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Urologist
23 years of experience
Accepting new patients

Credentials

Education ?

Medical School Score Rankings
UMDNJ (1989)
  •  
Top 50%

Awards & Distinctions ?

Awards  
Compassionate Doctor Recognition (2015)
On-Time Doctor Award (2014 - 2015)
Associations
American Urological Association
American Board of Urology

Affiliations ?

Dr. Friedman is affiliated with 13 hospitals.

Hospital Affiliations

Score

Rankings

  • Morristown Memorial Hospital
    Urology
    100 Madison Ave, Morristown, NJ 07960
    •  
    Top 25%
  • NewYork-Presbyterian / Weill Cornell
    Urology
    525 E 68th St, New York, NY 10065
    •  
    Top 25%
  • New York Presbyterian Hospital / Columbia
    Urology
    630 W 168th St, New York, NY 10032
    •  
    Top 25%
  • St. Clare's Hospital-Denville
    Urology
    25 Pocono Rd, Denville, NJ 07834
    •  
  • St. Clare's Hospital-Dover Div.
    25 Pocono Rd, Denville, NJ 07834
    •  
  • Hackettstown Regional Medical Center
    651 Willow Grove St, Hackettstown, NJ 07840
    •  
  • Saint Clare`s Hospital
  • Ahs Hosp Corp Mmh Morristown Memorial Hospital
  • Frankford Hospital
  • Saint Clare's Hospital - Boonton Township
    130 Powerville Rd, Boonton, NJ 07005
  • Saint Clare`s Health System Dover
  • St Clares Hospital
  • St. Clare`s Hosp - Dover, Dover
  • Publications & Research

    Dr. Friedman has contributed to 176 publications.
    Title Lack of Association Between Comt Polymorphisms and Apathy in Alzheimer's Disease.
    Date February 2012
    Journal Journal of Alzheimer's Disease : Jad
    Excerpt

    We tested the hypothesis that single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) are associated with apathy in individuals with Alzheimer's disease (AD). We analyzed a cohort of 105 Caucasian individuals with AD (age = 79.3 ± 7.03 years; MMSE = 20.2 ± 4.4) according to the presence of apathy, as defined either by the Neuropsychiatric Inventory or the Apathy Inventory. Polymorphisms in seventeen SNPs in COMT were examined. A replication cohort consisting of 176 Caucasian AD subjects in the ADNI database was also analyzed. None of the candidate gene SNPs were significantly associated with the presence of apathy in either cohort. We did not find any SNPs in COMT that were consistently associated with apathy in individuals with AD.

    Title Polycationic Glycosides.
    Date April 2011
    Journal Molecules (basel, Switzerland)
    Excerpt

    Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial results of our approach to this goal are presented.

    Title Molecular Classification of Thyroid Nodules Using High-dimensionality Genomic Data.
    Date January 2011
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    We set out to develop a molecular test that distinguishes benign and malignant thyroid nodules using fine-needle aspirates (FNA).

    Title Laparoscopic Management of Sigmoidorectal Intussusception.
    Date July 2010
    Journal Jsls : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons
    Excerpt

    Adult intussusception is an uncommon entity. Surgical resection is required because of the high incidence of pathological lead point. We report a case of sigmoidorectal intussusception caused by a large tubulovillous adenoma. The patient underwent laparoscopic sigmoidectomy.

    Title Sleep and Physical Functioning in Family Caregivers of Older Adults with Memory Impairment.
    Date April 2010
    Journal International Psychogeriatrics / Ipa
    Excerpt

    Sleep disturbance is common in caregivers of older adults with memory disorders. Little is known, however, about the implications of caregivers' poor sleep with regard to their physical functioning.

    Title Polycations. 17. Synthesis and Properties of Polycationic Derivatives of Carbohydrates.
    Date December 2009
    Journal Carbohydrate Research
    Excerpt

    In our continuing investigation of polycationic salts for purposes of antimicrobial action, ion-channel blocking, and construction of ionic liquids, we have prepared several series of polycationic salts derived from carbohydrate precursors. These salts are currently being investigated for optimal efficacy as antibacterials and antifungals, as well as for other applications. The syntheses of such series of salts are described here along with preliminary antibacterial testing results and a discussion of their properties indicating their potential utility for several purposes.

    Title Identifying Genotype-dependent Efficacy of Single and Combined Pi3k- and Mapk-pathway Inhibition in Cancer.
    Date November 2009
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    In cancer, genetically activated proto-oncogenes often induce "upstream" dependency on the activity of the mutant oncoprotein. Therapeutic inhibition of these activated oncoproteins can induce massive apoptosis of tumor cells, leading to sometimes dramatic tumor regressions in patients. The PI3K and MAPK signaling pathways are central regulators of oncogenic transformation and tumor maintenance. We hypothesized that upstream dependency engages either one of these pathways preferentially to induce "downstream" dependency. Therefore, we analyzed whether downstream pathway dependency segregates by genetic aberrations upstream in lung cancer cell lines. Here, we show by systematically linking drug response to genomic aberrations in non-small-cell lung cancer, as well as in cell lines of other tumor types and in a series of in vivo cancer models, that tumors with genetically activated receptor tyrosine kinases depend on PI3K signaling, whereas tumors with mutations in the RAS/RAF axis depend on MAPK signaling. However, efficacy of downstream pathway inhibition was limited by release of negative feedback loops on the reciprocal pathway. By contrast, combined blockade of both pathways was able to overcome the reciprocal pathway activation induced by inhibitor-mediated release of negative feedback loops and resulted in a significant increase in apoptosis and tumor shrinkage. Thus, by using a systematic chemo-genomics approach, we identify genetic lesions connected to PI3K and MAPK pathway activation and provide a rationale for combined inhibition of both pathways. Our findings may have implications for patient stratification in clinical trials.

    Title Role of Smoking in the Recurrence of Atrial Arrhythmias After Cardioversion.
    Date September 2009
    Journal The American Journal of Cardiology
    Excerpt

    We aimed to determine whether smoking status affects the recurrence of atrial fibrillation or atrial flutter in patients after cardioversion. The clinical data of patients undergoing cardioversion for atrial flutter from January 1, 2000 to December 31, 2005 were prospectively collected. Arrhythmia recurrences were detected by retrospective review of comprehensive medical records and were determined using electrocardiography. The smoking history was prospectively collected through a standardized clinical form and subsequently categorized as lifetime nonsmoker, exsmoker, or current smoker. Univariate and multivariate associations with end points for clinical and lifestyle variables were assessed with Cox proportional hazards models. Women who were current smokers at cardioversion had a greater risk of atrial arrhythmia recurrence than did nonsmokers (hazard ratio 1.71, 95% confidence interval 1.10 to 2.67, p = 0.02). The increased risk of arrhythmia recurrence in female smokers was not seen in male smokers. Compared to lifetime nonsmokers, the mortality hazard ratio among men was 1.18 (95% confidence interval 0.88 to 1.58; p = 0.28) in exsmokers and 1.93 (95% confidence interval 1.20 to 3.11; p = 0.007) in current smokers. The risk of death after cardioversion was not increased in women. In conclusion, smoking is an independent predictor of atrial arrhythmia recurrence after cardioversion in women; however, an increased mortality risk, but not arrhythmia recurrence risk, was seen in men.

    Title Impact of an Internet-based Emergency Department Appointment System to Access Primary Care at Safety Net Community Clinics.
    Date August 2009
    Journal Annals of Emergency Medicine
    Excerpt

    We evaluate the effect of an Internet-based, electronic referral system (termed IMPACT-ED for Improving Medical home and Primary care Access to the Community clinics Through the ED) on access and follow-up at primary care community clinics for safety net emergency department (ED) patients.

    Title Scheduled Bright Light for Treatment of Insomnia in Older Adults.
    Date March 2009
    Journal Journal of the American Geriatrics Society
    Excerpt

    To determine whether bright light can improve sleep in older individuals with insomnia.

    Title Acetylcholinesterase Inhibitor in Combination with Cognitive Training in Older Adults.
    Date October 2008
    Journal The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences
    Excerpt

    To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.

    Title Successful Placement of a Right Ventricular Assist Device for Treatment of a Presumed Amniotic Fluid Embolism.
    Date September 2008
    Journal Anesthesia and Analgesia
    Excerpt

    Amniotic fluid embolism is a rare and often fatal complication of pregnancy. We report the successful multidisciplinary management of a woman who developed a coagulopathy from a presumed amniotic fluid embolism after forceps-assisted vaginal delivery requiring recombinant factor VIIa, and pulmonary arterial hypertension requiring a right ventricular assist device.

    Title Street Corner Hazard Surveillance and Health Intervention Among Chicago Day Laborers.
    Date June 2008
    Journal Archives of Environmental & Occupational Health
    Excerpt

    Day laborers in Chicago are often hired for hazardous jobs and have little access to basic health care. In this study, the researchers offered tetanus vaccinations and blood lead tests to workers waiting on street corners, who then completed a survey on hazardous job tasks (N = 92). All participants were male, 97% were foreign-born, and 93% had performed demolition and rehabilitation, window removal and installation, or paint removal in the previous month. Most were not current with tetanus immunization. The geometric mean blood lead level was 3.8 mug/dL. Nonparametric statistical analysis showed a significant association (p < .05) between blood lead level and country of origin. The results demonstrate the feasibility of hazard surveillance and health intervention at street corner hiring sites.

    Title Chronic Smoking and the Bold Response to a Visual Activation Task and a Breath Hold Task in Patients with Schizophrenia and Healthy Controls.
    Date June 2008
    Journal Neuroimage
    Excerpt

    Many psychiatric patient groups smoke heavily, but little is known regarding the effects of this habit on functional brain imaging results. The present report assesses the effect of chronic smoking on the blood oxygen level-dependent (BOLD) response to a simple visual activation (VA) task and a breath hold (BH) task in patients with schizophrenia. Eight healthy controls and twelve patients with schizophrenia were studied. Half of each group had never smoked and the other half of each group had smoked for more than 10 pack years. Responses to the VA task were assessed in the visual cortex and responses to the BH task were assessed in gray matter generally. There were four fMRI-dependent measures: (1) median percent signal change; (2) activation volume (in voxels); (3) time-to-peak of the impulse response function (IRF); and (4) time-to-trough of the IRF. All measures were tested as dependent variables in an ANCOVA with diagnosis and smoking status as crossed factors and age as a covariate. Heavy smokers had 22% larger percent signal change for the VA task and 50% larger percent signal change for the BH task. Patients had a 40% larger percent signal change for the breath hold task. Other statistically significant effects of smoking history on activation volume and the timing of the brain responses were noted. If replicated, the results may have important implications for fMRI studies comparing groups with markedly different smoking habits, such as studies comparing patients with schizophrenia, 60-90% of whom smoke, and healthy controls, who smoke with a much lower frequency.

    Title The Impact of Privacy and Confidentiality Laws on the Conduct of Clinical Trials.
    Date June 2008
    Journal Clinical Trials (london, England)
    Excerpt

    Justifiable concerns about the use of personal data in many aspects of daily life have led to the recent introduction in many countries of laws intended to regulate data use. Although participation in randomized clinical trials is generally with informed consent, recruitment procedures, complete follow-up, and the efficient conduct of trials may be substantially affected by such national or local privacy legislation. The relevant laws often have exceptions that allow the use of patient information in the public interest - including the use of data collected to improve or monitor public health or as part of medical research. However, regulatory bodies often give conflicting interpretations of the law, and this affects the conduct of large-scale trials. In particular, unnecessarily restrictive interpretation of the law may be a serious impediment to identification of potential participants for a trial, access to records to confirm events, continued follow-up of patients after the trial has been concluded, and secondary use of the trial data for purposes not directly related to the original purpose of the study. These obstacles could be overcome by better informing patients of the uses of records for medical research purposes, by using informed consent procedures that explain the nature of the research and the uses of the data, and by the use of identifiers, such as social security numbers that allow central follow-up. The clinical trial research community needs to ensure that the substantial benefits of large-scale randomized trials are explained both to the public and to those responsible for introducing legislation. The negative impact of privacy legislation on the use of personal health information and on conducting large studies needs to be understood and minimized.

    Title Antioxidant Use in Friedreich Ataxia.
    Date June 2008
    Journal Journal of the Neurological Sciences
    Excerpt

    Many antioxidants have been suggested as potential treatments for Friedreich ataxia, but have not been tested in clinical trials. We found that a majority of patients in our cohort already use such antioxidants, including idebenone, which is not available at a pharmaceutical grade in the United States. Younger age, cardiomyopathy and shorter GAA repeat length were independent predictors of idebenone use, but no factors predicted use of other antioxidants. This confirms that non-prescription antioxidant use represents a major confounder to formal trials of existing and novel agents for Friedreich ataxia.

    Title Subclinical Anxiety Symptoms, Sleep, and Daytime Dysfunction in Older Adults with Primary Insomnia.
    Date May 2008
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    "Both Insomnia complaints and anxiety-related distress are common in older adults, and are associated with poor daytime functioning. We investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore but did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and shorter sleep sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse and social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia."

    Title Practice Parameters for the Treatment of Narcolepsy and Other Hypersomnias of Central Origin.
    Date March 2008
    Journal Sleep
    Excerpt

    These practice parameters pertain to the treatment of hypersomnias of central origin. They serve as both an update of previous practice parameters for the therapy of narcolepsy and as the first practice parameters to address treatment of other hypersomnias of central origin. They are based on evidence analyzed in the accompanying review paper. The specific disorders addressed by these parameters are narcolepsy (with cataplexy, without cataplexy, due to medical condition and unspecified), idiopathic hypersomnia (with long sleep time and without long sleep time), recurrent hypersomnia and hypersomnia due to medical condition. Successful treatment of hypersomnia of central origin requires an accurate diagnosis, individual tailoring of therapy to produce the fullest possible return of normal function, and regular follow-up to monitor response to treatment. Modafinil, sodium oxybate, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, and selegiline are effective treatments for excessive sleepiness associated with narcolepsy, while tricyclic antidepressants and fluoxetine are effective treatments for cataplexy, sleep paralysis, and hypnagogic hallucinations; but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness in narcolepsy patients. Based on available evidence, modafinil is an effective therapy for sleepiness due to idiopathic hypersomnia, Parkinson's disease, myotonic dystrophy, and multiple sclerosis. Based on evidence and/or long history of use in the therapy of narcolepsy committee consensus was that modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate are reasonable options for the therapy of hypersomnias of central origin.

    Title Practice Parameters for the Use of Autotitrating Continuous Positive Airway Pressure Devices for Titrating Pressures and Treating Adult Patients with Obstructive Sleep Apnea Syndrome: an Update for 2007. An American Academy of Sleep Medicine Report.
    Date March 2008
    Journal Sleep
    Excerpt

    These practice parameters are an update of the previously published recommendations regarding the use of autotitrating positive airway pressure (APAP) devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome. Continuous positive airway pressure (CPAP) at an effective setting verified by attended polysomnography is a standard treatment for obstructive sleep apnea (OSA). APAP devices change the treatment pressure based on feedback from various patient measures such as airflow, pressure fluctuations, or measures of airway resistance. These devices may aid in the pressure titration process, address possible changes in pressure requirements throughout a given night and from night to night, aid in treatment of OSA when attended CPAP titration has not or cannot be accomplished, or improve patient comfort. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine has reviewed the literature published since the 2002 practice parameter on the use of APAP. Current recommendations follow: (1) APAP devices are not recommended to diagnose OSA; (2) patients with congestive heart failure, patients with significant lung disease such as chronic obstructive pulmonary disease; patients expected to have nocturnal arterial oxyhemoglobin desaturation due to conditions other than OSA (e.g., obesity hypoventilation syndrome); patients who do not snore (either naturally or as a result of palate surgery); and patients who have central sleep apnea syndromes are not currently candidates for APAP titration or treatment; (3) APAP devices are not currently recommended for split-night titration; (4) certain APAP devices may be used during attended titration with polysomnography to identify a single pressure for use with standard CPAP for treatment of moderate to severe OSA; (5) certain APAP devices may be initiated and used in the self-adjusting mode for unattended treatment of patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (6) certain APAP devices may be used in an unattended way to determine a fixed CPAP treatment pressure for patients with moderate to severe OSA without significant comorbidities (CHF, COPD, central sleep apnea syndromes, or hypoventilation syndromes); (7) patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must have close clinical follow-up to determine treatment effectiveness and safety; and (8) a reevaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the APAP treatment otherwise appears to lack efficacy.

    Title Practice Parameters for the Clinical Evaluation and Treatment of Circadian Rhythm Sleep Disorders. An American Academy of Sleep Medicine Report.
    Date February 2008
    Journal Sleep
    Excerpt

    The expanding science of circadian rhythm biology and a growing literature in human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the American Academy of Sleep Medicine (AASM) to convene a task force of experts to write a review of this important topic. Due to the extensive nature of the disorders covered, the review was written in two sections. The first review paper, in addition to providing a general introduction to circadian biology, addresses "exogenous" circadian rhythm sleep disorders, including shift work disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the "endogenous" circadian rhythm sleep disorders, including advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), and the non-24-hour sleep-wake syndrome (nonentrained type) or free-running disorder (FRD). These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the AASM to present recommendations for the assessment and treatment of CRSDs based on the two accompanying comprehensive reviews. The main diagnostic tools considered include sleep logs, actigraphy, the Morningness-Eveningness Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep log or diary is indicated in the assessment of patients with a suspected circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in evaluation of patients suspected of circadian rhythm disorders (strength of recommendation varies from "Option" to "Guideline," depending on the suspected CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but may be indicated to rule out another primary sleep disorder (Standard). There is insufficient evidence to justify the use of MEQ for the routine clinical evaluation of CRSDs (Option). Circadian phase markers are useful to determine circadian phase and confirm the diagnosis of FRD in sighted and unsighted patients but there is insufficient evidence to recommend their routine use in the diagnosis of SWD, JLD, ASPD, DSPD, or ISWR (Option). Additionally, actigraphy is useful as an outcome measure in evaluating the response to treatment for CRSDs (Guideline). A range of therapeutic interventions were considered including planned sleep schedules, timed light exposure, timed melatonin doses, hypnotics, stimulants, and alerting agents. Planned or prescribed sleep schedules are indicated in SWD (Standard) and in JLD, DSPD, ASPD, ISWR (excluding elderly-demented/nursing home residents), and FRD (Option). Specifically dosed and timed light exposure is indicated for each of the circadian disorders with variable success (Option). Timed melatonin administration is indicated for JLD (Standard); SWD, DSPD, and FRD in unsighted persons (Guideline); and for ASPD, FRD in sighted individuals, and for ISWR in children with moderate to severe psychomotor retardation (Option). Hypnotic medications may be indicated to promote or improve daytime sleep among night shift workers (Guideline) and to treat jet lag-induced insomnia (Option). Stimulants may be indicated to improve alertness in JLD and SWD (Option) but may have risks that must be weighed prior to use. Modafinil may be indicated to improve alertness during the night shift for patients with SWD (Guideline).

    Title Vaccinating Adolescents in High-risk Settings: Lessons Learned from Experiences with Hepatitis B Vaccine.
    Date January 2008
    Journal Pediatrics
    Excerpt

    Meeting the health needs of adolescents who live in high-risk settings such as homeless shelters, migrant camps, juvenile detention centers, prisons, and other types of residential facilities presents many challenges. Although there is no doubt that adolescents in many high-risk settings are at increased risk for hepatitis B and human papillomavirus, acute medical and psychological problems may consume all of the provider's time and resources. Potential health threats such as vaccine-preventable diseases must necessarily be given lower priority. Lack of vaccination expertise, supplies, and access to records further complicate delivery of vaccines. Since the 1990s, a number of approaches have been used to deliver hepatitis B vaccine to adolescents in many high-risk settings. Close collaboration among state and federal programs, local health departments, and community-based organizations has been necessary to introduce and sustain the delivery of vaccines to these young people. Medicaid, Statute 317 of the Public Health Service Act, the Vaccines for Children program, and State Children's Health Insurance Program have been used to finance vaccinations for adolescents 18 years or younger, and the expanded Medicaid option in the Foster Care Independence Act of 1999 has been used for adolescents older than 18 years of age. A number of states allow adolescents under age 18 to consent to their own hepatitis B vaccination under laws passed to allow treatment of sexually transmitted infections without parental consent. In this article, we present the experiences of several model programs that developed successful hepatitis B vaccination programs in venues that serve adolescents at risk, the important role of state laws and state agencies in funding immunization and other preventive health services for adolescents in high-risk situations, and discuss barriers and means to resolve them.

