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Biomedical subjects

C W Johnson

Publications and source records attributed to C W Johnson.

At least 19 recordsLinked to original sources

Why did that happen? Exploring the proliferation of barely usable software in healthcare systems.

Clinicians and support staff are faced with increasingly complex computer applications. This complexity stems partly from the integration of heterogeneous systems ranging from computerized patient records to theatre management and dosage planning applications, and also from the increased functionality offered by the new generation of IT systems. Many members of clinical staff are bewildered by the vast array of configuration options and operating modes supported by computer based systems, while manufacturers often feel compelled to offer more and more software features to retain market position. These factors combine to create "usability" problems that have had a direct impact on patient outcomes as well as a number of indirect effects-for example, the costs of replacing and upgrading inadequate computer systems carry significant opportunity costs in terms of services that might otherwise have been funded. In the future we need to educate staff to reject substandard computer interfaces early in the acquisition process; encourage the use of human computer interaction techniques in health care; and train staff to recognize the dangers of "working around" poor interface design.

Attitude to Computers↗

Molecular markers linked to the blast resistance gene Pi-z in rice for use in marker-assisted selection.

Rice blast, caused by the fungal pathogen Pyricularia grisea, is a serious disease affecting rice-growing regions around the world. Current methods for identification of blast-resistant germplasm and progeny typically utilize phenotypic screening. However, phenotypic screens are influenced by environmental conditions and the presence of one resistance gene can sometimes phenotypically mask other genes conferring resistance to the same blast race. Pi-z is a dominant gene located on the short arm of chromosome 6 that confers complete resistance to five races of blast. Using sequence data found in public databases and degenerate primer pairs based on the P-loop, nucleotide binding sites and kinase domain motifs of previously cloned resistance genes, we have developed PCR-based DNA markers that cosegregate with the gene. These markers are polymorphic in a wide range of germplasm, including the narrow crosses characteristic of applied rice-breeding programs. They can now be used as a low cost, high-throughput alternative to conventional phenotypic screening for direct detection of blast resistance genes, allowing rapid introgression of genes into susceptible varieties as well as the incorporation of multiple genes into individual lines for more-durable blast resistance.

Chromosome Mapping↗

How will we get the data and what will we do with it then? Issues in the reporting of adverse healthcare events.

Incident reporting has been proposed as an important means of identifying and addressing the causes of human error in medicine, and initiatives to implement these schemes have been set up in many countries. However, incident reporting has its limitations. Many people have been too ready to believe the overstated claims about the effectiveness of incident reporting in other domains. Others have not listened to the more limited claims made by the operators of existing systems in aviation and in organizational health and safety applications. This paper argues that more attention should be paid to the problems of eliciting incident reports from a broad spectrum of healthcare workers. It is also argued that more sophisticated computation support should be recruited so that clinicians do not have to learn complex command languages when they want to search for common factors in those incidents that are submitted.

Attitude of Health Personnel↗

Flow cytometric enumeration of micronucleated reticulocytes: high transferability among 14 laboratories.

This laboratory previously described a single-laser flow cytometric method, which effectively resolves micronucleated erythrocyte populations in rodent peripheral blood samples. Even so, the rarity and variable size of micronuclei make it difficult to configure instrument settings consistently and define analysis regions rationally to enumerate the cell populations of interest. Murine erythrocytes from animals infected with the malaria parasite Plasmodium berghei contain a high prevalence of erythrocytes with a uniform DNA content. This biological model for micronucleated erythrocytes offers a means by which the micronucleus analysis regions can be rationally defined, and a means for controlling interexperimental variation. The experiments described herein were performed to extend these studies by testing whether malaria-infected erythrocytes could also be used to enhance the transferability of the method, as well as control intra- and interlaboratory variation. For these studies, blood samples from mice infected with malaria, or treated with vehicle or the clastogen methyl methanesulfonate, were fixed and shipped to collaborating laboratories for analysis. After configuring instrumentation parameters and guiding the position of analysis regions with the malaria-infected blood samples, micronucleated reticulocyte frequencies were measured (20,000 reticulocytes per sample). To evaluate both intra- and interlaboratory variation, five replicates were analyzed per day, and these analyses were repeated on up to five separate days. The data of 14 laboratories presented herein indicate that transferability of this flow cytometric technique is high when instrumentation is guided by the biological standard Plasmodium berghei.

Animals↗

The accuracy with which the human condyle can be expressed in the coordinate system of JAWS3D using a unilateral fiducial marker.

