Choroidal thickness in lupus nephritis.

OBJECTIVE: This study aimed to compare choroidal thickness between patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) in complete renal remission to that of patients with SLE without LN. METHODS: This was a retrospective case-control study of 23 SLE patients meeting either the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria and followed at Washington University School of Medicine Rheumatology or Nephrology, and Ophthalmology outpatient clinics. The diagnosis of LN was based on renal pathology, and complete renal remission was defined as proteinuria <500 mg/daily and serum creatinine at baseline. Extra-renal flare status was determined using modified Fortin criteria. Choroidal thickness was measured using spectral-domain optical coherence tomography and read by blinded reviewers. RESULTS: In SLE patients without extra-renal flare, choroidal thickness of LN patients was 281 ± 78 µm compared to 288 ± 70 µm in non-LN SLE patients (p = 0.766) at the fovea. CONCLUSION: Choroidal thickness was not different in patients with LN in remission compared to non-LN SLE patients in remission. Additional studies are needed to examine choroidal thickness in patients with SLE with active LN.

Investigation of Acidithiobacillus ferrooxidans in pure and mixed-species culture for bioleaching of Theisen sludge from former copper smelting.

AIMS: The aim of this study was to investigate the potential of bioleaching for the treatment of an environmentally hazardous waste, a blast-furnace flue dust designated Theisen sludge. METHODS AND RESULTS: Bioleaching of Theisen sludge was investigated at acidic conditions with Acidithiobacillus ferrooxidans in pure and mixed-species culture with Acidiphilium. In shaking-flask experiments, bioleaching parameters (pH, redox potential, zinc extraction from ZnS, ferrous- and ferric-iron concentration) were controlled regularly. The analysis of the dissolved metals showed that 70% zinc and 45% copper were extracted. Investigations regarding the arsenic and antimony species were performed. When iron ions were lacking, animonate (Sb(V)) and total arsenic concentration were highest in solution. The bioleaching approach was scaled up in stirred-tank bioreactors resulting in higher leaching efficiency of valuable trace elements. Concentrations of dissolved antimony were approx. 23 times, and of cobalt, germanium, and rhenium three times higher in comparison to shaking-flask experiments, when considering the difference in solid load of Theisen sludge. CONCLUSIONS: The extraction of base and trace metals from Theisen sludge, despite of its high content of heavy metals and organic compounds, was feasible with iron-oxidizing acidophilic bacteria. In stirred-tank bioreactors, the mixed-species culture performed better. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this study is the first providing an appropriate biological technology for the treatment of Theisen sludge to win valuable elements.

Effect of visual art on patient anxiety and agitation in a mental health facility and implications for the business case.

There is a growing body of evidence on the impact of the environment on health and well-being. This study focuses on the impact of visual artworks on the well-being of psychiatric patients in a multi-purpose lounge of an acute care psychiatric unit. Well-being was measured by the rate of pro re nata (PRN) medication issued by nurses in response to visible signs of patient anxiety and agitation. Nurses were interviewed to get qualitative feedback on the patient response. Findings revealed that the ratio of PRN/patient census was significantly lower on the days when a realistic nature photograph was displayed, compared to the control condition (no art) and abstract art. Nurses reported that some patients displayed agitated behaviour in response to the abstract image. This study makes a case for the impact of visual art on mental well-being. The research findings were also translated into the time and money invested on PRN incidents, and annual cost savings of almost $US30,000 a year was projected. This research makes a case that simple environmental interventions like visual art can save the hospital costs of medication, and staff and pharmacy time, by providing a visual distraction that can alleviate anxiety and agitation in patients.

Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs).