    Title Long-term Observation of Adolescents Initiating Haart Therapy: Three-year Follow-up.
    Date January 2008
    Journal Aids Research and Human Retroviruses
    Excerpt

    The PACTG 381 cohort included 120 adolescents infected via high-risk behaviors and treated with at least two NRTIs plus either a protease inhibitor or an efavirenz-containing HAART regimen. After 24 weeks of therapy, only 69 of 118 (59%) evaluable subjects had undetectable viral loads. We now present findings of the study after 3 years of follow-up. Virologic, immunologic, and treatment information were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Of the 120 subjects starting HAART, 44 (37%) stayed on study treatment for the 3 years of observation. Twenty-nine (24%) subjects reached and maintained undetectable viral loads. Poorer adherence (p = 0.016), higher baseline viral load (p = 0.010), and CD8 naive counts (p = 0.034) predicted virologic failure. Immunologic measurements improved from entry to the end of follow-up in the subjects with undetectable viral loads. CD4 counts at the end of study were not significantly different from HIV-uninfected youth, but CD4%, CD8 counts and percent, and CD8 activation markers remained significantly different. Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Immunologic improvement was demonstrated and CD4 counts in subjects with virologic control reached levels in HIV-uninfected adolescents. Interventions, especially those focused on adherence, are necessary to improve HAART outcomes in adolescents.

    Title Latency: an Important Consideration in Gulf War Syndrome.
    Date December 2007
    Journal Neurotoxicology
    Title Axial Oblique Mr Imaging of the Intrinsic Ligaments of the Wrist: Initial Experience.
    Date November 2007
    Journal Skeletal Radiology
    Excerpt

    To evaluate two separate MR sequences acquired in the axial oblique plane, parallel to the long axis of the scapholunate (SL) and lunotriquetral (LT) ligaments, to determine whether the addition of these sequences to the standard MR wrist examination improves visualization of the intrinsic ligaments, and the evaluation of their integrity. To our knowledge, this plane has not been described in the literature previously.

    Title Musculoskeletal Disorders of the Lower Limb--ultrasound and Magnetic Resonance Imaging Correlation.
    Date September 2007
    Journal Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes
    Excerpt

    The purpose of this paper is to familiarize general radiologists and specialists with the sonographic and corresponding magnetic resonance imaging (MRI) appearance of various musculoskeletal disorders of the lower limb. Technologists and radiologists should be familiar with all imaging techniques for the investigation and evaluation of musculoskeletal abnormalities. The role of high-resolution ultrasound (US) is highlighted, as well as the complementary relation between both imaging modalities. We also discuss some of the advantages of US over MRI in the investigation of musculoskeletal disorders of the lower limb. The MRI and US appearances of various articular, periarticular, and soft tissue pathologies of the lower limb are compared and reviewed, and where possible, the advantages of each modality are identified.

    Title Practice Parameters for the Use of Actigraphy in the Assessment of Sleep and Sleep Disorders: an Update for 2007.
    Date July 2007
    Journal Sleep
    Excerpt

    BACKGROUND: Actigraphy is increasingly used in sleep research and the clinical care of patients with sleep and circadian rhythm abnormalities. The following practice parameters update the previous practice parameters published in 2003 for the use of actigraphy in the study of sleep and circadian rhythms. METHODS: Based upon a systematic grading of evidence, members of the Standards of Practice Committee, including those with expertise in the use of actigraphy, developed these practice parameters as a guide to the appropriate use of actigraphy, both as a diagnostic tool in the evaluation of sleep disorders and as an outcome measure of treatment efficacy in clinical settings with appropriate patient populations. RECOMMENDATIONS: Actigraphy provides an acceptably accurate estimate of sleep patterns in normal, healthy adult populations and inpatients suspected of certain sleep disorders. More specifically, actigraphy is indicated to assist in the evaluation of patients with advanced sleep phase syndrome (ASPS), delayed sleep phase syndrome (DSPS), and shift work disorder. Additionally, there is some evidence to support the use of actigraphy in the evaluation of patients suspected of jet lag disorder and non-24hr sleep/wake syndrome (including that associated with blindness). When polysomnography is not available, actigraphy is indicated to estimate total sleep time in patients with obstructive sleep apnea. In patients with insomnia and hypersomnia, there is evidence to support the use of actigraphy in the characterization of circadian rhythms and sleep patterns/disturbances. In assessing response to therapy, actigraphy has proven useful as an outcome measure in patients with circadian rhythm disorders and insomnia. In older adults (including older nursing home residents), in whom traditional sleep monitoring can be difficult, actigraphy is indicated for characterizing sleep and circadian patterns and to document treatment responses. Similarly, in normal infants and children, as well as special pediatric populations, actigraphy has proven useful for delineating sleep patterns and documenting treatment responses. CONCLUSIONS: Recent research utilizing actigraphy in the assessment and management of sleep disorders has allowed the development of evidence-based recommendations for the use of actigraphy in the clinical setting. Additional research is warranted to further refine and broaden its clinical value.

    Title Long-term Effects of Mnemonic Training in Community-dwelling Older Adults.
    Date July 2007
    Journal Journal of Psychiatric Research
    Excerpt

    The purpose of our study was to investigate the long-term effect of mnemonic training on memory performance in older adults. Five years after participation in a mnemonic training study, we followed-up 112 community-dwelling older adults, 60 years of age and over. Delayed recall of a word list was assessed prior to, and immediately following mnemonic training, and at the 5-year follow-up. Overall, there was no significant difference between word recall prior to training and that exhibited at follow-up. However, pre-training performance, gain scores in performance immediately post-training and use of the mnemonic predicted performance at follow-up. Individuals who self-reported using the mnemonic exhibited the highest performance overall, with scores significantly higher than at pre-training. Our findings suggest that mnemonic training has long-term benefits for some older adults, particularly those who continue to employ the mnemonic.

    Title Sleep-related Epilepsy in the A/j Mouse.
    Date March 2007
    Journal Sleep
    Excerpt

    RATIONALE: Evident seizures during sleep are common in clinical practice but are uncommonly considered in animal models of epilepsy. A previous observation of spontaneous spike-and-wave activity during sleep in several A/J mice (A/J JAX) from Jackson Laboratory (Bar Harbor, ME) prompted this description of the inheritance of epileptic activity. METHODS: Mice from A/J, C57BI/6J (B6), and chromosomal substitutions strains were instrumented to record EEG and EMG activity over time without and with anti-epileptic drugs. Intercrosses were performed using linkage analysis to localize sub-chromosomal regions. RESULTS: Spike-discharge patterns (n = 12 mice) were of average duration of 1.9 seconds at a rate per hour of 17, with an intrinsic frequency of 6.41 Hz and an amplitude of 634.8 microV. Clonic movements were observed in < 10% of the episodes. Episodes were expressed (> 75%) either in slow-wave sleep or in transitions to and from slow-wave sleep. Events were rare in paradoxical sleep. Compared with vehicle, intraperitoneal administration of ethosuximide (150 mg/kg) or diazepam (5 mg/kg) inhibited or eliminated seizure activity, respectively. In contrast, spontaneous spike-and-wave activity was not observed in A/J mice from Harlan National Laboratories (Indianapolis, Ind) or in B6 mice from Jackson Laboratory. In an intercross between A/J JAX and B6 mice, the trait was not present in the first generation. The trait was observed in 2 chromosome-substitution strains, B6.A4 and B6.A7. In the intercross second generation of these chromosome-substitution strains (n = 113), significant linkage was observed to loci on chromosome 4. CONCLUSIONS: This is a sleep-related epilepsy phenotype that exhibits an oligogenic pattern of allelic inheritance.

    Title The Cost-time Index: a New Method for Measuring the Efficiencies of Recruitment-resources in Clinical Trials.
    Date February 2007
    Journal Contemporary Clinical Trials
    Excerpt

    Paid media are important resources used to recruit subjects in clinical trials. An index for evaluating which advertising resource has minimal cost and time requirement for patient accrual, for a given study design, has not been previously introduced. In this communication the authors present a new index, the Cost-Time Index, which represents a measure of the average amount of money and time spent, simultaneously, on a given advertising resource to recruit one analyzable subject. This index can be calculated using retrospective data and may be a useful tool for comparing recruitment efficiencies among various resources. The authors demonstrate the utility of the Cost-Time Index and recommend its use as an additional variable in future studies regarding recruitment strategies in clinical trials.

    Title Risk Factors for Failure to Extend Labor Epidural Analgesia to Epidural Anesthesia for Cesarean Section.
    Date February 2007
    Journal Acta Anaesthesiologica Scandinavica
    Excerpt

    OBJECTIVE: To identify parturients at risk of inability to extend labor epidural analgesia in whom alternative methods of anesthesia should be considered for Cesarean section (CS). METHODS: For 6 months, we prospectively studied women undergoing a CS with a functioning epidural catheter in place from the delivery ward. All parturients received the same epidural protocol: bolus of bupivacaine 0.1% and fentanyl, then bupivacaine 0.1% and fentanyl (2 microg/ml) 10-15 ml/h and an additional 5 ml of bupivacaine 0.125% top-ups according to patient request. Sixteen millilitres of lidocaine 2%, 1 ml of bicarbonate, and 100 microg of fentanyl were given for CS. Failed epidural analgesia was defined as the need to convert to general anesthesia. RESULTS: Of the 101 parturients studied, 20 (19.8%) required conversion to general anesthesia. In univariate analysis, the likelihood of failed epidural anesthesia was inversely correlated with parturient's age (P = 0.014) and directly correlated with pre-pregnancy weight (P = 0.019), weight at the end of pregnancy (P = 0.003), body mass index (BMI) at the end of pregnancy (P = 0.0004), gestational week (P = 0.008), number of top-ups (P = 0.0004) and visual analog scale (VAS) 2 h before CS (P = 0.03). In multivariate analysis, the number of top-ups in the delivery ward was the best predictor of epidural anesthesia failure (odds ratio 4.39, P = 0.005). CONCLUSION: Younger, more obese parturients at a higher gestational week, requiring more top-ups during labor, having a higher VAS in the 2 h before CS are at risk of inability to extend labor epidural analgesia to epidural anesthesia for CS.

    Title Practice Parameters for Behavioral Treatment of Bedtime Problems and Night Wakings in Infants and Young Children.
    Date January 2007
    Journal Sleep
    Excerpt

    Bedtime problems and frequent night wakings are highly prevalent in infants, toddlers, and preschoolers. Evidence suggests that sleep disruption and/or insufficient sleep have potential deleterious effects on children's cognitive development, regulation of affect, attention, health outcomes, and overall quality of life, as well as secondary effects on parental and family functioning. Furthermore, longitudinal studies have demonstrated that sleep problems first presenting in infancy may become chronic, persisting into the preschool and school-aged years. A solid body of literature now exists supporting the use of empirically-based behavioral management strategies to treat bedtime problems and night wakings in infants, toddlers, and preschoolers. The following practice parameters present recommendations for the use of behavioral (i.e., non-pharmacological) treatments of bedtime problems and night wakings in young children (aged 0 - 4. years 11 months). A companion review paper on which the recommendations are based was prepared by a taskforce appointed by the Standards of Practice Committee (SPC) of the American Academy of Sleep Medicine (AASM), and summarizes the peer-reviewed scientific literature on this topic. The authors of the review paper evaluated the evidence presented by the reviewed studies according to modified Sackett criteria. Using this information and a grading system described by Eddy (i.e., standard, guideline or option), the Standards of Practice Committee and Board of Directors of the American Academy of Sleep Medicine determined levels of treatment recommendation presented in the practice parameters below. These practice parameters provide 3 types of recommendations. First, recommendations are provided indicating that behavioral interventions are effective in the treatment of bedtime problems and night wakings in young children, producing reliable and significant clinical improvement in sleep parameters. Second, recommendations are made regarding specific behavioral therapies, including: (1) unmodified extinction, extinction with parental presence, and preventive parent education are all rated as individually effective therapies in the treatment of bedtime problems and night wakings (Standards), and (2) graduated extinction, bedtime fading/positive routines and scheduled awakenings are rated as individually effective therapies in the treatment of bedtime problems and night wakings but with less certainty (Guidelines). There was insufficient evidence to recommend standardized bedtime routines and positive reinforcement as single therapies. In addition, although behavioral therapies for bedtime problems and night wakings are often combined, there was insufficient evidence available to recommend one individual therapy over another or to recommend an individual therapy over a combination of therapies. Finally, recommendations are provided regarding the beneficial effects of behavioral treatments on secondary outcomes, including daytime functioning (child) and parental well-being.

    Title Practice Parameters for the Medical Therapy of Obstructive Sleep Apnea.
    Date January 2007
    Journal Sleep
    Excerpt

    Therapies for obstructive sleep apnea other than positive airway pressure, oral appliances, and surgical modifications of the upper airway are reviewed in this practice parameter. Several of these therapies such as weight loss and positional therapy hold some promise. Others, such as serotonergic agents, may gain credibility in the future but lack well-designed clinical trials. No practice parameters could be developed for a number of possible therapeutic modalities that had little or no evidence-based data on which to form a conclusion. The role of an organized, targeted weight-loss program either as a single therapy or as a supplement to PAP needs to be clarified. Although bariatric surgery is increasingly performed for refractory medically complicated obesity, its long-term effectiveness in treatment of obstructive sleep apnea in morbidly obese patients is not yet demonstrated. Positional therapy, or methods for preventing sleep in the supine position, has probably been underutilized due to lack of easily measured predictive factors and randomized controlled trials.

    Title Risk Factors for Failure to Extend Labor Epidural Analgesia to Epidural Anesthesia for Cesarean Section.
    Date December 2006
    Journal Acta Anaesthesiologica Scandinavica
    Excerpt

    AIM: To identify parturients at risk of inability to extend labor epidural analgesia in whom alternative methods of anesthesia should be considered for Cesarean section (CS). METHODS: For 6 months, we prospectively studied women undergoing CS with a functioning epidural catheter in place from the delivery ward. All parturients received the same epidural protocol: bolus of bupivacaine 0.1% and fentanyl, followed by bupivacaine 0.1% and fentanyl (2 microg/ml) 10-15 ml/h and an additional 5 ml of bupivacaine 0.125% as top-up according to patient request. Sixteen milliliters of lidocaine 2%, 1 ml of bicarbonate and 100 microg of fentanyl were given for CS. Failed epidural analgesia was defined as the need to convert to general anesthesia. RESULTS: Of the 101 parturients studied, 20 (19.8%) required conversion to general anesthesia. In univariate analysis, the likelihood of failed epidural anesthesia was inversely correlated with parturient age (P = 0.014) and directly correlated with pre-pregnancy weight (P = 0.019), weight at the end of pregnancy (P = 0.003), body mass index at the end of pregnancy (P = 0.0004), gestational week (P = 0.008), number of top-ups (P = 0.0004) and visual analog scale (VAS) score 2 h before CS (P = 0.03). In multivariate analysis, the number of top-ups in the delivery ward was the best predictor of epidural anesthesia failure (odds ratio, 4.39; P = 0.005). CONCLUSION: Younger, more obese parturients at a higher gestational week, requiring more top-ups during labor and having a higher VAS score in the 2 h before CS are at risk for inability to extend labor epidural analgesia to epidural anesthesia for CS.

    Title Sonography of Intramuscular Myxomas: the Bright Rim and Bright Cap Signs.
    Date November 2006
    Journal Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine
    Excerpt

    OBJECTIVE: The objective of this study was to retrospectively review sonographic images of pathologically proven soft tissue myxomas to determine whether a sonographic correlate to the bright rim and bright cap signs described in the magnetic resonance imaging literature is present. METHODS: The study group consisted of 6 patients with pathologically proven soft tissue myxomas (1 man and 5 women; age range, 41-72 years; mean, 56.5 years). The available sonographic images for each subject were retrospectively reviewed by 2 authors (L.F. and K.F.), with agreement reached by consensus. Among other findings, images were also reviewed for a peripheral rim of increased echogenicity (termed the "bright rim sign") and for the presence of a triangular hyperechoic area adjacent to at least one of the poles of the mass (termed the "bright cap sign"). RESULTS: The bright rim and bright cap signs were seen in 5 (83%) of the 6 myxomas. The single case without the bright cap sign was not the same case as the one lacking the bright rim sign. CONCLUSIONS: The sonographic bright rim and bright cap signs were associated with 5 (83%) of the 6 intramuscular myxomas. These findings correlate with their magnetic resonance imaging equivalents, which are well documented in the literature, due to muscle atrophy and adjacent fatty infiltration. Recognition of these features may assist in a more accurate sonographic diagnosis before biopsy.

    Title Practice Parameters for the Use of Continuous and Bilevel Positive Airway Pressure Devices to Treat Adult Patients with Sleep-related Breathing Disorders.
    Date July 2006
    Journal Sleep
    Excerpt

    Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBD) including obstructive sleep apnea (OSA). Currently, PAP devices come in three forms: (1) continuous positive airway pressure (CPAP), (2) bilevel positive airway pressure (BPAP), and (3) automatic self-adjusting positive airway pressure (APAP). After a patient is diagnosed with OSA, the current standard of practice involves performing full, attended polysomnography during which positive pressure is adjusted to determine optimal pressure for maintaining airway patency. This titration is used to find a fixed single pressure for subsequent nightly usage. A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guideline for using CPAP and BPAP appropriately (an earlier review and practice parameters for APAP was published in 2002). Major conclusions and current recommendations are as follows: 1) A diagnosis of OSA must be established by an acceptable method. 2) CPAP is effective for treating OSA. 3) Full-night, attended studies performed in the laboratory are the preferred approach for titration to determine optimal pressure; however, split-night, diagnostic-titration studies are usually adequate. 4) CPAP usage should be monitored objectively to help assure utilization. 5) Initial CPAP follow-up is recommended during the first few weeks to establish utilization pattern and provide remediation if needed. 6) Longer-term follow-up is recommended yearly or as needed to address mask, machine, or usage problems. 7) Heated humidification and a systematic educational program are recommended to improve CPAP utilization. 8) Some functional outcomes such as subjective sleepiness improve with positive pressure treatment in patients with OSA. 9) CPAP and BPAP therapy are safe; side effects and adverse events are mainly minor and reversible. 10) BPAP may be useful in treating some forms of restrictive lung disease or hypoventilation syndromes associated with hypercapnia.

    Title Practice Parameters for the Treatment of Snoring and Obstructive Sleep Apnea with Oral Appliances: an Update for 2005.
    Date May 2006
    Journal Sleep
    Excerpt

    These practice parameters are an update of the previously published recommendations regarding use of oral appliances in the treatment of snoring and Obstructive Sleep Apnea (OSA). Oral appliances (OAs) are indicated for use in patients with mild to moderate OSA who prefer them to continuous positive airway pressure (CPAP) therapy, or who do not respond to, are not appropriate candidates for, or who fail treatment attempts with CPAP. Until there is higher quality evidence to suggest efficacy, CPAP is indicated whenever possible for patients with severe OSA before considering OAs. Oral appliances should be fitted by qualified dental personnel who are trained and experienced in the overall care of oral health, the temporomandibular joint, dental occlusion and associated oral structures. Follow-up polysomnography or an attended cardiorespiratory (Type 3) sleep study is needed to verify efficacy, and may be needed when symptoms of OSA worsen or recur. Patients with OSA who are treated with oral appliances should return for follow-up office visits with the dental specialist at regular intervals to monitor patient adherence, evaluate device deterioration or maladjustment, and to evaluate the health of the oral structures and integrity of the occlusion. Regular follow up is also needed to assess the patient for signs and symptoms of worsening OSA. Research to define patient characteristics more clearly for OA acceptance, success, and adherence is needed.

