Laryngeal dystonia in psychiatry.
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Adolescent↗
Biomedical subjects
J Norton
Publications and source records attributed to J Norton.
[Development of the main indicators of perinatal health in metropolitan France between 1995 and 1998. Results of the national perinatal survey].
OBJECTIVE: To study trends in the main indicators of health, medical practice and risk factors. POPULATION AND METHOD: We compared two samples; both included all stillbirths and live births during one week in France: 13,318 in 1995 and 13,718 in 1998. RESULTS: Between 1995 and 1998, there was an increase in maternal age, a development of some characteristics of care (antenatal care by maternity unit staff, HIV screening procedure, antenatal classes) and an increase in the proportion of caesarean sections and epidurals. The proportion of live births before 37 weeks of gestation increased from 5.4% to 6.2%. This trend is explained by an increase in preterm deliveries among twins. Specific questions in the 1998 questionnaire showed that 6.3% of women had received fertility treatment before this pregnancy, 11.1% had an amniocentesis, and 1.1% had an intrauterine transfer. CONCLUSION: This type of survey carried out every three years can show major changes in health, risk factors and medical practices and can yield quick answers to specific questions.
Adult↗
Suppression of erythroid but not megakaryocytic differentiation of human K562 erythroleukemic cells by notch-1.
The Notch signal transduction pathway is a highly conserved regulatory system that controls multiple developmental processes. We have established an erythroleukemia cell model to study how Notch regulates cell fate and erythroleukemic cell differentiation. K562 and HEL cells expressed the Notch-1 receptor and the Notch ligand Jagged-1. The stable expression of the constitutively active intracellular domain of Notch-1 (NIC-1) in K562 cells inhibited erythroid without affecting megakaryocytic maturation. Expression of antisense Notch-1 induced spontaneous erythroid maturation. Suppression of erythroid maturation by NIC-1 did not result from down-regulation of GATA-1 and TAL-1, transcription factors necessary for erythroid differentiation. Microarray gene expression analysis identified genes activated during erythroid maturation, and NIC-1 disrupted the maturation-dependent changes in the expression of these genes. These results show that NIC-1 alters the pattern of gene expression in K562 cells leading to a block in erythroid maturation and therefore suggest that Notch signaling may control the developmental potential of normal and malignant erythroid progenitor cells.
Basic Helix-Loop-Helix Proteins↗
Tau polymorphisms are not associated with Alzheimer's disease.
Alzheimer's disease (AD) is one of a number of neurodegenerative conditions including frontotemporal dementia and progressive supranuclear palsy that are associated with abnormal tau protein aggregates in neurons. Mutations in the tau gene cause familial forms of frontotemporal dementia and alleles of the tau gene have been associated with risk for progressive supranuclear palsy. However, studies evaluating whether polymorphic variation in tau is associated with AD have produced conflicting results. We investigated the role of the tau exon 2 polymorphism in a large sample of AD cases and controls and found no evidence that polymorphic variation in tau is associated AD.
Aged↗
Linking Notch signaling, chromatin remodeling, and T-cell leukemogenesis.
Intercellular communication that controls the developmental fate of multipotent cells is commonly mediated by the Notch family of transmembrane receptors. Specific transmembrane ligands activate Notch receptors on neighboring cells inducing the proteolytic liberation and nuclear translocation of the intracellular domain of Notch (N(IC)). Nuclear N(IC) associates with a transcriptional repressor known as C-promoter binding factor/RBP-J kappa, suppressor of hairless, or LAG-1, converting it from a repressor into an activator. Through physical interactions with chromatin remodeling enzymes and potentially with components of the transcriptional machinery, N(IC) activates target genes that mediate cell fate decisions. As Notch1 is disrupted via a chromosomal translocation in a subset of human T-cell leukemia, leading to a truncated polypeptide resembling N(IC), deregulated chromatin remodeling and transcription may fuel uncontrolled cell proliferation in this hematopoietic malignancy. This review summarizes the mechanics of Notch signaling and focuses on prospective molecular mechanisms for how constitutively active Notch might derail nuclear processes as an initiating step in T-cell leukemogenesis. J. Cell. Biochem. Suppl. 35:46-53, 2000.
