CAD screening protocol, leading us to believe that the cost-effectiveness of a similar screening can be unacceptably high in our setting. [source] Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinomaCANCER, Issue 3 2004Anne-Renee Hartman M.D. Abstract BACKGROUND Intensive screening is an alternative to prophylactic mastectomy in women at high risk for developing breast carcinoma. The current article reports preliminary results from a screening protocol using high-quality magnetic resonance imaging (MRI), ductal lavage (DL), clinical breast examination, and mammography to identify early malignancy and high-risk lesions in women at increased genetic risk of breast carcinoma. METHODS Women with inherited BRCA1 or BRCA2 mutations or women with a > 10% risk of developing breast carcinoma at 10 years, as estimated by the Claus model, were eligible. Patients were accrued from September 2001 to May 2003. Enrolled patients underwent biannual clinical breast examinations and annual mammography, breast MRI, and DL. RESULTS Forty-one women underwent an initial screen. Fifteen of 41 enrolled women (36.6%) either had undergone previous bilateral oophorectomy and/or were on tamoxifen at the time of the initial screen. One patient who was a BRCA1 carrier had high-grade ductal carcinoma in situ (DCIS) that was screen detected by MRI but that was missed on mammography. High-risk lesions that were screen detected by MRI in three women included radial scars and atypical lobular hyperplasia. DL detected seven women with cellular atypia, including one woman who had a normal MRI and mammogram. CONCLUSIONS Breast MRI identified high-grade DCIS and high-risk lesions that were missed by mammography. DL detected cytologic atypia in a high-risk cohort. A larger screening trial is needed to determine which subgroups of high-risk women will benefit and whether the identification of malignant and high-risk lesions at an early stage will impact breast carcinoma incidence and mortality. Cancer 2004. © 2004 American Cancer Society. [source] Sensitivity and specificity of a visual acuity screening protocol performed with the Lea Symbols 15-line folding distance chart in preschool childrenACTA OPHTHALMOLOGICA, Issue 6 2006Francesca Bertuzzi Abstract. Purpose:, The aim of this study was to assess the feasibility of a visual acuity (VA) test using the Lea Symbols 15-line folding distance chart and its diagnostic validity in detecting VA deficiency in preschool children. Methods:, A group of 149 children aged 38,54 months underwent VA examination performed with the Lea 15-line folding optotype at a distance of 3 metres, according to a test protocol described in the Methods section. After the VA test, a complete ophthalmological examination, including cycloplegic retinoscopy, a cover test and examination of the anterior and posterior segments, was performed on each child in order to detect any VA-threatening ocular abnormality. The Lea Symbols test's sensitivity, specificity, positive and negative likelihood ratios (LR +, LR ,) and the receiver operating characteristic (ROC) curve were calculated by means of standard procedures using each VA level of the chart from 0.1 to 1 (1,0 logMAR) as a cut-off point. Results:, The Lea Symbols test could be successfully used in 95.9% of the population. The most useful cut-off points for screening preschool children were found to be 0.8 (LR +,5.73, LR ,,0.05) or 0.63 (LR +,11.7, LR ,,0.23). Conclusion:, The Lea Symbols test proved to be clinically useful in detecting VA deficiency in preschool children. The choice between the two best performing cut-off levels should be made according to the expected cost-effectiveness of the screening programme. [source] High prevalence of impaired fasting glucose in Chinese children and adolescents with prehypertension/hypertensionACTA PAEDIATRICA, Issue 10 2009Lei Zhao Abstract Aim:, To assess the prevalence of impaired fasting glucose among Chinese children and adolescents with prehypertension/hypertension (PHP/HP), overweight/obesity (OW/OB) or both in the general population. Methods:, In total, 3409 children and adolescents among the age group of 10,18 years were enrolled. These subjects were then divided into four groups: OW/OB, PHP/HP, OW/OB + PHP/HP and a control group. Fasting plasma glucose (FPG) and lipid levels were measured in children with a body mass index ,85th percentile and/or blood pressure ,90th percentile and in 100 subjects randomly selected from the control group. The oral glucose tolerance test was performed in all the subjects with fasting glucose ,5.6 mmol/L. Results:, Eighty-one impaired fasting glucose subjects and one girl with type 2 diabetes were identified. The prevalence of impaired fasting glucose in PHP/HP (7.03%) was not significantly different from that in the OW/OB + PHP/HP group (8.59%), but was higher than that in the OW/OB group (3.31%). Conclusion:, Although the American Diabetes Association does not recommend the FPG test for children and adolescents with PHP/HP, in this study, we found that children and adolescents with PHP/HP have a higher prevalence of impaired fasting glucose than those with OW/OB. Further validation of these findings is warranted and a type 2 diabetes screening protocol for Chinese children and adolescents needs to be established. [source] Validation of a screening protocol for identifying low-risk candidates with type 1 diabetes mellitus for kidney with or without pancreas transplantationCLINICAL TRANSPLANTATION, Issue 2 2006Irene W.Y. Ma Abstract: Background: Certain clinical