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Biomedical subjects

S Knight

Publications and source records attributed to S Knight.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Early expression of cyclo-oxygenase-2 during sporadic colorectal carcinogenesis.

Regular administration of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of colorectal cancer by targeting cyclo-oxygenase-2 (Cox-2), a key enzyme in arachidonic acid metabolism. To evaluate the role of Cox-2 in sporadic colorectal cancer development, Cox-2 expression was investigated by immunohistochemistry in 85 adenomas, 53 carcinomas, 34 hyperplastic lesions and 104 samples of histologically normal mucosa adjacent to adenoma or carcinoma. In addition, Cox-2 mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) in six adenomas and 14 carcinomas with paired grossly normal mucosa. Immunohistochemistry for the proliferation-associated antigen Ki-67 and in situ end labelling for demonstrating apoptotic bodies were also used to analyse the associations between Cox-2 expression and proliferation and apoptosis. Cox-2 protein expression was increased in 76/85 (89.4 per cent) adenomas and 44/53 (83.0 per cent) carcinomas compared with normal mucosa. Cox-2 protein expression was unrelated either to the degree of dysplasia or to the size of the adenomas (p > 0.50, p > 0.10, respectively) or to differentiation, Dukes stage or lymph node metastasis of carcinomas (all p > 0.50). Interestingly, 20/34 (58.8 per cent) hyperplastic lesions adjacent to adenomas or carcinomas displayed expression higher than in normal mucosa (18.3 per cent) (p < 0.0001) but lower than in adenomas or carcinomas (p < 10(-5), p < 0.001, respectively). There were no correlations between Cox-2 protein expression and proliferative or apoptotic index in either adenomas or carcinomas (all p > 0.25). Cox-2 mRNA expression was significantly increased in adenomas and carcinomas compared with normal mucosa (p < 0.005, p < 0.001, respectively). There were no differences between adenomas and carcinomas in either protein or mRNA levels (p > 0.25, p > 0.90, respectively). These data indicate that enhanced expression of Cox-2 occurs early during colorectal carcinogenesis and may contribute to tumour formation.

Adenoma↗
PubMed1999

Noninvasive evaluation of cardiac dysfunction by echocardiography in streptozotocin-induced diabetic rats.

BACKGROUND: There has not been a noninvasive in vivo longitudinal evaluation of cardiac function in diabetic rats. The objective of this study is to examine the time course of development of cardiac dysfunction in streptozotocin (STZ)-induced diabetic rats. METHODS AND RESULTS: Cardiac function was evaluated by M-mode and Doppler echocardiography in anesthetized Wistar rats at 2, 4, 5, 6, and 8 weeks after injection with 65 mg of STZ/kg and in age-matched control rats before and after the administration of isoproterenol. Body weight (BW) was significantly less and blood glucose level significantly greater in diabetic rats compared with controls at 2 weeks and remained at these levels at all time points. The calculated left ventricular (LV) mass appeared slightly decreased in diabetic rats. However, LV mass-BW ratios were similar in controls and diabetic rats at 2, 4, and 5 weeks, but were significantly greater in diabetic rats at 6 and 8 weeks. Basal heart rate (HR) was significantly lower in diabetic rats at all time points studied. Basal LV systolic and diastolic dimensions, fractional shortening (FS), velocity of circumferential shortening (Vcf), peak emptying rate (PER), peak filling rate (PFR), and aortic peak velocity (APV) were not significantly different between controls and diabetic rats at 2 and 4 weeks. PER and PFR were significantly less in 5-week diabetic rats. However, Vcf, PER, and PFR were significantly less and FS and APV were similar at 6 and 8 weeks. Administration of isoproterenol increased HR, Vcf, FS, PFR, and PER in controls at all time points, but the increases in diabetic rats at 5, 6, and 8 weeks were less compared with those in controls. The increase in APV was significantly less in diabetic rats at all time points studied. CONCLUSION: STZ-induced diabetic rats showed bradycardia before contractile dysfunction. Overt and covert contractile dysfunction unmasked by isoproterenol begins at 5 weeks of diabetes. The overt LV systolic and diastolic dysfunction are fully manifested after 6 weeks of diabetes.

