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Body mass index and functioning in long-term schizophrenia. Results of the DSP project.

OBJECTIVE: The study evaluates the association of body mass index (BMI) with functioning in male and female patients with long-term schizophrenia. METHOD: 722 long-term schizophrenia patients were interviewed three years after discharge from hospital. Their weight and height were recorded and data on their background, illness history, psychosocial functioning (Global Assessment Scale; GAS), health behaviour, daily doses of neuroleptics, and psychiatric symptoms were collected. RESULTS: BMI correlated significantly with GAS scores in male (r=0.202, p=0.000) but not in female patients. In male patients, BMI associated significantly (p=0.005) with GAS scores even when the effects of psychiatric symptoms and other confounding variables were taken into account. CONCLUSIONS: In male but not in female long-term patients with schizophrenia, low BMI associates with poor functioning. It is suggested that among male schizophrenia patients, low BMI may be an indicator of poor functioning.

Adult↗

Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates.

OBJECTIVE: Neuropsychological impairments are well documented in schizophrenia and are important targets of treatment. Information about the severity and pattern of deficits after treatment for the first psychotic episode and about relationships between these deficits and syndromal characteristics remains limited. METHOD: Comprehensive neuropsychological assessments including 41 individual tests were given to 94 patients with first-episode schizophrenia after initial stabilization of psychosis and to a comparison group of 36 healthy volunteers. Profiles of neuropsychological deficits and the relationship of deficits to sex and handedness were examined. Correlations of neuropsychological deficit with a broad range of historical and clinical characteristics, including outcome, were explored. RESULTS: Patients had a large generalized neuropsychological deficit (1.5 standard deviations compared to healthy volunteers). Patients also had, superimposed on the generalized deficit, subtle relative deficits (less than 0.5 standard deviation compared to their own average profile) in memory and executive functions. Learning/memory dysfunction best distinguished patients from healthy individuals; after accounting for this difference, only motor deficits further distinguished the groups. Patients with higher neuropsychological ability had only memory deficits, and patients with lower ability had both memory and executive deficits. No sex differences were observed beyond the normal advantage for men in motor speed. Dextral patients had less severe generalized deficit. Severity of residual symptoms was associated with greater generalized deficit. Executive and attentional deficits were most linked to global functional impairment and poor outcome. CONCLUSIONS: The results document a large generalized deficit, and more subtle differential deficits, in clinically stabilized first-episode patients. Learning/memory deficits were observed even in patients with less severe generalized deficit, but the pattern was unlike the amnestic syndrome and probably reflects different mechanisms. Executive and attentional deficits marked the more severely disabled patients, and may portend relatively poor outcome. Failure to develop typical patterns of cerebral dominance may increase the risk for greater generalized deficit.

Adult↗

[Assessment of global left ventricular function with multi-slice spiral computed tomography].

OBJECTIVE: To investigate the value of multi-slice spiral computed tomography (MSCT) in the determination of global left ventricular function. METHODS: Twenty-nine patients with confirmed or suspected coronary heart diseases were imaged with a contrast-enhanced retrospective electrocardiogram (ECG) -gated technique on a 64-slice spiral CT scanner. The data sets were reconstructed at both end-diastolic and end-systolic phases in order to measure left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF). The results were compared with corresponding values obtained from conventional left ventriculography (LVG). RESULTS: LVEDV, LVESV, LVSV, and LVEF obtained with 64-slice spiral CT were significantly correlated with the LVG data (r = 0. 887-0.956, P < 0.001). According to the Bland-Altman approach, the mean differences for LVEDV, LVESV, LVSV, and LVEF were -2.3 ml, 4.1 ml, -6.4 ml, and - 3.5%, respectively. The limits of agreement for LVEDV, LVESV, LVSV, and LVEF were -27.2-22.4 ml, -10.2-18.4 ml, -26.4-13.6 ml, and -9.8%-3.0%, respectively. CONCLUSION: MSCT has clinically acceptable agreement with LVG for the quantification of global left ventricular function.

Adult↗

A biomechanical analysis of rotator cuff deficiency in a cadaveric model.

