Search PubMed⌕ Search

Biomedical subjects

D G Munoz

Publications and source records attributed to D G Munoz.

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

Chromogranin A inhibits dopamine release from rat striatal slices.

Chromogranin A (CGA), a prohormone and a protein component of endocrine and neural secretory granules, neuritic plaques in Alzheimer's disease and Lewy bodies in Parkinson's disease, inhibited the release of dopamine (DA) from perfused rat striatal slices. Dopamine release was stimulated by a pulse of high potassium (40mM) medium introduced at 20 minutes (K1) and 55 minutes (K2) following equilibration. The ratio of K2/K1 was 0.80+/-0.04 in control tissues, but fell significantly to 0.26+/-0.08 when 100nM purified CGA was added prior to the second potassium pulse. This reduction in DA release was equivalent to that seen when calcium was excluded from the buffer (0.19+/-0.05). Pancreastatin, a centrally active peptide product of CGA, had no effect on stimulated DA release (0.77+/-0.06), although it, as well as the other treatments, did reduce basal DA release. It is likely that the parent molecule itself, CGA, or an as yet unidentified product is responsible for inhibition of K-stimulated striatal DA release.

Animals↗
PubMed1998

Contributions of the entorhinal cortex, amygdala and hippocampus to human memory.

Recent studies have indicated that, in the monkey, the rhinal cortex (consisting of the entorhinal and perirhinal cortices) is more important to visual recognition memory than the hippocampus or amygdala. The present study investigated the role of the entorhinal cortex in humans using memory scores from surgical epilepsy patients classified according to their mesial temporal lobe pathology. The temporal lobe removals included 4-5 cm of neocortex, amygdala, rhinal cortex and 2-3 cm of the hippocampus and parahippocampal gyrus. Compared to autopsied control subjects, all of the patients showed significant gliosis in the amygdala, but they differed as to whether or not there were entorhinal and/or hippocampal abnormalities. Both preoperatively and one or more years postoperatively, the patients performed tests of verbal recall (Wechsler Memory Scale Logical Memory), visual recall (Rey Figure), verbal recognition and visual recognition (Warrington Recognition Memory Test: Words and Faces, respectively). Preoperatively, patients with hippocampal pathology showed deficits in visual recall. Postoperatively, a significant drop in verbal and visual recall was seen only for patients who lost intact hippocampal tissue, irrespective of the condition of the excised entorhinal cortex. Together, the results argue that the hippocampus is more important than the entorhinal cortex for the recall of newly learned information.

Adolescent↗
PubMed1998

Fallacies in the pathological confirmation of the diagnosis of Alzheimer's disease.

OBJECTIVE: Necropsy confirmed clinical diagnostic accuracy for Alzheimer's disease is claimed to exceed 90%. This figure contains two fallacies; it includes cases in which Alzheimer's disease exists with other diseases affecting cognition and the studies that report these figures excluded cases without necropsy (verification bias). The effect of these errors is estimated. METHODS: Data were taken from the University of Western Ontario Dementia Study, a registry of dementia cases with clinical and psychometric follow up to necropsy based in a university memory disorders clinic with secondary and tertiary referrals. Data were available on 307 patients; 200 (65%) had clinically diagnosed Alzheimer's disease, 12 (4%) vascular dementia, 47 (15%) mixed dementia, and 48 (16%) had other diagnoses. One hundred and ninety two of 307 cases (63%) died and 122 of 192 fatalities (64%) had necropsies. The pathological material was interpreted in two ways, allowing and disallowing coexistent disease in making a diagnosis of Alzheimer's disease. In cases without necropsy, progressive cognitive loss was used as a marker for degenerative dementia. The outcome measures of interest were the positive predictive value of a clinical diagnosis of Alzheimer's disease allowing and disallowing coexistent diseases and with and without correction for cases that were not necropsied. RESULTS: The clinical diagnoses differed significantly between the population who died and those who did not. In cases without necropsy, 22% had no dementia on follow up, concentrated in early cases and men, showing considerable scope for verification bias. The positive predictive value of a diagnosis of Alzheimer's disease was 81% including coexistent diseases, falling to 44% when limited to pure cases. Combined, these factors reduce the positive predictive value to 38% for pure Alzheimer's disease. CONCLUSIONS: Correction for dual pathology and verification bias halves the positive predictive value of the clinical diagnosis of Alzheimer's disease. Data derived from necropsy studies cannot be extrapolated to the whole population. This has important implications including uncertainty about diagnosis and prognosis and a dilution effect in therapeutic trials in Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Factors affecting the age of onset and rate of progression of Alzheimer's disease.

