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Prediction of homelessness within three months of discharge among inpatients with schizophrenia.

OBJECTIVE: The authors' goal was to identify factors that place inpatients with schizophrenia at risk of becoming homeless after hospital discharge. METHODS: Patients with schizophrenia or schizoaffective disorder (N=263) were assessed at discharge from general hospitals in New York City and reassessed three months later to evaluate whether they had become homeless. Sociodemographic and clinical characteristics associated with homelessness were identified using likelihood ratio chi square analysis and logistic regression. RESULTS: Twenty patients (7.6 percent) reported an episode of homelessness during the follow-up period. Patients who had a drug use disorder at hospital discharge were significantly more likely to report becoming homeless than those without a drug use disorder. Patients with a total score above 40 on the Brief Psychiatric Rating Scale (BPRS) at hospital discharge were more likely to report becoming homeless than patients with lower scores, as were those with Global Assessment Scores less than 43. Twelve of 30 patients with a drug use disorder, a BPRS score above 40, and a GAS score less than 43 at hospital discharge reported becoming homeless. CONCLUSIONS: The combination of a drug use disorder, persistent psychiatric symptoms, and impaired global functioning at the time of hospital discharge poses a substantial short-term risk of homelessness among patients with schizophrenia. Patients who fit this profile may be candidates for community-based programs that are specifically aimed at preventing homelessness among patients with severe mental illness.

Adult↗

Selective serotonin reuptake inhibitor and venlafaxine use in children and adolescents with major depressive disorder: a systematic review of published randomized controlled trials.

OBJECTIVE: This review critiques published randomized placebo-controlled trials pertaining to the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine in the treatment of major depressive disorder in children and adolescents. METHOD: Medline was searched for articles meeting defined inclusion criteria. The following key terms were used: depressive disorders, antidepressive agents, fluoxetine, paroxetine, sertraline, citalopram, fluvoxamine, venlafaxine, child, and adolescent. RESULTS: Six articles met inclusion criteria. Only 2 studies claim efficacy by significant results in primary outcomes; both have since been contested in further analysis. Not one study adequately examines safety, particularly with respect to whether a link exists between antidepressant use and induction of suicidal ideation or attempts. CONCLUSION: Published studies on SSRI or venlafaxine use in children and adolescents are inconclusive with respect to safety and efficacy, owing to inappropriate claims of efficacy, lack of improvement in global functioning scores, nonstandardized data collection regarding adverse effects, exclusion of suicidal subjects in the recruitment process, grouping of children and adolescents together, small sample sizes, conflict of interest posed by pharmaceutical company sponsorship, and publishing bias. Future investigators should consider these factors when developing study designs.

Adolescent↗

The Safety, Efficacy, and Feasibility of Fecal Microbiota Transplantation in a Population With Bipolar Disorder During Depressive Episodes: A Pilot Parallel Arm Randomized Controlled Trial: Sécurité, efficacité et faisabilité de la transplantation de microbiote fécal chez une population atteinte de troubles bipolaires, au cours d'épisodes dépressifs : essai pilote contrôlé à répartition aléatoire et à groupes parallèles.

BackgroundThe gut microbiome has been proposed as a potential modifiable target to treat mental illness. This double-blind randomized control trial investigated fecal microbiota transplant (FMT) in bipolar disorder (BD) to assess efficacy, safety, and feasibility. The primary outcome evaluated the effectiveness of standard approved therapy for BD depression + FMT in individuals not responding to standard treatment, measured by change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 24. Secondary outcomes included FMT's impact on anxiety, global function, side-effects, and safety. The feasibility of this novel intervention was also assessed. Microbial analysis utilized whole-genome shotgun metagenomic sequencing, comparing outcomes between allogenic (donor) and autologous (participants own) FMT.MethodsA total of 35 participants (28 women and 7 men) with at least moderate depressive-phase BD (MADRS) were randomized to receive either allogenic FMT (n = 17) or autologous FMT (n = 18) via colonoscopy and were followed for 24 weeks.ResultsMADRS scores significantly improved from baseline to the last visit in both treatment arms. There was no significant difference between allogenic FMT (16.74-point improvement) and autologous FMT (15.4-point improvement) regarding clinical efficacy (t = -0.47, p-value = .64, 95% confidence interval [CI] = -7.3-4.6). Microbiota analysis showed that allogenic FMT let to a bacterial profile similar to the healthy donor and increased bacterial diversity at the 6-month mark, whereas those receiving autologous FMT did not. The intervention was well tolerated with no significant adverse events. Recruitment, randomization, and retention metrics support feasibility of a larger trial.ConclusionFeasibility and tolerability data indicate further investigation into microbial manipulation in BD is warranted. The absence of efficacy differences between the two types of FMT, despite microbial change, highlights the importance of a true placebo in future studies, as well as the importance of understanding exactly what bacteria are linked to improvements. ClinicalTrials.gov, NCT0327922Plain Language Summary TitleResults of a Double-Blind Randomized Control Trial Investigating Fecal Microbiota Transplant (FMT) as an Add-on Treatment for Depression in Bipolar Disorder and Analyzing Microbial Diversity Changes Over 24 Weeks.