We conducted this cadaveric study to define a biomechanical rationale for rotator cuff function in several deficiency states. A dynamic shoulder testing apparatus was used to examine change in middle deltoid muscle force and humeral translation associated with simulated rotator cuff tendon paralyses and various sizes of rotator cuff tears. Supraspinatus paralysis resulted in a significant increase (101%) in the middle deltoid force required to initiate abduction. This increase diminished to only 12% for full glenohumeral abduction. The glenohumeral joint maintained ball-and-socket kinematics during glenohumeral abduction in the scapular plane with an intact rotator cuff. No significant alterations in humeral translation occurred with a simulated supraspinatus paralysis, nor with 1-, 3-, and 5-cm rotator cuff tears, provided the infraspinatus tendon was functional. Global tears resulted in an inability to elevate beyond 25 degrees of glenohumeral abduction despite a threefold increase in middle deltoid force. These results validated the importance of the supraspinatus tendon during the initiation of abduction. Glenohumeral joint motion was not affected when the "transverse force couple" (subscapularis, infraspinatus, and teres minor tendons) remained intact. Significant changes in glenohumeral joint motion occurred only if paralysis or anatomic deficiency violated this force couple. Finally, this model confirmed that rotator cuff disease treatment must address function in addition to anatomy.

Aged↗

Molecular basis for Golgi maintenance and biogenesis.

The Golgi apparatus contains thousands of different types of integral and peripheral membrane proteins, perhaps more than any other intracellular organelle. To understand these proteins' roles in Golgi function and in broader cellular processes, it is useful to categorize them according to their contribution to Golgi creation and maintenance. This is because all of the Golgi's functions derive from its ability to maintain steady-state pools of particular proteins and lipids, which in turn relies on the Golgi's dynamic character - that is, its ongoing state of transformation and outgrowth from the endoplasmic reticulum. Here, we categorize the expanding list of Golgi-associated proteins on the basis of their role in Golgi reformation after the Golgi has been disassembled. Information gained on how different proteins participate in this process can provide important insights for understanding the Golgi's global functions within cells.

ADP-Ribosylation Factor 1↗

Risperidone in children with autism: randomized, placebo-controlled, double-blind study.

Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism. We aimed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior (aggressiveness, hyperactivity, irritability), social and emotional responsiveness, and communication skills. We conducted a randomized, double-blind, placebo-controlled trial with 40 consecutive children with autism, whose ages ranged from 2 to 9 years, who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months. Autism symptoms were monitored periodically. The outcome variables were total scores on the Childhood Autism Rating Scale (CARS) and the Children's Global Assessment Scale (CGAS) after 6 months. Of the 40 children enrolled, 39 completed the trial over a period of 18 months; 19 received risperidone, and 20 received placebo. In the risperidone group, 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children's Global Assessment Scale score in the placebo group (P < .001 and P = .035, respectively). Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression. Risperidone was associated with increased appetite and a mild weight gain, mild sedation in 20%, and transient dyskinesias in three children. Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated.

Autistic Disorder↗

What is the rationale for new treatment strategies in Alzheimer's disease?

Alzheimer's disease (AD) is characterized by the abnormal extracellular accumulation of amyloid beta-peptide (Abeta) into neuritic plaques and the intraneuronal aggregation of the microtubule-associated protein tau to form neurofibrillary tangles. These molecular events are implicated in the selective damage to neural systems critical for the brain functions that are impaired in AD. Impairment of cholinergic neurotransmission may be an important factor underlying the defects in cognition and memory that characterize AD. Cholinesterase (ChE) inhibitors, such as donepezil, rivastigmine, and galantamine, cause symptomatic improvement by inhibiting the breakdown of the neurotransmitter acetylcholine to increase its synaptic availability and, in the case of galantamine, by also allosterically potentiating nicotinic cholinergic receptors. Other agents, including vitamin E, monoamine oxidase inhibitors, and statins, have shown some benefit in epidemiological studies and clinical trials although compelling evidence of their efficacy is lacking. Memantine, shown to cause cognitive and functional improvement, is not an ChE inhibitor and does not interact with marketed ChE inhibitors. While the mechanism of action of memantine in AD is not known, the principal pharmacologic actions at therapeutic dose are inhibition of ionotropic neurotransmitter receptors, specifically N-methyl-D-aspartate (NMDA), 5-HT3, and nicotinic receptors. Like other NMDA antagonists, memantine causes behavioral activation associated with enhanced cerebral glucose utilization. Studies have shown that memantine can reverse the decreased metabolic activity associated with AD, possibly accounting for its beneficial effects on cognition and global functioning. Memantine also has neuroprotective properties and can inhibit Abeta-induced neurodegeneration.

