bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapy Options in Imatinib Failures
Authors: Ramirez Pablo , DiPersio John F. 
Published: April 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the mechanisms that result in resistance to imatinib in CML patients.Employ the current guidelines that define resistance at various time points.Assess the merits of the available therapeutic strategies following imatinib failure.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Chronic myelogenous leukemia (CML) is defined by the presence of the constitutively active tyrosine kinase breakpoint cluster region/Abelson (Bcr-Abl), which activates numerous signal transduction pathways leading to uncontrolled cell proliferation. The development of the Bcr-Abl–targeted imatinib represents a paradigm shift in the treatment of CML, because treatment with imatinib resulted in significantly better patient outcome, response rates, and overall survival compared with previous standards. Despite this advance, not all patients benefit from imatinib because of resistance and intolerance.
Resistance to imatinib can develop from a number of mechanisms that can be defined as Bcr-Abl–dependent (e.g., most commonly resulting from point mutations in the Abl kinase domain) and Bcr-Abl-independent mechanisms (including the constitutive activation of downstream signaling molecules, e.g., Src family kinases), which could result in the activation of the pathway regardless of Bcr-Abl inhibition.
Clearly, new treatment approaches are required for patients resistant to or intolerant of imatinib, which can be dose escalated in patients who demonstrate resistance. This does not result in long-term responses. Hematopoietic stem cell transplantation is limited by the availability of matched donors and the potential for morbidity. Dasatinib, a dual Bcr-Abl/Src kinase inhibitor, has shown efficacy against all imatinib-resistant Bcr-Abl mutations except for T315I. A large trial program showed that dasatinib is effective in patients previously exposed to imatinib and has a manageable safety profile in all phases of CML and Philadelphia chromosome–positive acute lymphoblastic leukemia, resulting in its approval. Nilotinib, an analogue of imatinib, also has demonstrated activity in a similar patient population. These agents and less clinically advanced strategies are discussed in this review.
Targeted Therapies for the Treatment of Breast Cancer in the Post-trastuzumab Era
Authors: Petrelli Fausto , Cabiddu Mary , Cazzaniga Marina Elena , Cremonesi Marco , Barni Sandro 
Published: April 2008

Abstract

Learning Objectives
After completing this course, the reader will be able to: Discuss the development of bevacizumab and lapatinib in the treatment of advanced breast cancer and evaluate the present role of these agents in clinical practice.Describe the current state of knowledge on the other small-molecule tyrosine kinase inhibitors using data from orally presented or published studies over the last few years in metastatic breast cancer.Assess the actual dilemmas for oncologists in the study design and prescription of these target agents.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Targeted therapies for breast cancer are evolving rapidly. Trastuzumab has revolutionized breast cancer treatment and outcome, reducing the risk for recurrence and significantly increasing survival, at least for a subgroup of patients. Other targeted therapies, such as bevacizumab, a monoclonal antibody targeting angiogenesis, lapatinib, a dual human epidermal growth factor receptor (HER)-1 and HER-2 inhibitor, other small-molecule tyrosine kinase inhibitors, and mammalian target of rapamycin inhibitors, have been developed in phase II and III clinical trials. Although there has been rapid approval of these new drugs by health authorities, some questions have emerged about their application in clinical practice. What is the appropriate drug or sequence of drugs? What is the ideal target? How should tumor response be evaluated? Are financial resources sufficient to treat patients? How do we design trials with these molecules? These are emerging as current dilemmas for clinical oncologists.
A Phase II Study of Gefitinib for Patients with Advanced HER-1 Expressing Synovial Sarcoma Refractory to Doxorubicin-Containing Regimens
Authors: Ray-Coquard Isabelle , Le Cesne Axel , Whelan Jeremy S. , Schoffski Patrick , Bui Binh N. , Verweij Jaap , Marreaud Sandrine , van Glabbeke Martine , Hogendoorn Pancras , Blay Jean-Yves 
Published: April 2008

Abstract

Rationale.
Advanced synovial sarcomas (SyS) refractory to doxorubicin and ifosfamide are highly resistant to the currently available cytotoxic agents. Based on a report showing a specific overexpression of HER-1 in SyS, we investigated an HER-1 inhibitor, gefitinib, in refractory SyS.

