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Biomedical subjects

C A Orengo

Publications and source records attributed to C A Orengo.

At least 55 records · Page 3Linked to original sources

Contribution of cognitive impairment, depression, and psychosis to the outcome of agitated geropsychiatric inpatients with dementia.

This study investigated the correlates of change in behavioral disturbance in geropsychiatric inpatients with dementia. It was hypothesized that improvement in specific psychiatric symptoms, such as psychosis and depression, contribute to the improvement of specific behavioral disturbances. All admissions between October 1993 and May 1995 were reviewed to identify those patients admitted to the Houston VA geropsychiatry unit with a diagnosis of dementia; 233 patients were included in the study. Improvement in behavioral disturbance symptoms was associated with decreases in depression, thought disorder, and hostility. However, the relative importance of depressive and psychotic symptoms varied depending upon the type of behavioral disturbance examined. These results may support a focused approach employing therapies specific to the type of behavioral disturbance.

Aged↗

Cognitive decline in patients on an acute geropsychiatric unit.

The authors compared patients in a geropsychiatric unit who showed marked cognitive decline during hospitalization with those who did not. Patients who declined in cognitive function were older, were more likely to have a diagnosis of dementia, and were more anergic on admission. These patients were also discharged to more restrictive living environments. The subgroup of demented patients who declined in cognitive function were also older and improved less on anxiety and depression.

Age Factors↗

CATH--a hierarchic classification of protein domain structures.

BACKGROUND: Protein evolution gives rise to families of structurally related proteins, within which sequence identities can be extremely low. As a result, structure-based classifications can be effective at identifying unanticipated relationships in known structures and in optimal cases function can also be assigned. The ever increasing number of known protein structures is too large to classify all proteins manually, therefore, automatic methods are needed for fast evaluation of protein structures. RESULTS: We present a semi-automatic procedure for deriving a novel hierarchical classification of protein domain structures (CATH). The four main levels of our classification are protein class (C), architecture (A), topology (T) and homologous superfamily (H). Class is the simplest level, and it essentially describes the secondary structure composition of each domain. In contrast, architecture summarises the shape revealed by the orientations of the secondary structure units, such as barrels and sandwiches. At the topology level, sequential connectivity is considered, such that members of the same architecture might have quite different topologies. When structures belonging to the same T-level have suitably high similarities combined with similar functions, the proteins are assumed to be evolutionarily related and put into the same homologous superfamily. CONCLUSIONS: Analysis of the structural families generated by CATH reveals the prominent features of protein structure space. We find that nearly a third of the homologous superfamilies (H-levels) belong to ten major T-levels, which we call superfolds, and furthermore that nearly two-thirds of these H-levels cluster into nine simple architectures. A database of well-characterised protein structure families, such as CATH, will facilitate the assignment of structure-function/evolution relationships to both known and newly determined protein structures.

Databases, Factual↗

Depression in male geropsychiatric inpatients with and without dementia: a naturalistic study.

The authors compared the presentation and course of major depression in male geriatric inpatients with and without a diagnosis of dementia. Of 326 consecutive admissions to an inpatient geropsychiatry unit, 22 (7%) had a diagnosis of major depression without dementia, 35 (11%) had major depression with dementia. Both groups presented with similar types and severity of depressive symptoms, which improved substantially with treatment in both groups, as measured by Hamilton Depression Rating Scale scores. In addition, agitation, psychiatric, and side-effects symptoms decreased significantly in both groups. Our naturalistic results suggest the clinical value of intensive treatment of depressive symptoms in elderly demented patients, whether or not they meet the criteria for major depressive episode.

Aged↗

Delirium in geropsychiatric patients: patient characteristics and treatment outcomes.

The authors examined the effect of hospitalization on cognitive and behavioral symptoms in delirious elderly patients with and without dementia. Forty-four (13%) of the patients admitted to a Veterans Affairs Medical Center geropsychiatric unit were diagnosed with delirium and were administered the Mini-Mental State Examination, the Hamilton Depression Rating Scale, the Brief Psychiatric Rating Scale (BPRS), the Rating Scale for Side Effects, and the Cohen-Mansfield Agitation Inventory. The total sample significantly improved on all measures. When patients with delirium were divided into subgroups with and without dementia, both subgroups improved similarly. Patients discharged to more restrictive environments improved significantly on the BPRS only.

Activities of Daily Living↗

Outcome of psychiatric hospitalization for very low-functioning demented patients.

The authors determined the outcome of geropsychiatric hospitalization for 73 very low-functioning demented patients (GAF score < 21). General psychiatric symptoms, depression, and agitation decreased significantly, and mean GAF scores increased significantly, with no significant change in cognitive function. Psychiatric hospitalization can meaningfully improve function and quality of life even in this very impaired population. Despite these improvements many patients are discharged to more restrictive settings.