Animals↗
Effect of altered gastric emptying and gastrointestinal motility on metformin absorption.
AIMS: The purpose of this in vivo human study was to assess the effect of altered gastric emptying and gastrointestinal motility on the absorption of metformin in healthy subjects. METHODS: An open-label, three treatment, three period crossover study was conducted in 11 healthy volunteers. Each subject received 550 mg metformin hydrochloride in solution alone; 5 min after a 10 mg i.v. dose of metoclopramide; and 30 min after a 30 mg oral dose of propantheline. Metformin solution was radiolabeled by the addition of 99mTc-DTPA. The gastrointestinal transit of the solution was monitored by gamma scintigraphy and the pharmacokinetic data were correlated with the scintigraphic findings. RESULTS: Scintigraphic data indicated that pretreatment with metoclopramide decreased gastric emptying time and increased gastrointestinal motility while pretreatment with propantheline had the opposite effect. The systemic disposition of metformin was not altered by pretreatment with metoclopramide and propantheline, as judged by unchanged renal clearance and elimination half-life of metformin. Extent of metformin absorption was essentially unchanged after pretreatment with metoclopramide. However, AUC(0,infinity) and % UR (percent dose excreted unchanged in urine) generally increased with increase in gastric emptying time and small intestinal transit times. GI overlay plots showed that the absorption phase of metformin plasma profile always coincided with gastric emptying and the beginning of decline of metformin plasma concentrations was usually associated with the colon arrival. Only in cases where the intestinal transit was drastically prolonged by propantheline pretreatment, was a decline in plasma levels observed prior to colon arrival. CONCLUSIONS: Metformin is primarily absorbed from the small intestine. The extent of metformin absorption is improved when the gastrointestinal motility is slowed. These findings have significant implications in the design of a metformin modified release dosage form.
Adult↗
Use of intravenous valproate sodium in status migraine.
Patients with migraines have typically been given one group of medications for abortive treatment and another for preventative. In the acute situation when the patient has severe nausea it is difficult to administer medications. Intravenous medications would avoid this problem but are limited to the opiates and dihydroergotamine. The following cases demonstrate the acute treatment of migraine with intravenous valproic acid (Depacon). The oral form of valproic acid has been used as a prophylactic agent, but the intravenous form may provide an alternative for abortive care as well. The ease of administration and lack of side effects are also important considerations. Double-blind studies will help clarify the situation.
Acute Disease↗
The neuropsychiatric symptoms of AIDS.
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AIDS Dementia Complex↗
The significant change for the Timed 25-foot Walk in the multiple sclerosis functional composite.
The Timed 25-Foot Walk is under evaluation as a clinical tool to follow patients with MS. Several approaches have been taken to define a clinically significant change in this measurement. This study was undertaken to define the range of values expected for the Timed 25-Foot Walk and to correlate prospectively the change in walk-time that occurs during an exacerbation of MS associated with subjective difficulty walking. Five results from this study are emphasized. (1) Patients who were minimally affected by MS frequently walked 25 feet between three and five seconds. (2) the walk-time variability, defined as the ratio of the longest to the shortest walk-time, minus 1, times 100%, for three consecutive trials was generally 20% or less; (3) if the two fastest walk-times obtained in three trials were compared, the walk-time variability was almost always 10% or less; (4) for clinically stable individuals, the walk-times of single trials separated by 12 months or less generally varied less than 20%; and (5) patients who complained of difficulty walking, but who did not have changes otherwise detectable by examination, generally had a prolongation of walk-time. These results suggest that an increase of more than 20% in the Timed 25-Foot Walk may indicate a significant change in gait. Multiple Sclerosis (2000) 6 286 - 290
Disability Evaluation↗
Clinical audit of 5 years provision of the Odstock dropped foot stimulator.
