bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Side Effects of Short-Course Preoperative Radiotherapy Combined With Total Mesorectal Excision for Rectal Cancer: Increased Bowel Dysfunction in Irradiated Patients—A Dutch Colorectal Cancer Group Study
Authors: Peeters K.C.M.J. , van de Velde C.J.H. , Leer J.W.H. , Martijn H. , Junggeburt J.M.C. , Kranenbarg E. Klein , Steup W.H. , Wiggers T. , Rutten H.J. , Marijnen C.A.M. 
Published: August 2005

Purpose Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision (TME). This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 × 5 Gy radiotherapy and TME. Also, hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment. Patients and Methods Long-term morbidity was assessed in patients from the prospective randomized TME trial, which investigated the efficacy of 5 × 5 Gy before TME surgery for mobile rectal cancer. Dutch patients without recurrent disease were sent a questionnaire. Results Results were obtained from 597 patients, with a median follow-up of 5.1 years. Stoma function, urinary function, and hospital treatment rates did not differ significantly between the treatment arms. However, irradiated patients, compared with nonirradiated patients, reported increased rates of fecal incontinence (62% v 38%, respectively; P < .001), pad wearing as a result of incontinence (56% v 33%, respectively; P < .001), anal blood loss (11% v 3%, respectively; P = .004), and mucus loss (27% v 15%, respectively; P = .005). Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone. Conclusion Although preoperative short-term radiotherapy for rectal cancer results in increased local control, there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone. Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME. Future strategies should be aimed at selecting patients for radiotherapy who are at high risk for local failure.
Phase I Trial of Bortezomib and Carboplatin in Recurrent Ovarian or Primary Peritoneal Cancer
Authors: Aghajanian C. , Dizon D.S. , Sabbatini P. , Raizer J.J. , Dupont J. , Spriggs D.R. 
Published: August 2005

Purpose To determine the maximum-tolerated dose, pharmacodynamics, and safety of the combination of bortezomib and carboplatin in recurrent ovarian cancer. Patients and Methods Fifteen patients were treated with a fixed dose of carboplatin (area under the curve [AUC] 5) and increasing doses of bortezomib (0.75, 1, 1.3, and 1.5 mg/m2/dose). Patients must have received upfront chemotherapy and up to two prior chemotherapy regimens for recurrent disease. Neurologic evaluation was performed at baseline and after every two cycles by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group neurotoxicity questionnaire and examination by an attending neurologist. All patients received carboplatin alone in cycle 1 to establish baseline pharmacodynamics for nuclear factor-kappa B (NF-kB). Starting with cycle 2, patients were treated with carboplatin on day 1 and bortezomib on days 1, 4, 8, and 11. Results Diarrhea, rash, neuropathy, and constipation (with colonic wall thickening on computed tomography) were dose-limiting toxicities, occurring in the two patients treated at the 1.5 mg/m2/dose level. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group neurotoxicity questionnaire was helpful in guiding the need for dose reductions. Neurotoxicity was manageable through six cycles, with appropriate dose reductions. Carboplatin had no effect on bortezomib pharmacodynamics as measured by percent inhibition of the 20S proteasome. Bortezomib decreased carboplatin-induced NF-kB. The overall response rate to this combination was 47%, with two complete responses (CR) and five partial responses, including one CR in a patient with platinum-resistant disease. Conclusion The recommended phase II dose of bortezomib administered in combination with carboplatin (AUC 5) is 1.3 mg/m2/dose.
Free Fatty Acid-Induced Insulin Resistance in the Obese Is Not Prevented by Rosiglitazone Treatment
Authors: Dhindsa Sandeep , Tripathy Devjit , Sanalkumar Nishanth , Ravishankar Shreyas , Ghanim Husam , Aljada Ahmad , Dandona Paresh 
Published: September 2005