Activities of Daily Living↗

Tolerability of clonazepam in demented and non-demented geropsychiatric patients.

OBJECTIVE: The tolerability of clonazepam in geropsychiatric inpatients was examined in patients with and without a diagnosis of dementia. DESIGN: Forward-looking retrospective study comprising consecutive patients placed on clonazepam. SETTING: A geropsychiatry unit of a large Veterans Affairs Medical Center. PATIENTS: All geropsychiatry inpatients placed on clonazepam over a 21-month period of time. MEASURE: Mini-Mental State Examination, Brief Psychiatric Rating Scale, Cohen-Mansfield Agitation Inventory and the Rating Scale for Side Effects were performed at admission and discharge as part of an ongoing database. RESULTS: Twenty-four geropsychiatric inpatients were treated with clonazepam (mean dose of 1.2 mg for a minimum of 2 weeks) during the 21 months studies. About one half of the patients had a primary diagnosis of dementia and the remainder had a diagnosis of an affective or psychotic disorder. Two of these patients were discontinued because they had responded to the acute need for clonazepam and a third patient was discontinued because of the development of sedation and confusion. For the remaining 21 patients, scores improved significantly on the Brief Psychiatric Rating Scale (p = 0.017), the Cohen-Mansfield Agitation Inventory (p = 0.011), the Rating Scale for Side Effects (0.004) and the Global Assessment of Functioning (p < 0.000), with no differences in amount of improvement between demented and non-demented patient groups. Scores on the Mini-Mental State Examination remained unchanged. CONCLUSIONS: Clonazepam shows promise as a benzodiazepine with good tolerability in the elderly.

Aged↗

Analysis of domain structural class using an automated class assignment protocol.

The extent to which the contemporary dataset of protein structures can be segregated into four structural "classes" as originally defined by Levitt & Chothia in 1976 is examined and a simple method presented for the assignment of protein domains into these classes. Assignments are based on known three-dimensional structures, and for successful assignment it was found that helix/sheet content, contacts between secondary structures and their sequential order had to be used. The procedure attempts to maximise the automatic separation into classes for a dataset of 197 manually classified, non-homologous domains. It was found that approximately 90% of the structures were classified automatically; the remainder were borderline and were left for manual inspection. The method was then applied to a test set of 43 protein domains with similar results. The data support the concept of distinct classes of protein structure, although a few intermediate structures are found, demonstrating that it is possible to define relatively simple parameters complying with commonly accepted nomenclature that automatically define 90% of protein domains with essentially 100% accuracy. However, re-examination of the data also suggested that the previously separate alpha/beta and alpha + beta classes show considerable overlap and are more naturally represented as a single alpha beta class. This large alpha beta class can then be most easily subdivided by consideration of whether the sheets are mainly parallel, antiparallel or mixed. The correlation between structural class and function is discussed, together with the conservation of class within a sequence superfamily. This represents the first step in an automated phenetic description of protein structure complementing the usual phylogenetic approach to protein structure classification.

Algorithms↗

Association of serum cholesterol and triglyceride levels with agitation and cognitive function in a geropsychiatry unit.

Several studies have reported an association between aggression and cholesterol levels. The purpose of this study was to investigate the relationship of serum cholesterol and triglyceride levels with aggression and cognitive function in elderly inpatients. One hundred ten patients consecutively admitted to the Geriatric Psychiatry inpatient unit at Houston's Veterans Affairs Hospital received comprehensive evaluations by a multidisciplinary team. Fasting serum cholesterol and triglyceride levels were obtained within 3 days of admission. In addition, two geriatric psychiatrists administered the Mini-Mental State Examination (MMSE) and the Cohen-Mansfield Agitation Inventory (CMAI). Correlation coefficients were calculated between lipid levels, CMAI total and subscale scores, and MMSE scores. Multiple linear-regression analyses were done to further investigate the relation between lipid concentrations and various confounders. We found no significant correlation between serum triglyceride levels and MMSE, CMAI total, and CMAI factor scores. In addition, we found a significant positive correlation between serum cholesterol levels and physical nonaggressive behavior, and a significant negative correlation between serum cholesterol levels and MMSE scores. We found no relationship between aggressive behavior and serum cholesterol or triglyceride levels. However, an association between high cholesterol levels and agitation exists, which may be mediated by the association between high cholesterol levels and impaired cognition.

Aged↗

The use and tolerability of fluoxetine in geropsychiatric inpatients.

