The granulation tissue preservation technique in regenerative periodontal surgery-a randomized controlled clinical trial.

OBJECTIVES: To investigate if the application of the granulation tissue preservation technique (GTPT) in regenerative therapy of infrabony periodontal defects results in more clinical attachment level (CAL) gain and more radiographic bone gain (RBG) than the conventional resective approach 12 months after surgery. MATERIALS AND METHODS: Forty patients exhibiting at least one infrabony defect with a probing pocket depth (PPD) ≥6 mm and a radiographic infrabony component (INFRAX-ray ) ≥3 mm were randomly treated with the GTPT (test group) or the double-flap approach with resection of the defect-filling granulation tissue (control group). Enamel matrix derivatives were applied in both groups. Clinical and radiographic parameters were recorded at baseline (t0), 6 months (t1), and 12 months (t2) after surgery. The primary outcome variable was CAL gain between t0 and t2. RESULTS: When all patients were considered, ΔCALt0-t2 did not differ significantly between the two groups (p = .160). Significant PPD reduction (test group: 4.38 ± 1.36 mm; control group: 4.06 ± 2.38 mm), CAL gain (test group: 3.75 ± 1.24 mm; control group: 2.88 ± 2.09 mm), and RBG (test group: 3.06 ± 1.74 mm; control group: 3.27 ± 2.19 mm) were achieved at t2 in both groups. Using multivariate linear regression, PPDt0 and group were identified as variables with the greatest influence on ΔCALt0-t2 . PPDt0 and INFRAX-ray were identified as variables with the greatest influence on RBGt0-t2 . Patients with a defect angle >22° showed significantly more CAL gain in the test group (t0-t1: 3.08 ± 1.38 mm; t0-t2: 3.62 ± 0.96 mm) than in the control group (t0-t1: 1.77 ± 1.54 mm; t0-t2: 2.18 ± 1.83 mm). CONCLUSIONS: Regarding all patients, the study failed to show significant differences between the test and control groups. However, the GTPT appears to lead to more CAL gain in noncontaining infrabony defects.

Relationship between Lipoprotein(a) and cardiovascular risk factors-data from 4602 participants of the ELITE study.

Lipoprotein(a) (Lp(a)) is becoming increasingly important as an independent risk factor for cardiovascular disease. Since no effective therapy currently exists other than lipid apheresis, the recommendation remains to optimally adjust all other cardiovascular risk factors (CVRF). In a Northwest German population study, the frequency of elevated Lp(a) levels and all other CVRF was investigated. The aim was to investigate whether individuals with elevated Lp(a) levels were also more likely to have other CVRFs. To date, 4602 individuals have been enrolled in the study, and blood pressure, weight, lipids, diabetes, medications, and pre-existing conditions were recorded in addition to Lp(a). In addition, questionnaires assessed physical activity, psychological stress, depression, and brain dysfunction. All participants received detailed individual recommendation about their CVRF and its treatment. In the further follow-up of 5 years, it will be examined how persons with elevated Lp(a) implemented these recommendations in comparison with participants without elevated Lp(a). The first group Lp(a) <75 nmol/L consisted of 3550 (80.2%), the Lp(a) 75-120 nmol/L group of 341 (7.4%) and the Lp(a) >120 nmol/L of 538 (11.7%). 81.6% of all participants had one or more CVRF. Age, sex, and prevalence of hypertension, diabetes, smoking, obesity, and exercise did not differ among the 3 groups. As expected, LDL-Cholesterol was significantly elevated in the Lp(a) >120 nmol/L group despite significantly more frequent use of statins. Significantly more often hypertensive patients were found in the Lp(a) >120 nmol/L group who were inadequately controlled by medication and significantly less often persons without further CVRF. No differences existed in the frequency of psychological stress, depression, and mild cognitive impairment. CVRF occur with comparable frequency in individuals with elevated Lp(a) levels. However, individuals with Lp(a) above 120 nmol/L were more likely to have poorly controlled blood pressure, elevated LDL-C, and less likely to have no other risk factors. This underlines that in case of Lp(a) elevation all further CVRF should be intensively adjusted, especially in case of strongly elevated values >120 nmol/L. However, these recommendations have not been adequately implemented in clinical care in this population to date.

Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy : Risk-modifying factors.

BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.

Dermoglandular rotation flaps for breast-conserving therapy: aesthetic results, patient satisfaction, and morbidity in comparison to standard segmentectomy.

