Movement Disorders.

Movement disorders are commonly encountered by the general practitioner and can be divided into 2 broad categories: hypokinetic and hyperkinetic. The former involves loss or slowing of movement, whereas the latter is characterized by excessive and involuntary movements. A careful history will guide the examiner to the appropriate category of movement disorders. As no laboratory test or radiologic study is confirmatory for these disorders, diagnosis must be made clinically and the neurologic examination is indispensable. In this article, we discuss physical examination techniques that will help diagnose common movement disorders.

Does patient gender impact resident physicians' approach to the cardiac exam?

BACKGROUND: Physical examination remains an important part of the initial evaluation of patients presenting with chest pain but little is known about the effect of patient gender on physician performance of the cardiovascular exam. OBJECTIVE: To determine if resident physicians are less likely to perform five key components of the cardiovascular exam on female versus male standardized patients (SPs) presenting with acute chest pain. DESIGN: Videotape review of SP encounters during Objective Structured Clinical Examinations (OSCEs) administered by the Emory University Internal Medicine Residency Program in 2006 and 2007. Encounters were reviewed to assess residents' performance of five cardiac exam skills: auscultation of the aortic, pulmonic, tricuspid, and mitral valve areas and palpation for the apical impulse. PARTICIPANTS: One hundred forty-nine incoming residents. MAIN MEASURES: Residents' performance for each skill was classified as correct, incorrect, or unknown. KEY RESULTS: One hundred ten of 149 (74 %) of encounters were available for review. Residents were less likely to correctly perform each of the five skills on female versus male SPs. This difference was statistically significant for auscultation of the tricuspid (p = 0.004, RR = 0.62, 95 % CI 0.46-0.83) and mitral (p = 0.007, RR = 0.58, 95 % CI = 0.41-0.83) valve regions and palpation for the apical impulse (p < 0.001, RR = 0.27, 95 % CI = 0.16-0.47). Male residents were less likely than female residents to correctly perform each maneuver on female versus male SPs. The interaction of SP gender and resident gender was statistically significant for auscultation of the mitral valve region (p = 0.006) and palpation for the apical impulse (p = 0.01). CONCLUSIONS: We observed significant differences in the performance of key elements of the cardiac exam for female versus male SPs presenting with chest pain. This observation represents a previously unidentified but potentially important source of gender bias in the evaluation of patients presenting with cardiovascular complaints.

A strategy for risk mitigation of antibodies with fast clearance.

A majority of human therapeutic antibody candidates show pharmacokinetic properties suitable for clinical use, but an unexpectedly fast antibody clearance is sometimes observed that may limit the clinical utility. Pharmacokinetic data in cynomolgus monkeys collected for a panel of 52 antibodies showed broad distribution of target-independent clearance values (2.4-61.3 mL/day/kg), with 15 (29%) having clearance > 10 mL/day/kg. Alteration in the interaction with the recycling FcRn receptor did not account for the faster than expected clearance observed for the antibodies; off-target binding was presumed to account for the fast clearance. We developed an assay based on ELISA detection of non-specific binding to baculovirus particles that can identify antibodies having increased risk for fast clearance. This assay can be used during lead generation or optimization to identify antibodies with increased risk of having fast clearance in both humans and cynomolgus monkeys, and thus increase the likelihood of obtaining a suitable drug candidate.

Through the looking glass: how reflective learning influences the development of young faculty members.

BACKGROUND: Faculty development is needed that will influence clinical teachers to better enable them to transmit humanistic values to their learners and colleagues. PURPOSE: We sought to understand the processes whereby reflective learning influenced professional growth in a convenience sample of young faculty members. METHODS: We analyzed appreciative inquiry narratives written over 4 years using the constant comparative method to identify major underlying themes and develop hypotheses concerning how reflective learning influenced participants in the faculty development program. Six of the participants and the facilitator were participant observers in the qualitative analysis. RESULTS: Group support, validation, and cohesion led to adoption of common values that informed the professional development of the participants over 4 years of the study. Common values influenced the group members as they progressed in their careers. CONCLUSIONS: Faculty development programs that focus on humanism and reflective learning can facilitate the growth of young faculty members by influencing their values and attitudes at crucial phases of their careers.

