Immortalized cell lines. Chromosome preparation and banding.
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Animals↗
Biomedical subjects
J Fletcher
Publications and source records attributed to J Fletcher.
Near patient testing in general practice: attitudes of general practitioners and practice nurses, and quality assurance procedures carried out.
BACKGROUND: The evaluation of near patient testing in British general practice has largely been confined to studies examining individual tests or comparing equipment. AIM: This study set out to determine the attitudes of practice staff to near patient testing, and the extent to which staff undertook quality assessment. METHOD: Four types of near patient testing machines were introduced into 12 general practices in two regions of England, south west Thames and west Midlands. General practitioner and practice nurse attitudes to near patient testing were assessed by semi-structured interview before and six months after the introduction of the machines. The extent to which routine quality assurance procedures were carried out within the surgery and as part of local and national schemes was examined. RESULTS: Although 80% of general practitioners anticipated changing patient management with near patient testing, only two fifths reported having done so after six months. Nurses generally were enthusiastic at the outset, although one third were unhappy about incorporating near patient testing into their work schedules. Time pressure was the most important factor restricting uptake of near patient testing. Nurses performed quality control regularly but complete local external quality assurance procedures were established in only half the practices. All the practices participated in a national scheme for cholesterol assays. CONCLUSION: General practitioners in this study did not find near patient testing a very useful addition to their resources. Pressure on nurses' time was the most frequently reported limitation.
Attitude of Health Personnel↗
Effectiveness and cost of different strategies for information feedback in general practice.
AIM: The aim of this study was to determine the effectiveness and relative cost of three forms of information feedback to general practices--graphical, graphical plus a visit by a medical facilitator and tabular. METHOD: Routinely collected, centrally-held data were used where possible, analysed at practice level. Some non-routine practice data in the form of risk factor recording in medical notes, for example weight, smoking status, alcohol consumption and blood pressure, were also provided to those who requested it. The 52 participating practices were stratified and randomly allocated to one of the three feedback groups. The cost of providing each type of feedback was determined. The immediate response of practitioners to the form of feedback (acceptability), ease of understanding (intelligibility), and usefulness of regular feedback was recorded. Changes introduced as a result of feedback were assessed by questionnaire shortly after feedback, and 12 months later. Changes at the practice level in selected indicators were also assessed 12 and 24 months after initial feedback. RESULTS: The resulting cost per effect was calculated to be 46.10 pounds for both graphical and tabular feedback, 132.50 pounds for graphical feedback plus facilitator visit and 773.00 pounds for the manual audit of risk factors recorded in the practice notes. The three forms of feedback did not differ in intelligibility or usefulness, but feedback plus a medical facilitator visit was significantly less acceptable. There was a high level of self-reported organizational change following feedback, with 69% of practices reporting changes as a direct result; this was not significantly different for the three types of feedback. There were no significant changes in the selected indicators at 12 or 24 months following feedback. The practice characteristic most closely related to better indicators of preventive practice was practice size, smaller practices performing significantly better. Separate clinics were not associated with better preventive practice. CONCLUSION: It is concluded that feedback strategies using graphical and tabular comparative data are equally cost-effective in general practice with about two thirds of practices reporting organizational change as a consequence; feedback involving unsolicited medical facilitator visits is less cost-effective. The cost-effectiveness of manual risk factor audit is also called into question.
Cost-Benefit Analysis↗
A traveller returning from Nepal with hepatitis E.
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Adult↗
Impact of introducing near patient testing for standard investigations in general practice.
OBJECTIVE: To assess the clinical and economic impact of surgery based near patient testing in general practice for six commonly used biochemical and bacteriological tests. DESIGN: After four months' monitoring, equipment for two bacteriological and four biochemical tests was introduced without cost into 12 practices using a crossover design. Structured request forms were used to monitor laboratory investigations. SETTING: 12 general practices in west midlands and south west Thames with list sizes above 9000. MAIN OUTCOME MEASURES: Investigation rates per 1000 consultations. Changes from baseline rates. Reasons for requesting investigations and provisional diagnoses. Cost per test and sensitivity of costs to rate of use. RESULTS: Investigation rates for the six tests rose by 16.5% (from 78.6/1000 consultations to 91.6/1000) when equipment was available in the surgery and reverted to baseline rates when it was withdrawn. The average weekly number of tests when equipment was available ranged from 0.5 to 10.5 (mean 9.0). Cholesterol tests were used as an addition to laboratory testing, usually for screening. Midstream urine analysis was often done in the surgery instead of in the laboratory, although 30% of samples were tested by both methods. Doctors' reasons for investigation and conditions tested were largely unaffected by availability of surgery tests. Costs for surgery tests were higher for all tests except midstream urine. CONCLUSIONS: Availability of surgery based testing increased the number of tests performed. It was cost effective only for midstream urine analysis.
Cholesterol↗
The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity.