Animals↗
PubMed1999

Quantitative effects of valacyclovir on the replication of cytomegalovirus (CMV) in persons with advanced human immunodeficiency virus disease: baseline CMV load dictates time to disease and survival. The AIDS Clinical Trials Group 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group.

Virus load is a major risk factor for disease in many human viral infections, especially human immunodeficiency virus (HIV) disease. The effect of cytomegalovirus (CMV) load on disease progression and the influence of antiviral chemotherapy on surrogate markers of replication was investigated in 310 patients with advanced HIV disease in a randomized controlled trial that compared the effects of valacyclovir with those of acyclovir. Sequential blood and urine samples were analyzed by polymerase chain reaction (PCR), for human CMV (HCMV) DNA. In multivariate analyses, elevated virus load in both blood and urine at baseline was associated with increased risk of HCMV disease (relative hazard, 1.49 and 1.44 per log increase, respectively). Elevated virus load in blood at baseline was also associated with a significantly shorter survival time (log rank, P=. 0001). In time-updated analyses, valacyclovir significantly suppressed the virus load in subjects who were PCR positive at baseline (in blood or urine), when compared with the combined acyclovir arms.

AIDS-Related Opportunistic Infections↗
PubMed1999

Application and results of the Manchester Short Assessment of Quality of Life (MANSA).

BACKGROUND: Based on experiences and empirical evidence gained in studies using the Lancashire Quality of Life Profile (LQLP), the Manchester Short Assessment of Quality of Life (MANSA) has been developed as a condensed and slightly modified instrument for assessing quality of life. Its properties have been tested in a sample of community care patients. METHOD: Fifty-five randomly selected patients on the Care Programme Approach were interviewed using the LQLP, the MANSA and the Brief Psychiatric Rating Scale. RESULTS: Correlations between subjective quality of life scores on MANSA and LQLP were all 0.83 or higher (0.94 for the satisfaction mean score). Cronbach's alpha for satisfaction ratings was 0.74, and association with psychopathology was in line with results for LQLP as reported in the literature. CONCLUSIONS: The MANSA is a brief instrument for assessing quality of life focusing on satisfaction with life as a whole and with life domains. Its psychometric properties appear satisfactory.

Adult↗
PubMed1999

Eniluracil treatment completely inactivates dihydropyrimidine dehydrogenase in colorectal tumors.

PURPOSE: To determine the effect of eniluracil on colorectal tumor dihydropyrimidine dehydrogenase (DPD) activity. PATIENTS AND METHODS: Patients who were to undergo primary colorectal tumor resection received oral eniluracil 10 mg/m(2) twice daily for 3 days before surgery. Mononuclear cells were obtained before the start of eniluracil and on the morning of surgery, to measure DPD activity, protein, and mRNA. Plasma uracil was also measured at these two time points to assess the effect of eniluracil on pyrimidine accumulation. DPD activity, protein, and mRNA were also assessed in colorectal tumors and adjacent normal mucosa of patients who received eniluracil and untreated control patients. RESULTS: DPD activity in tumors from 10 untreated patients ranged from 30 to 92 pmol/min/mg of protein. In contrast, there was no detectable tumor DPD activity in 10 patients who received eniluracil. A similar pattern was observed in mononuclear cells, where median pretherapy activity was 366.5 pmol/min/mg of protein (range, 265 to 494 pmol/min/mg of protein) and was undetectable immediately before surgery. Plasma uracil changed from a median less than 0.2 micromol/L before therapy to 27.76 micromol/L before surgery. No difference in DPD protein or mRNA was observed between pretherapy and presurgery mononuclear cell samples or between treated and untreated tumor samples. CONCLUSION: This study provides definitive evidence that eniluracil completely inactivates DPD activity in human solid tumors. The increased plasma uracil and decreased DPD activity are consistent with systemic inactivation of the enzyme. The mechanism of inactivation is at the catalytic level, because no changes in DPD protein or mRNA were observed. Treatment with eniluracil will eliminate DPD activity as a source of pharmacokinetic fluorouracil variability or resistance in human colorectal cancer.

Adenocarcinoma↗
PubMed1999

Prehospital emergency care for children at school and nonschool locations.