Acetylcholine↗

[Factors associated with peritoneal dialysis catheter failure in chronic renal insufficiency].

AIM: To determine the frequency, time of occurrence and factors associated with the failure of the permanent peritoneal catheter during dialysis in cases of chronic renal failure (CRF). MATERIAL AND METHODS: A retrospective cohort under a nested case control design was studied at a second level health care unit of the Instituto Mexicano del Seguro Social. A total of 149 catheters, double cushion straight Tenckhoff type, were evaluated in 74 patients with CRF due to diabetic nephropathy in 36/74 patients (49%). Information concerning functionality time and causes of catheter failure as well as the clinical and technical factors concerning insertion were obtained from the clinical chart. RESULTS: The cumulated time of dialysis was 814 months. Catheter failure occurred in 101 cases (68%): 67 due to obstruction, 24 due to infection, to leakage in 6 and to other causes in 4. Those of non-infectious origin were more frequent (p < 0.01). In the first month post-insertion there was a higher number of failures than after one month, (p < 0.0005). The global functionality of the catheter at one month, one and two years was 55%, 31% and 16%, respectively. There was a greater permanence of the catheters in continuous ambulatory peritoneal dialysis than in intermittent peritoneal dialysis (p = 0.02). CONCLUSIONS: It is concluded that the frequency of the peritoneal catheter failure was high; that the most frequent cause was due to non-infectious complications during the first month of insertion; and the factor associated to catheter failure was intermittent peritoneal dialysis as compared to continuous ambulatory dialysis.

Adult↗

Gated SPET myocardial perfusion acquisition within 5 minutes using focussing collimators and a three-head gamma camera.

Short acquisition protocols for gated single-photon emission tomography (SPET) myocardial perfusion imaging are desirable for sequential imaging to evaluate the myocardial response during pharmacological intervention. In this study a less than 5 min gated SPET acquisition protocol is proposed. Perfusion characteristics (defect severity) and left ventricular ejection fraction (LVEF), end-diastolic and end-systolic volumes (EDV, ESV), wall motion (WM) and wall thickening (WT) were calculated, checked for reproducibility and compared with data obtained using a standard gated SPET acquisition protocol. Gated SPET images were recorded in 20 patients starting 60 min after the administration of 925 MBq technetium-99m tetrofosmin at rest. The 5 min gated SPET studies were acquired with a three-head camera equipped with Cardiofocal collimators. This protocol was repeated twice. In addition gated SPET studies were acquired according to a standard protocol using parallel-hole collimators. The severity of perfusion defects was quantified on polar maps using the non-gated image data and a normal database. LVEF, EDV, ESV, WM and WT were calculated from the gated images. The agreement between 5-min and standard gated SPET acquisitions was excellent for all investigated parameters. The reproducibility of repeated 5-min acquisitions for the quantification of perfusion defect severity was excellent (r=0.97). The agreement for segmental WT scores between repeated 5-min gated SPET acquisitions was good: kappa=0.71; major differences in segmental classification were observed in 2.5%. For WM a good agreement was found for segments with a tracer uptake >/=30% of the maximum: kappa=0.65, major differences =7.7%. Excellent reproducibility was found for LVEF, EDV and ESV measurements: r=0.97, 0.99 and 0.99, respectively. It is concluded that fast gated SPET perfusion studies acquired in less than 5 min yield accurate and reproducible measurements of myocardial perfusion and function (global and regional). In addition the results obtained with the 5-min gated SPET protocol correlate well with those obtained using a standard acquisition protocol.