Noncompartmental kinetic analysis of DCE-MRI data from malignant tumors: Application to glioblastoma treated with bevacizumab.

Dynamic contrast enhanced MRI contrast agent kinetics in malignant tumors are typically complex, requiring multicompartment tumor models for adequate description. For consistent comparisons among tumors or among successive studies of the same tumor, we propose to estimate the total contrast agent-accessible volume fraction of tumor, including blood plasma, v(pe), and an average transfer rate constant across all tumor compartments, K(trans.av), by fitting a three-compartment tumor model and then calculating the area under the tumor impulse-response function (= v(pe)) and the ratio area under the tumor impulse response function over mean residence time in tumor (= K(trans.av)). If the duration of dynamic contrast enhanced MRI was too short to extrapolate the tumor impulse-response function to infinity with any confidence, then conditional parameters v(pe)(*) and K(trans.av*) should be calculated from the available incomplete impulse response function. Median decreases of 33% were found for both v(pe)(*) and K(trans.av*) in glioblastoma patients (n = 16) 24 hours after the administration of bevacizumab (P < 0.001). Median total contrast-enhancing tumor volume was reduced by 18% (P < 0.0001). The combined changes of tumor volume, v(pe)(*), and K(trans.av*) suggest a reduction of true v(pe), possibly accompanied by a reduction of true K(trans.av). The proposed method provides estimates of a scale and a shape parameter to describe contrast agent kinetics of varying complexity in a uniform way.

An automated method for nonparametric kinetic analysis of clinical DCE-MRI data: application to glioblastoma treated with bevacizumab.

Here, we describe an automated nonparametric method for evaluating gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) kinetics, based on dynamic contrast-enhanced-MRI scans of glioblastoma patients taken before and after treatment with bevacizumab; no specific model or equation structure is assumed or used. Tumor and venous blood concentration-time profiles are smoothed, using a robust algorithm that removes artifacts due to patient motion, and then deconvolved, yielding an impulse response function. In addition to smoothing, robustness of the deconvolution operation is assured by excluding data that occur prior to the plasma peak; an exhaustive analysis was performed to demonstrate that exclusion of the prepeak plasma data does not significantly affect results. All analysis steps are executed by a single R script that requires blood and tumor curves as the sole input. Statistical moment analysis of the Impulse response function yields the area under the curve (AUC) and mean residence time (MRT). Comparison of deconvolution results to fitted Tofts model parameters suggests that AUCMRT and AUC of the Impulse response function closely approximate fractional clearance from plasma to tissue (K(trans)) and fractional interstitial volume (v(e)). Intervisit variability is shown to be comparable when using the deconvolution method (11% [AUCMRT] and 13%[AUC]) compared to the Tofts model (14%[K(trans)] and 24%[v(e)]). AUC and AUCMRT both exhibit a statistically significant decrease (P < 0.005) 1 day after administration of bevacizumab.

A novel, Q-PCR based approach to measuring endogenous retroviral clearance by capture protein A chromatography.

Quantification of virus removal by the purification process during production is required for clinical use of biopharmaceuticals. The current validation approach for virus removal by chromatography steps typically involves time-consuming spiking experiments with expensive model viruses at bench scale. Here we propose a novel, alternative approach that can be applied in at least one instance: evaluating retroviral clearance by protein A chromatography. Our strategy uses a quantitative PCR (Q-PCR) assay that quantifies the endogenous type C retrovirus-like particle genomes directly in production Chinese Hamster Ovary (CHO) cell culture harvests and protein A pools. This eliminates the need to perform spiking with model viruses, and measures the real virus from the process. Using this new approach, clearance values were obtained that was comparable to those from the old model-virus spike/removal approach. We tested the concept of design space for CHO retrovirus removal using samples from a protein A characterization study, where a wide range of chromatographic operating conditions were challenged, including load density, flow rate, wash, pooling, temperature, and resin life cycles. Little impact of these variables on CHO retrovirus clearance was found, arguing for implementation of the design space approach for viral clearance to support operational ranges and manufacturing excursions. The viral clearance results from Q-PCR were confirmed by an orthogonal quantitative product-enhanced reverse transcriptase (Q-PERT) assay that quantifies CHO retrovirus by their reverse transcriptase (RT) enzyme activity. Overall, our results demonstrate that protein A chromatography is a robust retrovirus removal step and CHO retrovirus removal can be directly measured at large scale using Q-PCR assays.

