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Biomedical subjects

C Johnston

Publications and source records attributed to C Johnston.

At least 73 records · Page 4Linked to original sources
PubMed2000

Northwest Herts diabetic management system.

The Diabetic Management System was set up in Hemel Hempstead within the Dacorum district (population 119515 with 2176 registered patients with diabetes). The objective was to create a clinical management system for all patients with diabetes in a district using a computerised clinical base. To achieve this a database of agreed clinical information was collected from all general practitioners within the district. From the computerised data we can identify those patients who do not have data recorded and can recall them for review. Consultant advice can be given on patients with special or multiple risks identified from interrogation of the database. The outcome has been a higher percentage of patients with diabetes receiving clinical review and achieving optimal clinical targets within the reviews. We already have recorded data on 85% for retinal screening and 75% for comprehensive annual reviews. Conclusions drawn from the Dacorum Diabetic Management System are that effective diabetic care to a population can be provided by a combination of hospital and primary care. Primary care needs to be supported by adequate consultant advice with continued monitoring of the whole population to ensure standards are met. This system achieves this without increased hospital referrals.

Computer Systems↗
PubMed2000

Effects of stimulant medication treatment on mothers' and children's attributions for the behavior of children with attention deficit hyperactivity disorder.

Participants were 55 children with attention deficit hyperactivity disorder (ADHD) who were receiving ongoing treatment with stimulant medications and their mothers, and 31 children with ADHD who were beginning stimulant medication and their mothers. Mothers and children offered attributions for child behaviors that occurred when the child was medicated and not medicated. Mothers rated child compliance and prosocial behavior as more global and stable when the child was medicated and rated noncompliance, ADHD symptoms, and oppositional behavior as more externally caused, less global and stable, but more controllable by the child when the child was medicated. Children rated both their compliance and noncompliance as more controllable in the medicated condition. On a forced-choice measure, both mothers and children selected ability, effort, and task attributions for compliance more in the not-medicated condition, and pill-taking attributions more in the medicated condition. This was reversed for noncompliance, which was attributed more to effort, task, or ability in the medicated condition and more to not taking a pill in the not-medicated condition. The potential risks and benefits for parent-child interactions and children's self-perceptions of these medication-related differences in attributions are discussed.

Adolescent↗
PubMed2000

Induction of adaptation to inhaled lipopolysaccharide in young and old rats and mice.

Lipopolysaccharide (LPS) is a component of the gram-negative bacterial cell wall that is known to activate inflammatory cells and enhance the production of inflammatory mediators in the lung. As it is a ubiquitous compound, inhalation exposure is highly likely in the human environment. Adaptation is a phenomenon by which a previous exposure results in improved survival or reduced injury as compared to a single exposure alone. We hypothesized that the basic proinflammatory effects of LPS in the lung could result in the development of adaptation in animals. Based on evidence of age- and species-related differences in lung injury, we used an acute lung injury model with inhaled LPS to compare the development of adaptation in young and old Fisher 344 rats and C57Bl/6J mice. Animals were exposed to low-dose (predicted lung deposition approximately 20 ng in rats and approximately 5 ng in mice) LPS aerosols for 10 min on 3 consecutive days; on day 4, a high dose (rats approximately 200 ng; mice approximately 25 ng) was delivered. Another group of animals received only the high LPS dose on day 4, whereas controls were unexposed. Twenty-four hours after the last exposure, cellular and inflammatory parameters in bronchoalveolar lavage (BAL) were determined. An adaptive response was found in both rats and mice. Adapted animals showed significantly fewer BAL neutrophils compared to nonadapted ones; there was also a significantly lower release of oxidants from phorbol methyl ester-stimulated BAL cells from adapted compared to nonadapted animals, which, in turn, showed a greater response than controls. Furthermore, studies in old animals (21 mo of age) showed that adaptation also occurs in this age group. The adaptive response is clear in old mice; in rats, there is greater variability in the response, but an adaptive trend is apparent. Therefore, we have demonstrated that inhaled low-dose LPS can induce adaptation to subsequent higher doses, much as has been shown for other toxicants that induce oxidative lung injury.

Administration, Inhalation↗
PubMed2000

Opinions and use of advance directives by physicians at a tertiary care hospital.

