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Biomedical subjects

A Rosenblatt

Publications and source records attributed to A Rosenblatt.

At least 19 recordsLinked to original sources
PubMed2005

Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Preliminary evidence suggests beneficial effects of pure ethyl-eicosapentaenoate (ethyl-EPA) in Huntington disease (HD). METHODS: A total of 135 patients with HD were randomized to enter a multicenter, double-blind, placebo-controlled trial on the efficacy of 2 g/d ethyl-EPA vs placebo. The Unified Huntington's Disease Rating Scale (UHDRS) was used for assessment. The primary end point was outcome at 12 months on the Total Motor Score 4 subscale (TMS-4). Analysis of covariance (ANCOVA) and a chi2 test on response, defined as absence of increase in the TMS-4, were performed. RESULTS: A total of 121 patients completed 12 months, and 83 did so without protocol violations (PP cohort). Intent-to-treat (ITT) analysis revealed no significant difference between ethyl-EPA and placebo for TMS-4. In the PP cohort, ethyl-EPA proved better than placebo on the chi2 test on TMS-4 (p < 0.05), but missed significance on ANCOVA (p = 0.06). Secondary end points (ITT cohort) showed no benefit of ethyl-EPA but a significantly worse outcome in the behavioral severity and frequency compared with placebo. Exploring moderators of the efficacy of ethyl-EPA on TMS-4 showed a significant interaction between treatment and a factor defining patients with high vs low CAG repeats. Reported adverse events were distributed equally between treatment arms. CONCLUSIONS: Ethyl-eicosapentaenoate (ethyl-EPA) (purity > 95%) had no benefit in the intent-to-treat cohort of patients with Huntington disease, but exploratory analysis revealed that a significantly higher number of patients in the per protocol cohort, treated with ethyl-EPA, showed stable or improved motor function. Further studies of the potential efficacy of ethyl-EPA are warranted.

Adult↗
PubMed2005

Differential impairment of spatial location memory in Huntington's disease.

OBJECTIVE: To determine whether a differential impairment of spatial memory exists in Huntington's disease (HD). METHODS: Patients with HD and age matched neurologically normal subjects, as well as patients with Alzheimer's disease (AD) and Parkinson's disease (PD), learned the locations of nine items on a 3 x 3 grid over as many as 10 trials. Delayed recall of the items and their spatial locations was tested. RESULTS: Patient with HD performed worse than normal subjects on all measures, and intermediate between AD and PD patients. However, they were the only subject group in whom delayed recall of spatial locations was poorer than delayed recall of object identity. This effect was independent of the severity of dementia. CONCLUSIONS: HD patients have a differential impairment in memory for object-location information. This finding may relate to the involvement of the caudate nucleus, the primary site of pathology in HD, in corticostriatal circuits linking it with parietal association cortex. It is also consistent with views of the dorsal striatum as responsible for the acquisition over trials of specific place responses.

Alzheimer Disease↗
PubMed2004

Onset and rate of striatal atrophy in preclinical Huntington disease.

BACKGROUND: Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms. OBJECTIVE: To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur. METHODS: Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan. RESULTS: Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging. CONCLUSIONS: Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.

Adult↗
PubMed2004

Breast-feeding and early childhood caries: an assessment among Brazilian infants.

OBJECTIVES: The purpose of the present study was to evaluate early childhood caries among 12-36-month-old children from families living in poor socio-economic conditions in the city of Recife, Brazil, its association with the type and duration of feeding (e.g. natural, sugared, bottle and glass), as well as the relationship between a supplementary diet and the occurrence of this type of caries. METHODS: The present study consisted of a visual clinical examination of teeth that had been previously cleaned with gauze. This was carried out under natural light in a waiting room. Four calibrated examiners performed the examination and the kappa test value was 8.0. The parents or guardians were interviewed for the following information: name, address, age, type of feeding, number of sugary meals, sugar intake and habitual diet. Some 468 children were included in this study. Their ages ranged from 12 to 36 months. The sample was comprised of 222 (47.4%) males and 246 females (52.6%). RESULTS: Of the 468 children included in this study, 133 (28.4%) had caries. Only 59 (12.6%) of the children examined had been breast-fed, 20 (33.9%) of whom presented with caries. Three hundred and twenty-seven (69.9%) subjects had been bottle-fed with sugared milk, 86 (26%) of whom had caries. Two hundred and eight children had five or more sugary meals per day, 70 (33.6%) of whom had caries. No statistically significant relationship was seen between breast-feeding and the prevalence of tooth decay. CONCLUSIONS: The results of the present study show that the prevalence of early childhood caries in 12-36-month-old children from poor backgrounds in Recife is in accordance with the rate found in other Brazilian cities and is extremely high compared with that of the world population as a whole. Early childhood caries was not clearly related to the type of feeding in this sample. The prevalence of early childhood caries increased with age, and the number of sugary snacks between meals and a cariogenic diet were strongly related to early childhood caries. The lack of fluoridated water and high rates of early childhood caries in lead the authors to suggest that fluoride dentifrice should be introduced at 12 months of age as a fluoride supplement and an important aid in the prevention of childhood caries. Additional studies in different cultures and societies need to be undertaken before a definitive conclusion can be drawn.

