bluuebunny/crossref_metadata_2025 huggingface dataset:
ERCC22251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: A preliminary study
Authors: Huang Ming-Yii , Fang Wei-Yu , Lee Su-Chen , Cheng Tian-Lu , Wang Jaw-Yuan , Lin Shiu-Ru
Published: March 2008

Background

Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes.

Methods

Six gene polymorphisms functional in drug-metabolism – GSTP1 Ile105Val, ABCB1 Ile1145Ile, MTHFR Ala222Val, TYMS double (2R) or triple (3R) tandem repeat – and DNA-repair genes – ERCC2 Lys751Gln and XRCC1 Arg399Gln – were assessed in 201 CRC patients using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique and DNA sequencing. Patients were diagnosed as either high-risk stage II (T2 and 3 N0 M0) or III (any T N1 and 2 M0) and were administered adjuvant chemotherapy regimens that included 5-fluorouracil (5FU) and leucovorin (LV). The correlations between genetic polymorphisms and patient clinicopathological features and relapses were investigated.

Results

In this study, the distributions of GSTP1 (P = 0.003), ABCB1 (P = 0.001), TYMS (P < 0.0001), ERCC2 (P < 0.0001) and XRCC1 (P = 0.006) genotypes in the Asian population, with the exception of MTHFR (P = 0.081), differed significantly from their distributions in a Caucasian population. However, the unfavorable genotype ERCC2 2251A>C (P = 0.006), tumor invasion depth (P = 0.025), lymph node metastasis (P = 0.011) and cancer stage (P = 0.008) were significantly correlated with early relapse. Patients carrying the ERCC2 2251AC or2251CC genotypes had a significantly increased risk of early relapse (OR = 3.294, 95% CI, 1.272–8.532).

Conclusion

We suggest that ERCC2 2251A>C alleles may be genetic predictors of early CRC relapse.
New models and online calculator for predicting non-sentinel lymph node status in sentinel lymph node positive breast cancer patients
Authors: Kohrt Holbrook E , Olshen Richard A , Bermas Honnie R , Goodson William H , Wood Douglas J , Henry Solomon , Rouse Robert V , Bailey Lisa , Philben Vicki J , Dirbas Frederick M , Dunn Jocelyn J , Johnson Denise L , Wapnir Irene L , Carlson Robert W , Stockdale Frank E , Hansen Nora M , Jeffrey Stefanie S ,   The Bay Area SLN Study
Published: March 2008

Background

Current practice is to perform a completion axillary lymph node dissection (ALND) for breast cancer patients with tumor-involved sentinel lymph nodes (SLNs), although fewer than half will have non-sentinel node (NSLN) metastasis. Our goal was to develop new models to quantify the risk of NSLN metastasis in SLN-positive patients and to compare predictive capabilities to another widely used model.

Methods

We constructed three models to predict NSLN status: recursive partitioning with receiver operating characteristic curves (RP-ROC), boosted Classification and Regression Trees (CART), and multivariate logistic regression (MLR) informed by CART. Data were compiled from a multicenter Northern California and Oregon database of 784 patients who prospectively underwent SLN biopsy and completion ALND. We compared the predictive abilities of our best model and the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram) in our dataset and an independent dataset from Northwestern University.

Results

285 patients had positive SLNs, of which 213 had known angiolymphatic invasion status and 171 had complete pathologic data including hormone receptor status. 264 (93%) patients had limited SLN disease (micrometastasis, 70%, or isolated tumor cells, 23%). 101 (35%) of all SLN-positive patients had tumor-involved NSLNs. Three variables (tumor size, angiolymphatic invasion, and SLN metastasis size) predicted risk in all our models. RP-ROC and boosted CART stratified patients into four risk levels. MLR informed by CART was most accurate. Using two composite predictors calculated from three variables, MLR informed by CART was more accurate than the Nomogram computed using eight predictors. In our dataset, area under ROC curve (AUC) was 0.83/0.85 for MLR (n = 213/n = 171) and 0.77 for Nomogram (n = 171). When applied to an independent dataset (n = 77), AUC was 0.74 for our model and 0.62 for Nomogram. The composite predictors in our model were the product of angiolymphatic invasion and size of SLN metastasis, and the product of tumor size and square of SLN metastasis size.

Conclusion

We present a new model developed from a community-based SLN database that uses only three rather than eight variables to achieve higher accuracy than the Nomogram for predicting NSLN status in two different datasets.
Obesity and cardio-metabolic risk factors in urban adults of Benin: Relationship with socio-economic status, urbanisation, and lifestyle patterns
Authors: Sodjinou Roger , Agueh Victoire , Fayomi Benjamin , Delisle Hélène
Published: March 2008

Background

There is a dearth of information on diet-related chronic diseases in West Africa. This cross-sectional study assessed the rate of obesity and other cardiovascular disease (CVD) risk factors in a random sample of 200 urban adults in Benin and explored the associations between these factors and socio-economic status (SES), urbanisation as well as lifestyle patterns.

