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PubMed2005

Automatic repositioning of single voxels in longitudinal 1H MRS studies.

An automatic procedure, allowing the prospective registration of brain MRI images and the acquisition of nearly identical brain volumes (coverage and orientation) in longitudinal exams, is presented. This procedure, based on a fast registration algorithm and a tailored pulse sequence, is used to reposition single voxels for 1H MRS data acquired in vivo. The impact of the repositioning method on the extent of voxel overlap and on the reproducibility of metabolite concentration measurements is studied. A statistically significant increase in voxel overlap and generally decreased short-term measurement variability (decreased coefficients of variation and increased reproducibility coefficients) are observed. Differences in the long-term variances of metabolite concentrations and concentration ratios measured using the eye and automatic repositioning scheme, however, do not reach statistical significance. The improved workflow associated with the use of the automatic repositioning process, which obviates the need for skilled operator intervention for voxel repositioning, suggests that approaches similar to the one presented here may be a standard element in tomorrow's longitudinal MRI and MRS exams.

Algorithms↗
PubMed1993

Results of parenchymal and angiographic magnetic resonance imaging and neuropsychological testing of children after stroke as neonates.

We describe the long-term follow up of infants after neonatal stroke of the middle cerebral artery (MCA). Stroke was diagnosed by CT scan in eight full-term neonates. Three dimensional (volume) magnetic resonance angiography (MRA) is a noninvasive technique that images the arterial vessels without contrast agents. All patients, aged from 1.5 to 8.4 years, were investigated by MRI and MRA and by neuropsychological tests. Cognitive development was investigated by intelligence tests, tests of visual perception, motor and language development. Out of the eight patients, seven had a retarded mental and motor development, and 50% of the children were treated for epilepsy. Seven patients had a spastic hemiparesis. Seven out of eight children showed major cognitive deficits. In all patients, MRI revealed clear parenchymal defects with variable distribution patterns. MRA studies showed abnormalities corresponding to the expected vascular distribution. Children with complications at delivery, with seizures, and an interruption of the main stem of MCA as demonstrated on MRA had the least favourable long-term follow up prognosis with severe cognitive delays.

Cerebral Arteries↗
PubMed2006

Group therapy for memory impaired patients: a partial remediation is possible.

BACKGROUND AND PURPOSE: To analyse the prospect of memory training for patients with organic brain damage. METHODS: Sixty-two patients with memory disorder were assigned to three different groups: a control group (n=16) with low dose memory training, a process oriented memory training group (POT) (n=24) and a group (ST) who was taught to compensate for memory problems with different strategies (n=22). Most of the patients had suffered a stroke. Inclusion criteria were medium to weak memory impairment defined by the patients' performance in the California Verbal Learning Test. Patients with complete amnesia were excluded. Specific care was taken that the groups did not differ in age, time since illness, duration of rehabilitation effort, verbal and performance IQ, memory and attention performance. The two treatment groups received 20 hours memory training, the low dose memory training control group 7 sessions. RESULTS: The treatment groups improved in verbal and prospective memory, but only the group with POT experienced a significant improvement compared with the control group. Training effects were specific, i. e. they affected verbal memory, but were not encapsulated, i. e. generalized to the recall of prose passages and of appointments. The POT group also showed a statistically weak outperformance compared with the ST group and some attentional improvement as well. CONCLUSION: Memory training is effective in patients with organic brain lesion, but only if applied frequently. Comparing the two training high intensity treatments, a POT focus seems to be superior to teaching a set of compensation strategies.

Aged↗
PubMed2006

Tic symptom profiles in subjects with Tourette Syndrome from two genetically isolated populations.

BACKGROUND: Tourette Syndrome (TS) has a complex etiology and wide variability in phenotypic expression. Identifying underlying symptom patterns may be useful for etiological and outcome studies of TS. METHODS: Lifetime tic and related symptom data were collected between 1996 and 2001 in 121 TS subjects from the Central Valley of Costa Rica and 133 TS subjects from the Ashkenazi Jewish (AS) population in the US. Subjects were grouped by tic symptoms using an agglomerative hierarchical cluster analysis. Cluster membership was tested for association with available ancillary information (age of onset, tic severity, comorbid disorders, medication treatment and family history). RESULTS: Cluster analysis identified two distinct groups in each sample, those with predominantly simple tics (cluster 1), and those with multiple complex tics (cluster 2). Membership in cluster 2 was correlated with increased tic severity, global impairment, medication treatment, and presence of comorbid obsessive-compulsive symptoms in both samples, and with family history of tics, lower verbal IQ, earlier age of onset, and comorbid obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in the AS sample. CONCLUSIONS: This study provides evidence for consistent and reproducible symptom profiles in two independent TS study samples. These findings have implications for etiological studies of TS.

Adolescent↗
PubMed2001

Serum dioxin and cognitive functioning among veterans of Operation Ranch Hand.

