Biomedical subjects

David Munoz

Publications and source records attributed to David Munoz.

9 recordsLinked to original sources

PubMed2005

MPTP induces intranuclear rodlet formation in midbrain dopaminergic neurons.

Neuronal intranuclear rodlets (INRs; rodlets of Roncoroni) have been known to neuroanatomists since the turn of the century. However, the functional and/or pathological significance of these structures has remained enigmatic. We recently demonstrated that these structures are immunoreactive for class III beta tubulin and for glucocorticoid receptor. Moreover, they are markedly reduced in the temporal cortex of patients with Alzheimer's disease relative to age-matched controls and those with dementia with Lewy bodies, thereby implicating these structures in neurodegenerative disease pathogenesis. The present report represents an experimental pilot study to investigate the possible involvement of INRs in Parkinson's disease (PD). Specifically, we demonstrate significantly increased INRs in dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area in mice treated with the selective catecholaminergic neurotoxin MPTP, relative to saline-treated controls. We have hypothesized that INRs represent an intranuclear sequestrum of monomeric beta-tubulin and that their alteration in neurodegeneration may reflect disrupted or abnormal microtubule dynamics. We propose that the increased formation of INRs is related to the demonstrated ability of MPTP to cause microtubule disruption. Because tubulin has also been implicated in the pathogenesis of human PD, it is possible that the results of this study will have important implications for this most common neurodegenerative movement disorder.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2004

Indices of resective surgery effectiveness for intractable nonlesional focal epilepsy.

Among 70 patients with intractable focal epilepsy and no specific lesion, as determined by both MRI (magnetic resonance imaging) and histopathology, outcome after resective surgery was polarized: 26 (37%) became seizure free (SF), and 27 (39%) were not helped. Eighteen (42%) of 43 standard temporal resections rendered patients SF, somewhat more than eight (30%) of 27 other procedures. To seek reliable prognostic factors, the subsequent correlative data compared features of the 26 SF patients with those of the 27 not helped. Although ictal semiology guided the site of surgical resection, it and other aspects of seizure and neurologic history failed to predict surgical outcome. However, two aspects of preoperative scalp EEGs correlated with SF outcomes: (a) among 25 patients in whom >50% of clinical seizures arose from the later resected lobe and no other origins, 18 (72%) became SF compared with seven (28%) of 25 with other ictal profiles; (b) 13 (93%) of 14 temporal lobe patients whose interictal and ictal EEGs lacked features indicative of multifocal epileptogenesis became SF compared with five (33%) of 15 with such components. The considered need for subdural (SD) EEG reduced SF outcome from 18 (90%) of 20 patients without SD to eight (24%) of 33 with SD; this likely reflected an insufficient congruity of ictal semiology and interictal and ictal scalp EEG for localizing epileptogenesis. Within this SD group, >50% of clinical seizure origins from a later resected lobe increased SF outcome somewhat: from two (14%) of 14 without this attribute to six (40%) of 15 with it; 100% of such origins increased SF outcome from two (12%) of 16 to six (46%) of 13.

Adolescent↗

PubMed2004

Relationship between frontotemporal dementia and corticobasal degeneration/progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) were described as separate entities, but prior to that an extrapyramidal variety of Pick's disease was recognized. Subsequently a pathological overlap between these conditions and clinical overlap between frontotemporal dementia, primary progressive aphasia, corticobasal degeneration syndrome and more recently PSP was recognized. Initially only the movement disorder had been emphasized, but now the behavioral and language symptoms are considered common. The syndromes of frontotemporal dementia/Pick's disease can be produced by underlying CBD, PSP or Pick pathology as well as with neural inclusions of the motor neuron disease type. The concept of this overlap has been confirmed genetically finding a similar spectrum of pathology with different tau mutations and even with tau negative pathology, which could be a deficiency of normal tau. The overlap of CBD with PSP and both with PPA and FTD allows to consider these relatively rare conditions as part of a more commonly occurring degenerative disease than previously recognized.

Basal Ganglia Diseases↗

PubMed2003

Primary progressive aphasia: diagnosis, varieties, evolution.