The physician-patient relationship is an essential part of end-of-life planning, including discussions of advance directives (AD). Physicians likely to encounter AD issues with their patients were identified and queried as to their knowledge, opinion, and experience with ADs. Though most physicians felt ADs were helpful to both physicians and patients, considerably less were familiar with hospital policies and the different types of ADs. Formal education in the use and function of ADs also appears to be lacking, suggesting a need to improve the way in which ADs are addressed during medical training.

Adult↗
PubMed2000

Parental and child cognitions in the context of the family.

Parent and child family-related cognitions are reviewed with respect to (a) their origins, (b) their linkage to affect and behavior, (c) their transmission and perpetuation, (d) their alteration on the basis of first-hand experience, and (e) their collaborative negotiation and renegotiation. A distinction is offered between the functioning of implicit, relatively unaware, schematic cognitions and relatively aware, explicit, event-dependent cognitions. Consideration is also given to the differential content (or topics) of cognitions. As a positive outcome of recent research, many new insights have emerged with respect to the linkage of family members' cognitions and their individual and shared patterns of behavior. However, several limitations remain, including too little consideration of the shared influences of parents' and children's cognitions and the changes in these cognitions over time. As a growth area, there is emerging interest in the application of our knowledge of cognitions to the clinical context in programs designed to remediate and prevent family problems.

Adult↗
PubMed2000

Basic three-dimensional kinematics of the vertebral column of horses walking on a treadmill.

OBJECTIVE: To determine kinematic movements of the vertebral column of horses during normal locomotion. ANIMALS: 5 Dutch Warmblood horses without apparent lameness or problems associated with the vertebral column. PROCEDURE: Kinematics of 8 vertebrae (T6, T10, T13, T17, L1, L3, L5, and S3) and both tuber coxae were determined, using bone-fixated markers. Horses were recorded while walking on a treadmill at a constant speed of 1.6 m/s. RESULTS: Flexion-extension was characterized by 2 periods of extension and flexion during 1 stride cycle, whereas lateral bending and axial rotation were characterized by 1 peak and 1 trough. The range of motion for flexion-extension was fairly constant for vertebrae caudal to T10 (approximately 7 degrees). For lateral bending, the cranial thoracic vertebrae and segments in the pelvic region had the maximal amount of motion, with values of up to 5.6 degrees. For vertebrae between T17 and L5, the amount of lateral bending decreased to <4 degrees The amount of axial rotation increased gradually from 4 degrees for T6 to 13 degrees for the tuber coxae. CONCLUSIONS: This direct measurement method provides 3-dimensional kinematic data for flexion-extension, lateral bending, and axial rotation of the thoracolumbar portion of the vertebral column of horses walking on a treadmill. Regional differences were observed in the magnitude and pattern of the rotations. Understanding of the normal kinematics of the vertebral column in healthy horses is a prerequisite for a better understanding of abnormal function.

Animals↗
PubMed2000

Evaluation of novel assays in clinical chemistry: quantification of plasma total homocysteine.

BACKGROUND: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries. METHODS: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography-mass spectrometry (GC-MS). All laboratories performed the following procedures: (a) familiarization; (b) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; (c) correlation using patients' samples; and (d) assessment of long-term performance. RESULTS: Both immunological methods were linear for P-tHcy between 5 and 45 micromol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9% for EIA used with a sample processor. The bias was -2% to 3% for FPIA and 2-4% for EIA used with a sample processor. CONCLUSIONS: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).

Fluorescence Polarization Immunoassay↗
PubMed2000

Acute pulmonary effects of ultrafine particles in rats and mice.

