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Biomedical subjects

P Duncan

Publications and source records attributed to P Duncan.

At least 19 recordsLinked to original sources

Use and misuse of aspirin in rural Ethiopia.

OBJECTIVES: To investigate ability to distinguish simple analgesics, to document misconceptions about aspirin use, and to identify strategies to diminish potentially harmful aspirin use in Ethiopia. DESIGN: Qualitative study (eight focus group discussions) used to inform cross-sectional survey. SETTING: Butajira, a small town in southern Ethiopia, and surrounding rural areas. PARTICIPANTS: Purposively selected informants for focus groups; random sample of urban and rural residents for cross-sectional survey. MAIN OUTCOME MEASURES: Ability to distinguish aspirin from paracetamol; proportion using aspirin; proportion aware of common risks of aspirin. RESULTS: Questionnaires were completed by 204 of the 250 residents sampled (82% response). Three-quarters of survey participants knew the difference between aspirin and paracetamol. Aspirin was used by 7.3% of respondents, and was mainly taken for headache and fever. In focus group discussions there was a suggestion that aspirin was considered particularly useful for children. There was very low awareness of the risks of using aspirin in children (2.5% unprompted, 18.6% prompted) or in people with asthma (1% unprompted, 5.9% prompted). Aspirin is cheap and widely available in urban and rural areas. CONCLUSION: Awareness of the risks of aspirin use by children and in asthma is extremely low in this rural Ethiopian setting. Medications are purchased with minimal packaging by a population with low literacy. Drug dispensers and vendors must be trained to convey simple verbal warnings about aspirin use.

Acetaminophen↗

Detection breadth and limits for potential adventitious/endogenous contaminants in biopharmaceutical processes: a reality check for innovative methods.

In this presentation we address the "gold standards" among diagnostic tests used to detect some potential adventitious and endogenous contaminants in human biologics and vaccines, reflecting on the breadth as well as limits of detection of these assays. This perspective may help developers of innovative diagnostics to address the unique needs of this highly regulated industry.

Bacteria↗

Loss of heterozygosity on chromosomes 11 and 17 are markers of recurrence in TCC of the bladder.

Approximately 2/3 of patients diagnosed with superficial transitional cell carcinoma of the urinary bladder (TCC) will recur within 2 years. Loss of chromosome 9 and loss of heterozygosity (LOH) at 9q34 in index TCCs identify a subset of patients at high risk of recurrence. This study explores genetic alterations on chromosomes 4, 8, 11 and 17 as predictors of recurrence. A total of 109 carcinomas were investigated at 26 loci. DNA was extracted from microdissected archival normal/tumour tissue and was analysed for loss of heterozygosity (LOH). Fluorescent PCR was performed and genotyping carried out on a Perkin Elmer ABI377 sequencer. LOH of D11S490 or D17S928 was significantly more frequent in index carcinomas of patients who experienced recurrence compared to those with no recurrence (P = 0.004 and 0.019 respectively). These results suggest that loss of these regions is associated with recurrence of TCC. Further investigation is required to identify genes in these regions, which might be responsible for driving recurrence in TCC of the urinary bladder.

Carcinoma, Transitional Cell↗

Does the organization of postacute stroke care really matter?

BACKGROUND AND PURPOSE: Postacute rehabilitation stroke services represent a large component of stroke care. In the United States and elsewhere, major changes in the organization and funding of these services are limiting patient access to organized inpatient multidisciplinary care. We conducted a systematic review to evaluate the effectiveness of such services. SUMMARY OF REVIEW: We defined our intervention as organized inpatient multidisciplinary rehabilitation commencing at least 1 week after stroke and sought randomized trials that compared this model of care with an alternative. The analysis was stratified by the particular service characteristics. We identified a heterogeneous group of 9 trials (6 of stroke rehabilitation units; 3 of general rehabilitation wards) recruiting 1437 patients. Organized inpatient multidisciplinary rehabilitation was associated with a reduced odds of death (odds ratio, 0.66; 95% CI, 0.49 to 0.88; P:<0.01), death or institutionalization (odds ratio, 0.70; 95% CI, 0.56 to 0.88; P:<0.001), and death or dependency (odds ratio, 0.65; 95% CI, 0.50 to 0.85; P:<0.001), which was consistent across a variety of trial subgroups. For every 100 patients receiving organized inpatient multidisciplinary rehabilitation, an extra 5 returned home in an independent state. CONCLUSIONS: The results indicate that there can be substantial benefit from organized inpatient multidisciplinary rehabilitation in the postacute period, which is both statistically significant and clinically important.

Activities of Daily Living↗

Patient and tumor characteristics of colon cancers with microsatellite instability: a population-based study.