risk factors are associated with significant coronary artery disease in kidney transplant candidates with diabetes mellitus. We sought to validate the use of a clinical algorithm in predicting post-transplantation mortality in patients with type 1 diabetes. We also examined the prevalence of significant coronary lesions in high-risk transplant candidates. Methods: All patients with type 1 diabetes evaluated between 1991 and 2001 for kidney with/without pancreas transplantation were classified as high-risk based on the presence of any of the following risk factors: age ,45 yr, smoking history ,5 pack years, diabetes duration ,25 yr or any ST,T segment abnormalities on electrocardiogram. Remaining patients were considered low risk. All high-risk candidates were advised to undergo coronary angiography. The primary outcome of interest was all-cause mortality post-transplantation. Results: Eighty-four high-risk and 42 low-risk patients were identified. Significant coronary artery stenosis was detected in 31 high-risk candidates. Mean arterial pressure was a significant predictor of coronary stenosis (odds ratio 1.68; 95% confidence interval 1.14,2.46), adjusted for age, sex and duration of diabetes. In 75 candidates who underwent transplantation with median follow-up of 47 months, the use of clinical risk factors predicted all eight deaths. No deaths occurred in low-risk patients. A significant mortality difference was noted between the two risk groups (p=0.03). Conclusions: This clinical algorithm can identify patients with type 1 diabetes at risk for mortality after kidney with/without pancreas transplant. Patients without clinical risk factors can safely undergo transplantation without further cardiac evaluation. [source] The impact of new screening protocol on individuals at increased risk of colorectal cancerCOLORECTAL DISEASE, Issue 7 2007T. Mak Abstract Objective, Screening colonoscopy has been shown to reduce mortality and cancer stage in hereditary nonpolyposis colorectal cancer (HNPCC) individuals. However, the benefit of screening in intermediate risk groups is unknown. The most recent national guidelines have recommended a reduction of screening frequency for the intermediate risk group. Therefore, this study aims to compare the results of colonoscopic screening in HNPCC and intermediate risk groups and assess the effect of the most recent screening protocol recommendations. Method, A total of 244 individuals; 108 from HNPCC families (28 mismatch repair gene carriers) and 136 from intermediate risk families were referred for regular colonoscopic screening by the Regional Genetics Service. Findings from 417 colonoscopies performed between 1992 and 2003 were evaluated. Results, A total of three cancers, 39 adenomas and 41 hyperplastic polyps were found in the HNPCC group compared with one cancer, 22 adenomas and 19 hyperplasic polyps in the intermediate risk group. If the recent screening guidelines for the intermediate group were applied, then 89 (44%) fewer colonoscopies would have been performed. Although no cancers would have been missed, six adenomas (mean size = 5.7 mm, range 2,10 mm) with two graded as severely dysplasic and six hyperplastic polyps would not have been detected. Conclusion, The detection rate and distribution of adenomas were similar in both groups. If the new colonoscopic screening recommendations for the intermediate risk group had been applied, a small number of significant lesions would have been missed. [source] Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced?DIABETIC MEDICINE, Issue 5 2010J. Tomlinson Diabet. Med. 27, 498,515 (2010) Abstract Polycystic ovary syndrome (PCOS) is a risk factor for Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), but these risks are poorly defined. This study aimed to evaluate the evidence for these risks and whether screening and risk reduction are feasible. Medline reviews and data quality analysis were used using standard tools. Results showed that (i) polycystic ovary syndrome is a risk factor forT2DM but the magnitude of risk is uncertain, (ii) fasting plasma glucose is an inadequate screening test forT2DM in this population and the oral glucose tolerance test is superior, (iii) the identification of women with PCOS for diabetes screening is constrained by current diagnostic criteria for PCOS; however, women with oligomenorrhoea and those with diagnosed PCOS and obesity or a family history of T2DM are at highest risk, (iv) risk factors for T2DM are improved by weight loss interventions and by metformin. However, no studies have determined whether T2DM incidence is reduced, (v) polycystic ovary syndrome is associated with cardiovascular disease (CVD) risk factors but data on CVD incidence are weak, (vi) risk factors for CVD are improved by the same interventions and statins and (vi) no studies have evaluated whether CVD incidence is reduced. While PCOS has important metabolic associations, and short-term interventions reduce risk factors for T2DM and CVD, data on prevalence and incidence of T2DM and particularly CVD are poor. There is a need for a clear definition of PCOS, for diabetes screening protocols and for long-term studies to determine whether risks can be reduced. [source] Deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome,HUMAN MUTATION, Issue 2 2009Marietta E. Kovacs Abstract Several different genetic alterations in the etiology of Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) are known, mostly point mutations and genomic rearrangements in 1 of at least 3 mismatch-repair (MMR) genes. However, no susceptibility factor has yet been identified in a significant part (30,50%) of clinicopathologically well-defined HNPCC families, suggesting the presence of other predisposing mechanisms. In a set of probands from 27 Lynch syndrome families who lacked evidence of a germline mutation in either the MSH2 or MLH1 gene, we performed genomic deletion screening with the use of multiplex ligation-dependent probe amplification (MLPA) and sequencing. We used immunohistochemistry (IHC) and microsatellite instability (MSI) analyses on samples of the probands of all families. Comparative analysis of mRNA transcripts was performed on blood leukocyte,derived samples from mutation carriers and noncarrier controls. We report that large germline deletions encompassing the last exons of the TACSTD1 gene, upstream of MSH2, cosegregate with the HNPCC phenotype in 19% (5/27) of families tested. The tumors of the carriers show high-level MSI and MSH2 protein loss. We show that these deletions, by removing the transcriptional termination sequences of the upstream gene, give rise to multiple TACSTD1/MSH2 fusion transcripts. Our results provide evidence that deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome. Thus, analysis of the 3, region of the TACSTD1 gene should be included in the routine mutation screening protocols for HNPCC. Hum Mutat 30, 197,203, 2009. © 2009 Wiley-Liss, Inc. [source] Tissue Resonance Interaction Method (TRIMprob) has the potential to be used alongside the recognized tests in the screening protocols for prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2009Ozgur Gokce Abstract: The objective of this study was to evaluate the accuracy of the magnetic induction technique with a nonlinear tunable oscillator (the Tissue Resonance Interaction Method [TRIMprob]) in the diagnosis of prostate cancer (CaP). Overall, 148 men were split into two groups (patients at risk of CaP [Group 1] and controls [Group 2]) and evaluated with the TRIMprob. Group 1 consisted of 100 patients (mean age: 63.8 ± 7.2 years) with elevated prostate-specific antigen (>4 ng/mL) levels and/or abnormal digital rectal examination. Eleven patients (Group 2a, mean age: 59.5 ± 7.3) with previously biopsy-proven CaP served as positive controls. In addition, 37 voluntary men (Group 2b, mean age: 39.8 ± 10.4) with normal prostate-specific antigen and digital rectal examination without lower urinary tract symptoms served as negative controls. Non-linear resonance was analyzed at 465 MHz and a cut-off value of 40 units was detected as the resonance value for the best threshold to distinguish benign conditions from CaP after transrectal ultrasonography-guided biopsy with a standard 10,12 core technique in Group 1. Mean resonance values (±standard deviation) with the TRIMprob examination for patients in Groups 1 and 2b were 36.72 ± 22.35 and 73.64 ± 10.06, respectively, whereas for patients in Group 2a, it was 13.73 ± 12.12 (P < 0.01). Sensitivity, specificity, positive and negative predictive values of the TRIMprob using the study cohort of Group 1 were found as 76%, 61.3%, 39.6% and 88.5%, respectively. Despite some technical limitations, the non-invasive TRIMprob examination may have a role in screening protocols for CaP. [source] Properties and applications of supports for enzyme-mediated transformations in solid phase synthesisJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 10 2006Alessandra Basso Abstract With the increasing interest in automated synthesis and screening protocols, solid supported chemistry and biochemistry have become attractive technologies. Furthermore, the use of enzymes in solid phase synthesis has opened the route to selective and mild processes. The efficiency of enzymes in transforming substrates that are bound on solid supports is strictly related to the availability of polymers endowed with specific properties, above all permeability to enzymes. This review describes how the recent developments of this rapidly evolving area have made possible novel challenging applications of enzymes in solid phase synthesis. Copyright © 2006 Society of Chemical Industry [source] Central corneal thickness in European (white) individuals, especially children and the elderly, and assessment of its possible importance in clinical measures of intra-ocular pressureOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2002Michael J. Doughty Purpose:,To ascertain the impact of central corneal thickness (CCT, as assessed by pachometry) and central corneal curvature (as assessed by keratometry) on clinical measures of intra-ocular pressure (IOP, as assessed by tonometry), especially in the young and elderly. Methods:,Pachometry, keratometry and tonometry were carried out on three groups, namely children aged 5,15 years, adults aged 32,60 years, and elderly individuals aged between 61 and 82 years. For children, ultrasound pachometry was combined with non-contact tonometry (NCT), specular microscopy was used with Perkins tonometry in the adults, and ultrasound pachometry was used with Perkins tonometry for the elderly. Central corneal curvature was assessed by keratometry. Results:,The average CCT in children was 0.529 ± 0.034 mm (n=104, ±S.D.), averaged 0.533 ± 0.033 in adults (n=75) and 0.527 ± 0.034 mm (n=91) in the elderly. Tonometry values averaged 16.7 ± 2.9 mm in children, 13.0 ± 3.5 mmHg in adults and 13.6 ± 2.5 mm in the elderly group. Central corneal thickness values were not predictably different in relation to central corneal curvature values. Regression