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Biomedical subjects

P F Reyes

Publications and source records attributed to P F Reyes.

At least 19 recordsLinked to original sources
PubMed2000

Estrogen for Alzheimer's disease in women: randomized, double-blind, placebo-controlled trial.

BACKGROUND: AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. METHODS: Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. RESULTS: Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. CONCLUSION: Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Affect↗
PubMed2000

Evaluation of a measurement strategy for Parkinson's disease: assessing patient health-related quality of life.

This study evaluated the feasibility and psychometric properties of self-completed and telephone interview versions of a patient health-related quality-of-life (HQL) questionnaire for Parkinson's disease that included the SF-36 Health Survey (SF-36), the Parkinson's Disease Questionnaire (PDQ-39), and the Medical Outcomes Study Sexual Function Survey. Parkinson's disease patients (n = 150) completed the questionnaire twice: once at the study site and once over the telephone in a randomized order. Ninety-four percent of enrolled patients completed the first HQL assessment and 88% completed both assessments. Cronbach's alpha exceeded 0.70 for all scales except for the self-completed PDQ-39 Social Support subscale (0.57) and the telephone interview PDQ-39 Social Support (0.60) and Cognitions (0.67) subscales and the SF-36 General Health (0.60) and Social Function (0.61) subscales. There were no statistically significant differences in mean HQL scale scores across the two modes of administration. Mean scores for 3 of the PDQ-39 subscales and the Summary Index were significantly poorer (p < 0.05) for patients at later clinical stages. Similarly, patients with dyskinesias reported significantly poorer scores for 4 of the PDQ-39 subscales and the Summary Index and patients with self-reported comorbidities reported poorer SF-36 Physical Function and General Health subscale scores than patients without dyskinesias and comorbidities, respectively. This study suggests that the self-completed and telephone interview versions of the patient HQL questionnaire are feasible and valid for future clinical trial applications.

Aged↗
PubMed1998

Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Sträussler-Scheinker disease.

The clinicopathological phenotype of the Gerstmann-Sträussler-Scheinker disease (GSS) variant linked to the codon 102 mutation in the prion protein (PrP) gene (GSS P102L) shows a high heterogeneity. This variability also is observed in subjects with the same prion protein gene PRNP haplotype and is independent from the duration of the disease. Immunoblot analysis of brain homogenates from GSS P102L patients showed two major protease-resistant PrP fragments (PrP-res) with molecular masses of approximately 21 and 8 kDa, respectively. The 21-kDa fragment, similar to the PrP-res type 1 described in Creutzfeldt-Jakob disease, was found in five of the seven subjects and correlated with the presence of spongiform degeneration and "synaptic" pattern of PrP deposition whereas the 8-kDa fragment, similar to those described in other variants of GSS, was found in all subjects in brain regions showing PrP-positive multicentric amyloid deposits. These data further indicate that the neuropathology of prion diseases largely depends on the type of PrP-res fragment that forms in vivo. Because the formation of PrP-res fragments of 7-8 kDa with ragged N and C termini is not a feature of Creutzfeldt-Jakob disease or fatal familial insomnia but appears to be shared by most GSS subtypes, it may represent a molecular marker for this disorder.

Adult↗
PubMed1995

Rat strain and age differences in kainic acid induced seizures.

This study reports comparative dose-response data for kainic acid (KA) induced seizures in juvenile (35-40 days old) and adult (70-90 days old) Wistar-Furth (WF), Fisher 344 (F344), Sprague-Dawley (SD) and Long-Evans Hooded (LEH) rats. Juvenile male WF (n = 51), F344 (n = 55), SD (n = 60), LEH (n = 50) and adult male WF (n = 48), F344 (n = 52), SD (n = 52), LEH (n = 53) rats were given KA 6, 8, 10, 12 or 14 mg/kg, sc. As previously demonstrated adult WF and F344 rats showed the greatest sensitivity and most reliable convulsant responses to kainic acid; SD and LEH rats were less sensitive and showed more variable convulsant responses. Regardless of strain, all juvenile rats exhibited greater sensitivity and less variable convulsant response to KA compared to adults. This was most evident in juvenile SD and LEH rats. Results suggest that while seizure sensitivity to KA decreases with age, genetic factors may regulate the expression of this resistance.

