Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

BACKGROUND: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner. PATIENTS AND METHODS: We used machine learning models of fragmentation patterns at the first coding exon in standard targeted cancer gene cfDNA sequencing panels to distinguish between cancer and non-cancer patients, as well as the specific tumor type and subtype. We assessed this approach in two independent cohorts: a published cohort from GRAIL (breast, lung, and prostate cancers, non-cancer, n = 198) and an institutional cohort from the University of Wisconsin (UW; breast, lung, prostate, bladder cancers, n = 320). Each cohort was split 70%/30% into training and validation sets. RESULTS: In the UW cohort, training cross-validated accuracy was 82.1%, and accuracy in the independent validation cohort was 86.6% despite a median ctDNA fraction of only 0.06. In the GRAIL cohort, to assess how this approach performs in very low ctDNA fractions, training and independent validation were split based on ctDNA fraction. Training cross-validated accuracy was 80.6%, and accuracy in the independent validation cohort was 76.3%. In the validation cohort where the ctDNA fractions were all <0.05 and as low as 0.0003, the cancer versus non-cancer area under the curve was 0.99. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that sequencing from targeted cfDNA panels can be utilized to analyze fragmentation patterns to classify cancer types, dramatically expanding the potential capabilities of existing clinically used panels at minimal additional cost.

Oesophageal Doppler guided goal-directed haemodynamic therapy in thoracic surgery - a single centre randomized parallel-arm trial.

BACKGROUND: Postoperative pulmonary and renal complications are frequent in patients undergoing lung surgery. Hyper- and hypovolaemia may contribute to these complications. We hypothesized that goal-directed haemodynamic management based on oesophageal Doppler monitoring would reduce postoperative pulmonary complications in a randomized clinical parallel-arm trial. METHODS: One hundred patients scheduled for thoracic surgery were randomly assigned to either standard haemodynamic management (control group) or goal-directed therapy (GDT group) guided by an oesophageal Doppler monitoring-based algorithm. The primary endpoint was postoperative pulmonary complications, including spirometry. Secondary endpoints included haemodynamic variables, renal, cardiac, and neurological complications, and length of hospital stay. The investigator assessing outcomes was blinded to group assignment. RESULTS: Forty-eight subjects of each group were analysed. Compared to the control group, fewer subjects in the GDT group developed postoperative pulmonary complications (6 vs. 15 patients; P = 0.047), while spirometry did not differ between groups. Compared to the control group, patients of the GDT group showed higher cardiac index (2.9 vs. 2.1 [l min - 1 m - 2 ]; P < 0.001) and stroke volume index (43 vs. 34 [ml m 2 ]; P < 0.001) during surgery. Renal, cardiac and neurological complications did not differ between groups. Length of hospital stay was shorter in the GDT compared to the control group (9 vs. 11 days; P = 0.005). CONCLUSIONS: Compared to standard haemodynamic management, oesophageal Doppler monitor-guided GDT was associated with fewer postoperative pulmonary complications and a shorter hospital stay. CLINICAL TRIAL REGISTRATION.: The study was registered in the German Clinical Trials Register (DRKS 00006961). https://drks-neu.uniklinik-freiburg.de/drks_web/.

The effect of different collagen modifications for titanium and titanium nitrite surfaces on functions of gingival fibroblasts.