Adenosine triphosphate (ATP) bioluminescence was used to determine whether there was a linear relationship between cultured cell number and measured luminescence using the luciferin-luciferase reaction. In all the cells tested including peripheral blood mononuclear cells (MNC), MOLT-4, HL-60, TF-1, NFS-60 and L-929 cell lines there was a significant correlation as determined by Spearman's rank correlation coefficient (p > 0.00001). These observations were then used to determine whether ATP bioluminescence could be used as a suitable substitute for tritiated thymidine uptake as a measure of cell proliferation. The cell lines MOLT-4, HL-60, TF-1 and NFS-60 showed a strong correlation between thymidine uptake and ATP bioluminescence (p > 0.00001 for all cell types). Additionally the ATP method could detect the cytokine dependent proliferation on TF-1 and NFS-60 cells by granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) respectively. The tumour necrosis factor alpha (TNF)-induced cytotoxic effect on L-929 cells could also be accurately detected using this method. It would therefore appear to be possible to use ATP bioluminescence in the detection of cytokine activity in a number of different bioassays.
Adenosine Triphosphate↗
An investigation of the association between HLA-DQ heterodimers and type 1 (insulin-dependent) diabetes mellitus in five racial groups.
The association between HLA-DQ alpha Arg52-HLA-DQ beta non-Asp57 heterodimers and type 1 (insulin-dependent) diabetes was compared in Japanese, Chinese, Caucasian, North Indian Asian, and Afro-Caribbean patients to determine their importance in disease susceptibility. The potential to encode four Arg52-non-Asp57 DQ heterodimers, two in cis and two in trans, was significantly associated with increased risk of type 1 diabetes in all races except the Japanese. The possibility of encoding two Arg52-non-Asp57 heterodimers was also significantly associated with increased risk of the disease in all races except the Japanese. The possibility of encoding one heterodimer was not significantly associated with type 1 diabetes in any of the races studied. Heterogeneity testing revealed significant differences in RR values for four, two, and one heterodimers in all races except the Japanese and significant differences in RR for four and two heterodimers when compared across the races. This, together with the lack of an association between Arg52-non-Asp57 heterodimers and type 1 diabetes in the Japanese, suggests that, assuming the same genetic basis for disease in all races, the heterodimer is unlikely to be of primary importance in susceptibility to the disease.
Diabetes Mellitus, Type 1↗
The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma.
The tumour suppressor gene WT1 encodes a transcription factor expressed in tissues of the genito-urinary system. Inactivation of this gene is associated with the development of Wilms tumour a pediatric kidney cancer. We show that WT1 is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. We also describe a case of adult human mesothelioma, a tumour derived from the peritoneal lining, that contains a homozygous point mutation within WT1. This mutation, within the putative transactivation domain, converts the protein from a transcriptional repressor of its target sequence to a transcriptional activator. The role of WT1 in normal development thus extends to diverse structures derived from embryonic mesoderm and disruption of WT1 function contributes to the onset of adult, as well as pediatric, tumours.
Adult↗
Australian registered nurse medical device education: a comparison of life-sustaining and non-life-sustaining devices.
Registered nurses are primarily responsible for the use of medical devices in direct patient care. This cross-sectional survey compared how and what 139 registered nurses working in a variety of wards/units in a 1000-bed tertiary care hospital in South Australia initially learned about the life-sustaining and non-life-sustaining medical devices they use. Furthermore, the consequences of device use both for patients and staff were explored. How and what registered nurses initially learned about life-sustaining and non-life-sustaining devices were remarkably similar. Consequences of device use, which included increased or decreased quality of care, increased nurse stress and patient harm, were related, in part, to knowledgeable and proficient device use. Thus, device education for nurses is essential and warrants further exploration.
Adult↗
A phase II study of moderate hypothermia in severe brain injury.
Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.
Adolescent↗
Human olfactory marker protein maps close to tyrosinase and is a candidate gene for Usher syndrome type I.
Olfactory marker protein (OMP) shows olfactory neuron-specific expression in rodents. We recently reported tight linkage on mouse chromosome 7 of OMP to the shaker-1 deafness mutant, between the tyrosinase and globin loci. Here we isolate and map the human homologue. Our results show that OMP maps immediately centromeric to tyrosinase on the long arm of human chromosome 11. Genetic linkage to this region has recently been established for Usher Syndrome Type I, an autosomal recessive blindness and deafness disorder and a putative homologue of the shaker-1 mutant. OMP is thus a candidate gene for both congenital deafness defects.
Animals↗
Effect of peritoneal dialysis effluent on superoxide anion production by polymorphonuclear neutrophils.
Peritoneal dialysis effluent (PDE) contains at least 2 factors capable of affecting superoxide generation by polymorphonuclear neutrophils (PMN) in response to both particulate and soluble stimuli. A low molecular weight fraction (< 1.2 kD) enhanced the response to the chemotactic peptide fMLP and to preopsonised Staphylococcus epidermidis and Candida guilliermondii. A higher molecular weight fraction (> 1.2 kD) inhibited superoxide production in response to phorbol myristate acetate (PMA). The effects of PDE were dose dependent over the range of 10-70% (v/v) and simply augmented and reduced the dose-response curve to fMLP and PMA, respectively. There was no alteration in the concentration of stimulus required to give maximal superoxide production in either case. These data suggest that factors capable of affecting superoxide production by PMN accumulate in uraemia and are removed from the circulation into dialysis fluid.