Coronary Disease↗

Alterations of visual contrast sensitivity in Parkinson's disease.

Contrast sensitivity functions were determined in a population of 18 patients suffering from Parkinson's disease, and compared with the data obtained in an age-matched group of healthy controls. The controls were more sensitive at all spatial frequencies tested than the patients. The statistical comparisons were highly significant, indicating general differences between the PD patients and the controls not related to individual spatial frequency channels. When comparing the sensitivity loss between low and high spatial frequencies no significant differences were found suggesting that the decrease in contrast sensitivity is a global effect. We controlled for effects of age and cerebral atrophy, and our findings cannot be accounted for by these factors. In addition, the amount of contrast sensitivity loss was not correlated with the severity of the disease. These global functional alterations appear to be related to the reduction of dopamine at various sites of the visual system.

Adult↗

Management of cognition and function: new results from the clinical trials programme of Aricept(R) (donepezil HCl).

Ideally, treatment for Alzheimer's disease (AD) should prevent or cure the disease. Unfortunately, these goals appear unobtainable in the foreseeable future. Nevertheless, symptomatic relief is a feasible treatment option for AD patients and is available currently in the form of cholinesterase inhibitors such as tacrine, donepezil, metrifonate and rivastigmine. Donepezil is a second-generation, piperidine-class, selective and reversible acetylcholinesterase inhibitor. Four double-blind, placebo-controlled clinical trials of donepezil, involving over 1900 individuals with mild to moderate AD, have been published recently. In all trials, significant improvements in cognition were observed consistently for both therapeutic doses of donepezil (5 and 10 mg/d), relative to placebo. Similar donepezil-associated benefits were reported for global functioning. In addition, in one 24-wk, multinational clinical trial, patients receiving donepezil (10 mg/d) performed better than placebo-treated patients in their ability to perform complex daily functioning tasks. Donepezil was well tolerated in all trials, with approx. 79% of all donepezil-treated patients completing the studies compared with approx. 84% of placebo-treated patients. The most common adverse events associated with donepezil were generally cholinergic-induced and gastrointestinal in nature (e.g. nausea, diarrhoea, and vomiting) which were generally mild, transient and tended to occur after the dose was increased to 10 mg/d from 5 mg/d after 1 wk only. Sleep disturbances also occurred as the clinical trials utilized a bedtime dosing regimen. There was no evidence of organ toxicity or clinically significant treatment-emergent laboratory test abnormalities. Thus, donepezil appears to be a beneficial symptomatic treatment for patients with mild to moderate AD.

Journal Article↗

Analysis of right ventricular kinesis by means of transesophageal echocardiography: present problems and perspectives.

The evaluation of right ventricular (RV) kinesis by two-dimensional echocardiography represents a difficult task. Transthoracic echocardiography can visualize the RV in several projections, but the image quality and the variability of imaging views usually do not allow quantitative analysis. We investigated the potential of transesophageal echocardiography (TEE) for evaluating RV global function and regional kinesis, in 32 controls and in 16 patients with inferior myocardial infarction (MI) and asynergy involving the inferior wall of both ventricles. Good-quality images of at least one horizontal section of the RV were obtained in 73% of subjects by conventional, 90 degrees sector and in 100% of subjects by wide-angle, "panoramic" sector. Images of the RV in short-axis view at medium level were acquired and evaluated in 93% of cases, but at basal and apical levels only in 67% and 39%, respectively. The low percentage of successful detection and evaluation of the RV at apical level can be explained by prominent motion and trabeculation of the apex. Global systolic area changes (SAC) in controls attained similar values at apical and medium levels (60% and 59%, respectively), but were significantly lower (48%, P less than 0.05) at basal level. In patients with previous inferior MI and inferoposterior asynergy, global SAC were significantly (P less than 0.01) lower at medium and basal levels (32% and 27%, respectively) compared with controls. Regional kinesis of RV was assessed as segmental SAC in 12 different segments, by fixed and float system of center of cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia.

