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Biomedical subjects

S Knight

Publications and source records attributed to S Knight.

At least 19 recordsLinked to original sources
PubMed2003

A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies.

BACKGROUND: Oral eniluracil/5-fluorouracil (5-FU) was shown in early clinical studies to have promising activity against gastrointestinal malignancies. Oxaliplatin in combination with 5-FU also has activity against these tumour types. The primary objective of this study was to determine a tolerable dose for oral eniluracil/5-FU in combination with oxaliplatin. PATIENTS AND METHODS: Twenty-three patients with advanced gastrointestinal malignancies were recruited into this open-label study. Patients received a fixed dose of oxaliplatin (130 mg/m(2) on the first day of a 21-day cycle), and the dose intensity of oral eniluracil/5-FU was gradually increased by escalating the number of days of treatment per course. RESULTS: The maximum tolerated dose intensity was eniluracil/5-FU 10.0/1.0 mg/m(2) twice daily for 16 days in combination with oxaliplatin 130 mg/m(2) on the first day of a 21-day cycle. Dose-limiting toxicities included vomiting and diarrhoea. The objective tumour response rate was 26% with a median duration of response of 15.3 weeks (95% confidence interval 8.5-22.1). Twenty-two patients (96%) experienced neurotoxicity (sensory neuropathy or cold-related dysaesthesia), although only two events were severe (grade 3). CONCLUSIONS: The recommended dose for future study in patients with advanced gastrointestinal cancer is 10.0/1.0 mg/m(2) oral eniluracil/5-FU twice daily for 14 days in combination with oxaliplatin 130 mg/m(2) on the first day of each treatment cycle.

Administration, Oral↗
PubMed2002

[Effects of peripheral functional electrostimulation in obstructive bladder instability].

INTRODUCTION: The aim of this study was to assess the effects of peripheral functional electrical stimulation (FES) in patients with detrusor instability (DI) secondary to obstructive Benign Prostatic Hyperplasia (BPH). SUBJECTS, MATERIAL & METHODS: Nine patients with urodynamically proven DI secondary to BPH were investigated. Sensory and pudendo-anal reflex thresholds were determined in each patient to individually optimise FES. A standard fill cystometry was then performed and individually optimised FES was given when an unstable detrusor contraction occurred. Non stimulated contractions were used as controls. The effects of FES were analysed by measuring the mean area under the unstable pressure curves with and without FES and were expressed as percentage suppression. RESULTS: The percentage suppression in the mean area under the curves after stimulation was < 10%. There was no statistically significant difference between controls and FES using a two tailed, paired students t-Test (p > 0.1) at 95% confidence level (p > or = 0.05). CONCLUSION: FES did not significantly suppress unstable bladder contractions in patients with DI secondary to BPH. This finding suggests that obstructive DI does not depend on sacral reflex mechanisms and supports the view that it has a peripheral pathophysiological origin (myogenic and/or nerve endings).

Electric Stimulation Therapy↗
PubMed2002

Preliminary indication of a high prevalence of polycystic ovary syndrome in indigenous Australian women.

We aimed to estimate the likely prevalence of polycystic ovary syndrome (PCOS) in indigenous Australian women in a cross-sectional survey based on structured interviews. In the Kimberley region of Western Australia and south-western Victoria, between February and June 1999, women over the age of 18 available for interview and willing to participate were included. Menstrual status, anthropometric measures, fasting blood biochemistry and hirsutism were assessed. A total of 38 premenopausal women completed the survey. Of these, 50% had regular menstrual cycles of normal duration and no hirsutism; seven had oligomenorrhea and hirsutism/hyperandrogenemia; and of the nine women with hirsutism and regular menses, three had hyperandrogenemia. Thus, possibly ten women fulfilled the criteria of PCOS. This unique data set suggests a high prevalence of PCOS in indigenous Australian women. Further research to document this formally is warranted, in view of the potential adverse effects of PCOS on reproduction and metabolism.

Adult↗
PubMed2001

Shoulder belts in motor vehicle crashes: a statewide analysis of restraint efficacy.