Age Factors↗
PubMed2003

Caudate volume as an outcome measure in clinical trials for Huntington's disease: a pilot study.

Previous research has demonstrated that longitudinal change in caudate volume could be observed over a period of 3 years in subjects with Huntington's disease (HD). The current pilot study was designed to determine whether measurement of caudate change on magnetic resonance imaging (MRI) is a feasible and valid outcome measure in an actual clinical trial situation. We measured caudate volumes on pre- and post-treatment MRI scans from 19 patients at two sites who were participating in CARE-HD (Co-enzyme Q10 and Remacemide: Evaluation in Huntington's Disease), a 30-month clinical trial of remacemide and co-enzyme Q(10) in symptomatic patients with HD. Results from this pilot study indicated that decrease in caudate volume was significant over time. Power analysis indicated that relatively small numbers of subjects would be needed in clinical trials using caudate volume as an outcome measure. Advantages and disadvantages of using MRI caudate volume as an outcome measure are presented. We recommend the adoption of quantitative neuroimaging of caudate volume as an outcome measure in future clinical trials for treatments of HD.

Acetamides↗
PubMed2003

Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.

Adolescent↗
PubMed2003

Formocresol mutagenicity following primary tooth pulp therapy: an in vivo study.

OBJECTIVES: To investigate whether formocresol, in Buckley's original formulation, is mutagenic in vivo to lymphocyte cultures obtained from the peripheral blood of children aged from 5 to 10 years old. These children were recruited from those attending the dental clinics of Recife City Council and the University of Pernambuco School of Dentistry, Brazil. METHODS: The sample comprised 20 children who had primary teeth with cariously exposed vital pulps. Two venous blood samples were collected (6-8 ml) from each child, the first prior to vital pulpotomy (control group) and the second 24 h after pulpotomy (treated group). This research is a case-control study. The peripheral lymphocytes were grown in a complete culture medium consisting of 78% RPMI 1640 medium (a), supplemented with streptomycin (0.01 mg/ml), penicillin (0.005 ml(-1)), 20% fetal bovine serum (b) and 2% phytohemagglutinin (c). The lymphocytes were assessed for chromosomal aberrations via a previously published method which was modified. The cytogenetic analysis was performed in a blind test, where the slides were codified by an annotator and the scorers did not know which group they were analyzing. For each sample, this envolved the analysis of 200 metaphases. The level of significance adopted in the statistical test was 5.0% (p<0.05). RESULTS: There was no statistically significant difference in clinical doses between the control and treated groups, using Wilcoxon's Signed Ranks test, for the chromosomal aberrations (P=0.251) and for the total chromosomal breaks (P=0.149). Although there were no statistically significant differences between the control and treated groups, Buckley's formocresol was mutagenic for one patient, raising doubt about the desirability of its use for pulpotomies in children. CONCLUSIONS: The results revealed that, from a statistical standpoint, formocresol is not mutagenic. However, further investigations are required, preferably with a larger sample, in patients needing more than one pulpotomy in order to observe whether an increase in the quantity of the drug would increase the quantity of chromosome aberrations and also to verify individual susceptibility to chromosome alterations with the use of formocresol.

Case-Control Studies↗
PubMed2001

Familial influence on age of onset among siblings with Huntington disease.