OBJECTIVES: To assess the role of cerebrovascular disease, sex, education, occupation, year of birth, leukoaraiosis, congophilic angiopathy, family history, and other demographic factors on the reported age of onset and rate of progression of Alzheimer's disease. METHODS: Analysis of data from the University of Western Ontario Dementia Study, a prospective longitudinal study of dementia patients with clinical and 6 monthly psychometric follow up to postmortem based in a university memory disorders clinic with secondary and tertiary referrals. There were 172 patients with dementia. The main outcome measures were the reported age of onset of cognitive decline as described by the family (available in 168) and rate of progression as measured during the linear phase of the extended scale for dementia, which could be calculated in 66. The cases subdivided into 49 cases of definite Alzheimer's disease without infarcts, 25 cases of otherwise definite Alzheimer's disease with infarcts, 79 cases of probable Alzheimer's disease without infarcts, and 19 such cases with infarcts. RESULTS: The age of onset was not influenced by the rate of progression, the presence of cerebral infarcts, or congophilic angiopathy. Educational level, occupational level, sex, family history, year of birth, reported age of onset, severity at entry, an ischaemic score, and the presence of leukoariosis, affected neither age of onset nor the rate of progression. An earlier year of birth had a major effect and higher education had a minor effect on earlier age of onset. The earlier the year of birth, the lower the educational level and the greater the accrual of cerebral infarcts. CONCLUSIONS: Contrary to series without pathological verification, age of onset in this study was not affected by occupation. Education had a modest effect on earlier reported onset, probably reflecting earlier recognition. As birth year has a strong effect on educational level and the occurrence of cerebral infarcts, this must be taken into account when analysing for risk factors for Alzheimer's disease.

Adult↗
PubMed1998

Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging.

Anti-inflammatory drugs have been suggested as a possible treatment for Alzheimer's disease (AD). The association of immune proteins and immune-competent microglial cells with senile plaques (SP) in both AD and normal aging suggests that these drugs may be able to modify the course of AD, either by interfering with SP formation or by suppressing the inflammation associated with SP. We compared postmortem brain tissue from elderly, nondemented, arthritic patients with a history of chronic nonsteroidal anti-inflammatory drug (NSAID) use (n = 32, aged 77 +/- 7 years) and nondemented control subjects with no history of arthritis or other condition that might promote the regular use of NSAIDs (n = 34, aged 77 +/- 6 years). In both the NSAID-treated group and control subjects, 59% of patients had some SP. There was no difference between the two groups in the mean number of plaques or in the number of specific SP subtypes (diffuse or neuritic). The degree of neurofibrillary pathology was also similar. Activated microglia were identified using CR3/43, an anti-MHC class II antibody. Both patient age and the presence of SP correlated positively with the number of CR3/43+ microglia (p < 0.02), whereas NSAID use was associated with less microglial activation (p < 0.01). Control patients with SP had almost three times the number of activated microglia as NSAID-treated patients with SP (11 versus 4 cells/mm2, p < 0.02). These results suggest that if NSAID use is effective in treating AD, the mechanism is more likely to be through the suppression of microglial activity than by inhibiting the formation of SP or neurofibrillary tangles.

Aged↗
PubMed1998

MR in temporal lobe epilepsy: analysis with pathologic confirmation.