Methods

Anthropometric parameters (height, weight and waist circumference), blood pressure, fasting plasma glucose, and serum lipids (HDL-cholesterol and triglycerides) were measured. WHO cut-offs were used to define CVD risk factors. Food intake and physical activity were assessed with three non-consecutive 24-hour recalls. Information on tobacco use and alcohol consumption was collected using a questionnaire. An overall lifestyle score (OLS) was created based on diet quality, alcohol consumption, smoking, and physical activity. A SES score was computed based on education, main occupation and household amenities (as proxy for income).

Results

The most prevalent CVD risk factors were overall obesity (18%), abdominal obesity (32%), hypertension (23%), and low HDL-cholesterol (13%). Diabetes and hypertriglyceridemia were uncommon. The prevalence of overall obesity was roughly four times higher in women than in men (28 vs. 8%). After controlling for age and sex, the odds of obesity increased significantly with SES, while a longer exposure to the urban environment was associated with higher odds of hypertension. Of the single lifestyle factors examined, physical activity was the most strongly associated with several CVD risk factors. Logistic regression analyses revealed that the likelihood of obesity and hypertension decreased significantly as the OLS improved, while controlling for potential confounding factors.

Conclusion

Our data show that obesity and cardio-metabolic risk factors are highly prevalent among urban adults in Benin, which calls for urgent measures to avert the rise of diet-related chronic diseases. People with higher SES and those with a longer exposure to the urban environment are priority target groups for interventions focusing on environmental risk factors that are amenable to change in this population. Lifestyle interventions would appear appropriate, with particular emphasis on physical activity.
Sutureless prepuceplasty with wound healing by second intention: An alternative surgical approach in children's phimosis treatment
Authors: Christianakis Efstratios
Published: March 2008

Background

A new technique for the treatment of children's phimosis is presented that minimizes the repairing time, the postoperative complications and maintains the physical foreskin appearance intact.

Methods

Eightyseven children with phimosis were treated with this new developed technique, between 2003 and 2005. Sutureless prepuceplasty creates a permanent surgical extension of the close prepuce. Stretching and retraction of phimotic foreskin reveals a tight prepuce ring that is cutting in its dorsal surface longitudinally. Rarely triple symmetric incisions in the preputial outlet are necessary. The foreskin is loose and moves absolutely free in bilateral courses. The wounds are healing by second intention. Antisepsis, steroids and Elicina cream, (which contains allantoin, collagen, elastin, glycolic acid and vitamins A, D, and E) should apply daily, for twenty to thirty days.

Results

The foreskin is moving in centripetal or efferent courses absolutely loosely, painlessly and bloodlessly. The mean time of follow-up was 27 months (one to four years). No complications were observed.

Conclusion

Sutureless prepuceplasty may present an acceptable alternative in children's phimosis reconstruction.
Hospital emergency department utilisation rates among the immigrant population in Barcelona, Spain
Authors: Buron Andrea , Cots Francesc , Garcia Oscar , Vall Oriol , Castells Xavier
Published: March 2008

Background

The recent increase in the number of immigrants of Barcelona represents a challenge for the public healthcare system, the emergency department being the most used healthcare service by this group. However, utilisation rates in our environment have not yet been studied. We aimed to compare emergency department utilisation rates between Spanish-born and foreign-born residents in a public hospital of Barcelona.

Methods

The study population included all adults residing in the area of study and visiting the emergency department of Hospital del Mar in 2004. The emergency care episodes were selected from the Emergency Department register, and the population figures from the Statistics Department of Barcelona. Emergency care episodes were classified into five large clinical categories. Adjusted rate ratios (RR) of utilisation among foreign-born vs. Spanish-born residents were assessed through negative binomial regression.

Results

The overall utilisation rate was 382 emergency contacts per 1,000 persons-years. The RR for foreign-born versus Spanish-born residents was 0.62 (95% CI: 0.52; 0.74%). The RR was also significantly below one in surgery (0.51, 95% CI: 0.42; 0.63), traumatology (0.47, 95% CI: 0.38; 0.59), medicine (0.48, 95% CI: 0.38; 0.59) and psychiatry (0.42, 95% CI: 0.18; 0.97). No differences were found in utilisation of gynaecology and minor emergency services.

Conclusion

The overall lower utilisation rates obtained for foreign-born residents is consistent with previous studies and is probably due to the "healthy immigrant effect". Thus, the population increase due to immigration does not translate directly into a corresponding increase in the number of emergency contacts. The lack of differences in minor and gynaecological emergency care supports the hypothesis that immigrants overcome certain barriers by using the emergency department to access to health services. The issue of healthcare barriers should therefore be addressed, especially among immigrants.
Longitudinal microarray analysis of cell surface antigens on peripheral blood mononuclear cells from HIV+ individuals on highly active antiretroviral therapy
Authors: Wu Jing Qin , Dyer Wayne B , Chrisp Jeremy , Belov Larissa , Wang Bin , Saksena Nitin K
Published: March 2008

Background

The efficacy of highly active antiretroviral therapy (HAART) determined by simultaneous monitoring over 100 cell-surface antigens overtime has not been attempted. We used an antibody microarray to analyze changes in the expression of 135 different cell-surface antigens overtime on PBMC from HIV+ patients on HAART. Two groups were chosen, one (n = 6) achieved sustainable response by maintaining below detectable plasma viremia and the other (n = 6) responded intermittently. Blood samples were collected over an average of 3 years and 5–8 time points were selected for microarray assay and statistical analysis.