The Odstock dropped foot stimulator (ODFS) is a foot switch controlled single channel neuromuscular stimulator for correction of dropped foot. Following a randomized controlled trial, the ODFS was recommended for use in the United Kingdom's National Health Service and a clinical service established. The patient performance was assessed by measurement of walking speed over 10 m, physiological cost index (PCI), and by questionnaire. After 4.5 months stroke patients (n = 111) showed a mean increase in walking speed of 27% and reduction in PCI of 31% with stimulation and changes of 14% and 19%, respectively, unassisted. Multiple sclerosis patients (n = 21) gained similar orthotic benefit but no carry over. The principal reason cited for using the equipment was that it reduced the effort of walking. The principal reasons identified for discontinuing were an improvement in mobility, electrode positioning difficulties, and deteriorating mobility. A comprehensive clinical follow-up service is essential to achieve the maximum continuing benefit from FES based orthosis.
Cerebrovascular Disorders↗
Pharmacokinetics and pharmacodynamics of avitriptan during intravenous administration in healthy subjects.
Avitriptan, a selective 5-HT1-like receptor agonist, is an effective compound for the treatment of migraine headaches with a prolonged duration of response. A double-blind, placebo-controlled, parallel-group, ascending-dose study in 24 healthy subjects was designed to assess the safety, tolerance, pharmacokinetics, and pharmacodynamics of avitriptan. This antimigraine drug was administered as two consecutive constant-rate IV infusions at three dose levels (12.7, 25.3, and 38.0 mg), which were targeted to produce plasma concentrations in and above the therapeutic range. The best fitting of the plasma concentration-time data was obtained by using a triexponential function yielding a terminal t1/2 of 8 hours. The areas under the plasma concentration versus time curves were proportional to dose, indicating linear pharmacokinetics. Moreover, the clearance and steady-state volume of distribution values were independent of the dose. The change in pulse rate and supine systolic and diastolic blood pressure was determined as pharmacodynamic effects of avitriptan. A "threshold log-linear" model, which accounts for the linear increase in pharmacodynamic effect with the log of plasma concentrations when the latter was higher than a certain threshold value, adequately described the pharmacodynamic data. The threshold plasma drug concentrations for the pulse rate and the diastolic and systolic blood pressure were 14, 74, and 161 ng/ml, respectively. Overall, avitriptan has consistent, linear pharmacokinetics and increases systolic and diastolic blood pressure in a predictable manner at a higher plasma concentration. However, this drug does not produce a significant change in pulse rate at the dose levels (12.7-38 mg) evaluated in this study.
Adult↗
Breast feeding: the baby friendly initiative. The arts and the media can help.
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Breast Feeding↗
Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17.
Thirteen families have been described with an autosomal dominantly inherited dementia named frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), historically termed Pick's disease. Most FTDP-17 cases show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein Tau, although the Tau pathology varies considerably in both its quantity (or severity) and characteristics. Previous studies have mapped the FTDP-17 locus to a 2-centimorgan region on chromosome 17q21.11; the tau gene also lies within this region. We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon 10. The splice-site mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10. This causes more frequent usage of the 5' splice site and an increased proportion of tau transcripts that include exon 10. The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17.
Alternative Splicing↗
The new HIV therapies: implications for HIV prevention.
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Anti-HIV Agents↗
Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype.
OBJECTIVE: To study differences between subjects with Alzheimer disease (AD) and cognitively intact control subjects, with respect to brain histologic markers of AD, and the relationship of those markers in the AD group to severity of dementia, age at death, sex, and apolipoprotein E genotype. SETTING: Washington University Alzheimer's Disease Research Center, St Louis, Mo. DESIGN AND SUBJECTS: Consecutive neuropathologic series of 224 prospectively studied volunteer research subjects, 186 with dementia of the Alzheimer type (DAT) or "incipient" DAT and confirmed to have AD by postmortem examination and 13 cognitively intact subjects, confirmed to lack postmortem findings of AD. MAIN OUTCOME MEASURES: Brain densities (number per square millimeter) of senile plaques and neurofibrillary tangles, extent of cerebral amyloid angiopathy, cortical Lewy bodies, and apolipoprotein E genotype. RESULTS: Neocortical neurofibrillary tangle densities were substantially correlated with dementia severity, and to a greater degree