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Biomedical subjects

D Warden

Publications and source records attributed to D Warden.

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↗
PubMed2005

Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer's disease.

BACKGROUND: Although epidemiological, clinical, and experimental evidence indicates that the inducible isoform of cyclo-oxygenase (COX-2) may be involved in the pathogenesis of several neurodegenerative disorders, the mechanisms whereby COX-2 contributes to Alzheimer's disease are largely unknown. OBJECTIVE: To undertake a longitudinal study of CSF levels of a major product of COX activity, prostaglandin E2 (PGE2), in relation to cognitive decline and survival in patients with Alzheimer's disease. METHODS: CSF PGE2 was measured on at least three annual visits in 35 controls and 33 Alzheimer patients (26 necropsy confirmed) who completed the Cambridge cognitive assessment (CAMCOG). RESULTS: Compared with controls, CSF PGE2 was higher in patients with mild memory impairment, but lower in those with more advanced Alzheimer's disease. The median survival time of patients with higher initial PGE2 levels was five years longer than those with lower levels. CONCLUSIONS: COX activity in Alzheimer's disease varies with stage of the disease. PGE2 levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer's disease.

Aged↗
PubMed2005

Rate of progression of cognitive decline in Alzheimer's disease: effect of butyrylcholinesterase K gene variation.

OBJECTIVE: To determine whether individuals with Alzheimer's disease (AD) and the K variant allele of butyrylcholinesterase have a slower rate of cognitive decline than those without the K variant allele of butyrylcholinesterase. METHOD: The cognitive status of 339 community based subjects with AD was assessed with the Mini Mental State Examination at baseline and yearly over a three year follow up period. The rates of cognitive decline of subjects with and without the K variant allele were compared. RESULT: Presence of the K allele was associated with a slower average rate of cognitive decline in subjects with severe AD. CONCLUSIONS: This finding is consistent with the suggestion that the K variant of butyrylcholinesterase has an important role in disease progression in AD, and this may have implications for treatment.

Aged↗
PubMed2002

APOE genotype influences acquisition and recall following traumatic brain injury.

APOE has been demonstrated to influence traumatic brain injury (TBI) outcome. The relationship between APOE genotype and memory following TBI was examined in 110 participants in the Defense and Veterans' Head Injury Program. Memory performance was worse in those who had an APOE epsilon 4 allele (n = 30) than those who did not (n = 80), whereas genotype groups did not differ on demographic or injury variables or on measures of executive functioning. These data support a specific role for the APOE protein in memory outcome following TBI, and suggest an APOE isoform-specific effect on neuronal repair processes.

Adult↗
PubMed2001

Biased responding: a case series demonstrating a relationship between somatic symptoms and impaired recognition memory performance for traumatic brain injured individuals.

Biased responding on the Sternberg Recognition Memory Test was observed in four patients with traumatic brain injury. None of these individuals met the Diagnostic and Statistical Manual's (DSM-IV) criteria for malingering. Individual recognition memory scores were high shortly after injury, declined to chance or below at the 6- and 12-month evaluations, and then showed substantial recovery by the 24-month evaluation. Recall memory performance actually declined slightly across this same 2-year period. Recognition memory scores were related to the extent to which the patients endorsed somatic items on the Hamilton Rating Scale for Depression (HAM-D). Poor performance was associated with high somatic scores. The relationship between memory and somatic scores on the HAM-D in this case series suggests that unconscious processes can influence memory performance and, because of this, that clinicians should not use such performance as a primary indicator of malingering. More importantly, biased responding and actual memory deficits may coexist. This is indicated in the current cases by the failure of recall memory to improve during the 2 years these patients were followed.

Adult↗
PubMed2000

Stereotactic breast biopsy: recumbent biopsy using add-on upright equipment.

