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Biomedical subjects

L White

Publications and source records attributed to L White.

At least 19 recordsLinked to original sources

A series of infections due to Capnocytophaga spp in immunosuppressed and immunocompetent patients.

OBJECTIVE: To investigate the epidemiology, microbiology and outcome of infections caused by Capnocytophaga spp. at a single center. METHODS: We report on ten documented infectious episodes caused by Capnocytophaga observed between 1994 and 1999 at the Innsbruck University Hospital. RESULTS: In seven of ten patients, Capnocytophaga septicemia was diagnosed during periods of neutropenia. In contrast, the remaining three patients had normal white blood cell counts when acquiring Capnocytophaga septicemia (one) and pleural empyema (two). Blood cultures containing long, slender, Gram-negative rods, which grew slowly under anaerobic conditions and lacked susceptibility to metronidazole, were subcultivated in a CO2-enriched atmosphere (5%). Subcultivation yielded Capnocytophaga in all ten cases within 2-12 days. The patients were then placed on appropriate antibiotic therapy, with or without additional surgical intervention, and the organism was eradicated. CONCLUSION: Identification of Capnocytophaga facilitates appropriate, and in most cases effective, antimicrobial therapy.

Adult↗

A glycine to aspartic acid substitution of COL2A1 in a family with the Strudwick variant of spondyloepimetaphyseal dysplasia.

BACKGROUND: Spondyloepimetaphyseal dysplasia (SEMD) is one of a clinically heterogeneous group of skeletal disorders, characterized by defective growth and modelling of the spine and long bones. Common clinical features include disproportionate short stature, malformed vertebrae and abnormal epiphyses or metaphyses. Some cases have been associated with mutations in the COL2A1 gene. AIM: To determine whether the autosomal dominant Strudwick-type SEMD in a three-generation family, showing specific phenotypical features such as chest deformity, limb shortening, myopia and early-onset degenerative osteoarthrosis, might be caused by a novel COL2A1 mutation. DESIGN: Genetic testing and clinical examination of family members. METHODS: Direct sequencing of PCR-amplified genomic DNA from the COL2A1 gene. RESULTS: A point mutation within exon 20 of the COL2A1 gene was identified that substituted a glycine for an aspartic acid residue at codon 262. DISCUSSION: All previously reported autosomal dominant mutations causing SEMD have substituted an obligate glycine within the triple helix, in particular at codons 292, 304 and 709 in the three reported Strudwick-type patients. Additionally, a recurrent glycine substitution at codon 154 has been identified in two unrelated Finnish cases with radiological features consistent with the Strudwick subtype. Our sixth helical glycine substitution extends the mutational spectrum and genotype/phenotype correlations of Strudwick-type SEMD.

Aspartic Acid↗

Development and validation of a cholate binding capacity method for DMP 504, a bile acid sequestrant.

DMP 504, a highly cross-linked insoluble polymer, is a bile acid sequestrant developed by the DuPont Pharmaceuticals Company for serum cholesterol reduction. Since DMP 504 is insoluble, it was necessary to develop unique specific analytical methods to measure and control the quality of different lots of the drug. Since the mechanism of action of DMP 504 is believed to be by sequestration of bile acids, the in-vitro binding capacity of the polymer for cholic acid was chosen as a surrogate of in-vivo performance and used to assess potency of the compound. In this method, individual aliquots of DMP 504 at three different levels were incubated with a cholate solution of known concentration. The residual cholate solution was filtered and analyzed by a reversed-phase HPLC method using refractive index detection. When the bound cholate was plotted versus the mass of DMP 504, the resulting curve was linear. The slope of this curve is the cholate binding capacity of DMP 504. This method has been shown to be precise and robust. Precision of the method was shown to have an RSD of 2.0% with injection precision of 0.4% and stability of cholate solutions up to 73 h. It is also a unique binding capacity method due to its multi-point determination, and it has been shown to be a suitable quality control method for ensuring lot-to-lot consistency of drug substance.

Cholates↗

Guanfacine treatment of cognitive impairment in schizophrenia.

Norepinephrine plays a significant role in the working memory functions of the prefrontal cortex by its actions at alpha-2a noradrenergic receptors. Guanfacine has demonstrated efficacy in reversing working memory deficits in non-human primate. In the present study the effect of guanfacine adjunctive treatment to neuroleptics on the cognitive performance of schizophrenic patients was investigated in a four week, placebo-controlled, double-blind, parallel design trial. The primary analyses revealed no significant differences between guanfacine and placebo treatment; however, exploratory non-parametric statistics revealed some significant and some trend differences between guanfacine and placebo on spatial working memory test performance and CPT reaction time in those subjects treated with atypical neuroleptics.

