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Biomedical subjects

P D Harvey

Publications and source records attributed to P D Harvey.

At least 19 recordsLinked to original sources
PubMed2006

Effects of rivastigmine on cognitive function in patients with traumatic brain injury.

OBJECTIVE: To compare the efficacy and safety of rivastigmine (3 to 6 mg/day) vs placebo over 12 weeks in patients with traumatic brain injury and persistent cognitive impairment. METHODS: This prospective, randomized, double-blind, placebo-controlled study was conducted in 157 patients at least 12 months after injury. The primary efficacy measures were the Cambridge Neuropsychological Test Automated Battery (CANTAB) Rapid Visual Information Processing (RVIP) A' subtest and the Hopkins Verbal Learning Test (HVLT). The primary efficacy outcome was the proportion of patients who demonstrated 1.0 SD or greater improvement from baseline at week 12 on CANTAB RVIP A' or HVLT. RESULTS: The percentage of responders at week 12 on either the CANTAB RVIP A' or HVLT was 48.7% for rivastigmine and 49.3% for placebo (p = 0.940). Furthermore, for the overall study population, there were no significant differences for any of the secondary efficacy variables. In a subgroup of patients with moderate to severe memory impairment (n = 81), defined as 25% impairment or greater on HVLT at baseline, rivastigmine was significantly better than placebo for a number of measures, including the proportion of HVLT responders and CANTAB RVIP mean latency. CONCLUSIONS: Rivastigmine was safe and well tolerated in patients with traumatic brain injury with cognitive deficits. Rivastigmine shows promising results in the subgroup of patients with traumatic brain injury with moderate to severe memory deficits.

Adolescent↗
PubMed2004

A comprehensive analysis of verbal fluency deficit in geriatric schizophrenia.

Deficits in verbal fluency are common in schizophrenia and may provide keys to some of the abnormalities in the semantic system in schizophrenia. While a number of studies have outlined the severity and implications of verbal fluency deficits in younger schizophrenia patients, these findings have not yet been extended to older patients with schizophrenia. In this study, 392 older (age >/= 50) patients with schizophrenia were administered phonological and semantic (i.e., category) fluency examinations, as well as tests of learning, memory, language, and praxic skills, and rated for clinical symptoms and functional status. When compared to normative standards, 82% of the patients were impaired in semantic fluency and 83% were impaired in phonological fluency. Both semantic and phonological fluency impairment were significantly correlated with other cognitive variables, total scores on the functional status measure, and with the social and self-care subscales. Scores were uncorrelated with the severity of psychosis, but were correlated with the severity of negative symptoms. Furthermore, the severity of poverty of speech (a clinical measure of verbal underproductivity) was moderate in magnitude and failed to enter as a predictor of verbal fluency, indicating that impaired fluency scores are not simply an artifact of general underproductivity or mutism. The findings support conclusions from studies with younger schizophrenia patients that suggest that verbal fluency impairment is a consequence of a disorganized semantic system. Verbal fluency impairment remains common and functionally relevant in schizophrenia patients in late life.

Aged↗
PubMed2001

Preparation, characterization, and luminescence properties of gallium-metal face-to-face diporphyrins (M = H(2), GaL, Ru(CO)(OH), Co).

The preparation and characterization of a new series of mixed metal cofacial anthracene-bridged diporphyrins (DPA) containing a GaL fragment (L = OMe, OH) and another metallic center (M = GaL, Ru(CO)(OH), Co, and H(2) (i.e. free base)) are reported. The luminescence properties at 298 and 77 K, in degassed EtOH solution, are also reported, and are characterized by a weak pipi fluorescence (2 < tau(F) < 7 ns) arising from the low energy Q-bands (S(1)-->S(0)). In the mixed diporphyrin systems, a strong pipi fluorescence is detected from the free base, while the transition metalloporphyrins of Co(II) and Ru(II) do not emit. The homobimetallic di[Ga(OMe)] species exhibits an unprecedented double (pi)(pi) fluorescence arising from the two lowest energy absorption Q-bands. On the basis of a comparison with photophysical data on GaL monoporphyrins, the weak fluorescence and absence of phosphorescence for most cases indicate efficient intramolecular quenching. To define structural features, the X-ray structures of (DPA)[Ga(OMe)](2) (2), (DPA)[Ga-(OH)-Ru(CO)] (5a), and (DPA)[Ga(OMe)-Ru(MeOH)(CO)] (5b) have been obtained. The structures of 5a and 5b demonstrate an interesting aspect of the structural chemistry of these ligands related to the internal methoxide and methanolic ligands in 5b (resulting in a large interplanar separation and center-to-center distance) and the internal metal-bridging hydroxyl ligand in 5a (resulting in a small interplanar separation and center-to-center distance). These data support previously reported discussions on the ability of the DPA and the DPB analogue (diporphyrinylbiphenylenyl) ligands to open and close their "bite" around the binding pocket between the porphyrin macrocycles.