    Title Wdr5, a Novel Wd Repeat Protein, Regulates Osteoblast and Chondrocyte Differentiation in Vivo.
    Date May 2006
    Journal Journal of Musculoskeletal & Neuronal Interactions
    Title Hiv Infection and Aids in Adolescents: an Update of the Position of the Society for Adolescent Medicine.
    Date March 2006
    Journal The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine
    Title Practice Parameters for the Indications for Polysomnography and Related Procedures: an Update for 2005.
    Date December 2005
    Journal Sleep
    Excerpt

    These practice parameters are an update of the previously-published recommendations regarding the indications for polysomnography and related procedures in the diagnosis of sleep disorders. Diagnostic categories include the following: sleep related breathing disorders, other respiratory disorders, narcolepsy, parasomnias, sleep related seizure disorders, restless legs syndrome, periodic limb movement sleep disorder, depression with insomnia, and circadian rhythm sleep disorders. Polysomnography is routinely indicated for the diagnosis of sleep related breathing disorders; for continuous positive airway pressure (CPAP) titration in patients with sleep related breathing disorders; for the assessment of treatment results in some cases; with a multiple sleep latency test in the evaluation of suspected narcolepsy; in evaluating sleep related behaviors that are violent or otherwise potentially injurious to the patient or others; and in certain atypical or unusual parasomnias. Polysomnography may be indicated in patients with neuromuscular disorders and sleep related symptoms; to assist in the diagnosis of paroxysmal arousals or other sleep disruptions thought to be seizure related; in a presumed parasomnia or sleep related seizure disorder that does not respond to conventional therapy; or when there is a strong clinical suspicion of periodic limb movement sleep disorder. Polysomnography is not routinely indicated to diagnose chronic lung disease; in cases of typical, uncomplicated, and noninjurious parasomnias when the diagnosis is clearly delineated; for patients with seizures who have no specific complaints consistent with a sleep disorder; to diagnose or treat restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; or to establish a diagnosis of depression.

    Title Interaction of Sleep Disturbances and Anxiety in Later Life: Perspectives and Recommendations for Future Research.
    Date August 2005
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    Both sleep disturbances and anxiety are quite common in older adults. Although increasing research efforts have investigated sleep disturbances and anxiety in older adults, little has been written concerning the relation between sleep disturbances and anxiety in this population. This article reviews the epidemiological and clinical literature concerning the overall prevalence of sleep disturbances and relations between sleep and anxiety in later life. The article begins with a discussion of the prevalence of sleep and anxiety problems in older individuals, continues with a clinical review of the complex interrelationship between sleep and anxiety in older adults, and briefly considers possible neurobiological underpinnings of this interrelationship. This is followed by a brief discussion of the impact of medical illness on both anxiety and sleep disturbances. The article ends with a summary of findings from this review and provides recommendations for future research.

    Title Texaco and Its Consultants.
    Date July 2005
    Journal International Journal of Occupational and Environmental Health
    Title Ventilatory Behavior During Sleep Among A/j and C57bl/6j Mouse Strains.
    Date February 2005
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    The pattern of breathing during sleep could be a heritable trait. Our intent was to test this genetic hypothesis in inbred mouse strains known to vary in breathing patterns during wakefulness (Han F, Subramanian S, Dick TE, Dreshaj IA, and Strohl KP. J Appl Physiol 91: 1962-1970, 2001; Han F, Subramanian S, Price ER, Nadeau J, and Strohl KP, J Appl Physiol 92: 1133-1140, 2002) to determine whether such differences persisted into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Measures assessed in C57BL/6J (B6; Jackson Laboratory) and two A/J strains (A/J Jackson and A/J Harlan) included ventilatory behavior [respiratory frequency, tidal volume, minute ventilation, mean inspiratory flow, and duty cycle (inspiratory time/total breath time)], and metabolism, as performed by the plethsmography method with animals instrumented to record EEG, electromyogram, and heart rate. In all strains, there were reductions in minute ventilation and CO2 production in NREM compared with wakefulness (P < 0.001) and a further reduction in REM compared with NREM (P < 0.001), but no state-by-stain interactions. Frequency showed strain (P < 0.0001) and state-by-strain interactions (P < 0.0001). The A/J Jackson did not change frequency in REM vs. NREM [141 +/- 15 (SD) vs. 139 +/- 14 breaths/min; P = 0.92], whereas, in the A/J Harlan, it was lower in REM vs. NREM (168 +/- 14 vs. 179 +/- 12 breaths/min; P = 0.0005), and, in the B6, it was higher in REM vs. NREM (209 +/- 12 vs. 188 +/- 13 breaths/min; P < 0.0001). Heart rate exhibited strain (P = 0.003), state (P < 0.0001), and state-by-strain interaction (P = 0.017) and was lower in NREM sleep in the A/J Harlan (P = 0.035) and B6 (P < 0.0001). We conclude that genetic background affects features of breathing during NREM and REM sleep, despite broad changes in state, metabolism, and heart rate.

    Title Genetic and Phenotypic Analysis of Seizure Susceptibility in Pl/j Mice.
    Date February 2005
    Journal Mammalian Genome : Official Journal of the International Mammalian Genome Society
    Excerpt

    Epilepsy is one of the most common but genetically complex neurological disorders in humans. Identifying animal models that recapitulate human epilepsies is important for pharmacological studies of anticonvulsants, dissection of molecular and biochemical pathogenesis of epilepsy, and discovery of epilepsy susceptibility genes. We discovered that the PL/J inbred mouse strain is susceptible to handling- and rhythmic tossing-induced seizure. The tonic-clonic and generalized seizures observed after induction were accompanied by abnormal EEGs, similar to seizures observed in EL and SWXL-4 mice. PL/J mice also had an extremely low threshold to electroconvulsive seizures compared to other strains and showed variable sensitivity to pentylenetetrazole-induced seizures. Gross neurostructural abnormalities were not found in PL/J mice. Crosses with the seizure-resistant C57BL/6 J strain revealed semidominant inheritance of the rhythmic tossing seizure trait with low penetrance. F2 progeny indicated that the genetic inheritance of seizure susceptibility in PL/J is non-Mendelian. We crossed DBA/2 J mice, which are resistant to rhythmic tossing seizure but susceptible to audiogenic seizures, to PL/J. We found that seizure penetrance in (DBA/2 J x PL/J)F1 mice was similar to the penetrance in (C57BL/6 J x PL/J)F1 mice but the severity and frequency of seizure were higher in (DBA/2 J x PL/J)F1 mice. The PL/J strain serves as an interesting new model for studying the genetics, neurobiology, and pharmacology of epilepsy.

    Title Cellular Changes in the Postmortem Hippocampus in Major Depression.
    Date January 2005
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Imaging studies report that hippocampal volume is decreased in major depressive disorder (MDD). A cellular basis for reduced hippocampal volume in MDD has not been identified. METHODS: Sections of right hippocampus were collected in 19 subjects with MDD and 21 normal control subjects. The density of pyramidal neurons, dentate granule cell neurons, glia, and the size of the neuronal somal area were measured in systematic, randomly placed three-dimensional optical disector counting boxes. RESULTS: In MDD, cryostat-cut hippocampal sections shrink in depth a significant 18% greater amount than in control subjects. The density of granule cells and glia in the dentate gyrus and pyramidal neurons and glia in all cornv ammonis (CA)/hippocampal subfields is significantly increased by 30%-35% in MDD. The average soma size of pyramidal neurons is significantly decreased in MDD. CONCLUSION: In MDD, the packing density of glia, pyramidal neurons, and granule cell neurons is significantly increased in all hippocampal subfields and the dentate gyrus, and pyramidal neuron soma size is significantly decreased as well. It is suggested that a significant reduction in neuropil in MDD may account for decreased hippocampal volume detected by neuroimaging. In addition, differential shrinkage of frozen sections of the hippocampus suggests differential water content in hippocampus in MDD.

    Title Task Force 1: The Accf and Aha Codes of Conduct in Human Subjects Research.
    Date November 2004
    Journal Journal of the American College of Cardiology
    Title Sonography of Injury of the Ulnar Collateral Ligament of the Elbow-initial Experience.
    Date November 2004
    Journal Skeletal Radiology
    Excerpt

    OBJECTIVE: The purpose of this study is to describe the sonographic appearance of injuries of the ulnar collateral ligament (UCL) of the elbow. DESIGN AND PATIENTS: Eight non-professional male baseball pitchers, ages 13-35 years, with medial elbow pain and clinical suspicion of ulnar collateral ligament injury, were referred for imaging. All eight underwent sonography of the affected and contralateral asymptomatic elbow, and six also underwent MR imaging. Neither valgus stress nor power Doppler was used during the sonographic examinations. Time from onset of symptoms to imaging was 1.5 weeks to 6 months. Three patients had surgical confirmation of their injuries, with time from imaging to surgery of 2 days to 9 months. RESULTS: In four patients, the UCL was ruptured, manifest sonographically in three cases as discontinuity of the normally hyperechoic ligament with anechoic fluid in the gap and in one case as non-visualization of the ligament with heterogeneous echogenicity in the expected location of the ligament. Two adolescent patients had avulsions of the UCL from the medial epicondyle, with sonographic demonstration of the avulsed echogenic bony fragment in both cases. One patient had a mild sprain, manifest as mild thickening and decreased echogenicity of the ligament sonographically compared with the contralateral normal elbow, with mild surrounding hypoechoic edema. The eighth patient had a small partial tear of the deep surface of the distal aspect of the ligament, visualized as a hypoechoic focus between the deep surface of the ligament and its ulnar attachment. CONCLUSION: Tears of the ulnar collateral ligament are manifested sonographically as non-visualization of the ligament or alteration of the normal morphology.

    Title The Measurement of Sleep by Actigraphy: Direct Comparison of 2 Commercially Available Actigraphs in a Nonclinical Population.
    Date November 2004
    Journal Sleep
    Excerpt

    To compare 2 commercially available actigraphs.

    Title Insight and Its Relationship to Violent Behavior in Patients with Schizophrenia.
    Date October 2004
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: Lack of insight affects the management of schizophrenia. The interrelationship between lack of insight and illness attributes in patients with schizophrenia who commit violent acts is important and underresearched. METHOD: One hundred fifteen violent patients with schizophrenia in a jail or court psychiatric clinic were evaluated on measures of symptoms, illness severity, insight into illness, and the legal consequences of their illness ("forensic insight"). A sample of nonviolent patients served as a comparison group. RESULTS: Compared with the nonviolent cohort, violent patients were more symptomatic, had poorer functioning, and had a more prominent lack of insight. Deficits of insight into illness coexisted with a lack of forensic insight, which was also associated with psychosis. CONCLUSIONS: Patients with schizophrenia who commit violent acts have insight deficits, including lack of awareness of the legal implications of their behavior. Targeted interventions to improve insight and treatment compliance in this population are warranted.

    Title Virologic and Immunologic Outcomes After 24 Weeks in Hiv Type 1-infected Adolescents Receiving Highly Active Antiretroviral Therapy.
    Date August 2004
    Journal The Journal of Infectious Diseases
    Excerpt

    BACKGROUND: Adolescents represent the fastest growing demographic group of new human immunodeficiency virus (HIV) infections in the United States. At present, there is little information available about their response to therapy. METHODS: We studied 120 adolescents infected via high-risk behaviors who began receiving highly active antiretroviral therapy (HAART), to determine their virologic and immunologic response to therapy. RESULTS: Subjects were enrolled at 28 sites of the Pediatric Acquired Immunodeficiency Syndrome Clinical Trials Group. After 16-24 weeks of HAART, 59% of subjects had reproducible undetectable virus loads, according to repeat measurements (virologic success). As enumerated by flow-cytometric analysis, increases in levels of CD4 helper cells (both naive and memory) and decreases in levels of CD8 suppressor cells were observed. Partial restoration of some immunologic parameters for patients who did not achieve virologic success was also observed, but to a more limited extent than for adolescents with virologic success. Adherence to HAART was the only predictor of achieving undetectable virus loads. CONCLUSIONS: Adolescents have the capacity to improve their immunologic status with HAART. Lower than expected success in virologic control is related to lack of adherence, and efforts to improve treatment outcome must stress measures to assure adherence to medication.

    Title Sleep/wake Disruption in Alzheimer's Disease: Apoe Status and Longitudinal Course.
    Date August 2004
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    Disturbed sleep is a major clinical problem in Alzheimer's disease (AD). Apolipoprotein epsilon4 (APOE epsilon4) carrier status may increase risk of AD, yet there are no data on relations between APOE status and progression of sleep disturbance in AD. The objective of this study was to determine if sleep parameters in AD patients change over time as a function of APOE carrier status. Forty-four community-dwelling AD patients with diagnosis of probable AD were followed from early stages of disease. Their sleep/wake parameters were compared according to APOE status. For APOE epsilon4 carriers, only wake after sleep onset (WASO) increased in association with lower cognitive function as indicated by the Mini-Mental State Examination (MMSE); for non-epsilon4 subjects, increases in WASO and declines in total sleep time, sleep efficiency, and the amplitude of the rest/activity circadian rhythm over time were associated with lower performance on the MMSE. In these data, APOE status was associated with the progression of sleep/wake disturbances in AD. Overall, there was greater deterioration on sleep parameters in patients negative for the epsilon4 allele.

    Title Mechanical Cardiac Support 2000: Current Applications and Future Trial Design: June 15-16, 2000 Bethesda, Maryland.
    Date July 2004
    Journal Circulation
    Title Systematic Generation of High-resolution Deletion Coverage of the Drosophila Melanogaster Genome.
    Date May 2004
    Journal Nature Genetics
    Excerpt

    In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task.

    Title Age and Disease Severity Predict Choice of Atypical Neuroleptic: a Signal Detection Approach to Physicians' Prescribing Decisions.
    Date March 2004
    Journal Journal of Psychiatric Research
    Excerpt

    OBJECTIVE: We used a novel application of a signal detection technique, receiver operator characteristics (ROC), to describe factors entering a physician's decision to switch a patient from a typical high potency neuroleptic to a particular atypical, olanzapine (OLA) or risperidone (RIS). METHODS: ROC analyses were performed on pharmacy records of 476 VA patients who had been treated on a high potency neuroleptic then changed to either OLA or RIS. RESULTS: Overall 68% patients switched to OLA and 32% to RIS. The best predictor of neuroleptic choice was age at switch, with 78% of patients aged less than 55 years receiving OLA and 51% of those aged greater than or equal to 55 years receiving OLA (chi(2)=38.2, P<0.001). Further analysis of the former group indicated that adding the predictor of one or more inpatient days to age increased the likelihood of an OLA switch from 78% to 85% (chi(2)=7.3, P<0.01) while further analysis of the latter group indicated that adding the predictor of less than 10 inpatients days to age decreased the likelihood of an OLA switch from 51% to 45% (chi(2)=7.0, P<0.01). CONCLUSIONS: ROC analyses have the advantage over other analyses, such as regression techniques, insofar as their "cut-points" are readily interpretable, their sequential use forms an intuitive "decision tree" and allows the potential identification of clinically relevant "subgroups". The software used in this analysis is in the public domain (http://mirecc.stanford.edu).

    Title Differential Associations Between Entorhinal and Hippocampal Volumes and Memory Performance in Older Adults.
    Date February 2004
    Journal Behavioral Neuroscience
    Excerpt

    Magnetic resonance imaging-derived entorhinal and hippocampal volumes were measured in 14 nondemented, community-dwelling older adults. Participants were selected so that memory scores from 2 years prior to scanning varied widely but were not deficient relative to age-appropriate norms. A median split of these memory scores defined high-memory and low-memory groups. Verbal memory scores at the time of imaging were lower, and entorhinal and hippocampal volumes were smaller, in the low-memory group than in the high-memory group. Left entorhinal cortex volume showed the strongest correlation (r= .79) with immediate recall of word lists. Left hippocampal volume showed the strongest correlation (r= .57) with delayed paragraph recall. These results suggest that entorhinal and hippocampal volumes are related to individual differences in dissociable kinds of memory performance among healthy older adults.

    Title Development of Diagnostic Criteria for Defining Sleep Disturbance in Alzheimer's Disease.
    Date November 2003
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    This article proposes new standards for identifying, defining, and naming sleep/wake cycle disturbances associated with Alzheimer's disease (AD) to aid in more effective research, including the development and testing of potential treatments. Many AD patients develop sleep/wake cycle disturbances associated with distress, depression, and sleep disturbances in the caregiver, as well as early nursing home placement for the patient. The Food and Drug Administration Psychopharmacological Drugs Advisory Committee has emphasized the need for a comprehensive diagnostic system. A key point made by the committee was that behavioral problems associated with dementia (including sleep and chronobiological disturbances) are scientifically and clinically valid targets of pharmacologic treatment. However, current diagnostic criteria preclude development of FDA-acceptable studies of pharmacological interventions because they do not include the required specific indications for treatment. This article attempts to develop better-defined provisional criteria with the goal of promoting epidemiological, physiological, and, especially, pharmacological research on sleep/wake disturbances.

    Title Use of an External Mnemonic to Augment the Efficacy of an Internal Mnemonic in Older Adults.
    Date October 2003
    Journal International Psychogeriatrics / Ipa
    Excerpt

    OBJECTIVES: To evaluate the impact of external memory devices on the efficacy of a package of internal mnemonic techniques. Participants wrote two types of lists during the study phase: (a) a list of study words and/or (b) a loci list. At recall, participants were not allowed to refer to either of the lists they had written during the study. DESIGN: 2 x 2 factorial with writing study words ("write" or "not write") and writing down a previously established loci list ("write" or "not write") manipulated as between-participants variables. PARTICIPANTS: 68 community-dwelling adults 55 years of age and older who wished to improve their memory. MEASUREMENTS: Free word recall. RESULTS: There were statistically significant effects of writing the loci list, but not of writing the list of study words. Scores were higher when participants wrote the loci lists compared to when they did not. CONCLUSIONS: Use of external mnemonics may enhance the efficacy of internal mnemonics, even when the external mnemonic is not used at the time of recall.

    Title Do Arrhythmia Patients Improve Survival by Participating in Randomized Clinical Trials? Observations from the Cardiac Arrhythmia Suppression Trial (cast)and the Antiarrhythmics Versus Implantable Defibrillators Trial (avid).
    Date October 2003
    Journal Controlled Clinical Trials
    Excerpt

    It is debatable whether patients benefit directly from participation in a randomized clinical trial. We attempt to address this question for participants in the Cardiac Arrhythmia Suppression Trial (CAST) and the Antiarrhythmics Versus Implantable Defibrillators (AVID) studies. Survival rates were compared between eligible patients who enrolled in the trials and eligible patients who did not enroll, adjusting for baseline covariates. In CAST, despite that the active therapy was found to confer an almost threefold increased risk of death, survival was similar between the 3163 enrolled and the 1363 nonenrolled eligible patients. However, when patients were under study management, their risk of death was approximately 20% lower than when they left study management. In AVID, overall survival was similar between the 1016 enrolled and the 1246 nonenrolled eligible patients. However, mortality was substantially higher among patients not enrolled because the referring physician mandated the type of therapy. Overall these observational analyses suggest a net improvement in survival for the participants in these two trials.

    Title Screening Latino Adolescents for Latent Tuberculosis Infection (ltbi).
    Date September 2003
    Journal Public Health Reports (washington, D.c. : 1974)
    Excerpt

    To investigate the rates of latent TB infection (LTBI) in a sample of young people in San Diego County and examine potential predictors of a positive tuberculin skin test (TST).