Ambient fine particles consist of ultrafine particles (< 100 nm) and accumulation-mode particles (approximately 100 to 1,000 nm). Our hypothesis that ultrafine particles can have adverse effects in humans is based on results of our earlier studies with particles of both sizes and on the finding that urban ultrafine particles can reach mass concentrations of 40 to 50 micrograms/m3, equivalent to number concentrations of 3 to 4 x 10(5) particles/cm3. The objectives of the exploratory studies reported here were to (1) evaluate pulmonary effects induced in rats and mice by ultrafine particles of known high toxicity (although not occurring in the ambient atmosphere) in order to obtain information on principles of ultrafine particle toxicology; (2) characterize the generation and coagulation behavior of ultrafine particles that are relevant for urban air; (3) study the influence of animals' age and disease status; and (4) evaluate copollutants as modifying factors. We used ultrafine Teflon (polytetrafluoroethylene [PTFE]*) fumes (count median diameter [CMD] approximately 18 nm) generated by heating Teflon in a tube furnace to 486 degrees C to evaluate principles of ultrafine particle toxicity that might be helpful in understanding potential effects of ambient ultrafine particles. Teflon fumes at ultrafine particle concentrations of approximately 50 micrograms/m3 are extremely toxic to rats when inhaled for only 15 minutes. We found that neither the ultrafine Teflon particles alone when generated in argon nor the Teflon fume gas-phase constituents when generated in air were toxic after 25 minutes of exposure. Only the combination of both phases when generated in air caused high toxicity, suggesting the existence of either radicals on the particle surface or a carrier mechanism of the ultrafine particles for adsorbed gas-phase compounds. We also found rapid translocation of the ultrafine Teflon particles across the epithelium after their deposition, which appears to be an important difference from the behavior of larger particles. Furthermore, the pulmonary toxicity of the ultrafine Teflon fumes could be prevented by adapting the animals with short 5-minute exposures on 3 days prior to a 15-minute exposure. This shows the importance of preexposure history in susceptibility to acute effects of ultrafine particles. Aging of the fresh Teflon fumes for 3.5 minutes led to a predicted coagulation resulting in particles greater than 100 nm that no longer caused toxicity in exposed animals. This result is consistent with greater toxicity of ultrafine particles compared with accumulation-mode particles. When establishing dose-response relationships for intratracheally instilled titanium dioxide (TiO2) particles of the size of the urban ultrafine particles (20 nm) and of the urban accumulation-mode particles (250 nm), we observed significantly greater pulmonary inflammatory response to ultrafine TiO2 in rats and mice. The greater toxicity of the ultrafine TiO2 particles correlated well with their greater surface area per mass. Ultrafine particles of carbon, platinum, iron, iron oxide, vanadium, and vanadium oxide were generated by electric spark discharge and characterized to obtain particles of environmental relevance for study. The CMD of the ultrafine carbon particles was approximately 26 nm, and that of the metal particles was 15 to 20 nm, with geometric standard deviations (GSDs) of 1.4 to 1.7. For ultrafine carbon particles, approximately 100 micrograms/m3 is equivalent to 12 x 10(6) particles/cm3. Homogeneous coagulation of these ultrafine particles in an animal exposure chamber occurred rapidly at 1 x 10(7) particles/cm3, so that particles quickly grew to sizes greater than 100 nm. Thus, controlled aging of ultrafine carbon particles allowed the generation of accumulation-mode carbon particles (due to coagulation growth) for use in comparative toxicity studies. We also developed a technique to generate ultrafine particles consisting of the stable isotope 13C by using 13C-graphite electrodes made in our laboratory from amorphous 13C powder. These particles are particularly useful tools for determining deposition efficiencies of ultrafine carbon particles in the respiratory tracts of laboratory animals and the translocation of particles to extrapulmonary sites. For compromised animals, we used acute and chronic pulmonary emphysema; a low-dose endotoxin inhalation aimed at priming target cells in the lung was also developed. Other modifying factors were age and copollutant (ozone) exposure. Exposure concentrations of the generated ultrafine particles for acute rodent inhalation studies were selected on the basis of lung doses predicted to occur in people inhaling approximately 50 micrograms/m3 urban ultrafine particles. Concentrations that achieved the same predicted lung burden per unit alveolar surface were used in rodents. (ABSTRACT TRUNCATED)

Administration, Inhalation↗
PubMed1999

Silica binds serum proteins resulting in a shift of the dose-response for silica-induced chemokine expression in an alveolar type II cell line.

There is a growing concern about whether the myriad of culture conditions, cell lines, and doses of nonfibrous and fibrous particles used in vitro are truly representative of the complex environment of the in vivo particle exposure situation. The use of serum as a supplement to the growth medium of cultured cells is a widely accepted practice. However, little is known about whether the various serum proteins may interact with the surfaces of particles, consequently altering their toxicity, inflammatory properties, or fibrogenicity, etc. observed in vivo. Using a murine alveolar type II cell line, MLE-15, we measured the early changes in various chemokine mRNA species following exposure of the cells to silica (cristobalite) in the presence or absence of serum. Total mRNA was isolated and assayed using an RNase protection assay after 6 h of particle exposure. We observed that the addition of serum to the culture media reduced the in vitro silica-induced chemokine response (i.e., shift in the dose-response curve) in MLE-15 cells. Further, using Western blot analysis and protein sequencing techniques, we have identified a specific serum component, apolipoprotein-A1 (apo-A1), as a protein in serum that binds selectively to silica, thus leading to the altered chemokine response. We also found that apo-A1 not only binds to silica but also binds to other nonfibrous and fibrous particles such as titanium dioxide and asbestos. These results demonstrate the importance of culture conditions for modifying the outcome of an experiment when performing in vitro particle exposure studies.