OBJECTIVE: The purpose of the study was to show that stereotactic breast biopsy can be performed effectively and accurately using add-on stereotactic equipment when it is performed with the patient in a decubitus or recumbent position. MATERIALS AND METHODS: We retrospectively reviewed the results of 225 stereotactic core breast biopsies performed during a 42-month period. The biopsies were performed using a reclining mammography chair and add-on stereotactic equipment. Procedures were performed with the patient in the right or left lateral decubitus position or upright. Patients with benign biopsy results were followed up mammographically at 6 months initially, then yearly. RESULTS: Of the 225 lesions biopsied stereotactically, 205 lesions (91%) were biopsied with the patient in the decubitus (right or left) position and 20 (9%) biopsied with the patient upright. Pathology results were classified as abnormal in 45 lesions (20%) and normal in 180 lesions (80%). All but one of the abnormal lesions were followed up with surgical excision. One hundred thirty-four of the 180 benign lesions have been followed up with at least one 6-month mammogram (follow-up range, 6-40 months), and none of the lesions has been subsequently proven malignant. CONCLUSION: Stereotactic core biopsy can be performed effectively and accurately using standard add-on equipment when it is performed with the patient in the decubitus position. This approach obviates the use of dedicated prone stereotactic equipment.

Biopsy, Needle↗
PubMed1997

Salutary change after frontal brain trauma.

Adverse behavioral effects of frontal traumatic brain injury are well-known. Patients may suffer changes in personality ranging from disinhibition to apathy. Beneficial effects of traumatic brain injury are rarely described. We report three cases of patients who sustained frontal traumatic brain injury, one of whose social phobia resolved and the other two of whom had an improvement in impulsive and antisocial behavior. In one case the brain injury may have caused disinhibition of an inhibited state; in the other cases disinhibition associated with impulsivity was replaced by a more restrained state. This adds to the data on the integrative role of the frontal lobes in varied psychopathologic conditions.

Adult↗
PubMed1996

Renal oxidant injury and oxidant response induced by mercury.

The role of oxidative stress in mercuric chloride (HgCl2)-induced nephrotoxicity is uncertain and controversial. We demonstrate that I.L.C-PK1 cells, exposed to HgCl2, generate massive amounts of hydrogen peroxide, the latter completely quenched by the hydrogen peroxide scavenger, pyruvate. HgCl2 exerts a dose-dependent cytotoxicity which is attenuated by pyruvate and catalase. Cellular generation of hydrogen peroxide arises, at least in part, from mitochondria since mitochondrial rates of generation of hydrogen peroxide increase in response to HgCl2; HgCl2 also provokes a shift in absorbance spectra in rhodamine 123 loaded-mitochondria and stimulates mitochondrial state 4 respiration. HgCl2, applied for one hour, impairs cellular vitality as demonstrated by the MTT assay, an assay dependent in part on mitochondrial function. HgCl2 impairs function in other organelles such as lysosomes that maintain a transmembrane proton gradient; these latter effects are partially attenuated by pyruvate. We complement these in vitro findings with in vivo evidence demonstrating that HgCl2 stimulates renal generation of hydrogen peroxide. The functional significance of such generation of hydrogen peroxide was evaluated in rats deficient in selenium and vitamin E, a nutrient deficiency that impairs the scavenging of hydrogen peroxide and promotes the toxicity of this oxidant. In these rats serum creatinine values were significantly higher on sequential days following the administration of HgCl2. To probe the renal response to oxidative stress induced by HgCl2, we examined hydrogen peroxide-scavenging enzymes and redox-sensitive genes. Catalase activity was unaltered whereas glutathione peroxidase activity was decreased, effects that may contribute to the net renal generation of hydrogen peroxide. The redox sensitive enzyme, heme oxygenase, was markedly up-regulated in the kidney in response to HgCl2. HgCl2 also induced members of the bcl family, bcl2 and bclx, genes that protect against apoptosis and oxidant injury. In another model of oxidant-induced renal injury, the glycerol model, bcl2 mRNA was not induced at 6 and 24 hours after the administration of glycerol. In summary, we demonstrate that HgCl2 potently stimulates renal generation of hydrogen peroxide in vitro and in vivo and such generation of peroxide contributes to renal dysfunction in vitro and in vivo. We also demonstrate that in response to HgCl2, redox sensitive genes are expressed including heme oxygenase and members of the bcl family.