    Title Psychoactive Drugs and Pilot Performance: a Comparison of Nicotine, Donepezil, and Alcohol Effects.
    Date September 2003
    Journal Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
    Excerpt

    The cholinergic system plays a major role in cognitive abilities that are essential to piloting an aircraft: attention, learning, and memory. In previous studies, drugs that enhance the cholinergic system through different pharmacologic mechanisms have shown beneficial effects on cognition; but dissimilar cognitive measures were used and samples were not comparable. A comparison within the same cognitive tasks, within comparable samples appears desirable. Toward this aim, we compared effect sizes (ES) of performance-enhancing doses of nicotine (a nicotinic receptor agonist) and donepezil (an acetylcholinesterase inhibitor) as found in our prior work on pilot performance. We also compared cholinergic ES to those of performance-impairing doses of alcohol. In three randomized, placebo-controlled trials, we assessed the flight performance of aircraft pilots in a Frasca 141 simulator, testing I: the acute effects of nicotine gum 2 mg; II: the effects of administration of 5 mg donepezil/day for 30 days; and III: the acute and 8 h-carryover effects of alcohol after a target peak BAC of 0.10%. We calculated the ES of nicotine, donepezil, and alcohol on a flight summary score and on four flight component scores. Compared to placebo, nicotine and donepezil significantly improved, while alcohol significantly impaired overall flight performance: ES (nicotine)=0.80; ES (donepezil)=1.02; ES (alcohol acute)=-3.66; ES (alcohol 8 h)=-0.82. Both cholinergic drugs showed the largest effects on flight tasks requiring sustained visual attention. Although the two tested cholinergic drugs have different pharmacologic mechanisms, their effects on flight performance were similar in kind and size. The beneficial effects of the cholinergic drugs on overall flight performance were large and the absolute (ie nondirectional) sizes were about one-fourth of the absolute ES of acute alcohol intoxication and roughly the same as the absolute 8 h-carryover ES of alcohol.

    Title Predictors of Adherence to Treatment for Latent Tuberculosis Infection in High-risk Latino Adolescents: a Behavioral Epidemiological Analysis.
    Date June 2003
    Journal Social Science & Medicine (1982)
    Excerpt

    The objective was to test whether theoretical variables predict adherence to treatment for latent tuberculosis infection in high-risk Latino adolescents. 286 Latino adolescents, age 13-18 years, were recruited from 10 middle/high schools in San Diego County, San Diego, USA. Participants completed a baseline interview and up to 9 monthly interviews. The cumulative number of pills consumed in 9 months was regressed on 16 independent variables, entered hierarchically in seven blocks. The final model accounted for 25% of the variance in adherence to isoniazid (INH), F (16, 230)=4.69, p<0.001. Adherence counseling (+), age (-), grades (+), being bicultural (+), and risk behaviors (-) were significantly related to adherence. Learning theories presume that adherence to medical regimens requires social support and freedom from physical and social barriers. Results support these theories. Future studies should explore additional precepts in order to identify additional predictors and to maximize adherence to INH among Latino adolescents and other high-risk populations. Doing so should decrease the risk of active TB among high-risk racial/ethnic and foreign-born populations.

    Title Sonographic Findings in Patients with Anterior Knee Pain.
    Date May 2003
    Journal Journal of Clinical Ultrasound : Jcu
    Title On Disentangling States Versus Traits: Demonstration of a New Technique Using the Alzheimer's Disease Assessment Scale.
    Date March 2003
    Journal Alzheimer Disease and Associated Disorders
    Excerpt

    Part of the challenge in research on degenerative neurologic disease relates to distinguishing those measurements that essentially describe patient characteristics stable across the course of illness (traits) from those that vary systematically within subjects (states), particularly those specifically related to stage or duration of illness. A components-of-variance approach was used to examine the state versus trait aspects of the Alzheimer's Disease Assessment Scale (ADAS) Cognitive and Noncognitive subscales, a clinical instrument frequently used in research on Alzheimer disease. Subjects were 190 patients with probable AD followed longitudinally. Stage of illness was indexed by mental status scores. Analysis of variance was used to partition total variance into that associated with subjects (trait), stages (state: stage), subjects x stages (state: other), and error. ADAS Cognitive scores were strongly related to stage of illness (83% of true variance). ADAS Noncognitive scores were modestly related to stage (approximately 21% of true variance) and moderately related to state: other (47%). We discuss how state-trait analyses can be helpful in focusing attention on those areas of assessment most likely to accomplish specific objectives.

    Title Sleep/wake Cycle Disturbance in Alzheimer's Disease: How Much is Due to an Inherent Trait?
    Date December 2002
    Journal International Psychogeriatrics / Ipa
    Excerpt

    Major advances in understanding the physiology and genetics of circadian rhythm in the past decade challenge the researcher of sleep/wake disorders in Alzheimer's disease (AD) to distinguish patient characteristics stable across the course of illness ("traits") from characteristics that vary with stage of illness ("states"). A components-of-variance approach with a repeated measures model was used to examine the between-subjects variance over time ("trait") vs. within-subjects ("state") variance in 42 patients with probable AD followed, on average, over 2 years on actigraphic sleep/wake measures. Mental status scores indexed stage of illness. Actigraphic measures of sleep efficiency and circadian rhythmicity appeared predominantly "trait," with between-individual differences accounting for over 55% of variance compared to the less than 5% of variance related to stage of cognitive impairment. We discuss how "state-trait" analyses can be helpful in identifying areas of assessment most likely to be fruitful objectives of physiologic and genetic research on sleep/wake disturbance in AD.

    Title Modeling the Prevalence and Incidence of Alzheimer's Disease and Mild Cognitive Impairment.
    Date November 2002
    Journal Journal of Psychiatric Research
    Excerpt

    A number of systems have been proposed for classifying older adults who suffer from cognitive impairment or decline but do not yet meet criteria for Alzheimer's disease (AD). The classification, Mild Cognitive Impairment (MCI), has attracted much attention. It uses relatively specific diagnostic criteria and individuals who meet these criteria appear to be at substantial risk for the development of AD. However, little data is available to define the prevalence of MCI in any age group. We propose a simple mathematical model for the progression of patients from Non-Affected (NA) to MCI to AD. This first-order Markov model defines the likely prevalence of MCI at specific ages. Primary assumptions of the model include an AD prevalence of 1% at age 60 increasing to 25% at age 85 and a conversion rate from MCI to AD of 10% constant across all ages considered. We used the best available information for our model and found (1) that the MCI prevalence increased from 1% at age 60 to 42% at age 85 and (2) that the conversion rate from NA to MCI increased from 1% per year at age 60 to 11% at age 85. In conclusion, this model allows estimation of prevalence of MCI and conversion from NA to MCI based upon known prevalences of AD, conversion rates of MCI to AD, and death rates. Due to its substantial prevalence, MCI may be an important target for screening and possible intervention.

    Title Neurokinin-1 Receptors Are Decreased in Major Depressive Disorder.
    Date September 2002
    Journal Neuroreport
    Excerpt

    Treatment with an antagonist at the neurokinin-1 (NK-1) receptor may alleviate depression, however the brain region(s) in which the NK-1 receptor antagonist exerts its therapeutic effect is unknown. [125I]BH-Substance P was used to measure NK-1 receptors postmortem in cytoarchitectonically defined areas of rostral orbitofrontal cortex (Brodmann's area 47) of subjects with major depressive disorder (n = 12, six females) and psychiatrically normal subjects (n = 11, five females). Six subjects with depression died by suicide. Subjects with depression showed decreased binding to NK-1 receptors across all cortical layers (p = 0.024). The pathophysiology of depression, and the reported therapeutic benefit of NK-1 receptor antagonists, may thus involve NK-1 receptors in prefrontal cortex.

    Title Donepezil and Flight Simulator Performance: Effects on Retention of Complex Skills.
    Date July 2002
    Journal Neurology
    Excerpt

    We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.

    Title Increased Presence of White Matter Hyperintensities in Adolescent Patients with Bipolar Disorder.
    Date April 2002
    Journal Psychiatry Research
    Excerpt

    Several reports have noted an increase in white matter hyperintensities (WMH) on MRI scans of adult patients with bipolar disorder. We investigated whether this increase was also evident in a group of adolescent patients with bipolar disorder. The sample consisted of 15 bipolar patients, 19 patients with schizophrenia and 16 healthy comparison subjects. All subjects were adolescents. WMH were blindly rated on T2-weighted and PD-weighted MRI scans using our own scale with documented inter-rater reliability. WMH were present in 10 of 15 bipolar patients (67%), seven of 19 patients with schizophrenia (37%) and five of 16 comparison subjects (31%). The bipolar adolescent group had a statistically significant increased presence of WMH compared both with healthy comparison subjects and the schizophrenic group. The association between WMH and bipolar disorder appears to extend to the adolescent years.

    Title Urine Testing to Monitor Adherence to Tb Preventive Therapy.
    Date March 2002
    Journal Journal of Clinical Epidemiology
    Excerpt

    This study examined the validity of the Arkansas urine test. One hundred ninety-four adolescents submitted an unannounced urine specimen monthly (for 6 to 8 months). Duplicate specimens were blindly tested with high agreement (kappa >90%). Sensitivity and specificity were estimated. In 68% of test runs, adolescents recalled taking INH within 24 hr of specimen collection. For recall intervals of 24, 48, and 72 hr, sensitivity was 87, 85, and 83%, respectively. Females were less likely to test positive when INH was taken within the previous 24 hr (sensitivity 84 versus 92% males). Specificity was 57, 91, and 95% at 24, 48, and 72 hr, respectively. The Arkansas urine test was practical to use, and results correlated well with self-reported adherence to INH for treatment of latent tuberculosis infection (LTBI), over several months of follow-up. The test may be useful as part of an adherence-monitoring program when used in conjunction with self-reported measures.

    Title Influence of the Menstrual Cycle on Flight Simulator Performance After Alcohol Ingestion.
    Date January 2002
    Journal Journal of Studies on Alcohol
    Excerpt

    OBJECTIVE: Previous studies investigating the influence of the menstrual cycle on cognitive functioning of women after alcohol ingestion have obtained inconsistent results. The present study tested the hypothesis that flight simulator performance during acute alcohol intoxication and 8 hours after drinking differs between the menstrual and the luteal phase of the menstrual cycle. METHOD: White female pilots (N = 24) were tested during the menstrual and the luteal phases of their menstrual cycles. On each test day they performed a baseline simulator flight, consumed 0.67 g/kg ethanol, and performed an acute-intoxication and an 8-hour-carryover simulator flight. RESULTS: Subjects reached highly significant increases in estradiol (E2) as well as progesterone (P) levels during the luteal test day. Yet, there were no significant differences in overall flight performance after alcohol ingestion between the menstrual and luteal phases during acute intoxication or at 8-hour carryover. We found no correlations between E, or P levels and overall flight performance. However, there was a statistically significant Phase x Order interaction: Pilots who started the experiment with their menstrual day were less susceptible to the effects of alcohol during the second test day than were pilots who started with their luteal day. CONCLUSIONS: The tested menstrual cycle phases and varying E2 and P levels did not significantly influence postdrink flight performance. Because the present study included a comparatively large sample size and because it involved complex "real world" tasks (piloting an aircraft), we believe that the present findings are important. We hope that our failure to detect menstrual cycle effects will encourage researchers to include women in their investigations of alcohol effects and human performance.

    Title Relationship Between Variations in Estradiol and Progesterone Levels Across the Menstrual Cycle and Human Performance.
    Date October 2001
    Journal Psychopharmacology
    Excerpt

    RATIONALE: Studies about whether or not the cognitive performance of women is influenced by changes in levels of sex steroid hormones across the menstrual cycle have produced ambiguous results. OBJECTIVES: This study tested whether flight simulator performance differs significantly between the menstrual and the luteal phase of the menstrual cycle. METHODS: In a within-subjects design, 24 female pilots were tested twice during their menstrual cycle: once during the menstrual and once during the luteal phase. On both test days they performed a 75-min simulator flight in a Frasca 141, a popular pilot training device. RESULTS: Despite highly significant differences in estradiol (E2) as well as progesterone (P) levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analyses, there were no significant differences in overall flight performance between the menstrual and luteal phases. We found no significant correlations between E2 or P levels and flight performance. CONCLUSIONS: We found no evidence that the tested menstrual cycle phases and their associated E2 and P levels significantly influence flight simulator performance. We consider these negative findings based on 24 subjects meaningful because previous studies on the influence of menstrual cycle on cognitive performance have not involved complex "real world" tasks such as piloting an aircraft and they obtained inconsistent results.

    Title Considerations in the Evaluation of Surrogate Endpoints in Clinical Trials. Summary of a National Institutes of Health Workshop.
    Date October 2001
    Journal Controlled Clinical Trials
    Excerpt

    We report on recommendations from a National Institutes of Health Workshop on methods for evaluating the use of surrogate endpoints in clinical trials, which was attended by experts in biostatistics and clinical trials from a broad array of disease areas. Recent advances in biosciences and technology have increased the ability to understand, measure, and model biological mechanisms; appropriate application of these advances in clinical research settings requires collaboration of quantitative and laboratory scientists. Biomarkers, new examples of which arise rapidly from new technologies, are used frequently in such areas as early detection of disease and identification of patients most likely to benefit from new therapies. There is also scientific interest in exploring whether, and under what conditions, biomarkers may substitute for clinical endpoints of phase III trials, although workshop participants agreed that these considerations apply primarily to situations where trials using clinical endpoints are not feasible. Evaluating candidate biomarkers in the exploratory phases of drug development and investigating surrogate endpoints in confirmatory trials require the establishment of a statistical and inferential framework. As a first step, participants reviewed methods for investigating the degree to which biomarkers can explain or predict the effect of treatments on clinical endpoints measured in clinical trials. They also suggested new approaches appropriate in settings where biomarkers reflect only indirectly the important processes on the causal path to clinical disease and where biomarker measurement errors are of concern. Participants emphasized the need for further research on development of such models, whether they are empirical in nature or attempt to describe mechanisms in mathematical terms. Of special interest were meta-analytic models for combining information from multiple studies involving interventions for the same condition. Recommendations also included considerations for design and conduct of trials and for assemblage of databases needed for such research. Finally, there was a strong recommendation for increased training of quantitative scientists in biologic research as well as in statistical methods and modeling to ensure that there will be an adequate workforce to meet future research needs.

    Title Identification of Risk Factors for Exertional Heat-related Illnesses in Long-distance Cyclists: Experience from the California Aids Ride.
    Date July 2001
    Journal Wilderness & Environmental Medicine
    Excerpt

    OBJECTIVES: To identify risk factors for exertional heat-related illnesses and to determine if patients who are afflicted with the human immunodeficiency virus or have acquired immunodeficiency syndrome have an increased risk of exertional heat-related illness. DESIGN: Descriptive, retrospective, matched case-control study. SETTING: Mobile community of 2,650 participants in the California AIDS Ride 3. PARTICIPANTS: Participants included 117 patients presenting for medical care with heat-related illnesses and 234 age-, gender-, and registration site-matched control subjects who did not develop a heat-related illness. METHODS: Retrospective, matched case-control study utilizing univariate and multivariate conditional logistic regression to determine if human immunodeficiency virus seropositivity, the number of chronic medical illnesses, or the number of current medications known to affect heat dissipation increased the risk of exertional heat-related illnesses. RESULTS: The multivariate model revealed that patients with a greater number of chronic medical illnesses were at a significantly increased risk of a heat-related illness (odds ratio = 1.6, 95% CI = 1.2-2.1). The number of current medications (odds ratio = 1.1, 95% CI = 0.8-1.5) and human immunodeficiency virus seropositivity (odds ratio = 0.7, 95% CI = 0.2-3.1) were not significant predictors of risk for exertional heat-related illness. CONCLUSIONS: Those riders suffering from a greater number of chronic medical illnesses were at a greater risk for developing an exertional heat-related illness. Human immunodeficiency virus seropositivity alone was not associated with increased risk of exertional heat-related illness.

    Title Hearing Impairment and Serial Word Recall in Older Adults.
    Date May 2001
    Journal Experimental Aging Research
    Excerpt

    The objective of this work was to study the differences in performance on a nonauditory memory task between older volunteers with and without hearing impairment. The design was cross-sectional. Three-hundred-forty-four community-dwelling adults aged 55 to 93 years, who volunteered for a mnemonic training class served as participants. Participants' hearing was tested with a Maico MA-27 portable audiometer. The dependent measure was performance on a visually presented serial word recall test. Participants were also asked to report whether they had a problem with their hearing. Hearing impairment was associated with poor performance on a serial word recall task, even after controlling for age-related differences on that task. Hearing acuity appears to be related to serial word recall in older adults. Because auditory presentations were not involved, this relation raises the question of whether hearing loss may be concomitant with other changes that affect cognitive abilities.

    Title One Year of Insulin-like Growth Factor I Treatment Does Not Affect Bone Density, Body Composition, or Psychological Measures in Postmenopausal Women.
    Date May 2001
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 +/- 2.0 yr, 71.8 +/- 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 microg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 +/- 11.9 ng/mL) at 6 months (330.0 +/- 52.8) and 12 months (297.7 +/- 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.

    Title Imaging of Chronic Recurrent Multifocal Osteomyelitis.
    Date May 2001
    Journal Radiologic Clinics of North America
    Excerpt

    The disease of CRMO is a "great clinical and radiologic mimic. There are no specific clinical or laboratory findings and no pathognomonic imaging or pathologic features have been described. Because the disease is not well known by clinician, radiologist, and pathologist alike, it is likely to be more common than the literature implies. It has been suggested that the diagnosis of CRMO requires an interdisciplinary team approach dependent on the cooperation of the pediatrician, orthopedic surgeon, pathologist, and microbiologist. We strongly advocate the addition of the radiologist to this list. We believe that it is the informed radiologist who frequently suggests the correct diagnosis.

    Title Mechanical Cardiac Support 2000: Current Applications and Future Trial Design. June 15-16, 2000 Bethesda, Maryland.
    Date January 2001
    Journal Journal of the American College of Cardiology
    Title Trends and Disparities in Coronary Heart Disease, Stroke, and Other Cardiovascular Diseases in the United States: Findings of the National Conference on Cardiovascular Disease Prevention.
    Date January 2001
    Journal Circulation
    Excerpt

    A workshop was held September 27 through 29, 1999, to address issues relating to national trends in mortality and morbidity from cardiovascular diseases; the apparent slowing of declines in mortality from cardiovascular diseases; levels and trends in risk factors for cardiovascular diseases; disparities in cardiovascular diseases by race/ethnicity, socioeconomic status, and geography; trends in cardiovascular disease preventive and treatment services; and strategies for efforts to reduce cardiovascular diseases overall and to reduce disparities among subpopulations. The conference concluded that coronary heart disease mortality is still declining in the United States as a whole, although perhaps at a slower rate than in the 1980s; that stroke mortality rates have declined little, if at all, since 1990; and that there are striking differences in cardiovascular death rates by race/ethnicity, socioeconomic status, and geography. Trends in risk factors are consistent with a slowing of the decline in mortality; there has been little recent progress in risk factors such as smoking, physical inactivity, and hypertension control. There are increasing levels of obesity and type 2 diabetes, with major differences among subpopulations. There is considerable activity in population-wide prevention, primary prevention for higher risk people, and secondary prevention, but wide disparities exist among groups on the basis of socioeconomic status and geography, pointing to major gaps in efforts to use available, proven approaches to control cardiovascular diseases. Recommendations for strategies to attain the year 2010 health objectives were made.

    Title A Longitudinal Study of Apolipoprotein-e Genotype and Depressive Symptoms in Community-dwelling Older Adults.
    Date August 2000
    Journal The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry
    Excerpt

    The Apolipoprotein-E (APOE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and cognitive decline in older adults. Depression may also be a risk factor for dementia, and depression is important in the differential diagnosis of dementia. The authors performed a 5-year longitudinal study of APOE genotype and change in Geriatric Depression Scale scores in 113 community-dwelling older adults. No association was observed between APOE genotype and change in depressive symptoms. These results do not support the hypothesis that the APOE epsilon 4 allele is associated with depression. Important objections have been raised to APOE genotyping in the diagnosis of AD. However, the specificity of APOE genotyping in AD diagnosis would not appear to be compromised by an association with depression.

    Title Drosophila P53 is a Structural and Functional Homolog of the Tumor Suppressor P53.
    Date May 2000
    Journal Cell
    Excerpt

    The importance of p53 in carcinogenesis stems from its central role in inducing cell cycle arrest or apoptosis in response to cellular stresses. We have identified a Drosophila homolog of p53 ("Dmp53"). Like mammalian p53, Dmp53 binds specifically to human p53 binding sites, and overexpression of Dmp53 induces apoptosis. Importantly, inhibition of Dmp53 function renders cells resistant to X ray-induced apoptosis, suggesting that Dmp53 is required for the apoptotic response to DNA damage. Unlike mammalian p53, Dmp53 appears unable to induce a G1 cell cycle block when overexpressed, and inhibition of Dmp53 activity does not affect X ray-induced cell cycle arrest. These data reveal an ancestral proapoptotic function for p53 and identify Drosophila as an ideal model system for elucidating the p53 apoptotic pathway(s) induced by DNA damage.