Animals↗
PubMed1999

Antioxidant treatment attenuates cytokine and chemokine levels in murine macrophages following silica exposure.

Alveolar macrophages play a key role in the development of silicosis by releasing a host of mediators, such as, cytokines and chemokines, which contribute to a complex network of interactions that result in the onset of lung injury, inflammation, and potentially fibrosis. Using a murine macrophage cell line, RAW 264.7, we exposed the cells to cristobalite-silica (35 micrograms/cm(2)) in the presence or absence of antioxidants and various modifiers of cellular antioxidant status. Treatment with dimethyl sulfoxide, extracellular glutathione, or N-acetyl-L-cysteine (NAC) decreased cristobalite-induced tumor necrosis factor (TNF)-alpha mRNA levels by 40%, 20%, and 42%, respectively. TNF-alpha protein levels were decreased by 90%, 32%, and 53%, respectively. Cristobalite-induced macrophage inflammatory protein (MIP)-2 mRNA levels were reduced by 52%, 38%, and 57%, with DMSO, GSH, and NAC treatment, respectively. Both MIP-1alpha and MIP-1beta mRNA levels were reduced at a magnitude similar to the reduction in TNF-alpha mRNA levels, whereas monocyte chemotactic protein (MCP)-1 mRNA levels were reduced at a magnitude similar to the reduction in MIP-2 mRNA levels following antioxidant treatment. These results suggests that the macrophage response to cristobalite exposure is mediated at least in part by oxidant stress.

Acetylcysteine↗
PubMed1999

Effect on survival of delays in referral of patients with breast-cancer symptoms: a retrospective analysis.

BACKGROUND: From April 1, 1999, family physicians are required to refer all patients who have suspected breast cancer in the UK urgently to hospital, to be seen within 14 days of referral. We investigated whether delays by providers in routine practice for diagnosis influence survival. METHODS: We did a retrospective analysis of 36,222 patients with breast cancer listed in the Yorkshire Cancer Registry. Data on delay after family-physician referral, hospital visit, and start of treatment were available, as well as on tumour grade and stage of presentation. RESULTS: There was no evidence that provider delays of longer than 90 days adversely influenced survival. The time from family-physician referral to first hospital visit changed little (median 10 vs 13 days) from 1976 to 1995, whereas time from first visit to first treatment doubled (7 vs 13 days). More than 8% of patients younger than 50 years delayed longer than 90 days, compared with 3% of patients older than 50 years (p<0.001). 48% of younger patients had their first treatment within 30 days compared with 64% of those older than 50 (p<0.001). The survival for 5708 patients diagnosed in 1986-90 selected for survival analysis was 63% at 5 years, and 51% at 8 years. Patients who presented early and were treated in less than 30 days had significantly worse outcomes (p<0.001). INTERPRETATION: Delays by providers in diagnosis of 3 months or more do not seem to be associated with decreased survival in patients presenting with breast cancer. The drive for all women with possible breast cancer to be seen within 14 days will divert resources from other services and is not supported by this study.

Adult↗
PubMed1999

Improved solution for solitary waves in arteries.

Nonlinear waves are investigated numerically by a direct analysis of the field equations, thereby establishing the magnitude of the errors inherent in the commonly used reductive perturbation technique. The method is also applied beyond the long-wave approximation and a comparative assessment of the results obtained is presented.

Arteries↗
PubMed1999

A decade of doctoral research in nutrition.