We compared a dermoglandular rotation flap (DGR) in the upper inner, lower inner, and upper outer quadrant regarding similar aesthetic results, patient satisfaction, and comfort after breast-conserving therapy with standard segmentectomy (SE). Between 2003 and 2011, 69 patients were treated with breast-conserving surgery using DGR for cancers with high tumor-to-breast volume ratios or skin resection in the three above mentioned quadrants; 161 patients with tumors in the same quadrants were treated with SE. The outcome of the procedures was assessed at least 7 months after completed radiation therapy using a patient and breast surgeon questionnaire and the BCCT.core software. Symmetry, visibility of the scars, the position of the nipple-areola complex, and the appearance of the treated breast were each assessed on a scale from 1 to 4 by an expert panel and by the patients. Univariate and multivariate analysis were used to evaluate the relationship between patient-, tumor-, and treatment-dependent factors and patient satisfaction. 94.2% of the patients with rotation flaps and 83.5% of the patients with lumpectomy were very satisfied with the cosmetic appearance of their breast. Younger patient age was significantly associated with a lower degree of satisfaction. DGR provides good cosmetic results compared with SE and shows high patient satisfaction despite longer scarring and higher median resection volume.

Long-term health-related quality of life after complex and/or complicated esophageal atresia in adults and children registered in a German patient support group.

BACKGROUND: Health-related quality of life (HRQoL) after esophageal atresia (EA) repair is postulated to be good. However, little is known about the long-term results after repair of complex and/or complicated EA regarding HRQoL. We investigated long-term HRQoL after delayed anastomosis, esophageal replacement, major revisions, or multiple dilatations in patients registered in a support group. METHODS: Patients registered in the German patient support group database (KEKS) were enrolled and allocated to subgroups according to surgical treatment and age. HRQoL was evaluated using validated questionnaires (GIQLI, WHO-5, KIDSCREEN27). RESULTS: Complete follow-up (mean 14.5 ± 9.8 years) was available for 90/92 patients. Patients were allocated to subgroups delayed anastomosis (n=28), esophageal replacement (n=27), major revisions (n=15), and multiple dilatations (n=20). Adult patients presented with impaired well-being according to WHO-score and gastrointestinal function (GIQLI). In contrast, HRQoL of children was comparable to controls in most KIDSCREEN27-dimensions. Delayed anastomosis was associated with most-favourable HRQoL. Regarding physical well-being, these children scored significantly better than controls [64.01 ± 10.40 vs. 52.36 ± 8.73;p=0.0011], children after replacement [51.40 ± 5.70;p=0.008], revisions [52.04 ± 6.97;p=0.026], and multiple dilatations [50.22 ± 9.67,p=0.04]. CONCLUSIONS: HRQoL after complex and/or complicated EA is excellent in children registered in a patient support group. In adults, disease-specific symptoms negatively affect HRQoL. Our data indicate that saving the esophagus may achieve the best HRQoL.

Aneuploidy screening during pregnancy by a three-dimensional Advanced First Trimester Screening model: description of the AFS-3D algorithm.

BACKGROUND: A novel screening method for fetal aneuploidies was developed, in which nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A), and free-ß human chorionic gonadotropin (free-ß hCG) are placed into a three-dimensional scatter plot. Likelihood ratios are directly inferred from the ratio of already observed healthy and diseased fetuses. This method is called 'Three-dimensional Advanced First trimester Screening' (AFS-3D). It was aimed to develop and test a new algorithm based on the results of previous studies. METHODS: A new static-sized sphere model was developed. Several scaling factors of the axes and the optional application of the modifications 'simulation' (SIM) and 'empty sphere positive' were tested on 15,227 data sets. An additional examination was performed on a second collective (n = 458). RESULTS: The application of the new AFS-3D model with static-sized spheres, a re-sampled ∆NT axis by a scaling factor of 0.125, and the application of SIM and Empty Box Positive resulted in a marked improvement of the test performance (area under curve, AUC = 0.9668). Analogous results (AUC = 0.9807) were found for the second test collective. CONCLUSIONS: This novel approach is promising and should be tested on a larger, independent collective.

In vivo monitoring of natural killer cell-dependent clearance of lung metastasis using dynamic positron emission tomography.