Previous studies have indicated that the selection of condylar referencing points can significantly influence condylar point trajectories, and the use of radiographically determined condylar points is essential for accurate representation of condylar movement. The aim of this investigation was to determine the accuracy with which the three-dimensional locations of condylar points could be determined in the coordinate system of the JAWS3D tracking device when an ipsilateral fiducial marker is used. A perspex mandible containing condylar radiographic markers was constructed. A JAWS3D target frame and a fiducial marker, supporting radiographic markers, were secured to the perspex mandible. The image data from computer tomography scans of the condyles and fiducial marker, together with photographs of the fiducial marker and the JAWS3D target frame were used to calculate condylar point coordinates in the JAWS3D coordinate system. These data were then compared with the data obtained by direct measurement of the condylar radiographic markers in the JAWS3D coordinates. The results suggest that a unilateral fiducial marker is sufficient to allow the registration of ipsilateral condylar point coordinates to an accuracy of approximately 1.0 mm.

Cephalometry↗

Salvage cryotherapy using an argon based system for locally recurrent prostate cancer after radiation therapy: the Columbia experience.

PURPOSE: Cryosurgical ablation of the prostate has been reported as potential treatment for radioresistant clinically localized prostate cancer. We report our experience with the safety and efficacy of salvage cryosurgery using the argon based CRYOCare system (Endocare, Inc, Irvine, California). MATERIALS AND METHODS: Between October 1997 and September 2000, 38 men with a mean age of 71.9 years underwent salvage cryosurgery for recurrent prostate cancer after radiation therapy failed. All patients had biochemical disease recurrence, defined as an increase in prostate specific antigen (PSA) of greater than 0.3 ng./ml. above the post-radiation PSA nadir. Subsequently prostate biopsy was positive for cancer. Pre-cryosurgery bone scan demonstrated no evidence of metastatic disease. In addition, these patients received 3 months of neoadjuvant androgen deprivation therapy before cryotherapy. RESULTS: The PSA nadir was 0.1 or less, 1 or less and greater than 1 ng./ml. in 31 (81.5%), 5 (13.2%) and 2 (5.3%) patients, respectively. Biochemical recurrence-free survival calculated from Kaplan-Meier curves was 86% at 1 year and 74% at 2 years. Reported complications included rectal pain in 39.5% of cases, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria in 7.9% and scrotal edema in 10.5%. The rate of rectourethral fistula, urethral sloughing and urinary retention was 0%. CONCLUSIONS: Our study supports cryosurgery of the prostate as safe and effective treatment in patients in whom radiation therapy fails. Using the CRYOCare machine resulted in a marked decrease in complications.

Aged↗

Sensitivity of the SRBC PFC assay versus ELISA for detection of immunosuppression by TCDD and TCDD-like congeners.

The splenic antibody plaque forming cell (PFC) assay is a widely used assay in immunotoxicity testing. A recent revision of the Federal Insecticide, Fungicide and Rodenticide (FIFRA) Immunotoxicity test guidelines by the EPA recommended that either the PFC assay or the sheep red blood cell (SRBC) specific serum IgM enzyme-linked immunosorbent assay (ELISA) be used to assess the primary humoral response to SRBCs. The PFC assay quantifies the number of plasma cells in the spleen producing SRBC-specific antibody, while the ELISA measures SRBC-specific IgM antibody in the serum. Because these two assays measure different endpoints, there is a need for comparison of their sensitivity and reliability. The purpose of this project was to determine if these two assays are equally sensitive to suppression of the SRBC response in B6C3F1 female mice. Female B6C3F1 mice were given a single oral exposure to different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or four TCDD-like congeners. One week later, two sets of mice were immunized with SRBC. The first set was evaluated for the PFC response and the second for the ELISA response, on day 4 or 5 post-immunization, respectively. The four TCDD-like congeners tested were: 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,4,7-pentachlorodibenzofuran (4PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 2,3',4,4',5-pentachlrorbiphenyl (PCB118). The results were used to generate dose-response curves for the determination of the ED(50) for TCDD and each TCDD-like congener. For all chemicals tested, measuring the level of SRBC-specific IgM antibody by ELISA was more sensitive than the PFC assay to detect immunosuppression, as indicated by lower ED(50) values. These results indicate that the SRBC-specific IgM ELISA is a more sensitive assay for detecting the T-cell mediated immunotoxicity of dioxin-like chemicals in this rodent model.

Animals↗

Interstitial fibrosis of unilateral ureteral obstruction is exacerbated in kidneys of mice lacking the gene for inducible nitric oxide synthase.

Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function and increases in interstitial fibrosis. Previous studies have indicated that pharmacologic manipulations that increase nitric oxide (NO) are beneficial to the obstructed kidneys. NO is produced from arginine by nitric oxide synthase (NOS), an enzyme that exists in both constitutive and inducible (iNOS) forms. To determine the role of the inducible form of NOS in UUO, we used mice with a targeted deletion of iNOS (iNOS -/- mice) and compared them with wild-type (WT) mice. Kidneys were obstructed for 2 weeks in both WT and iNOS -/- mice, and were then removed and bisected. Half of the kidney was embedded in paraffin and tissue sections were examined for interstitial volume or the presence of macrophages. The remainder was flash-frozen and samples were used to measure tissue collagen (hydroxyproline) or transforming growth factor-beta (TGF-beta). This study demonstrates that both cortex and medulla of obstructed kidneys of iNOS -/- mice exhibit significantly increased interstitial volume and interstitial macrophages as compared with their WT counterparts. Furthermore tissue collagen was increased to 9.2+/-1.3 microg/mg tissue in WT obstructed kidneys, whereas in iNOS -/- kidneys, collagen was increased to 13.2+/-0.8 microg/mg tissue. The profibrotic cytokine TGF-beta was also significantly increased in obstructed kidneys of iNOS -/- mice, as compared with WT mice. No differences were noted between the unobstructed kidneys of iNOS -/- mice compared with WT mice in any of the parameters examined. These results demonstrate that targeted deletion of the iNOS results in exacerbation of fibrotic events in the obstructed kidney. These results confirm previous pharmacologic studies, and suggest that NO produced via the inducible NOS normally serves a protective function in UUO.

Animals↗

Trajectories of condylar points during nonworking side and protrusive movements of the mandible.

STATEMENT OF PROBLEM: During lateral excursive and protrusive jaw movements, condylar points are distant from any instantaneous rotational center. Therefore, it is likely that different condylar points would follow similar trajectories during these movements. PURPOSE: This study evaluated the effect of changes in condylar point location on trajectories of condylar points on the nonworking side and during a protrusive jaw movement and compared these changes with the effects described for open-close and working-side condylar movements in the same group of subjects. METHODS: The movements of 5 clinically determined condylar points were recorded in 44 subjects during a contralateral excursion and during protrusion (7 radiographically determined condylar points in 2 subjects). RESULTS: During any single jaw movement, the trajectory of each condylar point was similar in form and dimension to the other condylar points within that subject. CONCLUSION: Changes in condylar point location had little effect on the trajectories of condylar points on the nonworking side and during protrusive jaw movement.

Adult↗

Trajectories of condylar points during working-side excursive movements of the mandible.

STATEMENT OF PROBLEM: Trajectories of different condylar points provide different interpretations of condylar movement during open-close jaw movements. Movement of the working-side condyle is often assessed clinically by recording the trajectory of a single arbitrary condylar point. PURPOSE: This study examined the effect of the differences in condylar point location on condylar point movement trajectories during a working-side movement. METHODS: Different points exhibited different trajectories during a single working-side movement in each of 44 subjects. RESULTS: Up to 40% of a point's displacement could be attributed simply to the location of the point. CONCLUSIONS: Interpretation of condylar movement on the working side within a subject depends on the point chosen.

Adult↗

Quality of obturation in student cases instructed by endodontic versus general dentistry faculty.

Endodontic literature suggests that only about 60% of endodontic therapy meets current technical standards and that general dentists may be making a significant contribution to this compromised care. If so, where in the continuum of dental education does this begin. This study evaluated the quality of obturation in mandibular molars provided on the one hand by 3rd year dental students instructed by endodontic faculty, and on the other hand by 4th year students instructed by general dentistry faculty, versus the quality of obturation achieved by endodontic residents who served as a control for both groups. Final radiographs were chosen from students in all three groups so that there were 22 samples per group. Three evaluators rank-ordered the radiographs. In order of excellence, the results were: (a) residents, (b) 3rd year students, and (c) 4th year students. There was no significant difference between the 3rd year students or the residents, only between residents and 4th year students (p < 0.05). The reasons for this outcome may range from dental school objectives to the private practice procedures of the general dentists who instructed the 4th year students.

Analysis of Variance↗

The variability of condylar point pathways in open-close jaw movements.