Abstract
Objective: Elevation of free fatty acids (FFAs) by the infusion of triglyceride-heparin emulsion infusion (TG-Hep) causes insulin resistance (IR). We examined the effect of insulin sensitizer (rosiglitazone) on FFA-induced IR.
Design: Nine obese subjects underwent a 6-h infusion of TG-Hep before and after 6 wk of rosiglitazone (8 mg/d) treatment. Hyperinsulinemic euglycemic clamps were performed during 0–2 and 4–6 h of TG-Hep.
Results: After rosiglitazone for 6 wk, fasting FFA concentration fell, but not significantly (489 ± 63 at 0 wk; 397 ± 58 μmol/liter at 6 wk; P = 0.16), whereas C-reactive protein (4.26 ± 0.95 at 0 wk; 2.03 ± 0.45 μg/ml at 6 wk) and serum amyloid A (17.36 ± 4.63 at 0 wk; 8.77 ± 1.63 μg/ml at 6 wk) decreased significantly. At 0 wk, TG-Hep infusion caused a decrease in glucose infusion rate (GIR) from 4.49 ± 0.95 mg/kg·min to 3.02 ± 0.59 mg/kg·min (P = 0.018). Rosiglitazone treatment resulted in an increase in baseline GIR to 6.29 ± 0.81 mg/kg·min (P = 0.03 vs. 0 wk), which decreased to 4.52 ± 0.53 mg/kg·min (P = 0.001) after 6 h of TG-Hep infusion. The decrease in GIR induced by TG-Hep infusion was similar before and after rosiglitazone therapy [1.47 ± 0.50 vs. 1.77 0.3 mg/kg·min (28.9 ± 6.5 vs. 26.4 ± 3.7%); P = 0.51]. The rise in FFAs and triglycerides after TG-Hep infusion was significantly lower at 6 wk (P = 0.006 for FFAs; P = 0.024 for triglycerides).
Conclusions: We conclude that rosiglitazone: 1) causes a significant increase in GIR; 2) induces a decrease in inflammatory mediators, C-reactive protein, and serum amyloid A; 3) decreases the rise in FFAs and triglycerides after TG-Hep infusion; and 4) does not prevent FFA-induced IR.
Corticotropin-Releasing Hormone (CRH) and Urocortin Act through Type 1 CRH Receptors to Stimulate Dehydroepiandrosterone Sulfate Production in Human Fetal Adrenal Cells
Authors: Sirianni Rosa , Mayhew Bobbie A. , Carr Bruce R. , Parker C. Richard , Rainey William E. 
Published: September 2005

Abstract
Context: Near term, the human fetal adrenal increases the production of cortisol and dehydroepiandrosterone sulfate (DHEAS). DHEAS, which acts as substrate for placental estrogen production, induces key changes involved in parturition.
Objective: The objective of this study was to determine quantitatively the effect of CRH on mRNA levels of enzymes needed for DHEAS production (steroidogenic acute regulatory protein, CYP11A, CYP17, and SULT2A1), to determine the CRH receptor (CRH-R) subtype(s) responsible for CRH action, and to determine the effect of CRH on CRH-R mRNA expression in human adrenal fetal zone (FZ) cells.
Design: Human adrenal FZ cells were treated with CRH, ACTH, urocortin (Unc), and CRH antagonists, and RNA was analyzed by microarray and real-time RT-PCR.
Setting: This study was performed at an academic research laboratory.
Main Outcome Measure: The main outcome measure was the expression of steroidogenic enzymes and CRH-R.
Results: Microarray analysis of human FZ cells treated for 24 h with CRH or ACTH showed increased mRNA expression levels of the genes needed for DHEAS production. Real-time RT-PCR analysis confirmed these data. Induction was lost in the presence of CRH-R1 antagonists, but not CRH-R2 antagonists. Stimulation was reproduced by Unc. The CRH-R1α mRNA splice variant was the only type 1 receptor isoform expressed in the fetal adrenal, and treatment with CRH up-regulates its mRNA levels.
Conclusions: CRH, Unc, and ACTH stimulate all elements of the DHEAS synthetic pathway and activate CRH-R1 as well. The resulting increased DHEAS levels can be used for placental estrogen synthesis and contribute to the process leading to parturition in humans.
Chemotherapy Dosing with Elevated Liver Function Test Results in Acute Leukemia
Authors: Comeau Terrance B , Phillips Debra L 
Published: August 2005