Molecular screening for microsatellite instability (MSI) in colon cancers has been proposed to identify individuals with hereditary nonpolyposis colorectal cancer. To date, most reports of MSI in colorectal cancer have been based on studies of clinical case series or high-risk families. We examined the proportion of incident colon cancers in the general population that exhibit MSI by patient and tumor characteristics. We interviewed 201 colon cancer cases ascertained by the New Mexico Tumor Registry in the metropolitan Albuquerque area for demographic information, lifestyle factors, medical history, and family cancer history. Paired normal and tumor tissue specimens were obtained for each case. Three microsatellite markers were used; instability was defined as observed alteration at two or more loci. Overall, 37 of 201 (18%) colon cancers exhibited instability. MSI was more common among cases >70 years (26%) and most common among cases >80 years (38%). MSI was significantly associated with tumors in the proximal colon and with later stage and poor differentiation among cases >70 years. MSI was not associated with a history of polyps. Family history of colorectal cancer was associated with MSI only among cases <50 years. When all factors were analyzed jointly in a regression model, proximal subsite and poor differentiation remained significantly associated with MSI. One patient, whose tumor exhibited MSI, fulfilled the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer. Our study provides a population-based estimate of MSI in colon tumors and a representative estimate of the proportion of colorectal cancer patients in the general population who consent to be interviewed for family cancer history and to have biological samples analyzed.

Adult↗

Pediatricians' response to the demand for school health programming.

OBJECTIVE: Because of the broad and increasing interest in school health, the American Academy of Pediatrics (AAP) surveyed its members to determine their awareness of school health education/programs, their level of participation, their desire to participate, and their resource needs to participate more effectively. METHODS: Self-administered questionnaires were mailed to a randomized representative sample of AAP members (N = 1602). Overall response rate was 64.5%. Some responses were stratified for analysis by gender; age (>45 years or </=45 years); practice area (urban, suburban, or rural); practice setting (solo, group, or hospital); and type of practice (general versus specialty). chi2 Tests were used to compare responses. RESULTS: Greater than half of the pediatricians who responded to the questionnaire were aware of school health education curriculum on risky adolescent behaviors in their community, counseling services (58%), school nursing services (63%), and screening services (71%); however, more than half were not aware of curriculum on injury/violence prevention, fitness, or whether a school health advisory council was available. Most pediatricians supported comprehensive school health education (pregnancy prevention, 82%; violence prevention, 77%; mental health, 56%). Also, respondents supported services (counseling, 76%; nutrition, 65%; screening/referral, 58%; school-based primary care, 58%). Although 22% of AAP pediatricians are currently working with local school programs, >70% wanted to become involved or more involved and needed information on how they may be able to participate. Only 25% believed they were adequately prepared. Two thirds believed school-based clinics were one of the best ways to reach underserved children and adolescents and should include preteens. CONCLUSION: AAP pediatricians want to become more involved with comprehensive school health programs. The ways in which they want to participate vary substantially. Most pediatricians thought they needed additional education. The AAP has developed recommendations for graduate medical education and continuing medical education for pediatricians to participate in integrated school health services.

Attitude of Health Personnel↗

A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke.

BACKGROUND AND PURPOSE: Many stroke survivors have minimal to moderate neurological deficits but are physically deconditioned and have a high prevalence of cardiovascular problems; all of these are potentially modifiable with exercise. The purposes of this randomized, controlled pilot study were (1) to develop a home-based balance, strength, and endurance program; (2) to evaluate the ability to recruit and retain stroke subjects; and (3) to assess the effects of the interventions used. METHODS: Twenty minimally and moderately impaired stroke patients who had completed inpatient rehabilitation and who were 30 to 90 days after stroke onset were randomized to a control group or to an experimental group that received a therapist-supervised, 8-week, 3-times-per-week, home-based exercise program. The control group received usual care as prescribed by the patients' physicians. Baseline and postintervention assessments included the Fugl-Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL), the Lawton Scale of Instrumental ADL, and the Medical Outcomes Study-36 Health Status Measurement. Functional assessments of balance and gait included a 10-m walk, 6-Minute Walk, and the Berg Balance Scale. Upper extremity function was evaluated by the Jebsen Test of Hand Function. RESULTS: Of 22 patients who met study criteria, 20 completed the study and 2 refused to participate. The experimental group tended to improve more than the control group in motor function (Fugl-Meyer Upper Extremity: mean change in score, 8. 4 versus 2.2; Fugl-Meyer Lower Extremity: 4.7 versus -0.9; gait velocity: median change, 0.25 versus .09 m/s; 6-Minute Walk: 195 versus 114 ft; Berg Balance Score: 7.8 versus 5; and Medical Outcomes Study-36 Health Status Measurement of Physical Function: 15. 5 versus 9). There were no trends in differences in change scores by the Jebsen Test of Hand Function, Barthel Index, and Lawton Instrumental ADL Scale. CONCLUSIONS: This study demonstrated that a randomized, controlled clinical trial of a poststroke exercise program is feasible. Measures of neurological impairments and lower extremity function showed the most benefit. Effects of the intervention on upper extremity dexterity and functional health status were equivocal. The lasting effects of the intervention were not assessed.