Aging↗
PubMed1993

Olfactory-related changes in Alzheimer's disease: a quantitative neuropathologic study.

Neuropathological studies of 10 confirmed cases of Alzheimer's disease (AD) revealed increased numbers of neurofibrillary tangles and neuritic plaques in olfactory cortex compared to other brain regions. This was most evident when AD tissues were compared to tissues from seven gender- and age-matched controls. In the AD cases, examination of other brain regions which receive olfactory projections also revealed high concentrations of neuritic plaques and neurofibrillary tangles. These data also confirm previous observations that neurofibrillary tangle formation is more prevalent than neuritic plaque formation in AD. This is the first quantitative neuropathological study that demonstrates significant damage to various components of the central olfactory apparatus in AD. Our data suggest that damage to these areas may be related to the behavioral, emotional, and cognitive abnormalities commonly observed in affected patients. The use of antemortem evaluation of the olfactory system as a diagnostic tool for AD is discussed.

Aged↗
PubMed1992

In vivo modulation of excitatory amino acid receptors: microdialysis studies on N-methyl-D-aspartate-evoked striatal dopamine release and effects of antagonists.

Striatal dopamine (DA) release was measured following intrastriatal (i.s.) administration of N-methyl-D-aspartate (NMDA) to unanesthetized, freely-moving rats. One hour after insertion of a removable microdialysis probe and perfusion with normal Ringer's solution, a modified Ringer's solution containing 100 mM potassium (high-K+ Ringer's) was used to standardize the preparation. DA release following i.s. administration of NMDA (12.5 mM in normal Ringer's) was dose-dependent. When NMDA (12.5 mM) was administered in high-K+ Ringer's, DA release was greatly potentiated. Administration of the competitive NMDA receptor antagonist aminophosphonovalerate (APV) in normal Ringer's prior to treatment with NMDA in high-K+ Ringer's resulted in a significant reduction of DA release compared to control animals. In contrast, administration of APV priot to treatment with NMDA in normal Ringer's resulted in a significantly increased release of DA compared to controls. Administration of the non-competitive NMDA antagonist, dextromethorphan (DXT) prior to treatment with NMDA in normal Ringer's or NMDA in high-K+ Ringer's caused significant reductions of DA release compared to controls. Intrastriatal DXT also caused dose-dependent inhibition of high-K+ Ringer's-induced DA release. Similarly, administration of the non-specific calcium channel blocker, cadmium, prior to treatment with NMDA resulted in a significant decrease when compared to control values. Results of this study indicate that dose-dependent NMDA-induced striatal DA release is greatly potentiated by potassium suggesting that under physiological conditions in vivo, striatal NMDA receptors are mostly inactivated.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid.

Sensitisation to retinal S-antigen has been implicated in the pathogenesis of several clinical forms of posterior uveitis. S-antigen-like molecules have recently been demonstrated in the brain and choroid plexus of experimental animals. We used a panel of four monoclonal antibodies (MAbs), MAbF4-C1, MAbC10-C10, MAbA2-G5 and MAbA9-C6, which define specific epitopes in the amino, mid and carboxyl terminal portions of S-antigen in order to identify an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid (CSF). Three MAbs, MAbF4-C1, MAbC10-C10 and MAbA9-C6, localised an S-antigen-like molecule to the cytoplasm of the epithelial cells of the human choroid plexus. Polymerase chain reaction of cDNA from choroid plexus verified the presence of S-antigen homologues in the choroid plexus. The presence of an S-antigen-like molecule in the CSF was demonstrated by western blots in seven CSF samples from patients with a variety of neuropathological disorders. It is proposed that immunological cross-reactivity and biochemical similarity between retinal S-antigen and an S-antigen-like molecule in human choroid plexus and CSF could form a basis for neurological manifestations observed in certain clinical forms of uveitides.