Results

Significant trends over time were observed for the expression of 7 cell surface antigens (CD2, CD3epsilon, CD5, CD95, CD36, CD27 and CD28) for combined patient groups. Between groups, expression levels of 10 cell surface antigens (CD11a, CD29, CD38, CD45RO, CD52, CD56, CD57, CD62E, CD64 and CD33) were found to be differential. Expression levels of CD9, CD11a, CD27, CD28 and CD52, CD44, CD49d, CD49e, CD11c strongly correlated with CD4+ and CD8+ T cell counts, respectively.

Conclusion

Our findings not only detected markers that may have potential prognostic/diagnostic values in evaluating HAART efficacy, but also showed how density of cell surface antigens could be efficiently exploited in an array-like manner in relation to HAART and HIV-infection. The antigens identified in this study should be further investigated by other methods such as flow cytometry for confirmation as biological analysis of these antigens may help further clarify their role during HAART and HIV infection.
Feasibility of an automated telephone survey to enable prospective monitoring of subjects whose confidentiality is paramount: a four-week cohort study of partner violence recurrence after Emergency Department discharge
Authors: Wiebe Douglas J , Carr Brendan G , Datner Elizabeth M , Elliott Michael R , Richmond Therese S
Published: March 2008

Objective

A goal in intimate partner violence (IPV) research is to identify victims when they are treated in a hospital Emergency Department (ED) and predict which patients will sustain abuse again after discharge, so interventions can be targeted. Following patients to determine those prognostic factors is difficult, however, especially to study IPV given the risk to be assaulted if their partner learns of their participation. We assessed the feasibility of an automated telephone survey and a wireless incentive delivery system to follow ED patients after discharge, enabling detection of IPV recurrence.

Methods

A four-week prospective cohort pilot study was conducted at an urban academic medical center ED in the U.S. Thirty patient subjects (24 women, 6 men; 18–54 years) who had sustained IPV in the past six months, 12 of whom presented for an acute IPV-related condition, were interviewed in the ED and were asked to report weekly for four weeks after discharge to a toll-free, password protected telephone survey, and answer recorded questions using the telephone keypad. A $10 convenience store debit card was provided as an incentive, and was electronically recharged with $10 for each weekly report, with a $20 bonus for making all four reports.

Results

Twenty-two of 30 subjects (73.3%) made at least one report to the telephone survey during the four weeks following discharge; 14 of the 30 subjects (46.7%) made all four weekly reports. Each time the telephone survey was accessed, the subject completed all questions (i.e., no mid-survey break-offs). Eight months after follow-up ended, almost all debit cards (86.7%) had been used to make purchases.

Conclusion

Approximately three of every four subjects participated in follow-up after ED discharge, and approximately two of every four subjects completed all follow-up reports, suggesting the method of an automated telephone survey and wireless incentive delivery system makes it feasible to study IPV prospectively among discharged patients. That finding, along with evidence that IPV recurrence risk is high, suggests the protocol tested is warranted for use conducting full-scale studies of IPV. The protocol could benefit efforts to study other outcomes, especially when patient confidentiality is paramount for their safety.
Pathogenesis of cerebral malformations in human fetuses with meningomyelocele
Authors: de Wit Olga A , den Dunnen Wilfred FA , Sollie Krystyne M , Muñoz Rosa Iris , Meiners Linda C , Brouwer Oebele F , Rodríguez Esteban M , Sival Deborah A
Published: March 2008

Background

Fetal spina bifida aperta (SBA) is characterized by a spinal meningomyelocele (MMC) and associated with cerebral pathology, such as hydrocephalus and Chiari II malformation. In various animal models, it has been suggested that a loss of ventricular lining (neuroepithelial/ependymal denudation) may trigger cerebral pathology. In fetuses with MMC, little is known about neuroepithelial/ependymal denudation and the initiating pathological events.

The objective of this study was to investigate whether neuroepithelial/ependymal denudation occurs in human fetuses and neonates with MMC, and if so, whether it is associated with the onset of hydrocephalus.

Methods

Seven fetuses and 1 neonate (16–40 week gestational age, GA) with MMC and 6 fetuses with normal cerebral development (22–41 week GA) were included in the study. Identification of fetal MMC and clinical surveillance of fetal head circumference and ventricular width was performed by ultrasound (US). After birth, MMC was confirmed by histology. We characterized hydrocephalus by increased head circumference in association with ventriculomegaly. The median time interval between fetal cerebral ultrasound and fixing tissue for histology was four days.