Humans↗

Role of cholinesterase inhibitors in Parkinson's disease and dementia with Lewy bodies.

This article reviews the cholinergic changes in Parkinson's disease and dementia (PDD) and dementia with Lewy bodies (DLB), their potential clinical implications, and the available evidence for cholinesterase inhibitors in the treatment of PDD and DLB. Marked neuronal loss of cholinergic nuclei, reduced cholinergic markers in the neocortex, hippocampus, and selected thalamic nuclei, and receptor changes have been reported. One large and 2 small placebo-controlled trials and nearly 20 open-label studies suggest that cholinesterase inhibitors have a positive effect on cognition, psychiatric symptoms, and global function in patients with DLB and PDD. The treatment is well tolerated in most patients without any apparent worsening of extrapyramidal motor features. Given the high risk of severe sensitivity reactions and increased risk of cerebrovascular incidents during treatment with neuroleptics, more clinical trials of cholinesterase inhibitors are encouraged to establish their precise role in DLB and PDD.

Cholinesterase Inhibitors↗

Presenting problems and assigned diagnoses among young Latino children with disruptive behaviors.

It is unclear whether the behaviors that alert families to the need for services are those that classify children for the diagnoses they receive. This study describes the behaviors that Latina mothers from Cuba, Puerto Rico, and the Dominican Republic report to have induced them to seek services for their young children. Both qualitative and quantitative analyses were used. Results indicated that mothers most frequently cited behaviors that fell in the categories of Hyperactivity, Aggression/Temper Tantrums, and School Complaints as reasons for help seeking. Whereas aggression and self-injurious acts were most alarming to mothers, School Complaints appeared to be a strong motivator for help seeking. Children whose mothers cited school behavior as a reason for help seeking had significantly poorer global functioning and presented significantly higher care giving demands than peers. In addition, their mothers reported significantly more disciplinary laxity than the mothers of peers without School Complaints. Maternal narratives of children's behaviors moderately concurred with assigned diagnoses. Mothers overlooked inattentive behaviors in children with ADHD and reported much more aggression and oppositionality than might be expected from the number of diagnoses of ODD that were assigned.

Attention Deficit Disorder with Hyperactivity↗

Effect of rivastigmine in the treatment of behavioral disturbances associated with dementia: review of neuropsychiatric impairment in Alzheimer's disease.

Cognitive decline is conventionally regarded as the defining clinical symptom of Alzheimer's disease (AD), but behavioral and neuropsychiatric symptoms are also present throughout the course of the disease. In fact, behavioral symptoms may appear before cognitive decline is diagnosed. The presence of these symptoms may predict an increasing need for community-based services or even nursing home placement. The characteristic behavioral and neuropsychiatric symptoms associated with AD may be related to the same pathophysiology that underlies the cognitive abnormalities. AD is characterized by a loss of cholinergic neurons as well as by the presence of neurofibrillary tangles (NFTs) and senile plaques in brain regions with cholinergic deficits, resulting in a deficiency in acetylcholine (ACh) in areas of the brain that modulate cognition, behavior, and emotion. Cholinesterase inhibitors are thought to augment or maximize the concentration of ACh in the synaptic cleft. Rivastigmine is a dual inhibitor of both acetylcholin esterase (AChE) and butyrylcholinesterase (BuChE), enzymes involved in hydrolysis of ACh. Literature searches using MEDLINE and EMBASE databases were performed to identify studies of rivastigmine (through August 2005) that assessed neuropsychiatric aspects of AD. Rivastigmine has been demonstrated to be safe and effective in stabilizing or improving the cognitive symptoms of AD in 3 large, well-controlled, randomized clinical trials, which also demonstrated that rivastig mine improves overall global functioning. Smaller studies and meta-analyses of pooled data from the 3 large trials have suggested that rivastigmine may improve the behavioral and neuropsychiatric symptoms associated with AD.