Adult↗
PubMed1991

Partial characterization of kainic acid-induced striatal dopamine release using in vivo microdialysis.

The aim of this study was to characterize interactions between striatal kainate (KA) receptors and dopamine (DA) release using in vivo microdialysis. After insertion of a microdialysis probe and establishment of baseline DA release, each preparation was standardized with a pulse of an iso-osmotic solution of 100 mM KCl in Ringer's solution. DA release following pharmacological manipulation was compared to potassium-induced release and expressed as a percent value. In one group of animals, KA (12.5 mM in Ringer's solution) was administered via the microdialysis probe in 2, 3, 5 or 10 min pulses 30 min following standardization with potassium resulting in release of DA which was 15.7 +/- 3.9, 30.3 +/- 11.3, 67.5 +/- 15.0 and 92.9 +/- 19.8% of potassium-induced DA release, respectively. Perfusion of CdCl2 (0.6 mM in Ringer's solution) 30-45 min prior to a 10 min KA pulse significantly reduced KA-induced DA release compared to control values. Intrastriatal administration of kynurenate (Kyn) attenuated KA-induced DA release in a dose-dependent manner. Levels of DA metabolites in striatal perfusates were significantly reduced following KA administration. This effect was partially reversed by cadmium pretreatment but not affected by Kyn pretreatment. Findings of this study indicate that KA induces striatal DA release in a dose-dependent manner, and this effect is at least partially dependent upon activation of calcium channels. Results also indicate dose-dependent inhibition of KA-induced striatal DA release by the excitatory amino acid receptor antagonist, Kyn, suggesting that this compound interacts with striatal KA receptors and that these receptors are involved with modulating striatal DA release in vivo.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Strain differences in convulsive response to the excitotoxin kainic acid.

We describe a strain of rats (Wistar-Furth) that is highly susceptible to the neurotoxic effects of kainic acid (KA) and presents a reliable and quantifiable (with low within-group variability) animal model of status epilepticus. Wistar-Furth rats are more sensitive and demonstrate a less variable convulsant response than Sprague-Dawley and Long-Evans rats when tested for total time in seizure activity, latency to onset of first seizure, latency to status epilepticus, seizure severity scores, and percentage exhibiting behavioral seizures and status epilepticus. Results suggest that significant heterogeneity exists in the rodent population with regard to neuronal sensitivity to an excitotoxic amino acid and indicate that strain differences are an important consideration in studies using KA.

Animals↗
PubMed1989

Morphological and functional studies of rat tectal transplants.

Donor tectal tissue from fetal rats was transplanted to the tectal region of intact host newborn rats. Histological and ultrastructural characteristics of mature tectal grafts were examined with special emphasis placed on glial elements and the interface between transplant and host brain. Most transplants survived, proliferated, and differentiated to mature neurons and glial cells. Mature transplants were found to contain small and medium sized neurons which formed clusters along the transplant border. Neurites traversed the interface between transplant and host brain. There was an absence of phagocytosis, inflammatory reactions and chromatolytic neurons throughout the transplant. Classical staining techniques and GFAP immunoreactive stains revealed only mild focal astrogliosis confined mostly to the subpial and perivascular regions of the transplant-host interface. Ultrastructural examination of the transplant revealed numerous axodendritic synapses with aggregates of synaptic vesicles and well formed postsynaptic membranes. The absence of a leptomeningeal membrane at several points along the transplant-host interface may allow neurites from both sides to establish functional synaptic contacts. Single unit recording combined with anterograde WGA-HRP neuronal tract tracing was used to determine the presence and extent of host retinal innervation of tectal transplants.

Action Potentials↗
PubMed1987

The prepiriform cortex in dementia of the Alzheimer type.

Histopathologic examination of the prepiriform cortex (PPC) in four documented cases of dementia of the Alzheimer type revealed increased numbers of neurofibrillary tangles and neuritic plaques. These findings indicate that some early- and late-onset cases of Alzheimer's disease may be associated with significant damage to the PPC, a relay center of the mammalian olfactory system that has extensive connections with structures concerned with cognitive and behavioral functions. Involvement of the PPC may be related to the complex neuropsychiatric manifestations observed in this disorder.