Subjects and Methods.
To establish the efficacy and safety of gefitinib in HER-1 – positive SyS refractory to one or two lines of doxorubicin- and ifosfamide-based chemotherapy, a phase II study was conducted from December 2002 to October 2005 by 12 centers of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Gefitinib was given at a 500-mg/day oral dose until progression or intolerance.

Results.
Forty-eight patients were included (46 eligible). All patients had previously received chemotherapy for metastatic disease, with a median number of two lines (range, 1–4). The most frequent metastatic sites were the lungs (n = 44, 92%), lymph nodes (n = 11, 23%), and soft tissues (n = 10, 21%). The median duration of treatment was 43 days (range, 13–315). Treatment was interrupted in five patients (10%). Treatment was halted for progression in 45 (94%) patients. The best response was stable disease in 10 patients (21%). Disease progression occurred in 32 patients (70%), with a median time to disease progression of 6 weeks. Progression-free survival at 4 and 6 months was 21% and 6%, respectively.

Conclusion.
The results show that gefitinib monotherapy in advanced SyS refractory to conventional chemotherapy did not demonstrate sufficient activity to warrant further investigation in this setting. This may suggest that HER-1 is not a critical protein in tumor progression in this disease.
Determinants of Recent HIV Infection Among Seattle-Area Men Who Have Sex with Men
Authors: Thiede Hanne , Jenkins Richard A. , Carey James W. , Hutcheson Rebecca , Thomas Katherine K. , Stall Ronald D. , White Edward , Allen Iris , Mejia Roberto , Golden Matthew R. 
Published: April 2008

Objectives. We sought to identify HIV-infection risk factors related to partner selection and sexual behaviors with those partners among men who have sex with men (MSM) in King County, Washington. Methods. Participants were recruited from HIV testing sites in the Seattle area. Recent HIV infection status was determined by the Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) or a self-reported previous HIV-negative test. Data on behaviors with 3 male partners were collected via computer-based self-interviews. Generalized estimating equation models identified partnership factors associated with recent infection. Results. We analyzed data from 32 HIV-positive MSM (58 partners) and 110 HIV-negative MSM (213 partners). In multivariate analysis, recent HIV infection was associated with meeting partners at bathhouses or sex clubs, bars or dance clubs, or online; methamphetamine use during unprotected anal intercourse; and unprotected anal intercourse, except with HIV-negative primary partners. Conclusions. There is a need to improve efforts to promote condom use with casual partners, regardless of their partner's HIV status. New strategies to control methamphetamine use in MSM and to reduce risk behaviors related to meeting partners at high-risk venues are needed.
HIV Infection, Sexual Risk Behavior, and Substance Use Among Latino Gay and Bisexual Men and Transgender Persons
Authors: Ramirez-Valles Jesus , Garcia Dalia , Campbell Richard T. , Diaz Rafael M. , Heckathorn Douglas D. 
Published: April 2008

Objectives. We examined HIV prevalence and the socioeconomic correlates of HIV infection, sexual risk behaviors, and substance use among Latino gay and bisexual men and transgender persons in Chicago and San Francisco. Methods. Data were collected from a sample of 643 individuals (Chicago: n=320; San Francisco: n=323) through respondent-driven sampling and computer-assisted self-administered interviews. Results. HIV prevalence in San Francisco (0.325; 95% confidence interval [CI]=0.260, 0.393) was higher than in Chicago (0.112; 95% CI=0.079, 0.163). In San Francisco, HIV prevalence was higher among US-born residents than among those born outside the country; in Chicago, the opposite was true. Heavy use of alcohol was prevalent, especially in Chicago (0.368; 95% CI=0.309, 0.432; San Francisco: 0.154; 95% CI=0.116, 0.192). Drug use and more education were positively correlated and greater age was negatively correlated with unprotected anal intercourse. Conclusions. Heavy alcohol drinking and use of drugs remain a significant public health problem in this population. Drug use was more closely linked to HIV sexual risk behaviors than was heavy drinking.
Sexual Risk Taking Among Young Internet-Using Men Who Have Sex With Men
Authors: Horvath Keith J. , Rosser B.R. Simon , Remafedi Gary 
Published: April 2008