OBJECTIVE: Our purpose was to develop a geographically localized, multi-institution strategy for improving enrolment in a trial of secondary stroke prevention. METHODS: We invited 11 Connecticut hospitals to participate in a project named the Local Identification and Outreach Network (LION). Each hospital provided the names of patients with stroke or TIA, identified from electronic admission or discharge logs, to researchers at a central coordinating center. After obtaining permission from personal physicians, researchers contacted each patient to describe the study, screen for eligibility, and set up a home visit for consent. Researchers traveled throughout the state to enroll and follow participants. Outside the LION, investigators identified trial participants using conventional recruitment strategies. We compared recruitment success for the LION and other sites using data from January 1, 2005, through June 30, 2007. RESULTS: The average monthly randomization rate from the LION was 4.0 participants, compared with 0.46 at 104 other Insulin Resistance Intervention after Stroke (IRIS) sites. The LION randomized on average 1.52/1,000 beds/month, compared with 0.76/1,000 beds/month at other IRIS sites (p = 0.03). The average cost to randomize and follow one participant was $8,697 for the LION, compared with $7,198 for other sites. CONCLUSION: A geographically based network of institutions, served by a central coordinating center, randomized substantially more patients per month compared with sites outside of the network. The high enrollment rate was a result of surveillance at multiple institutions and greater productivity at each institution. Although the cost per patient was higher for the network, compared with nonnetwork sites, cost savings could result from more rapid completion of research.

Apolipoprotein E genotype and memory in the sixth decade of life.

BACKGROUND: Virtually all adult studies of APOE genotypes and cognition have included individuals over 60. In older adults, epsilon 4 carriers may manifest greater cognitive asymmetries than non-epsilon 4 carriers even in the absence of overall mean differences. General cognitive ability may also be affected by aging and APOE genotype, but most studies have inadequately addressed this potential confound. The goals of this study were to examine, in middle age, the relationship of APOE genotype with episodic memory and verbal-visuospatial episodic memory asymmetries, after accounting for prior general cognitive ability. METHOD: We compared epsilon 4+ and epsilon 4- individuals in 626 male twins in their 50s. We examined verbal and visuospatial episodic memory and verbal-visual asymmetry scores after adjusting for cognitive ability at age 20. Analyses corrected for correlations between twin pair members. RESULTS: Compared with epsilon 4- individuals, epsilon 4 carriers performed significantly more poorly on verbal, but not visuospatial memory, manifested significantly greater cognitive asymmetry, and also had significantly more concerns about memory. At age 20, epsilon 4 carriers had higher general cognitive ability than epsilon 4- individuals, and current memory differences were enhanced after adjusting for age 20 cognitive ability. CONCLUSIONS: Small, but significant, APOE-epsilon 4-related memory deficits appear in the sixth decade of life in individuals who show no signs of preclinical dementia. The results partially support studies of older adults that suggest that increased cognitive asymmetries reflect risk for dementia and are associated with the APOE-epsilon 4 genotype. The results also highlight the potential problems of not having accurate data on prior cognitive ability.

Psychometric properties of the BASIS-24© (Behaviour and Symptom Identification Scale-Revised) Mental Health Outcome Measure.

Objective. Outcome measurement in mental health services is an area of considerable clinical interest and policy priority. This study sought to assess the Behaviour and Symptom Identification Scale-24 (BASIS-24©), a brief, patient self-reported measure of psychopathology and functioning, in a UK sample, including establishing population norms for comparative purposes. Methods. Participants were 588 adults recruited from psychiatric inpatient, outpatient and primary care settings; and 630 adults randomly sampled from primary care lists who completed the BASIS-24©, and the Brief Symptom Inventory (BSI) at two time points. Results. BASIS-24© demonstrated adequate reliability (coefficient α values for combined clinical sample across subscales ranged from 0.75 to 0.91), validity and responsiveness to change (effect size for change of the BASIS-24© was 0.56 compared with 0.48 for BSI Global Severity Index). Population norms were established for the general population and adult in-patients (at in-take). The scale proved straightforward to complete across clinical settings. Variable rates of questionnaire distribution across clinical settings highlighted the ongoing challenge of incorporating outcome measures in clinical settings. Conclusion. BASIS-24© is a brief, easily administered, self-complete measure of mental well-being and functioning that adequately meets the requirements of reliability, validity and responsiveness to change required of an outcome measure.

Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation.