    Title An Actigraphic Comparison of Sleep Restriction and Sleep Hygiene Treatments for Insomnia in Older Adults.
    Date May 2000
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG.

    Title If Patients with Schizophrenia Have Small Brains, Why Don't They Have Small Heads?
    Date May 2000
    Journal Schizophrenia Research
    Excerpt

    Although patients with schizophrenia have reduced brain size, there is no conclusive evidence that they have reduced head size. This begs the question: 'What is the precise relationship between head size and brain size?' We used a unique osteological collection to explore the relationship between external head measures and cranial capacity. The external measures accounted for, at most, 60% of the variance in cranial capacity - a value low enough to question the oft-assumed tight relationship between head measures and brain size. Obviously, various tissues and spaces [skull, sinus, muscle (frontalis, temporalis and occipitalis), subcutaneous fat and epidermal layers] contribute to head size without contributing to brain volume. The contribution of these other tissues and spaces tends to decrease the signal and increase the noise in the estimation of brain volume. Thus, it is understandable that patients with schizophrenia can have reduced cranial capacity and not reduced head size.

    Title Tuberculosis Chemoprophylaxis Using a Liquid Isoniazid-methadone Admixture for Drug Users in Methadone Maintenance.
    Date April 2000
    Journal Addiction (abingdon, England)
    Excerpt

    BACKGROUND: Tuberculosis is common in drug users, although compliance with therapy may be difficult in this population. OBJECTIVE: To evaluate an approach to enhancing compliance with tuberculosis chemoprophylaxis in drug users enrolled on methadone maintenance utilizing an isoniazid (INH)-methadone admixture. DESIGN: A prospective cohort study. SETTING: A drug treatment program in New Haven, Connecticut, USA. PATIENTS: Opioid-dependent drug users enrolled in methadone maintenance. INTERVENTION: Liquid isoniazid was mixed into subjects' daily dose of methadone. Vitamin B6 was given to subjects for self-administration. MEASUREMENTS AND MAIN RESULTS: Number of eligible subjects, reasons for not starting therapy, number starting therapy, proportion completing therapy and median duration of INH therapy were calculated. Thirty-nine subjects were eligible for INH chemoprophylaxis: 34 (87%) received INH mixed directly in their methadone and five (13%) had their INH consumption supervised by a nurse. Among these subjects, 72% (28/39) completed therapy. Among the 11 subjects who discontinued INH, discharge from the methadone maintenance program was the most common reason--73% (8/11). Thus, among the 31 subjects who were not discharged from methadone maintenance, 90% (28/31) successfully completed INH prophylaxis. The median duration of therapy was 182 days. CONCLUSIONS: Tuberculosis chemoprophylaxis using a liquid isoniazid-methadone admixture appears to be an effective approach to enhancing compliance with this therapy in methadone-maintained drug users.

    Title Functional Magnetic Resonance Imaging in Schizophrenia: Initial Methodology and Evaluation of the Motor Cortex.
    Date March 2000
    Journal Psychiatry Research
    Excerpt

    The purpose of the present study was to evaluate the differential activation of the motor cortex during finger tapping in patients with schizophrenia using the newly available imaging method of functional magnetic resonance imaging (fMRI). Nine patients with DSMIII-R schizophrenia and 9 well-matched healthy volunteer subjects underwent fMRI examination on a conventional MR unit; activation of the primary motor cortex was evaluated during performance of a finger motion task. Localized activation of the motor cortex was observed in 17 of 18 subjects during fMRI. Patients and controls were, however, indistinguishable with respect to signal intensity or area thereof within the motor cortex. fMRI did not reveal motor cortical dysfunction in schizophrenia. Despite its infancy, fMRI holds considerable promise to advance understanding of the neurodynamics of psychiatric disorders, particularly schizophrenia.

    Title Prevention Conference V: Beyond Secondary Prevention: Identifying the High-risk Patient for Primary Prevention: Noninvasive Tests of Atherosclerotic Burden: Writing Group Iii.
    Date January 2000
    Journal Circulation
    Title Meta-analysis of Brain Size in Bipolar Disorder.
    Date December 1999
    Journal Schizophrenia Research
    Excerpt

    A recent meta-analysis concluded that patients with schizophrenia have reduced cerebral volume, and this finding has been used to implicate neurodevelopmental events in the etiology of this disorder. Since bipolar-disorder patients and schizophrenia patients have some similar brain abnormalities, it was of interest to meta-analytically review the literature on brain size in bipolar disorder. Only seven studies met the inclusion/exclusion criteria for our meta-analysis, but none reported the brain size differences between the bipolar patients and the controls to be statistically significant. The composite effect size was a negligible 0.04 (95% CI: -0.17 to 0.25) and statistically not significantly different from 0.0 (no effect). Thus, it appears that bipolar disorder is not associated with the same cerebral volume reductions noted in schizophrenia. Implications for hypotheses regarding the etiology of the two disorders are discussed.

    Title An Mri Study of Adolescent Patients with Either Schizophrenia or Bipolar Disorder As Compared to Healthy Control Subjects.
    Date December 1999
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: There are few imaging studies in adolescent patients with either schizophrenia or bipolar disorder. Such studies are of interest because adolescents may have a more severe illness and neurodevelopmental events may have a greater role in their pathophysiology. METHODS: We compared 20 patients with schizophrenia and 15 patients with bipolar disorder (10 to 18 years) to 16 normal adolescents on magnetic resonance imaging (MRI) measures of intracranial volume and ventricular and sulcal enlargement. Two planned comparison contrasts were employed, one comparing the two patient groups to each other (contrast 1), and one comparing both patient groups combined to control subjects (contrast 2). RESULTS: None of the contrast 1 comparisons (schizophrenia vs bipolar) were statistically significant. Contrast 2 comparisons (control subjects vs patients) were statistically significant for intracranial volume (reduced in patients) as well as frontal and temporal sulcal size (increased in patients). CONCLUSIONS: The patient groups were not statistically significantly different from each other on any measure. The combined patient groups were different from control subjects on intracranial volume and frontal and temporal sulcal size. Also, there was evidence for ventricular enlargement, after removal of a control subject with an extreme value. These findings indicate that the same abnormalities noted in adult populations are present in adolescents.

    Title Clozapine and Other 5-hydroxytryptamine-2a Receptor Antagonists Alter the Subcellular Distribution of 5-hydroxytryptamine-2a Receptors in Vitro and in Vivo.
    Date August 1999
    Journal Neuroscience
    Excerpt

    In this study, we demonstrate that clozapine and other atypical antipsychotic drugs induce a paradoxical internalization of 5-hydroxytryptamine-2A receptors in vitro and a redistribution of 5-hydroxytryptamine-2A receptors in vivo. We discovered that clozapine, olanzapine, risperidone and the putative atypical antipsychotic drug MDL 100,907 all induced 5-hydroxytryptamine-2A receptor internalization in fibroblasts stably expressing the 5-hydroxytryptamine-2A receptor in vitro. Two 5-hydroxytryptamine-2A antagonists (mianserin and ritanserin), which have been demonstrated to reduce negative symptoms in schizophrenia, also caused 5-hydroxytryptamine-2A receptor internalization. Four different drugs, each devoid of 5-hydroxytryptamine-2A antagonist activity, had no effect on the subcellular distribution of 5-hydroxytryptamine-2A receptors in vitro. Treatment of rats for seven days with clozapine induced an increase in intracellular 5-hydroxytryptamine-2A receptor-like immunoreactivity in pyramidal neurons, while causing a decrease in labeling of apical dendrites in the medial prefrontal cortex. This redistribution of 5-hydroxytryptamine-2A receptors in pyramidal neurons was also seen when rats were chronically treated with another atypical antipsychotic drug, olanzapine. The typical antipsychotic drug haloperidol, however, did not induce a redistribution of 5-hydroxytryptamine-2A receptors in pyramidal neurons in the medial prefrontal cortex. Taken together, these results demonstrate that several atypical antipsychotic drugs with high 5-hydroxytryptamine-2A receptor affinities induce a redistribution of 5-hydroxytryptamine-2A receptors both in vivo and in vitro. It is conceivable that the loss of 5-hydroxytryptamine-2A receptors from the apical dendrites of pyramidal neurons is important for the beneficial effects of atypical antipsychotic drugs and other 5-hydroxytryptamine-2A antagonists in schizophrenia.

    Title Emergency Department Airway Management Before and After an Emergency Medicine Residency.
    Date July 1999
    Journal The Journal of Emergency Medicine
    Excerpt

    To determine whether the start of an Emergency Medicine (EM) training program affects the appropriateness, timeliness, and safety of Emergency Department (ED) intubations, all ED intubations performed 12 months before and after the start of an EM residency were reviewed. In addition, all patients intubated within 12 h after being admitted through the ED were reviewed. We found that all ED intubations before and after the start of a residency program were deemed appropriate. Of patients intubated after admission, 13 of 20 (65%) were felt to have warranted intubation while in the ED for the pre-residency group, compared with 9 of 29 patients (31%) for the post-residency group. There were no differences between the complication rates of these groups. We conclude that an EM residency program did not increase the number of inappropriate intubations or complications, and reduced the number of patients who required but did not receive intubation in the ED.

    Title How to Drastically Reduce Priming in Word Stem Completion--and Still Present the Words.
    Date June 1999
    Journal Memory & Cognition
    Excerpt

    This paper describes a series of experiments in which we demonstrated that "dysphonemic" word stems, which are likely not pronounced in isolation as they are within a word (e.g., MUS in MUSHROOM or LEG in LEGEND), showed less priming than did "phonemic stems" (e.g., MUS in MUSTARD or LEG in LEGACY). Furthermore, words with either dysphonemic or phonemic three-letter stems gave rise to equivalent levels of priming when test cues were four-letter stems (LEGE) or word fragments (L_G_ND). Moreover, the difference between phonemic and dysphonemic stems persisted when nonpresented completion rates were matched. A final cued-recall experiment revealed that performance was greater for phonemic stems than for dysphonemic stems and that this difference was greater for older participants than for younger ones. These results are not readily accounted for by extant theoretical approaches and point to important methodological issues regarding stem completion.

    Title Mnemonic Training in Older Adults: Effects of Age, Length of Training, and Type of Cognitive Pretraining.
    Date May 1999
    Journal International Psychogeriatrics / Ipa
    Excerpt

    OBJECTIVES: To improve performance with mnemonic techniques for remembering words and proper names. DESIGN: For word recall, a 2 x 2 factorial in which type of pretraining and length of training were between-subjects manipulations. For proper name recall, a two-group design in which type of pretraining was manipulated between subjects. SETTING: Community. PARTICIPANTS: 268 community-dwelling adults over the age of 55 years who wished to improve their memory. MEASUREMENTS: Recall of words and proper names both before and after training in mnemonics. INTERVENTION: Participants received a 2-week training course on two mnemonic techniques, the method of loci for words and a name association technique for proper names. RESULTS: There was no effect of the pretraining manipulation on proper name recall. For word recall, however, a multiple regression that included age indicated that the older-old participants benefited more from a combination of comprehensive pretraining and extended mnemonic training than did the younger-old. CONCLUSIONS: Increased training time coupled with a comprehensive pretraining regimen can improve the performance of the older-old in using mnemonics; this improved performance cannot be attributed solely to enhanced knowledge of the mnemonic.

    Title Global Structural Brain Abnormalities in Mood Disorders: Evidence from a Meta-analysis Versus a Traditional Review.
    Date May 1999
    Journal Biological Psychiatry
    Title Three-dimensional Magnetic Resonance-based Morphometrics and Ventricular Dysmorphology in Schizophrenia.
    Date March 1999
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Recent methodological refinements in magnetic resonance (MR) imaging have led to brain averaging and morphometric approaches that are sensitive to subtle anatomical distinctions in schizophrenia. METHODS: Using a novel morphometric technique for surface analysis, 48 selected landmarks of the rendered ventricular system were extracted and compared between the ventricles of 20 patients with schizophrenia and 20 normal subjects. RESULTS: There was no significant difference in ventricular shape between groups, but significant (p = .015) and highly localized shape deformity was detected at the foramen of Monro and at the proximal temporal horn of the lateral ventricle of male (but not female) patients relative to controls. CONCLUSIONS: Three-dimensional MR-based morphometrics complements established volumetric approaches and can detect minute shape deformities that may be associated with schizophrenia.

    Title Serotonergic Antagonist Effects on Trafficking of Serotonin 5-ht2a Receptors in Vitro and in Vivo.
    Date February 1999
    Journal Annals of the New York Academy of Sciences
    Excerpt

    The mechanism by which antagonists down-regulate 5-HT2A receptors in unknown. We here report that a variety of 5-HT2A antagonists induce a change in the subcellular distribution of 5-HT2A receptors both in vitro and in vivo. In a stably transfected NIH 3T3 cell-line, brief exposure to 1 muM clozapine caused a 2.5-fold increase in intracellular 5-HT2A-like immunoreactivity, as measured by confocal microscopy. Confirmatory studies utilizing a biotin-trap technique, demonstrated that the increase in intracellular immunoreactivity results from internalization of receptor from the cell surface. Exposure of transfected cells to other 5-HT2A receptor antagonists produced similar increases in intracellular 5-HT2A-like immunoreactivity. In vivo administration of clozapine (20 mg/kg, sc, X 7 days) caused a greater than twofold increase in intracellular immunoreactivity in cell bodies of cortical pyramidal neurons. Additionally, chronic clozapine administration was associated with decrease in labeling of apical dendrites on pyramidal cells. These results show that clozapine causes a change in subcellular distribution of 5-HT2A receptors in vitro and in vivo.

    Title Newer Antidepressants. Beyond Selective Serotonin Reuptake Inhibitor Antidepressants.
    Date January 1999
    Journal Pediatric Clinics of North America
    Excerpt

    This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years. Many of these agents will be used by pediatricians and child psychiatrists for treatment of depression in children, and although much further research is needed, the future for alternative antidepressants and augmenting strategies is extremely promising.

    Title A Follow-up Study of Actigraphic Measures in Home-residing Alzheimer's Disease Patients.
    Date October 1998
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    This article reports cross-sectional and follow-up data with actigraphic measures of nocturnal sleep and rest/activity in 61 Alzheimer's disease (AD) patients as well as the relation of actigraphic measures to levels of behavioral disturbance across different stages of the disease. Over the course of approximately 1.5 years' follow-up, patients showed significant deterioration of nocturnal sleep parameters, but no significant change in rest/activity circadian rhythm parameters. There were also significant correlations among nocturnal sleep, rest/activity circadian rhythm, and behavioral disturbance measures, but only in relatively early stages of AD. It is argued that study of nocturnal sleep and circadian rhythm in relation to behavioral disturbance in AD requires longitudinal data and analyses that take into account the stage of disease at which patients are assessed.

    Title Brain Activation During Silent Word Generation Evaluated with Functional Mri.
    Date October 1998
    Journal Brain and Language
    Excerpt

    This is a study of word generation during functional MRI (fMRI). Eleven normal healthy subjects were instructed to generate words covertly, (i.e., silently) that began with particular letters. Images were acquired on a conventional 1.5T scanner at three contiguous axial planes encompassing language-related areas of the temporal and frontal lobe. The data were analyzed at the level of a Talairach box, after individually fitting the proportional Talairach grid system to each slice. The main variable of interest was the number of activated pixels within a Talairach box. Boxes with a significant increase in the proportion of activated pixels were located in three regions of the left neocortex: (1) Brodmann areas 44 and 45 in the dorsolateral frontal cortex (Broca's area), (2) areas 21 and 37 in the temporal cortex, (3) and the striate/extrastriate cortex (areas 17 & 18). The results are discussed in terms of a cognitive model of word generation and are compared, in detail, with the results of prior relevant imaging studies.

    Title The Carpal Stretch Test.
    Date May 1998
    Journal Canadian Journal of Surgery. Journal Canadien De Chirurgie
    Excerpt

    OBJECTIVE: To compare the sensitivity of traditional motion studies, bone scintigraphy and radiocarpal arthrography to a "carpal stretch test," for evaluation of dynamic dissociative carpal instability. DESIGN: Experimental study comparing the results of the tests to the findings of arthroscopy, the "gold standard." SETTING: A university hospital-based upper extremity practice. PATIENTS: Six patients with chronic wrist pain, arthroscopically confirmed proximal row ligamentous disruption and radiographs not suggestive of proximal row instability. INTERVENTIONS: The carpal stretch test: both affected and unaffected wrists were subjected to the same testing, wherein the wrist was suspended from finger traps for 10 minutes by a 4.5-kg weight. Standardized posteroanterior radiographs were taken of the suspended wrists. MAIN OUTCOME MEASURES: Disruption of Gilula's arcs I and II, and sensitivity of the carpal stretch test compared with other investigations. MAIN RESULTS: Step deformities ranging from 2.5 to 6 mm (average 3.7 mm) were recorded in the affected wrists and 0 to 4 mm (average 1.5 mm) in the "unaffected" wrists. The test was more sensitive than traditional radiography, arthrography and scintigraphy in defining both presence and site of proximal carpal row ligamentous tears and was almost as sensitive as arthroscopy. CONCLUSION: In patients with chronic wrist pain and dynamic dissociative wrist instability, the carpal stretch test may prove to be a valuable screening tool for detecting ligamentous tears of the proximal carpal row.

    Title Treatment and Outcomes in Adolescents with Schizophrenia.
    Date February 1998
    Journal The Journal of Clinical Psychiatry
    Excerpt

    The pharmacologic treatment and assessment of outcomes in adolescents with schizophrenia have been inadequately addressed. Structural brain imaging and brain function studies both point to a continuity between adolescent and adult stages of schizophrenia. Because the teenage population seems to be less tolerant of physical side effects, the advent of atypical antipsychotic medications may offer increased safety and efficacy. Studies support the notion that adolescent illness is associated with a more severe form of schizophrenia and that length of illness before treatment is correlated with long-term outcome. As a consequence, the authors recommend assertive pharmacologic intervention in adolescents with schizophrenia and future research focused on the issues of treatment and outcome in teenagers suffering a psychotic disorder.

    Title Anesthetic Management of Labor and Postpartum Bleeding in a Patient with Fontan Physiology.
    Date January 1998
    Journal Israel Journal of Medical Sciences
    Excerpt

    We describe the obstetric anesthetic management of a patient with complex congenital heart anomaly consisting of transposed great arteries, double inlet left ventricle and subpulmonic stenosis. Successful management of a patient with Fontan physiology mandates a thorough understanding of the hemodynamic consequences of this procedure and the alterations during pregnancy. The major considerations are related to the fact that the systemic venous return reaches the pulmonary vasculature without the augmentation of a functioning ventricle.

    Title Stressful Life Events and Risk of Symptomatic Kidney Stones.
    Date December 1997
    Journal International Journal of Epidemiology
    Excerpt

    BACKGROUND: It has been reported that a substantial proportion of cases of hypercalciuria and nephrolithiasis are idiopathic. Several studies suggested that stressful life events increase lithogenic urinary constituents (calcium, oxalate and uric acid). OBJECTIVE: To test the hypothesis that there is an association between stressful life events and symptomatic kidney stone. METHODS: A case-control study of 200 symptomatic kidney stone cases and 200 matched controls was designed to test the hypothesis. In this study, the stressors include those life events that the subjects perceived as highly stressful and inflicted upon them an intense emotional impact with apprehension and distress for at least one week in duration. RESULTS: Ten of eleven (91%) categories and 41 of 60 (68%) subcategories of stressful events occurred more frequently among cases than controls. Eighteen stressful events had odds ratios of 1.5 or greater. Of the seven significant (P < 0.05) variables that were entered into a multivariate logistic regression model, the following three remained statistically significant between cases and controls: annual family income (lower for cases); stressful morgage problems; and emotional life events. CONCLUSION: The overall prevalence rate of stressful life events was significantly (P < 0.00001) higher among cases than controls. The data support the hypothesis that there is an association between stressful life event(s) and symptomatic kidney stones.