Results

At 16 weeks GA, we observed neuroepithelial/ependymal denudation in the aqueduct and telencephalon together with sub-cortical heterotopias in absence of hydrocephalus and/or Chiari II malformation. At 21–34 weeks GA, we observed concurrence of aqueductal neuroepithelial/ependymal denudation and progenitor cell loss with the Chiari II malformation, whereas hydrocephalus was absent. At 37–40 weeks GA, neuroepithelial/ependymal denudation coincided with Chiari II malformation and hydrocephalus. Sub-arachnoidal fibrosis at the convexity was absent in all fetuses but present in the neonate.

Conclusion

In fetal SBA, neuroepithelial/ependymal denudation in the telencephalon and the aqueduct can occur before Chiari II malformation and/or hydrocephalus. Since denuded areas cannot re-establish cell function, neuro-developmental consequences could induce permanent cerebral pathology.
One hub-one process: a tool based view on regulatory network topology
Authors: Axelsen Jacob Bock , Bernhardsson Sebastian , Sneppen Kim
Published: March 2008

Background

The relationship between the regulatory design and the functionality of molecular networks is a key issue in biology. Modules and motifs have been associated to various cellular processes, thereby providing anecdotal evidence for performance based localization on molecular networks.

Results

To quantify structure-function relationship we investigate similarities of proteins which are close in the regulatory network of the yeast Saccharomyces Cerevisiae. We find that the topology of the regulatory network only show weak remnants of its history of network reorganizations, but strong features of co-regulated proteins associated to similar tasks. These functional correlations decreases strongly when one consider proteins separated by more than two steps in the regulatory network. The network topology primarily reflects the processes that is orchestrated by each individual hub, whereas there is nearly no remnants of the history of protein duplications.

Conclusion

Our results suggests that local topological features of regulatory networks, including broad degree distributions, emerge as an implicit result of matching a number of needed processes to a finite toolbox of proteins.
A high serum level of eotaxin (CCL 11) is associated with less radiographic progression in early rheumatoid arthritis patients
Authors: Syversen Silje W , Goll Guro L , Haavardsholm Espen A , Bøyesen Pernille , Lea Tor , Kvien Tore K
Published: March 2008

Introduction

Prognosis in rheumatoid arthritis (RA) is difficult to assess. The aim of this study was to examine whether serum levels of a spectrum of cytokines were predictive of radiographic progression in early RA patients.

Methods

A total of 82 early RA patients (disease duration < 1 year) were followed for 12 months. Clinical assessments, X-rays of hands and magnetic resonance imaging (MRI) of the dominant wrist were assessed at baseline and after 3, 6 and 12 months. The X-rays were scored according to the van der Heijde modified Sharp score (vdHSS). Cytokine analyses were performed with multiplex technology. Associations between cytokines and radiographic progression were examined by logistic regression.

Results

In all, 49% of the patients developed radiographic progression. The median (interquartile range (IQR)) baseline eotaxin level (pg/ml) was significantly lower in patients with (193 (119 to 247)) than without progression (265 (166 to 360)). In the univariate logistic regression analyses, eotaxin was negatively associated to radiographic progression, and this association was maintained in the multivariate model with an odds ratio (OR) (95% confidence interval (CI)) for progression of 0.58 (0.41 to 0.82) per 50 pg/ml increase in eotaxin level. None of the other measured cytokines showed any association to radiographic progression.

Conclusion

This study raises the hypothesis that high serum levels of eotaxin predict less radiographic progression in early RA patients.
Brca1 breast tumors contain distinct CD44+/CD24- and CD133+cells with cancer stem cell characteristics
Authors: Wright Mollie H , Calcagno Anna Maria , Salcido Crystal D , Carlson Marisa D , Ambudkar Suresh V , Varticovski Lyuba
Published: March 2008

Introduction

Whether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known.

Methods

We generated and characterized 16 cell lines from five distinct Brca1deficient mouse mammary tumors with respect to their cancer stem cell characteristics.

Results

All cell lines derived from one tumor included increased numbers of CD44+/CD24- cells, which were previously identified as human breast cancer stem cells. All cell lines derived from another mammary tumor exhibited low levels of CD44+/CD24- cells, but they harbored 2% to 5.9% CD133+ cells, which were previously associated with cancer stem cells in other human and murine tumors. When plated in the absence of attachment without presorting, only those cell lines that were enriched in either stem cell marker formed spheroids, which were further enriched in cells expressing the respective cancer stem cell marker. In contrast, cells sorted for CD44+/CD24- or CD133+ markers lost their stem cell phenotype when cultured in monolayers. As few as 50 to 100 CD44+/CD24- or CD133+ sorted cells rapidly formed tumors in nonobese diabetic/severe combined immunodeficient mice, whereas 50-fold to 100-fold higher numbers of parental or stem cell depleted cells were required to form few, slow-growing tumors. Expression of stem cell associated genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased in CD44+/CD24- and CD133+ cells. In addition, cells sorted for cancer stem cell markers and spheroid-forming cells were significantly more resistant to DNA-damaging drugs than were parental or stem cell depleted populations, and they were sensitized to the drugs by the heat shock protein-90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride).