The relative potencies of cholecystokinin (CCK)-8 and CCK-33 for decreasing meal size depend on the route of administration. Inhibitory potencies are equal after intraperitoneal administration, but CCK-33 is significantly more potent after intraportal administration. This suggests that CCK-33 is a more effective stimulant of hepatic afferent vagal nerves than is CCK-8. To investigate this possibility, we administered both peptides intraperitoneally in rats with abdominal vagotomies that spared only the hepatic proper vagal nerves (H) and in rats with abdominal vagotomies that spared the common hepatic branch that contains the fibers of the hepatic proper and gastroduodenal nerves (HGD). The vagal afferent innervation in H and HGD rats was verified with a wheat germ agglutinin-horseradish tracer strategy. Intraperitoneal administration of CCK-33 decreased 30-min intake of 10% sucrose in H rats as much as in sham rats, but CCK-8 decreased intake significantly less in H rats than in sham rats. The larger inhibitory effect of CCK-33 than of CCK-8 in H rats is consistent with the hypothesis that CCK-33 is a more effective stimulant of the hepatic proper vagal afferent nerves than CCK-8. In contrast to the results in H rats, the inhibitory potencies of both peptides were significantly and equivalently reduced in HGD rats compared with sham rats. This suggests that there is an inhibitory interaction between the stimulation of the gastroduodenal and hepatic proper afferent fibers by CCK-33.

Cardiac magnetic resonance imaging abnormalities in systemic lupus erythematosus: a preliminary report.

The purpose of this prospective, pilot study was to determine whether differences in myocardial T2 relaxivity can be identified among active systemic lupus erythematosus (SLE) patients with clinically suspected SLE myocarditis, other active SLE patients, inactive SLE patients and age and gender matched controls. Eleven consecutive female patients (six with active SLE and five with inactive SLE), and five age, gender and race matched healthy controls underwent imaging with echocardiography and cardiac magnetic resonance imaging (MRI). Echocardiographic measurements included left ventricular end diastolic (LVEDV) and end systolic volumes (LVESV), and mass (LVM) (all indexed to body mass); ejection fraction and cardiac output. The cardiac MRI measurement was the T2 relaxation time (an index of soft tissue signal, with higher levels suggestive of increased tissue water content). Patients with active SLE had significantly higher LVEDV and LVM than inactive SLE patients and healthy controls, and significantly larger LVESV than healthy controls. Myocardial T2 relaxation times were significantly higher in patients with active SLE compared to those with inactive SLE and to healthy controls, and remained higher even after excluding the two active SLE patients who had clinical myocarditis. The four active SLE patients who underwent repeat cardiac imaging studies after clinical improvement showed normalization of these myocardial abnormalities. The conclusion was that active SLE patients demonstrate abnormalities in myocardial structure manifested by high myocardial T2 relaxation times that normalized after clinical improvement in disease activity. These findings suggest that T2 relaxation values are a sensitive indicator of myocardial disease in patients with SLE and that myocardial T2 relaxation abnormality frequently occur in patients with active SLE, even in the absence of myocardial involvement by clinical criteria.

Clinical and laboratory assessment of distal peripheral nerves in Gulf War veterans and spouses.

BACKGROUND: The prevalence of symptoms suggesting distal symmetric polyneuropathy (DSP) was reported to be higher among deployed veterans (DV) to the Persian Gulf in 1990-1991 than to control non-deployed veterans (NDV). The authors therefore compared the prevalence of DSP by direct examination of DV and their spouses to control NDV and spouses. METHODS: The authors performed standardized neurologic examinations on 1,061 DV and 1,128 NDV selected from a cohort of veterans who previously participated in a national mail and telephone survey. Presence of DSP was evaluated by history, physical examination, and standardized electrophysiologic assessment of motor and sensory nerves. Similar examinations were performed without electrophysiologic tests in 484 DV spouses and 533 NDV spouses. Statistical analyses were performed with appropriate adjustments for the stratified sampling scheme. RESULTS: No differences between adjusted population prevalence of DSP in DV and NDV were found by electrophysiology (3.7% vs 6.3%, p = 0.07), by neurologic examination (3.1% vs 2.6%, p = 0.60), or by the methods combined (6.3% vs 7.3%, p = 0.47). Excluding veterans with non-military service related diseases that may cause DSP did not alter outcomes. DV potentially exposed to neurotoxins from the Khamisiyah ammunition depot explosion did not significantly differ in DSP prevalence compared to non-exposed DV. The prevalence of DSP in DV spouses did not differ from NDV spouses (2.7% vs 3.2%, p = 0.64). CONCLUSIONS: Neither veterans deployed during the Gulf War era nor their spouses had a higher prevalence of DSP compared to NDV and spouses.