PURPOSE: We evaluated the MR findings in patients with temporal lobe epilepsy to determine the predictive value of MR imaging in assessing patient outcome. METHODS: MR studies from 186 of 274 consecutive patients who underwent temporal lobectomy for intractable epilepsy were reviewed retrospectively. Images were interpreted by an experienced neuroradiologist, who was blinded to the side of seizure activity and to pathologic findings. RESULTS: MR imaging exhibited 93% sensitivity and 83% specificity in detecting hippocampal/amygdalar abnormalities (n = 121), and 97% sensitivity and 97% specificity in detecting abnormalities in the rest of the temporal lobe (n = 60). Abnormal high signal of the hippocampus on T2-weighted images had a sensitivity of 93% and specificity of 74% in predicting mesial temporal sclerosis (n = 115). The presence of hippocampal atrophy on MR correlated with the duration of seizures. Sensitivity and specificity of MR imaging in detecting temporal lobe tumors (n = 42) were 83% and 97%, respectively, based on abnormal signal and mass effect. After surgery, 63% of patients were seizure free and 28% had a significant reduction of seizure frequency at an average of 24 months (range, 12 to 78 months) after surgery. Patients with a single lesion in the anterior temporal lobe or hippocampus/amygdala had a better outcome than patients with multiple lesions (n = 22). Interrater agreement varied from 0.4 to 0.93, with best agreement for tumors or abnormal hippocampal signal on T2-weighted images. CONCLUSION: MR imaging is highly sensitive in detecting and locating abnormalities in the temporal lobe and the hippocampus/amygdala in patients with temporal lobe epilepsy. Hippocampal atrophy appears to correspond to the duration of seizure disorder.

Adult↗
PubMed1997

Cerebrovascular pathology in Alzheimer's disease: cause, effect or epiphenomenon?

Cerebrovascular pathology abounds in Alzheimer's disease. Changes in the endothelium, disruption of the blood-brain barrier and amyloid deposition in the cerebral blood vessels are almost universal in advanced cases. Do these changes represent the cause, the effect, or the consequences of a common pathogenesis of Alzheimer's disease? This volume addresses some of these issues by presenting new knowledge gained from a diversity of fields. Recognition of the mechanisms involved will open new possibilities for therapeutic trials.

Aged↗
PubMed1997

Serum protein leakage in Alzheimer's disease revisited.

Leakage of serum proteins into the brain parenchyma has been repeatedly used as evidence of blood-brain barrier (BBB) damage in experimental and human studies. However, there is no consensus in the literature concerning this phenomenon in Alzheimer's disease (AD). We have examined this question by comparing frontal lobe sections in seven groups of patients: Multi-infarct dementia (n = 6), AD with (n = 10) and without (n = 10) infarcts, age-matched controls with (n = 10) and without (n = 10) infarcts, controls with neurodegenerative diseases other than AD, and young controls (n = 10). An additional series compared prospectively followed patients with a diagnosis of either multi-infarct dementia (n = 5) or AD (n = 4). Albumin was detected in white-matter astrocytes in all cases, without significant variation in intensity. In addition, diverse combinations of neurons, astrocytes, and (in AD patients) senile plaques were present in the cerebral cortex in an inconsistent manner. Semiquantitative analysis showed no statistically significant differences among groups. Anti-IgG labeled astrocytes in infarcts only. Complement C3c component was detected in rare amyloid plaques in a minority (15%) of AD cases. Selective labeling of AD-specific lesions in a patchy manner was observed for serum amyloid P. We conclude that there is no immunohistochemical evidence of alteration of the BBB in Alzheimer's disease with or without vascular factors or in old age. Serum amyloid P binds avidly to AD lesions, but our findings are consistent with leakage through the BBB during the agonal or immediate postmortem period. Finally, no specific pattern of abnormality in the BBB was detected in multi-infarct dementia.

Alzheimer Disease↗
PubMed1997

Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia.

OBJECTIVE: To compare the evolution of Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia by cognitive domain. SETTING: The University of Western Ontario Dementia Study, which is a registry of cases of dementia seen for secondary and tertiary assessment in a university memory disorders clinica with extensive follow-up data and histopathological confirmation of clinical diagnoses. PATIENTS: One hundred twenty-nine patients with definite or probable AD, 12 patients with definite or probable VaD, and 36 patients with definite or probable mixed dementia. METHODS: Patients were grouped as having an early, moderate, or advanced stage of disease according to the extended scale for dementia (ESD). The ESD was subdivided into cognitive domains, and the domain scores were compared for each stage of disease by diagnostic category with the use of a 2-way analysis of variance with repeated measures. RESULTS: As expected, the scores in all domains decreased significantly with increasing severity. There was a significant difference in the decline in memory among the diagnostic groups (P = .02) that was mostly attributable to the difference between AD and mixed dementia (P = .03), with the difference between AD and VaD only approaching significance (P = .06). There was a similar finding for praxis. The interaction between diagnosis (AD and VaD) and severity was significant only for memory (P = .02), showing a less severe memory deficit at onset but a proportionately more rapid progression in VaD and arithmetic ability (AD and mixed dementia [P = .03]). CONCLUSIONS: Alzheimer disease, VaD, and mixed dementia evolve similarly as assessed using cognitive domains obtained by subdivision of the ESD in a patient population derived from a memory clinic and by analyzing VaD as a single entity. Only memory impairment evolves differently between AD and VaD, with this depending on the severity. Memory is more severely impaired in the early stage of AD; however, with increasing severity of dementia, memory impairment in VaD accelerates and catches up with AD at the level of moderate impairment. The differences between AD and mixed dementia are greater than those between mixed dementia and VaD, suggesting an important role for the ischemic component of mixed dementia. Simple neuropsychological tools (eg, the ESD) may be incapable of distinguishing between AD and VaD, and more focused instruments may be required. Inherent bias in case selection may prevent extrapolation of these results to VaD in general, but the neuropsychological criteria for VaD may need to vary, depending on the severity.

