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Biomedical subjects

M Richards

Publications and source records attributed to M Richards.

At least 145 records · Page 8Linked to original sources

Effects of lymphoma on the peripheral nervous system.

Peripheral nervous system abnormalities occur in 5% of patients with lymphoma and have a wide differential diagnosis. Herpes zoster is the commonest cause. Vinca alkaloids are the only drugs used in lymphoma which commonly cause neuropathy. Compression or infiltration of nerve roots by lymphoma is a rare presenting feature but becomes more common with advanced disease. Radiation plexopathy does not usually develop until at least 6 months after irradiation and can be difficult to distinguish from neoplastic infiltration. Either multifocal infiltration of nerves or lymphoma-associated vasculitis may present as a peripheral neuropathy. The incidence of Guillain-Barré (GBS) syndrome, and possibly chronic idiopathic demyelinating polyradiculoneuropathy, appears to be increased in association with lymphoma, especially Hodgkin's disease. Subacute sensory neuronopathy and subacute lower motor neuronopathy have both been reported as paraneoplastic syndromes associated with Hodgkin's disease. Treatment of the underlying lymphoma is only rarely followed by recovery of the associated neuropathy.

Antineoplastic Agents↗

Comparison of cognitive changes in patients with Alzheimer's and Parkinson's disease.

OBJECTIVE: To compare cognitive changes in the dementias of Parkinson's disease (PD) and Alzheimer's disease (AD). DESIGN: Case series, group comparisons. SETTING: Ambulatory care referral center. PATIENTS: Consecutive sample of 14 patients with PD dementia and 27 with probable AD matched for overall intellectual function using a mental status test, as well as 14 non-demented PD and 12 mild probable AD patients, similarly matched for overall intellectual function. All demented patients met Diagnostic and Statistical Manual, Revised Third Edition, criteria for dementia. MAIN OUTCOME MEASURES: Performance on a battery of neuropsychological tests assessing verbal and nonverbal memory, verbal fluency, and constructional ability. RESULTS: Nondemented and demented patients with PD performed worse than their probable AD comparison groups on verbal fluency and visuospatial tasks. Cognitive changes attributable to dementia were similar in PD and probable AD but were not identical. The patients with probable AD demonstrated more marked change in memory performance with delay. CONCLUSIONS: Our findings suggest that when dementia occurs in PD it is overlaid on cognitive changes that already exist in nondemented patients but that the dementing process in PD involves systems other than those responsible for cognitive change in nondemented PD patients. We hypothesize that in most cases, dementia in PD involves changes in a nondopaminergic neurotransmitter system but is not due to concomitant AD.

Alzheimer Disease↗

Relationships between extrapyramidal signs and cognitive function in a community-dwelling cohort of patients with Parkinson's disease and normal elderly individuals.

The relationship between extrapyramidal sign (EPS) severity and cognitive function was investigated in 184 patients with idiopathic Parkinson's disease (PD) and 301 normal elderly individuals from a community-dwelling cohort in northern Manhattan, New York City. Fifty-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of memory, orientation, abstract reasoning, language, construction, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD patients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but without overt idiopathic PD, showed widespread cognitive changes, including impairment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia.

Aged↗

Executive function in Parkinson's disease: set-shifting or set-maintenance?

In order to distinguish impairment in set-shifting in Parkinson's disease (PD) from inability to inhibit distraction by stimuli that compete for attention, 18 nondemented patients with idiopathic PD and 13 normal controls equated for age and education, were administered the Odd-Man Out (OMO) test and the Stroop Color-Word Test. PD patients were significantly impaired on the OMO test but showed no evidence of interference during the Stroop test. Analysis of error patterns during the OMO test indicated that the requirement to repeatedly switch rules, rather than the requirement to maintain steady responding between rule switches, was responsible for impaired OMO performance. It is concluded that the OMO test is fundamentally a test of set shifting, rather than a test of set maintenance in PD. In addition, analysis of a larger sample of PD patients revealed a significant positive relationship between number and severity of extrapyramidal signs and error production on the OMO, and between the latter and global mental function. These relationships were independent of each other, suggesting that impairment in set-shifting function in PD may arise from pathology of the fronto-striatal system independently of changes in cognitive ability.

Aged↗

Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). I. Study design, cohort description, and intersite comparisons.

Clinicians should be able to provide the patient with Alzheimer disease (AD) and the family with an accurate prediction of what to expect, but the variability in the rate of disease progression precludes this. In several previous studies, specific clinical signs such as muscular rigidity, myoclonus, and hallucinations or delusions were associated with rapid progression to a more severe stage of dementia or death. The "Predictors Study," a longitudinal study at three independent sites, was designed to develop a predictor model of the natural history of Alzheimer disease. The study was conducted at three study sites, New York, Baltimore, and Boston in a cohort of 224 patients with early probable AD. This article describes the design and implementation of the Predictors Study, and compares features of the study cohort at baseline across sites. Patients were all at the mild stage of disease at entry and were relatively comparable across sites. Extrapyramidal signs and delusions were common, but myoclonus was rarely observed.