A referred cohort of 67 clinically defined PPA patients were compared to 99 AD patients with formal language and nonverbal cognitive tests in a case control design. Language fluency was determined at the first and last follow up visits. Quantitation of sulcal and ventricular atrophy on MRI was carried out in 46 PPA and 53 AD patients. Most PPA patients (57%) are relatively fluent when first examined. Visuospatial and memory functions are initially preserved. Aphemic, stuttering, "pure motor" presentation, or agrammatic aphasia are seen less frequently. Later most PPAs become logopenic and nonfluent, even those with semantic aphasia (dementia). In contrast, AD patients were more fluent and had relatively lower comprehension, but better overall language performance. MRI showed significant left sided atrophy in most PPA patients. Subsequent to PPA, 25 patients developed behavioral manifestations of frontotemporal dementia and 15 the corticobasal degeneration syndrome, indicating the substantial clinical overlap of these conditions. Language testing, particularly fluency scores supported by neuroimaging are helpful differentiating PPA from AD. The fluent-nonfluent dichotomy in PPA is mostly stage related. The aphemic-logopenic-agrammatic and semantic distinction is useful, but the outcomes converge.

Aged↗

PubMed2002

Frontal lobe atrophy due to a mutation in the cholesterol binding protein HE1/NPC2.

This is the first description of slowly progressive Niemann-Pick disease type C (NPC) without the typical lysosomal storage in bone marrow and viscera in two descendants of a group of 17th century French-Canadians. The index patient was a married 43-year-old woman with onset of dementia in her thirties, later followed by the development of ataxia and athetoid movements. Her autopsy disclosed frontal lobe atrophy, neurolysosomal storage with oligolamellar inclusion and tau-positive neurofibrillary tangles. Of the 119 family members screened, only a married 42-year-old sister displayed symptoms of a dementia. Both women displayed vertical supranuclear ophthalmoplegia; expressive aphasia; concrete, stimulus-bound, perseverative behavior; and impaired conceptualization and planning. Cultured fibroblasts showed decreased cholesterol esterification and positive filipin staining, but no mutation was detected in coding or promoter regions of the NPC1 gene using conformation sensitive gel electrophoresis and sequencing. Sequencing showed a homozygous gene mutation that is predicted to result in an amino acid substitution, V39M, in the cholesterol binding protein HE1 (NPC2). Adult-onset NPC2 with lysosomal storage virtually restricted to neurons represents a novel phenotypic and genotypic variant with diffuse cognitive impairment and focal frontal involvement described for the first time.

Adult↗

PubMed2002

Survey of the black howler monkey, alouatta pigra, population at the Mayan site of Palenque, Chiapas, Mexico.

A survey of the population of the black howler monkey (Alouatta pigra) present at the Mayan site of Palenque was conducted during 2000. A total of 911 man/hours, spread over 112 days were spent surveying the 600 ha area of pristine forest at the site for howler troops. We detected the presence of 136 individuals of which 131 were members of 20 troops, the rest were 3 solitary adult males and 2 adult males travelling as a pair. Ecological density was estimated at 23 individuals/km(2). Mean troop size was 7.0 individuals and it ranged from 2 - 12 individuals; 60% of the troops were multimale. All sighting of howler monkeys were in evergreen rain forest and 75% were in trees > or = 20 m in height. The reported densities and mean troop size are higher than those reported for the species in Guatemala and in central Quintana Roo, Mexico. The vegetation of the forest contains tree species reported to be used by species of Alouatta in the Moraceae, Sapotaceae, Leguminosae, and Lauraceae plant families. Protection of a large perimeter area (ca 1700 ha) around the archeological site by the Mexican government ensures the conservation of the forest and of the black howler monkey population present at the site.

Alouatta↗

PubMedDate not supplied

Behavioral quantitation is more sensitive than cognitive testing in frontotemporal dementia.