OBJECTIVES: Targeted modifications of the bulk implant surfaces using bioactive agents provide a promising tool for improvement of the long-term bony and soft tissue integration of dental implants. In this study, we assessed the cellular responses of primary human gingival fibroblasts (HGF) to different surface modifications of titanium (Ti) and titanium nitride (TiN) alloys with type I collagen or cyclic-RGDfK-peptide in order to define a modification improving long-term implants in dental medicine. MATERIALS AND METHODS: Employing Ti and TiN implants, we compared the performance of simple dip coating and anodic immobilization of type I collagen that provided collagen layers of two different thicknesses. HGF were seeded on the different coated implants, and adhesion, proliferation, and gene expression were analyzed. RESULTS: Although there were no strong differences in initial cell adhesion between the groups at 2 and 4 hours, we found that all surface modifications induced higher proliferation rates as compared to the unmodified controls. Consistently, gene expression levels of cell adhesion markers (focal adhesion kinase (FAK), integrin beta1, and vinculin), cell differentiation markers (FGFR1, TGFb-R1), extracellular protein markers (type I collagen, vimentin), and cytoskeletal protein marker aktinin-1 were consistently higher in all surface modification groups at two different time points of investigation as compared to the unmodified controls. CONCLUSION: Our results indicate that simple dip coating of Ti and TiN with collagen is sufficient to induce in vitro cellular responses that are comparable to those of more reliable coating methods like anodic adsorption, chemical cross-linking, or RGD coating. TiN alloys do not possess any positive or adverse effects on HGF. CLINICAL RELEVANCE: Our results demonstrate a simple, yet effective, method for collagen coating on titanium implants to improve the long term integration and stability of dental implants.

Intensive intravenous infusion of insulin in diabetic cats.

BACKGROUND: Remission occurs in 10-50% of cats with diabetes mellitus (DM). It is assumed that intensive treatment improves ß-cell function and increases remission rates. HYPOTHESIS: Initial intravenous infusion of insulin that achieves tight glycemic control decreases subsequent insulin requirements and increases remission rate in diabetic cats. ANIMALS: Thirty cats with newly diagnosed DM. METHODS: Prospective study. Cats were randomly assigned to one of 2 groups. Cats in group 1 (n = 15) received intravenous infusion of insulin with the goal of maintaining blood glucose concentrations at 90-180 mg/dL, for 6 days. Cats in group 2 (n = 15) received subcutaneous injections of insulin glargine (cats ≤4 kg: 0.5-1.0 IU, q12h; >4 kg 1.5-2.0 IU, q12h), for 6 days. Thereafter, all cats were treated with subcutaneous injections of insulin glargine and followed up for 6 months. Cats were considered in remission when euglycemia occurred for ≥4 weeks without the administration of insulin. Nonparametric tests were used for statistical analysis. RESULTS: In groups 1 and 2, remission was achieved in 10/15 and in 7/14 cats (P = .46), and good metabolic control was achieved in 3/5 and in 1/7 cats (P = .22), respectively. Overall, good metabolic control or remission occurred in 13/15 cats of group 1 and in 8/14 cats of group 2. In group 1, the median insulin dosage given during the 6-month follow-up was significantly lower than in group 2 (group 1: 0.32 IU/kg/day, group 2: 0.51 IU/kg/day; P = .013). CONCLUSIONS AND CLINICAL IMPORTANCE: Initial intravenous infusion of insulin for tight glycemic control in cats with DM decreases insulin requirements during the subsequent 6 months.

Remission of diabetes mellitus in cats cannot be predicted by the arginine stimulation test.

BACKGROUND: Cats with diabetes mellitus frequently achieve clinical remission, suggesting residual ß-cell function. Responsiveness of ß-cells to arginine persists the longest during diabetes progression, making the intravenous arginine stimulation test (IVAST) a useful tool to assess residual insulin and glucagon secretion. HYPOTHESIS: Diabetic cats with and without remission will have different arginine-induced insulin or glucagon response. ANIMALS: Seventeen cats with diabetes, 7 healthy cats. METHODS: Blood samples collected on admission and during subsequent IVAST. Glucose, insulin, and glucagon were measured. Response to IVAST was assessed by calculating the insulin and glucagon area under the curve (AUC) and the AUC glucagon-to-insulin ratio. Diabetic cats were treated with insulin and were followed for 18 weeks. Remission was defined as normoglycemia and disappearance of clinical signs of diabetes for ≥4 weeks, without requiring insulin. RESULTS: Seven diabetic cats (41%) achieved remission. On admission, blood glucose concentration was significantly lower in cats with remission (median, 389 mg/dL; range, 342-536 mg/dL) than in those without remission (median, 506 mg/dL; range, 266-738 mg/dL). After IVAST, diabetic cats with remission had higher AUC glucagon-to-insulin ratios (median, 61; range, 34-852) than did cats without remission (median, 26; range, 20-498); glucose, insulin, and glucagon AUCs were not different. Diabetic cats had lower insulin AUC than did healthy cats but comparable glucagon AUC. CONCLUSIONS AND CLINICAL IMPORTANCE: Diabetic cats with and without remission have similar arginine-stimulated insulin secretion on admission. Although cats with remission had lower blood glucose concentrations and higher AUC glucagon-to-insulin ratios, large overlap between groups prevents use of these parameters in clinical practice.