Adrenergic alpha-Agonists↗

Omega-3 polyunsaturated fatty acids in adolescents: knowledge and consumption.

OBJECTIVE: To assess adolescents' knowledge about n-3 polyunsaturated fatty acids (PUFA) and their dietary intake of these important nutrients. METHODS: A questionnaire consisting of 12 questions assessing the knowledge and intake of n-3 PUFA and of a 24-h dietary recall was administered to 1117 ninth-grade adolescents (52% girls and 48% boys) attending five public schools. The adolescents were subsequently provided with verbal and written information on the health benefits, requirements, and dietary sources of n-3 PUFA. Dietary recalls were analyzed for energy and n-3 PUFA intake. Descriptive statistics, Student's t-tests, Chi-square analysis, and multiple regression analysis were used to assess adolescents' knowledge about n-3 PUFA as well as to examine relationships of independent variables with n-3 PUFA intake. RESULTS: Most adolescents (89%) believed that eating fish, a main source of very long chain (VLC) n-3 PUFA, is healthy and may prevent heart disease (59%), but only a few knew about n-3 PUFA's role in alleviating inflammation (29%) and its potential for cancer prevention (25%). Many were aware of marine sources of n-3 PUFA, such as salmon (67%), tuna (46%), mackerel (30%), and herring (26%), but only 36% knew about adequate intake of VLC n-3 PUFA. The main source of n-3 PUFA information was parents (58%), whereas only 21% of adolescents reported that their care providers had discussed health benefits of n-3 PUFA with them. About one-third of adolescents consumed fish at least once a week, and 29% consumed fish once a month. Dislike (22% of participants) and allergy (3%) were the main reasons for rarely (< or = 3 times/year; 18%) or never (17%) consuming fish. Only one adolescent reported daily consumption of a fish concentrate supplement. Daily consumption of linolenic acid was higher in boys (0.38 +/- 0.02 g) than in girls (0.31 +/- 0.01 g; p =.002). Total intake of n-3 PUFA represented only 30% of the presently available (Canadian) recommended daily allowance (CRDA) for 14- to 15-year-old boys (1.4 g/day) and 29% of the CRDA for 14- to 15-year-old girls (1.2 g/day). CONCLUSIONS: Adolescents are aware of some of the health benefits of n-3 PUFA but lack concrete information about dietary requirements of n-3 PUFA and about n-3 PUFA content of various dietary sources.

Adolescent↗

Working children and accidents: understanding the risks.

Recent research suggests that a significant proportion of school children aged 10-16 years are employed outside the home during the school term. Delivery work represents only a minority of such employment and children are found working in a wide range of 'adult' jobs, particularly in the service sector. This raises concerns about health and safety hazards faced by working children. There is an absence of data on the effects of different kinds of work and working conditions on child health and development, which is thus a barrier to defining goals, policies and effective action. This paper aims to address these issues through presenting some research findings on child employment and incidences of accident. The study is based on surveys of school children in North Tyneside and Norfolk. Our analysis shows that there is a high level of accidents occurring at work among children aged 10-16 years old. While legislation exists in the UK to prevent children from working in the most hazardous environments and to prohibit young children from undertaking any employment, it is clear that such work does take place. Our findings indicate that it is time to look at the occupational health of children as a major concern.

Accidents, Occupational↗

Daytime sleepiness is associated with 3-year incident dementia and cognitive decline in older Japanese-American men.