Conclusion

Brca1-deficient mouse mammary tumors harbor heterogeneous cancer stem cell populations, and CD44+/CD24- cells represent a population that correlates with human breast cancer stem cells.
Venous thromboembolism and bleeding in critically ill patients with severe renal insufficiency receiving dalteparin thromboprophylaxis: prevalence, incidence and risk factors
Authors: Cook Deborah , Douketis James , Meade Maureen , Guyatt Gordon , Zytaruk Nicole , Granton John , Skrobik Yoanna , Albert Martin , Fowler Robert , Hebert Paul , Pagliarello Guiseppe , Friedrich Jan , Freitag Andreas , Karachi Tim , Rabbat Christian , Heels-Ansdell Diane , Geerts William , Crowther Mark ,   the Canadian Critical Care Trials Group
Published: March 2008

Background

Critically ill patients with renal insufficiency are predisposed to both deep vein thrombosis (DVT) and bleeding. The objective of the present study was to evaluate the prevalence, incidence and predictors of DVT and the incidence of bleeding in intensive care unit (ICU) patients with estimated creatinine clearance <30 ml/min.

Methods

In a multicenter, open-label, prospective cohort study of critically ill patients with severe acute or chronic renal insufficiency or dialysis receiving subcutaneous dalteparin 5,000 IU once daily, we estimated the prevalence of proximal DVT by screening compression venous ultrasound of the lower limbs within 48 hours of ICU admission. DVT incidence was assessed on twice-weekly ultrasound testing. We estimated the incidence of major and minor bleeding by daily clinical assessments. We used Cox proportional hazards regression to identify independent predictors of both DVT and major bleeding.

Results

Of 156 patients with a mean (standard deviation) creatinine clearance of 18.9 (6.5) ml/min, 18 had DVT or pulmonary embolism within 48 hours of ICU admission, died or were discharged before ultrasound testing – leaving 138 evaluable patients who received at least one dose of dalteparin. The median duration of dalteparin administration was 7 days (interquartile range, 4 to 12 days). DVT developed in seven patients (5.1%; 95% confidence interval, 2.5 to 10.1). The only independent risk factor for DVT was an elevated baseline Acute Physiology and Chronic Health Evaluation II score (hazard ratio for 10-point increase, 2.25; 95% confidence interval, 1.03 to 4.91). Major bleeding developed in 10 patients (7.2%; 95% confidence interval, 4.0 to 12.8), all with trough anti-activated factor X levels ≤ 0.18 IU/ml. Independent risk factors for major bleeding were aspirin use (hazard ratio, 6.30; 95% confidence interval, 1.35 to 29.4) and a high International Normalized Ratio (hazard ratio for 0.5-unit increase, 1.68; 95% confidence interval, 1.07 to 2.66).

Conclusion

In ICU patients with renal insufficiency, the incidence of DVT and major bleeding are considerable but appear related to patient comorbidities rather than to an inadequate or excessive anticoagulant from thromboprophylaxis with dalteparin.

Clinical Trial Registration

Number NCT00138099.
The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands
Authors: van Beest Paul A , Hofstra Jorrit J , Schultz Marcus J , Boerma E C , Spronk Peter E , Kuiper Michael A
Published: March 2008

Background

Low mixed or central venous saturation (S(c)vO2) can reveal global tissue hypoxia and therefore can predict poor prognosis in critically ill patients. Early goal directed therapy (EGDT), aiming at an ScvO2 ≥ 70%, has been shown to be a valuable strategy in patients with sepsis or septic shock and is incorporated in the Surviving Sepsis Campaign guidelines.

Methods

In this prospective observational multi-center study, we determined central venous pressure (CVP), hematocrit, pH, lactate and ScvO2 or SvO2 in a heterogeneous group of critically ill patients early after admission to the intensive care units (ICUs) in three Dutch hospitals.

Results

Data of 340 acutely admitted critically ill patients were collected. The mean SvO2 value was > 65% and the mean ScvO2 value was > 70%. With mean CVP of 10.3 ± 5.5 mmHg, lactate plasma levels of 3.6 ± 3.6 and acute physiology, age and chronic health evaluation (APACHE II) scores of 21.5 ± 8.3, the in-hospital mortality of the total heterogeneous population was 32.0%. A subgroup of septic patients (n = 125) showed a CVP of 9.8 ± 5.4 mmHg, mean ScvO2 values of 74.0 ± 10.2%, where only 1% in this subgroup revealed a ScvO2 value < 50%, and lactate plasma levels of 2.7 ± 2.2 mmol/l with APACHE II scores 20.9 ± 7.3. Hospital mortality of this subgroup was 26%.