Neuropsychological consequences of regular marijuana use: a twin study.

BACKGROUND: Results of previous research examining long-term residual effects of marijuana use on cognition are conflicting. A major methodological limitation of prior studies is the inability to determine whether differences between users and non-users are due to differences in genetic vulnerability preceding drug use or due to the effects of the drug. METHOD: Fifty-four monozygotic male twin pairs, discordant for regular marijuana use in which neither twin used any other illicit drug regularly, were recruited from the Vietnam Era Twin Registry. A minimum of 1 year had passed since the marijuana-using twins had last used the drug, and a mean of almost 20 years had passed since the last time marijuana had been used regularly. Twins were administered a comprehensive neuropsychological test battery to assess general intelligence, executive functioning, attention, memory and motor skills. Differences in performance between marijuana-using twins and their non-using co-twins were compared using a multivariate analysis of specific cognitive domains and univariate analyses of individual test scores. Dose response relationships were explored within the marijuana-using group. RESULTS: Marijuana-using twins significantly differed from their non-using co-twins on the general intelligence domain; however, within that domain only the performance of the block design subtest of the Wechsler Adult Intelligence Scale--Revised reached a level of statistical significance. CONCLUSIONS: Out of the numerous measures that were administered, only one significant difference was noted between marijuana-using twins and their non-using co-twins on cognitive functioning. The results indicate an absence of marked long-term residual effects of marijuana use on cognitive abilities.

Will pharmacogenetics allow better prediction of methotrexate toxicity and efficacy in patients with rheumatoid arthritis?

Methotrexate (MTX) remains the most commonly used disease modifying antirheumatic drug in rheumatoid arthritis (RA) because of its cost and experience in its use, despite the availability of new treatments such as leflunomide and the biological agents. However, a significant number of patients with RA either do not benefit from the drug or are unable to tolerate it. Pharmacogenetic approaches may help optimise treatment with MTX, and also other agents, in RA.

A twin study of genetic and environmental influences on suicidality in men.

BACKGROUND: Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders. METHODS: Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors. RESULTS: The prevalence of suicidal ideation and suicide attempt were 16.1% and 2.4% respectively. In a multinomial regression model, co-twin's suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin's suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects. CONCLUSIONS: There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.

A twin study of generalized anxiety disorder symptoms, panic disorder symptoms and post-traumatic stress disorder in men.

Generalized anxiety disorder (GAD), panic disorder (PD) and post-traumatic stress disorder (PTSD) often co-occur. We investigated whether and to what degree genetic and environmental contributions overlap among symptoms of GAD, symptoms of PD and PTSD. Subjects were 3327 monozygotic and dizygotic male-male twin pair members of the Vietnam Era Twin Registry who participated in a 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD. The liability for GAD symptoms was due to a 37.9% additive genetic contribution common to PD symptoms and PTSD. Liability for PD symptoms was due to a 20.7% additive genetic contribution common to GAD symptoms and PTSD, and a 20.1% additive genetic influence specific to PD symptoms. Additive genetic influences common to symptoms of GAD and PD accounted for 21.3% of the genetic variance in PTSD. Additive genetic influences specific to PTSD accounted for 13.6% of the genetic variance in PTSD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that these disorders each have etiologically distinct components and also have significant genetic and unique environmental contributions in common.

Gastric negative feedback produced by volume and nutrient during a meal in rats.