Insulin resistance and increased lipolysis in bone marrow derived adipocytes stimulated with agonists of Toll-like receptors.

Our objectives were to identify Toll-like receptors (TLRs) in human bone marrow derived adipocytes, to test specific TLR agonists for their ability to induce a proinflammatory response, and to investigate possible metabolic effects after TLR activation, in particular, those associated with insulin resistance and lipolysis. Mesenchymal stem cells were isolated from human bone marrow and differentiated into adipocytes. Total RNA before or after stimulation with agonists specific for TLR was extracted for analysis of expression of TLRs proinflammatory signals and molecules involved in glucose metabolism (IRS-1 and GLUT4). Furthermore, cytokine protein expression was measured from cell lysates. Finally, insulin induced glucose uptake and lipolysis were measured. Human bone marrow-derived adipocytes express TLR1-10. They react to stimulation with specific ligands with expression of inflammatory markers (IL-1beta, IL-6, TNFalpha, IL-8, MCP-1) at the RNA and protein levels. IRS-1 and GLUT4 expression was downregulated after stimulation with the TLR4 and TLR3 specific ligands LPS and poly (I:C), respectively. Insulin-induced glucose uptake was decreased and lipolysis increased. We conclude that adipocytes express TLR 1-10 and react to agonists specific for TLR 1-6. As a consequence proinflammatory cytokine are induced, in particular, IL-6, IL-8, and MCP-1. Since stimulation is followed by decreased insulin-induced glucose uptake and increased lipolysis we conclude that TLRs may be important linking molecules in the generation of insulin resistance in fat tissue.

10-day hyperlipidemic clamp in cats: effects on insulin sensitivity, inflammation, and glucose metabolism-related genes.

Obesity and hyperlipidemia are associated with impaired insulin sensitivity in human type 2 diabetes mellitus, possibly due to activation of a mild inflammatory response. Because obesity-induced insulin resistance predisposes cats to diabetes and because hyperlipidemia is a frequent concurrent finding, excess lipids may also impair insulin sensitivity in cats. Healthy cats (n=6) were infused with lipids (Lipovenoes 10%) for 10 days to clamp blood triglycerides at the approximate concentration of untreated feline diabetes (3-7 mmol/l). Controls received saline (n=5). On day 10, plasma adiponectin and proinflammatory markers were measured. Whole-body insulin sensitivity was calculated following an intravenous glucose tolerance test. Tissue mRNAs of glucose metabolism-related genes were quantified in subcutaneous and visceral fat, liver, and skeletal muscles. Accumulation of lipids was assessed in liver. At the termination of infusion, whole-body insulin sensitivity did not differ between groups. Compared to saline, cats infused with lipids had 50% higher plasma adiponectin and 2-3 times higher alpha(1)-acid glycoprotein and monocyte chemoattractant protein-1. Unexpectedly, lipid-infused cats had increased glucose transporter-4 (GLUT4) mRNA in the visceral fat, and increased peroxisome proliferative activated receptor-gamma2 (PPARgamma2) in subcutaneous fat; adiponectin expression was not affected in any tissue. Lipid-infused cats developed hepatic steatosis. Although hyperlipidemia induced systemic inflammation, whole-body insulin sensitivity was not impaired after 10 day infusion. Increased circulating adiponectin may have contributed to prevent insulin resistance, possibly by increasing GLUT4 and PPARgamma2 transcripts in fat depots.

Amylin reduces plasma glucagon concentration in cats.