The purpose of our study was to evaluate the impact of shoulder belt use on motor vehicle crash ejection, morbidity and mortality. We analyzed motor vehicle crash records linked to hospital inpatient data for front seat occupants of passenger cars in Utah between 1994 and 1996 (n = 103,035). Stochastic simulations were used to adjust for possible seatbelt misclassification. There were 276 (0.3%) occupants coded as using only a shoulder belt. The adjusted odds of ejection for shoulder only belted occupants was higher compared to lap-shoulder belted (odds ratio (OR) = 18.9; 95% confidence interval (CI) = 15.1, 25.1) and lap only belted occupants (OR = 4.3; 95% Cl = 2.9, 7.7). There was no difference in the odds of ejection for an occupant using a shoulder belt only and an occupant using no seatbelt (OR = 1.1; 95% CI = 1.0, 1.3). Occupants using a shoulder belt only were more likely to sustain a fatal or hospitalizing injury than lap-shoulder belted (OR = 2.3; 95% Cl = 1.9, 3.0), and lap only belted occupants (OR = 1.8; 95% CI = 1.3, 2.7), while controlling for other covariates. Occupants using only a shoulder belt had the same odds of a fatal or hospitalizing injury as unbelted occupants (OR = 1.1; 95% Cl = 0.9, 1.4). Average hospital inpatient length of stay, charges and injury severity scores were similar for all restraint types. These results stress the need for the use of a lap belt in conjunction with the shoulder belt.

Accidents, Traffic↗
PubMed2001

Fc gamma RIII mediates neutrophil recruitment to immune complexes. a mechanism for neutrophil accumulation in immune-mediated inflammation.

Neutrophil accumulation is a hallmark of immune complex-mediated inflammatory disorders. Current models of neutrophil recruitment envision the capture of circulating neutrophils by activated endothelial cells. We now demonstrate that immobilized immune complexes alone support the rapid attachment of neutrophils, under physiologic flow conditions. Initial cell tethering requires the low-affinity Fc gamma receptor IIIB (Fc gamma RIIIB), and the beta(2) integrins are additionally required for the subsequent shear-resistant adhesion. The attachment function of Fc gamma RIIIB may be facilitated by its observed presentation on neutrophil microvilli. In vivo, in a model of acute antiglomerular basement membrane nephritis in which immune complexes are accessible to circulating neutrophils, Fc gamma RIII-deficient mice had a significant reduction in neutrophil recruitment. Thus, the interaction of immune complexes with Fc gamma RIII may mediate early neutrophil recruitment in immune complex-mediated inflammation.

Animals↗
PubMed2001

The synergistic relationship between a level I trauma center and a regional pediatric trauma center.

A regional pediatric trauma center and a level I trauma center with pediatric commitment in the same city developed a synergistic relationship addressing all aspects of care for pediatric trauma patients. Although it is unlikely that this model could be used in its entirety by all similar institutions, the principles may prove helpful in creating guidelines and relationships. Categorization, optimal use of resources, timely transportation of seriously injured children to the appropriate facility, and maintaining urgent care capabilities of each institution to care for seriously injured children are imperative. The combined effort resulted in our level I trauma center being verified by the American College of Surgeons and designated by our state Health Department as meeting all the criteria for pediatric trauma care. This experience should encourage every pediatric trauma center located in a children's hospital to become a regional pediatric trauma center. The real benefit from the relationship is that injured children receive optimal care at both institutions.

Adult↗
PubMed2001

Analysis of school injuries resulting in emergency department or hospital admission.

OBJECTIVE: To describe the epidemiology of school injuries resulting in emergency department (ED) visits, hospital admission, or death. METHODS: Utah statewide school injuries from 1992 to 1996 were probabilistically linked to statewide ED records (1996 only), inpatient hospital records (1992-1996), and death certificate records (1992-1996). RESULTS: There were 43,881 school injuries for the years 1992 through 1996. In 1996, 1,534 of 6,354 total school injuries (17.5%) resulted in ED evaluation. Between 1992 and 1996, 354 school injuries (0.8%) necessitated hospital admission. The overall rates of school injuries (per 1,000 students) of primary (kindergarten-grade 6) and secondary (grades 7-12) school students requiring ED evaluation were 3.29 and 3.28, respectively; for hospital admission, 0.165 and 0.139. Abbreviated Injury Scale-1990 (AIS-90) regions identified in ED patients were the upper extremity (39.2%), face (20.8%), and lower extremity (17.1%), while AIS regions among inpatients were lower extremity (29.1%), upper extremity (26.6%), and head (22.6%). There were a total of 1,123 hospital days, and total charges of $2.16 million. The ED charges totaled $545,000. Median length of hospital stay was 1 day, and median hospital charge was $3,080. There were four fatalities. CONCLUSIONS: This study emphasizes the significance of school injuries and the need for interventions to prevent these injuries

Adolescent↗
PubMed2001

Towards integrated catchment management, Whaingaroa, New Zealand.