OBJECTIVES: To assess the longitudinal association between sleep disturbances (insomnia and daytime sleepiness) and incidence of dementia and cognitive decline in older men. DESIGN: Community-based longitudinal cohort study. SETTING: The Honolulu-Asia Aging Study of dementia that is linked to the Honolulu Heart Program's fourth examination, conducted 1991-1993, and the 3-year follow-up fifth examination, conducted 1994-1996. PARTICIPANTS: Two thousand three hundred forty-six Japanese-American men age 71 to 93 years who screened negative for prevalent dementia at baseline and were screened again for dementia incidence in a 3-year follow-up examination. MEASUREMENTS: Baseline self-reports of trouble falling asleep or early morning awakening (insomnia) and being sleepy during the day (daytime sleepiness); Cognitive Abilities Screening Instrument (CASI) scores from baseline and followup; clinical diagnosis of incident dementia; and other baseline measures including age, years of education, body mass index, depressive symptoms, and history of hypertension, heart disease, diabetes mellitus, asthma, and use of benzodiazepines. RESULTS: After adjusting for age and other factors, persons reporting excessive daytime sleepiness at baseline (8%) were twice as likely to be diagnosed with incident dementia than were those not reporting daytime sleepiness (odds ratio (OR)=2.19, 95% confidence interval (CI)=1.37-3.50) and about 40% more likely to have >or=9 point drop in their CASI score between examinations (OR=1.44, 95% CI=1.01-2.08). In contrast, insomnia was not associated with cognitive decline or incidence of dementia. CONCLUSIONS: Daytime sleepiness in older adults may be an early indicator of decline in cognitive functioning and onset of dementia.

Aged↗

Medulloblastoma/primitive neuroectodermal tumour studied as a Matrigel enhanced subcutaneous xenograft model.

An important role for pre-clinical models of medulloblastoma/primitive neuroectodermal tumour (MB/PNET) is inhibited by the limitations of conventional heterotransplantation. Nine cohorts of MB/PNET were studied for subcutaneous engraftment in nude mice by both conventional and Matrigel supplemented methods. While no subcutaneous tumours resulted from 63 conventional attempts, an aggregate 41 xenografts from 72 injections (57%) were produced when Matrigel was added to the cell suspension. In subsequent passage, engraftment rate approached 100%. To study the response to chemotherapeutic agents in the model, a total of 221 tumours in 3 cohorts were treated using one of the following: cisplatin, carboplatin, vincristine, cyclophosphamide, diaziquone, or saline control. While all agents demonstrated statistically significant activity, cyclophosphamide proved to be particularly effective. The potential applications of this xenograft model in the biologic as well as therapeutic study of MB/PNET deserve continuing investigation.

Animals↗

Gender differences in poor outcome patients with lifelong schizophrenia.

Gender effects have been reported quite consistently in schizophrenia, with male patients having an earlier age of onset, poorer functional outcome, greater negative symptoms and cognitive impairment, and less severe positive symptoms. Because age of onset, cognitive impairments, and negative symptoms are all correlated with poorer functional status, it is not clear if previously reported gender differences in symptoms are just recapturing gender differences in functional outcome. In this study, 205 geriatric patients with lifelong poor-outcome schizophrenia (43% male) were examined for the severity of schizophrenic symptoms, cognitive impairments, and specific deficits in adaptive skills, as well as for demographic differences such as age at first psychiatric admission, premorbid education, and current treatment status. Previously reported gender differences were replicated in these patients with a uniformly poor functional outcome, with male patients having more severe negative symptoms and an earlier age of first psychiatric admission. No differences in cognitive functioning or specific functional deficits were found, however. These findings suggest that negative symptom severity is greater in male patients regardless of functional outcome and that the association of cognitive deficits with gender may be found only in patients with better functional outcome. The study of gender-related differences in brain structure or function and their interaction with overall course of illness might help understand these differences in symptom presentation.

Activities of Daily Living↗

Gender differences in the relationship of homelessness to symptom severity, substance abuse, and neuroleptic noncompliance in schizophrenia.

This study examined gender differences in the relationship of homelessness in schizophrenia to symptom severity, risk behaviors, and prognostic features. Four hundred subjects with schizophrenia were studied: 100 homeless men, 100 homeless women, 100 never homeless men, and 100 never homeless women. Assessments included derivation of five symptom factors by using the Positive and Negative Syndrome Scale (PANSS). Homelessness for the entire sample was associated with greater severity of positive, activation, and autistic preoccupation symptoms, younger age at first hospitalization, and substance abuse (SA). For men only, homelessness was associated with neuroleptic noncompliance (NN). When NN and SA were statistically controlled, symptom severity was not different between the homeless and never homeless. Women, independent of residential status, had more severe negative, activation, and autistic preoccupation symptoms that were not associated with prognostic features or risk behaviors. For both men and women, SA was associated with homelessness, but independent of residence, SA was less severe in women. Additionally, SA was less severe in homeless women than never homeless men. Thus, symptom severity in homeless individuals with schizophrenia appears as an interaction of symptom profiles and risk behaviors that are gender specific. Although cross-sectional analyses cannot distinguish cause from effect, these findings suggest gender-specific routes to homelessness among indigent urban adults with schizophrenia.