OBJECTIVE: To describe North American dissertation research in human nutrition from 1986 through 1995. DESIGN: A census collection. SUBJECTS/SETTING: The unit of observation was the dissertation abstract submitted to Dissertation Abstracts International for the years 1986 through 1995. Only dissertations written in English with a human nutrition subject code (0570) that lead to a PhD, DrPH, EdD, or ScD at a North American university were included (N = 2,044). Abstracts were reviewed by 2 raters who extracted pertinent data on variables describing the dissertation research (e.g., topic of dissertation, type of sample). ANALYSES: Analyses were descriptive. RESULTS: The majority (n = 1,147) of doctoral dissertations were completed by female students. Male students were more likely to study in vitro samples than female students (11% vs 4%) and female students were more likely to study human subjects (64%). Male students tended to have male advisers, although overall male advisers appeared to predominate (34% men, 24% women, 42% unknown or missing). Topic areas for dissertation work reflected gender differences. Popular topics for dissertation research have changed over time; biochemical-, micronutrient-, and obesity-related research decreased and research in development of theoretical constructs and examination of dietary habits of selected groups increased. CONCLUSIONS: From 1986 through 1995 there was an increase in the proportion of female doctoral students. Female and male students varied in the type of sample studied, gender of advisers, age group of human subjects, and topics of their dissertations. Universities emphasized different topic areas and methodologies. There appears to have been an increase in areas of applied research (e.g., dietary habits) and a decrease in basic science topic areas (e.g., micronutrients) over the 10-year period examined.

Academic Dissertations as Topic↗
PubMed1999

Changing trends in prostatic cancer.

OBJECTIVES: To examine the diagnosis and treatment of prostatic cancer in a population-based study, reporting incidence trends and survival, in the decade before the introduction of prostate-specific antigen (PSA) testing, and thus determine whether the overall incidence of prostatic cancer is increasing or not. PATIENTS AND METHODS: The study included all men registered as having prostatic cancer in the Yorkshire region between 1981 and 1990. The Northern and Yorkshire Cancer Registry and Information Service has an active registration policy and after notification, the information received is validated by histopathology reports and case-note review. Of the patients registered, 68% were over 70 years old at the time of diagnosis (mean age 74 years). Prostatic cancer was often diagnosed incidentally, after prostatectomy for presumed benign disease. Indications for treatment were not recorded, but most patients had treatment which was designed to control outlet bladder symptoms rather than with intent to cure cancer. RESULTS: In all, 8118 patients with prostatic cancer were registered, of whom 6587 had histological confirmation. There was a 30% increase in the age-standardized incidence of prostatic cancer during the study period (P<0.001). The mortality from prostatic cancer increased by 35% (P<0.001) and the percentage of patients known to have metastases at the time of presentation increased from 18% to 24%. These changes were seen in all age groups. The overall survival was 49% at 5 years and 34% at 10 years. CONCLUSIONS: There has been a real increase in the incidence of prostatic cancer which pre-dates the use of serum PSA testing. The percentage relative survival of patients with prostatic cancer in Yorkshire during the study period is similar to that seen in other parts of the UK, but compares badly with reported survival in other countries.

Adult↗
PubMed1999

Management of pain from heel lance with lidocaine-prilocaine (EMLA) cream: is it safe and efficacious in preterm infants?

Hospitalized preterm infants undergo multiple painful heel lances. A two-phase, randomized, controlled trial was undertaken to determine the safety and efficacy of lidocaine-prilocaine 5% cream (EMLA, Astra Pharmaceuticals, L.P, Westborough, MA) for relieving pain from heel lance. One hundred twenty infants were randomly assigned to receive 0.5 g of EMLA or placebo cream for 30 minutes (Phase 1) or 60 minutes (Phase 2) before a routine heel lance. Efficacy was assessed using the Premature Infant Pain Profile (PIPP). Safety was determined by methemoglobin concentration 8 hours after EMLA application and by clinical signs of methemoglobinemia. No significant differences existed on PIPP scores between EMLA and placebo groups in Phase 1 (p < .480) or Phase 2 (p < .831). No infant had any clinical signs of methemoglobinemia. The mean methemoglobin concentration was 1.19% (.47). Approximately 10% of infants had minor skin reactions, and approximately 20% of EMLA-treated infants had blanching at the application site. The authors conclude that EMLA is safe but not efficacious for relieving pain from heel lance in preterm infants.

Anesthetics, Combined↗
PubMed1999

Advance directive use among patients undergoing selected high-risk surgical procedures.

Since 1991, the Patient Self-Determination Act has required that all patients entering Medicare-reimbursed institutions be asked if they have an advance directive (AD) and be given information about advance directives if they do not have one. Patients undergoing elective high-risk surgery for diseases with a poor prognosis were identified as being most likely to benefit from an AD. The charts of patients being explored for possible pancreaticoduodenectomy or esophagectomy at a tertiary referral hospital in 1996 were retrospectively reviewed. Few patients had an AD, and there was little evidence that the presence of an AD affected patient care.

Advance Directives↗