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R Jacoby

Publications and source records attributed to R Jacoby.

At least 37 records · Page 2Linked to original sources
PubMed1998

A randomized, placebo-controlled trial of low-dose alpha-difluoromethylornithine in individuals at risk for colorectal cancer.

DFMO is an irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in mammalian polyamine biosynthesis. The goal of this study was to determine the effects of DFMO 0.5 g/m2/day as a single oral dose on polyamine and ODC levels in rectal, rectosigmoidal, and cecal colonic mucosae of individuals at risk for colon cancer because of a personal history of adenomatous polyps of the colon or a family history of colon cancer in at least one first-degree relative. A second goal was to determine toxicity of this treatment given over 1 year. Forty-five randomized subjects had a flexible sigmoidoscopy with no preparation and a colonoscopy after lavage preparation at baseline, a sigmoidoscopy with no preparation after 3 months, and both procedures (as at baseline) after 12 months, with mucosal biopsies taken from the rectosigmoid area (sigmoidoscopy) or rectal and cecal areas (colonoscopy) for evaluations of ODC and polyamine levels. Significantly decreased levels of putrescine and spermidine were found in rectosigmoid colonic mucosae of DFMO-treated (n = 24) compared with placebo (n = 21) subjects at 3 months (P = 0.03 and 0.04) and 12 months (P = 0.005, P = 0.004). Similar trends, none reaching statistical significance, were found for individual polyamine levels in rectal and cecal mucosae. No significant differences in ODC levels were detected marginally. There was evidence of global suppression of ODC and polyamine levels in the treatment group (P = 0.035). Three DFMO recipients (12.5%) developed clinically noticeable and audiologically demonstrated hearing loss, which was reversible and attributed to DFMO after 3 months (two subjects) and 12 months (one subject). The tissue polyamine changes demonstrated in this study are consistent with findings in other studies in colon and other tissues. The ototoxicity findings here suggest that investigation of other DFMO schedules, such as ones with a drug "holiday," will be a necessary step before Phase III chemoprevention studies can be pursued.

Adult↗
PubMed1997

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up.

OBJECTIVE: To investigate the contribution of neuroleptic drugs to cognitive decline in dementia. DESIGN: Two year prospective, longitudinal study consisting of interviews every four months, with necropsy follow up. SETTING: Community settings in Oxfordshire. SUBJECTS: 71 subjects with dementia, initially living at home with informant. MAIN OUTCOME MEASURES: Cognitive function (score from expanded minimental state examination); behavioural problems (physical aggression, hallucinations, persecutory ideas, and disturbance of diurnal rhythm); and postmortem neuropathological assessment (cortical Lewy body pathology). RESULTS: The mean (SE) decline in cognitive score in the 16 patients who took neuroleptics was twice that in the patients who did not (20.7 (2.9) v 9.3 (1.3), P = 0.002). An increased rate of decline was also associated with aggression, disturbed diurnal rhythm, and persecutory ideas. However, only use of neuroleptics and severity of persecutory ideas were independently associated with more rapid cognitive decline when all other variables were adjusted for. The start of neuroleptic treatment coincided with more rapid cognitive decline: median rate of decline was 5 (interquartile range 8.5) points per year before treatment and 11 (12) points per year after treatment (P = 0.02). Cortical Lewy body pathology did not account for association between neuroleptic use and more rapid decline. CONCLUSIONS: Neuroleptic drugs that are sometimes used to treat behavioural complications of dementia may worsen already poor cognitive function. Randomised controlled trials are needed to confirm a causal relation.

Aged↗
PubMed1997

Behaviour changes in dementia. 1: Point of entry data of a prospective study.

OBJECTIVE: This article analyses behaviour changes in dementia at the point of entry to a longitudinal study. DESIGN: Prospective, longitudinal study of behaviour in dementia, with autopsy follow-up. SETTING: Subjects with dementia, living at home with a carer. All lived in Oxfordshire, UK. PARTICIPANTS: Ninety-seven people with dementia (Alzheimer's disease and/or vascular dementia) who were living at home with a carer. MEASURES: At 4-monthly intervals, the carers were interviewed and the subjects with dementia were assessed cognitively. Subjects' behaviour was assessed using the Present Behavioural Examination. This is an investigator-based, semi-structured interview consisting of eight main sections covering many different aspects of behaviour. The 121 main questions, with 66 further 'nested' questions, have been shown to have high reliability. RESULTS: This article analyses the types of behaviour change reported by carers at the point of entry to this long-term study. Few correlations were found between behaviour and age, gender and time since onset of dementia. Some types of behaviour were significantly more prevalent in those with greater cognitive impairment. CONCLUSIONS: Many of these changes create problems for carers, for example increased aggressive behaviour, wandering, wakefulness at night, incontinence and persecutory ideas. In general, they are more prevalent in people with more severe dementia.

