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Biomedical subjects

R Coen

Publications and source records attributed to R Coen.

At least 19 recordsLinked to original sources

Behavioural disturbance triggers recognition of dementia by family informants.

OBJECTIVE: To determine the frequency of unrecognised dementia in a group of community dwelling elderly, and to identify factors associated with dementia recognition by informants. SAMPLE SELECTION: People over 65 years with an AGECAT case or subcase organic diagnosis or an MMSE < or = 23 were identified from a database of community dwelling elderly. A psychiatrist to confirm the diagnosis of dementia according to ICD-10 criteria interviewed these individuals. STUDY PARTICIPANTS: Sixty-two community dwelling elderly meeting ICD-10 criteria for dementia whom had reliable informants. METHODS: Prior to the start of the interview the informant was questioned about whether they felt the patient had memory difficulties and if so whether they had a medical evaluation for their memory problems. A psychiatrist then interviewed the patient and informant to establish whether that patient met ICD-10 criteria for dementia. Basic sociodemographic details were collected and the following assessments were carried out: the Blessed Dementia Rating Scale, the Clinical Dementia Rating Scale, the Behave-AD and the Baumgarten Behavioural Disturbance Scale. ANALYSIS: Univariate and step-wise forward logistic regression analysis were used to examine the factors associated with recognition of memory difficulties. RESULTS: Twenty-nine percent of family informants of people with dementia failed to recognise a problem with their relatives'memory. Where memory difficulties were recognised only 39% of this group received a medical evaluation. Using univariate analysis recognition of memory difficulties by family informants was associated higher levels of behaviour disturbance ( p = or < 0.0011), greater functional impairment ( p = 0.0039), with increasing cognitive impairment ( p = 0.013). Using a logistic regression model, to test the independence of these variables, increasing behavioural disturbance (p = 0.0001) was associated with recognition of dementia by family informants. CONCLUSIONS: Recognition of memory problems by family members is associated with increasing behavioural disturbance. Even with recognition of dementia, families often fail to seek medical attention. Education of the lay public on the early signs and symptoms of dementia must be a key first step in improving recognition of dementia in the community dwelling elderly.

Activities of Daily Living↗

Sleep disturbance in mild to moderate Alzheimer's disease.

BACKGROUND AND PURPOSE: To determine the prevalence of sleep disturbance in a memory clinic population of Alzheimer's disease (AD) patients and identify its clinical correlates. PATIENTS AND METHODS: Data from 215 attendees at a memory clinic, who were diagnosed with Alzheimer's disease, were examined. This included data from cognitive, functional and neuropsychological assessments. Sleep disturbance was determined using the question about diurnal rhythm disturbance on the BEHAVE-AD questionnaire. Two groups, with and without sleep disturbance, were compared. Group differences were analysed using univariate analysis and stepwise logistic regression analysis. RESULTS: The prevalence of sleep disturbance in this sample was 24.5%. The BEHAVE-AD 'aggressiveness' (P=0.009) and 'global rating' (P=0.029) (a measure of global impact of behavioural disturbance) were found to be significant predictors of sleep disturbance in AD. CONCLUSIONS: Sleep disturbance in AD is associated with other behavioural symptoms, notably aggressiveness. Sleep disturbance in AD has significant impact on the patient and/or caregiver. Consideration of co-morbid behavioural symptoms may aid the clinician in choosing a suitable treatment for sleep disturbance in AD.

Aged↗

A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease.

BACKGROUND: Non-cognitive symptoms are a frequent feature of Alzheimer's disease (AD). Much of the literature that has accumulated pertains to cross-sectional prevalence of these symptoms. There has been relatively little attention paid to the longitudinal course of Behavioural and Psychological Symptoms of Dementia (BPSD). AIMS: The purpose of this study is to examine the longitudinal course of BPSD in a group of patients with mild AD. METHODS: A retrospective review of a database was performed to identify patients with NINCDS/ADRDA criteria for probable AD and who had been evaluated three times at yearly interval over a two-year period. Fifty-two subjects were identified with probable AD that had completed follow-up for 24 months. The BEHAVE-AD was used to evaluate BPSD and data was analysed using a Markov analysis. RESULTS: Activity disturbance is a common and relatively persistent symptom in the mild stages of AD. Anxiety, paranoid ideation, and aggression were moderately persistent. Affective symptoms were not persistent with less than half the patients having the symptoms a year later. CONCLUSIONS: Activity disturbance is common and persistent in early AD. Paranoid and delusional ideation shows moderate persistence and depressive symptoms infrequently last longer than a year. These findings may have clinical relevance for the pharmacological and non-pharmacological management of BPSD.