Alzheimer Disease↗
PubMed1997

Increased apolipoprotein E epsilon 4 in epilepsy with senile plaques.

Inheritance of the apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and is associated with increased deposition of beta-amyloid (A beta) in AD, Down's syndrome, and normal aging. A beta deposition in the form of senile plaques (SPs) has recently been described in patients with temporal lobe epilepsy (TLE). We studied the relationship between ApoE epsilon 4 genotype and the deposition of A beta in temporal lobe tissue from patients who underwent temporal lobectomy for intractable epilepsy. TLE patients with SPs had a 70% ApoE epsilon 4 carrier frequency compared with a 27% carrier frequency among age-matched TLE controls without SPs. Our data suggest that the association between ApoE epsilon 4 and intracerebral A beta accumulation is not unique to the elderly or to those with dementia, and may be a feature of conditions in which there is both an ApoE epsilon 4 allele and over-production of A beta precursor protein, and, presumably, A beta.

Amyloid beta-Peptides↗
PubMed1997

A familial syndrome of congenital cataract, mental impairment, and dentate gyrus atrophy.

We present a family with congenital cataract with, in some cases, mental retardation and emotional instability, but intellectual deterioration in all affected members. The latter was accompanied by psychosis in some. The inheritance is most likely autosomal dominant, affecting two generations and consisting of a congenitally blind parent and 6 of 11 of her offspring. In addition to these features, some affected individuals had dysphagia and movement disorder, especially choreiform movements. They all showed small body mass, due possibly to poor nutrition from dysphagia. The pathological findings were unique, demonstrating selective atrophy of the granule cell layer of the dentate gyrus. There was selective expression in paraffin-embedded sections of alpha B-crystallin (CRYA2) in oligodendroglia in all areas of the nervous system examined. alpha B-Crystallin is a major optic lens protein but also a heat shock protein and molecular chaperone found in brain and a number of other tissues. Because of the association of congenital cataract and the accumulation in oligodendroglia of alpha B-crystallin, the gene for this protein was sequenced for possible mutation. No mutation was found indicating other genetic locus. This family appears to have a newly recognized genetic disorder.

Adult↗
PubMed1997

Fatal reaction from inadvertent intrathecal entry of ionic contrast medium during a nephrogram.

A fatal case of inadvertent intrathecal entry of an ionic contrast medium during a nephrogram is reported. The patient developed seizures and failed to regain consciousness following the event. Computerized tomography revealed extensive intraventricular and subarachnoid hyperdensity and cerebrospinal fluid analysis revealed markedly elevated protein content. At autopsy a traumatic communication between the kidney and thecal sac was identified. Histopathological examination revealed cytoplasmic shrinkage and eosinophilia, nuclear pyknosis and karyorrhexis in neocortical neurons. Central chromatolysis was seen in brain stem motor nuclei and anterior horn cell neurons. The neuropathological findings appear to be on the basis of direct neurotoxicity from the contrast medium and excitotoxic injury secondary to seizure activity. Inadvertent intrathecal administration of ionic contrast media is a rare occurrence with often fatal consequences despite aggressive medical management.

Brain↗
PubMed1997

Prevalence and disease associations of argyrophilic grains of Braak.