Objectives. We examined the characteristics of young Internet-using men who have sex with men (MSM) and risks associated with seeking sex online, offline, or through both strategies. Methods. Data were obtained from MSM aged 18 to 24 years who completed a 45-minute online survey regarding sex and Internet use in the preceding 3 months. Results. Significantly more Internet-using MSM who had met sexual partners both online and offline (43%) reported unprotected anal intercourse than did those who had met sexual partners exclusively online (29%) or offline (34%). MSM who met sexual partners exclusively offline reported the fewest partners but the greatest proportion of partnerships involving unprotected anal intercourse (49%). Meeting sexual partners both online and offline (odds ratio [OR]=3.38–58.42) and being drunk (OR=1.57) or high (OR=2.24) increased the odds of having more sexual partners. The same factors increased the odds of having unprotected anal intercourse (online and offline sexual partners, OR=1.60; being drunk, OR=1.43; being high, OR=1.61). Conclusions. Risky sexual behavior was prevalent among all of the study subgroups. Our findings suggest that online sex seeking is associated with greater numbers of sexual partners but neither promotes nor discourages unprotected anal intercourse. Regardless of where sexual partners met, being drunk and high were significant risks for unprotected anal intercourse.
Condom Use and Hip Hop Culture: The Case of Urban Young Men in New York City
Authors: Muñoz-Laboy Miguel A. , Castellanos Daniel H. , Haliburton Chanel S. , del Aguila Ernesto Vasquez , Weinstein Hannah J. , Parker Richard G. 
Published: April 2008

Objectives. We explored how young men’s perceptions of and participation in hip hop culture—urban social and artistic expressions, such as clothing style, breakdancing, graffiti, and rap music—and how contextual factors of the hip hop scene may be associated with their condom use, condom-use self-efficacy, and sense of community. Methods. We conducted a cross-sectional survey of 95 African American and Latino men aged 15 to 25 years as part of a 4-year ethnographic study in New York City. Results. Differences in young men’s perceptions of and levels of affiliation with hip hop culture were not statistically associated with differences in their sense of community or condom-use self-efficacy. Frequency of participation in the hip hop nightclub scene was the strongest factor negatively associated with condom use. Conclusions. Popular discourses on young men’s health risks often blame youths’ cultures such as the hip hop culture for increased risk practices but do not critically examine how risk emerges in urban young men’s lives and what aspects of youths’ culture can be protective. Further research needs to focus on contextual factors of risk such as the role of hip hop nightlife on increased HIV risk.
Resilience to Urban Poverty: Theoretical and Empirical Considerations for Population Health
Authors: Sanders Anne E. , Lim Sungwoo , Sohn Woosung 
Published: April 2008

Objectives. To better understand the trajectory that propels people from poverty to poor health, we investigated health resilience longitudinally among African American families with incomes below 250% of the federal poverty level. Methods. Health resilience is the capacity to maintain good health in the face of significant adversity. With higher levels of tooth retention as a marker of health resilience, we used a social–epidemiological framework to define capacity for health resilience through a chain of determinants starting in the built environment (housing quality) and community context (social support) to familial influences (religiosity) and individual mental health and health behavior. Results. Odds of retaining 20 or more teeth were 3 times as likely among adults with resilience versus more-vulnerable adults (odds ratio=3.1; 95% confidence interval [CI]=1.3, 7.4). Children of caregivers with resilience had a lower incident rate of noncavitated tooth decay at 18- to 24-month follow-up (incidence risk ratio=0.8; 95% CI=0.7, 0.9) compared with other children. Conclusions. Health resilience to poverty was supported by protective factors in the built and social environments. When poverty itself cannot be eliminated, improving the quality of the built and social environments will foster resilience to its harmful health effects.
The Prevalence of Metabolic Syndrome Among US Women of Childbearing Age
Authors: Ramos Rosemarie G. , Olden Kenneth 
Published: April 2008