OBJECTIVE: The purpose of this study was to ascertain whether school-based emergency medical services (EMS) incidents are different from nonschool-based EMS incidents for school-aged children. METHODS: We examined South Dakota EMS incident reports involving children ages 5 to 18 years old from 1994 through 1996 (n = 12603). Patient characteristics, dispatch reason, primary medical complaint, injury type, contributing factor of injury, and performed interventions were analyzed. RESULTS: During the study period, there were 140455 total EMS incident reports, of which 12603 (9.0%) were for school-aged children. EMS dispatches to a school represented 755 (6.0%) of all EMS incidents for school-aged children. The number of school-based EMS incidents was highest at the beginning of the school year, whereas the number of nonschool-based EMS incidents was highest during the summer months. School-based EMS incidents peaked at noon, whereas nonschool-based EMS incidents peaked after school. For both locations, the average age of the patient was 14 years old. The dispatch reason for school-based EMS incidents differed from those for nonschool-based EMS incidents. The top three school-based EMS dispatch reasons were falls (36.2%), other trauma (27.0%), and medical illness (24.5%). Motor vehicle crashes (30.8%), medical illness (26.2%), and other trauma (11.4%) were the leading nonschool-based EMS dispatch reasons. Injuries accounted for a significantly greater proportion of school-based than nonschool-based EMS incidents (70.7% vs 62.6%). Excluding pain, the most frequent type of injury was a fracture or dislocation in school-based EMS incidents and open soft-tissue injury in nonschool-based EMS incidents. A total of 11 students sustained an injury resulting in paralysis. The body region that was most commonly injured was a lower extremity (23%) in school-based incidents, whereas the head was the most commonly injured body region in nonschool-based incidents (20%). Sports were the largest contributing factor in school-based incidents, whereas alcohol/drug use was the largest contributing factor in nonschool-based EMS incidents among school-aged children. A medical illness was the primary complaint for 206 (27.3%) of the school-based incidents and 3599 (30.4%) of the nonschool-based incidents. The chief medical complaints were breathing difficulty (18.4%), seizure (16%), and other illness (12.3%) for school-based EMS incidents. Other illness (20.0%), breathing difficulty (13.7%), and abdominal pain (12.0%) were the chief complaints for nonschool-based EMS incidents. Treatment was rendered by the EMS provider in 11 753 (93.3%) of the incidents. Frequency of EMS intervention was the same for school-based incidents and nonschool-based incidents. Transportation to a medical facility was more frequent in school-based incidents than nonschool-based incidents. CONCLUSION: Compared with nonschool-based EMS incidents, school-based EMS incidents are more often attributable to injury, more often related to a sports activity, and more often result in transport to a medical facility. Understanding the characteristics of school emergencies resulting in an EMS dispatch may help emergency medical providers be better prepared for school-based incidents. School personnel may benefit from increased knowledge about the EMS system and EMS programs. In addition, EMS incident data may provide useful information about school-based injuries and may provide a means for injury surveillance.

Adolescent↗
PubMed1999

Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres.

Recently much attention has been given to the detection of submicroscopic chromosome rearrangements in patients with idiopathic mental retardation. We have screened 27 subjects with mental retardation and dysmorphic features for such rearrangements using a genetic marker panel screening. The screening was a pilot project using markers from the subtelomeric regions of all 41 chromosome arms. The markers were informative for monosomy in both parents at 3661902 loci (40.6%, 95% confidence interval 37.0-44.2%) in the 22 families where DNA was available from both parents. In two of the 27 subjects, submicroscopic chromosomal aberrations were detected. The first patient had a 5-6 Mb deletion of chromosome 18q and the second patient had a 4 Mb deletion of chromosome 1p. The identification of two deletions in 27 cases gave an aberration frequency of 7.5% without adjustment for marker informativeness (95% confidence interval 1-24%) and an estimated frequency of 18% if marker informativeness for monosomy was taken into account. This frequency is higher than previous estimates of the number of subtelomeric chromosome abnormalities in children with idiopathic mental retardation (5-10%) although the confidence interval is overlapping. Our study suggests that in spite of the low informativeness of this pilot screening, submicroscopic chromosome aberrations may be a common cause of dysmorphic features and mental retardation.

Adolescent↗