Aged↗

Verbal aggression in Alzheimer's disease. Clinical, functional and neuropsychological correlates.

OBJECTIVES: To determine the clinical, functional and neuropsychological correlates of verbal aggression in Alzheimer's disease in a group of consecutive first attendees to a memory clinic. METHODS: 150 people were evaluated and diagnosed as suffering with probable Alzheimer's disease. These people were tested using the Behave-AD for the presence of verbal aggression, delusions, depression and agitation. They were also assessed with cognitive, functional and neuropsychological scales. RESULTS: Twenty-eight per cent of this group of Alzheimer patients had exhibited some verbal aggression in the preceding month. Male gender (p = 0.022), the presence of paranoid and delusional ideation (p = 0.003) and agitation (p = 0.042) were significantly associated with verbal aggression in a stepwise backward logistic regression analysis. CONCLUSION: The presence of verbal aggression should prompt the clinician to search for delusional ideation, which may respond to pharmacotherapy.

Aged↗

Burden in carers of dementia patients: higher levels in carers of younger sufferers.

A comparative study of the clinical characteristics of early onset dementia (onset before the age of 65) and late onset dementia sufferers was conducted. The level of carer burden among carers of both groups was measured. Carer burden was significantly higher among carers of younger sufferers, although there were no significant differences between the groups in terms of clinical features such as severity of dementia or behavioural disturbance. Higher carer burden showed an inverse relationship to patient's age. Our results have implications in terms of encouraging community care for dementia sufferers, and suggest that further exploration to identify factors associated with burden in younger carers is required.

Adaptation, Psychological↗

DNA single-strand breaks in peripheral lymphocytes of clinical personnel with occupational exposure to volatile inhalational anesthetics.

The rates of DNA single-strand breaks in peripheral lymphocytes of 41 persons administering anesthesia daily and 44 control persons were determined by nucleoid sedimentation. There is a significantly higher rate of DNA single-strand breaks in nonsmoking anesthesia persons than in nonsmoking control persons (P < 0.01). Smoking anesthesia persons and smoking control persons presented increased rates of DNA single-strand breaks. Nonsmoking nurse anesthetists showed an insignificantly higher rate of damage than nonsmoking anesthesiologists. DNA single-strand breaks indicate damage before the start of DNA repair. Therefore, detected DNA single-strand breaks may be reversible. As not every DNA repair is perfect, increased rates of DNA single-strand breaks may possibly lead to irreversible DNA damage.

Adult↗

Antenatal origin of neurologic damage in newborn infants. II. Multiple gestations.

Necrosis of the cerebral white matter may be identified in living infants with echoencephalography. Echoencephalographic studies were performed in 89 twins and 12 triplets at less than 36 weeks of gestation to determine the incidence and complications associated with antenatal necrosis of the cerebral white matter. Antenatal necrosis of the cerebral white matter was identified when brain atrophy or cavities in the white matter were present by day 3 of life. Fourteen infants (13.8%) were considered to have antenatal necrosis of the cerebral white matter. The incidence of antenatal necrosis of the cerebral white matter was higher in monochorionic than in dichorionic infants (30% vs 3.3%; p less than 0.001). Univariate analysis showed that antenatal necrosis of the cerebral white matter was significantly associated with polyhydramnios, intrauterine fetal death of the cotwin, hydrops, multiple placental vascular connections, and placental artery-to-artery, vein-to-vein, and artery-to-vein anastomosis. Logistic regression analysis showed that antenatal necrosis of the cerebral white matter was predicted by the presence of either artery-to-artery or vein-to-vein anastomosis and by intrauterine fetal death of a cotwin. Vein-to-vein anastomosis had the strongest association, because 89% of seven infants with vein-to-vein anastomosis demonstrated antenatal necrosis of the cerebral white matter (p = 0.003). Monochorionic multiple gestations frequently are complicated by antenatal necrosis of the cerebral white matter. Multiple vascular connections with vein-to-vein anastomosis appear as the most important associated factor for antenatal necrosis of the cerebral white matter in this population.

Analysis of Variance↗

EEG brain mapping in evaluating the time-course of the central action of DUP 996--a new acetylcholine releasing drug.