Conclusion

The incidence of low ScvO2 values for acutely admitted critically ill patients is low in Dutch ICUs. This is especially true for patients with sepsis/septic shock.
Small-volume resuscitation with hyperoncotic albumin: a systematic review of randomized clinical trials
Authors: Jacob Matthias , Chappell Daniel , Conzen Peter , Wilkes Mahlon M , Becker Bernhard F , Rehm Markus
Published: March 2008

Background

Small-volume resuscitation can rapidly correct hypovolemia. Hyperoncotic albumin solutions, long in clinical use, are suitable for small-volume resuscitation; however, their clinical benefits remain uncertain.

Methods

Randomized clinical trials comparing hyperoncotic albumin with a control regimen for volume expansion were sought by multiple methods, including computer searches of bibliographic databases, perusal of reference lists, and manual searching. Major findings were qualitatively summarized. In addition, a quantitative meta-analysis was performed on available survival data.

Results

In all, 25 randomized clinical trials with a total of 1,485 patients were included. In surgery, hyperoncotic albumin preserved renal function and reduced intestinal edema compared with control fluids. In trauma and sepsis, cardiac index and oxygenation were higher after administration of hydroxyethyl starch than hyperoncotic albumin. Improved treatment response and renal function, shorter hospital stay and lower costs of care were reported in patients with liver disease receiving hyperoncotic albumin. Edema and morbidity were decreased in high-risk neonates after hyperoncotic albumin administration. Disability was reduced by therapy with hyperoncotic albumin in brain injury. There was no evidence of deleterious effects attributable to hyperoncotic albumin. Survival was unaffected by hyperoncotic albumin (pooled relative risk, 0.95; 95% confidence interval 0.78 to 1.17).

Conclusion

In some clinical indications, randomized trial evidence has suggested certain benefits of hyperoncotic albumin such as reductions in morbidity, renal impairment and edema. However, further clinical trials are needed, particularly in surgery, trauma and sepsis.
Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock
Authors: Kumar Anand , Schupp Elizabeth , Bunnell Eugene , Ali Amjad , Milcarek Barry , Parrillo Joseph E
Published: March 2008

Introduction

During septic shock, resistance to the haemodynamic effects of catecholamine vasopressors and inotropes is a well-recognised marker of mortality risk. However, the specific cardiovascular or metabolic response elements that are most closely associated with outcome have not been well defined. The objective of this study was to assess cardiovascular and metabolic responses to dobutamine as correlates of outcome in patients with severe sepsis or septic shock.

Methods

A prospective, non-randomised, non-blinded interventional study of graded dobutamine challenge (0, 5, 10, and 15 μg/kg/min) in adult patients who had undergone pulmonary artery catheterisation within 48 hours of onset of severe sepsis or septic shock (8 survivors/15 non-survivors) was performed. Radionuclide cineangiography during graded infusion was used to determine biventricular ejection fractions at each increment of dobutamine.

Results

In univariate analysis, a variety of cardiovascular or haemodynamic and oxygen transport or metabolic variables (at the point of maximum cardiac index response for a given subject) were associated with survival including: increased stroke volume index (p = 0.0003); right ventricular end-diastolic volume index (p = 0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left ventricular end-systolic volume index ratio (p = 0.0188); left ventricular ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p = 0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5 mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate profile construction showed stroke volume index as the dominant discriminating variable for survival with the systolic blood pressure/left ventricular end-systolic volume index ratio alone among all other variables significantly improving the model.

Conclusion

Survivors maintain cardiac responsiveness to catecholamine stimulation during septic shock. Survival from severe sepsis or septic shock is associated with increased cardiac performance and contractility indices during dobutamine infusion. Further studies are required to determine whether these parameters are predictive of outcome in a larger severe sepsis/septic shock population.
Gene expression-based screening for inhibitors of PDGFR signaling
Authors: Antipova Alena A , Stockwell Brent R , Golub Todd R
Published: March 2008

Here we describe a proof-of-concept experiment designed to explore the possibility of using gene expression-based high-throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example. The previously unrecognized ability of aurintricarboxylic acid to inhibit PDGFR signaling, discovered through a screen of 1,739 compounds, demonstrates the feasibility and generalizability of GE-HTS for the discovery of small molecule modulators of any signaling pathway of interest.
Bioinformatics in High School Biology Curricula: A Study of State Science Standards
Authors: Wefer Stephen H. , Sheppard Keith
Published: March 2008

The proliferation of bioinformatics in modern biology marks a modern revolution in science that promises to influence science education at all levels. This study analyzed secondary school science standards of 49 U.S. states (Iowa has no science framework) and the District of Columbia for content related to bioinformatics. The bioinformatics content of each state's biology standards was analyzed and categorized into nine areas: Human Genome Project/genomics, forensics, evolution, classification, nucleotide variations, medicine, computer use, agriculture/food technology, and science technology and society/socioscientific issues. Findings indicated a generally low representation of bioinformatics-related content, which varied substantially across the different areas, with Human Genome Project/genomics and computer use being the lowest (8%), and evolution being the highest (64%) among states' science frameworks. This essay concludes with recommendations for reworking/rewording existing standards to facilitate the goal of promoting science literacy among secondary school students.
Integrating PCR Theory and Bioinformatics into a Research-oriented Primer Design Exercise
Authors: Robertson Amber L. , Phillips Allison R.
Published: March 2008