Activities of Daily Living↗

Multiple mechanisms of N-phosphonacetyl-L-aspartate resistance in human cell lines: carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase gene amplification is frequent only when chromosome 2 is rearranged.

Rodent cells resistant to N-phosphonacetyl-L-aspartate (PALA) invariably contain amplified carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase (CAD) genes, usually in widely spaced tandem arrays present as extensions of the same chromosome arm that carries a single copy of CAD in normal cells. In contrast, amplification of CAD is very infrequent in several human tumor cell lines. Cell lines with minimal chromosomal rearrangement and with unrearranged copies of chromosome 2 rarely develop intrachromosomal amplifications of CAD. These cells frequently become resistant to PALA through a mechanism that increases the aspartate transcarbamylase activity with no increase in CAD copy number, or they obtain one extra copy of CAD by forming an isochromosome 2p or by retaining an extra copy of chromosome 2. In cells with multiple chromosomal aberrations and rearranged copies of chromosome 2, amplification of CAD as tandem arrays from rearranged chromosomes is the most frequent mechanism of PALA resistance. All of these different mechanisms of PALA resistance are blocked in normal human fibroblasts.

Aspartate Carbamoyltransferase↗

Delivery of newly synthesized Na(+)-K(+)-ATPase to the plasma membrane of A6 epithelia.

Na(+)-K(+)-ATPase is localized to the basolateral cell surface of most epithelial cells. Conflicting results regarding the intracellular trafficking of Na(+)-K(+)-ATPase in Madin-Darby canine kidney cells have been reported, with delivery to both apical and basolateral membranes or exclusively to the basolateral cell surface. We examined the delivery and steady-state distribution of Na(+)-K(+)-ATPase in the amphibian epithelial cell line A6 using an antibody raised against Na(+)-K(+)-ATPase alpha-subunit and sulfo-N-hydroxysuccinimidobiotin to tag cell surface proteins. The steady-state distribution of the Na(+)-K(+)-ATPase was basolateral, as confirmed by immunocytochemistry. Delivery of newly synthesized Na(+)-K(+)-ATPase to the cell surface was examined using [35S]methionine and [35S]cysteine in a pulse-chase protocol. After a 20-min pulse, the alpha-subunit and core glycosylated beta-subunit were present at both apical and basolateral cell surfaces. The alpha-subunit and core glycosylated beta-subunit delivered to the apical cell surface were degraded within 2 h. Mature alpha/beta-heterodimer was found almost exclusively at the basolateral surface after a 1- to 24-h chase. These data suggest that immature Na(+)-K(+)-ATPase alpha-subunit and core glycosylated beta-subunits are not retained in the endoplasmic reticulum of A6 cells and apparently lack sorting signals. Mature Na(+)-K(+)-ATPase is targeted to the basolateral surface, suggesting that basolateral targeting of the protein is conformation dependent.

Animals↗

Perioperative on-site haemoglobin determination: as accurate as laboratory values?

PURPOSE: This study assessed the accuracy of photometer based haemoglobin (Hb) determination technology (HemoCue) when used by different anaesthetists in situations of rapidly changing Hb values during anaesthesia. METHODS: (Part 1) In the laboratory, repeated measurements were done on 16 split samples of blood using both the Hematology Analyzer (CELL-DYN 3500 System, Abbot Laboratories, San Jose, California) and the photometer. (Part 2) Twelve patients had blood samples drawn from an arterial line for simultaneous Hb determination in the hospital laboratory and by the photometer. At the same time, capillary samples were taken from the patient's earlobe for Hb determination by the photometer. All sample collection and photometer measurements were done by the same operator. (Part 3) The Part 2 protocol was then repeated with different anaesthetists performing both the sampling and the photometer measurements. Statistical comparison was by ANOVA and a two-tailed paired t-test. RESULTS: (Part 1) Samples determined by the photometer and the laboratory were highly correlated (r2 = 1.0, P < 0.001). The average error of each method was similar ( < 4%). (Part 2) Using a 2-tailed paired t-test, the photometer arterial measurements were not different from the laboratory measurements, however the photometer capillary measurements were consistently approximately 8% higher (P = 0.003). (Part 3) When multiple operators performed the sampling there were no differences on arterial or capillary samples (r2 = 0.942, r2 = 0.851 respectively), although the variance was greater. CONCLUSIONS: The HemoCue haemoglobinometer has sufficient accuracy to support treatment decisions regarding blood transfusions.

Anesthesia↗

Biosynthesis and cell surface delivery of the NHE1 isoform of Na+/H+ exchanger in A6 cells.