    Title Cognitive Impairment in Adolescents with Schizophrenia.
    Date November 1997
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: The purpose of this study was to determine whether adolescent schizophrenia is characterized by neuropsychological deficits. METHOD: The performance on a battery of neuropsychological tests of 17 adolescents with schizophrenia (mean age = 15.71 years) was compared with that of 17 normal adolescents (mean age = 15.12 years). RESULTS: Compared with the normal subjects, the patients were impaired on 10 of the 13 measures; larger effect sizes were shown for measures involving working memory and attention than for those involving secondary memory, generative naming, and executive functions. CONCLUSIONS: Adolescents with schizophrenia have generalized cognitive dysfunction, which is most apparent on tests of attention and working memory.

    Title Pictorial Review: Magnetic Resonance Imaging of the Paediatric Elbow.
    Date September 1997
    Journal Clinical Radiology
    Title Disruptive Behavior and Actigraphic Measures in Home-dwelling Patients with Alzheimer's Disease: Preliminary Report.
    Date August 1997
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    The purpose of this preliminary report was to explore overall level and diurnal patterning of caregiver reports of abnormal behavior and to explore relationships with actigraphic measures of sleep/wake activity in Alzheimer's disease (AD) patients. Our primary behavioral measure was the Time-based Behavioral Disturbance Questionnaire (TBDQ). The overall score on this measure was shown to have adequate test-retest reliability and convergent validity with another behavioral measure. Significant correlations were obtained between the TBDQ overall score and actigraphically scored sleep efficiency (r = -.35, P < .05) and wake after sleep onset (r = .43, P < .01) in 41 subjects. The data suggest a moderate relationship between actigraphic measures of sleep/wake and disturbed behavior in home-dwelling AD patients.

    Title Eye Tracking, Attention, and Schizotypal Symptoms in Nonpsychotic Relatives of Patients with Schizophrenia.
    Date March 1997
    Journal Archives of General Psychiatry
    Excerpt

    BACKGROUND: Biological relatives of patients with schizophrenia demonstrate an increased prevalence of schizotypal personality disorder symptoms, eye tracking deficits, and attentional disturbances. We investigated whether these hypothesized components of a schizophrenia-related phenotype are associated with one another or are independent in nonpsychotic relatives of patients with schizophrenia. METHODS: Eighty-three nonpsychotic first-degree relatives of 38 patients with schizophrenia and 45 control subjects without a psychiatric diagnosis underwent clinical evaluation, eye tracking evaluation, and the Continuous Performance Test (CPT) of visual attention. RESULTS: Eye tracking qualitative rating was more powerful than quantitative eye tracking measures or CPT measures in discriminating relatives of patients with schizophrenia from control subjects. Correlations between neurocognitive variables and DSM-III-R schizotypal personality disorder symptom clusters suggested that CPT errors of omission are associated with positive schizotypal symptoms. Eye tracking measures were not significantly correlated with schizotypal symptoms or CPT errors in relatives of patients with schizophrenia. CONCLUSIONS: Eye tracking deficits in the relatives of patients with schizophrenia are unrelated to CPT deficits and schizotypal symptoms. Eye tracking deficits and disturbances in visual attention may be separate components of a schizophrenia-related phenotype and should be considered as independent factors in genetic studies of schizophrenia.

    Title Psychiatry. The Brain Hallucinates and Gets Caught in the Web.
    Date January 1997
    Journal Lancet
    Title Adolescent Schizophrenia: a Methodologic Review of the Current Neuroimaging and Neuropsychologic Literature.
    Date October 1996
    Journal Journal of Autism and Developmental Disorders
    Excerpt

    This paper reviews all relevant articles that reported structural neuroimaging or neuropsychological data in adolescent patients with schizophrenia. These papers were subsequently examined from a methodological perspective. Few papers have been written that have examined whether adolescent schizophrenia is associated with structural neuroimaging abnormalities or cognitive dysfunction. In these studies, major methodologic issues exist. Therefore, at present, firm conclusions cannot be made regarding the presence or absence of neuropsychologic dysfunction or structural neuroimaging abnormalities in this population. Attention to certain methodologic issues may improve future studies of this topic.

    Title Cortical Localization of Human Sustained Attention: Detection with Functional Mr Using a Visual Vigilance Paradigm.
    Date October 1996
    Journal Journal of Computer Assisted Tomography
    Excerpt

    PURPOSE: Our goal was to determine whether functional MRI on a standard 1.5 T system can localize activation during a visual vigilance sustained attention task and whether this corresponds to results described in a PET investigation of a similar task. METHOD: Sixteen volunteers were studied on a 1.5 T system using a gradient echo technique. A single axial section was oriented within a stereotaxic coordinate space, 40 mm superior to the anterior-posterior commissure line. Images with eyes closed were followed by images during subject concentration on a small dim spot. Motion correction and pixel-by-pixel statistical analysis were performed. Talairach grids were applied for summary statistical analysis and comparison to PET data, with analysis using a series of planned contrasts within a repeated measures analysis of variance. RESULTS: Predominantly right-sided frontal and parietal activation was observed, with statistical significance across subjects in the right frontal lobe (F > or = 5.9, p < or = 0.041). Comparison with previously reported PET data yielded a very similar pattern of activation (F = 13.2; df = 1,8; p = 0.007). CONCLUSION: Activation of the right middle frontal gyrus and right parietal lobe during visual vigilance is detectable across functional imaging modalities.

    Title Alcohol Elimination and Simulator Performance of Male and Female Aviators: a Preliminary Report.
    Date September 1996
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    OBJECTIVES: In this preliminary study of alcohol effects on aviators' flight simulator performance, we addressed some methodological issues regarding possible gender-related differences in response to alcohol. METHODS: Subjects were 11 male and 12 female general aviation pilots, ages 21-40. Subjects received 8 h of training before they were tested with alcohol. On the alcohol test day they were tested before drinking, while intoxicated (target BAC of 0.08%), and 8 h after drinking. RESULTS: The average, observed peak BAC readings for men and women were within 0.003% of each other. We observed faster disappearance rates for women such that women reached the FAA cutoff of 0.04% approximately 1 h before men, on average. Compared to predrink performance, there was a significant decrement in simulator performance during acute intoxication, but not 8 h after drinking. There were no significant gender differences in performance before or after drinking alcohol. Slower rates of alcohol elimination were associated with larger performance changes 8 h after drinking. This is the first report to our knowledge suggesting a possible relation between alcohol elimination rate and change in performance after drinking alcohol. CONCLUSIONS: A 12.5% dose reduction for women appears to be adequate for achieving comparable peak BAC's for male and female groups. Future studies using measures of circadian rhythmicity in conjunction with pharmacokinetic and performance measures could potentially shed light on differences in subjects' acute and delayed responses to alcohol.

    Title Inclusion of Women and Minorities in Clinical Trials and the Nih Revitalization Act of 1993--the Perspective of Nih Clinical Trialists.
    Date March 1996
    Journal Controlled Clinical Trials
    Title Haplotype and Phenotype Analysis of Six Recurrent Brca1 Mutations in 61 Families: Results of an International Study.
    Date February 1996
    Journal American Journal of Human Genetics
    Excerpt

    Several BRCA1 mutations have now been found to occur in geographically diverse breast and ovarian cancer families. To investigate mutation origin and mutation-specific phenotypes due to BRCA1, we constructed a haplotype of nine polymorphic markers within or immediately flanking the BRCA1 locus in a set of 61 breast/ovarian cancer families selected for having one of six recurrent BRCA1 mutations. Tests of both mutations and family-specific differences in age at diagnosis were not significant. A comparison of the six mutations in the relative proportions of cases of breast and ovarian cancer was suggestive of an effect (P = .069), with 57% of women presumed affected because of the 1294 del 40 BRCA1 mutation having ovarian cancer, compared with 14% of affected women with the splice-site mutation in intron 5 of BRCA1. For the BRCA1 mutations studied here, the individual mutations are estimated to have arisen 9-170 generations ago. In general, a high degree of haplotype conservation across the region was observed, with haplotype differences most often due to mutations in the short-tandem-repeat markers, although some likely instances of recombination also were observed. For several of the instances, there was evidence for multiple, independent, BRCA1 mutational events.

    Title Perceptions of Life Stress and Chronic Insomnia in Older Adults.
    Date January 1996
    Journal Psychology and Aging
    Excerpt

    This study compared the level of self-reported stress of 42 older good sleepers (M age = 68.2 years) and 42 poor sleepers (M age = 68.7 years). The relations among subjective ratings of sleep, level of perceived stress, and negative mood were analyzed for each group. Good and poor sleepers reported similar amounts of life stress, but the relations between life stress and sleep perceptions differed for the 2 groups. Specifically, within the group of poor sleepers, those with higher life stress had greater difficulty falling asleep and less early morning waking than did poor sleepers with lower life stress. There was no association between life stress and any sleep measures for good sleepers. These results are compatible with the notion that good and poor sleepers may have different susceptibilities to poor sleep despite experiencing similar stressful life events.

    Title Indana: a Meta-analysis on Individual Patient Data in Hypertension. Protocol and Preliminary Results.
    Date December 1995
    Journal Thérapie
    Excerpt

    The overall effect of antihypertensive drug treatment has been well documented. The proportion of patients who benefit varies according to their baseline cardiovascular risk, and is small for the majority of people treated. Some investigators propose limiting the treatment target population to patients at high cardiovascular risk, but several assumptions must be made to justify this procedure. The INDANA project is a meta-analysis based on individual patient data, and thus offers the opportunity to check the validity of these assumptions. Its main objective is to identify responders (and non-responders) in the drug treatment of hypertension. The rationale and methods for such an approach are presented here, with the solution for some technical problems. The conclusion of the data collection has shown that the project is feasible. The results of the main analysis should be available in 1996, and should contribute to the selection of responders and to the individualization of the treatment of hypertension.

    Title Spontaneous Mnemonic Strategies Used by Older and Younger Adults to Remember Proper Names.
    Date December 1995
    Journal Memory (hove, England)
    Excerpt

    Little attention has been focused on the spontaneous mnemonic strategies that people use to remember proper names. In the experiment reported here, groups of younger (< 25 years old) and older subjects (> or = 55 years old) were shown a series of 12 name-face pairs and instructed to remember them. In a subsequent test, they were shown the same faces and asked to recall the corresponding names. After the recall task, subjects completed a questionnaire about the mnemonic strategies they used. Our analyses revealed not only that the younger subjects recalled more names than did the older subjects, but also that older and younger subjects reported using certain strategies more frequently than other strategies. Moreover, regression analyses indicated that use of certain mnemonic strategies accounted for a significant proportion of recall performance beyond that accounted for by age alone. Older-old subjects (> or = 70 years old) recalled fewer names than did younger-old subjects (> or = 55 and < 70 years old), but they did not differ in the extent to which they used specific mnemonic strategies. Our results suggest that the use of spontaneous mnemonic strategies may play a role in the difference in proper name recall between younger and older adults.

    Title Smooth Pursuit Performance in Patients with Affective Disorders or Schizophrenia and Normal Controls: Analysis with Specific Oculomotor Measures, Rms Error and Qualitative Ratings.
    Date October 1995
    Journal Psychological Medicine
    Excerpt

    Smooth pursuit performance in schizophrenia and affective disorders has generally been found to be abnormal using a variety of measures. The purpose of this study was to assess patients with these disorders and normal controls in order to compare the different measures across diagnoses. Smooth pursuit was assessed using quantitative specific measures (gain, catch-up saccade rate and amplitude, square-wave jerk rate, number of anticipatory saccades and total time scored), as well as two global measures: root mean-square error (RMS) and qualitative rating. As previously reported, patients with schizophrenia had low gain, increased catch-up saccade rate and spent less time engaged in scoreable smooth pursuit than normal controls. Patients with affective disorders were not statistically different from controls on any of these measures, and had significantly higher gain than patients with schizophrenia. RMS error and qualitative rating measures were highly correlated (r = 0.87). In linear regression analyses, the quantitative specific measures were highly significant predictors of both RMS error and qualitative ratings (P < 0.0001). Linear regression analyses and a modelling study indicated that one quantitative specific measure, the percent of time engaged in scoreable smooth pursuit (total time scored), was most related to global ratings. However, RMS error and qualitative ratings were less sensitive than total time scored to the difference between controls and patients with schizophrenia. These data indicate two smooth pursuit performance deficits in schizophrenia: patients spend less time engaged in scoreable smooth pursuit and have low gain (accompanied by increased compensatory saccades) when the smooth pursuit is engaged.

    Title Growth Patterns in Selected Organs of the Miniature Swine As Determined by Gross Macromolecular Composition.
    Date October 1995
    Journal Journal of Animal Science
    Excerpt

    As part of a larger study designed to characterize the early developmental stages of the Hormel-Hanford strain miniature pig, the brain, kidney, liver, pancreas, and spleen from male animals were examined for changes in RNA, DNA, and protein contents from 1 to 196 d after birth. Distinct patterns were found for changes with age in macromolecular levels. Protein levels increased from d 1 to 56 in all organs except spleen, in which little change was noted. Gel electrophoresis showed little qualitative change in the liver protein profile during this period. A fat-free, non-nucleic acid, protein-containing fraction, insoluble in hot alkali, appeared in the brain after approximately 1 wk following birth. DNA concentrations decreased markedly from d 1 to d 196 for brain, kidney, and spleen but decreased more gradually for liver and pancreas. RNA levels declined slightly or remained the same in all organs except pancreas, where a large increase occurred from d 1 to weaning (56 d). Growth proceeded in all organs by increases in cell number (hyperplasia), as evidenced by increases in total (level or concentration x organ weight) DNA, or by hypertrophy, as evidenced by increases in the ratio of protein to DNA or by a combination of both processes. Hypertrophic growth was attained by d 56 and continued to sexual maturity in all organs except spleen. Hyperplastic growth continued to sexual maturity in all organs except brain.

    Title Normal Variation in Mri of the Brain.
    Date September 1995
    Journal Seminars in Ultrasound, Ct, and Mr
    Excerpt

    Compared with CT, much more detail and information is seen on any standard MRI sequence. The task of reviewing MRI head scans can therefore be daunting to the new radiologist. This article outlines and emphasizes many of the predictable normal variants, hopefully lessening the burden and preventing the reader from misidentifying many of the common structures.

    Title Prediction of Outcome in Behaviorally Based Insomnia Treatments.
    Date September 1995
    Journal Journal of Behavior Therapy and Experimental Psychiatry
    Excerpt

    Factors related to successful behavioral intervention for individuals with insomnia are not well understood. In this study we employed the Neuroticism, Extraversion and Openness (NEO) Personality Inventory, to predict successful treatment outcome. Two behavioral treatments for insomnia, sleep restriction therapy (SRT) and relaxation training (RT) were employed in 32 elderly insomniacs. Following two baseline weeks, subjects underwent four weeks of individual treatment. Daily telephone call-ins generated data on sleep times and sleep latency. Follow-up occurred three months after the end of treatment. Results indicated that subjects showing the greatest improvement in total sleep time with both treatments were more traditional, conventional and rigid. Improvement in sleep onset latency was unrelated to NEO Scores. SRT appeared to be more effective for increasing total sleep time in these older subjects.

    Title Modification of Conditioned Apneas in Rats: Evidence for Cortical Involvement.
    Date August 1995
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    Apneic patterns in breathing can be classically conditioned in rats by brief neonatal exposures to hypoxia, noise, and petting during sleep (A. J. Thomas, W. Austin, L. Friedman, and K. P. Strohl, J. Appl. Physiol. 73: 1530-1536, 1992); thus animals may acquire apneic patterns by exposure to not only respiratory but also nonrespiratory stimuli. We hypothesized that conditioned apneas in these animals can be reduced or abolished by presentation of counterconditioning stimuli, which would prevent the respiratory controller from being influenced by nonrespiratory stimuli and affecting breathing rhythmicity. In five female rats conditioned during neonatal life to exhibit apneic breathing during adulthood and in five female unconditioned control rats, the effect of a brief quiet repetitive auditory stimulus (white noise, 50 Hz, 30 dB) presented for periods of 20 min on and 20 min off was assessed. In conditioned apneic rats, white noise reduced the frequencies of apneas by approximately 79% (P < 0.01) but did not alter the number of apneas in unconditioned control rats. In either group, white noise had no effect on the number of apneas preceded by a sigh. In a second experiment, the effect of Equithesin anesthetic was examined in five female conditioned apneic rats. In contrast to the white noise effect, not only apneic breathing but also apneas preceded by a sign were completely abolished by anesthesia (P < 0.0001). These findings suggest a role for counterconditioning and cortical influences on respiratory rhythm in the adult mammal.

    Title Relationship Between Smooth Pursuit Eye-tracking and Cognitive Performance in Schizophrenia.
    Date May 1995
    Journal Biological Psychiatry
    Excerpt

    The relationship between measures of smooth pursuit and neuropsychological performance was assessed in 20 unmedicated schizophrenics. Eye-tracking measures included gain, catch-up saccade parameters, and rate of saccadic intrusions. Neuropsychological measures included tests generally considered as "frontal": Wisconsin Card Sorting Test (WCST), Consonant Trigram Test (CTT), and Controlled Oral Word Association Test (COWAT). The Digit Symbol Test (DST), which is generally considered to be a measure of global functioning, was also included. Gain and other pursuit measures were significantly correlated with the DST and the COWAT, but were not correlated with the WCST or the CTT.

    Title Magnetic Resonance Imaging in Acute Physeal Injuries.
    Date April 1995
    Journal Skeletal Radiology
    Excerpt

    Magnetic resonance imaging (MRI) permits noninvasive evaluation of the cartilage of the growth plate and epiphysis. This paper reports three cases where MRI was used to supplement conventional radiography in the assessment of acute physeal injuries. In the first patient, MRI was used for postoperative assessment of a radial neck fracture, avoiding further surgical exploration. In the second case, MRI was compared with ultrasonography in the diagnosis of proximal humeral epiphyseal separation in a neonate. In the third case MRI and computed tomography were compared in evaluation of a Salter-Harris type 4 distal femur fracture. In all cases MRI was diagnostic. MRI is the investigation of choice in acute complex physeal injuries, and is particularly appropriate for use prior to the appearance of the secondary ossification center.

    Title The Negative Tuberculin Test: Tuberculin, Hiv, and Anergy Panels.
    Date March 1995
    Journal American Journal of Respiratory and Critical Care Medicine
    Title Acute and 8-hour Effects of Alcohol (0.08% Bac) on Younger and Older Pilots' Simulator Performance.
    Date December 1994
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    This preliminary study examined the acute and 8-hour effects of alcohol at a target peak BAC of 0.08% on pilot performance. Fourteen younger (mean age 27.6 years) and fourteen older (mean age 60.3 years) pilots flew a Frasca 141 simulator in a scenario that included ATC communications and emergencies. Plots were tested during an alcohol and placebo condition at three timepoints: predrink, acute intoxication, and 8 h postdrink. Of eight performance measures, two showed statistically significant effects related to alcohol. First, cockpit monitoring was poorer when pilots were intoxicated, with recovery at 8 h. Second, younger pilots made more communication errors under the influence and there was no significant recovery at 8 h. Older pilots made more communication errors than younger pilots, but possibly because of methodological problems, older pilots' communication performance was not significantly impaired by alcohol. These results provide direction for future research.

    Title The Gene for Pancreatic Polypeptide (ppy) and the Anonymous Marker D17s78 Are Within 45 Kb of Each Other on Chromosome 17q21.
    Date October 1994
    Journal Genomics
    Title Eye Movement Impairment and Schizotypal Psychopathology.
    Date August 1994
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: Eye movement dysfunction in relation to a smooth pursuit task has been documented in schizophrenic patients and in patients with the related personality disorder, schizotypal personality disorder. To investigate which quantitative measures are associated with the eye movement dysfunction and whether the dysfunction is more related to the psychotic-like or the deficit-like symptoms of schizotypal personality disorder, ratings of eye movements in several groups of subjects were compared. METHOD: The study groups consisted of 26 patients with schizotypal personality disorder, 42 patients with other personality disorders (22 who also had two or more schizotypal personality traits and 20 who had fewer than two), and 37 normal comparison subjects. Smooth pursuit eye tracking of sinusoidal and constant velocity targets was recorded by an infrared eye tracking system. Two raters evaluated pursuit gain and large and small saccades in the direction of the target and in the direction opposite to that of the target (quantitative ratings) and constant velocity (qualitative rating). RESULTS: Patients with schizotypal personality disorder and patients with other personality disorders and two or more schizotypal traits, but not those with fewer than two schizotypal traits, had significantly poorer qualitative ratings of tracking than the normal comparison subjects. Neither gain nor any of the saccadic measures significantly differed between groups. The number of large saccades in the direction of the target was the only quantitative variable that predicted low qualitative ratings. Qualitatively poor tracking was associated with the deficit-like, but not the psychotic-like, symptoms of schizotypal personality disorder. CONCLUSIONS: Patients with schizotypal personality disorder demonstrate qualitatively poorer tracking than comparison groups, and the impaired tracking is associated with deficit-like symptoms.