STATEMENT OF PROBLEM: Clinical assessments of condylar movement often rely on the movement of a single clinically determined or average value condylar point. PURPOSE: The aim of this investigation was to study the effect of differences in condylar point location on recorded movement trajectories with an open-close jaw movement. METHODS: Recordings were made of the movements of various condylar points in 44 subjects. The points were identified clinically (average value points) and radiographically. RESULTS: The trajectory of each condylar point, whether average value or radiographically determined, was different in form and dimension from any other condylar point within a subject for the same open-close jaw movement. CONCLUSIONS: Depending on the point chosen in the vicinity of the condyle, quite different interpretations of condylar movement within a subject could be made. The data underscore the caution that must be exercised when interpreting condylar movement from the movement of a single condylar point.

Adult↗

The effect of posterior tooth guidance on non-working side arbitrary condylar point movement.

Occlusal form is frequently modified in clinical practice and yet we do not have detailed knowledge of the possible effects of these changes on condylar movement. The aim of this study was to quantify the effects of an alteration in the occlusion on condylar movement during a lateral excursive jaw movement. Posterior tooth guidances (i.e. metal overlays) were attached to both maxillary first molars. The movement of arbitrary condylar points on the non-working side was recorded in seven subjects during lateral excursion under natural tooth guidance (control) and was compared with that after placement of the overlays (guidance). The guidance resulted in statistically significant changes to the displacement of the arbitrary condylar points on the non-working side. For example, at a standardized (3 mm) displacement along the mid-incisor point trajectory during the lateral excursion for both control and guidance in all subjects, the corresponding displacements of the condylar points were statistically significantly decreased under the guidance situation in comparison with the control situation. These data suggest that, for the same magnitude of mandibular displacement during lateral excursion, the introduction of a posterior tooth guidance limits condylar displacement on the non-working side.

Adult↗

Risk factors associated with stress reactions in female Marines.

Women have a higher stress fracture rate than men in military studies, although the exact cause of this is not clear. Hyperpronation has been implicated as a potential risk factor for injury. In this prospective observational study, we measured subtalar joint range of motion in 101 women (ages 20-27 years) enrolled in Marine Corps Officer Candidate School in June 1994. The purpose of this study was to identify risk factors for injury in female Marine Corps officer candidates. The primary area of interest was the association between the amount of subtalar joint range of motion and stress reactions. Questionnaires were administered that explored previous physical activities, sports participation, and menstrual history. Anthropometric measurements were performed, including subtalar joint range of motion. During the 10 weeks of physical training, 11.5% of the women (N = 12) had stress reactions compared with 7% of the men (N = 10). There was no statistically significant difference in the means of subtalar joint range of motion in the stress reaction group compared with the non-stress reaction group. Differences in stress reaction rate across quartiles of subtalar joint range of motion were not significant. Those women who ran fewer miles (< or = 2.8 miles per session) before training had a higher rate of stress reactions (p < 0.04). Younger individuals (< 23 years) had a higher rate of stress reactions (p < 0.01). Women with fewer menstrual periods (< 10 per year) had a higher rate of stress reactions (p < 0.02). A narrow pelvis (< or = 26 cm) was associated with a higher rate of stress reactions (p < 0.09). We conclude that an increased subtalar joint range of motion is not a risk factor for stress reactions in women. However, further studies with a larger study population should be performed to confirm these findings.

Adult↗

Impact of working environments upon human-machine dialogues: a formal logic for the integrated specification of physical and cognitive ergonomic constraints on user interface design.

A range of techniques have been developed to improve the integration of computer systems into complex working environments. For instance, computer aided design tools can be used to simulate operators' posture at a particular workstation. Fitting studies can then be used to validate potential layouts. Unfortunately, few of these techniques can also be used to support the development of interactive dialogues. This is a critical problem for systems where designers must distribute application data amongst a number of different presentation devices. The position of these displays can be used to reflect the salience and priority of information. This paper presents techniques that support both user interface development and workstation layout. First order logic can be used to represent and reason about constraints on the design of human computer dialogues. The same formalism can also be used to identify appropriate locations for presentation devices within their working context; control rooms and offices. The findings of ergonomic studies can then be applied to analyze the mental and physical demands imposed by the interactive dialogues that are supported by particular devices. Unfortunately, formal specifications provide little impression of what it would be like to interact with a system within a particular environment. We have developed simulation tools to address this problem. Prototype displays can be presented within three dimensional models of their working context. The resulting simulations are directly derived from formal specifications and can be shown to members of concurrent design teams. They also provide a medium for communication with potential operators.

Computer Systems↗

Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier.