Pancreatic amylin plays an important role in the control of nutrient fluxes and is an established therapy in human diabetes as it reduces post-prandial glucagon secretion and slows gastric emptying. Given the similar pathophysiology of human type-2 and feline diabetes mellitus, we investigated whether amylin reduces plasma glucagon levels in cats. Healthy cats were tested using an intravenous arginine stimulation test (IVAST), a meal response test with the test meal comprising 50% of average daily food intake, and an IV glucose tolerance test (IVGTT). Non-amyloidogenic rat amylin injected 5 min before the respective stimulus significantly reduced plasma glucagon levels under all test situations. In the IVAST and IVGTT, cats treated with amylin also had lower plasma insulin concentrations. It was concluded that amylin does reduce plasma glucagon levels in cats, a feature that has treatment potential in diabetic animals as co-administration of amylin would reduce the insulin requirement to control glycaemia.

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study.

Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 microg kg(-1) (lower-dose) ghrelin; 11 received 8 microg kg(-1) (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4-5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml(-1) with lower-dose and 42 ng ml(-1) with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (P<0.05) for upper-dose patients at end of study (3580 pg ml(-1)) than at baseline (990 pg ml(-1)). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower- and upper-dose group.

Monitoring survival and function of transfused platelets in Glanzmann thrombasthenia by flow cytometry and thrombelastography.

Patients with Glanzmann thrombasthenia (GT) may form isoantibodies which induce refractoriness or inhibition of function of transfused platelets. We monitored the survival and function of transfused platelets by flow cytometry and thrombelastography in a patient with GT. Gating on CD42a+ allowed identification of even a few transfused platelets. Only by gating on these CD41+ CD42a+ cells were we able to demonstrate their capability to bind fibrinogen and PAC-1 upon activation. Platelets were rapidly cleared from the circulation as a result of boosted isoantibodies. The contribution of transfused platelets to clot formation was also demonstrated by thrombelastography by blocking their function with abciximab.

Development, parallelization, and automation of a gas-inducing milliliter-scale bioreactor for high-throughput bioprocess design (HTBD).

A novel milliliter-scale bioreactor equipped with a gas-inducing impeller was developed with oxygen transfer coefficients as high as in laboratory and industrial stirred-tank bioreactors. The bioreactor reaches oxygen transfer coefficients of >0.4 s(-1). Oxygen transfer coefficients of >0.2 s(-1) can be maintained over a range of 8- to 12-mL reaction volume. A reaction block with integrated heat exchangers was developed for 48-mL-scale bioreactors. The block can be closed with a single gas cover spreading sterile process gas from a central inlet into the headspace of all bioreactors. The gas cover simultaneously acts as a sterile barrier, making the reaction block a stand-alone device that represents an alternative to 48 parallel-operated shake flasks on a much smaller footprint. Process control software was developed to control a liquid-handling system for automated sampling, titration of pH, substrate feeding, and a microtiter plate reader for automated atline pH and atline optical density analytics. The liquid-handling parameters for titration agent, feeding solution, and cell samples were optimized to increase data quality. A simple proportional pH-control algorithm and intermittent titration of pH enabled Escherichia coli growth to a dry cell weight of 20.5 g L(-1) in fed-batch cultivation with air aeration. Growth of E. coli at the milliliter scale (10 mL) was shown to be equivalent to laboratory scale (3 L) with regard to growth rate, mu, and biomass yield, Y(XS).

A novel MADS-box gene subfamily with a sister-group relationship to class B floral homeotic genes.

Class B floral homeotic genes specify the identity of petals and stamens during the development of angiosperm flowers. Recently, putative orthologs of these genes have been identified in different gymnosperms. Together, these genes constitute a clade, termed B genes. Here we report that diverse seed plants also contain members of a hitherto unknown sister clade of the B genes, termed B(sister) (B(s)) genes. We have isolated members of the B(s) clade from the gymnosperm Gnetum gnemon, the monocotyledonous angiosperm Zea mays and the eudicots Arabidopsis thaliana and Antirrhinum majus. In addition, MADS-box genes from the basal angiosperm Asarum europaeum and the eudicot Petunia hybrida were identified as B(s) genes. Comprehensive expression studies revealed that B(s) genes are mainly transcribed in female reproductive organs (ovules and carpel walls). This is in clear contrast to the B genes, which are predominantly expressed in male reproductive organs (and in angiosperm petals). Our data suggest that the B(s) genes played an important role during the evolution of the reproductive structures in seed plants. The establishment of distinct B and B(s) gene lineages after duplication of an ancestral gene may have accompanied the evolution of male microsporophylls and female megasporophylls 400-300 million years ago. During flower evolution, expression of B(s) genes diversified, but the focus of expression remained in female reproductive organs. Our findings imply that a clade of highly conserved close relatives of class B floral homeotic genes has been completely overlooked until recently and awaits further evaluation of its developmental and evolutionary importance. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00438-001-0615-8.