    Title Typography Manipulations Can Affect Priming of Word Stem Completion in Older and Younger Adults.
    Date March 1994
    Journal Psychology and Aging
    Excerpt

    The experiments reported here investigated whether changes of typography affected priming of word stem completion performance in older and younger adults. Across all experiments, the typeface in which a word appeared at presentation either did or did not match that of its 3-letter stem at test. In Experiment 1, no significant evidence of a typography effect was found when words were presented with a sentence judgment or letter judgment task. However, subsequent experiments revealed that, in both older and younger adults, only words presented with a syllable judgment task gave rise to the typography effect (Experiments 2-4). Specifically, performance was greater, when the presentation and test typeface matched than when they did not. Experiment 5, which used stem-cued recall, did not reveal a difference between syllable and letter judgment tasks. These findings highlight the complex nature of word stem completion performance.

    Title Cognitive Decline in Alzheimer's Disease: Elaborating on the Nature of the Longitudinal Factor Structure of the Mini-mental State Examination.
    Date March 1994
    Journal International Psychogeriatrics / Ipa
    Excerpt

    The purpose of this paper was to use the Wechsler Adult Intelligence Scale (WAIS) to further define the nature of the underlying factors of the Mini-Mental State Examination (MMSE) as proposed by Tinklenberg et al. (1990). The MMSE was administered to 51 patients once every 6 months for at least one year; the WAIS was administered only at the beginning of the study. Stepwise regression analyses yielded these results: for the Following Commands factor, the best correlate was the Comprehension subtest; for the Language Repetition factor, the best correlate was the Picture Arrangement subtest; and for the Language Expression factor, the best correlates were the Digit Symbol and Object Assembly subtests. These relations help clarify the correlates of decline of AD patients on the MMSE.

    Title Improvement in Cognitive Functions and Psychiatric Symptoms in Treatment-refractory Schizophrenic Patients Receiving Clozapine.
    Date February 1994
    Journal Biological Psychiatry
    Excerpt

    Cognitive functions and psychopathology were assessed in 36 treatment-refractory schizophrenic patients before initiation of clozapine, and at 6 weeks and 6 months, thereafter. Before treatment, cognitive impairment was found in each measure of memory, attention, and executive function as compared with 26 normal controls. After both 6 weeks and 6 months of treatment, significant improvement occurred in the Controlled Oral Word Association Test, a measure of retrieval from reference memory. Improvement was also noted at 6 months in the Category Instance Generation Test, another measure of retrieval from reference memory, and in some, but not all, tests of executive function, attention, and recall memory. Clozapine treatment also resulted in significant improvement in Brief Psychiatric Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month assessment points. There was some evidence for a relationship between improvement in psychopathology and cognitive function. The improvement in cognitive function during clozapine treatment could have consequences for capacity to work and social function.

    Title Depression As a Confounding Variable in the Estimation of Habitual Sleep Time.
    Date October 1993
    Journal Journal of Clinical Psychology
    Excerpt

    Self-reported habitual sleep time is an important variable because short and long sleep times are associated with mortality. Speculation with regard to these results usually focuses on physical health, rather than psychological factors. We investigated the role of anxiety and depression in reports of habitual sleep times by examining the relative and absolute discrepancy between individuals' initial estimates of their sleep times and sleep diaries made over a 2-week period. Results indicated that depressed mood was associated not only with a tendency initially to underestimate length of sleep (relative discrepancy), but also to exaggerate reported sleep time regardless of direction (absolute discrepancy). These results imply that studies that examine relationships between reported sleep times and mortality should take mental health factors into account.

    Title A Limited, Low-dose Computed Tomography Protocol to Examine the Sacroiliac Joints.
    Date September 1993
    Journal Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes
    Excerpt

    Limited, low-dose, three-scan computed tomography (CT) was shown to be as accurate as a complete CT series in examining the sacroiliac joints and is suggested as an effective alternative to plain radiography as the primary means to detect sacroiliitis. The advantages include the brevity of the examination, a 2-fold to 4-fold reduction in radiation exposure relative to conventional radiography and a 20-fold to 30-fold reduction relative to a full CT series. The technique was developed from studies of anatomic specimens in which the articular surfaces were covered with a film of barium to show clearly the synovial surfaces and allow the choice of the most appropriate levels of section. From the anteroposterior scout view the following levels were defined: at the first sacral foramen, between the first and second sacral foramina and at the third sacral foramen. In the superior section a quarter of the sacroiliac joint is synovial, whereas in the inferior section the entire joint is synovial. The three representative cuts and the anteroposterior scout view are displayed on a single 14 x 17 in. (36 x 43 cm) film. Comparative images at various current strengths showed that at lower currents than conventionally used no diagnostic information was lost, despite a slight increase in noise. The referring physicians at the authors' institution prefer this protocol to the imaging routine previously used.

    Title A Study of the Problems Older Adults Encounter when Using a Mnemonic Technique.
    Date June 1993
    Journal International Psychogeriatrics / Ipa
    Excerpt

    This study explored problems older adults experience when using a mnemonic technique known as the method of loci. Older subjects received six hours of imagery, judgment, and relaxation pretraining followed by mnemonic training for either four or six hours (Regular or Extended training, respectively). At the end of training, subjects were given a list of the constituent steps of the method of loci and asked to indicate which, if any, were problematic. The factor structure of the relations among the problems varied according to the length of the training subjects received. Specifically, the factor structure of the difficulties reported by the Regular training group reflected problems with using the steps involved in the application of the method of loci, whereas for the Extended training group the factor structure reflected problems with abilities called upon in using the technique. Thus, even with Extended training, subjects may need additional pretraining to develop specific abilities necessary for the successful application of the mnemonic.

    Title Use of the Wrist Actigraph to Study Insomnia in Older Adults.
    Date April 1993
    Journal Sleep
    Excerpt

    Measures derived from the wrist actigraph have been found to correlate highly with EEG measures of normal sleep. Although the actigraph has been used to study normal sleep, few studies have used the actigraph as a measure of sleep of elderly insomniacs. The present study, which used elderly insomniacs, sought to investigate the sensitivity of the actigraph to detect the effects of an insomnia treatment. The actigraph was sufficiently sensitive to detect the effect of the sleep restriction therapy used on several sleep measures. Subsidiary analyses suggested that the sleep log, although not an accurate measure of sleep, may be useful as a measure of elderly insomniacs' subjective perception of sleep. Because the actigraph can be used more easily and less expensively than the polysomnogram, the actigraph appears to be a promising measure for assessing the efficacy of treatment interventions in elderly insomniacs.

    Title A Model of Ventilatory Instability Induced in the Unrestrained Rat.
    Date December 1992
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    A classic conditioning paradigm was used to examine the hypothesis that perturbations during sleep in the neonate rat can have a lasting impact on breathing. During the first 4 wk of life, stimuli were presented to rats during behaviorally defined sleep. In a conditioned hypoxic (CH) group, brief periods of hypoxic gas were used as the unconditioned stimulus. Tactile and auditory stimuli were used as the conditioned stimuli. In a conditioned control (CC) group, air was used as the unconditioned stimulus. A third group of unconditioned control (UC) rats was not exposed to the conditioning paradigm. Animals were provided routine care for 3.5 mo; ventilation was then assessed using plethysmography. Conditioning during neonatal life produced increased ventilatory irregularities and apnea during behaviorally defined sleep in adult rats. Both CH and CC rats showed a significantly greater number of apneic events compared with UC rats. Over a 2-h sleep period, CH rats exhibited a total of 105.1 +/- 9.4 (SE) apneic events, CC rats 69.4 +/- 4.2 events, and UC rats 42.1 +/- 3.1 events [F(2,18) = 25.568; P < 0.0001]. These findings suggest that experiences in the first few weeks of life will alter ventilatory patterning in the adult animal.

    Title Prognostic Significance of Ventricular Premature Depolarizations Measured 1 Year After Myocardial Infarction in Patients with Early Postinfarction Asymptomatic Ventricular Arrhythmia.
    Date August 1992
    Journal Journal of the American College of Cardiology
    Excerpt

    OBJECTIVES. The objective of this study was to examine the relation between death and the frequency of premature ventricular depolarizations measured approximately 1 year after myocardial infarction. BACKGROUND. The reported association between premature ventricular depolarizations and death in the weeks after myocardial infarction is in part the basis for the use of antiarrhythmic drugs. Such an association has not been reported on for observations obtained at a much greater interval after myocardial infarction. METHODS. We examined the association between mortality and premature ventricular depolarization rates measured 1 year after myocardial infarction in patients with asymptomatic ventricular arrhythmia early (between 6 and 90 days, median 28) after infarction, as measured by 24-h ambulatory electrocardiographic recording. The study group consisted of 502 patients enrolled in the Cardiac Arrhythmia Pilot Study during 1983 to 1985. They were followed up during the course of the study and subsequently by a National Death Index search (average follow-up interval 1,080 days). RESULTS. Death was recorded for 87 patients through 1987. Because patients were admitted to the Cardiac Arrhythmia Pilot Study only if they had greater than or equal to 10 ventricular premature depolarizations/h, the arrhythmia rate measured at baseline (that is, early after infarction) was not expected to, and did not, predict mortality. In 360 patients ventricular premature depolarization rates were measured approximately 1 year from their index myocardial infarction while they were not receiving antiarrhythmic therapy. In these patients, who had survived 1 year after the index infarction, the rate of ventricular premature depolarizations/h measured 1 year after infarction was highly predictive of subsequent death (p less than 0.001). Recent heart failure and a history of diabetes mellitus were also strongly predictive of death. CONCLUSION. The prognostic value of ventricular premature depolarizations observed 1 year after a myocardial infarction may be significant even in a sample selected for frequent ventricular premature depolarizations observed early after the event.

    Title Effects of Advancing Age on the Efficacy and Side Effects of Antiarrhythmic Drugs in Post-myocardial Infarction Patients with Ventricular Arrhythmias. The Cast Investigators.
    Date July 1992
    Journal Journal of the American Geriatrics Society
    Excerpt

    OBJECTIVE: To determine the effect of age on the response to anti-arrhythmic drugs. DESIGN: Randomized controlled trial comparing particular drugs. SETTING: Multi-institutional (The Cardiac Arrhythmia Suppression Trial, CAST). PARTICIPANTS: 2,371 patients, age less than 80, with ventricular arrhythmias after a recent myocardial infarction. Subjects classified by age as less than or equal to 55, 56-65, and 66-79 years. INTERVENTION: Upwardly titrated doses of encainide, flecainide or moricizine. After identification of a tolerated and effective dose of one of the drugs, participants were randomized to that drug and dose versus its placebo for up to 10 months. MAIN OUTCOME MEASURES: Efficacy of drug (suppression of ventricular premature depolarizations and/or non-sustained ventricular tachycardia), side effects and mortality. RESULTS: Older patients had more previous MIs, congestive heart failure (CHF), hypertension, NSVT, repolarization abnormalities, digitalis use, and diuretic use. They had less pathologic Q-waves or electrocardiographic injury pattern, and their left ventricular ejection fraction (LVEF) was lower. First dose VPD suppression with the first drug averaged 53% and is not associated with age (P = 0.29). Adverse events including death are more frequent in older patients taking study drugs (P less than 0.001). This trend is consistent in all three study drugs and at varying LVEFs. History of prior MI, low LVEF, VPD (in log scale), and digitalis therapy also correlates with adverse events (all P less than 0.05). Following adjustment for these factors, older age is an independent predictor of adverse events (relative risk 1.30 per decade of age, P less than 0.001). CONCLUSIONS: Older age increases the susceptibility to adverse cardiac events from a class of relatively toxic antiarrhythmic agents.

    Title Closing in on a Breast Cancer Gene on Chromosome 17q.
    Date July 1992
    Journal American Journal of Human Genetics
    Excerpt

    Linkage of early-onset familial breast and ovarian cancer to 11 markers on chromosome 17q12-q21 defines an 8-cM region which is very likely to include the disease gene BRCA 1. The most closely linked marker is D17S579, a highly informative CA repeat polymorphism. D17S579 has no recombinants with inherited breast or ovarian cancer in 79 informative meioses in the seven families with early-onset disease (lod score 9.12 at zero recombination). There is no evidence for linkage heterogeneity in the families with early-onset disease. The proportion of older-onset breast cancer attributable to BRCA 1 is not yet determinable, because both inherited and sporadic cases occur in older-onset families.

    Title Effect of the Serotonin Agonist, Mk-212, on Body Temperature in Schizophrenia.
    Date June 1992
    Journal Biological Psychiatry
    Excerpt

    The effects of 6-chloro-2-(1-piperaziny)pyrazine (MK-212), a centrally acting 5-HT1C/5-HT2 agonist, on body temperature and behavior were assessed using a single-blind cross-over design in 23 schizophrenic patients and 22 normal controls. Body temperature was assessed before drug administration and at 30-min intervals for 3 hr. Each subject was administered placebo or MK-212. MK-212 significantly elevated temperature in normal controls. There was no overall MK-212-induced increase in temperature compared to placebo in the schizophrenic patients; however, 13 of 23 (56.5%) patients had a larger increase in temperature after MK-212 than placebo, 3 of 23 (13.1%) had no change, whereas the temperature change after placebo was greater than after MK-212 in 7 of 23 (30.4%) patients. MK-212 produced significant increases in nausea, feeling strange, and arousal but these effects did not differ between groups. These results are consistent with decreased 5-HT2 receptor responsivity in some patients with schizophrenia.

    Title Proposed Factor Structure of the Geriatric Depression Scale.
    Date September 1991
    Journal International Psychogeriatrics / Ipa
    Excerpt

    The Geriatric Depression Scale (GDS) is commonly used to measure depression in the elderly. However, there have been no reports of the underlying structure of the GDS. To this end, the GDS was administered to 326 community-dwelling elderly subjects, and the data were subjected to a factor analysis. A five-factor solution was selected and, after a varimax rotation, the factors that emerged could be described as: (1) sad mood, (2) lack of energy, (3) positive mood, (4) agitation, and (5) social withdrawal. This solution accounted for 42.9% of the variance. Knowledge of the factor structure should aid both clinicians and researchers in the interpretation of responses on the GDS.

    Title Mortality and Morbidity in Patients Receiving Encainide, Flecainide, or Placebo. The Cardiac Arrhythmia Suppression Trial.
    Date April 1991
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND AND METHODS. In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo. RESULTS. Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty. CONCLUSIONS. There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

    Title A Preliminary Study Comparing Sleep Restriction and Relaxation Treatments for Insomnia in Older Adults.
    Date February 1991
    Journal Journal of Gerontology
    Excerpt

    This study compared Sleep Restriction Therapy (SRT) and Relaxation Therapy (RLT) as treatments for insomnia in a sample of community-residing elderly (mean age, 69.7 years). SRT subjects (n = 10) and RLT subjects (n = 12) reported information about their sleep twice daily to a telephone recording machine for 2 weeks of baseline, 4 weeks of treatment, and 2 weeks at 3-month follow-up. Results showed sleep latency and waking after sleep onset were significantly reduced for both treatment groups under active treatment. Predictable reductions in time in bed and improved sleep efficiency reported during active treatment by SRT subjects were still apparent at 3-month follow-up; no corresponding changes were found for RLT. In both groups, increased total sleep time was reported at follow-up; the improvement for SRT subjects was approximately twice that seen in RLT. These findings, at this early stage in the development of behavioral treatments for insomnia in older adults, encourage further study.

    Title Self-report Vs. Instrumental Measure in the Assessment of the Subjective Effects of D-amphetamine.
    Date December 1990
    Journal Psychopharmacology Bulletin
    Title Learning Mnemonics: Roles of Aging and Subtle Cognitive Impairment.
    Date May 1990
    Journal Psychology and Aging
    Excerpt

    Previously validated methods of memory training were used in conjunction with the Folstein Mini-Mental State Examination (MMSE) to explore the relationship between complexity of learned mnemonic, aging, and subtle cognitive impairment. Subjects were 218 community-dwelling elderly. Treatment included imagery mnemonics for remembering names and faces and lists. There was a significant interaction among age, type of learning task (face-name vs. list), and improvement when controlling for MMSE score. There was also a significant interaction among MMSE score, type of learning task, and improvement when controlling for age. Scores on the more complex list-learning mnemonic were more affected by age and MMSE scores than were scores on the face-name mnemonic. Implications of the findings for cognitive training of the old old and the impaired are discussed.

    Title Ct Appearance of an Oncocytic Papillary Cystadenoma of the Larynx.
    Date April 1990
    Journal Journal of Computer Assisted Tomography
    Excerpt

    The CT appearance of an oncocytic papillary cystadenoma of the right laryngeal false cord is presented. This unusual tumor of the larynx with similar CT appearance to that of a cyst of the laryngeal saccule is discussed.

    Title Glycopyrrolate Versus Atropine in Post-ect Amnesia in the Elderly.
    Date August 1989
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    The neurotransmitter acetylcholine is important in memory function, and low brain concentrations may be associated with cognitive impairment. Our hypothesis was that atropine, a centrally acting anticholinergic drug known to cause amnesia, confusion, and delirium, may further exacerbate the amnesia and/or confusion resulting from electroconvulsive therapy (ECT) when used as a preanesthetic, and that the peripherally acting glycopyrrolate would by comparison decrease these side effects. We randomly administered glycopyrrolate versus atropine in equivalent doses as the preanesthetic agent to 20 consecutively admitted geriatric patients with major depression, for whom ECT was the clinical treatment of choice. Patients were matched for age, Hamilton Scale for Depression, and baseline performance on the Buschke Selective Reminding Task (BSRT). We found no significant difference in outcome between patients treated prior to ECT with atropine versus glycopyrrolate, as assessed by the above measures. We conclude from this study that atropine is no more deleterious to memory than is glycopyrrolate when given before ECT.

    Title Benign Histiocytic Fibroma of Rib with Ct Correlation.
    Date May 1989
    Journal Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes
    Excerpt

    Benign fibrous histiocytoma is a benign tumor with fibroblastic and histiocytic differentiation, most commonly found in soft tissues and less frequently in adult bones. It is identical histologically to non-ossifying fibromas of childhood but differs in its clinical and radiological features. We here report a 26-year-old woman with benign histiocytic fibroma in a rare location, a rib, with computed tomographic correlation. Such correlation has not been reported previously.

    Title Closing of the Nurse-midwifery Service at Boston City Hospital. What Were the Issues Involved?
    Date May 1989
    Journal Journal of Nurse-midwifery
    Excerpt

    This article describes the experiences of 11 staff CNMs practicing in an inner-city hospital serving low-income women. A history of the conflicts between the OB/GYN Department and the Midwifery Service at Boston City Hospital is presented, as well as an overview of events in 1987-88 that resulted in the unanimous resignation of the staff CNMs and the closing of the service. Discussion of the issues is presented, as well as implications for midwifery practice.

    Title Basal Temporal Subdural Electrodes in the Evaluation of Patients with Intractable Epilepsy.
    Date April 1989
    Journal Epilepsia
    Excerpt

    In evaluation of patients with complex partial seizures who are candidates for surgical treatment, exact definition of the epileptogenic focus is essential for a good surgical outcome. We report a new technique which permits detailed mapping of the epileptogenic activity in the basal temporal lobe and the convexity of the temporal lobe. The technique consists of placement of at least 16 basal temporal electrodes and an additional 64 electrodes covering the temporal convexity. This extensive coverage permits accurate definition of the limits of the epileptogenic focus and also of adjacent functional areas and therefore allows more significant determination than have previous techniques of the ideal extent of the surgical resection. This accuracy cannot be achieved with depth electrodes or the limited coverage provided by previously reported epidural or subdural electrode techniques.