We used the Halstead-Reitan neuropsychological test battery, the Wechsler adult intelligence scale-revised, the Wechsler memory scale, and the wide range achievement test to assess cognitive functioning among Air Force veterans exposed to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam war The index subjects were veterans of Operation Ranch Hand (N = 937), the unit responsible for aerial herbicide spraying in Vietnam from 1962 to 1971. A comparison group of other Air Force veterans (N= 1,052), who served in Southeast Asia during the same period but were not involved with spraying herbicides served as referents. Cognitive functioning was assessed in 1982, and dioxin levels were measured in 1987 and 1992. We assigned each Ranch Hand veteran to the background, low, or high dioxin exposure category on the basis of a measurement of dioxin body burden. Although we found no global effect of dioxin exposure on cognitive functioning, we did find that several measures of memory functioning were decreased among veterans with the highest dioxin exposure. These results became more distinct when we restricted the analysis to enlisted personnel, the subgroup with the highest dioxin levels. An analysis based on dioxin quintiles in the combined cohort produced consistent results, with veterans in the fifth quintile exhibiting reduced verbal memory function. Although statistically significant, these differences were relatively small and of uncertain clinical significance.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2005

Pharmacotherapy of disruptive behavior and item changes on a standardized rating scale: pooled analysis of risperidone effects in children with subaverage IQ.

BACKGROUND: Disruptive behavior disorders (DBDs), excluding attention deficit/hyperactivity disorder (ADHD), are characterized by a repetitive pattern of antisocial, aggressive, and defiant behavior involving major violations of age-appropriate norms, resulting in significant functional impairment. Risperidone is licensed for the treatment of DBDs in children, adolescents, and adults in several countries. The aim of this study was to determine the effect of risperidone in a clinical setting on the symptom items of the Nisonger Child Behavior Rating Form (N-CBRF), used for the assessment of DBD patients. METHOD: Data from two 6-week, randomized, double-blind, placebo-controlled trials of risperidone oral solution (0.02-0.06 mg/kg/day) in children with DBDs and subaverage IQ (mild, moderate mental retardation and borderline IQ) were pooled for analysis. RESULTS: Risperidone produced improvement in both the Social Competence and the Problem Behavior N-CBRF subscales. Risperidone reduced symptoms in the Problem Behavior subscales (e.g., Conduct Problem, Insecure/Anxious) but also improved positive behaviors on the Social Competence subscales. Unlike most problem-behavior items, certain items reflecting "Affective insecurity" (e.g., shy, timid; clings to adults; crying, tearful episodes) failed to improve. This was also true of social disinterest and certain rituals. No items showed any worsening of symptoms with active medication. CONCLUSION: Whereas most categories of problem behavior improved with risperidone, items reflecting "affective insecurity" and some infrequently endorsed items were unaffected in these children with DBDs and subaverage IQ. These data may provide a more refined knowledge of risperidone's therapeutic effects in such children.

Analysis of Variance↗
PubMed1995

A self-organizing spatial vocabulary.

Language is a shared set of conventions for mapping meanings to utterances. This paper explores self-organization as the primary mechanism for the formation of a vocabulary. It reports on a computational experiment in which a group of distributed agents develop ways to identify each other using names or spatial descriptions. It is also shown that the proposed mechanism copes with the acquisition of an existing vocabulary by new agents entering the community and with an expansion of the set of meanings.

Artificial Intelligence↗
PubMed1999

Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia.

OBJECTIVE: Whether cognitive function in schizophrenia deteriorates, improves, or remains stable is a crucial question. Few studies have examined the longitudinal stability of cognitive function and the relationship between cognitive performance and clinical symptoms over time in a cohort of well-treated patients with schizophrenia. METHOD: In the present study, 54 patients with first-episode and recent-onset schizophrenia completed a comprehensive cognitive test battery and were rated on symptom measures at index hospitalization and again after 5 years. RESULTS: Performance IQ and full-scale IQ significantly improved, whereas verbal IQ did not change. Group performance improved on some of the neuropsychological tests, including the Circle A letter-cancellation task, free recall of logical memory test score, and the Wisconsin Card Sorting Test. Mean finger-tapping performance worsened over time, whereas performance on other neuropsychological tests did not change. Negative, psychotic, and disorganized symptoms significantly improved over the time period. Changes in negative symptoms were correlated with performance changes in verbal IQ and full-scale IQ but not performance IQ. Improvement in verbal cognition was observed when negative symptoms improved. Psychotic and disorganized symptom dimensions were not correlated with any IQ measure. CONCLUSIONS: These results indicate that in a cohort of young patients receiving neuroleptic treatment early in their illness, cognitive performance does not deteriorate--and may improve. Only one of the three symptom dimensions--negative--was associated with change in cognitive performance. This study supports the view that negative symptoms are associated with a poor long-term cognitive outcome and may be closely related to the primary cognitive deficit in schizophrenia.

