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W W Pendlebury

Publications and source records attributed to W W Pendlebury.

At least 19 recordsLinked to original sources
PubMed2001

Light and electron microscopic observations of a direct projection from mesencephalic trigeminal nucleus neurons to hypoglossal motoneurons in the rat.

A direct projection from rat mesencephalic trigeminal nucleus (Vme) neurons to the hypoglossal nucleus (XII) motoneurons was studied using a double labeling method of anterogradely biotinylated dextran amine (BDA) tracing combined with retrogradely horseradish peroxidase (HRP) transport at both light and electron microscopic levels. BDA was iontophoresed unilaterally into the caudal Vme, and 7 days later HRP was injected into the ipsilateral tongue to label hypoglossal motoneurons. The BDA-labeled fibers were seen descended along Probst' tract and were traced to the caudal medulla. In this course, the fibers gave off axon collaterals bearing varicosities in the trigeminal motor nucleus (Vmo), the parvicellular reticular formation (PCRt), the dorsomedial portions of the subnuclei of oralis (Vodm) and interpolaris (Vidm) and in the XII ipsilaterally. The labeling of terminals was most dense in the PCRt at the levels of caudal pons and rostral medulla, which displayed a "dumbbell-shaped" form in the transverse planes. In the XII, labeled terminals were distributed mainly in the dorsal compartment of the nucleus. One hundred sixty-eight appositions made by BDA-labeled terminals on HRP-labeled motoneurons were seen in the dorsal compartment (71%) and in the lateral subcompartment (24%) of the ventral XII. Under electron microscopy BDA-labeled boutons containing clear, spherical synaptic vesicles were found to form synaptic contacts with the somata and dendrites of hypoglossal motoneurons with asymmetric specializations. The present study provides new evidence that the trigeminal proprioceptive afferent neurons terminate in the XII and make synaptic contacts with their motoneurons.

Animals↗
PubMed2000

Chronic inflammatory demyelinating polyradiculoneuropathy: a study of proposed electrodiagnostic and histologic criteria.

OBJECTIVE: To examine the sensitivity of the 3 proposed electrodiagnostic (EDX) criteria for demyelination, the sensitivity and specificity of the proposed Ad Hoc Subcommittee of the American Academy of Neurology AIDS [Acquired Immunodeficiency Syndrome] Task Force histologic criteria (AAN criteria), the degree of agreement among these criteria, and the diagnostic value of sural nerve histologic criteria in patients with idiopathic chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). DESIGN AND METHODS: A retrospective analysis of 24 patients with idiopathic CIDP and 12 patients with diabetic polyneuropathy (DP) who underwent comparable testing of clinical, histologic, and EDX features. RESULTS: We found 42%, 50%, and 79% sensitivity of the proposed EDX, AAN teased fiber, and AAN electron microscopic (EM) criteria, respectively, for demyelination in CIDP. The specificity of the proposed AAN teased fiber and EM criteria for demyelination was greater than 80% when tested against patients with DP. There was lack of agreement between the EDX and histologic criteria. Almost two thirds of patients with CIDP who met the EM criteria but none of the EDX criteria for demyelination showed a favorable response to immunomodulatory therapy. CONCLUSIONS: Sural nerve histologic criteria offer unique sensitivity and acceptable specificity toward the diagnosis of CIDP. Sural nerve biopsy should be considered when a clinical suspicion of CIDP remains in patients who do not meet the proposed EDX criteria for demyelination.

Adult↗
PubMed2000

Identifying dementia in the primary care practice.

BACKGROUND: The purpose of this study was to evaluate the utility (i.e., positive and negative predictive value) of the 7 Minute Screen in identifying patients with probable Alzheimer's disease (AD) in a primary care practice. A second objective was to estimate the number of undiagnosed AD patients in a typical primary care practice. METHODS: One hundred thirty-seven successive admissions (96%) of patients over the age of 60 to a primary care practice over a 53-day period who completed informed consent documents were administered the 7 Minute Screen. All patients who screened positive (n = 13) and a random sample of those who screened negative (n = 26) returned for full diagnostic evaluation. Positive predictive value (PPV) and negative predictive value (NPV) of the 7 Minute Screen were determined using the criterion standard of clinical diagnosis established by examination, history, and laboratory studies. Test-retest reliability and time for administration were also determined. RESULTS: Of the 137 patients evaluated, 13 screened positive and 124 screened negative. Eleven of the 13 patients who screened positive were willing to return to the primary care practice for follow-up evaluation. A random sample of 26 patients who screened negative all agreed to return for follow-up evaluation. Of the 11 patients who screened positive and who returned for evaluation, 10 were subsequently diagnosed with probable AD. The remaining patient was diagnosed with mixed dementia. The caregivers of the two patients who refused to return were contacted and both indicated that the patients were having significant cognitive problems as verified by an activities of daily living scale. Of the 26 patients who screened negative, 25 were judged to be cognitively normal and the 26th was judged to have mild cognitive impairment. DISCUSSION: In successive admissions of patients over the age of 60 in a primary care practice, the 7 Minute Screen showed a PPV of 91% and an NPV of 96% in identifying patients who were subsequently identified with AD or other dementing disorder. These data suggest that this may be a useful instrument in identifying patients who should undergo diagnostic evaluation for AD and other dementing disorders. Additionally, extrapolation from the data in this practice suggests that there may be between 75 and 100 AD patients in the typical primary care practice, many of whom may not be diagnosed.