analyses indicated that the tonometry values were higher in both children and the elderly who had thicker corneas (and vice versa) (p , 0.003), with the measures increasing by 1.3 ± 0.4 and 2.6 ± 0.4 mmHg for a 10% difference in CCT in children and the elderly, respectively. For adults, no statistically significant difference in tonometry values could be demonstrated with respect to CCT (<1 mmHg for a 10% difference in CCT), and for no group were the CCT or tonometry values predictably different in relation to central corneal curvature values. Conclusions:,The results of these studies, albeit relatively small scale, indicate that in young or elderly individuals with essentially normal IOP and CCT measures, the tonometry values show only small differences with respect to CCT. The slope in the observed relationship was not that different from an average of 1.5 mmHg for a 10% different in CCT, as obtained from a literature analysis over a 30-year period. The magnitude of the effect does not provide evidence that pachometry needs to be routinely performed in glaucoma screening protocols based on tonometry. Notwithstanding, the finding of higher than expected tonometry values should be further investigated, by pachometry, especially in very young children and in the elderly. [source] Current dilemmas in Down syndrome clinical care: Celiac disease, thyroid disorders, and atlanto-axial instability,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2006William I. Cohen Abstract This study will discuss our current understanding of celiac disease (CD), thyroid disorders, and atlanto-axial instability, three important areas of medical management in individuals with Down syndrome (DS). In this study, we highlight our current knowledge, as well as what we need to study in order to gather the necessary data to refine the empirically based screening protocols which are now in place. © 2006 Wiley-Liss, Inc. [source] Screening for diabetic retinopathy by non-ophthalmologists: an effective public health toolACTA OPHTHALMOLOGICA, Issue 4 2003Lalit Verma Abstract. Purpose:, To investigate and report the reliability of detection and grading of diabetic retinopathy by direct ophthalmoscopy through a dilated pupil by general physicians (non-ophthalmologists) and optometrists who have undergone a short period of training. Methods:, A total of 400 eyes of 200 diabetes patients were examined by two non-ophthalmologists. Their observations were compared with an ophthalmologist's diagnoses for the same patients. Results:, The diagnoses made by the general physician (kappa = 0.8381, SE = 0.041) and the optometrist (kappa = 0.7186, SE = 0.051) showed good rates of agreement with the ophthalmologist's diagnoses. Conclusions:, The provision of appropriate screening protocols and follow-up parameters can enable primary care physicians and support personnel to reliably screen individuals for retinopathy in diabetes. This will reduce the workload of tertiary hospitals, and provide optimal services to the huge majority of the Indian population that has limited access to eye care services. [source] Revealing the human mutomeCLINICAL GENETICS, Issue 4 2010JM Chen Chen JM, Férec C, Cooper DN. Revealing the human mutome. The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database). However, for a variety of reasons, this figure is likely to represent only a small proportion of the clinically relevant genetic variants that remain to be identified in the human genome (the ,mutome'). With the advent of next-generation sequencing, we are currently witnessing a revolution in medical genetics. In particular, whole-genome sequencing (WGS) has the potential to identify all disease-causing or disease-associated DNA variants in a given individual. Here, we use examples of recent advances in our understanding of mutational/pathogenic mechanisms to guide our thinking about possible locations outwith gene-coding sequences for those disease-causing or disease-associated variants that are likely so often to have been overlooked because of the inadequacy of current mutation screening protocols. Such considerations are important not only for improving mutation-screening strategies but also for enhancing the interpretation of findings derived from genome-wide association studies, whole-exome sequencing and WGS. An improved understanding of the human mutome will not only lead to the development of improved diagnostic testing procedures but should also improve our understanding of human genome biology. [source] Methicillin-resistant Staphylococcus aureus: risk assessment and infection control policiesCLINICAL MICROBIOLOGY AND INFECTION, Issue 5 2008E. Tacconelli Abstract The endemic state of methicillin-resistant Staphylococcus aureus (MRSA) occurs through a constant influx of MRSA into the healthcare setting from newly admitted MRSA-positive patients, followed by cross-transmission among inpatients and an efflux of MRSA from the hospital with discharged patients. To date, most MRSA prevention strategies have targeted cross-transmission among hospitalised patients. Intensive concerted interventions that include isolation can reduce the MRSA incidence substantially. However, debate continues about the cost-effectiveness of infection control policies, including screening protocols, to control the influx of MRSA into hospitals. The rationale and cost-effectiveness of wide screening, as compared to targeted screening, should be further studied using appropriate statistical approaches and economic modelling. [source] | ||||||||||||||||