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Biomedical subjects

G W Small

Publications and source records attributed to G W Small.

At least 145 records · Page 8Linked to original sources

Mass hysteria among schoolchildren. Early loss as a predisposing factor.

On May 21, 1979, an outbreak of illness spread swiftly among elementary school students in a Boston suburb. Of 224 boys and girls attending an assembly, 34 were hospitalized with severe dizziness, weakness, hyperventilation, headache, nausea, and abdominal pain. Sudden remission of symptoms, preponderance in girls, and failure of an extensive epidemiological investigation to detect an organic cause indicated mass hysteria. To test the hypothesis that previous loss influenced a child's vulnerability to current loss and predisposed that child to mass hysteria, we compared the incidence of family disruption in the hospitalized children with that in the nonhospitalized children. A significantly higher rate of parental divorce (P less than .00005) and death within the family (P less than .0005) occurred among the hospitalized children. These findings suggest a relationship between childhood loss and susceptibility to mass hysteria.

Adolescent↗

Diagnosis and treatment of dementia in the aged.

Dementia affects an estimated 5 percent of the population 65 years of age and older, with 20 percent being affected at 75 years or older. Although the most common forms, primary degenerative and multi-infarct dementia, currently lack specific treatments, it is estimated that a thorough diagnostic evaluation will uncover a treatable cause in 10 percent to 20 percent. The differential diagnosis includes benign senescent forgetfulness, depression, adjustment disorder, paranoid states, amnestic syndrome, delirium, drug effects, systemic illnesses and intracranial conditions. The approach to each patient involves a history, physical examination, mental status evaluation and laboratory tests that focus on identifying treatable conditions. When no specific treatments are available, however, symptomatic treatments, including pharmacotherapy, environmental management, family supports and psychotherapy, can offer relief for both patients and their families and improve the daily functioning of the elderly patient with dementia.

Aged↗

HLA-A2 as a possible marker for early-onset Alzheimer disease in men.

We performed HLA typing on 36 patients with clinically diagnosed Alzheimer disease and 25 controls. Antigen A2 was present in all ten men (100%) with early-onset (less than 60 years) dementia, a frequency significantly higher than the 30% frequency found in the cognitively intact men of a comparable age (p = 0.009, corrected). This increased A2 frequency was also significantly greater than the frequencies for all other patient subgroups, including late-onset men (40%, p = 0.008), early-onset women (44%, p = 0.004), and late-onset women (42%, p = 0.028). Our findings, if repeated in future studies with larger samples, suggest that HLA-A2 positive men may comprise a subgroup with increased susceptibility to early-onset disease.

Age Factors↗

Variable association of HLA-A2 in men with early-onset Alzheimer disease.

In the present study, we attempted to replicate the finding of an increased frequency of HLA-A2 in men with early-onset (less than or equal to 60 years) Alzheimer disease (AD). HLA data obtained on 167 patients (including 19 men with early-onset AD) from three geographic regions (North Carolina, Great Britain, and Finland) failed to replicate the result. A recent prospective study from Oregon, however, confirmed the association. Studies demonstrating the association suggest its presence in sporadic rather than familial AD. These results indicate a variable HLA/AD association, with some factor such as geographic region or disease familiality contributing to this variability.

Aged↗

An economic evaluation of donepezil in the treatment of Alzheimer's disease.

Using data from a longitudinal survey of caregivers of Alzheimer's disease patients, we calculated the average per-patient direct medical costs over a 6-month period for a matched sample of patients (N = 376). A group of patients receiving donepezil for 6 months was compared with a group not receiving this form of drug therapy. The groups were matched by disease severity, age, sex, and comorbidity. The average age in the two groups was 74 years, with 50% female and 90% white. Patients in both groups had a mean of 1.6 comorbid conditions. No patients in either group were institutionalized at the beginning of the 6-month period, and all patients were taking at least one prescription drug, including donepezil. Mean 6-month direct medical expenses for a patient receiving donepezil were $3443, including the cost of the drug, whereas the per-patient mean expenses for the comparison group were $3476. Although the patients receiving donepezil had greater expenditures for prescription drugs, these costs were offset by a slower rate of institutionalization. At the end of the 6-month period, 5% of donepezil patients were institutionalized, compared with 10% of the nondonepezil patients. The cost of receiving donepezil treatment for 6 months did not result in a significantly higher per-patient mean direct cost.

Aged↗

Complete genomic screen in late-onset familial Alzheimer's disease.