1. In a double-blind, placebo-controlled study the encephalotropic effects of DUP 996, a novel phenylindolinone derivative for Alzheimer's disease enhancing the release of acetylcholine in cholinergic nerve terminals in the brain only when its release is triggered, were studied with special consideration of the pharmacodynamic time-course. 2. Thirteen healthy male volunteers aged 18-40 years received randomized and at weekly intervals, single oral doses of placebo and 30 mg DUP 996. Blood sampling for plasma concentration analysis, EEG recordings and evaluation of pulse, blood pressure and side effects were carried out at 0, 1, 2, 4, 8, 12 and 24 h. 3. Computer-assisted spectral analysis of the EEG and subsequent topographic brain mapping of the drug-induced EEG changes demonstrated significant central effects of DUP 996 suggesting vigilance-improving properties. The findings were characterized mostly by an augmentation of total power as well as by an increase of absolute power in the alpha and alpha-adjacent beta activity. 4. Time-course investigations demonstrated two pharmacodynamic peaks: a first one in the 2nd h and a second one in the 12th h. In detail CNS effects increased up to the 2nd h, showed a drop in the 4th h, increased again thereafter to peak in the 12th h. Even in the 24th h there were significant differences between DUP 996 and placebo. The latter suggests an indirect effect and/or an active metabolite, as the parent drug is rapidly absorbed and has a rather short plasma half-life between 1-3 h. 5. DUP 996-induced EEG-changes over time were most pronounced over temporo-occipital, temporo-frontal, parietal and frontal regions, e.g. over brain areas afflicted most by Alzheimer's disease. 6. Evaluation of vital signs, laboratory findings and ECG as well as adverse effects showed a very good tolerability of DUP 996.

Acetylcholine↗

Antenatal origin of neurologic damage in newborn infants. I. Preterm infants.

Currently, the diagnosis of white matter necrosis may be performed with echoencephalography when cysts are observed in the white matter adjacent to the lateral ventricles. One hundred twenty-seven infants with a gestational age less than 36 weeks (mean [+/- SE] gestational age = 31 +/- 3.2 weeks) were studied in the neonatal period with echoencephalography to determine the incidence of white matter necrosis and the perinatal variables associated with this complication. Twenty-three infants (18.3%) had white matter necrosis. Thirteen (10.3%) had cysts by day 3 (11 on day 1), indicating that the onset of white matter necrosis occurred antenatally. The incidence of antenatal white matter necrosis was inversely related to birth weight and was more frequent in infants weighing less than 1000 gm (19%). Stepwise logistic regression analysis of 31 antenatal variables showed that placental vascular anastomoses in multiple pregnancies, funisitis, and purulent amniotic fluid were the only complications associated with antenatal white matter necrosis. Follow-up neurologic evaluations were abnormal in four of six patients with antenatal white matter necrosis. The findings in this study focus attention on prenatal, rather than intrapartum and postnatal, factors as causative agents of neurologic morbidity and emphasize the importance of early and sequential evaluation of neonatal brain structures.

Cerebral Hemorrhage↗

Insidious hydrocephalus in the preterm newborn following discharge from the nursery.

Posthemorrhagic ventriculomegaly may be due to perinatal brain damage and consequent cerebral atrophy, or represent progressive hydrocephalus due to impairment of CSF flow and reabsorption. 'Arrested' hydrocephalus occurs when the CSF pathways are adequate and, hence, intracranial hypertension no longer exists. The differential diagnosis is often difficult and insidious progressive hydrocephalus should always be a concern in the high-risk preterm newborn. We report 10 preterm infants who were discharged with the diagnosis of arrested hydrocephalus (7) or cerebral atrophy (3), and who later developed progressive severe hydrocephalus 1.5-15 months after the discharge. Five had been treated with intermittent lumbar punctures, while 4 had not received any treatment prior to nursery discharge. One infant died prior to the shunt procedure. Progressive insidious hydrocephalus should be suspected in preterm infants with intracranial hemorrhage following discharge from the nursery.

Cerebral Ventricles↗

Periodic lateralized epileptiform discharges in asphyxiated neonates.