BACKGROUND: The efficacy and tolerability of fluoxetine were examined in 31 patients admitted to a geropsychiatric inpatient unit who were initiated and maintained on a regimen of fluoxetine. METHOD: The Hamilton Rating Scale for Depression, the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, and the Rating Scale for Side Effects were administered at admission and discharge, and scores were compared using paired t tests. Two patients were withdrawn from fluoxetine prior to discharge because of side effects; their data are not included in the analysis. RESULTS: We found significant improvement both in depressive symptoms and in general psychiatric symptoms and nonsignificant improvement in cognitive function. Fluoxetine was well-tolerated, and a significant decrease in the total scores of the Rating Scale for Side Effects was found. Subgroups of older patients (mean age = 75 years), less depressed patients, and demented patients were also examined. In all three groups, we found a statistically significant improvement in depressive symptoms, general psychiatric symptoms, and total side effects. CONCLUSION: Fluoxetine appears to be an effective and well-tolerated antidepressant in elderly inpatients of varying age, levels of depression, and psychiatric diagnoses.

Age Factors↗

Structural similarity between the pleckstrin homology domain and verotoxin: the problem of measuring and evaluating structural similarity.

An unexpected structural similarity is described between the pleckstrin homology (PH) domain and verotoxin. This similarity has escaped detection primarily due to the differences in topology that exist between the two proteins. By comparing this result with two previously reported similarities for the PH domain, one with the lipocalins and another with the FK506 binding protein, we discuss the problems of measuring and assessing structural similarities.

Amino Acid Sequence↗

Protein superfamilies and domain superfolds.

As the protein sequence and structure databases expand rapidly a better understanding of the relationships between proteins is required. A classification is considered that extends the sequence-based superfamilies to include proteins with similar function and three-dimensional structures but no sequence similarity. So far there are only nine protein folds known to recur in proteins having neither sequence nor functional similarity. These folds dominate the structure database, representing more than 30 per cent of all determined structures. This observation has implications for protein-fold recognition.

Algorithms↗

Multiple protein structure alignment.

A method was developed to compare protein structures and to combine them into a multiple structure consensus. Previous methods of multiple structure comparison have only concatenated pairwise alignments or produced a consensus structure by averaging coordinate sets. The current method is a fusion of the fast structure comparison program SSAP and the multiple sequence alignment program MULTAL. As in MULTAL, structures are progressively combined, producing intermediate consensus structures that are compared directly to each other and all remaining single structures. This leads to a hierarchic "condensation," continually evaluated in the light of the emerging conserved core regions. Following the SSAP approach, all interatomic vectors were retained with well-conserved regions distinguished by coherent vector bundles (the structural equivalent of a conserved sequence position). Each bundle of vectors is summarized by a resultant, whereas vector coherence is captured in an error term, which is the only distinction between conserved and variable positions. Resultant vectors are used directly in the comparison, which is weighted by their error values, giving greater importance to the matching of conserved positions. The resultant vectors and their errors can also be used directly in molecular modeling. Applications of the method were assessed by the quality of the resulting sequence alignments, phylogenetic tree construction, and databank scanning with the consensus. Visual assessment of the structural superpositions and consensus structure for various well-characterized families confirmed that the consensus had identified a reasonable core.

Amino Acid Sequence↗

Alpha plus beta folds revisited: some favoured motifs.

BACKGROUND: By performing extensive pairwise structural comparisons, we recently identified a set of unique folds from the Brookhaven protein structure data bank. This analysis revealed considerable similarities between a large subgroup of the alpha+beta folds, which led us to re-examine the types of folds occurring in this class and the nature of the relationships between them. RESULTS: Two major alpha+beta fold groups can be distinguished. In the first, described as alpha-beta sandwiches because alpha-helices and beta-strands occupy separate and distinct layers, a split beta alpha beta motif recurs frequently. The other group, alpha-beta rolls, contains fewer helices and is more diverse. In these, the beta-sheet has folded or rolled over, providing a cradle for the alpha-helix. A beta beta beta alpha-meander motif is found throughout the alpha+beta class. CONCLUSION: Although many alpha-beta sandwiches have very similar folds, few share common functions and the active sites are distributed over the whole surface of the fold. The ability of the alpha-beta sandwich to accommodate a range of functions suggests that it is a stable fold and one that is able to adapt a number of sites to satisfy different functional requirements. In contrast, amongst the alpha-beta rolls, folds having the same roll type often have common functions.

Animals↗

A local alignment method for protein structure motifs.

A method for the comparison of protein three-dimensional substructures was developed. The method employs the double dynamic programming method of Taylor & Orengo but identifies multiple local alignments rather than a single global alignment. A modification based on the Smith Waterman algorithm for sequence alignment enables the automatic identification and growth of the most structurally similar local alignments irrespective of length and composition. The method can also be used in a search mode to match substructures. Roughly five minutes is required to find all Greek-key motifs in a protein of 100 residues. Two novel globin folds have been detected using the method, the antibiotic protein colicin A and diphtheria toxin, neither of which have any functional relationship to the globins.

Amino Acid Sequence↗