Reactive hyperemia and BOLD MRI demonstrate that VEGF inhibition, age, and atherosclerosis adversely affect functional recovery in a murine model of peripheral artery disease.

PURPOSE: To develop magnetic resonace imaging (MRI) methods for functional assessment of arteriogenesis in a murine model of peripheral artery disease to quantify the influences of vascular endothelial growth factor (VEGF), age, and atherosclerosis. MATERIALS AND METHODS: Reactive hyperemia (RH), which was induced using a device designed for remote and transient occlusion of the aorta and vena cava, was measured by blood-oxygen-level-dependent MRI. Twenty-eight days after femoral artery ligation, peak height (PH) and time to peak (TTP) of the RH response was compared with sham-operated animals in 10-week-old C57Bl6, 9-month-old C57Bl6, and 9-month-old Ldlr(-/-)Apobec(-/-) mice. The contribution of VEGF to functional recovery was assessed in young mice. Angiogenesis was quantified using an anti-PECAM1 radioimmunoassay. RESULTS: In young animals, angiogenesis was maximal 7 days after ligation, whereas functional recovery took 28 days. Inhibition of VEGF eliminated the angiogenesis seen at 7 days and reduced RH (PH, P < 0.05). At day 28, RH was altered in old (TTP, P < 0.05) and atherosclerotic (PH, P < 0.05; TTP, P < 0.05) animals. RH was different in young, old, and atherosclerotic sham animals. Old and atherosclerotic mice showed reduced angiogenesis. CONCLUSION: The method presented herein can provide a sensitive assay for the functional assessment of arteriogenesis and highlights the contribution of VEGF, age, and atherosclerosis to this process.

Factors associated with lack of interest in HIV testing in older at-risk women.

OBJECTIVE: To determine the factors and reasons associated with lack of interest in HIV testing among older women from a high prevalence community. METHODS: We conducted a cross-sectional study of women aged >or=50 seeking medical care. The main outcome measures were (1) interest in HIV testing and (2) reasons for women's interest or lack of interest assessed using open-ended questions. We compared the characteristics of women based on testing interest and fit two multivariable logistic regression models to identify factors associated with lack of testing interest among never tested women and women with moderate or high HIV risk factors. Responses to short answer questions were analyzed according to participants' HIV testing interest. Coding was performed by two independent reviewers using deductive application of themes identified in previously published literature on HIV testing interest. RESULTS: Of 564 eligible women, 514 (91%) enrolled. Only 22% were interested in HIV testing. Those who lacked interest were more likely to be older (63.3 vs. 58.4, p < 0.001), African American (77% vs. 60%, p < 0.001), have poor HIV knowledge (68% vs. 57%, p = 0.02), and have low perceived HIV risk (82% vs. 69%, p = 0.01). Lack of interest in HIV testing was associated with increasing age and African American race among women with moderate or high-risk factors, whereas age, African American race and low perceived risk were important for never tested women. Common reasons for lacking interest in testing were perceived lack of need, perceived lack of risk, and a prior history of HIV testing. CONCLUSIONS: Few of these older, high-risk women were interested in HIV testing despite the fact that more than half had risk factors for having been exposed to HIV during their life-time. Efforts to increase HIV testing interest should educate older women about HIV risk and transmission factors and promote accurate risk self-assessment.

Repaving the road to academic success: the IMeRGE approach to peer mentoring.