Immunohistological methods indicated a rapid onset of cellular defence shortly after seeding of mammary adenocarcinoma cells into the lungs of F344 rats. The purpose of the present study was to monitor natural killer (NK) cell-mediated effects on tumour cell clearance in vivo, in this model of lung metastasis using dynamic positron-emission tomography (dPET). MADB106 breast cancer cells were labelled with 2'-[(18)F]-2'-deoxy-D-glucose (FDG) then injected intravenously, after the F344 rats had been anaesthetized and placed in a PET scanner. NK cell-depleted and sham-treated control rats were investigated in parallel. The radioactivity per region of interest (ROI) over the lungs peaked at 60 s past injection and was followed by a slow decline over the observation time of 40 min in both groups. Statistical analysis using a linear mixed model revealed that release of radioactivity from tumour cells or tumour cell disintegration was significantly slower in animals after depletion of NK cells compared with controls. There was no significant tumour cell homing in organs other than the lungs. Early kinetics of tumour cells after injection were defined. PET with FDG was shown to be an adequate method to further investigate novel options for using cellular host defence mechanisms in cancer patients.

Biopsy-controlled liver fibrosis staging using the enhanced liver fibrosis (ELF) score compared to transient elastography.

BACKGROUND AND AIMS: Chronic liver diseases are characterized by inflammatory and fibrotic liver injuries that often result in liver cirrhosis with its associated complications such as portal hypertension and hepatocellular carcinoma. Liver biopsy still represents the reference standard for fibrosis staging, although transient elastography is increasingly used for non-invasive monitoring of fibrosis progression. However, this method is not generally available and is associated with technical limitations emphasizing the need for serological biomarkers staging of liver fibrosis. The enhanced liver fibrosis (ELF) score was shown to accurately predict significant liver fibrosis in different liver diseases, although extracellular matrix components detected by this score may not only mirror the extent of liver fibrosis but also inflammatory processes. METHODS: In this prospective biopsy-controlled study we evaluated the utility of the ELF score in comparison to transient elastography to predict different stages of fibrosis in 102 patients with chronic liver diseases. RESULTS: Both techniques revealed similar area under receiver operating characteristic curve values for prediction of advanced fibrosis stages. Compared to transient elastography, the ELF score showed a broader overlap between low and moderate fibrosis stages and a stronger correlation with inflammatory liver injury. CONCLUSIONS: Both the ELF score as well as transient elastography allowed for high quality fibrosis staging. However, the ELF score was less discriminative in low and moderate fibrosis stages and appeared more strongly influenced by inflammatory liver injury. This should be considered when making clinical interpretations on the basis of ELF score values.

Asymmetric dimethylarginine in children with homocystinuria or phenylketonuria.

Plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis from L-arginine and a cardiovascular risk factor, was found to be elevated in plasma of homocysteinemic adults. Enhanced cardiovascular risk due to homocystinuria and impaired renal function has been found in patients with phenylketonuria (PKU) on protein-restricted diet. However, it is still unknown whether ADMA synthesis is also elevated in children with homocystinuria due to cystathionine beta-synthase deficiency (classical homocystinuria), and whether ADMA may play a role in phenylketonuria in childhood. In the present study, we investigated the status of the L-arginine/NO pathway in six young patients with homocystinuria, in 52 young phenylketonuria patients on natural protein-restricted diet, and in age- and gender-matched healthy children serving as controls. ADMA in plasma and urine was determined by GC-MS/MS. The NO metabolites nitrate and nitrite in plasma and urine, and urinary dimethylamine (DMA), the dimethylarginine dimethylaminohydrolase (DDAH) metabolite of ADMA, were measured by GC-MS. Unlike urine ADMA excretion, plasma ADMA concentration in patients with homocystinuria was significantly higher than in controls (660±158 vs. 475±77 nM, P=0.035). DMA excretion rate was considerably higher in children with homocystinuria as compared to controls (62.2±24.5 vs. 6.5±2.9 µmol/mmol creatinine, P=0.068), indicating enhanced DDAH activity in this disease. In contrast and unexpectedly, phenylketonuria patients had significantly lower ADMA plasma concentrations compared to controls (512±136 vs. 585±125 nM, P=0.009). Phenylketonuria patients and controls had similar L-arginine/ADMA molar ratios in plasma. Urinary nitrite excretion was significantly higher in phenylketonuria as compared to healthy controls (1.7±1.7 vs. 0.7±1.2 µmol/mmol creatinine, P=0.003). Our study shows that the L-arginine/NO pathway is differently altered in children with phenylketonuria and homocystinuria. Analogous to hyperhomocysteinemic adults, elevated ADMA plasma concentrations could be a cardiovascular risk factor in children with homocystinuria. In phenylketonuria, the L-arginine/NO pathway seems not be altered. Delineation of the role of ADMA in childhood phenylketonuria and homocystinuria demands further investigation.