Aged↗
PubMed1998

A 7 minute neurocognitive screening battery highly sensitive to Alzheimer's disease.

OBJECTIVE: To determine the validity and reliability of a rapidly administered neurocognitive screening battery consisting of 4 brief tests (Enhanced Cued Recall, Temporal Orientation, Verbal Fluency, and Clock Drawing) to distinguish between patients with probable Alzheimer's disease (AD) and healthy control subjects. SUBJECTS: Sixty successive referrals to the Memory Disorders Clinic at Southwestern Vermont Medical Center, Bennington, who were diagnosed as having probable AD and 60 community-dwelling volunteers of comparable age, sex distribution, and education. DESIGN: Interrater and test-retest reliability, intergroup comparisons between patients with AD and control subjects on the 4 individual tests, and determination of probability of dementia for patients with AD and control subjects using the entire battery of tests. SETTING: Outpatient care. MAIN OUTCOME MEASURE: Comparison of the probability of dementia on the 7 Minute Screen with the criterion standard of clinical diagnosis established by examination and laboratory studies. SECONDARY OUTCOME MEASURES: Test-retest and interrater reliability (correlation coefficients), time for administration. RESULTS: Mean time of administration was 7 minutes 42 seconds. Mean scores for patients with AD and control subjects on all 4 individual tests were significantly different (for each, P<.001). When the 4 tests were combined in a logistic regression, the battery had a sensitivity of 100% and a specificity of 100%. A series of 1000 repeated random samples of 30 patients with AD and 30 control subjects taken from the overall sample of 60 patients with AD and 60 control subjects had a mean sensitivity of 92% and a mean specificity of 96%. The battery was equally sensitive to patients with mild AD as demonstrated by correctly classifying all 13 patients with AD using Mini-Mental State Examination scores of 24 or higher. Neither age nor education was a statistically significant factor when added as a covariate. Test-retest reliabilities for individual tests ranged from 0.83 to 0.93. Test-retest reliability for the entire battery was 0.91. Interrater reliability for the entire battery was 0.92. CONCLUSIONS: The 7 Minute Screen appears highly sensitive to AD and may be useful in helping to make initial distinctions between patients experiencing cognitive changes related to the normal aging process and those experiencing cognitive deficits related to dementing disorders such as AD. It has reasonable interrater and test-retest reliability, can be administered in a brief period, and requires no clinical judgment and minimal training.

Aged↗
PubMed1998

Recognition of Alzheimer's disease: the 7 Minute Screen.

BACKGROUND AND OBJECTIVES: Because Alzheimer's disease (AD) tends to be underdiagnosed, we developed a brief neurocognitive screening battery to identify AD patients. The 7 Minute Screen consists of four individual tests (orientation, memory, clock drawing, verbal fluency). The screen can be rapidly administered and scored and therefore may be appropriate for use in the primary care setting. This study determined the validity and reliability of the 7 Minute Screen in distinguishing patients with AD from healthy controls. METHODS: The 7 Minute Screen was administered to 60 consecutive referrals to a memory disorders clinic who were subsequently diagnosed with probable AD and to 60 community-dwelling individuals. Analysis of the combined scores on the four individual tests was used to determine the probability of dementia in each subject. We also evaluated test-retest and inter-rater reliability, as well as the time required to administer the battery. RESULTS: When compared with the normal subjects, the patients with AD were significantly more impaired on each of the four tests included in the 7 Minute Screen. When the four tests were combined into a logistic regression model, the battery correctly diagnosed 92% of the patients with AD and 96% of the normal subjects. The battery performed equally well when only patients with mild and very mild AD were included. Mean time for administration and scoring was 7 minutes 42 seconds. CONCLUSIONS: The 7 Minute Screen is a reliable and valid instrument for identifying patients with AD. It appears to be a potentially useful tool for identifying patients with AD in a primary care setting.

Aged↗
PubMed1996

Skeletal muscle and cardiovascular adaptations to exercise conditioning in older coronary patients.