Objectives. We sought to determine whether the prevalence of metabolic syndrome among US women of childbearing age (18–44 years) has increased since 1988 and to estimate its current prevalence by race/ethnicity and risk that a maternal history of select metabolic syndrome characteristics imposes on offspring. Methods. We used survey-specific data analysis methods to examine data from the National Health and Nutrition Examination Surveys conducted from 1988 to 2004. Results. The prevalence of the metabolic syndrome phenotype and 2 of its clinical correlates significantly increased between 1988 and 2004 (increase for metabolic syndrome phenotype=7.6%, for obesity=13.3%, and for elevated C-reactive protein=10.6%; P<.001 for all 3). Hispanic women were more likely than were White women to possess the phenotype (P= .004). Women who reported that their mothers had been diagnosed with diabetes were more likely to possess the phenotype than those whose mothers had not been so diagnosed (odds ratio=1.9; 95% confidence interval=1.3, 2.8). Conclusions. The current trends of metabolic syndrome among women of childbearing age demonstrate the need for additional rigorous investigations regarding its long-term effects in these women and their offspring.
Moving Upstream: Ecosocial and Psychosocial Correlates of Sexually Transmitted Infections Among Young Adults in the United States
Authors: Buffardi Anne L. , Thomas Kathy K. , Holmes King K. , Manhart Lisa E. 
Published: April 2008

Objectives. We determined the associations of ecosocial factors and psychosocial factors with having a prevalent sexually transmitted infection (STI), recent STI diagnoses, and sexual risk behaviors. Methods. Young adults aged 18 to 27 years in the National Longitudinal Study of Adolescent Health (n=14322) provided ecosocial, psychosocial, behavioral, and STI-history data. Urine was tested for Chlamydia trachomatis and Neisseria gonorrhoeae by ligase chain reaction and for Trichomonas vaginalis, human papillomavirus, and Mycoplasma genitalium by polymerase chain reaction. Results. Prevalent STI was associated with housing insecurity (adjusted odds ratio [AOR] = 1.3; 95% confidence interval [CI] = 1.00, 1.72), exposure to crime (AOR=1.4; 95% CI=1.02, 1.80), and having been arrested (AOR=1.4; 95% CI=1.07, 1.84). STI prevalence increased linearly from 4.9% for 0 factors to 14.6% for 4 or more (P< .001, for trend). Nearly all contextual conditions predicted more lifetime partners and earlier sexual debut. Recent STI diagnosis was associated with childhood sexual abuse, gang participation, frequent alcohol use, and depression, adjusted for sexual risk behaviors. Conclusions. Often present before sexual debut, contextual conditions enhance STI risk by increasing sexual risk behaviors and likelihood of exposure to infection. These findings suggest that upstream conditions such as housing and safety contribute to the burden of STIs and are appropriate targets for future intervention.
Ensuring Success on an Extended Reach Well: Expandable Liner Hangers and the Use of Advanced Software Modeling
Authors: Wardak Ajmal , Williford James , Walker Angus , Nughaimish Faisal , Atanu Ogacheko , Al-Saggaf Hatem 
Published: April 2008

AbstractOver the course of time, the oil and gas industry has increased its usage of state-of-the-art equipment and advanced software to access oil and gas reserves that were previously considered as technically and/or economically prohibitive. Today's well designs are inherently more complex since the current targets are deeper, require extended reach configurations or are in locations that present greater difficulties in developing appropriate well designs. Success, therefore, depends upon careful up-front planning to ensure that the goals sought are attained. The planning requires detailed calculations at each step of the well development — from the geological survey to drilling to completing the well. The advanced modeling software available in the market today has made the required analysis possible.Extended-reach wells carry significant risks where cost of failure regarding the deployment of the liner and liner hanger system could consume the whole well. One of the major risks with deploying such a long liner is the risk of pre-setting the liner hanger and/or the liner hanger packer. An expandable liner hanger (ELH) system, recently introduced to the industry, inherently eliminates this risk with its design and setting procedure and is the focus of this paper. When the liner is deployed using the detailed analysis generated during the planning stages, the risks mentioned above can be significantly reduced and greater assurance that the liner can be run to depth can be provided.The extended-reach section of these wells creates additional problems relating to friction during the deployment of the liner hanger. This phenomenon can be addressed with ‘torque and drag' software as well as ‘surge and swab' software to optimize the solution with a detailed analytical output that will determine the best method to use to deploy the liner into the hole. The analysis will help determine whether centralizers should be used (and if so, specific spacing), whether fluids that will reduce the friction coefficients should be considered, and will also examine whether there is the possibility of floating the liner hanger to depth.To summarize, the ultimate goal of the well designer is to apply the available software to develop and optimize a plan to reduce friction during deployment of an expandable liner hanger to depth while reducing cost impact and eliminating nonproductive time.The case history in this well will verify how the proper planning and use of the ELH system selected was capable of addressing the challenges of successfully deploying the ELH system in an extended-reach well for Saudi Aramco. These wells have a measured depth (MD) of 19,000 to 31,000+ feet and true vertical depths (TvD) between 7,000 and 9,000 feet. The liner lengths ranged from 5,000 to 10,000 feet in length.
Intracranial pressure monitoring with the Neurodur-P epidural sensor: a prospective study in patients with adult hydrocephalus or idiopathic intracranial hypertension
Authors: Poca Maria A. , Martínez-Ricarte Francisco , Sahuquillo Juan , Lastra Roberto , Torné Ramón , Armengol Maria S. 
Published: April 2008