Journal Article↗
PubMed2001

Diagnosis of manic episodes in adolescent inpatients: structured diagnostic procedures compared to clinical chart diagnoses.

This study examined the accuracy of clinical chart diagnoses of manic episodes in adolescent psychiatric patients, as well as treatment selection and patient outcome. A consecutive sample of 120 consenting adolescent patients was assessed at admission, discharge, and 30 and 120 days post-discharge. Clinical chart diagnoses were compared to research-quality diagnoses involving structured interview, chart review, and consensus. Agreement statistics were computed, and the symptom and treatment differences were compared between patients for whom there was and was not diagnostic agreement. Clinical diagnoses of manic episodes were more common than research diagnoses, and the rate of agreement between diagnoses was low (kappa = 0.15). Patients diagnosed as experiencing a manic episode by the clinical chart, but not via the research procedure, had reduced severity scores on elation and activity, and higher scores on depression. These patients also had more severe scores on depressive symptoms at follow-up. Manic episodes were diagnosed more frequently by clinicians relative to research-quality procedures. Patients who were diagnosed as experiencing manic episodes by the clinician, but not the research procedure, appeared to have depression and hostility, but not elation. The depression in these patients may not be adequately treated, and there are potential clinical implications of over-diagnosis of manic episodes in adolescents.

Adolescent↗
PubMed2001

Cognitive impairment in elderly patients with schizophrenia: age related changes.

Cognitive impairment in schizophrenia is a major feature of the illness. Like many of the other aspects of the illness, however, it has not been studied extensively in older patients. Several studies of older patients with a lifetime course of poor outcome and chronic institutional stay have indicated that some patients manifest evidence of profound cognitive impairments on a cross-sectional basis and cognitive and functional decline over longitudinal follow-ups of 30 months or longer. Risk factors for this decline include lower educational attainment and more severe positive symptoms, but do not include more severe symptoms of physical illness. These impairments have been shown to be discriminable from normal age-related changes and from the changes associated with Alzheimer's Disease. In contrast, studies of patients with no history of lifetime institutional stay find no such evidence of either age-related changes in cognitive functioning or longitudinal decline in cognitive or functional status. Since there is accumulating evidence of progressive brain changes over the lifespan in patients with schizophrenia, the course of cognitive deficits in later life will remain an important topic, both for understanding the lifetime course of schizophrenia and for developing interventions aimed at reduction of disability in the illness.

Aged↗
PubMed2001

Cognition in schizophrenia.

Cognitive dysfunction has been described as a hallmark feature of schizophrenia since the first descriptions of the illness. Kraepelin described a number of features of the disorder that he thought reflected impairments in cognition and attention. He also speculated that cognitive impairments were mediated by neurobiologic dysfunction, specifically impairments in the functions of the frontal lobe. Since Kraepelin's time, there have been many changes in the general conceptions of schizophrenia, including ideas regarding the status and importance of cognitive impairment in the illness. Due to increased sophistication of neuropsychologic assessment and neuroimaging techniques, cognitive impairment has again has risen to the forefront of importance in terms of theories regarding the etiology and treatment of schizophrenia.

Attention↗
PubMed2001

Guanfacine treatment of cognitive impairment in schizophrenia.

Norepinephrine plays a significant role in the working memory functions of the prefrontal cortex by its actions at alpha-2a noradrenergic receptors. Guanfacine has demonstrated efficacy in reversing working memory deficits in non-human primate. In the present study the effect of guanfacine adjunctive treatment to neuroleptics on the cognitive performance of schizophrenic patients was investigated in a four week, placebo-controlled, double-blind, parallel design trial. The primary analyses revealed no significant differences between guanfacine and placebo treatment; however, exploratory non-parametric statistics revealed some significant and some trend differences between guanfacine and placebo on spatial working memory test performance and CPT reaction time in those subjects treated with atypical neuroleptics.

Adrenergic alpha-Agonists↗
PubMed2001

Gender differences in poor outcome patients with lifelong schizophrenia.