Activities of Daily Living↗

Multicenter study of predictors of disease course in Alzheimer disease (the "predictors study"). II. Neurological, psychiatric, and demographic influences on baseline measures of disease severity.

The "Predictors Study" is a prospective cohort study of the natural history of Alzheimer disease (AD), the aim of which is to identify milestones in disease progression and to develop a model to predict disease course in individual patients. The empirical background to this study is based on previous reports that the presence of extrapyramidal signs (EPS), myoclonus, and psychosis in AD may signify greater disease severity at any given stage and a more rapid course of the disease over time. The present analyses were conducted to determine whether these independent "predictor" variables were associated with greater disease severity at baseline within a new cohort of 224 mild AD patients recruited from three different medical centers (in New York, Baltimore, and Boston). Measures of disease severity were provided by the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale (BDRS), which measures functional capacity. Independent variables were EPS, delusions, and slowing of the posterior dominant EEG rhythm. The frequency of myoclonus and hallucinations was too low to permit adequate statistical assessment of their effects at this time. EPS and EEG slowing were associated with low mMMSE scores, whereas delusions were primarily associated with impaired functional capacity. These effects were independent of the influence of age and disease duration. These results indicate that the effects of these independent variables can be detected at mild stages of AD and that these effects can be generalized across different geographical regions.

Aged↗

The relationship between visuospatial ability and perceptual motor function in Parkinson's disease.

To assess the contribution of visuoperceptual function to complex visuomotor responding in Parkinson's disease, 14 patients with idiopathic PD and 12 normal controls matched for age, education and general intellectual function were administered a visual tracing task. No difference was found between the groups on two visuoperceptual tests, the Benton Line Orientation test and a test of trajectory judgement. However, patients were significantly impaired in tracing a sawtooth design when two consecutive angles of the sawtooth were occluded. This impairment occurred in reproducing the basic form of the stimulus and not with accuracy of fine detail. These results suggest higher-order perceptual motor dysfunction independent of any breakdown in basic visuoperceptual processing or loss of fine motor control. It is concluded that Parkinsonian patients are unable to use sensory information accurately to plan and execute complex or new movements.

Activities of Daily Living↗

Subtle extrapyramidal signs can predict the development of dementia in elderly individuals.

To assess the significance of mild extrapyramidal signs (EPSs) in aging, we prospectively followed 228 elderly individuals without dementia or major neurologic disease at baseline. Seventy-three (32%) showed mild idiopathic EPSs at baseline assessment and 32 (14%) of these 228 individuals met NINCDS-ADRDA criteria for probable or possible Alzheimer's disease on follow-up. While none of these individuals developed Parkinson's disease, those with more than one EPS at baseline were significantly more likely to become demented during follow-up than were those with one or no EPS, an association not confounded by age, education, or gender. Individuals with more than one EPS and with cognitive impairment (CI) at baseline were at highest risk for dementia. EPSs were also independently associated with incident dementia in the absence of CI at baseline. We conclude that mild EPSs are a significant predictor of dementia in elderly individuals.

Aged↗

Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment.

We obtained data from 111 gay men who entered a longitudinal study of the natural history of human immunodeficiency virus (HIV) without clinical evidence of acquired immunodeficiency syndrome (AIDS), and examined them regularly over a 36-month period. Using a Cox proportional-hazard regression model to compare cumulative risk of mortality in subjects with and without cognitive impairment and several putative risk factors present at baseline, we found that the mortality risk ratio (RR) associated with poor neuropsychologic test performance was significantly increased (RR = 2.9; 95% confidence interval [CI], 1.1 to 7.8), and increased further (RR = 4.1; 95% CI, 1.3 to 12.5) when adjusted for other factors associated with mortality (a history of a disturbance in movement or gait, CD4-lymphocyte and red blood-cell counts, and age). A significant increase in symptoms related to cognitive impairment and gait, a decline in neuropsychologic test performance, and declines in CD4-lymphocyte and red-cell counts occurred over the study period. A second model was constructed to adjust for changes in CD4-lymphocyte and red-cell counts, age, medical stage, and motor symptoms over the study period, but the mortality RR for poor neuropsychologic test performance at baseline changed very little (RR = 4.7; 95% CI, 1.5 to 14.9). We conclude that the presence of cognitive impairment, manifest by poor neuropsychologic test performance in both asymptomatic and symptomatic gay men with HIV infection, is associated with a significantly increased risk of death. This effect progresses in parallel with the immunologic and systemic effects of HIV.