Object
Continuous intracranial pressure (ICP) monitoring using an epidural sensor is a common technique used in selected neurosurgical patients. The aim of this study was to assess the safety and accuracy of the Neurodur-P epidural sensor in the clinical setting.

Methods
The zero drift, as well as the medical and technical complications, of using the Neurodur-P sensor placed in the epidural space was evaluated in 106 patients with hydrocephalus of varying causes or with suspected intracranial hypertension.

Results
The median duration of ICP monitoring was 8 days (interquartile range [IQR] 6–12 days). In 78 (73.6%) of the 106 patients the pressure reading was recorded at sensor removal. No zero drift was observed in 28 sensors. The median drift was 0 mm Hg with an IQR of −1 to 1 mm Hg. No significant differences were found between patients monitored for ≤ 5 days and those monitored for > 5 days (t = 535, p = 0.100). No correlation was found between zero drift and monitoring time (r = 0.153, p = 0.181). Of the 83 patients with a follow-up computed tomography scan, 3 showed a < 1 ml collection of blood at the catheter tip. No clinical infections could be attributed to the devices. Only 1 sensor malfunctioned.

Conclusions
Continuous ICP monitoring using the Neurodur-P sensor is safe, reliable, and easy to perform. At present, using this device is the authors' standard method for the long-term monitoring of patients with alterations in complex cerebrospinal fluid dynamics or with implanted shunts.
Lateral lakes of Trolard: anatomy, quantitation, and surgical landmarks
Authors: Tubbs R. Shane , Loukas Marios , Shoja Mohammadali M. , Apaydin Nihal , Ardalan Mohammad R. , Oakes W. Jerry 
Published: April 2008

Object
There is scant and conflicting information in the literature regarding the lateral lacunae, or lateral lakes of Trolard. As these venous structures can be encountered surgically, this study aimed at further elucidating their anatomy, identifying surgical landmarks, and associated quantitation.

Methods
Thirty-five adult cadavers were dissected of lateral lacunae. Following quantitation of the lacunae, these structures were measured, as were the distances from them to the coronal and sagittal sutures.

Results
A mean of 1.9 lacunae were identified on the right sides and 1.4 lacunae on the left sides. Although there tended to be slightly more lacunae on the right sides, this difference did not reach statistical significance (p > 0.05). The average lengths of the lacunae were 3.2 and 2.0 cm for the right and left sides, respectively. The mean widths of these venous lakes were 1.5 cm for the right sides and 0.8 cm for the left sides. Lacunae were variably positioned but tended to cluster near the vertex of the skull. None were identified posterior to the lambdoid sutures, and only 5 were found to lie anterior to the coronal suture, with 4 of these located on right sides (p < 0.05). When lacunae were identified anterior to the coronal suture, they were generally 5–6 cm from this structure. The majority of lacunae could be identified between the coronal and lambdoid sutures and within 3 cm of the midline.

Conclusions
Although the situation varies, lateral lacunae are concentrated posterior to the coronal suture and anterior to the lambdoid sutures. They are most often found within 3 cm of the sagittal suture. These previously unreported data could be useful to the neurosurgeon in planning surgical procedures that traverse the calvaria.