Epidermal growth factor and platelet-derived growth factor induce expression of Egr-1, a zinc finger transcription factor, in human malignant glioma cells.

Amplification and/or mutations of the epidermal growth factor (EGF) receptor have been frequently reported in human malignant gliomas, the most common primary tumor of the adult central nervous system. We have analyzed a panel of established human glioma cell lines for EGF receptor expression. The EGF receptor was expressed in all of the glioma cell lines tested, with highest levels found in the cell line U343MG-a. In addition, various amounts of a truncated form of the EGF receptor were detected. The platelet-derived growth factor (PDGF) alpha receptor, analyzed for comparison, was expressed at low levels in human glioma cells, with the exception of U-118MG and U-373MG cells. The truncated form of the EGF receptor has been discussed as a constitutively active variant of the receptor. Using antibodies directed against the active form of the EGF receptor, we show here that the truncated variant of the EGF receptor in U343MG-a cells is not in the active conformation. However, the full-length EGF receptor, highly expressed in U343MG-a cells, was very rapidly activated following EGF treatment. In line with this, phosphorylation and activation of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) in U343MG-a cells required administration of EGF. Moreover, using highly specific riboprobes we observed that EGF signaling increased the Egr-1 mRNA concentration in human glioma cells within 30 min. The increase in the Egr-1 mRNA concentration was followed by a transient synthesis of the Egr-1 protein. Likewise, Egr-1 mRNA and protein concentrations were increased in U-118MG and U-373MG cells treated with PDGF. The synthesis of Egr-1 in human glioma cells as a result of EGF or PDGF stimulation indicates that Egr-1 may be an important "late" part of the EGF and PDGF-initiated signaling cascades suggesting that Egr-1 functions as a "third messenger" in glioma cells connecting growth factor stimulation with changes in gene transcription.

The extracellular signal-regulated protein kinases Erk1/Erk2 stimulate expression and biological activity of the transcriptional regulator Egr-1.

The zinc finger protein early growth response 1 (Egr-1) is a transcriptional activator involved in the regulation of growth and differentiation. We show here that a constitutive active mutant of mitogen-activated kinase kinase-1 (MAPKK-1) strongly stimulates the activity of the Egr-1 promoter, thus explaining the effects of mitogens upon Egr-1 mRNA and protein levels. Moreover, we show that a constitutive active MAPKK-1 leads to an increase in the biological activity of Egr-1 to activate transcription. We conclude that the signaling pathway involving mitogen-activated protein kinase/extracellular signal-regulated protein kinase has a dual impact on the biology of Egr-1 by controlling the transcription of the Egr-1 gene and the transcriptional activity of the Egr-1 protein.

Anthracycline-induced acute cardiotoxicity in adults treated for leukaemia. Analysis of the clinico-pathological aspects of documented acute anthracycline-induced cardiotoxicity in patients treated for acute leukaemia at the University Hospital of Zürich, Switzerland, between 1990 and 1996.

