Biomedical subjects

J Willmer

Publications and source records attributed to J Willmer.

10 recordsLinked to original sources

PubMed1998

Evaluation of selection criteria used in Alzheimer's disease clinical trials.

BACKGROUND: In the absence of a biological marker for Alzheimer's disease (AD), diagnosis has to be achieved using clinical criteria sets such as those outlined in DSM-IV, NINCDS-ADRDA, or ICD-10. As these criteria are quite broadly defined, there may be inter-rater variability in interpretation. METHODS: Using a previously published CT scan measuring technique which correlates well with diagnoses achieved using the NINCDS-ADRDA criteria as interpreted at our clinic, we chose to independently examine and reach a diagnosis in patients selected for participation in clinical trials of therapeutic agents for the treatment of AD. Forty-four CT scans from six investigators across Canada were examined using this model. All patients had been diagnosed as having AD by NINCDS-ADRDA criteria and were deemed acceptable to participate in a clinical trial. RESULTS: The diagnostic concordance achieved in the original published model was 91.5%. The diagnostic concordance in the population currently being studied was 77.3%. However when examined by site, results ranged from 57.1% to 100%. Using the model, an index of atrophy and a probability of diagnosis of AD can be determined. Across sites, there were statistically significant differences in these measures (p < or = 0.035). The mean probability of diagnosis of AD across sites ranged from 0.56 to 0.94. Although the sites with lower probabilities had slightly lower mean ages and slightly less atrophy, there was no overall correlation of the atrophy measures with age. CONCLUSIONS: Current results raise the possibility that the selection of patients for AD clinical trials using current diagnostic criteria sets may not be adequate and conclusions with respect to agent efficacy could be flawed.

Aged↗

PubMed1996

Do long tests yield a more accurate diagnosis of dementia than short tests? A comparison of 5 neuropsychological tests.

OBJECTIVE: To provide comparative evidence for a valid and practical measure of mental-status functioning that could be used in dementia clinics. DESIGN: Five mental-status neuropsychological tools for dementia screening were administered to patients in a memory disorder clinic. These included the Mini-Mental State Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation-Memory-Concentration Test, a short Mental Status Questionnaire, and a composite tool we labeled the Ottawa Mental Status Examination, which assessed orientation, memory, attention, language, and visual-constructive functioning. The tools were compared using various criteria, including the statistical factors of sensitivity and reliability; effects of gender, native language, and language of testing; the utility of these tests for the differential diagnosis of Alzheimer-type and vascular dementia; and sensitivity to cognitive decline in the entire sample and among patients with severe dementia. RESULTS: All of the tests were highly intercorrelated, suggesting that they are interchangeable. CONCLUSION: The comparisons along the various criteria indicate that if the objective is to have a general index of dementia of the Alzheimer type, short tests are at least as good and sometimes better than the longer tests.

Aging↗

PubMed1996

Diagnosis of dementia. Methods for interpretation of scores of 5 neuropsychological tests.

OBJECTIVE: To provide methods to interpret and compare different neurobehavioral screening tests for the diagnosis of dementia. DESIGN: Five mental-status neuropsychological tools for dementia screening were administered to patients in a memory disorder clinic. These included the Mini-Mental State Examination, the Dementia Rating Scale, the 6-item derivative of the Orientation-memory-Concentration Test, a short Mental Status Questionnaire, and a composite tool we labeled the Ottawa Mental Status Examination, which assessed orientation, memory, attention, language, and visual-constructive functioning. RESULTS: To obtain z and percentile scores, norms are for the different tests, computed separately for patients with dementia of the Alzheimer type, vascular dementia, or no dementia. Another set of norms is reported in which a test score is translated directly into the posttest probability of dementia. Translation formulas are given to allow the estimation of the score on one test from the result on another test. CONCLUSION: The interpretation of tests used to diagnose dementia must be based on an understanding of the meaning of an individual score, which is based on the question asked and the population to which the patient is referenced.

Alzheimer Disease↗

PubMed1993

Capture errors and sequencing after frontal brain lesions.

This study addresses the effect of strong routine associations (capture errors) in hindering the control of on-line serial or sequencing tasks. Patients with focal frontal lobe lesions were significantly inferior to normal control subjects and patients with posterior brain lesions, when conditions that may lead to capture errors were present. The results suggest that the primary dysfunction exhibited by patients with frontal lobe lesions on capture error tasks may lie not in the disengagement from the invalid associations but in focusing attention to alternative strategies of response.

Adult↗

PubMed1993

The usefulness of CT scanning in diagnosing dementia of the Alzheimer type.

In order to determine the usefulness of Computerized Tomography (CT) scanning in making a diagnosis of dementia of the Alzheimer type, a group of patients diagnosed by NINCDS-ADRDA criteria (n = 22) were compared to a group of normal subjects (n = 49) using certain defined linear CT scan measurements. These measurements included specific measurements of the temporal lobes (temporal horns). Subjects were classified correctly 91.5% of the time with a high degree of probability. A diagnostic equation is presented which will allow testing of these methods in a prospective fashion.