In order to provide data relevant to a search for modifying genes for age of onset in Huntington disease, we examined the relationship between CAG number and age of onset in a total of 370 individuals from 165 siblingships, in two cohorts of siblings with Huntington disease: an American group of 144 individuals from 64 siblingships, and a Canadian population of 255 individuals from 113 siblingships. Using a logarithmic model to regress the age of onset on the number of CAG triplets, we found that CAG number alone accounted for 65%-71% of the variance in age of onset. The siblingship an individual belonged to accounted for 11%-19% of additional variance. This adds to the previous evidence that there are familial modifiers of the age of onset, independent of the CAG number. Such modifiers may consist of additional genes, which could be the target of a linkage study. A linkage study is feasible with the cooperation of a number of major centers and may be made more efficient by concentrating on sibling pairs that are highly discordant for age of onset.

Age of Onset↗
PubMed2001

The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis.

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine expansion in the protein huntingtin (htt). Pathogenesis in HD appears to involve the formation of ubiquitinated neuronal intranuclear inclusions containing N-terminal mutated htt, abnormal protein interactions, and the aggregate sequestration of a variety of proteins (noticeably, transcription factors). To identify novel htt-interacting proteins in a simple model system, we used a yeast two-hybrid screen with a Caenorhabditis elegans activation domain library. We found a predicted WW domain protein (ZK1127.9) that interacts with N-terminal fragments of htt in two-hybrid tests. A human homologue of ZK1127.9 is CA150, a transcriptional coactivator with a N-terminal insertion that contains an imperfect (Gln-Ala)(38) tract encoded by a polymorphic repeat DNA. CA150 interacted in vitro with full-length htt from lymphoblastoid cells. The expression of CA150, measured immunohistochemically, was markedly increased in human HD brain tissue compared with normal age-matched human brain tissue, and CA150 showed aggregate formation with partial colocalization to ubiquitin-positive aggregates. In 432 HD patients, the CA150 repeat length explains a small, but statistically significant, amount of the variability in the onset age. Our data suggest that abnormal expression of CA150, mediated by interaction with polyglutamine-expanded htt, may alter transcription and have a role in HD pathogenesis.

Age of Onset↗
PubMed2001

A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion.

Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.

Adult↗
PubMed2001

A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion.

Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.

Adult↗
PubMed2000

Delusions and hallucinations in Alzheimer's disease: prevalence and clinical correlates.

OBJECTIVES: The purpose of this study was to examine the frequency of delusions and hallucinations in patients with Alzheimer's disease (AD) and to investigate factors associated with each or the combination of the two. DESIGN: This was a cross-sectional, case-control study. SETTING: Neuropsychiatry and Memory Group, The Johns Hopkins University, USA. PARTICIPANTS: Three hundred and forty-two community-residing patients with probable AD according to NINCDS/ADRDA criteria were included in the study. MEASURES: Patients were assessed clinically for the presence of psychotic symptoms using the DSM-IV glossary definitions. The patients were also rated on standardized measures of cognitive impairment, depression, extrapyramidal symptoms, functional impairment and general health. RESULTS: Seventy-five (22%) AD patients had delusions only, nine (3%) had hallucinations only and 30 (9%) had both delusions and hallucinations. Hallucinations were associated with less education, African-American race, more severe dementia, longer duration of illness, falls and use of anxiolytics. Delusions were associated with older age, depression, aggression, poor general health and use of antihypertensives. Patients with both delusions and hallucinations were similar to the patients with delusions only. CONCLUSIONS: This study confirms the high prevalence of psychotic symptoms in AD patients encountered in clinical practice and suggests that individual psychotic symptoms have different associations.

Aged↗
PubMed2000

Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington's disease.

Previous research by our group demonstrated a longitudinal change in caudate volume for symptomatic subjects with Huntington's disease (HD), and suggested that volume of the caudate may be a useful outcome measure for therapeutic studies in symptomatic patients. The current study was designed to determine whether longitudinal change in caudate atrophy could be documented in presymptomatic carriers of the HD gene mutation, and to compare rate of change in these subjects with rate of change in mildly and moderately affected symptomatic patients. We measured caudate volumes on serial magnetic resonance image scans from 30 patients at three stages of HD: 10 presymptomatic; 10 with mild symptoms, as indicated by scores on the Quantified Neurological Exam (QNE) < or =35; and 10 with moderate symptoms (QNE >45). The mean interscan interval was 36 months. When analyzed separately, both symptomatic groups and the presymptomatic group demonstrated a significant change in caudate volume over time. Amount of change over time did not differ significantly among the three groups. We conclude that change in caudate volume may be a useful outcome measure for assessing treatment effectiveness in both presymptomatic and symptomatic subjects.