Aged↗
PubMed1997

Behaviour changes in dementia. 2: Are there behavioural syndromes?

OBJECTIVE: To establish whether robust behavioural 'syndromes' can be identified from among the widely heterogeneous behavioural changes which occur in dementia. DESIGN: Longitudinal, prospective study with follow-up at 4 and 8 months. SETTING: Community settings in Oxfordshire, UK. PARTICIPANTS: 97 elderly people with a diagnosis of Alzheimer's disease or vascular dementia (in many cases confirmed by postmortem examination) and who were living at home with a carer. MEASURES: Each subject's behaviour was assessed in detail at each interview using the Present Behavioural Examination to assess subject's behaviour over the preceding 4 weeks. Seventeen key behaviour items which were both common and clinically important were selected for further analysis. RESULTS: Three syndromes were identified: (a) overactivity (walking more, walking aimlessly, trailing the carer or checking where the carer was); (b) aggressive behaviour (physical aggression, aggressive resistance, verbal aggression); (c) psychosis (anxiety, persecutory ideas and hallucinations). The same syndromes were found using data collected at three different time points and by using a variety of statistical techniques, confirming their robustness. CONCLUSIONS: Overactivity, aggressive behaviour and psychosis form three distinct behavioural syndromes in dementia.

Aged↗
PubMed1997

Cognitive impairment in medical inpatients. I: Screening for dementia--is history better than mental state?

BACKGROUND: evaluation of the short version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and the Abbreviated Mental Test (AMT) as screening tools for dementia in medical inpatients. METHODS: 201 patients over 65 were assessed. Assessment included administration of the AMT, a delirium screening instrument and a brief psychiatric interview. Relatives were interviewed and the IQCODE administered. Diagnostic and Statistical Manual (DSM) IIIR diagnoses of various causes of cognitive impairment were made. Sensitivity and specificity values of the screening tests for a DSM IIIR diagnosis of dementia were calculated. RESULTS: our study suggests that the IQCODE is more accurate than the AMT as a screening instrument for dementia. Using a cut-off point of > 3.44, sensitivity and specificity of the IQCODE for diagnosing dementia were 100 and 86% respectively. Equivalent values for the AMT (cut-off point < 8) were 96 and 73%. It was possible to use the IQCODE in eight of the 10 patients unable to complete the AMT. CONCLUSION: using both the IQCODE and a brief cognitive function test when screening for dementia in medical inpatients will maximize the number of patients who can be screened.

Aged↗
PubMed1997

Cognitive impairment in medical inpatients. II: Do physicians miss cognitive impairment?

AIM: to study the recognition of cognitive impairment in elderly medical inpatients by medical staff. METHODS: 201 patients over 65 were assessed by administration of standard cognitive screening tests and an interview with relatives. We made Diagnostic and Statistical Manual (DSM) IIIR diagnoses of various causes of cognitive impairment and clinical diagnoses for those patients not fulfilling DSM IIIR criteria. Medical notes were scrutinized for any mention of cognitive impairment. RESULTS: 46% of the patients found to be cognitively impaired by the researcher had no record of cognitive impairment in the medical notes. However, 14 out of 15 of the patients with DSM IIIR delirium, and 22 out of the 26 patients with DSM IIIR dementia, were identified as cognitively impaired by the physicians. This suggests that the physicians were detecting the vast majority of patients with clinically significant cognitive impairment.

Aged↗
PubMed1996

Synaptic inputs to ON parasol ganglion cells in the primate retina.

In primates, the retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nucleus have distinctive responses to light, and one of these has been identified morphologically as the parasol ganglion cell. To investigate their synaptic connections, we injected parasol cells with Neurobiotin in lightly fixed baboon retinas. The five ON-center cells we analyzed by electron microscopy received approximately 20% of their input from bipolar cells. The major synaptic input to parasol cells was from amacrine cells via conventional synapses and, in this respect, they resembled alpha ganglion cells of the cat retina. We also found the gap junctions between amacrine cells and parasol ganglion cells that had been predicted from tracer-coupling experiments. To identify the presynaptic amacrine cells, ON-center parasol cells were injected with Neurobiotin and Lucifer yellow in living macaque retinas, which were then fixed and labeled by immunofluorescence. Two kinds of amacrine cells were filled with Neurobiotin via gap junctions: a large, polyaxonal cell containing cholecystokinin and a smaller one without cholecystokinin. There were also appositions between cholecystokinin-containing amacrine cell processes and parasol cell dendrites. Cholinergic amacrine cell processes often followed parasol cell dendrites and made extensive contacts. In other mammals, the light responses of polyaxonal amacrine cells like these and cholinergic amacrine cells have been recorded, and the effects of acetylcholine and cholecystokinin on ganglion cells are known. Using this information, we developed a model of parasol cells that accounts for some properties of their light responses.