BACKGROUND: Older coronary patients suffer from a low functional capacity and high rates of disability. Supervised exercise programs improve aerobic capacity in middle-aged coronary patients by improving both cardiac output and peripheral extraction of oxygen. Physiological adaptations to aerobic conditioning, however, have not been well studied in older coronary patients. METHODS AND RESULTS: The effect of a 3-month and a 1-year program of intense aerobic exercise was studied in 60 older coronary patients (mean age, 68 +/- 5 years) beginning 8 +/- 5 weeks after myocardial infarction or coronary bypass surgery. Outcome measures included peak aerobic capacity, cardiac output, arterio-venous oxygen difference, hyperemic calf blood flow, and skeletal muscle fiber morphometry, oxidative enzyme activity, and capillarity. Training results were compared with a sedentary, age- and diagnosis-matched control group (n = 10). Peak aerobic capacity increased in the intervention group at 3 months and at 1 year by 16% and 20%, respectively (both P < .01). Peak exercise cardiac output, hyperemic calf blood flow, and vascular conductance were unaffected by the conditioning protocol. At 3 and 12 months, arteriovenous oxygen difference at peak exercise was increased in the exercise group but not in control subjects. Histochemical analysis of skeletal muscle documented a 34% increase in capillary density and a 23% increase in succinate dehydrogenase activity after 3 months of conditioning (both P < .02). At 12 months, individual fiber area increased by 29% compared with baseline (P < .01). CONCLUSIONS: Older coronary patients successfully improve peak aerobic capacity after 3 and 12 months of supervised aerobic conditioning compared with control subjects. The mechanism of the increase in peak aerobic capacity is associated almost exclusively with peripheral skeletal muscle adaptations, with no discernible improvements in cardiac output or calf blood flow.

Adaptation, Physiological↗
PubMed1996

Alzheimer's disease.

Explore the source record for details and available documents.

Activities of Daily Living↗
PubMed1995

Classical conditioning in patients with Alzheimer's disease: a multiday study.

Previous studies demonstrated that patients with Alzheimer's disease (AD) do not acquire the classically conditioned eyeblink response. These studies, however, were only tested over a single conditioning session and, hence, raise the question of whether AD patients are capable of acquiring the response if sufficient training is given. This question may be of some importance whether AD patients can ultimately acquire the response has implications for the underlying neurobiological deficit in disrupted conditioning in AD. This study tested AD patients and age-matched controls over 4 days. As in previous studies, AD patients performed significantly worse than controls on Day 1, but by Day 4, they were not significantly different from controls. Subsequent testing indicated that these effects were not due to nonassociative variables such as changes in sensitivity to stimuli or disruption of the motor response. Also, it was reported that neither AD patients nor controls showed any evidence of acquisition in an explicitly unpaired paradigm, suggesting that neither pseudoconditioning nor sensitization is contributory. Data are discussed in terms of the possible role of the hippocampus in mediating conditioning deficits in AD patients.

Aged↗
PubMed1994

A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The Tacrine Study Group.

OBJECTIVE: To evaluate the efficacy and safety of high-dose tacrine hydrochloride over 30 weeks in patients with probable Alzheimer's disease. DESIGN: A 30-week randomized, double-blind, placebo-controlled, parallel-group trial. SETTING: Outpatients at 33 US centers. PATIENTS: Men and women at least 50 years of age with mild to moderate Alzheimer's disease and otherwise in good health. INTERVENTIONS: Group 1 received placebo; group 2 received 40 mg/d of tacrine for 6 weeks, then 80 mg/d for 24 weeks; groups 3 and 4 received 40 mg/d of tacrine for 6 weeks, 80 mg/d for 6 weeks, and 120 mg/d for 6 weeks. Group 3 remained on a dosage of 120 mg/d for a total of 18 weeks; after 6 weeks at 120 mg/d, group 4 titrated to 160 mg/d for the last 12 weeks. PRIMARY OUTCOME MEASURES: Clinician Interview-Based Impression (CIBI), Alzheimer's Disease Assessment Scale--Cognitive subscale (ADAS-Cog), and Final Comprehensive Consensus Assessment (FCCA). RESULTS: A total of 663 patients entered the study; 653 patients were included in an intent-to-treat (ITT) analysis; 263 had evaluable data at 30 weeks. The results of the ITT analysis revealed significant (P < or = .05) dose-response trends and between-group comparisons on CIBI and ADAS-Cog. In evaluable patients, significant dose-response trends were observed for all three primary measures (P < or = .001). Significant differences in favor of 160 mg/d of tacrine vs placebo were observed on the CIBI (P < or = .002) and ADAS-Cog and FCCA (P < or = .001), as well as caregiver-global and quality-of-life assessments (P < or = .05). On the CIBI, 23% and 42% of tacrine-treated patients in the ITT and evaluable-patient populations, respectively, were rated improved compared with 17% and 18% of placebo patients, respectively. The primary reasons for withdrawal of tacrine-treated patients were asymptomatic liver transaminase elevations (28%) and gastrointestinal complaints (16%). These adverse events were reversible on discontinuation of treatment, and many patients were able to restart tacrine. CONCLUSIONS: Tacrine produced statistically significant, dose-related improvements on objective performance-based tests, clinician- and caregiver-rated global evaluations, and measures of quality of life. There was no evidence that the large number of patient withdrawals biased the overall conclusions of the study.