Alzheimer Disease↗

Effects of CPAP on right ventricular myocardial performance index in obstructive sleep apnea patients without hypertension.

OBJECTIVES: Obstructive sleep apnoea (OSA) might cause right ventricular dysfunction and pulmonary hypertension. We aimed to determine the effects of nasal continuous positive airway pressure (CPAP) therapy on right ventricular myocardial performance index (MPI) in OSA patients without hypertension. METHODS: 49 subjects without hypertension, diabetes mellitus, any cardiac and pulmonary disease had overnight polysomnography and echocardiography. In 18 moderate-severe OSA (apnea-hypopnea index > or = 15) patients, right ventricular free wall diameter (RVFWD) was measured by M-mode, and right ventricular MPI was calculated as (isovolumic contraction time+ isovolumic relaxation time) / pulmonary ejection time using Doppler at baseline and after 6 months CPAP therapy. RESULTS: Mean age was 46.5 +/- 4.9 year. Patients had high body mass index (BMI: 30.6 +/- 4,0 kg/m2), but there was no change in either BMI or blood pressures after 6 months. Right ventricular end-diastolic and end-systolic diameters were in normal limits at baseline, and did not change after CPAP usage. Baseline RVFWD (7.1 +/- 2.1 mm) significantly decreased after CPAP therapy (6.2 +/- 1.7 mm, p < 0.001). 15 of patients (83%) had right ventricular diastolic dysfunction at baseline, and it was completely improved in 11 of them (73%) by CPAP usage. Right ventricular global dysfunction was shown in 11 patients (61%) with a high MPI (62.2 +/- 9.3%) at baseline; and MPI was significantly decreased after CPAP therapy (47.3 +/- 8.4%, p < 0.0001), and it was completely corrected in 4 of them (36%). CONCLUSION: CPAP therapy significantly decreases RVFWD and improves right ventricular diastolic and global functions (MPI) in OSA patients without hypertension.

Adult↗

WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data.

BACKGROUND: Analysis of High Throughput (HTP) Data such as microarray and proteomics data has provided a powerful methodology to study patterns of gene regulation at genome scale. A major unresolved problem in the post-genomic era is to assemble the large amounts of data generated into a meaningful biological context. We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data. RESULT: WPS extracts gene lists with shared biological themes through color cue templates. WPS statistically evaluates global functional category enrichment of gene lists and pathway-level pattern enrichment of data. WPS incorporates well-known biological pathways from KEGG (Kyoto Encyclopedia of Genes and Genomes) and Biocarta, GO (Gene Ontology) terms as well as user-defined pathways or relevant gene clusters or groups, and explores gene-term relationships within the derived gene-term association networks (GTANs). WPS simultaneously compares multiple datasets within biological contexts either as pathways or as association networks. WPS also integrates Genetic Association Database and Partial MedGene Database for disease-association information. We have used this program to analyze and compare microarray and proteomics datasets derived from a variety of biological systems. Application examples demonstrated the capacity of WPS to significantly facilitate the analysis of HTP data for integrative discovery. CONCLUSION: This tool represents a pathway-based platform for discovery integration to maximize analysis power. The tool is freely available at http://www.abcc.ncifcrf.gov/wps/wps_index.php.

Computer Graphics↗

Rivastigmine: an open-label, observational study of safety and effectiveness in treating patients with Alzheimer's disease for up to 5 years.

BACKGROUND: Rivastigmine, a butyl- and acetylcholinesterase inhibitor, is approved for symptomatic treatment of Alzheimer's disease (AD). Data supporting the safety and efficacy of second-generation cholinesterase inhibitors, such as rivastigmine, are available for treatment up to 1 year, with limited data up to 2 1/2 years. The purpose of this report is to present safety and effectiveness data for rivastigmine therapy in patients with mild to moderately severe AD receiving treatment for up to 5 years. METHODS: An observational approach was used to study 37 patients with originally mild to moderate AD receiving rivastigmine as a therapy for AD in an open-label extension (ENA713, B352 Study Group, 1998). RESULTS: The initial trial demonstrated rivastigmine was well-tolerated and effective in terms of cognition, global functioning and activities of daily living. In this open label extension, high-dose rivastigmine therapy was safe and well tolerated over a 5-year period. Two thirds of the participants still enrolled at week 234 were in the original high-dose rivastigmine group during the double-blind phase, suggesting that early therapy may confer some benefit in delaying long-term progression of symptoms. CONCLUSIONS: Long-term cholinesterase inhibition therapy with rivastigmine was well tolerated, with no dropouts due to adverse effects past the initial titration period. Early initiation of treatment, with titration to high-dose therapy, may have an advantage in delaying progression of the illness.