BACKGROUND: Therapeutic angiogenesis in ischemic myocardium has been shown to be a feasible and effective strategy to improve regional blood flow and myocardial function. However, the optimal mode of growth factor administration still needs to be established. METHODS: Using a pig model of chronic myocardial ischemia, we evaluated the efficacy of intravenous and intracoronary infusion of FGF-2 at 2 and 6 microg/kg compared with a vehicle control. Improvement in myocardial perfusion and function was assessed by angiography, colored microspheres, and function and perfusion magnetic resonance imaging. RESULTS: Intracoronary 6-microg/kg FGF-2 increased angiographic collaterals (p = 0.046) and increased regional blood flow to the ischemic area from 0.36 +/- 0.07 to 0.59 +/- 0.08 mL/min/g at stress (vs control, p = 0.032). Also, after 6 microg/kg intracoronary FGF-2, ejection fraction, regional wall motion, and thickening improved significantly by 9.9% +/- 1.9%, 126% +/- 39%, and 13.8% +/- 3.6%, respectively. Intravenous FGF-2 and intracoronary 2 microg/kg FGF-2 were ineffective. CONCLUSIONS: A single 6-microg/kg intracoronary treatment with FGF-2 resulted in significant improvement in collateralization and regional and global function of chronically ischemic myocardium. Single intravenous infusion of FGF-2 was not effective in this model.

Animals↗

Relationship between outflow obstruction and left ventricular functional impairment in hypertrophic cardiomyopathy: a Doppler echocardiographic study.

Left ventricular outflow tract (LVOT) obstruction is predictive of a worse outcome in hypertrophic cardiomyopathy (HCM). In a detailed Doppler echocardiographic study of 178 selected HCM patients, the group of patients (n = 73) with the obstructive form (resting peak gradient > or = 30 mmHg) presented more hypertrophy and poorer systolic and diastolic left ventricular (LV) functions than the HCM group (n = 105) without obstruction. LVOT peak gradient was positively correlated with hypertrophy (P < 0.0001) and negatively to tissue Doppler mitral annulus systolic (P = 0.0001) and early diastolic (P < 0.0001) velocities. The gradient significantly correlated with E/Ea ratio (r = 0.67; P < 0.0001). By multiple regression, LVOT gradient was related to E/Ea, LV maximal thickness and left atrial size. In comparison with patients without obstruction, patients with obstruction presented greater hypertrophy (P < 0.0001), lower systolic and early diastolic mitral annulus velocities (both P < 0.0001), higher E/Ea ratio (P < 0.0001) and higher global function index (P < 0.0001). In HCM, beyond the effects on hypertrophy, LVOT obstruction is an independent determinant of LV functional abnormalities.

Adolescent↗

Improved contractile function in the reperfused rat heart by the radical scavenger 2-[3-aminopropylamino] ethane thiol.

The action of the radioprotector WR 10 65 on regional function of the left ventricular muscle in ischemic injured and reperfused rat heart was investigated employing a new fiber optic based method for determination of segment shortening. In anesthetized rats exposed to regional myocardial ischemia by ligation of the left anterior descending coronary artery for 60 minutes followed by 60 minutes of reperfusion WR 10 65 applicated in a dosage of 1 mM/kg body weight intraperitoneally 30 minutes prior to ischemia induced an improvement of post ischemic recovery of segment shortening from 31% of pre-ischemic values in untreated animals to 64.6%. Because only moderate alterations in global functional parameters compared to control group were found in WR 10 65 treated animals, it is presumed that the observed influence on regional myocardial function is less due to changes in cardiac load than to the radical scavenger activity of the tested agent. A possible contribution of hypoxic and hypocalcemic activity of the substance remains to elucidate.

Animals↗

Personality disorder, psychiatric symptoms and experience of childbirth among childbearing women in Sweden.