Braak's argyrophilic grains (BAG) are spindle-shaped structures originally described in patients with dementia. We have determined that the prevalence of BAGs in an unselected series of 300 consecutive autopsies of subjects over the age of 30 is 5.6%, or 11.7% if only subjects older than 65 are considered. All the 17 subjects identified were older than 68; 6 received other neuropathological diagnoses of degenerative disease and 11 did not. Only 2 of the latter had shown clinical evidence of mental impairment. Braak's argyrophilic grains were associated with ballooned neurons, superficial linear spongiosis, and gliosis of entorhinal cortex and amygdala. Subcortical neurofibrillary tangles were consistently found in patients with dementia, but not in other subjects. In a separate series studying the prevalence of BAG in neurodegenerative diseases, we found a strong, but not universal association with progressive supranuclear palsy, and to a lesser degree with the lobar atrophies (Pick's disease and corticobasal ganglionic degeneration). Numerous BAG were present in occasional cases of diffuse Lewy body disease, multiple systems atrophy, and motor neuron disease. We conclude that rather than defining a single disease, BAG constitute lesions that accompany several degenerative diseases, but also occur in normal elderly subjects, and rarely in demented subjects without other major histological findings.

Adult↗
PubMed1997

Meningioangiomatosis is associated with neurofibromatosis 2 but not with somatic alterations of the NF2 gene.

Meningioangiomatosis occurs sporadically and in patients with neurofibromatosis. The literature, however, is unclear concerning the type of neurofibromatosis associated with meningioangiomatosis. Because determining which form of neurofibromatosis predisposes to meningioangiomatosis would clarify the genetic alterations of this lesion, we reviewed all reported cases of meningioangiomatosis associated with neurofibromatosis in light of current diagnostic criteria for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2). All well-documented cases of meningioangiomatosis occurred in the setting of NF2, implying that germline alterations of the NF2 gene predispose to meningioangiomatosis. To determine whether sporadic (non-NF) cases of meningioangiomatosis arise from somatic alterations of the same gene, we screened the NF2 gene for mutations in 12 sporadic cases of meningioangiomatosis and in constitutional DNA from 6 of these 12 patients. No mutations were found in either the lesional or constitutional DNA, which suggests that sporadic meningioangiomatosis is not a forme fruste of NF2 and that somatic alterations of the NF2 gene do not play a major role in sporadic meningioangiomatosis. For some tumor suppressor genes, germline mutations may predispose to specific tumors, while similar sporadic lesions only rarely suffer somatic mutations in these genes. The present findings suggest a similar dichotomy for the NF2 gene in meningioangiomatosis.

Angiomatosis↗
PubMed1997

Primary progressive aphasia.

Primary progressive aphasia is an important recently emphasized clinical syndrome that is a common early manifestation of Pick's disease and Pick complex pathology. It is defined clinically as slowly progressive language disturbance that remains relatively isolated from other cognitive or behavioral deficits for at least 2 years. Subsequently, it may become associated with behavioral changes similar to those in frontal lobe dementia (FLD), extrapyramidal manifestations, and apraxia similar to corticobasal degeneration (CBD) and with motor neuron disease. Both the common nonfluent or logopenic variety leading to mutism (frontal involvement) and fluent or semantic varieties (temporal involvement) are recognized. Neuroimaging with CT, MRI, and SPECT are useful adjuncts confirming the diagnosis. PPA is a manifestation of frontotemporal degeneration or Pick complex, which is probably the second most common degenerative dementia after AD.

Aphasia, Primary Progressive↗
PubMed1997

Orbital aspergillosis. A fatal masquerader.

Ocular manifestations of aspergillosis are emerging as increasingly more atypical, with a wide spectrum of presentations. The classic teaching is that this fungus presents as an endogenous endophthalmitis in immunocompromised hosts. In most other ocular conditions, the index of suspicion for this infection has typically been low, especially in apparently immunocompetent individuals. However, reports continue to appear that confirm involvement of Aspergillus species in a wide variety of primary ocular and orbital conditions characterized by rapid, uncontrollable progression and, not uncommonly, death. This report highlights a case of autopsy-proven orbital aspergillosis that masqueraded as temporal arteritis in terms of initial clinical presentation and response to standard therapy. Any ocular condition that manifests even subtle atypical features, including temporal arteritis, should be regarded as suspect, and an aggressive approach to secure a biopsy of any involved sites should follow.

Aged↗