than was true for senile plaque densities. When infarcts, hemorrhages, and Parkinson disease changes coexisted with AD, neurofibrillary tangle and senile plaque densities were lower. Plaque-predominant AD was found in a greater proportion of subjects with milder than more severe dementia. Entorhinal cortical Lewy bodies were no more frequent in plaque-predominant AD than in the remaining AD cases. Increasing age at death was negatively correlated with dementia severity and densities of senile plaques and neurofibrillary tangles. The apolipoprotein E epsilon4 allele frequency was greater in AD than in control subjects but decreased with increasing age. After controlling for dementia severity, senile plaque densities were only weakly related to epsilon4 allele frequency, and only in hippocampus. However, the degree of cerebral amyloid angiopathy was clearly related to epsilon4 allele frequency. Among subjects diagnosed during life as having DAT or incipient DAT, only 7% were found to have a neuropathologic disorder other than AD causing their dementia. CONCLUSIONS: (1) The order of the strength of relationships between densities of histologic markers and dementia severity in AD is neurofibrillary tangles greater than cored senile plaques greater than total senile plaques. (2) Advanced age at death is associated with somewhat less severe dementia and fewer senile plaques and neurofibrillary tangles. (3) Plaque-predominant AD may represent a developmental stage in AD. (4) Despite a substantial effect of apolipoprotein E epsilon4 as a risk factor for AD, on decreasing the age at AD onset, and increasing the amount of cerebral amyloid angiopathy, its effect on senile plaque densities is variable and complex, being confounded with age, dementia severity, and methodologic differences. (5) Stringent clinical diagnostic criteria for DAT, even in the very mild stage, and senile plaque-based neuropathologic criteria for AD are highly accurate.
Aged↗
Hereditary dysphasic disinhibition dementia: a frontotemporal dementia linked to 17q21-22.
OBJECTIVE: The clinical and pathologic features of hereditary dysphasic disinhibition dementia (HDDD) are described to determine whether it is a variant of known dementias. BACKGROUND: Several dementing disorders have clinical and pathologic similarities with AD, Pick's disease, and the "nonspecific" dementias. A detailed description of clinical and pathologic presentation will aid classification, but ultimately the discovery of causative gene(s) will define these disorders. METHODS: The authors performed a clinical assessment: gross and microscopic pathologic evaluation of brain tissue, genetic linkage studies, and sequence analyses. RESULTS: HDDD is an autosomal-dominant frontotemporal dementia with many similarities to Pick's disease. Salient clinical features are global dementia with disproportionate dysphasia and "frontotemporal" symptoms. A linkage between HDDD and 17q21-22 was shown, with a maximum lod score of 3.68 at zero recombination. CONCLUSIONS: Several dementias have been linked to the same region and have been termed frontotemporal dementia with parkinsonism linked to chromosome 17. These disorders may represent phenotypic variants arising from mutations within a common gene.
Adult↗
Age and sexual risk behaviour.
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Adolescent↗
Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation.
OBJECTIVES: To characterize clinical features of a very large pedigree with early-onset Alzheimer disease (AD) in which all affected individuals carry the identical glutamic acid-to-alanine mutation at codon 280 in the presenilin-1 gene. DESIGN: Clinical histories were obtained by patient and family interviews and through medical or civil records. Using standard diagnostic criteria, a case series of 128 individuals was identified, of which 6 have definitive (autopsy-proven) early-onset AD, 93 have probable early-onset AD, and 29 have possible early-onset AD. SETTING: Community based in Antioquia, Colombia. PATIENTS: A population-based sample in which all members of 5 extended families (nearly 3000 individuals) were surveyed. Criteria for inclusion required obtaining sufficient information to categorize the individual as affected. MAIN OUTCOME MEASURES: Age at onset, neuropsychological profile, neurologic history, and examination. RESULTS: The patients had a mean age at onset of 46.8 years (range, 34-62 years). The average interval until death was 8 years. Headache was noted in affected individuals significantly more frequently than in those not affected. The most frequent presentation was memory loss followed by behavior and personality changes and progressive loss of language ability. In the final stages, gait disturbances, seizures, and myoclonus were frequent. CONCLUSIONS: Other than the early onset, this clinical phenotype is indistinguishable from sporadic AD except that affected individuals frequently complained of headache preceding and during the disease. Despite the uniform genetic basis for the disease, there was significant variability in the age at onset, suggesting an important role for environmental factors or genetic modifiers in determining the age at onset.
Adult↗