OBJECTIVE: to investigate the importance of having a personality disorder or psychiatric symptoms during pregnancy for women's experience of childbirth. DESIGN: a prospective study of women consecutively recruited during mid-pregnancy. On study entry, the women completed self-rating scales for personality disorders, global functioning level and psychiatric symptoms. Two weeks after the birth, the women completed a questionnaire about their childbirth experiences. Obstetric and neonatal data were collected from maternity ward records. Multivariate logistic regression was used to estimate the likelihood for negative birth experiences. SETTING: antenatal clinics in Stockholm, Sweden. PARTICIPANTS: 625 primiparous women. FINDINGS: 40 out of 624 (6.4%) women fulfilled the criteria for personality disorder, and 28 out of 625 (4.5%) women were defined as psychiatric cases. No significant differences were found between women with personality disorders, or defined as psychiatric cases, and women without any mental problems regarding their global experience of birth. Women defined as psychiatric cases were more anxious (z=-2.5, p=0.04) during labour than women without mental problems. The strongest predictors of having had a negative global experience of birth were instrumental vaginal delivery (OR 3.2, 95% CI 2.1-5.1) and epidural analgesia (OR 2.4, 95% CI 1.5-3.9). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: obstetric factors, such as instrumental delivery, seem to be more important than mental problems during pregnancy for women's global experience of birth. Women with psychiatric symptoms during pregnancy need extra support during labour.

Adult↗

Assessment of systemic right ventricular function in patients with transposition of the great arteries using the myocardial performance index: comparison with cardiac magnetic resonance imaging.

BACKGROUND: Assessment of systemic right ventricular (RV) function is a key point in the follow-up of patients with transposition of the great arteries (TGA). Current echocardiographic assessment of RV function is at best an estimate, and cardiac magnetic resonance (CMR) is considered the gold standard. However, this technique is expensive, has limited availability, and requires significant expertise to acquire and interpret the images. The myocardial performance index (MPI) has recently been studied for assessment of pulmonary RV function and shows promise as a simple yet powerful tool for assessing patients with RV dysfunction of various origins. We set out to compare MPI and CMR assessment of systemic RV function in patients with TGA. METHODS AND RESULTS: Data from patients with TGA (11 with congenitally corrected TGA, 18 with surgically corrected TGA) who had CMR within 6 months of their echocardiogram were reviewed. The average systemic RV ejection fraction (RVEF) by CMR was 39.4+/-11.4%, and the systemic RVMPI for this group was 0.56+/-0.21. There was a strong negative correlation between the systemic RVMPI and systemic RVEF by CMR (r=-0.82, P<0.01). The systemic RVEF can be estimated from this formula: RVEF=65%-(45.2xMPI). CONCLUSIONS: MPI can be used in patients with systemic RVs to assess global function and to estimate an EF with good accuracy.

Adult↗

Randomized controlled trial of the use of compensatory strategies to enhance adaptive functioning in outpatients with schizophrenia.

OBJECTIVE: Cognitive adaptation training is a novel psychosocial treatment approach designed to improve adaptive functioning by using compensatory strategies in the home or work environment to bypass the cognitive deficits associated with schizophrenia. The authors tested the effect of cognitive adaptation training on level of adaptive functioning in outpatients with schizophrenia. METHOD: Forty-five patients with DSM-IV schizophrenia or schizoaffective disorder were randomly assigned for 9 months to one of three treatment conditions: 1) standard medication follow-up, 2) standard medication follow-up plus cognitive adaptation training, and 3) standard medication follow-up plus a condition designed to control for therapist time and provide environmental changes unrelated to cognitive deficits. Comprehensive assessments were conducted every 3 months by raters who were blind to treatment condition. RESULTS: Significant differences were found between the three treatment groups in levels of psychotic symptoms, motivation, and global functioning at the end of the 9-month study period. Patients in the cognitive adaptation training group overall had higher levels of improvement, compared with those in the remaining treatment conditions. In addition, the three groups had significantly different relapse rates over the 9-month study: 13% for the cognitive adaptation training group, 69% for the group in which therapist time and environmental changes were controlled, and 33% for the group who received standard follow-up only. CONCLUSIONS: Compensatory strategies may improve outcomes for patients with schizophrenia.

Adult↗