The paper examines progress towards integrated catchment management and sustainable agriculture at Whaingaroa (Raglan), New Zealand. Application of the Canadian "Atlantic Coastal Action Program" model (ACAP) has been only partially successful within New Zealand's bicultural setting. Even before the introduction of the ACAP process there existed strong motivation and leadership by various sectors of the community. A merging of resource management planning and implementation processes of the larger community and that of the Maori community has not occurred. Research carried out by Crown Research Institutes has clearly shown the actions required to make pastoral farming more sustainable. There are difficulties in the transference to, and uptake of, these techniques by farmers. An examination of the socio-economic context is required. There has been a requirement on local government bodies to tighten their focus as part of recent reform. This has occurred concurrently with a widening of vision towards integrated and sustainable forms of management. This (as well as a clear belief in empowerment of local communities) has lead to Council reliance on voluntary labour. There is a need to account for the dynamic interaction between social and political history and the geological and biophysical history of the area. As part of a re-examination of sustainable development, New Zealand needs to reconcile the earning of the bulk of its foreign income from primary production, with the accelerating ecological deficit that it creates. A sustainability strategy is required linking consumer demand, property rights and responsibilities.

Agriculture↗
PubMed2000

Convergent evolution with combinatorial peptides.

Once the sequence of a genome is in hand, understanding the function of its encoded proteins becomes a task of paramount importance. Much like the biochemists who first outlined different biochemical pathways, many genomic scientists are engaged in determining which proteins interact with which proteins, thereby establishing a protein interaction network. While these interactions have evolved in regard to their specificity, affinity and cellular function over billions of years, it is possible in the laboratory to isolate peptides from combinatorial libraries that bind to the same proteins with similar specificity, affinity and primary structures, which resemble those of the natural interacting proteins. We have termed this phenomenon 'convergent evolution'. In this review, we highlight various examples of convergent evolution that have been uncovered in experiments dissecting protein-protein interactions with combinatorial peptides. Thus, a fruitful approach for mapping protein-protein interactions is to isolate peptide ligands to a target protein and identify candidate interacting proteins in a sequenced genome by computer analysis.

Amino Acid Sequence↗
PubMed2000

Increase in prevalence of obesity and diabetes and decrease in plasma cholesterol in a central Australian aboriginal community.

OBJECTIVE: To document change in prevalence of obesity, diabetes and other cardiovascular disease (CVD) risk factors, and trends in dietary macronutrient intake, over an eight-year period in a rural Aboriginal community in central Australia. DESIGN: Sequential cross-sectional community surveys in 1987, 1991 and 1995. SUBJECTS: All adults (15 years and over) in the community were invited to participate. In 1987, 1991 and 1995, 335 (87% of eligible adults), 331 (76%) and 304 (68%), respectively, were surveyed. MAIN OUTCOME MEASURES: Body mass index and waist: hip ratio; blood glucose level and glucose tolerance; fasting total and high density lipoprotein (HDL) cholesterol and triglyceride levels; and apparent dietary intake (estimated by the store turnover method). INTERVENTION: A community-based nutrition awareness and healthy lifestyle program, 1988-1990. RESULTS: At the eight-year follow-up, the odds ratios (95% CIs) for CVD risk factors relative to baseline were obesity, 1.84 (1.28-2.66); diabetes, 1.83 (1.11-3.03); hypercholesterolaemia, 0.29 (0.20-0.42); and dyslipidemia (high triglyceride plus low HDL cholesterol level), 4.54 (2.84-7.29). In younger women (15-24 years), there was a trembling in obesity prevalence and a four- to fivefold increase in diabetes prevalence. Store turnover data suggested a relative reduction in the consumption of refined carbohydrates and saturated fats. CONCLUSIONS: Interventions targeting nutritional factors alone are unlikely to greatly alter trends towards increasing prevalences of obesity and diabetes. In communities where healthy food choices are limited, the role of regular physical activity in improving metabolic fitness may also need to be emphasised.