Adult↗

Patterns of neuropsychological performance in Alzheimer's disease patients with and without extrapyramidal signs.

We investigated the relationship between extrapyramidal signs (EPS) and the cognitive function in 90 patients meeting NINCDS-ADRDA criteria for probable Alzheimer's disease (AD) by dividing them into those showing no evidence of EPS and those showing at least one EPS on the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological tests of verbal memory, orientation, abstract reasoning, language, and construction. Patients with EPS were significantly more impaired than patients without EPS on tests of short-term learning and memory, orientation, naming, verbal fluency, and construction, but not on tests of long-term memory, abstract reasoning, or verbal comprehension. These results could not be explained by any differences in age, education, or disease duration between the groups. Since this pattern of neuropsychological impairment resembles that of patients with Parkinson's disease and other EPS syndromes, we hypothesize that EPS are associated with neuropathologic and neuropsychological changes that are superimposed over the classic features of AD.

Aged↗

Brachial plexus injury in two red-tailed hawks (Buteo jamaicensis).

Two red-tailed hawks (Buteo jamaicensis), found near Deltaville, Virginia (USA), were evaluated because of inability to use a wing. Results of needle electromyographic studies of the affected wing muscles in both hawks were compatible with denervation. On euthanasia, one hawk had extensive axon and myelin loss with multifocal perivascular lymphocytic inflammation of its brachial plexus and radial nerve. Demyelination and axon loss in the dorsal white matter of the spinal cord on the affected side also were found at the origin of the brachial plexus. The other hawk's wing had not returned to functional status > 2 yr after injury.

Animals↗

The inverse dose-rate effect for oncogenic transformation by charged particles is dependent on linear energy transfer.

Mouse C3H 10T1/2 cells were exposed to single or fractionated doses of charged particles of defined linear energy transfer (LET) from 25 to 200 keV/microns. Dose fractionation with prolonged time intervals enhanced the yield of transformed foci compared with a single acute dose for a range of LET values between 40 and 120 keV/microns. Radiations of lower or higher LET did not show the enhancement that is commonly referred to as the inverse dose-rate effect. The fractionation scheme that was used consisted of three dose fractions; the maximum enhancement of transformation occurred with an interval of 150 min between dose fractions. This inverse dose-rate effect, demonstrated for cycling cells in log phase, was not seen for cells in plateau phase.

Animals↗

Bivariate assay for cleaved atrial natriuretic factor (ANF(101-105/106-126)) in sheep plasma.

A bivariate assay has been developed to measure both ANF, and cleaved ANF (ANF(101-105/106-126)) the primary product of endopeptidase-24.11 action on rat ANF(101-126). The assay employed two different antisera directed to the carboxy-terminal and ring regions of ANF to enable discrimination and measurement of intact endogenous ANF(99-126) and infused cleaved ANF (rat ANF(101-105/106-126)) in sheep plasma extracts. The assay which was validated by HPLC analysis of plasma extracts, had sufficient accuracy and precision to measure the metabolic clearance rate and half-life of cleaved ANF when infused in normal sheep.

Analysis of Variance↗

Hepatitis due to nitrofurantoin.

OBJECTIVE: To report three cases of hepatitis related to the use of nitrofurantoin. CLINICAL FEATURES: Two patients who had been taking nitrofurantoin for several years, presented with severe liver failure. In both, the drug had been continued despite evidence of liver injury. A third patient presented with acute hepatitis after six weeks of nitrofurantoin therapy. INTERVENTION AND OUTCOME: One of the patients with liver failure died and the other underwent a successful liver transplantation. The third patient recovered after withdrawal of the drug. CONCLUSION: These cases emphasise the potential for serious hepatic reactions with nitrofurantoin, the danger of continuing the drug once liver damage has occurred and the need for careful monitoring of liver function during long-term therapy.

Adult↗

The Columbia University Scale for Psychopathology in Alzheimer's disease.

The Columbia University Scale for Psychopathology in Alzheimer's disease is a new screening instrument developed for use by clinicians or trained lay interviewers. Interrater reliability was established between a psychiatrist and a lay interviewer in 20 patients. In an independent sample of 91 outpatients with very mild to moderate probable Alzheimer's disease, caregiver informants reported that depressed mood was common (46.2%) but rarely persistent (2.2%), and that sleep disturbance occurred frequently (41.8%) but was never severe (0%). There were significant but weak associations between the presence of specific subtypes of delusions and severity of dementia. Although a variety of delusional symptoms were reported, they were frequently transient and patients often accepted the truth if corrected by the caregiver. As a result, few patients met broad or narrow operational criteria used to define delusions. Prior studies may have overestimated the prevalence of psychotic features in Alzheimer's disease by not employing standard definitional criteria. The findings also indicate that new methodology such as that employed in this instrument needs to be evaluated more widely.

Aged↗