The Na+/H+ exchanger isoform NHE1 is localized to the basolateral membrane of renal and intestinal epithelia. We examined the plasma membrane distribution, biosynthesis, and cell surface delivery of NHE1 in A6 epithelia. NHE1 was localized to the basolateral membrane. Studies of NHE1 biosynthesis with a pulse-chase protocol demonstrated that a core glycosylated, endoglycosidase H-sensitive, 90-kDa NHE1 was present 0-5 h into the chase period and that mature 110-kDa NHE1 was present 1-24 h into the chase period. Studies of plasma membrane delivery of newly synthesized NHE1 demonstrated that the 90-kDa NHE1 was detected at both apical and basolateral membranes 2-5 h into the chase period. The 110-kDa NHE1 was observed at the basolateral membrane 5-24 h into the chase period. These results suggest that NHE1 is expressed primarily at the basolateral membrane of A6 cells, that core glycosylated NHE1 is delivered to the plasma membrane in a nonpolarized manner, and that nature 110-kDa NHE1 is delivered to the basolateral membrane.

Animals↗

On the carrying capacity for large ungulates of African savanna ecosystems.

The effect of pastoral management on the standing crop biomass of large ungulates, an index of carrying capacity, is analysed at a regional level by using data compiled from published sources covering east and south Africa. The effect of primary production is controlled for by using two environmental factors, rainfall and soil nutrient availability, and the effect of species richness of the ungulate community is evaluated. The results confirm the dominant effect of rainfall, and demonstrate that soil nutrient levels also strongly affect the biomass of large ungulate communities. For a given level of rainfall, on rich soils (high nutrient availability) the biomass of large ungulates is about 20 times as great as on poor soils with low nutrient availability. The model based on rainfall and soil nutrient classes accounts for 87% of the variance in large ungulate biomass. Pastoral and natural ecosystems do not differ significantly in large ungulate biomass; there is therefore currently no evidence that extensive pastoral management increases carrying capacity for large ungulates above the levels observed in natural communities. Species richness, a measure of biodiversity, had a significant but very small effect on the biomass-rainfall relation in the complete data set. When analysed by pastoral management, the effect of this factor was significant for the set of natural ecosystems only. Pastoral management and species richness may therefore have compensatory effects. These results suggest that the carrying capacity is limited at the community, rather than the species, level.

Africa↗

Dual specificity kinases--a new family of signal transducers.

Phosphorylation/dephosphorylation reactions are one of the dynamic mechanisms through which cells modulate protein activity in response to environmental stimuli. The eukaryotic molecules which are responsible for the phosphorylation of serine, threonine and tyrosine residues appear to have co-ordinately evolved from simple prokaryotic enzymes which primarily respond to nutritional cues. In multicellular eukaryotes the complexity of data transfer greatly exceeds that of simple bacteria. The eukaryotic cell needs to exchange information with neighbouring and distant sister cells. Positional, nutritional and hormonal data are transmitted from the extracellular milieu across the plasma membrane and into the cytoplasm. In certain cases the signal must pass into the nucleus or other subcellular organelles where it is decoded and the proper cellular response initiated. All of these events have been shown to have a protein kinase component and it seems likely that in mammalian cells over 1,000 different kinase molecules have evolved to form the requisite signal transducing networks. In this review we describe a previously unappreciated family of protein kinases, the dual specificity or DSK kinases, which play important roles in the regulation of normal cellular growth and differentiation.

Animals↗

When I'm calling you ....

Discussion groups among sectors of the population often excluded from consultation homed in on healthcare needs, say Paul Duncan and Liz Higgins, looking at findings from Waltham Forest HA.

Attitude to Health↗

Job satisfaction among hospital nurses: facility size and location comparisons.

Despite recent declines in turnover and vacancy rates, maintaining a stable nursing staff continues to be critical to the effective operation of American hospitals. Job satisfaction is a pivotal element in nurse retention, and organizational theory suggests that some of the factors that influence job satisfaction vary by facility size. This is a study of job satisfaction among a sample of 731 nurses providing direct patient care in 22 hospitals. The sample includes approximately equal numbers of nurses employed in very small rural hospitals (1-49 beds), medium sized facilities located in small towns (50-99 beds), and larger metropolitan institutions (> 100 beds). Differences by hospital size were observed in overall job satisfaction and in five sub-dimensions of that concept (i.e., professional status, task requirements, pay, organizational policies, and autonomy). With the exception of pay, the results indicated that nurses employed in the very small rural hospitals were more satisfied with their jobs. Differences by hospital size were also observed in the personal characteristics of the nurses, several specific aspects of their job, and in their perceptions of job mobility. A set of four hierarchically nested ordinary least squares regression models indicated that job-specific characteristics were the most powerful predictors of job satisfaction.

Attitude of Health Personnel↗