Adult↗

Six-year follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer's disease and normal aging.

OBJECTIVE: Follow-up studies of cognitive functions of poor-outcome (long-term institutionalized) elderly patients with schizophrenia have demonstrated deterioration over time, while stable cognitive functions over time have been reported for younger, better-outcome schizophrenic patients. This study examined whether cognitive changes in elderly schizophrenic patients with a history of long-term institutional stay extended to institutionalized younger patients. The rate of decline was compared to changes associated with Alzheimer's disease. METHOD: Patients with schizophrenia (N=107) age 20-80 years were followed over 6 years and assessed with the Clinical Dementia Rating and the Mini-Mental State Examination. The schizophrenic subjects age 50 and older were compared to 136 healthy comparison subjects and 118 Alzheimer's disease patients age 50 and older who were assessed over a similar follow-up period. RESULTS: There was a significant age group effect on the magnitude of cognitive decline for the schizophrenic subjects, with older subjects experiencing greater levels of decline over the follow-up. Neither the healthy individuals nor the Alzheimer's disease patients demonstrated similar age-related differences in the magnitude of cognitive change over the follow-up, with healthy comparison subjects showing no change and Alzheimer's disease patients manifesting decline regardless of age at the initiation of the follow-up. CONCLUSIONS: Institutionalized schizophrenic patients demonstrated an age-related pattern of cognitive change different from that observed for Alzheimer's disease patients and healthy individuals. The cognitive and functional status of these schizophrenic patients was fairly stable until late life, suggesting that cognitive change may not be occurring in younger patients over an interval as long as 6 years.

Adult↗

Aggression in elderly schizophrenia patients: a comparison of nursing home and state hospital residents.

This study examined the role of cognitive functioning, adaptive functioning, and symptomatology in predicting aggression in institutionalized geriatric schizophrenic patients residing in either a state institution (n=56) or a nursing home (n=113). Patients were assessed with a neuropsychological battery and rated for positive and negative symptoms, social functioning, and aggressiveness. Nursing home residents were older and more cognitively and functionally impaired than institutional residents. The prevalence of verbal, but not physical, aggression was similar to findings in younger, acutely hospitalized patients in previous studies. In the hospitalized group, severity of negative symptoms was predictive of physical aggression. In the nursing home group, severity of positive symptoms was predictive of verbal aggression and self-care deficit was predictive of physical aggression. Results indicate that verbal aggression, like positive symptoms, decreases little with aging in institutionalized schizophrenic patients, and that predictors of aggressive behavior are as difficult to identify in elderly patients as in younger ones.

Aged↗

E-health, phase two: the imperative to integrate process automation with communication automation for large clinical reference laboratories.

The initial efforts of e-health have fallen far short of expectations. They were buoyed by the hype and excitement of the Internet craze but limited by their lack of understanding of important market and environmental factors. E-health now recognizes that legacy systems and processes are important, that there is a technology adoption process that needs to be followed, and that demonstrable value drives adoption. Initial e-health transaction solutions have targeted mostly low-cost problems. These solutions invariably are difficult to integrate into existing systems, typically requiring manual interfacing to supported processes. This limitation in particular makes them unworkable for large volume providers. To meet the needs of these providers, e-health companies must rethink their approaches, appropriately applying technology to seamlessly integrate all steps into existing business functions. E-automation is a transaction technology that automates steps, integration of steps, and information communication demands, resulting in comprehensive automation of entire business functions. We applied e-automation to create a billing management solution for clinical reference laboratories. Large volume, onerous regulations, small margins, and only indirect access to patients challenge large laboratories' billing departments. Couple these problems with outmoded, largely manual systems and it becomes apparent why most laboratory billing departments are in crisis. Our approach has been to focus on the most significant and costly problems in billing: errors, compliance, and system maintenance and management. The core of the design relies on conditional processing, a "universal" communications interface, and ASP technologies. The result is comprehensive automation of all routine processes, driving out errors and costs. Additionally, compliance management and billing system support and management costs are dramatically reduced. The implications of e-automated processes can extend beyond the specific transaction problems they are designed to solve. The ready access and communication of process details required by e-automation can apply to many other business functions.

Accounts Payable and Receivable↗