Aged↗

Ethnicity, sleep, mood, and illumination in postmenopausal women.

BACKGROUND: This study examined how ethnic differences in sleep and depression were related to environmental illumination and circadian rhythms. METHODS: In an ancillary study to the Women's Health Initiative, 459 postmenopausal women were recorded for one week in their homes, using wrist monitors. Sleep and illumination experience were estimated. Depression was self-rated with a brief adjective check list. Affective diagnoses were made using the SCID interview. Sleep disordered breathing was monitored with home pulse oximetry. RESULTS: Hispanic and African-American women slept less than European-American women, according to both objective recordings and their own sleep logs. Non-European-American women had more blood oxygen desaturations during sleep, which accounted for 26% of sleep duration variance associated with ethnicity. Hispanic women were much more depressed. Hispanic, African-American and Native-American women experienced less daily illumination. Less daily illumination experience was associated with poorer global functioning, longer but more disturbed sleep, and more depression. CONCLUSIONS: Curtailed sleep and poor mood were related to ethnicity. Sleep disordered breathing was a factor in the curtailed sleep of minority women. Less illumination was experienced by non-European-American women, but illumination accounted for little of the contrasts between ethnic groups in sleep and mood. Social factors may be involved.

Black or African American↗

The COSTAR programme. 1: Improving social networks of the long-term mentally ill.

The present study examined the socio-demographic, clinical, cognitive, social behaviour and social network characteristics of the 97 patients in contact with the COSTAR programme--a mobile treatment and case management service for the long-term mentally ill in inner-city Baltimore. Compared with shorter-contact patients, those in contact for more than one year showed no change in symptoms, or in cognitive or global function. They did manifest improved social function, especially for slowness, personal hygiene and posturing. The long-contact group showed improvements in the quality and quantity of their social networks. Our results suggest that a home-based treatment system can help patients to reverse a vicious cycle of social isolation and to establish supportive social contacts.

Activities of Daily Living↗

The Maine and Vermont three-decade studies of serious mental illness. I. Matched comparison of cross-sectional outcome.

BACKGROUND: This study compared long-term outcome of serious mental illness in two states using a matched design to assess psychiatric rehabilitation programmes; Vermont subjects participated in a model psychiatric rehabilitation programme, while the Maine group received more traditional care. METHOD: Maine and Vermont subjects (n = 269) were matched by age, sex, diagnosis, and chronicity. Demographic, illness, and life history information were abstracted from hospital records by clinicians blind to outcome. DSM-III criteria were applied retrospectively. Outcome was assessed by clinicians blind to history. RESULTS: Vermont subjects alive at follow-up (n = 180) were more productive (P < 0.0009), had fewer symptoms (P < 0.002), better community adjustment (P < 0.001) and global functioning (P < 0.001) than Maine subjects (n = 119). CONCLUSIONS: Outcome differences may be due to Vermont's model programme and a policy of allowing an earlier opportunity for community life.

Activities of Daily Living↗

Music therapy for in-patients with schizophrenia: exploratory randomised controlled trial.

BACKGROUND: Music therapy may provide a means of improving mental health among people with schizophrenia, but its effects in acute psychoses have not been explored. AIMS: To examine the feasibility of a randomised trial of music therapy for inpatients with schizophrenia, and explore its effects on mental health. METHOD: Up to 12 weeks of individual music therapy plus standard care were compared with standard care alone. Masked assessments of mental health, global functioning and satisfaction with care were conducted at 3 months. RESULTS: Of 115 eligible patients 81 (70%) were randomised. Two-thirds of those randomised to music therapy attended at least four sessions (median attendance, eight sessions). Multivariate analysis demonstrated a trend towards improved symptom scores among those randomised to music therapy, especially in general symptoms of schizophrenia. CONCLUSIONS: A randomised trial of music therapy for in-patients with schizophrenia is feasible. The effects and cost-effectiveness of music therapy for acute psychosis should be further explored in an explanatory randomised trial.