OBJECTIVE: To report a case of massive blast infiltration of the liver by acute lymphoblastic leukemia (ALL) manifested by worsening liver function test (LFT) results and concern over how to dose chemotherapy in this patient. CASE SUMMARY: A 36-year-old male presenting with productive cough, abdominal pain, and lower back pain was diagnosed with pre-B cell ALL. Of note, the patient developed worsening LFT results within the first few days of diagnosis. Because of concern over increasing liver dysfunction and the need to administer vincristine and daunorubicin with induction therapy, a transvenous liver biopsy was performed, revealing massive lymphoblast infiltration. DISCUSSION: A short course of prednisone was given to determine whether the LFT abnormalities would reverse with treatment. Once a downward trend in the abnormalities was noted, full-dose induction chemotherapy was administered. CONCLUSIONS: It is important to discern the cause of elevated LFT values in patients with acute leukemia who require induction chemotherapy, as this may affect treatment decisions and patient outcomes.
A Semiparametric Analysis of the Relationship of Body Mass Index to Mortality
Authors: Gronniger Jerome Timothy 
Published: August 2005

Objectives. I used a semi-parametric analysis of the relationship between body mass index (BMI) and mortality to assess the adequacy of conventional BMI categories for planning public health programs to reduce mortality. Methods. I linked supplements from the 1987 and 1989 versions of the National Health Interview Survey to the 1995 Multiple Cause of Death File to obtain mortality information. I constructed nonlinear estimates of the association between BMI and mortality using a semiparametric regression technique. Results. The mortality risk among “normal” weight men (i.e., those in the BMI range of 20 to 25 kg/m2) was as high as that among men in the mild obesity category (BMIs of 30–35 kg/m2), with a minimum risk observed at a BMI of approximately 26 kg/m2. Among women, the mortality risk was smallest at approximately 23 to 24 kg/m2, with the risk increasing steadily with BMIs above 27 kg/m2. In each specification, the slope of the line was small and volatile through the BMI range of 20 to 35 kg/m2, suggesting negligible risk differences with minor differences in weight for much of the population. Conclusions. Traditional BMI categories do not conform well to the complexities of the BMI–mortality relationship. In concurrence with conclusions from previous literature, I found that the current definitions of obesity and overweight are imprecise predictors of mortality risk.
Diabetes Portrayals in North American Print Media: A Qualitative and Quantitative Analysis
Authors: Rock Melanie 
Published: August 2005

Objectives. This study investigated how media coverage has portrayed diabetes as newsworthy. Methods. The quantitative component involved tabulating diabetes coverage in 2 major Canadian newspapers, 1988–2001 and 1991–2001. The qualitative component focused on high-profile coverage in 2 major US magazines and 2 major Canadian newspapers, 1998–2000. Results. Although coverage did not consistently increase, the quantitative results suggest an emphasis on linking diabetes with heart disease and mortality to convey its seriousness. The qualitative component identified 3 main ways of portraying type 2 diabetes: as an insidious problem, as a problem associated with particular populations, and as a medical problem. Conclusions. Overall, the results suggest that when communicating with journalists, researchers and advocates have stressed that diabetes maims and kills. Yet even when media coverage acknowledged societal forces and circumstances as causes, the proposed remedies did not always include or stress modifications to social contexts. Neither the societal causes of public health problems nor possible societal remedies automatically received attention from researchers or from journalists. Skilled advocacy is needed to put societal causes and solutions on public agendas.
Risk Factors for Long-Term Homelessness: Findings From a Longitudinal Study of First-Time Homeless Single Adults
Authors: Caton Carol L. M. , Dominguez Boanerges , Schanzer Bella , Hasin Deborah S. , Shrout Patrick E. , Felix Alan , McQuistion Hunter , Opler Lewis A. , Hsu Eustace 
Published: August 2005