Prospective biopsy-controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis.

UNLABELLED: Fibrosis and steatosis are major histopathological alterations in chronic liver diseases. Despite various shortcomings, disease severity is generally determined by liver biopsy, emphasizing the need for simple noninvasive methods for assessing disease activity. Because hepatocyte cell death is considered a crucial pathogenic factor, we prospectively evaluated the utility of serum biomarkers of cell death to predict different stages of fibrosis and steatosis in 121 patients with chronic liver disease. We compared the M30 enzyme-linked immunosorbent assay (ELISA), which detects a caspase-cleaved cytokeratin-18 (CK-18) fragment and thereby apoptotic cell death, with the M65 ELISA, which detects both caspase-cleaved and uncleaved CK-18 and thereby overall cell death. Both biomarkers significantly discriminated patients with different fibrosis stages from healthy controls. However, whereas both markers differentiated low or moderate from advanced fibrosis, only the M65 antigen could discriminate even lower stages of fibrosis. The M65 assay also performed better in distinguishing low (≤10%) and higher (>10%) grades of steatosis. In a subgroup of patients, we evaluated the biomarkers for their power to predict nonalcoholic steatohepatitis (NASH). Importantly, both markers accurately differentiated healthy controls or simple steatosis from NASH. However, only serum levels of M65 antigen could differentiate simple steatosis from healthy controls. CONCLUSION: Cell death biomarkers are potentially useful to predict fibrosis, steatosis, or NASH. Compared with the widely used apoptosis marker M30, the M65 assay had a better diagnostic performance and even differentiated between lower fibrosis stages as well as between healthy individuals and patients with simple steatosis.

Introduction of e-learning in dental radiology reveals significantly improved results in final examination.

PURPOSE: Because a traditionally instructed dental radiology lecture course is very time-consuming and labour-intensive, online courseware, including an interactive-learning module, was implemented to support the lectures. The purpose of this study was to evaluate the perceptions of students who have worked with web-based courseware as well as the effect on their results in final examinations. MATERIALS AND METHODS: Users (n(3+4)=138) had access to the e-program from any networked computer at any time. Two groups (n(3)=71, n(4)=67) had to pass a final exam after using the e-course. Results were compared with two groups (n(1)=42, n(2)=48) who had studied the same content by attending traditional lectures. In addition a survey of the students was statistically evaluated. RESULTS: Most of the respondents reported a positive attitude towards e-learning and would have appreciated more access to computer-assisted instruction. Two years after initiating the e-course the failure rate in the final examination dropped significantly, from 40% to less than 2%. CONCLUSIONS: The very positive response to the e-program and improved test scores demonstrated the effectiveness of our e-course as a learning aid. Interactive modules in step with clinical practice provided learning that is not achieved by traditional teaching methods alone. To what extent staff savings are possible is part of a further study.

Is there an association between comorbidities and the outcome of microvascular free tissue transfer?

The aim of this study was to evaluate the relevant conditions for safe free flap transfers. The authors retrospectively studied the data from 150 patients who received free flaps at a single institution. Many parameters were analyzed to reveal if there was a correlation with respect to surgical or medical complications. Regarding safety of free tissue transfer, we found a worse prognosis in flaps where a revision of the microanastomosis had to be performed. Platelet count and leukocyte count had an impact on the prognosis. Patients older than 60 years did not have an increased rate of surgical complications. Apart from active osteomyelitis, the presence of comorbid conditions did not significantly impair the outcome of flap transfer, although smoking and diabetes correlated with minor surgical complications like wound breakdown or hematoma, respectively. Besides one case of lethal heart failure of an octogenarian patient, no severe medical complications occurred in this series of patients. Microvascular free tissue transfer is not significantly impaired by age and most comorbidities. Osteomyelitis as well as elevated leukocytes and lowered platelets may increase the complication rate and worsen the surgical prognosis. Smoking and diabetes might prolong the hospital course of the patients.

[Comparison of current methods of prenatal screening for down syndrome]. / Comparación de los métodos actuales de cribado prenatal del síndrome de down.