Adult↗
PubMed2001

Stability of olfactory identification deficits in neuroleptic-naive patients with first-episode psychosis.

OBJECTIVE: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. METHOD: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. RESULTS: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. CONCLUSIONS: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms.

Adolescent↗
PubMed1985

Effect of buflomedil on behaviour, memory, and intellectual capacity in patients with dementia. A placebo-controlled study.

A double-blind, placebo-controlled clinical study of the efficacy and safety of buflomedil in the treatment of dementia was conducted in 55 patients. A statistically significant improvement was achieved for such characteristics as mood, self-care, alertness, emotional lability, indifference, hostility, and anxiety. Compared with placebo, buflomedil showed a clear superiority with regard to improvement in cognitive dysfunction and psychosomatic dysfunction, with a trend toward statistical significance in improvement in interpersonal relations. Secondary analysis of a subset of patients without evidence of earlier cerebrovascular accident showed similar clinical responses and statistical findings. Buflomedil was well tolerated.

Affective Symptoms↗
PubMed1984

Depression and anorexia nervosa of persons with Down syndrome.

The manifestations of major depression in three adults with Down syndrome, one of whom also suffered from anorexia nervosa, were described. The clinical manifestations depended on patient's developmental level, particularly on verbal language skills. Behavioral and vegetative symptoms predominated when the retardation was more severe, whereas in the higher functioning patient affective symptoms were more readily recognizable. The overall findings indicate that major depression in persons with Down syndrome may be more frequent than previously assumed and that it can be diagnosed with standard diagnostic DSM III criteria, modified according to the patient's developmental level.

Adult↗
PubMed2026

Metabolic convergence of diabetes and prostate cancer: from dysglycemia to tumor microenvironment reprogramming.

The relationship between diabetes mellitus and prostate cancer (PC) represents one of the most intriguing paradoxes in cancer epidemiology, with diabetic individuals exhibiting a reduced incidence of PC yet poorer prognosis following diagnosis. This apparent contradiction underscores the need for an integrated understanding of how systemic metabolic dysfunction influences prostate carcinogenesis and disease progression. The present review critically synthesizes contemporary epidemiological, mechanistic, and translational evidence to establish metabolic convergence as a unifying framework linking diabetes-associated metabolic abnormalities with PC biology. Current evidence indicates that chronic dysglycemia, hyperinsulinemia, insulin resistance, and endocrine perturbations orchestrate interconnected intracellular signaling networks involving PI3K-AKT-mTOR, AMPK, AGE-RAGE signaling, oxidative stress, mitochondrial dysfunction, and epigenetic reprogramming, collectively driving metabolic adaptation and tumor evolution. Beyond tumor-intrinsic mechanisms, diabetes profoundly remodels the prostate tumor microenvironment through alterations in stromal metabolism, cancer-associated fibroblast activation, adipocyte-tumor crosstalk, extracellular matrix (ECM) remodeling, hypoxic adaptation, and vascular dysfunction, while simultaneously promoting immunometabolic reprogramming characterized by macrophage polarization, T-cell dysfunction, immune checkpoint activation, and immune evasion. The review further examines the bidirectional interactions between antidiabetic therapies and PC treatment, critically evaluating the translational potential of metformin and emerging glucose-lowering agents within the context of precision metabolic therapeutics. Finally, future directions encompassing biomarker-guided patient stratification, longitudinal metabolic profiling, multi-omics integration, artificial intelligence, and clinically relevant mechanistic validation are discussed as essential components of next-generation precision oncology. Collectively, this review reframes diabetes as an active metabolic determinant of PC rather than a coincidental comorbidity and highlights metabolism-centered precision strategies as promising avenues for improving risk stratification, therapeutic decision-making, and clinical outcomes in diabetes-associated PC.

Humans↗
PubMed1985

Immunomodulating effects of synthetic polyribonucleotides.

The polynucleotide complexes are a class of compounds whose activities to date deserve close scrutiny with respect to their potential role as biological response-modifying agents in human disease. The challenge for the future lies in directing and controlling their activity with respect to a single desired effect, such that intelligent interference in patients with immunological aberrancies might occur.

Humans↗
PubMed2006

A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer.

The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis found no significant interactions or main effect of group after controlling for age and intelligence. Using a calculation to examine performance at an individual level, reliable decline on multiple tasks was seen in 20% of chemotherapy patients, 26% of nonchemotherapy patients and 18% of controls at T2 (18%, 14 and 11%, respectively, at T3). Patients who had experienced a treatment-induced menopause were more likely to show reliable decline on multiple measures at T2 (OR=2.6, 95% confidence interval (CI) 0.823-8.266 P=0.086). Psychological distress, quality of life measures and self-reported cognitive failures did not impact on objective tests of cognitive function, but were significantly associated with each other. The results show that a few women experienced objective measurable change in their concentration and memory following standard adjuvant therapy, but the majority were either unaffected or even improve over time.

Adult↗