OBJECTIVE: To compare behavioral and cognitive testing in the clinical diagnosis of frontotemporal dementia (FTD). METHODS: A clinically defined cohort of FTD (n = 52) is compared with 52 Alzheimer disease (AD) patients on a Frontal Behavioral Inventory (FBI) and cognitive tests (e.g., Mini-Mental State Examination, Mattis Dementia Rating Scale, Western Aphasia Battery, Wechsler Intelligence Scale, Wechsler Memory Scale). Fourteen patients with FTD had autopsy confirmation, and their tests are also compared with the rest of the FTD population. RESULTS: The FTD and AD groups were matched in sex, duration, and severity of dementia. The total scores on the FBI showed the largest difference. Mini-Mental State Examination and Mattis Dementia Rating Scale total scores did not discriminate between the two groups. Memory subscores were lower in the AD group, and conceptualization and language-related scores were worse in the FTD group. Milder and earlier affected patients, who could carry on a large battery of neuropsychological tests, were much better distinguished by the FBI scores on discriminant function analysis. In contrast to 78% by the cognitive tests, 98% of the FTD and AD patients were differentiated by the FBI. CONCLUSIONS: Although memory scores were lower in AD and language scores in the FTD population, many of the cognitive tests do not distinguish between FTD and AD. On the other hand, a behavioral inventory is a useful adjunct in the diagnosis of FTD. Postmortem validation was carried out in a sizeable subset of the population, showing similar behavioral and cognitive data.

Aged↗

PubMedDate not supplied

Can MRI signal characteristics of lumbar disk herniations predict disk regression?

PURPOSE: To assess whether or not MRI signal characteristics of lumbar disk herniations can predict subsequent disk regression. MATERIALS AND METHODS: Medical and radiology records from 1999-2003 were reviewed, and 123 patients who had more than one lumbar MRI during the study interval were identified. Of these, 42 patients had a disk herniation (protrusion, extrusion, or free fragment) identified on their first examination. Six of the 42 patients were not included because of prior lumbar surgery, or inadequate examinations. The remaining 36 patients had a total of 77 examinations to evaluate 44 disk herniations. The herniated disks were evaluated by two CAQ neuroradiologists for size, morphology and a qualitative assessment of the T2 signal. RESULTS: Between the first and last examination, 25 of 44 (57%) herniated disks decreased, 17 (39%) were unchanged, and two increased in size. 9 of 11 (82%) of disk extrusions improved. The mean size of the disks that regressed was significantly larger than those that were unchanged (8.6 mm vs. 6 mm, p=.001). On average, the disks decreased 3.2 mm (37%). Of the disks that decreased in size, 15 (63%) had an area of increased signal on T2-weighted images (T2WI) compared to the parent disk on the initial study. Of the disks that were unchanged, 6 (35%) had increased signal on the T2WI's. CONCLUSION: 57% of herniated disks in this study group decreased in size over time. Larger herniations and extrusions were more likely to regress than smaller herniations. Disks that regressed were more likely to have high signal on T2WI's than those that were stable.

Humans↗

PubMedDate not supplied

Follicular carcinoma of the thyroid with aggressive metastatic behavior in a pregnant woman: report of a case and review of the literature.

Distant metastases as initial presentation of follicular carcinoma of the thyroid is rare, especially in young patients. We report the clinical and pathological features of a 33-year old pregnant patient with follicular carcinoma of the thyroid who presented with widespread bone and lung metastases at the time of diagnosis. the resected tumor had a focal insular component that showed extensive vascular invasion spreading beyond the thyroid capsule, and was associated with widespread bone and lung metastases. Despite its aggressive behavior, the tumor had low mitotic activity and Ki-67 nuclear labeling index. tumor cells showed high microvascular density and down-regulation of E-cadherin, a calcium-dependent trans-membrane epithelial protein molecule known to promote intercellular adhesion. We suggest that architectural differentiation of the tumor and cell proliferation rate are not reliable markers of metastatic behavior in this particular thyroid neoplasm. Microvascular density and down-regulation of E-cadherin expression in the tumor should be included among histologic hallmarks of metastatic potential. the role of pregnancy in the aggressive behavior of this tumor is discussed along with a literature review.

Adenocarcinoma, Follicular↗