Aged↗
PubMed1987

Presence of both odor identification and detection deficits in Alzheimer's disease.

Recent studies of Alzheimer's disease patients have demonstrated (a) marked structural and biochemical alterations in brain regions associated with olfactory function (including the olfactory bulb and entorhinal cortex) and (b) decrements in the ability to identify odorants. In light of such findings, we administered the University of Pennsylvania Smell Identification Test (UPSIT) and a forced-choice phenyl ethyl alcohol odor detection threshold test to a relatively large number of patients diagnosed, on the basis of stringent criteria, as having mild to moderately severe Alzheimer's disease. Compared to age-, gender-, and race-matched normal controls, these individuals evidenced consistent and marked decrements on both types of olfactory tests (ps less than 0.001). Surprisingly few of the patients were aware of their disorder, despite its appearance early in the disease process. These findings indicate that both odor identification and odor detection problems are present in dementia of the Alzheimer's type, and raise the possibility that the odor identification problem may be secondary to the odor detection problem.

Aged↗
PubMed1986

Intracranial calcification in adults with chronic lead exposure.

Computed tomographic (CT) findings of cerebral and cerebellar calcification are described in three American adults with raised serum lead levels and known exposure to lead for 30 or more years. Calcification patterns were punctiform, curvilinear, speck-like, and diffuse and were found in the subcortical area, basal ganglia, vermis, and cerebellum. Admission serum lead levels ranged from 54 to 72 micrograms/dl (normal, 0-30 micrograms/dl). Nonspecific neurologic manifestations consisted of dementia, diminished visual acuity, peripheral neuropathy, syncope, dizziness, nystagmus, easy fatigue, and back pain. Two patients developed chronic renal disease and hypertension; in both cases, serum parathormone was elevated. Blood, calcium, and phosphorus were normal in all three. No other structural abnormalities were observed with CT. Although the pathophysiologic mechanism of these findings remains poorly understood, it is suggested that chronic lead exposure should be included in the differential diagnosis of unexplained intracranial calcifications in adults.

Brain Diseases↗
PubMed1982

Neuroradiological correlates of frontally predominant intermittent rhythmic delta activity (FIRDA).

A correlative, retrospective review of 80 consecutive cases of EEG FIRDA was performed with regard to the neuroradiological findings: 62 of the 80 patients had had CAT scan evaluations. Of the 61 patients with structural pathology, 53 had CAT scans which were abnormal in 40 (76%); of the 19 patients with 'non-structural' (mostly metabolic) brain lesions, 10 had normal CAT scans. In the structural group with normal CAT scans, the presence of pathology was demonstrated by arteriography (5 cases), radionuclide cysternography (1 case), brain scan (1 case), or pathological examination. Patients with 'non-structural' FIRDA had a significantly higher probability of being in an altered state of consciousness and of having abnormal background activity in their EEG. Focal EEG abnormalities are more frequently associated with structural lesions and FIRDA. If FIRDA is present on the EEG, further neuroradiological studies should be considered, especially with other electroclinical information suggests a non-metabolic substrate.

Central Nervous System Diseases↗
PubMed1981

New form of adrenoleukodystrophy.

Male and female siblings demonstrated similar facial features and had seizures from birth. Neurologic development, which was delayed, began to deteriorate at 1 year. Sudden death occurred at 2 8/12 and 2 3/12 years of age associated with respiratory infections. Tanning of the skin was noted 2 months before death in the first child. In the second child, blood cortisol levels failed to increase after intravenous ACTH administration, and computerized axial tomography (CAT) scans were normal. At autopsy both patients demonstrated adrenal atrophy and degenerative changes of the white matter throughout the neuraxis. We propose that these siblings have a new form of adrenoleukodystrophy that can be distinguished from the X-linked form by onset at birth, clinical appearance, and pattern of inheritance. A comparison of these cases with a second disorder, Zellweger's syndrome, suggests that a distinctive phenotype is associated with intrauterine degeneration of white matter.

Adrenal Cortex↗