Polymerase chain reaction (PCR) is a conceptually difficult technique that embodies many fundamental biological processes. Traditionally, students have struggled to analyze PCR results due to an incomplete understanding of the biological concepts (theory) of DNA replication and strand complementarity. Here we describe the design of a novel research-oriented exercise that prepares students to design DNA primers for PCR. Our exercise design includes broad and specific learning goals and assessments of student performance and perceptions. We developed this interactive Primer Design Exercise using the principles of scientific teaching to enhance student understanding of the theory behind PCR and provide practice in designing PCR primers to amplify DNA. In the end, the students were more poised to troubleshoot problems that arose in real experiments using PCR. In addition, students had the opportunity to utilize several bioinformatics tools to gain an increased understanding of primer quality, directionality, and specificity. In the course of this study many misconceptions about DNA replication during PCR and the need for primer specificity were identified and addressed. Students were receptive to the new materials and the majority achieved the learning goals.
Aligning Goals, Assessments, and Activities: An Approach to Teaching PCR and Gel Electrophoresis
Authors: Phillips Allison R. , Robertson Amber L. , Batzli Janet , Harris Michelle , Miller Sarah
Published: March 2008

Polymerase chain reaction (PCR) and gel electrophoresis have become common techniques used in undergraduate molecular and cell biology labs. Although students enjoy learning these techniques, they often cannot fully comprehend and analyze the outcomes of their experiments because of a disconnect between concepts taught in lecture and experiments done in lab. Here we report the development and implementation of novel exercises that integrate the biological concepts of DNA structure and replication with the techniques of PCR and gel electrophoresis. Learning goals were defined based on concepts taught throughout the cell biology lab course and learning objectives specific to the PCR and gel electrophoresis lab. Exercises developed to promote critical thinking and target the underlying concepts of PCR, primer design, gel analysis, and troubleshooting were incorporated into an existing lab unit based on the detection of genetically modified organisms. Evaluative assessments for each exercise were aligned with the learning goals and used to measure student learning achievements. Our analysis found that the exercises were effective in enhancing student understanding of these concepts as shown by student performance across all learning goals. The new materials were particularly helpful in acquiring relevant knowledge, fostering critical-thinking skills, and uncovering prevalent misconceptions.
Student Learning of Early Embryonic Development via the Utilization of Research Resources from the Nematode Caenorhabditis elegans
Authors: Lu Fong-Mei , Eliceiri Kevin W. , Squirrell Jayne M. , White John G. , Stewart James
Published: March 2008

This study was undertaken to gain insights into undergraduate students' understanding of early embryonic development, specifically, how well they comprehend the concepts of volume constancy, cell lineages, body plan axes, and temporal and spatial dimensionality in development. To study student learning, a curriculum was developed incorporating resources from the Caenorhabditis elegans research community. Students engaged in a preactivity assessment, followed by instructional materials (IMs) emphasizing inquiry-based learning and a postinstruction assessment to gauge their learning. This study, conducted at two research sites with eight and nine students, respectively, shows that before instruction, most students confused embryonic cell cleavage, where total volume is constant, with regular cell division, in which total cell volume doubles. Despite their ability to construct a cell lineage tree, most of the study participants were not aware of its biological significance. All students correctly identified cells of anterior and posterior axis, but not cells of the dorsal and ventral axis. Although the students had no difficulty with the time dimensional aspect of development, most viewed an embryo as spatially two-dimensional rather than three-dimensional. Furthermore, this study indicates that combining authentic research resources with inquiry-based learning benefits student learning of key concepts in embryology.
A Kinesthetic Model Demonstrating Molecular Interactions Involved in Anterior-Posterior Pattern Formation in Drosophila
Authors: Douglas Kristin R.
Published: March 2008

Prerequisites for the Developmental Biology course at Augustana College are introductory courses in zoology and cell biology. After introductory courses students appreciate the fact that proteins have three-dimensional structures; however, they often fail to recognize how protein interactions with other cellular components can lead to specific cellular responses. One of the first topics covered in Augustana's Developmental Biology course is anterior-posterior axis determination in Drosophila. In the past, the subject was taught with a series of graphs demonstrating mRNA and protein concentrations along the anterior-posterior axis. However, this pedagogy was too conceptual for the majority of students enrolled in the course. To aid their understanding, a kinesthetic model of the molecular interactions involving bicoid, nanos, hunchback, and caudal transcripts and proteins utilizing colored pipe cleaners and beads was created. Students model molecular interactions between proteins (beads) and transcripts (pipe cleaners) by placing the appropriate bead on the appropriate pipe cleaner. After working with the model, the concept of molecular interactions became more concrete to students, and they were able to conceptualize anterior-posterior axis determination in Drosophila more clearly. Throughout the rest of the course, students were able to understand molecular interactions without the aid of additional models.
Alternation of Generations and Experimental Design: A Guided-Inquiry Lab Exploring the Nature of theher1Developmental Mutant ofCeratopteris richardii(C-Fern)
Authors: Spiro Mark D. , Knisely Karin I.
Published: March 2008