    Title Comparative Study of the Abuse Liability of Alprazolam, Lorazepam, Diazepam, Methaqualone, and Placebo.
    Date February 1989
    Journal The International Journal of the Addictions
    Excerpt

    Subjective effects of two benzodiazepines--alprazolam and lorazepam--were compared with two drugs of known abuse potential--diazepam and methaqualone--and placebo. This double-blind, crossover trial tested 30 casual recreational sedative users in a seminaturalistic setting. Methaqualone was more euphoriant and less sedative than the benzodiazepines. Diazepam and lorazepam were more euphoriant than placebo; alprazolam's euphoriant effect did not differ from these treatments. On other measures of abuse liability the benzodiazepines rated similarly, diazepam rating highest.

    Title Brain Computed Tomography in Morbid Obesity Before and After Gastric Restriction Surgery: a Prospective Quantitative Study.
    Date March 1988
    Journal Neuroradiology
    Excerpt

    Linear brain parameters were measured by CT in 19 patients with morbid obesity (mean weight 126.4 +/- 20.5 kg) and 20 age and sex matched normal weight subjects (mean weight 62.6 +/- 14.9 kg). Ventricular parameters were slightly smaller and cortical parameters were slightly larger in the preoperative obese than in control subjects. However, only the four cortical sulci ratio was significantly different in the two groups (P = 0.02). After gastric restriction surgery and drastic weight loss (mean postoperative weight 82.9 +/- 27.4 kg), all the ventricular and cortical parameters increased, with significant change in the frontal interhemispheric fissure ratio (P less than 0.05). Obese patients followed for 23 months after surgery had less striking changes than those followed for 6 months. Morbidly obese subjects have altered brain CT dimensions which are partly reversible after weight correction.

    Title Methionine and Iron As Growth Factors for Rat Embryos Cultured in Canine Serum.
    Date February 1988
    Journal The Journal of Experimental Zoology
    Excerpt

    Development of headfold-staged rat embryos cultured in canine serum containing various supplements was compared with development in rat serum to seek suitable alternatives to rat serum in rodent embryo culture and to identify nutritional factors for cultured rodent embryos that may have relevance for normal mammalian embryonic growth and development. Supplementation of canine serum with glucose, methionine, and a lipophilic iron chelate allowed growth and development of cultured rat embryos, approximating those obtained with rat serum. These findings suggest that properly supplemented canine serum can serve as a suitable rodent embryo culture medium and that glucose, iron, and methionine may be important nutrients in mammalian embryonic development.

    Title Effects of Puromycin on Rat Embryos in Vitro.
    Date May 1987
    Journal Experientia
    Excerpt

    Somite-staged rat embryos were exposed to varying concentrations of puromycin for 48 h in vitro. Medium concentrations below 0.92 microM had no significant effects, while concentrations above 1.84 microM were lethal. Between these extremes, there were concentration dependent increases in the incidence of malformations in a close relationship to growth retardation.

    Title Chronic Pancreatitis Presenting As Protracted Abdominal Pain in Infancy and Childhood.
    Date March 1987
    Journal South African Medical Journal = Suid-afrikaanse Tydskrif Vir Geneeskunde
    Title Prosthetic Fit in Below-knee Amputation: Evaluation with Xeroradiography.
    Date January 1987
    Journal Ajr. American Journal of Roentgenology
    Title Macromolecular Levels, Dna Synthesis and Ornithine Decarboxylase Activity in Leg Muscles from 6-mercaptopurine-treated Rats.
    Date January 1987
    Journal Toxicology and Industrial Health
    Excerpt

    Sprague-Dawley male and female rats were treated with 6-mercaptopurine (6-MP) (2 mg/kg sc) daily from 2 to 22 days of age and killed at 7, 15, 27 and 64 days of age. At 7 and 27 days of age rats were injected with 3H thymidine for measurement of DNA synthesis. Fore- and hindlimb muscles were removed and analyzed for ornithine decarboxylase (ODC) activity (all ages), DNA radioactivity (7 and 27 days), DNA level (27 and 64 days) and RNA level (64 days). As expected, ODC activity and DNA synthesis were higher in muscles of 7-day-old rats than in muscles of the older rats studied. A consistently lower ODC activity was seen in 6-MP-treated vs. control rats for 5-25 days after start of treatment, but the effect was essentially the same for the hindlimb and forelimb muscles. During the 7-27-day time course ODC activity was higher in hindlimb than forelimb muscles. By 27 days of age DNA synthesis was also higher in the hindlimb muscles. DNA synthesis was decreased after 5 days of treatment relative to that of control rats, to an approximately equal extent in forelimb and hindlimb muscles. Five days after the last treatment a trend was seen for slower recovery from inhibition of DNA synthesis in hindlimb muscles, particularly in male rats. DNA levels were reduced in treated rats relative to those in control rats 5 days after the last treatment to approximately the same degree in forelimb and hindlimb muscles. Forty-two days after the last treatment a trend toward increased activity of ODC and increased DNA and RNA levels was seen in muscles of treated rats, probably reflective of recovery processes. These early biochemical effects of 6-MP, which were seen to about the same extent in the forelimb and hindlimb muscles cannot explain by themselves the delayed hindlimb fat atrophy resulting from 6-MP treatment of neonatal rats.

    Title Weight Changes in Antidepressants: a Comparison of Amitriptyline and Trazodone.
    Date August 1986
    Journal Neuropsychobiology
    Excerpt

    Weight data taken from a 6-week randomized double-blind study comparing amitriptyline, trazodone and placebo were analyzed to determine differential weight changes between the two drugs. In 272 depressed outpatients doses were increased over a period of 4 days to reach a maximum level of 200 mg amitriptyline or 400 mg trazodone. After grouping the subjects according to initial weights (ideal, overweight, 20% above, and underweight, 20% below) mean changes were determined for each treatment. The results indicate that amitriptyline, which differed from placebo and trazodone, produced significantly higher weight gains in the ideal and overweight groups. Trazodone on the other hand produced a slight weight loss in the overweight group. Due to a low number of patients in the underweight group, the results were not significantly statistically. The antidepressant effects of both trazodone and amitriptyline were the same and no correlations between Hamilton scores and weight change were found.

    Title Hypoparathyroidism with Cerebral Calcification Extending Beyond the Extrapyramidal System. A Case Report.
    Date June 1984
    Journal South African Medical Journal = Suid-afrikaanse Tydskrif Vir Geneeskunde
    Excerpt

    Cerebral calcification extending beyond the extra-pyramidal system in post-surgical hypoparathyroidism is very rare. This report describes one such case; in addition to basal ganglia calcification there was gross calcification of the dentate nuclei, thalami, centrum semiovale and occipital lobes.

    Title Isolation and Identification of Dihydrocitrinone, a Urinary Metabolite of Citrinin in Rats.
    Date February 1984
    Journal Journal of Toxicology and Environmental Health
    Excerpt

    Dihydrocitrinone, 3,4-dihydro-6,8-dihydroxy-3,4,5-trimethylisocoumarin-7-carboxylic acid, was isolated and identified as a urinary metabolite after oral administration of citrinin to rats. Male and female Osborne-Mendel rats received 30 mg citrinin/kg body weight by oral intubation. The metabolite dihydrocitrinone was present in urine collected at 0-2, 2-4, 4-6, 6-8, and 8-24 h after treatment. Only unchanged citrinin was found in blood collected 24 h after administration of the compound. The metabolite had a blue fluorescence and the same Rf on thin-layer chromatography, the same retention time on reverse-phase high-pressure liquid chromatography, and the same mass spectrum as an authentic sample of dihydrocitrinone.

    Title Methodology for Assessing Agents That Suppress Methadone Withdrawal: a Study of Baclofen.
    Date December 1982
    Journal Nida Research Monograph
    Title Money and Health Messages As Incentives for Smoking Low Tar/nicotine Cigarettes: Changes in Consumption and Exhaled Carbon Monoxide.
    Date August 1982
    Journal British Journal of Addiction
    Title [radioactive Dacryocystography]
    Date May 1980
    Journal Harefuah
    Title Species Difference in the Binding of Aflatoxin B1 to Hepatic Macromolecules.
    Date May 1980
    Journal Toxicology and Applied Pharmacology
    Title Comparative Toxicity of Polychlorinated Biphenyl and Polybrominated Biphenyl in the Rat Liver: Light and Electron Microscopic Alterations After Subacute Dietary Exposure.
    Date February 1979
    Journal Journal of Environmental Pathology and Toxicology
    Excerpt

    The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in livers was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, or 500 ppm for 5 weeks and then sacrificed. The mean liver-body weight ratios of the 50 and 500 ppm groups were increased. Histopathologic examination of the livers revealed fatty degenerative change associated with both compounds. This change was more marked at 500 than at 50 ppm. Various sized lamellar cytoplasmic inclusions were detected in livers of animals fed 500 ppm of either compound. However, the inclusions were more numerous in the PBB-treated rats. Several animals fed 50 ppm PBB had a few inclusions. In rats that received 500 ppm PBB, hypertrophic degenerative hepatocytes were present around the central veins. On the periphery of this change there were occasionally multinucleated hepatocytes. Electron microscopic examination at a dose level of 5 ppm in both the PCB and PBB groups showed a slight proliferation of smooth endoplasmic reticulum (SER), a moderate increase of lipid droplets and some liposomes, and a marked proliferation of Golgi condensing vesicles containing lipoprotein particles. A decreased number of mitochondria and lysosomes was also observed. At 50 ppm, similar but more marked ultrastructural alterations were seen. In addition, an increased number of branched and cup-shaped profiles of mitochondria and a decreased number of Golgi condensing vesicles containing lipoprotein particles were observed. Concentric membranous cytoplasmic whorls were encountered only in the 50 ppm PBB-treated rats. At 500 ppm the number of mitochondria decreased in both groups. There was also a marked increase in the number of SER and liposomes concomitant with a decreased number of Golgi condensing vesicles containing lipoprotein granules. Membranous whorls were also present in the 500 ppm groups.

    Title Patient Compliance in Glaucoma.
    Date December 1977
    Journal The British Journal of Ophthalmology
    Excerpt

    Of a randomly selected sample of 40 patients with chronic simple glaucoma 11 were identified as having failed to comply adequately with medical advice. Noncompliers were more likely: to be men, to have had no other medical disorder but glaucoma, not to rank glaucoma as most troubling if they had another illness, to have experienced side effects from the treatment, and not to have appreciated the association between glaucoma and blindness. Detailed clinical study revealed that several interrelated psychosocial factors contributed to noncompliance.

    Title Capsule Size of Cryptococcus Neoformans: Control and Relationship to Virulence.
    Date August 1977
    Journal Infection and Immunity
    Excerpt

    Capsule size of five isolates of Cryptococcus neoformans was controlled by cultivation in media containing varying amounts of sugar. High concentrations of sugar (e.g., 16%) suppressed encapsulation whereas low concentrations (e.g., 1%) allowed maximal encapsulation. Suppression of capsule size was attributed at least in part to the increased osmolarity of the medium because a medium with low sugar concentration but having high osmolarity (by virtue of added sodium chloride) also produced cells having small capsules. The extent of control was more marked with certain of the isolates than with others. Mice were intravenously inoculated with cells of a single isolate cultivated so as to have either small or large capsules, and virulence was measured by comparing death rates. Results indicate that virulence after such an inoculation is a constant characteristic of an isolate and is not affected by size of the capsule of the cells in the inoculum.

    Title Factors Affecting Filamentation in Candida Albicans: Changes in Respiratory Activity of Candida Albicans During Filamentation.
    Date October 1975
    Journal Infection and Immunity
    Excerpt

    Glucose metabolism and respiration of Candida albicans were compared under conditions which permitted either maximal filamentous or maximal yeast growth. Changes in metabolism were monitored by comparing the quantities of ethanol produced, CO2 evolved, and oxygen consumed. Filamenting cultures produced more ethanol and less CO2 than yeasts, with oxygen consumption in the former concomitantly slower than that of the latter. Studies involving cofactors and inhibitors associated with electron transport imply that a transfer of electrons away from flavoprotein is required for maintenance of yeast morphology. Conditions consistent with a buildup of reduced flavoprotein, however, favored filament formation. These changes were expressed metabolically as a shift from an aerobic to a fermentative metabolism. The results presented are consistent with hypotheses correlating filament production with changes in carbohydrate metabolism and an interruption of electron transfer within the cell.

    Title Toxic Response of Rats to Cyclamates in Chow and Semisynthetic Diets.
    Date March 1973
    Journal Journal of the National Cancer Institute
    Title Acute Physiological Effects of Feeding Rats Non-urea-adducting Fatty Acids (urea-filtrate).
    Date April 1968
    Journal The Journal of Nutrition
    Title Chick Edema Factor: Some Tissue Distribution Data and Toxicologic Effects in the Rat and Chick.
    Date August 1966
    Journal Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (new York, N.y.)
    Title Cluster-impact Fusion Ii: Time-of-flight Experiments.
    Date
    Journal Physical Review Letters
    Title Assessment and Management of "sundowning" Phenomena.
    Date
    Journal Seminars in Clinical Neuropsychiatry
    Excerpt

    Approximately one quarter of patients with AD-type dementia reportedly exhibit disruptive, restless, and/or confused behavior that tends to be more apparent in late afternoon or early evening. Research has yet to document the phenomenon in a definitive manner to facilitate standardized assessment and clinical trials. Recent work attempting to define precisely the prevalence of abnormal behaviors during different periods of time of day in AD patients is reviewed. Caregiver reports of confusion and aggressive, disruptive behavior have been associated with going to bed early, increased use of sedative-hypnotics, and more severe cognitive impairment. Because there is evidence that the sleep of many AD patients is of poor quality, one might try to treat such patients with behavioral approaches useful in insomnia in other populations. Futhermore, as psychotropic medications can adversely affect sleep and/or have "hangover" effects on daytime cognition, one should carefully manage these medications to optimize care. Advances in assessment of sundowning, combined with longitudinal studies of sleep and circadian rhythm changes associated with dementia progression, should enhance efforts to treat behavioral and sleep disturbances.

    Title Test-retest and Between-site Reliability in a Multicenter Fmri Study.
    Date
    Journal Human Brain Mapping
    Excerpt

    In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

    Title Subclinical Anxiety Symptoms, Sleep, and Daytime Dysfunction in Older Adults with Primary Insomnia.
    Date
    Journal Journal of Geriatric Psychiatry and Neurology
    Excerpt

    Both insomnia complaints and anxiety disorders are common in older adults, and are associated with poor daytime functioning. The present study investigated whether subclinical levels of anxiety were associated with sleep disturbance and daytime functioning in older adults who met diagnostic criteria for primary insomnia, and therefore did not meet criteria for depression or an anxiety disorder. After adjustment for depressive symptoms, elevated state anxiety was associated with higher levels of wake after sleep onset (measured by both actigraphy and sleep log) and shorter sleep onset latency (measured by sleep log). Higher levels of trait anxiety were associated with greater wake after sleep onset (measured by sleep log). Elevated state and trait anxiety were associated with worse social functioning, and higher levels of trait anxiety were associated with worse role functioning. Thus, subclinical anxiety symptoms may be an important target for clinical intervention to improve sleep and functioning in older adults with primary insomnia.

    Title Guest Editorial: Overlap of Mild Tbi and Mental Health Conditions in Returning Oif/oef Service Members and Veterans.
    Date
    Journal Journal of Rehabilitation Research and Development
    Title Sleep-disordered Breathing in Vietnam Veterans with Posttraumatic Stress Disorder.
    Date
    Journal The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry
    Excerpt

    OBJECTIVE:: To study the prevalence of sleep-disordered breathing (SDB) in Vietnam-era veterans. METHODS:: This was an observational study of Vietnam-era veterans using unattended, overnight polysomnography, cognitive testing, and genetic measures. RESULTS:: A sample of 105 Vietnam-era veterans with posttraumatic stress disorder: 69% had an Apnea Hypopnea Index >10. Their mean body mass index was 31, "obese" by Centers for Disease Control and Prevention criteria, and body mass index was significantly associated with Apnea Hypopnea Index (Spearman r = 0.41, N = 97, p < 0.0001). No significant effects of sleep-disordered breathing or apolipoprotein status were found on an extensive battery of cognitive tests. CONCLUSION:: There is a relatively high prevalence of SDB in these patients which raises the question of to what degree excess cognitive loss in older PTSD patients may be due to a high prevalence of SDB.

    Title Reliability of the Ama Guides to the Evaluation of Permanent Impairment.
    Date
    Journal Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine
    Excerpt

    AMA's Guides to the Evaluation of Permanent Impairment is used to rate loss of function and determine compensation and ability to work after injury or illness; however, there are few studies that evaluate reliability or construct validity.

    Title A Large Multicenter Correlation Study of Thyroid Nodule Cytopathology and Histopathology.
    Date
    Journal Thyroid : Official Journal of the American Thyroid Association
    Excerpt

    Background: Fine-needle aspiration (FNA) biopsies are the cornerstone of preoperative evaluation of thyroid nodules, but FNA diagnostic performance has varied across different studies. In the course of collecting thyroid FNA specimens for the development of a molecular diagnostic test, local cytology and both local and expert panel surgical pathology results were reviewed. Methods: Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected from two academic centers. Cytology and corresponding local and expert panel surgical pathology results were compared to each other and to a meta-review of 11 recently published U.S.-based thyroid FNA studies. Results: FNA diagnostic performance was comparable between the study specimens and the meta-review. Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology indeterminate cases and 98% for cytology malignant cases, comparable to the figures found in the meta-review (34% and 97%, respectively). However, histopathology malignancy rates were higher for cytology benign cases in the prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta-review rates of 10% at community sites and 2% at academic centers, p < 0.0001). Resection rates for prospective clinic FNAs were also comparable to the meta-review for both cytology indeterminate cases (62% vs. 59%, respectively) and cytology malignant cases (82% vs. 81%, respectively). Surgical pathology categorical disagreement (benign vs. malignant diagnosis) was higher between local pathology and a consensus of the two expert panelists (11%) than between the two expert panelists both pre- (8%) and postconferral (3%). Conclusions: Although recent guidelines for FNA biopsy and interpretation have been published, the rates of false-positive and false-negative results remain a challenge. Two-thirds of cytology indeterminate cases were benign postoperatively and may decrease with the development of an accurate molecular diagnostic test. High disagreement rates between local and expert panel histopathology diagnosis suggests that central review for surgical diagnoses should be used when developing diagnostic tests based on resected thyroid specimens.

    Title Decreased Daytime Motor Activity Associated With Apathy in Alzheimer Disease: An Actigraphic Study.
    Date
    Journal The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry
    Excerpt

    OBJECTIVE:: Across all stages of Alzheimer disease (AD), apathy is the most common neuropsychiatric symptom. Studies using the Neuropsychiatric Inventory (NPI) have found that apathy is present in up to 70% of individuals with Alzheimer disease. One of the main difficulties in assessing apathy and other neuropsychiatric symptoms is the absence of reliable, objective measures. Motor activity assessment using ambulatory actigraphy could provide an indirect, objective evaluation of apathy. The aim of our study was to assess the relationship between apathy and daytime motor activity in AD, using ambulatory actigraphy. METHODS:: One hundred seven AD outpatients wore a wrist actigraph (Motionlogger) during seven consecutive 24-hour periods to evaluate motor activity. Participants were divided into two subgroups according to their apathy subscores on the NPI: individuals with apathy (NPI-apathy subscores >4) and those without. Daytime mean motor activity scores were compared between the two subgroups. RESULTS:: Individuals with AD who had symptoms of apathy (n = 43; age = 79 ± 4.7 years; Mini-Mental State Exam = 20.9 ± 4.8) had significantly lower daytime mean motor activity than AD patients without apathy (n = 64; age = 76.3 ± 7.7; Mini-Mental State Exam = 21.5 ± 4.7), while nighttime mean motor activity did not significantly differ between the two subgroups. CONCLUSIONS:: Ambulatory actigraphy could be added to currently used questionnaires as a simple, objective technique for assessing apathy in the routine assessment of AD patients.

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