BACKGROUND: In Spain all pregnant women aged 35 years and older are offered genetic examination through invasive testing in order to detect fetal trisomy 21 cases (maternal age indication (MAI)). In the last decade five distinct software programs utilizing the "first trimester screening (FTS)" were developed. The objective of this study is to compare the test performance of the different screening methods in order to detect the best current approach. METHODS: 7.736 complete first trimester screenings, including the fetal outcome, were realized between 31.08.1999 and 24.05.2007 in three prenatal health centres in Hannover, Peine, and Wolfenbüttel in Germany. Out of these 6.508 cases were analyzed retrospectively in this study. Maternal age was determined and risk calculation with the software programs PIA, PRC, JOY, AFS and AFS-3D was executed. RESULTS: The MAI reached a sensitivity of 57.50%, detecting only 23 out of 40 trisomy 21 cases, and a false positive rate of 21.60%. In comparison, all risk calculation programs obtained superior results, attaining a sensitivity between 90.00% (AFS) and 92.50% (PIA, PRC, JOY, AFS-3D) and a false positive rate between 2.64% (AFS-3D) and 7.87% (PIA). The difference was highly significant (p<0.0001) CONCLUSIONS: The MAI is obsolete and inadequate in comparison with the risk calculation software, out of which all obtained test performances within the range of comparable international publications. Among these programs, JOY, AFS, and AFS-3D obtained the best results.

Partial rescue of the KIT-deficient testicular phenotype in KitW-v/KitW-v Tg(TSPY) mice.

TSPY encodes the testis-specific protein Y-linked. In man, expression of TSPY is restricted to the testis, where TSPY is expressed in spermatogonia, primary spermatocytes, and round spermatids, and to the prostate gland. There is circumstantial evidence that TSPY is involved in spermatogonial proliferation and gonadal tumorigenesis. Because the laboratory mouse carries the Tspy gene in a naturally silenced state (Tspy-ps), we previously restored TSPY activity in mice and generated a TSPY transgenic mouse line in which the organization and expression of the human TSPY transgene follow the human pattern. In the present study, we generated TSPY transgenic KIT-deficient Kit(W-v)/Kit(W-v) mice and analyzed the histology of the testes and epididymides in order to contribute to understanding TSPY function in early germ cell development and spermatogenesis. The KIT receptor and its ligand KITL, previously called stem cell factor, have an indispensable role in hematopoiesis, melanogenesis, and gametogenesis. Homozygous Kit(W-v) mutant male mice on a C57BL/6J background with a mutation in the Kit gene are infertile due to an almost total loss of germ cells in the testes. In this study, histological analyses of testes and epididymides showed an increased number of meiotic and postmeiotic germ cells in Kit(W-v)/Kit(W-v) Tg(TSPY) mice compared with age-matched Kit(W-v)/Kit(W-v) controls. TSPY was able to restore fertility of some but not all TSPY transgenic Kit(W-v)/Kit(W-v) males. Our findings show that TSPY is able to partially rescue spermatogenesis and fertility of Kit(W-v)/Kit(W-v) mutants and thereby point to a putative role of TSPY in fetal and adult germ cell proliferation.

IL-6 predicts organ dysfunction and mortality in patients with multiple injuries.

BACKGROUND: Although therapeutic concepts of patients with major trauma have improved during recent years, organ dysfunction still remains a frequent complication during clinical course in intensive care units. It has previously been shown that cytokines are upregulated under stress conditions such as trauma or sepsis. However, it is still debatable if cytokines are adequate parameters to describe the current state of trauma patients. To elucidate the relevance of cytokines, we investigated if cytokines predict development of multiple organ dysfunction syndrome (MODS) or outcome. METHODS: A total of 143 patients with an injury severity score >or= 16, between 16 and 65 years, admitted to the Hannover Medical School Level 1 Trauma Center between January 1997 and December 2001 were prospectively included in this study. Marshall Score for MODS was calculated for at least 14 days and plasma levels of TNF-alpha, IL-1beta, IL-6, IL-8 and IL-10 were measured. To determine the association between cytokine levels and development of MODS the Spearman rank correlation coefficient was calculated and logistic regression and analysis were performed. RESULTS AND DISCUSSION: Patients with MODS had increased plasma levels of IL-6, IL-8 and IL-10. IL-6 predicted development of MODS with an overall accuracy of 84.7% (specificity: 98.3%, sensitivity: 16.7%). The threshold value for development of MODS was 761.7 pg/ml and 2176.0 pg/ml for mortality during the in patient time. CONCLUSION: We conclude that plasma IL-6 levels predict mortality and that they are a useful tool to identify patients who are at risk for development of MODS.