To investigate the gastric negative-feedback control of eating during a meal, we implanted male rats with pyloric cuffs and gastric catheters and gave them access to sweet milk for 30 min after overnight deprivation. Ingested milk and infused milk or saline were confined to the stomach because the pyloric cuffs were closed in all tests. Rats received five consecutive tests with no gastric infusion or with infusions of 3, 6, or 12 ml of milk or saline during the first 6 min of the test meal. Only 12-ml infusions decreased intake significantly compared with no infusion. Because 12 ml of saline inhibited intake as much as 12 ml of milk, the decreased intake was due to volume or rate of infusion, not nutrient. Although infusions of 3 and 6 ml of milk did not decrease intake, they decreased the number of licks after the infusions significantly more than equal volumes of saline. Thus a large volume or rapid rate of gastric infusion decreases intake, and some other aspect of small milk infusions decreases the rate of licking.

Toward a national consumer survey: evaluation of the CABHS and MHSIP instruments.

This article describes a study evaluating the Consumer Assessment of Behavioral Health Survey (CABHS) and the Mental Health Statistics Improvement Program (MHSIP) surveys. The purpose of the study was to provide data that could be used to develop recommendations for an improved instrument. Subjects were 3,443 adults in six behavioral health plans. The surveys did not differ significantly in response rate or consumer burden. Both surveys reliably assessed access to treatment and aspects of appropriateness and quality. The CABHS survey reliably assessed features of the insurance plan; the MHSIP survey reliably assessed treatment outcome. Analyses of comparable items suggested which survey items had greater validity. Results are discussed in terms of consistency with earlier research using these and other consumer surveys. Implications and recommendations for survey development, quality improvement, and national policy initiatives to evaluate health plan performance are presented.

Genetic and environmental influences on the relationship among combat exposure, posttraumatic stress disorder symptoms, and alcohol use.

The role of genetic and environmental influences on the relationship between combat exposure, posttraumatic stress disorder (PTSD) symptoms, and alcohol use were examined in 4072 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975). Results indicate that the relationship between combat and alcohol use and between PTSD symptom factors and alcohol use were both substantially influenced by genetic factors. Findings are most consistent with a shared vulnerability model for the etiology of the association between PTSD symptoms and alcohol use. Specific unique environmental factors were more important than genetic factors for PTSD symptoms, and both factors were equally important for alcohol use. Further support is also found for the role of the unique environment in PTSD symptoms.

The genetics of pathological gambling.

Problem and pathological gambling (PG) occurs in about 5% of Americans. Gambling is associated with substantial psychosocial and psychiatric health problems, and the increasing ease of access to gambling may increase its future prevalence. Therefore, it is important to gain greater insight into the causes of PG. Family studies of PG are consistent with a substantial familial impact on vulnerability to PG. However, family studies cannot distinguish genetic from family environmental influences. By contrast, the study of twin pairs permits the genetic and environmental influences on PG to be estimated. The study of gambling behavior among 3,359 twin pair members of the Vietnam Era Twin Registry suggests that: (1) inherited factors explain a substantial proportion of the variance in the report of symptoms of gambling; (2) there is a single continuum of genetic vulnerability that underlies gambling problems of varying severities; and, (3) the co-occurrence of PG with conduct disorder, antisocial personality disorder, and alcohol abuse/dependence is partially explained by genes that influence both PG and these other psychiatric disorders. Neurophysiological correlates of gambling problems and genetically based differences in neurotransmitter systems may provide biological mechanisms that explain the genetic basis for a predisposition to PG.

A twin study of the association between pathological gambling and antisocial personality disorder.

Many individuals with a history of pathological gambling (PG) also have a history of engaging in antisocial behaviors, and this has often been interpreted as a result of the former causing the latter. In a sample of 7,869 men in 4,497 twin pairs from the Vietnam Era Twin Registry, the authors examined (a) the association between PG and antisocial personality disorder (ASPD), (b) the extent to which PG might be differentially associated with childhood conduct disorder (CD) and adult antisocial behavior (AAB), and (c) the contribution of genetic and environmental factors to the association of PG with ASPD, CD, and AAB. PG was significantly associated with all 3 antisocial behavior disorders, and the association of PG with ASPD, CD, and AAB was predominantly explained by genetic factors. The results of this study suggest that the greater-than-chance co-occurrence of PG and antisocial behavior disorders is partially due to their sharing a common genetic vulnerability. The antisocial behavior observed among many individuals with PG probably cannot be interpreted as being simply a consequence of the PG.