Gender effects have been reported quite consistently in schizophrenia, with male patients having an earlier age of onset, poorer functional outcome, greater negative symptoms and cognitive impairment, and less severe positive symptoms. Because age of onset, cognitive impairments, and negative symptoms are all correlated with poorer functional status, it is not clear if previously reported gender differences in symptoms are just recapturing gender differences in functional outcome. In this study, 205 geriatric patients with lifelong poor-outcome schizophrenia (43% male) were examined for the severity of schizophrenic symptoms, cognitive impairments, and specific deficits in adaptive skills, as well as for demographic differences such as age at first psychiatric admission, premorbid education, and current treatment status. Previously reported gender differences were replicated in these patients with a uniformly poor functional outcome, with male patients having more severe negative symptoms and an earlier age of first psychiatric admission. No differences in cognitive functioning or specific functional deficits were found, however. These findings suggest that negative symptom severity is greater in male patients regardless of functional outcome and that the association of cognitive deficits with gender may be found only in patients with better functional outcome. The study of gender-related differences in brain structure or function and their interaction with overall course of illness might help understand these differences in symptom presentation.

Activities of Daily Living↗
PubMed2001

Convergent validity and neuropsychological correlates of the schedule for the assessment of negative symptoms (SANS) attention subscale.

Cognitive deficits have come to be viewed as a hallmark feature of schizophrenic illness. Although laboratory based assessment of patients' cognitive deficits has been well investigated, few studies to date have examined the utility of clinical ratings of cognitive symptoms using the Schedule for the Assessment of Negative Symptoms (SANS) attention subscale. In this report, we examined the convergence between clinical ratings of cognitive impairment using the SANS attention subscale and performance on a variety of neurocognitive tests designed to measure attentional impairment, as well as other cognitive constructs such as working memory and executive functioning. A total of 56 acute schizophrenic inpatients were clinically rated with the SANS and completed the Continuous Performance Test, Digit Span Distraction Test, Wisconsin Card Sorting Task, and the Trailmaking Test. A series of correlational and regression analyses were conducted to test the concurrent and discriminant validity of the SANS attention subscale. Performance measures of attention, but not working memory or executive functioning, were significantly correlated with and moderately predicted the severity of SANS rated inattention. Additionally, the attention subscale was discriminated from the other SANS negative symptom subscales in predicting a laboratory measure of attentional functioning. The SANS attention subscale demonstrated both concurrent and discriminant validity. These data indicate that attentional dysfunction in schizophrenia can be meaningfully rated and interpreted using the SANS.

Adolescent↗
PubMed2001

Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment.

OBJECTIVE: Novel antipsychotic medications have been reported to have beneficial effects on cognitive functioning in patients with schizophrenia. However, these effects have been assessed in studies with considerable variation in methodology. A large number of investigator-initiated and industry-sponsored clinical trials are currently underway to determine the effect of various novel antipsychotics on cognitive deficits in patients with schizophrenia. The ability to discriminate between high- and low-quality studies will be required to understand the true implications of these studies and their relevance to clinical practice. METHOD: This article addresses several aspects of research on cognitive enhancement in schizophrenia, emphasizing how the assessment of cognitive function in clinical trials requires certain standards of study design to lead to interpretable results. RESULTS: Novel antipsychotic medications appear to have preliminary promise for the enhancement of cognitive functioning. However, the methodology for assessing the treatment of cognitive deficits is still being developed. CONCLUSIONS: Researchers and clinicians alike need to approach publications in this area with a watchful eye toward methodological weaknesses that limit the interpretability of findings.

Antipsychotic Agents↗
PubMed2001

Six-year follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer's disease and normal aging.

OBJECTIVE: Follow-up studies of cognitive functions of poor-outcome (long-term institutionalized) elderly patients with schizophrenia have demonstrated deterioration over time, while stable cognitive functions over time have been reported for younger, better-outcome schizophrenic patients. This study examined whether cognitive changes in elderly schizophrenic patients with a history of long-term institutional stay extended to institutionalized younger patients. The rate of decline was compared to changes associated with Alzheimer's disease. METHOD: Patients with schizophrenia (N=107) age 20-80 years were followed over 6 years and assessed with the Clinical Dementia Rating and the Mini-Mental State Examination. The schizophrenic subjects age 50 and older were compared to 136 healthy comparison subjects and 118 Alzheimer's disease patients age 50 and older who were assessed over a similar follow-up period. RESULTS: There was a significant age group effect on the magnitude of cognitive decline for the schizophrenic subjects, with older subjects experiencing greater levels of decline over the follow-up. Neither the healthy individuals nor the Alzheimer's disease patients demonstrated similar age-related differences in the magnitude of cognitive change over the follow-up, with healthy comparison subjects showing no change and Alzheimer's disease patients manifesting decline regardless of age at the initiation of the follow-up. CONCLUSIONS: Institutionalized schizophrenic patients demonstrated an age-related pattern of cognitive change different from that observed for Alzheimer's disease patients and healthy individuals. The cognitive and functional status of these schizophrenic patients was fairly stable until late life, suggesting that cognitive change may not be occurring in younger patients over an interval as long as 6 years.