Candida↗
Eye-movement rhythmicity and reading comprehension.
The purpose of these two studies was to examine the rhythmical patterns displayed by subjects with and without reading disabilities while they were reading (Study 1), and to vary rhythmicity through priming and observe the effects on parsing ability using eye-movement and comprehension measures (Study 2). Rhythmicity during silent reading was operationalized by transcribing eye-movement measures into pitch, rhythm, and rests. In Study 1, 17 subjects with reading disabilities and 15 control subjects (M age = 15, male = 60%) parsed 20 flawed and control sentences. In Study 2, 35 control subjects (M age = 21, male = 43%) parsed 9 phrases from familiar songs under one of three rhythm-priming conditions. Results (Study 1) indicated significant differences in rhythm patterns. Subjects with reading disabilities exhibited rhythm variability, unpredictability, and lethargic tempos. In Study 2, significant differences across priming conditions were found, with primed subjects exhibiting improved parsing and comprehension. Rhythm may be an organizational substrate for syntax.
Adolescent↗
Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin.
The iron-binding protein lactoferrin (Lf) is a constituent of neutrophil secondary granules and is discharged into the surrounding medium when neutrophils are activated. Lf released from neutrophils phagocytosing opsonized particles inhibits proliferation of mixed lymphocyte cultures (MLC) and has also been shown to inhibit granulopoiesis, suppress antibody production, and regulate natural killer cell activity. All of these processes are controlled by cytokines, suggesting that Lf may modulate immune responses by inhibiting cytokine activity. When MLC were cultured in round-bottomed wells to crowd the cells together, Lf, 50% saturated with iron, inhibited both proliferation and interleukin-2 (IL-2) release into the supernatants. Inhibition was concentration-dependent and lost at concentrations of Lf greater than 10(-12) mol/L. Lf at 10(-10) mol/L inhibited release of tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1) into MLC supernatants, as well as inhibiting IL-2 release. TNF in the supernatant was significantly reduced at 5 and 24 hours, becoming less and losing significance by 72 hours. IL-1 in the supernatant was not significantly reduced at 5 and 24 hours, becoming significant at 48 and 72 hours. IL-2 was significantly reduced at 48 and 72 hours and followed the same time course as proliferation. Inhibition was blocked by specific antiserum to Lf, but not by a preimmune serum. Lf, 10(-10) mol/L, also inhibited the production of TNF (49.15% +/- 7.98%; n = 10, P = .032) and IL-1 (42.67% +/- 6.72%; n = 6, P = .032) from endotoxin-stimulated mononuclear cells. As with MLC, inhibition was dose-dependent and abrogated by specific antiserum. Lf did not block the biological action of TNF, IL-1, or IL-2 in specific assays using cytokine-sensitive cell lines. These data suggest that Lf, released from activated neutrophils, acts as a negative feedback mechanism to prevent recruitment and activation of leukocytes in sites of inflammation.
Dose-Response Relationship, Drug↗
Cost effectiveness of magnetic resonance imaging.
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Cost-Benefit Analysis↗
An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene.
Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.
Alleles↗
Abnormal cytoplasmic pH regulation during activation in uremic neutrophils.
Neutrophils isolated from ESRF patients demonstrated abnormal cytoplasmic pH changes after FMLP stimulation; the initial cytoplasmic acidification was absent (P less than 0.001 compared to controls) and the degree of alkalinization enhanced (P less than 0.05 compared to controls). This effect was not due to the absence of any of the factors associated with acidification in normal PMN since superoxide production was enhanced (P less than 0.05 compared to controls) and intracellular calcium release was normal. Our observations are not explicable by alterations in the function of the Na:H antiport since the kinetics of antiport activation by cytoplasmic pH were not different in uremic and control cells. Other factors must therefore be important in generating the abnormal pH response to chemotactic factors in uremic PMN. Cells from CAPD patients had some degree of initial acidification (P less than 0.001 compared to controls and P less than 0.05 compared to ESRF) and enhanced alkalinization (P less than 0.05 compared to controls). Preincubation of normal PMN in four-hour dwell PDE reproduced the responses of uremic PMN with absent acidification, enhanced alkalinization and enhanced superoxide generation after FMLP stimulation (P less than 0.05 compared to controls). Changes in the control of cytoplasmic pH in stimulated PMN may influence PMN function, and our observations may be relevant to the susceptibility of uremic patients to infection.
Adult↗
Cytogenetic and experimental models.
The sarcomas, particularly those of soft tissue origin, often contain characteristic immunohistochemical and cytogenetic features that are of diagnostic relevance. Over the past year, novel findings have been reported that are likely to improve present sarcoma diagnostic capabilities. Findings of particular interest have been reported for Ewing's sarcoma, peripheral primitive neuroectodermal tumor, rhabdomyosarcoma, and clear cell sarcoma.
12E7 Antigen↗