Adolescent↗
PubMed2000

Neurodevelopmental profile of a new dysmorphic syndrome associated with submicroscopic partial deletion of 1p36.3.

We describe four children with dysmorphic syndrome with severe learning disability (SLD). Their chromosomes had been normal on conventional cytogenetic examination. However, screening using a multiprobe fluorescence in situ hybridisation (FISH) technique for subtelomeric abnormalities revealed a deletion of the p arm of chromosome 1. The physical features include body asymmetry, microcephaly, distinctive facies with deep-set eyes, sharply defined eye sockets, and mid-face hypoplasia; the neurodevelopmental profile was characterised by SLD, motor delay with hypotonia, markedly delayed visual maturation, and postural asymmetry together with epilepsy. This phenotype is consistent with that described for partial monosomy for 1p36.3.

Abnormalities, Multiple↗
PubMed2000

Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.

BACKGROUND: Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis. METHODS: The roles of alphabeta and gammadelta T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell receptor (TCR)beta and TCRdelta knockout mice]. The model, induced by the injection of rabbit anti-mouse glomerular basement membrane antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice. RESULTS: Mice deficient in either alphabeta or gammadelta T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In gammadelta T-cell-deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while alphabeta T-cell-deficient mice had no autologous IgG production. Autologous antibody production was not required for the development of glomerulonephritis since mice that lack IgG and B cells (micro-chain-/-) developed similar proteinuria to that observed in wild-type mice. CONCLUSIONS: These studies suggest a proinflammatory role for both alphabeta and gammadelta T cells in glomerular injury, independent of the humoral response. This is the first demonstration, to our knowledge, that both T-cell subsets contribute to the progression of a disease, and it suggests that complex regulatory interactions between alphabeta and gammadelta T cells play a role in glomerular injury.

Animals↗
PubMed2000

Injuries sustained by students in shop class.

OBJECTIVE: Injuries in the school environment are a serious public health problem. Injuries occurring within the school shop class are a part of this problem that has received little to no attention. The purpose of our study was to describe the epidemiology of shop class injuries in Utah public schools for the years 1992-1996. METHODS: Utah statewide grades 7 through 12 school injury data for 1992-1996 were used. The data were generated from a standardized Student Injury Report form completed by school personnel immediately after the occurrence of an injury on school premises that: 1) caused loss of at least one half of a day of school; and/or 2) warranted medical attention and treatment. Shop injuries were defined as injuries that occurred in industrial art classes, vocational educational classes, or automotive classes. To determine the medical outcome and hospital charges associated with shop class injuries, we linked the Student Injury Report database to Utah statewide emergency department (ED) records (available for 1996 only), and to Utah statewide hospital inpatient discharge records (1992-1996). RESULTS: During 1992-1996, 14 133 students in grades 7 through 12 were injured at school, of which 1008 (7.1%) were injured during a shop class. The majority (88. 4%) of shop injuries involved equipment use. Equipment was misused in 37.9% and malfunctioned in 3.5% of the incidents. The leading injuries reported for shop equipment were lacerations (70.9%), burns (6.0%), and abrasions (4.6%), whereas the leading for nonequipment injuries were lacerations (45.4%), fractures (9.2%), and pain/tenderness (6.7%). In 1996, 167 students were injured in a shop class and 45 (26.9%) visited an ED as a result of the shop injury. Equipment was a factor in 88.9% of the shop injuries admitted to the ED. Table saws (15.0%), other saws (15.0%), and band saws (12.5%) were involved in nearly one half of the equipment injuries. Equipment was misused in 44.7% and malfunctioned in 10.5% of the incidents resulting in an ED visit. The majority (64.4%) of students sustained an open wound injury. The total ED charges were $16 571. For 1992-1996, 1008 students were injured in a shop class, 7 (.7%) required inpatient hospital care. Six of the students were injured using a table saw and 1 sustained injuries attributable to automotive cleaning fluid. Equipment was used improperly in 4 of the table saw injuries. Six of the students sustained hand injuries, with 3 suffering a traumatic amputation of a finger or thumb. The total inpatient charges were $26 747. CONCLUSION: School shop injuries have a great impact on students, their families, and schools because of the loss of productivity for the student and the financial impact. Many of the injuries are preventable. These findings stress the need for school administrators, teachers, and students to develop and improve safety policies and practices in school shop classes. In addition, the findings may provide useful information to pediatricians and enable them to better inform patients of risks in school shop classes.