Non-invasive coronary angiography: the clinical value of multi-slice computed tomography in the assessment of patients with prior coronary bypass surgery. Evaluating grafts and native vessels.

BACKGROUND: Contrast enhanced multi-slice computed tomography (MSCT) is the leading modality in non-invasive coronary angiography (CTA) today. We investigated MSCT based assessment of coronary artery bypass grafts (CABG) by analyzing assets and drawbacks of CTA in order to define demands on latest technology. METHODS: In a clinical setting 39 CABG patients (69.2 +/- 1.4 years; male n = 36) underwent CTA (collimation 16 x 0.75 mm, contrast medium 100 ml; 320 mAs, 120 KV). Ninety-seven CABG (61 venous, 36 arterial grafts) were evaluated. A subgroup of 18 patients underwent additional invasive coronary angiography (CA). RESULTS: CTA for CABG assessment resulted in an overall sensitivity (sens.) of 100%, specificity (spec.) of 92.4% and positive and negative predictive values (PPV, NPV) of 60% and 100%, respectively. CABG anastomoses showed slightly inferior diagnostic accuracy than other CABG segments. Limitations in imaging quality caused 21% unevaluable segments of the CABG anastomoses. Evaluation of native vessel segments proximal and distal to the anastomoses resulted in a sens, spec, PPV and NPV of 57.5, 94.6, 92 and 67.3%, respectively. With 28.5% unevaluable segments, the native vessel segments showed serious limitations in imaging quality. Radiation exposure was 9.88 +/- 3.20 mSv (9.69 +/- 3.25 mSv male; 12.08 +/- 1.35 mSv female). CONCLUSION: 16-slice MSCT based CABG assessment offers sufficient diagnostic accuracy. However, focussing on the bypass anastomoses and the native revascularized coronary arteries, clinical value is limited.

Improved prenatal aneuploidy screening using the novel advanced first-trimester screening algorithm: a multicenter study of 10,017 pregnancies.

PURPOSE: : It has been postulated that the maternal age component should be completely excluded from first-trimester screening (FTS) for fetal aneuploidies. In this study, we tested a new algorithm known as advanced first-trimester screening (AFS), which disregards maternal age. METHOD: : In a multicenter study, FTS findings were retrieved from 10,017 pregnancies. FTS risk assessment was performed using the Nicolaides method, and the AFS score was calculated. The results of both methods were compared. RESULTS: : Within this population, 81 fetuses had an abnormal karyotype. The sensitivity of the 2 algorithms was 86.4%. When the AFS method was used, the positive predictive value rose from 9.6% (FTS) to 12.4% (AFS). Using AFS, the test positive rate could be decreased by 161 cases (-22.2%) (p < 0.0001), due to a reduction of false positive cases. As a result, the false positive rate of AFS was 24.5% lower than that of FTS, while the same number of aneuploidies was detected. CONCLUSION: : AFS can markedly reduce the rate of false positive test results. If these results are confirmed by larger multicenter studies, the new AFS will represent a great improvement in fetal aneuploidy screening. (c) 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008.

TSPY expression is variably altered in transgenic mice with testicular feminization.

TSPY (testis-specific protein, Y-encoded) genes are expressed in premeiotic germ cells and round spermatids. The topology and timing of TSPY expression, and also its homology to members of the TTSN-family, suggest that TSPY is a proliferation factor for germ cells. There is also evidence for a role of TSPY in the aetiology of testis cancer. TSPY is a candidate for GBY, the elusive gonadoblastoma locus on the human Y chromosome, which is thought to predispose dysgenetic gonads of 46, XY sex-reversed females to develop gonadoblastoma. We have previously generated a TSPY transgenic mouse line (Tg(TSPY)9Jshm) that carries approximately 50 copies of the human TSPY gene on the mouse Y chromosome. In order to elucidate TSPY expression under complete androgen insensitivity and to investigate a possible role of TSPY in gonadal tumorigenesis, we have now generated sex-reversed TSPY transgenic Ar(Tfm) mice hemizygous for the X-linked testicular feminization mutation (Ar(Tfm)). We can show that the TSPY transcript is aberrantly spliced in the testes of TSPY-Ar(Tfm) mice, and that TSPY expression is upregulated by androgen insensitivity in some but not all animals. TSPY transgenic mice showed significantly increased testes weights. In one TSPY transgenic Ar(Tfm) animal, spermatogenesis proceeded beyond meiotic prophase. No tumors of germ cell origin were found in the testes of TSPY-Ar(Tfm) mice. Five out of 46 TSPY transgenic Ar(Tfm) mice, and 3 out of 31 age-related NMRI-Ar(Tfm) controls developed Leydig cell tumors, whereas none of the age-matched Ar(Tfm) mice (n=44) on a wild type background were affected by Leydig cell tumorigenesis.