Feasibility Studies↗

Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: To compare two cisplatin based chemotherapy schedules in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 332 patients with advanced NSCLC were randomized to receive cisplatin 80 mg/m2 on day 1 either in combination with teniposide 100 mg/m2 on days 1, 3, and 5 (arm A) or paclitaxel 175 mg/m2 by 3-hour infusion on day 1 (arm B); cycles were repeated every 3 weeks. RESULTS: Fifteen patients were ineligible; patient characteristics were well balanced between the two arms: 71% were male, 71% had less than 5% weight loss, 89% had a World Health Organization (WHO) performance status of 0 to 1, 51% had adenocarcinoma, and 61% had stage IV disease. Hematologic toxicity was significantly more severe in arm A (leukopenia, neutropenia, and thrombocytopenia grade 3 or 4: 66% v 19%, 83% v 55%, 36% v 2% in arms A and B, respectively), which resulted in more febrile neutropenia (27% v 3% in arms A and B, respectively), dose reductions, and treatment delays. There were a total of nine toxic deaths, six due to neutropenic sepsis: five in arm A and one in arm B. In contrast, arthralgia/myalgia (grade 2 or 3, 4% v 17%), peripheral neurotoxicity (grade 2 or 3, 6% v 29%), and hypersensitivity reactions (1% v 7%, all grades) were significantly more frequent in arm B. The frequency and severity of other toxicities were comparable between the two arms. Responses were one complete and 44 partial on arm A (28%) and two complete and 61 partial (41%) on arm B (P = .018). There was no significant difference in survival, with median and 1-year survivals 9.9 versus 9.7 months and 41% versus 43%, respectively in arm A and B. Progression-free survival was 4.9 and 5.4 months in arm A and B, respectively. Selected centers participated in a quality-of-life (QoL) assessment, which was performed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and LC-13 administered at baseline and every 6 weeks thereafter. Arm B achieved a better score at week 6 for emotional, cognitive and social functioning, global health status, fatigue, and appetite loss, which was lost at 12 weeks. In conclusion, arm B appears superior to arm A with regard to response rate, side effects, and QoL. CONCLUSION: Although survival was not improved, arm B offers a better palliation for advanced NSCLC patients than arm A.

Adult↗

Health-related quality of life in patients treated with temozolomide versus procarbazine for recurrent glioblastoma multiforme.

PURPOSE: To determine whether chemotherapy with temozolomide (TMZ) versus procarbazine (PCB) for recurrent glioblastoma multiforme (GBM) was associated with improvement in health-related quality of life (HRQOL). PATIENTS AND METHODS: HRQOL was assessed at baseline and during treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a Brain Cancer Module (BCM20) in two clinical trials that enrolled a total of 366 patients. Two hundred eighty-eight patients provided HRQOL data that could be used for analysis; 109 patients received TMZ in a phase II study, whereas 89 patients received TMZ and 90 received PCB in a randomized phase III study. Changes from baseline in the scores of seven preselected HRQOL domains (role and social functioning, global quality of life [QOL], visual disorders, motor dysfunction, communication deficit, and drowsiness) were calculated for all groups. Statistical significance, effect sizes, and proportions of patients with improved HRQOL scores (changes of > or = 10 points) were calculated. RESULTS: Before disease progression, patients treated with TMZ were found to have an improvement in most of the preselected HRQOL domain scores compared with their baseline (pretreatment) scores. Those who were progression-free on TMZ at 6 months had improvement in all the preselected HRQOL domains. Conversely, patients treated with PCB reported deterioration in HRQOL that was independent of whether or not the disease had progressed by 6 months. Patients with disease progression, regardless of treatment, experienced a sharp decline in all domains at the time of progression. CONCLUSION: Treatment with TMZ was associated with improvement in HRQOL scores compared with treatment with PCB. The deterioration reported by PCB-treated patients was likely because of toxicity. Delaying disease progression by treatment with TMZ is beneficial to the HRQOL status of patients with recurrent GBM.

Adult↗

Psychosis in advanced Parkinson's disease: treatment with ondansetron, a 5-HT3 receptor antagonist.