Objectives. We examined risk factors for long-term homelessness among newly homeless men and women who were admitted to New York City shelters in 2001 and 2002. Methods. Interviews were conducted with 377 study participants upon entry into the shelter and at 6-month intervals for 18 months. Standardized assessments of psychiatric diagnosis, symptoms, and coping skills; social and family history; and service use were analyzed. Kaplan—Meier survival analysis and Cox regression were used to examine the association between baseline assessments and duration of homelessness. Results. Eighty-one percent of participants returned to community housing during the follow-up period; the median duration of homelessness was 190 days. Kaplan—Meier survival analysis showed that a shorter duration of homelessness was associated with younger age, current or recent employment, earned income, good coping skills, adequate family support, absence of a substance abuse treatment history, and absence of an arrest history. Cox regression showed that older age group P<.05) and arrest history (P<.01) were the strongest predictors of a longer duration of homelessness. Conclusions. Identification of risk factors for long-term homelessness can guide efforts to reduce lengths of stay in homeless shelters and to develop new preventive interventions.
Capturing Intervention Effects Over Time: Reanalysis of a Critical Time Intervention for Homeless Mentally Ill Men
Authors: Lennon Mary Clare , McAllister William , Kuang Li , Herman Daniel B. 
Published: August 2005

Objectives. We analyzed whether a method for identifying latent trajectories—latent class growth analysis (LCGA)—was useful for understanding outcomes for individuals subject to an intervention. Methods. We used LCGA to reanalyze data from a published study of mentally ill homeless men in a critical time intervention (CTI) program. In that study, 96 men leaving a shelter’s onsite psychiatric program were randomly assigned to experimental and control groups. The former received CTI services and the latter usual services. Each individual’s housing circumstances were observed for 18 months after program initiation. Our outcome measure was monthly homelessness: a person was considered homeless in a month if he was homeless for even 1 night that month. Results. Four latent classes were found among the control group, but just 3 among the experimental group. Control, but not experimental, group individuals showed a small class of chronically homeless men. The size of the never-homeless class was 19 percentage points larger for the experimental than for the control group. J- and inverted-U-shaped patterns were also found among both groups, but with important differences in timing of patterns. Conclusions. Our results reveal effects not apparent in the original analysis, suggesting that latent class growth models improve intervention evaluation.
SPEAKING OUT to Improve the Health of Inmates
Authors: Heines Vivienne 
Published: August 2005

Prison public health is becoming increasingly important to our society as growing numbers of men and women are incarcerated and later released. Numerous studies indicate that the prison population has a higher risk of certain infectious diseases and a higher rate of mental illness than the general population. Two community leaders, Dr Melanie Spector in the area of public health and Judge Steven Leifman in the judicial system, have addressed the vital issues of womens health and mental illness, respectively. Their efforts have had a positive impact both on prisoners themselves and on the overall health of their communities.
3‐D Reconstruction of Neurons from Multichannel Confocal Laser Scanning Image Series
Authors: Wouterlood Floris G. 
Published: August 2005

AbstractA confocal laser scanning microscope (CLSM) collects information from a thin, focal plane and ignores out‐of‐focus information. The operator configures separate channels (laser, filters, detector settings) for each fluorochrome used in a particular experiment. Then, 3‐D reconstructions are made from Z‐series of confocal images: one series per channel. Channel signal separation is extremely important and measures to avoid bleaching are vital. Post‐acquisition deconvolution of the image series is then performed to increase resolution. In the 3‐D reconstruction program described in this unit, reconstructions can be inspected in real time from any viewing angle. By altering viewing angles and by switching channels off and on, the spatial relationship of 3‐D‐reconstructed structures with respect to structures seen in other channels can be studied. Since each brand of CLSM, computer program, and 3‐D reconstruction package has its own proprietary set of procedures, a general approach is provided wherever possible.
Two‐Photon Imaging in Live Rodents
Authors: Belluscio Leonardo 
Published: August 2005

AbstractTwo‐photon imaging is an innovative optical technique that has quickly become state of the art for imaging fluorescent signals in a variety of organisms. With many advantages over conventional confocal microscopy, such as greater image resolution, deeper access (∼400 µm), and much less photo damage, two‐photon microscopy has already proven to be an extremely useful tool for imaging live cells or tissue. Due to its tremendous versatility, recent efforts have adapted this technique to allow visualization of fluorescent cells directly in living animals. This unit describes a basic procedure for performing two‐photon imaging in vivo as applied to the dorsal surface of the brain in live anesthetized mice or rats. The protocol outlines a surgical preparation to enable the capture of stable, high‐resolution (<1 µm) images of fluorescently labeled neurons in intact brain with very little detrimental effect to either cells or tissue.
Chronic Intravenous Drug Self‐Administration in Rats and Mice
Authors: Thomsen Morgane , Caine S. Barak 
Published: August 2005