Adiposity and age are statistically related to enhanced RASSF1A tumor suppressor gene promoter methylation in normal autopsy kidney tissue.

Age, adiposity, and smoking are risk factors for the development of renal cell carcinoma. Hypermethylation of the RAS association domain family 1A gene (RASSF1A) promoter belongs to the most frequently detected epigenetic alterations in human cancers including renal cell carcinoma. RASSF1A is functionally involved in cell cycle control in normal cells and depletion promotes a number of cellular changes increasing the risk for neoplastic growth. We investigated the hypothesis that age, modulated by the factors adiposity and anthracosis as a surrogate for smoking, is a predictor of RASSF1A promoter methylation in normal kidney tissue. Using a cross-sectional study design, we quantitatively analyzed RASSF1A methylation in 78 normal autopsy kidney tissues by quantitative combined bisulfite and restriction analysis and bisulfite sequencing, and statistically evaluated the degree of relative methylation for a relationship with the predictor age and study factors adiposity and state of anthracosis. Statistical analysis showed that age (regression analysis; P < 0.001), adiposity (univariate analysis; P = 0.016), and state of anthracosis (t test; P = 0.005) are each significantly associated with an increase of RASSF1A promoter methylation in normal kidney tissue. However, only age (P = 0.008) and adiposity (P = 0.008) were identified as independent predictors of RASSF1A promoter methylation using covariance analysis. This study provides statistical evidence that the common cancer risk factors age and adiposity enhance RASSF1A promoter methylation in nonmalignant kidney tissue.

Advanced first trimester screening (AFS): an improved test strategy for the individual risk assessment of fetal aneuploidies and malformations.

OBJECTIVE: First trimester risk assessment for fetal aneuploidies is computed on the base of a general background risk, which is depending on the maternal age. Thereby, the adjusted risk tends to rise with increasing age. Obversely, more unsuspicious fetal parameters [measurement of the nuchal translucency (NT) and biochemical parameters, free beta human chorionic gonadotropine (fbetaB-Hcg) and pregnancy associated plasma protein A (Papp-A)] have to be observed to result in an unsuspicious test at higher age. It was the aim of this study to investigate the potential value of a novel risk assessment algorithm explicitly disregarding the maternal age. METHODS: This was an ultrasound cohort study of 1,463 singleton pregnancies at 11-14 weeks of gestation undergoing a first trimester screening for fetal aneuploidies by measuring the (NT), Papp-A and fbeta-hCG. In each case, the pregnancy outcome was obtained. Regarding either the detection of genetic affections or the combined detection of genetic or somatic anomalies, the test performance parameters (sensitivity, specificity, positive and negative predictive values) were calculated and compared with each other. For risk calculation the standard Fetal Medicine Foundation (FMF)-Software and an alternative software with a similar algorithm (JOY-Software) were utilized. Compared to this, the risk assessment had been modified by implementing a novel calculation algorithm (advanced first trimester screening algorithm, AFS) purposely disregarding the maternal age and again, the test performance parameters had been computed and were compared with the first ones. RESULTS: At the mere genetic analysis, all four test-strategies revealed to have identical sensitivity and negative predictive values. Compared to the standard FMF-Software, the JOY-Software showed a reduced false positive rate. In addition, in both softwares, the false positive rate is highly significant-reduced by implementing the AFS-algorithm. At combined genetic and somatic analysis, analogous results on different counts could be found. CONCLUSION: In the effort to create an algorithm characterising somatic and fetal conditions of the fetus most properly, the inclusion of maternal age is not a helpful value and excluding the age from risk calculation leads to a high significant reduction of the false positive rate. Further, a comparable marked increase of both, specificity and positive predictive values, can be achieved for the FMF- and JOY-Software on the background of the generally more favourable JOY test performance.