Psychosis, linked to chronic levodopa and other antiparkinsonian drug treatments, is a common and incapacitating complication of advanced Parkinson's disease (PD). The psychosis may be due, in part, to overstimulation of central serotonergic (5-HT) receptors. We treated 16 PD patients who had psychosis of 6 to 60 months' duration with the 5-HT3 receptor antagonist ondansetron (12 to 24 mg daily) in an open-label, short-term (4 to 8 weeks) trial. There was marked to moderate improvement (p < 0.01) in measures of visual hallucinations, paranoid delusions, confusion, and the associated global functional impairment in all but one of the patients, and there was moderate improvement in the Brief Psychiatric Rating Scale and the Nurse's Observation Scale for Inpatient Evaluation; the Mini-Mental State Examination scores remained unaltered. Ondansetron did not cause any worsening in basic PD symptoms or levodopa efficacy and was well tolerated with no major side effects. Our study suggests that pharmacologic blockade of central 5-HT receptors may become a strategy to attenuate PD psychosis without inducing motor deterioration or suppression of antiparkinsonian action of levodopa, and it lends support to the hypothesis that serotonergic mechanisms are pathogenetically important in the emergence of psychosis in PD.

Aged↗

Efficacy and safety of eptastigmine for the treatment of patients with Alzheimer's disease.

OBJECTIVE: To evaluate the efficacy and safety of eptastigmine in patients with moderate to moderately severe AD. BACKGROUND: Eptastigmine is a centrally acting cholinesterase inhibitor. METHODS: The study was carried out according a multicenter, randomized, double-blinded, placebo-controlled, parallel-group design. Patients received a 24-week treatment with placebo or eptastigmine 15 mg or 20 mg three times daily after a 4-week, stepwise dose escalation. The effects of treatment on cognition, global function, and activities of daily living were evaluated with the Alzheimer's Disease Assessment Cognitive Subscale (ADAS-Cog), the Clinician's Interview-Based Impression of Change Plus (CIBIC-Plus), and the Instrumental Activities of Daily Living scale (IADL), respectively. RESULTS: Thirty-six centers recruited 491 patients: 164 on placebo, 166 on eptastigmine 15 mg three times daily, and 161 on eptastigmine 20 mg three times daily. Percentages of patients completing double-blinded treatment were 87% in the placebo group and 86% in both the eptastigmine-treated groups. At the end of treatment, the intent-to-treat analysis on 463 patients showed a dose-dependent effect of eptastigmine on all efficacy variables, with a statistically significant effect of the 20 mg three times daily dose compared with placebo on the ADAS-Cog, CIBIC-Plus, and IADL. Patients on eptastigmine 15 mg three times daily performed significantly better than placebo-treated patients only on the ADAS-Cog. Eleven patients on placebo (7%), 13 patients on eptastigmine 15 mg three times daily (8%), and 12 patients on eptastigmine 20 mg three times daily (8%) discontinued study treatment because of adverse events. Adverse events were recorded in 49% of patients on placebo compared with 54% on eptastigmine 15 mg three times daily and 48% on eptastigmine 20 mg three times daily. Cholinergic side effects (nausea, vomiting, diarrhea, and abdominal pain) were reported with similar frequency in the eptastigmine- and placebo-treated patients. There was a dose-dependent transient and mild neutropenic effect associated with eptastigmine treatment, and one patient on 20 mg three times daily had an asymptomatic pancytopenia. CONCLUSIONS: Eptastigmine produces significant cognitive, clinical, and functional benefits in patients with probable AD. Although the cholinergic tolerability of eptastigmine was found to be favorable, its potential adverse hematologic effects limit its clinical utility.

Aged↗

Hox genes and morphological identity: axial versus lateral patterning in the vertebrate mesoderm.

The successful organization of the vertebrate body requires that local information in the embryo be translated into a functional, global pattern. Somite cells form the bulk of the musculoskeletal system. Heterotopic transplants of segmental plate along the axis from quail to chick were performed to test the correlation between autonomous morphological patterning and Hox gene expression in somite subpopulations. The data presented strengthen the correlation of Hox gene expression with axial specification and focus on the significance of Hox genes in specific derivatives of the somites. We have defined two anatomical compartments of the body based on the embryonic origin of the cells making up contributing structures: the dorsal compartment, formed from purely somitic cell populations; and the ventral compartment comprising cells from somites and lateral plate. The boundary between these anatomical compartments is termed the somitic frontier. Somitic tissue transplanted between axial levels retains both original Hox expression and morphological identity in the dorsal compartment. In contrast, migrating lateral somitic cells crossing the somitic frontier do not maintain donor Hox expression but apparently adopt the Hox expression of the lateral plate and participate in the morphology appropriate to the host level. Dorsal and ventral compartments, as defined here, have relevance for experimental manipulations that influence somite cell behavior. The correlation of Hox expression profiles and patterning behavior of cells in these two compartments supports the hypothesis of independent Hox codes in paraxial and lateral plate mesoderm.

Animals↗