BACKGROUND: Acute cardiotoxicity due to anthracyclines is a rare, but life-threatening event. Interindividual sensitivity to anthracyclines is highly variable and cannot be predicted for the individual patient. PATIENTS AND METHODS: This is a retrospective study. Medical charts and autopsy reports of patients treated for acute leukemia between 1990 and 1996 at the University Hospital of Zürich, Switzerland were reviewed and searched for anthracycline-associated acute cardiotoxicity. Patients with pre-existing heart disease known to be associated with cardiotoxicity were excluded. RESULTS: Seven patients treated for leukemia with proven anthracycline-associated acute cardiotoxicity were included. In six patients the direct cause of death was acute cardiotoxicity due to the treatment. One patient recovered from cardiac failure but died a few months later from refractory leukemia. Clinical symptoms were those of a heart failure. Pathological findings were dilatative cardiac hypertrophy and pericardial effusion. Microscopically the typical findings of myocardial fibrosis and perinuclear vacuolisated myocytes were seen. CONCLUSIONS: The awareness of acute adverse effects on cardiac performance by anthracyclines faciliates early recognition and prevention of heart failure. Reliable tests are needed for the early diagnosis of subclinical myocardial damage in order to identify patients at risk.

The human transcriptional repressor protein NAB1: expression and biological activity.

The zinc finger protein early growth response 1 (Egr-1) is a transcriptional activator involved in the regulation of growth and differentiation. Egr-1 has a large activating domain and three zinc finger motifs that function as a DNA binding region. We show here that a third functional domain of the Egr-1 protein, localized between the extended activation domain and the zinc finger DNA binding region, acts as a transcriptional repressor domain when fused to a heterologous DNA binding domain (DBD). Through protein-protein interaction this inhibitory domain of Egr-1 brings the transcriptional corepressor NAB1 in close proximity to the transcription unit. NAB1 is expressed ubiquitously in human cell lines as shown by RNase protection mapping. Overexpression studies revealed that NAB1 is able to completely block transcription mediated by Egr-1. In addition, the transcriptional repression activity of a fusion protein containing the inhibitory domain of Egr-1 and the DBD of the yeast transcription factor GAL4 was increased by overexpression of NAB1. A fusion protein consisting of the DBD of GAL4 and the coding region of human NAB1 repressed transcription from model promoters with engineered upstream GAL4 binding sites. The GAL4-NAB1 fusion protein functioned from proximal and distal positions indicating that NAB1 displays transcriptional repressor activity at any position within the transcription unit. Thus, the biological function of the inhibitory domain of Egr-1 is solely to provide a docking site for NAB1 via protein-protein interaction.

Measurement of cardiac troponin T is an effective method for predicting complications among emergency department patients with chest pain.

STUDY OBJECTIVES: To determine the test performance characteristics of serum cardiac troponin T (cTnT) measurement for diagnosis of acute myocardial infarction (AMI), and to determine the ability of cTnT to stratify emergency department patients with chest pain into high- and low-risk groups for cardiac complications. METHODS: We conducted a prospective observational cohort study with convenience sampling in a tertiary care, urban ED. The study sample comprised 667 patients presenting to the ED with a complaint of chest pain or other symptoms suggesting acute ischemic coronary syndrome (AICS). Patients were assigned to different blood sampling protocols for cTnT therapy on the basis of their ECG at presentation: nondiagnostic for AMI at 0, 3, 6, 9, 12, and 24 hours after ED presentation; or ECG diagnostic for AMI at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 18, and 24 hours after ED presentation. RESULTS: Of 667 patients, 34 had AMI diagnosed within 24 hours of ED arrival. Using a .2 microgram/L discrimination level for cTnT, sensitivity for AMI within 24 hours of ED arrival was 97% (95% confidence interval, 91.4% to 99.9%), and specificity was 92% (89.8%-94.1%). When the effects of age, race, sex, and creatine kinase-MB isoenzyme subunit test results were controlled, a patient with cTnT of .2 microgram/L or greater was 3.5 (1.4 to 9.1) times more likely to have a cardiac complication within 60 days of ED arrival than a patient with a cTnT value below .2 microgram/L. CONCLUSION: Measurement of cTnT will accurately identify myocardial necrosis in patients presenting to the ED with possible AICS. Elevated cTnT values identify patients at increased risk of cardiac complications.

Ultrasound detection of Apert syndrome: a case report and literature review.

Apert Syndrome is characterized by craniosynostosis, bilateral syndactyly, and midfacial hypoplasia. Although it was first described by Wheaton in 1894, it was first diagnosed prenatally only a decade ago-with only five cases reported in the literature. A sixth case is reported here. Prenatal diagnosis of Apert syndrome is reviewed.