Animals↗
PubMed1996

Frontal lobe injuries, violence, and aggression: a report of the Vietnam Head Injury Study.

Knowledge stored in the human prefrontal cortex may exert control over more primitive behavioral reactions to environmental provocation. Therefore, following frontal lobe lesions, patients are more likely to use physical intimidation or verbal threats in potential or actual confrontational situations. To test this hypothesis, we examined the relationship between frontal lobe lesions and the presence of aggressive and violent behavior. Fifty-seven normal controls and 279 veterans, matched for age, education, and time in Vietnam, who had suffered penetrating head injuries during their service in Vietnam, were studied. Family observations and self-reports were collected using scales and questionnaires that assessed a range of aggressive and violent attitudes and behavior. Two Aggression/Violence Scale scores, based on observer ratings, were constructed. The results indicated that patients with frontal ventromedial lesions consistently demonstrated Aggression/Violence Scale scores significantly higher than controls and patients with lesions in other brain areas. Higher Aggression/Violence Scale scores were generally associated with verbal confrontations rather than physical assaults, which were less frequently reported. The presence of aggressive and violent behaviors was not associated with the total size of the lesion nor whether the patient had seizures, but was associated with a disruption of family activities. These findings support the hypothesis that ventromedial frontal lobe lesions increase the risk of aggressive and violent behavior.

Adult↗
PubMed1991

Memory for temporal order in schizophrenia.

Memory for temporal order information was examined in patients with chronic schizophrenia using the recency discrimination task. In this task, subjects were shown a pair of previously studied words and were asked to choose which one of the two words they had seen more recently. In addition, subjects performed the Wisconsin Card Sorting Test (WCST). The results showed that schizophrenic patients differed from normal control subjects in their performance on the recency discrimination task. In addition, for schizophrenic patients, performance on the recency discrimination task was inversely related to the number of perseverative errors on the WCST. These results provide further evidence of prefrontal-type cognitive deficits in schizophrenia.

Adult↗
PubMed1982

The relationship between blood and cerebrospinal fluid prolactin in nonhuman primates.

We studied the relationship between plasma and cerebrospinal fluid (CSF) concentrations of prolactin (PRL) in repeated and simultaneous samples of blood and CSF from chair-restrained rhesus monkeys. Following administration of thyrotropin releasing hormone (TRH), each of 4 monkeys showed increased plasma and lumbar CSF PRL concentrations. Increases in CSF PRL concentrations were muted and delayed until 60 min after peak plasma concentrations were attained. In 3 other monkeys we compared PRL concentrations in simultaneous lateral ventricular and lumbar CSF samples. ALthough we found no difference in PRL concentrations under baseline conditions, a ventricular-lumbar PRL concentration gradient became apparent after TRH stimulation. These studies demonstrate that changes in plasma PRL concentrations are reflected in CSF concentrations. They suggest that a significant blood-CSF barrier exists for PRL and the PRL may enter the CSF selectively via the ventricles.

Animals↗
PubMed1978

Day-old vaccination of maternally immune turkeys against Newcastle disease.

Maternally immune day-old turkey poults were vaccinated against Newcastle Disease with La Sota live vaccine and, concurrently, with emulsion killed vaccine. After an initial fall in maternal antibody the haemagglutination inhibition (HAI) geometric mean titre (GMT) of these birds rose to log2(6) and persisted at that level for eight months. Re-vaccination of some birds at 10 weeks with the emulsion vaccine caused GMTs to rise to log2(11). Six months later these levels were at log2(7). Further emulsion vaccination at 28 weeks produced a good anamnestic effect, the titre rising to log2(12). The authors discuss the possible advantages of this programme of vaccination as a routine for the immunisation of both fattening and breeding birds.

Animals↗