Aged↗

PubMed1989

Sulfated glycosaminoglycans in amyloid plaques of prion diseases.

Brain sections from cases of human Creutzfeldt-Jakob disease, Gerstmann-Sträussler syndrome, kuru, and hamster scrapie containing amyloid were examined for the presence of sulfated glycosaminoglycans (GAGs), the anionic component of proteoglycans, using the sulfated Alcian blue method and Alcian blue technique with 0.3 M and 0.7 M magnesium chloride. These studies suggest that sulfated glycosaminoglycans are part of the CNS amyloid plaques in each of the above human prion disorders as well as in experimental scrapie. All the amyloid plaques stained positively with Alcian blue at 0.3 M, and less so at 0.7 M magnesium chloride indicating the presence of sulfated GAGs. Therefore, the amyloid plaques of prion diseases possess similar histochemical features to those found in Alzheimer's disease.

Alzheimer Disease↗

PubMed1987

Spinal artery aneurysm.

A case of a spinal artery aneurysm is presented and the relevant literature is reviewed. The pathology of this aneurysm differed from that of standard intracranial aneurysms. The coexistence of a spinal aneurysm and fibromuscular hyperplasia has not been previously reported.

Aneurysm↗

PubMed1987

Sulfated glycosaminoglycans: a common constituent of all amyloids?

In the present investigation, we analyzed whether sulfated glycosaminoglycans are a common constituent in many different types of amyloid. Serial sections of amyloidotic tissue were stained for the presence of: (a) amyloid by using Congo Red, and (b) glycosaminoglycans by using both the sodium sulfate Alcian blue method and Alcian blue, pH 5.7, with varying concentrations of magnesium chloride. Our results show that sulfated glycosaminoglycans are always associated anatomically with amyloid deposits regardless of the nature of the protein deposited. Sulfated glycosaminoglycans were found in tissues containing AA, AL, inherited cutaneous amyloid, and senile cardiac amyloid (prealbumin). Additionally, we provide evidence that sulfated glycosaminoglycans are closely associated with the amyloid of medullary carcinoma of the thyroid (prothyrocalcitonin), and neuritic plaques, neurofibrillary tangles, and congophilic angiopathy in Alzheimer's disease. It is postulated that these sulfated glycosaminoglycans can influence the folding of diverse proteins such that all forms of amyloid show a significant beta-pleated sheet component.

Amyloid↗

PubMed1987

A close ultrastructural relationship between sulfated proteoglycans and AA amyloid fibrils.

Two cationic reagents, Ruthenium red (RR) and Cuprolinic blue (CB), were used to assess the morphologic and structural relationship between sulfated proteoglycans and AA amyloid fibrils in amyloidotic spleen and liver, and in isolated fibril preparations. Amyloidotic tissue fixed in the presence of RR showed RR granules, measuring 15 to 25 nm in diameter, over areas of electrondense fibrils. In isolated fibril preparations, RR granules were specifically localized on amyloid fibrils. Amyloidotic tissue fixed in the presence of CB at 0.1 M and 0.7 M MgCl2 showed both granule and filamentous (50 to 90 nm in length) staining only over areas of amyloid fibrils. This same staining localization was also seen in isolated fibril preparations. The RR and CB granules and filaments, are believed to represent proteoglycan monomers with the glycosaminoglycan chains collapsed onto the protein core. The persistent CB staining at 0.7 M magnesium chloride suggested that highly sulfated proteoglycans were present. The glycosaminoglycan moiety has previously been identified as heparin/heparan sulphate. The intimate structural relationship between sulfated proteoglycans and AA amyloid fibrils, both in situ and in isolated fibril preparations, further suggests that these highly negatively charged molecules may have an important role in the pathogenesis of amyloidosis. Several pathogenetic scenarios are suggested.

Amyloidosis↗

PubMed1982

Further characterization of amyloid-enhancing factor.

Amyloid-enhancing factor (AEF) is a transferable activity that in CBA/J mice reduces the induction time of splenic amyloid deposition to 48 hours. Azocasein, or AgNo3, can induce AEF in the spleen and liver. In the liver several subcellular organelles possess this activity. This is likely due to AEF's adherent properties. AEF is most effective when given by the intravenous route. After intravenous injection, AEF particulates localize to the perifollicular areas of the spleen and Kuppfer cells in the liver. The effects of AEF administration persist for at least 4 weeks. AEF can be solubilized in 4 M glycerol, is not the amyloid A protein, and is not likely to be the serum amyloid P component. The extract can be fractionated by Sepharose 4B column chromatography. The active component is of high molecular weight, and tentative identification by disc electrophoresis has been made.

Amyloid↗