Adult↗
PubMed2000

Criminal behavior and emotional disorder: comparing youth served by the mental health and juvenile justice systems.

This study explored whether youth involved in joint service systems differed from single-agency users in terms of types of crimes committed and clinical functioning. Data from 4,924 youth involved in one county's public mental health and juvenile justice service systems were examined. Twenty percent of those youth receiving mental health services had recent arrest records, and 30% of youth arrested received mental health services. Of all youth arrested in the county, mental health service users had more arrests than non-mental health service users. A subsample of 94 mental health service users with arrests was matched on demographics with 94 mental health service users without arrests. Youth with arrests had a higher frequency of conduct disorder, higher Child Behavior Checklist Externalizing and Total Problem Scale scores, and more functional impairment on the Child and Adolescent Functional Assessment Scale as compared to youth without arrests. Implications for behavioral health service delivery were discussed.

Adolescent↗
PubMed2000

Vascular dementia and Alzheimer's disease: is there a difference? A comparison of symptoms by disease duration.

This study examined differences between vascular dementia (VaD) by the NINDS/AIRENS criteria and Alzheimer's disease (AD) on clinical grounds. A consecutive series of 517 patients with probable and possible VaD or AD were evaluated for cognitive, functional, and behavioral symptoms and separated into three subgroups by duration of dementia. These AD and VaD subgroups were then compared on a series of standardized clinical measures. The only consistent trends were for VaD patients to be more depressed, more functionally impaired, and less cognitively impaired within each disease duration subgroup. The authors conclude that there are few differences between clinically diagnosed VaD and AD. Subclassification of VaD into subgroups will improve the clinical utility of this nosologic entity.

Aged↗
PubMed1999

Trinucleotide repeat expansion and neuropsychiatric disease.

Trinucleotide, or triplet, repeats consist of 3 nucleotides consecutively repeated (e.g., CCG CCG CCG CCG CCG) within a region of DNA, a not uncommon motif in the genome of humans and other species. In 1991, a new type of genetic mutation was discovered, known as a dynamic or expansion mutation, in which the number of triplets in a repeat increases and the length becomes unstable. During the past decade, nearly 20 diseases-including Huntington disease, 2 forms of the fragile X syndrome, and myotonic dystrophy-caused by trinucleotide repeat expansions have been identified. The unstable nature of the expanded repeat leads to remarkable patterns of inheritance in these diseases, distinctly at odds with traditional notions of mendelian genetics. We review the clinical and genetic features of these disorders, with a particular emphasis on their psychiatric manifestations. We also critically examine the hypothesis that expansion mutations may have an etiologic role in psychiatric diseases such as bipolar disorder, schizophrenia, and autism.

Autistic Disorder↗
PubMed1999

Wandering behaviour in community-residing persons with dementia.

OBJECTIVES: To examine wandering behaviour in elderly demented persons in the community setting with respect to dementia characteristics and other factors that might influence wandering behaviour; to generate a statistical model to assess the relative importance of these various factors in predicting wandering behaviour. DESIGN: Cross-sectional, case-control investigation. SETTING: University-affiliated outpatient neuropsychiatric assessment center. PARTICIPANTS: Six hundred and thirty-eight consecutive community-residing new patients with dementia referred for evaluation. MEASUREMENTS: Comprehensive neuropsychiatric evaluation, including rating with Mini-Mental State Examination; General Medical Health Rating; Comell Scale of Depression in Dementia and caregiver interview. RESULTS: Wandering behaviour occurred in 17.4% of participants. It was significantly more prevalent in patients with Alzheimer Dementia (AD), patients with dementia of longer duration, and patients with more severe dementia. Wandering behaviour was associated with moderate to severe depression, delusions, hallucinations, and sleep disorder. Other significant associations of wandering behaviour included use of neuroleptic medication and male gender. After statistical adjustment for other variables, duration of dementia, severity of dementia and presence of sleep disorder retained significant statistical association with wandering behaviour. CONCLUSIONS: Wandering behaviour among community-residing elderly dementia patients is associated with a number of factors, some of which may be subject to modification. It is possible that management of coexistent psychopathology, particularly of sleep disorder, and of the underlying disease process of AD would help to ameliorate this problematic behavioural disorder. Further investigation is warranted into the relationship between neuroleptic medication and wandering behaviour and into possible alternative measures to control agitation in elderly dementia patients.

Age Distribution↗