In recent years, academic health centers have made a considerable effort to encourage medical students and physicians-in-training to consider academic medicine as a career choice. For physicians, selecting a career in academic medicine may be the first hurdle, but the challenge of successfully maintaining an academic career is perhaps a more formidable task. Mentoring is a much-needed response to this challenge. But the success of traditional mentoring programs at academic institutions is often limited by, among other things, the availability of senior faculty who can serve as mentors. The authors describe the formation and organization of the Internal Medicine Research Group at Emory (IMeRGE), an innovative peer mentoring group within the Division of General Medicine at Emory University. This group, born partially out of the mentoring needs of our women and minority faculty, shared the primary goal of fostering a collaborative atmosphere among junior faculty, while simultaneously acquiring experience through advanced faculty development. The authors present our methods of garnering division support for designated time and financial resources, defining member responsibilities, developing a curriculum, providing peer support, and seeking advisors with expertise in the areas on which we wished to focus. In addition to the development of IMeRGE, the authors provide an overview of the pros and cons of traditional mentoring versus peer mentoring; discuss the challenges faced by IMeRGE and strategies for addressing these issues; and present the paradigm of IMeRGE as a template for alternative forms of academic mentorship.

Effect of relationship factors on safer sex decisions in older inner-city women.

OBJECTIVES: Heterosexual transmission of the human immunodeficiency virus (HIV) in older women is on the rise, yet little is known about safer sex practices in these women. We sought to determine the prevalence of and effect of relationship factors on safer sex practices among older women living in a high HIV incidence region. METHODS: In a cross-sectional study at an ambulatory medicine clinic of a large inner-city hospital, participants were women over age 50 seeking medical services at the study site. Measurements included (1) partner trust, (2) dependence on partner, (3) personally obtaining condoms, (4) safer sex (frequent condom use or abstinence), (5) knowledge of condom efficacy, and (6) perceived HIV risk. RESULTS: Of 155 participants in a current relationship, 81% were sexually active; however, only 13% of these women used condoms frequently. No significant differences were found between participants who did and did not practice safer sex with respect to their age, race, employment, marital status, knowledge of condom efficacy, or perceived HIV risk. Trust in partner was independently associated with lower odds of safer sex (OR 0.3, 95% CI 0.08-1.06). Personally obtaining condoms (OR 9.2, 95% CI 1.9-44.2) and dependence on partner for condoms (OR 12.3, 95% CI 3.0-50.3) were independently associated with higher odds of safer sex. CONCLUSIONS. Few older women in high HIV incidence areas practice safer sex. Relationship factors impact the risk of acquiring HIV through safer sex decisions. HIV prevention messages geared to older women should incorporate references to the role these factors can play in reducing their HIV risk.

Older women and HIV: how much do they know and where are they getting their information?

OBJECTIVES: To assess older urban women's knowledge about sexual transmission of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and to evaluate the relationship between their HIV/AIDS knowledge level and sources of information. DESIGN: Cross-sectional survey conducted between June 2001 and July 2002. Trained research assistants administered a questionnaire in a face-to-face interview. SETTING: General medicine clinic in a large public hospital in a high HIV/AIDS incidence area. PARTICIPANTS: Five hundred fourteen women aged 50 and older. MEASUREMENTS: Nine questions assessing knowledge of risk of HIV sexual transmission with potential scores ranging from 0 to 9 correct answers. Participants identified all sources of HIV information. RESULTS: The mean knowledge score was 3.7 out of a possible 9 correct responses (range 0 (3%) to 8 (1%)). Younger age, employment, and higher educational level were associated with higher knowledge scores, whereas marital status was unrelated. No respondent correctly answered all of the nine questions. The most commonly identified sources of HIV/AIDS information were television (85%), friends (54%), and newspapers (51%). Only 38% of respondents identified health professionals as a source of information about HIV/AIDS. Health professionals, newspapers, and family members were each independently associated with higher knowledge scores (P<.05). CONCLUSION: Older women in a general medicine clinic had limited knowledge of sexual transmission of HIV. HIV/AIDS education specifically targeted to this subpopulation is warranted, and health professionals may have an important role in disseminating such messages.