Aged↗
PubMed1992

Quantitative morphometric study of muscle in inclusion body myositis.

Clinical and electromyographic findings do not clearly distinguish inclusion body myositis (IBM) from chronic polymyositis (PM). The rimmed vacuoles and filamentous nuclear and cytoplasmic inclusions that characterize IBM are often sparse and may be overlooked; conversely, these features may occasionally be seen in other diseases. Preliminary studies suggested that muscle fiber hypertrophy occurred more frequently in IBM than in PM. To investigate whether fiber hypertrophy can be used to improve the ability to separate IBM from PM, we report a morphometric analysis of 28 IBM cases, 22 PM and 22 dermatomyositis (DM) cases. The analysis, using a computer automated system, included proportion of hypertrophied fibers and also fiber type proportions, average fiber diameter, proportion of atrophic and angulated fibers, and the co-dispersion index (CDI). The proportion of hypertrophied fibers was greater in IBM than the other two conditions (IBM (mean +/- SEM) 31.0 +/- 4.7% and 12.2 +/- 2.4% for type 1 and type 2 fibers, respectively, compared to 9.8 +/- 3.0% and 3.3 +/- 1.7% in PM, and 7.7 +/- 2.7% and 3.9 +/- 1.9% in DM). These differences were statistically significant (P < 0.05) in both sexes for type 1 fibers and in women for type 2 fibers. Also, the average fiber size and hypertrophy factors for type 1 and type 2 fibers were increased in IBM compared to PM and DM. This study confirms that the presence of muscle fiber hypertrophy in biopsies from IBM patients may help differentiate them from other clinically similar inflammatory myopathies.

Dermatomyositis↗
PubMed1992

Orbital paraganglioma: case report and review of the literature.

Paragangliomas of the orbit are extremely rare. A case of an orbital paraganglioma, including the first magnetic resonance imaging description of this tumour is described here. The patient underwent surgery with gross total removal of the tumour and relief of his initial chief complaint of visual blurring. The differential diagnosis and therapeutic options for the management of this tumour are discussed.

Humans↗
PubMed1992

Analysis of the prion protein gene in thalamic dementia.

Thalamic degenerations or dementias are poorly understood conditions. The familial forms are (1) selective thalamic degenerations and (2) thalamic degenerations associated with multiple system atrophy. Selective thalamic degenerations share clinical and pathologic features with fatal familial insomnia, an autosomal dominant disease linked to a mutation at codon 178 of the prion protein (PrP) gene that causes the substitution of asparagine for aspartic acid (178Asn mutation). We amplified the carboxyl terminal coding region of the PrP gene from subjects with selective thalamic dementia or thalamic dementia associated with multiple system atrophy. Three of the four kindreds with selective thalamic dementia and none of the three kindreds with thalamic dementia associated with multiple system atrophy had the PrP 178Asn mutation. Thus, analysis of the PrP gene may be useful in diagnosing the subtypes of thalamic dementia. Moreover, since selective thalamic dementia with the PrP 178Asn mutation and fatal familial insomnia share clinical and histopathologic features, we propose that they are the same disease.

Base Sequence↗
PubMed1991

Congenital monomelic hypertrophy with progressive myopathy.

We describe a patient with congenital monomelic hypertrophy who later developed progressive footdrop due to a degenerative myopathy. The clinical, electrophysiologic, and pathologic features of the case are described and compared with those of a previously reported case.

Adult↗
PubMed1991

Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment.

Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable.

Amyloid beta-Peptides↗
PubMed1991

Primary central nervous system T-cell lymphoma. Case report.

Primary central nervous system (CNS) T-cell lymphoma is extremely rare. The present case report provides immunocytochemical evidence for a cerebellar CNS T-cell lymphoma. The patient underwent surgery followed by radiation therapy and is alive and well 36 months postoperatively. The clinical and pathological features of primary CNS T-cell lymphoma as well as diagnostic measures and treatment options are discussed, together with a compilation of all previous case reports of primary CNS T-cell lymphomas.

Adult↗