Afferent Pathways↗
PubMed1995

Urinary N1-acetylspermidine and N8-acetylspermidine excretion in normal humans and in patients with colorectal cancer.

Urinary N1-acetylspermidine (N1SPD) and N8-acetylspermidine (N8SPD) were measured in 24-hr urine specimens from 42 patients with colon adenocarcinoma and 29 healthy controls to assess their use as markers for colon cancer screening. Serial spot urines in four controls demonstrated significant fluctuations in these polyamine levels throughout the day without a distinct circadian pattern and therefore all subsequent analyses were performed on 24-hr collections. Both N1SPD and N8SPD were significantly increased in colon cancer patients compared to controls. Neither test correlated with tumor stage or location, but N8SPD was elevated in patients with poorly differentiated adenocarcinoma when compared to moderate or well-differentiated tumors. Using receiver operator characteristic (ROC) analysis, N1SPD had a higher information content than N8SPD, N1SPD + N8SPD, or the ratio of N1SPD/N8SPD and at a normal cut-off value of 4.0 nmol/mg creatinine, yielded a 95% specificity and 50% sensitivity for colon cancer.

Adenocarcinoma↗
PubMed1992

Psychiatric morbidity in bus crews following violent assault: a follow-up study.

In a prospective study 22 bus crews who were victims of physical assault were assessed using standardized psychiatric instruments, followed up for 18 months and compared to a non-assaulted control group drawn from the same bus garage. At initial assessment the assaulted group, compared to the controls showed a significant increase in psychiatric impairment and distress (as measured by the GHQ-30 and IES respectively), with 23% of assault victims developing post-traumatic stress disorder as defined by DSM-III-R. At follow-up, while high levels of both psychiatric impairment and distress persisted there was evidence that they may be separate phenomena.

Adult↗
PubMed1991

Computed tomography in Alzheimer's disease: a longitudinal study.

Sixty-three patients satisfying NINCDS/ADRDA criteria for Alzheimer's disease (AD) received neuropsychological tests and computed tomography (CT) scans 12 months apart. Significant deterioration occurred in all the cognitive tests and in the CT measures used, that is, lateral ventricular size, third ventricular size, and cortical atrophy. There was a wide variation in the size of the changes taking place; 14 of 63 patients showed no significant change and 6 showed a marked increase in ventricular size. However, neither group differed from the others in any demographic, cognitive, or other CT variables which suggested, on the CT measures used, that no clearly identifiable subgroups of AD were present. Change in CT indices was not related to initial severity of disease. An increase in ventricular size was related to deterioration of cognitive function. These results require further replication. The methodological drawbacks of such studies are discussed.

Aged↗
PubMed1991

Evidence for a common molecular pathogenesis in colorectal, gastric, and pancreatic cancer.

We examined tissue extracted from 19 gastric, 7 pancreatic, and 23 colorectal carcinoma specimens to determine the comparative incidence of allele loss on chromosomes 5, 17, and 18 and that of KRAS2 point mutations. Chromosome 5 allele loss occurred at the same frequency in all three gastrointestinal tumors (approximately 30%), whereas chromosome 17 and 18 allele losses were seen at a significantly lower frequency in gastric (20%) and pancreatic (0%) malignancies than in colorectal cancer (57%). Point mutations in KRAS2 were seen in 83% of pancreatic and 52% of colon cancers, but not in gastric cancer specimens. In pancreatic tumors, these mutations were always found in the second nucleotide of codon 12. In colorectal cancer, the distribution was more variable, involving the second nucleotide of codon 13 and both the first and second nucleotides of codon 12. These results suggest that inactivation of the adenomatous polyposis coli gene on chromosome 5 may be an initiating step for carcinomas of the stomach and pancreas as well as of the colon, but that the genes involved in tumor progression events may be tissue- or tumor-specific.

Adenocarcinoma↗
PubMed1991

Factors affecting survival in Alzheimer's disease.

Factors affecting survival of 178 patients diagnosed using NINCDS/ADRDA criteria for Alzheimer's disease were studied. All patients were drawn from the Camberwell Health Authority Area and so were a representative sample of subjects from a clinical old age psychiatry service. The mortality rate of the sample was 3.5 times that expected after adjustment for age. Younger subjects had a higher standardized mortality ratio than older subjects. The cumulative three-year mortality of the sample was 47%. Factors shown to be associated with a reduced survival included: increasing age, longer duration of illness, male sex, presence of physical illness, poor cognitive function, observed depression and absence of misidentification syndromes. Apraxia was a stronger predictor of early death than aphasia or dysmnesia.

Aged↗