Adolescent↗
PubMed2000

Reduced prevalence of impaired glucose tolerance and no change in prevalence of diabetes despite increasing BMI among Aboriginal people from a group of remote homeland communities.

OBJECTIVE: To examine trends in glucose tolerance and coronary risk among Aboriginal people from a group of homeland communities in central Australia during a 7-year follow-up period. RESEARCH DESIGN AND METHODS: Community-based screenings of adult volunteers were performed in 1988 (n = 437; 93% response rate) and in 1995 (n = 424; 85% response rate). A health promotion intervention program commenced after the 1988 survey that focused on the benefits of exercise and appropriate diet. RESULTS: Mean (95% CI) BMI increased significantly from 22.8 kg/m2 (22.3-23.2) to 24.2 kg/m2 (23.8-24.7) during the follow-up period (P < 0.001). This increase was similar for men and women and across all age-groups. The increase in BMI was greater among subjects residing adjacent to a store compared with those residing in communities located far from a store (P < 0.001). Decreases were evident in the prevalence of impaired glucose tolerance (IGT) (from 22.5 to 10.1% among women, P < 0.001; from 12.2 to 6.5% among men, P = 0.074) and hypercholesterolemia (from 36.7 to 25.8% among women, P < 0.01; from 52.4 to 44.0% among men, P = 0.147), but no change was evident in the prevalence of diabetes. Smoking remained rare among women (<4%) and decreased among men (from 52.9 to 40.8%, P < 0.05). CONCLUSIONS: The trends in glucose intolerance were clearly better than have been observed in other Aboriginal communities. The institution of an intervention program corresponded with reductions in the prevalence of IGT, hypercholesterolemia, and smoking. The prevalence of diabetes remained unaltered despite a significant increase in mean BMI, possibly because of the promotion of increased physical activity levels.

Adolescent↗
PubMed2000

Motor vehicle crash characteristics and medical outcomes among older drivers in Utah, 1992-1995.

STUDY OBJECTIVE: We sought to compare the characteristics and medical outcomes of motor vehicle crashes for drivers 70 years and older with those of drivers between the ages of 30 and 39 years. METHODS: We probabilistically linked statewide motor vehicle crash and hospital discharge data between the years of 1992 and 1995 for the state of Utah. We calculated the odds of older drivers exhibiting certain motor vehicle crash characteristics compared with younger drivers. Adjusting for nighttime crash, high-speed crash, and seatbelt use, we calculated the odds of an older driver being killed or hospitalized compared with those of a younger driver. RESULTS: During the study years, there were 14,466 drivers older than 69 years and 68,706 drivers between the ages of 30 and 39 years involved in motor vehicle crashes in Utah. Older drivers were less likely to have crashes involving drug or alcohol use (odds ratio [OR] 0.1; 95% confidence interval [CI] 0.1 to 0.2) and less likely to have crashes at high speed (OR 0.6; 95% CI 0.6 to 0.7). Although older drivers were no more likely to have a crash involving a right-hand turn (OR 1.0; 95% CI 0.9 to 1.1) than younger drivers, they were over twice as likely to have a crash involving a left-hand turn (OR 2.3; 95% CI 2.2 to 2.5). Also, older drivers were more likely to be killed or hospitalized than younger drivers (OR, 3.5; P <.001). Among belted drivers, an older driver was nearly 7 times more likely to be killed or hospitalized than a younger driver (OR 6. 9; 95% CI 5.4 to 8.9). CONCLUSION: Older drivers do have distinctive motor vehicle crash patterns. Interventions must be taken to reduce the number of left-hand turn crashes involving older drivers. In addition, further research is needed to design, implement, and evaluate countermeasures that may enable older drivers to continue driving while keeping public safety in the forefront.

Accidents, Traffic↗