Adult↗
PubMed2001

Aggression in elderly schizophrenia patients: a comparison of nursing home and state hospital residents.

This study examined the role of cognitive functioning, adaptive functioning, and symptomatology in predicting aggression in institutionalized geriatric schizophrenic patients residing in either a state institution (n=56) or a nursing home (n=113). Patients were assessed with a neuropsychological battery and rated for positive and negative symptoms, social functioning, and aggressiveness. Nursing home residents were older and more cognitively and functionally impaired than institutional residents. The prevalence of verbal, but not physical, aggression was similar to findings in younger, acutely hospitalized patients in previous studies. In the hospitalized group, severity of negative symptoms was predictive of physical aggression. In the nursing home group, severity of positive symptoms was predictive of verbal aggression and self-care deficit was predictive of physical aggression. Results indicate that verbal aggression, like positive symptoms, decreases little with aging in institutionalized schizophrenic patients, and that predictors of aggressive behavior are as difficult to identify in elderly patients as in younger ones.

Aged↗
PubMed2001

Are the interpersonal and identity disturbances in the borderline personality disorder criteria linked to the traits of affective instability and impulsivity?

This study examines the degree to which two putative biologically influenced personality traits, affective instability and impulsive aggression, are associated with some of the interpersonal and intrapsychic disturbances of borderline personality disorder (BPD) and with choice of defense mechanism. In a sample of 152 personality disorder patients, affective instability and impulsive aggression were measured. Defense mechanisms were assessed in 140 of these patients using the Defensive Style Questionnaire (DSQ). The correlations between the traits of affective instability and impulsive aggression and the eight DSM-III-R criteria for borderline personality disorder and 20 DSQ defenses were examined. Affective instability was significantly correlated with the DSM-III-R criteria of identity disturbance, chronic emptiness or boredom, inappropriate anger, suicidality, and the affective instability criteria. It also was associated with the defenses of splitting, projection, acting out, passive aggression, undoing, and autistic fantasy. Impulsive aggression was related to unstable interpersonal relationships, inappropriate anger and impulsiveness and with the defense of acting out. It was negatively correlated with the defenses of suppression and reaction formation. A number of the interpersonal and experiential disturbances and defense mechanisms that are features of BPD are associated with the traits of affective instability and impulsive aggression among patients with personality disorders.

Adult↗
PubMed2000

Practice-related improvement in information processing with novel antipsychotic treatment.

BACKGROUND: Attentional deficits are prominent in schizophrenia, and skill learning is impaired. Novel antipsychotic treatment has been reported to improve certain cognitive skills in schizophrenic patients, but no information is yet available about the effect of newer medications on skill learning. METHODS: Clinically stable patients with schizophrenia (n=16) and chronically hospitalized inpatients (n=8) were recruited while receiving conventional antipsychotic treatment. Subjects were tested at baseline on a visual continuous performance test (CPT), performed alone and simultaneously with an auditory CPT. Normal controls (n=8) were also tested at baseline. The inpatients and half of the outpatients were switched to treatment with risperidone. All patients then performed the visual CPT on a daily basis and performed the dual tasks once per week, for 4weeks. RESULTS: Patients who remained on conventional medications did not improve in their performance despite the extensive practice on the test. Both chronic and stable patients receiving risperidone treatment manifested a statistically significant (P<0.05) improvement from baseline on both single and dual-task visual CPT. Stable outpatients performed significantly better at the end of the protocol than the normal controls performance at baseline (P<0.05). IMPLICATIONS: These results suggest that practice-related improvements in the performance of information processing tests are enhanced by novel antipsychotic medications. Although the specific biological mechanism of this effect is not yet known, the results may suggest that use of newer medications will enhance skill development and perhaps facilitate rehabilitation of patients with schizophrenia.

Adult↗
PubMed2000

Preparation and characterization of [[M(dmb)2]TCNQ.xTCNQo]n polymers (M=Cu,Ag; dmb = 1,8-diisocyano-p-menthane; x = 0, 0.5, 1.0, 1.5; TCNQ = 7,7,8,8-tetracyano-p-quinodimethane) and design of new semi- and photoconducting organometallic materials.