Inquiry-based labs have been shown to greatly increase student participation and learning within the biological sciences. One challenge is to develop effective lab exercises within the constraints of large introductory labs. We have designed a lab for first-year biology majors to address two primary goals: to provide effective learning of the unique aspects of the plant life cycle and to gain a practical knowledge of experimental design. An additional goal was to engage students regardless of their biology background. In our experience, plant biology, and the plant life cycle in particular, present a pedagogical challenge because of negative student attitudes and lack of experience with this topic. This lab uses the fern Ceratopteris richardii (C-Fern), a model system for teaching and research that is particularly useful for illustrating alternation of generations. This lab does not simply present the stages of the life cycle; it also uses knowledge of alternation of generations as a starting point for characterizing the her1 mutation that affects gametophyte sexual development. Students develop hypotheses, arrive at an appropriate experimental design, and carry out a guided inquiry on the mechanism underlying the her1 mutation. Quantitative assessment of student learning and attitudes demonstrate that this lab achieves the desired goals.
Contribution of viral and cellular cytokines to Kaposi’s sarcoma-associated herpesvirus pathogenesis
Authors: Gasperini Paola , Sakakibara Shuhei , Tosato Giovanna
Published: March 2008

Kaposi’s sarcoma (KS)-associated herpesvirus is associated with the proliferative/malignant disorders KS, primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD) in patients with AIDS. In spite of recent advances in the treatment of KS, PEL and MCD represent therapeutic challenges. Recent advances in dissecting the pathogenesis of these diseases have indicated that the viral cytokine IL-6 and the cellular cytokines/growth factors IL-10, IL-6, stromal cell-derived factor 1, and vascular endothelial growth factor are important contributors to the growth, survival, and spread of PEL and MCD and are therefore potential targets for drug development.
Double-Blind, Randomized Placebo Controlled Trial of Fulvestrant Compared With Exemestane After Prior Nonsteroidal Aromatase Inhibitor Therapy in Postmenopausal Women With Hormone Receptor–Positive, Advanced Breast Cancer: Results From EFECT
Authors: Chia Stephen , Gradishar William , Mauriac Louis , Bines Jose , Amant Frederic , Federico Miriam , Fein Luis , Romieu Gilles , Buzdar Aman , Robertson John F.R. , Brufsky Adam , Possinger Kurt , Rennie Pamela , Sapunar Francisco , Lowe Elizabeth , Piccart Martine
Published: March 2008

Purpose

The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor–positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure.

Materials and Methods

Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily.

Results

A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane (n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups (hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate (7.4% v 6.7%; P = .736) and clinical benefit rate (32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant.

Conclusion

Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.
Plasma Isoflavone Level and Subsequent Risk of Breast Cancer Among Japanese Women: A Nested Case-Control Study From the Japan Public Health Center-Based Prospective Study Group
Authors: Iwasaki Motoki , Inoue Manami , Otani Tetsuya , Sasazuki Shizuka , Kurahashi Norie , Miura Tsutomu , Yamamoto Seiichiro , Tsugane Shoichiro
Published: March 2008

Purpose

Because they have large variations in consumption, Asian countries are suitable settings for studies of the effect of relatively high-dose isoflavone intake on breast cancer risk. Nevertheless, no prospective study from Asia has assessed blood or urine levels as biomarkers of isoflavone intake.

Patients and Methods

A total of 24,226 women ages 40 to 69 years in the Japan Public Health Center–based prospective study who responded to the baseline questionnaire and provided blood in 1990 to 1995 were observed to December 2002. During a mean 10.6 years of follow-up, 144 patients newly diagnosed with breast cancer were identified. Two matched controls for each patient were selected from the cohort. Isoflavone levels were assessed by plasma level and food frequency questionnaire, and the odds ratio of breast cancer according to isoflavone level was estimated using a conditional logistic regression model.

Results

We found a statistically significant inverse association between plasma genistein and risk of breast cancer, but no association for plasma daidzein. Adjusted odds ratios for the highest versus lowest quartile of plasma level were 0.34 for genistein (95% CI, 0.16 to 0.74; P for trend, .02) and 0.71 for daidzein (95% CI, 0.35 to 1.44; P for trend, .54). Median plasma genistein values in the control group were 31.9 ng/mL for the lowest and 353.9 ng/mL for the highest quartile groups. Regarding dietary intake of isoflavones, nonsignificant inverse associations were observed for both genistein and daidzein.

Conclusion

This nested case-control study found an inverse association between plasma genistein and the risk of breast cancer in Japan.