Electrographic seizures (EGS) were detected in 13 of 16 asphyxiated neonates who were undergoing continuous electroencephalographic monitoring for detection of evidence of central nervous system injury. Five of the 13 neonates with EGS also had periodic lateralized epileptiform discharges (PLEDs). The electrographic characteristics of PLEDs in these infants were similar to those reported in neonatal herpes simplex encephalitis and in older children and adults. Of the 5 neonates with PLEDs, 2 died, 2 are developmentally delayed and only 1 is normal at 12 months. This is in contrast to the normal outcome for 8 of the 11 infants who did not have PLEDs. One other was neurologically normal but died of pulmonary disease at 3 months and the other two were developmentally delayed. PLEDs in neonates, as in other age groups, lack diagnostic specificity, but when associated with neonatal asphyxia, may indicate a poor prognosis. Continuous EEG monitoring is helpful in identifying PLEDs in these cases.

Asphyxia Neonatorum↗

Ventriculoperitoneal shunts in high risk newborns weighing under 2000 grams: a clinical report.

Fifty-three low birth weight high risk newborns who developed progressive hydrocephalus despite a trial period of intermittent lumbar punctures underwent cribside ventriculoperitoneal shunt placement. They all weighed less than 2000 g at the time of shunting (mean, 1308.6 g +/- 398.2 SD). The operative procedures were performed at a mean age of 31.5 days +/- 16.1 (SD). There were no deaths in this series. During the nursery stay, 14 patients required operative revisions for obstruction. The most common problem was infection, which occurred in 13 (24.5%) after the primary intervention and in another 5 of the 14 (35.7%) patients who required revision. The overall infection rate/patient was 26.9%. Shunt removal and intensive antibiotic therapy cured the infection in all but 1 patient. Premature, low birth weight newborns may undergo ventriculoperitoneal shunting, but close follow-up for complications such as infection and shunt obstruction is always required.

Anti-Bacterial Agents↗

The effects of maternally administered magnesium sulfate on the neonate.

The effects of parenterally administered magnesium sulfate on maternal and neonatal calcium and magnesium metabolism in nonasphyxiated, term pregnancies complicated by pregnancy-induced hypertension were studied prospectively. In addition, the neurobehavioral effects of neonatal hypermagnesemia were investigated by means of a neonatal assessment scale that specifically measures reflex activity and both passive and active muscle tone. Maternal magnesium sulfate infusion was associated with maternal and neonatal hypermagnesemia when compared with that of control subjects (1.8 +/- 0.10 to 3.6 +/- 0.5 mg/dl, p less than 0.001, and 1.75 +/- 0.2 to 3.6 +/- 0.5 mg/dl, p less than 0.005, respectively). Maternal serum calcium levels fell with magnesium therapy (9.3 +/- 0.18 to 7.9 +/- 0.1 mg/dl, p less than 0.001), while neonatal calcium levels were unaffected (10.8 +/- 0.44 to 10.5 +/- 0.38 mg/dl, p less than 0.05). Neurological status examinations in the neonate were similar in both the control and treatment groups. In addition, neurological performance of the neonate did not correlate with cord magnesium levels or to the total dose of magnesium administered.

Adult↗

The cardiovascular effects of dopamine in the severely asphyxiated neonate.

The cardiovascular effects of dopamine were evaluated in 14 severely asphyxiated neonates. After a period of stabilization, either dopamine 2.5 micrograms/kg/minute or placebo was infused in a randomized double-blind protocol. In seven dopamine-treated infants, echocardiographically determined shortening fraction and mean velocity of circumferential fiber shortening increased when compared to preinfusion values (P less than 0.05). There was no significant change in these echo indices of cardiac function in the placebo-treated group. Systolic blood pressure rose in the dopamine group when compared to predopamine infusion values and to the postinfusion values of the placebo group (P less than 0.001 and 0.025, respectively). Diastolic blood pressure increased to a small degree in the dopamine group. There was no significant change in heart rate or echocardiographically measured systolic time intervals. Low doses of dopamine increase cardiac performance and raise systolic blood pressure in the severely asphyxiated neonate.

Asphyxia Neonatorum↗

The experimental production of hyaline membranes in premature rhesus monkeys.

When premature rhesus monkeys are ventilated with oxygen or air, hyaline membranes are formed within 5 minutes in alveolar ducts and respiratory bronchioles. Studies with fluorescein-labeled antiserum to porcine pepsinogen provide evidence that the monkey fetuses have aspirated gastric fluid. The findings suggest that some component of gastric fluid plays an important role in the formation of the hyaline membranes, either directly by causing necrosis of susceptible bronchiolar epithelium or secondarily by sensitizing the bronchiolar epithelium to another necrotizing agent such as oxygen.

Animals↗