AbstractChronic intravenous drug self‐administration in rodents is a useful procedure for predicting the abuse liability of novel drugs in humans, for evaluating candidate treatments for drug abuse and dependence, and for studying the biological basis of addiction. This unit focuses on recent technical innovations for conducting long‐term studies of i.v. drug self‐administration behavior in healthy, freely moving rats and mice. Included are protocols for construction, implantation, and maintenance of chronic indwelling jugular catheters, commentary on critical parameters, a troubleshooting guide, and anticipated results.
Intravenous Self‐Administration Techniques in Monkeys
Authors: Platt Donna M. , Carey Galen , Spealman Roger D. 
Published: August 2005

AbstractDrug self‐administration is a procedure in which a subject performs a response, called an operant, that results in the delivery of a drug injection. This procedure is viewed as a relevant model for the study of human drug‐taking behavior. Drug self‐administration in primates has several characteristics that resemble drug‐taking behavior in humans, and drugs that are commonly abused by humans also typically maintain self‐administration behavior in monkeys. Drug self‐administration procedures allow for the study of a variety of drug properties. For instance, they are used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of drug addiction. These procedures also can be used to study the process of drug reinforcement. This unit describes intravenous drug self‐administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.
Modification and Production of BAC Transgenes
Authors: Jeong Yongsu , Epstein Douglas J. 
Published: August 2005

AbstractBacterial artificial chromosomes (BACs) are the vectors of choice for the construction of genomic DNA libraries and, as such, have proven instrumental in the generation of large‐scale physical maps; positional cloning projects; and the sequencing of human, mouse, and a plethora of other genomes. A number of methods have recently been developed to modify BAC DNA (e.g., insertion, deletion, substitution), making BACs even more useful for functional genomic research. This unit describes two protocols for BAC modification in E. coli, one that allows for specific changes at a given DNA sequence and another that is more suited for rapid and nonspecific integration of foreign DNA (such as a reporter cassette) into a BAC insert. In addition, a simple and reliable method for preparing BAC DNA for pronuclear microinjection is also provided.
Detecting Gene‐Gene Interaction in Linkage Analysis
Authors: Li Chun 
Published: August 2005

AbstractLinkage analysis has been very successful in identifying genes for many Mendelian diseases, but has not enjoyed the same level of success for complex diseases. A major reason is that complex diseases are multifactorial, involving multiple genes and environmental factors. Linkage analysis is powerful for localizing disease genes with moderate marginal effects with most realistic sample sizes. Traditionally it has been used to search for a single disease locus at one time, and most implementations lack the power to detect genes with small marginal effect but moderate to strong interaction effect with other genes. Thus, methods for detecting gene‐gene interaction in linkage analysis are needed. A brief background on gene‐gene interaction in linkage analysis is given, with a review of two major approaches: two‐locus linkage analysis and interaction analysis. Three methods of interaction analysis are also reviewed: conditional linkage analysis, ordered subset analysis, and generalized estimating equations.
The BAC Resource: Tools for Array CGH and FISH
Authors: Nowak Norma J. , Snijders Antoine M. , Conroy Jeffrey M. , Albertson Donna G. 
Published: August 2005

AbstractBacterial Artificial Chromosome (BAC) vector clones carrying human DNA were chosen as the intermediate templates for the sequencing of the human genome due to their inherent stability and fidelity to the genome sequence from which they were derived. In this unit, we describe a set of protocols for BAC‐based array comparative genomic hybridization (aCGH) that comprise the generation of targets for printing solutions onto glass slides, the subsequent hybridization steps, and CGH analysis of a test sample compared to a reference normal sample. The BAC clones through their sequence allow the extent and gene content of numerical aberrations to be delineated by aCGH, and also provide cytogeneticists with tools for subsequent validation or fine mapping studies.