Alzheimer's disease (AD) is a complex genetic disorder. Linkage analysis has helped unravel a portion of the genetic component of AD by identifying four loci that play a role in the genetics of AD (amyloid precursor protein, presenilin 1, presenilin 2, and apolipoprotein E). These loci account for approximately 50% of the genetic etiology of AD. A total genomic screen is an efficient way to identify additional genetic effects in AD. A series of multiplex late-onset (>60 years) AD families were ascertained (NINDS-ADRDA diagnostic criteria) and sampled. A subset (n = 16) of the largest families (52 affecteds with DNA, 83 unaffecteds with DNA) were used to rapidly screen the genome (n = 280 markers) for additional major genetic effects. Critical values for regional follow-up were p < or =0.05 for SimIBD or sibpair analysis and/or a LOD score > or = 1.00. Fifteen regions warranted initial follow-up based on these criteria. An additional screening set was used (n = 38 families, 89 affecteds with DNA, 216 unaffecteds with DNA) for the follow-up analysis. These analyses revealed four regions of continued interest on chromosomes 4, 6, 12, and 20. Chromosome 12 presented the strongest results. Peak two point "affecteds only" LOD scores were 1.3, 1.6, 2.7, and 2.2 and (affected relative pair SimIBD) p values were 0.04, 0.03, 0.14, and 0.04 for D12S373, D12S1057, D12S1042, and D12S390, respectively. These markers span approximately 30 cm near the centromeric region of chromosome 12. Sibpair analysis resulted in two point Maximum Lod Score (MLS) results of 0.4, 1.2, 3.2, and 1.0 for the above markers. Multipoint MLS analysis supported these findings. Saturation mapping of all available markers in the chromosome 12 region as well as further investigation of the regions on 4, 6, and 20 is ongoing with candidate gene analysis to follow.

Age of Onset↗

Neuroimaging findings in twins discordant for Alzheimer's disease.

Data from computed tomography (CT) scans of 12 twin pairs in which one partner had Azheimer's disease (AD) and the other partner is cognitively intact were analyzed to study structural brain features associated with AD while controlling for familial factors. Visual ratings and analysis of quantified areas and volumes indicated that AD twins showed more dilation of temporal horns, lateral ventricles and third ventricle, and more atrophy of temporal lobes, particularly in the anterior temporal/perisylvian area, than their healthy cotwins. Demented twins did not have smaller intracranial areas or overall brain volumes than their intact partners. The apolipoprotein sigma-4 allele was associated with greater dilation of lateral ventricles and ventricular volume. Significant intrapair correlations were found for total intracranial area and volume, cerebellar area and white matter lesions.

Aged↗

Clinical characterization of Alzheimer's disease: reliability of 'age at onset' and a new descriptor, 'age at shift'.

To determine the interrater reliability of clinical descriptors for Alzheimer's disease (AD), we assessed the degree of agreement among four clinicians who rated 21 patients during a longitudinal study. Despite variability in response patterns, degree of agreement for determining age at onset of dementia was statistically significant (P less than 0.005). We also found significant agreement (P less than 0.0001) among three clinicians for the clinical descriptor, "age at shift" from questionable to probable AD, according to the National Institutes of Health Consensus Criteria. These data demonstrate that both retrospective and prospective descriptors can be reliably determined in the clinical assessment of AD.

Age Factors↗

HLA antigens in depressed, demented, and nondemented elderly.

To identify HLA antigen associations with geriatric depression, the authors typed 36 elderly patients with major depression and, for comparison, 36 patients with Alzheimer-type dementia and 29 nondemented elderly controls. The frequency for antigen Aw32 was significantly higher in the group of patients with major depression (14%) than in the demented (0%) and control (3%) groups. The frequencies for antigens Aw32 (22%) and Bw51 (22%) were significantly higher in the subgroup of 23 patients with endogenous depression than in the demented (Aw32 = 0%; Bw51 = 11%) and the control (Aw32 = 3%; Bw51 = 0%) groups. Although these results were derived from a relatively small sample (n = 101) and become nonsignificant when corrected for multiple comparisons, they suggest that HLA antigen associations may be present for only certain depressive subtypes in geriatric depression.

Age Factors↗

Estrogen effects on the brain.

This article reviews available data on the effects of estrogen on the brain. Such information is derived from basic laboratory studies, inferences from comparisons of gender differences, observational epidemiologic studies, and clinical trials of estrogen in humans. Findings suggest the potentially favorable influences of estrogen on mood and cognition in older women and augment current knowledge about physical risks and benefits of estrogen use.

Affect↗

Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease.

OBJECTIVE: Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. DESIGN: After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. SETTING: University medical center. PATIENTS: At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). MAIN OUTCOME MEASURES: Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. RESULTS: Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. CONCLUSIONS: These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.

Adult↗