New thermoplastic organometallic materials of the type [[M(dmb)2]TCNQ.xTCNQo.y solvent], (M = Cu(I), Ag(I); dmb = 1,8-diisocyano-p-menthane; TCNQ = 7,7,8,8-tetracyano-p-quinodimethane, x = 0, 0.5, 1.0, 1.5; solvent = none, THF or toluene) have been prepared and characterized from X-ray powder diffraction patterns, X-ray crystallography (for some Ag polymers), DSC, and conductivity measurements. While the [[M(dmb)2]TCNQ.xTCNQo]n polymers (M = Cu,Ag; x = 0, 0.5) are insulating, the others (x = 1.0 and 1.5) are semiconducting, and the relative conductivity is found to be a function of the molecular weight and crystallinity. The [[Cu(dmb)2]TCNQ.1.5TCNQ]n material is also photoconducting, while the Ag analogue is not. Photochemical and luminescence quenching experiments in the solid-state established that the Cu+ center and TCNQo act as electron donor and acceptor, respectively, in this photoprocess. Finally photocells of the type glass/SnO2/[Cu(dmb)2]TCNQ.TCNQo]n + 0.5 acceptor/Al (acceptor = TCNQo, C60 and TCNN (13,13,14,14-tetracyano-5,12-naphthacenequinodimethane)) have been designed and characterized. The quantum yields (number of photoproduced electrons/number of photons) are as follows: TCNQ, 1.6 x 10(-4), C60, 5 x 10(-5), TCNN, 3.0 x 10(-4) at lambdaexc = 330 nm. X-ray data for [[Ag(dmb)2]TCNQ.2THF]n: space group P2(1/c), monoclinic, a = 13.5501(10), b = 9.9045(10), c = 32.564(2) A, beta = 91.130(10) degrees, Z = 4. X-ray data for [[Ag(dmb)2]TCNQ.0.5TCNQo.0.5 toluene]n: space group P2(1/c), monoclinic, a = 14.3669(19), b = 9.1659(3), c = 34.012(3) A, beta = 92.140(8) degrees, Z = 4. X-ray data for [[Ag(dmb)2]TCNQ.1.5TCNQo]n: space group C2/c, monoclinic, a = 25.830(11), b = 9.680(2), c = 42.183(19) A, beta = 104.87(4) degrees, Z = 8. X-ray data for [[Ag(dmb)2]DCTC]n: space group P2(1/a), monoclinic, a = 26.273(3), b = 9.730(3), c = 31.526(3) A, beta = 112.12(2)degrees, Z = 4.

Journal Article↗
PubMed2000

Chemical properties of the Pd4(dppm)4(H)2(2+) cluster and the homogeneous electrocatalytical behavior of hydrogen evolution and formate decomposition.

Two new reductive electrochemical (CO2 + H2O + 2e-; HCO2H + 2e-) and two new chemical methods (Al(CH3)3 + proton donor; NaO2CH) to prepare the title compound from Pd2(dppm)2Cl2 are reported. For the latter method, an intermediate species formulated as Pd2(dppm)4(O2CH)2(2+) is identified spectroscopically (1H NMR, 31P NMR, IR, and FAB-MS). Limited stability of the title compound in the presence of Cl- and Br- as counteranions is noticed and is due to sensitivity of the cluster toward nucleophilic attack of the halide ions. This result is corroborated by the rapid decomposition of these clusters in the presence of CN- to form the binuclear species Pd2(dppm)2(CN)4 and by the preparation of the stable salts [Pd4(dppm)4(H)2](X)2(X- = BF4-, PF6-, BPh4-). Upon a two-electron electrochemical reduction of this cluster to the neutral species (E1/2 = -1.42 V vs SCE in DMF) in the presence of 1 equiv of HCO2H, a highly reactive species formulated as [Pd4(dppm)4(H)3]+ is generated and characterized by 1H NMR, 31P NMR, and cyclic voltammetry. Subsequent addition of H+ (via RCO2H; R = H, CH3, CF3, C6H5) under the same reducing conditions, induces the homogeneous catalysis of H2 evolution. The turnover number is found to be 134 in 2 h, with no evidence for catalyst decomposition. This same species also exhibits a one-electron oxidation process (E1/2 = -0.61 V vs SCE in DMF) that induces the catalytical decomposition of formate (HCO2- --> CO2 + 1/2H2 + 1e-). This double catalysis from the same cluster intermediate is unprecedented.

Journal Article↗