Interleukin-2 (IL-2) is reputed to cause a "vascular leak syndrome." We studied pulmonary hemodynamics and lymph dynamics in six sheep treated for 7 days with IL-2 (1.8 million IU/kg twice daily or 1.8 million IU/kg each day as a continuous infusion). Lung lymph flow increased from 4.8 +/- 2 ml/15 min pre-IL-2 to 14.4 +/- 6.8 ml/15 min on the seventh day of IL-2. The lymph-to-plasma protein concentration ratio was unchanged (0.70 +/- 0.06 vs. 0.63 +/- 0.13). The plasma-to-lymph equilibration half-time of radiolabeled albumin was 2.0 +/- 0.6 h pre-IL-2 and 1.0 +/- 0.7 h on day 7 of IL-2. Pulmonary arterial pressure was 24 +/- 7 cmH2O pre-IL-2, increased to 32 +/- 4 cmH2O on the fourth day of IL-2, and returned to 29 +/- 5 cmH2O on the seventh day of IL-2. Extravascular lung water was normal (4.07 +/- 0.25 g/g dry lung). To clearly determine whether the increase in lung lymph flow was due to hemodynamic changes or to increased leakiness of the microvascular barrier, we volume loaded six sheep with lactated Ringer solution before and after 3 days of IL-2 treatment (1.8 million IU/kg twice daily). Lung lymph flows increased fivefold during 4 h of crystalloid infusion compared with baseline and were higher after 3 days of IL-2. However, lymph-to-plasma protein concentration ratios decreased to the same low levels pre-and post IL-2 (0.39 +/- 0.06 vs. 0.41 +/- 0.10), indicating and intact microvascular barrier. Extravascular lung water was elevated (5.56 +/- 0.39 g/g dry lung) but was not different from lung water in three volume-loaded control sheep (4.87 +/- 0.53 g/G dry lung). We conclude that IL-2 causes minimal or no injury to the pulmonary microvascular barrier and that volume expansion during IL-2 treatment can cause hydrostatic pulmonary edema.

Animals↗

Effects of interleukin-2 on the pulmonary microvasculature in anesthetized sheep.

Interleukin-2 (IL-2) is reputed to cause pulmonary microvascular injury. We studied the pulmonary and splanchnic microcirculation of anesthetized sheep after one dose (1.8 x 10(6) IU/kg) of IL-2 (n = 9) and after six doses (1.8 x 10(6) IU.kg-1.dose-1) of IL-2 over 3 days (n = 9). Seven control sheep received only 5% dextrose diluent. We measured hemodynamics and lymph dynamics in anesthetized sheep after the final dose of IL-2 or diluent. After one dose of IL-2, caudal mediastinal node (mainly pulmonary) lymph flow was stable, whereas thoracic duct lymph flow increased from a baseline of 54 +/- 6 to 124 +/- 22 ml/h. After 3 days of IL-2, the caudal mediastinal node lymph flow increased from 7.7 +/- 5.5 to 19.0 +/- 14.8 ml/h 5-6 h after the final dose of IL-2, and thoracic duct lymph flow increased from 84 +/- 43 to 143 +/- 42 ml/h. The lymph-to-plasma protein concentration ratio increased after IL-2 for thoracic duct but not for caudal mediastinal node lymph. The equilibration rate of 125I-albumin from plasma to caudal mediastinal node lymph did not change, whereas plasma-to-thoracic duct lymph equilibration was faster after both one dose and 3 days of IL-2. Positron emission tomography showed no increase in the pulmonary transcapillary escape rate for 68Ga-labeled transferrin or in extravascular lung water (n = 4). We conclude that IL-2 at doses two to three times those used clinically does not significantly injure the pulmonary microcirculation of sheep.

Animals↗

The recording and analysis of EMG and jaw tracking. II. Reproducibility of jaw tracking.

In 10 male and 10 female adults jaw movements and muscle activity were monitored during chewing. Subjects had a Class I occlusion and fluent unrestricted jaw movements; non exhibited signs or symptoms of craniomandibular disorders. Recordings were made on two occasions separated by 2 weeks. Within each recording session the subjects carried out a number of tasks under direction, including eating nuts and gum. The jaw movements were monitored with a Sirognathograph which had been interfaced to a computer for data logging and analysis. A computer program identified each chewing stroke and after scrutiny a data base was constructed of measurements from a subset of 4447 suitable strokes. Mean values of 10 parameters selected to describe jaw movements during chewing were entered into an ANOVA. This indicated that the major contribution to variance was due to the subject from whom the data was recorded. This intersubject variability is well known, but can its separation from the other contributions to the variation within the data be assessed? To provide an estimate of the spread of data the variance for each parameter was calculated, transformed and these values entered into an analysis of variance. All subject differed significantly in their chewing movements from one another. But 15 of the 20 subjects showed a greater degree of consistency than the other five: they exhibited good inter- and intra-recording reproducibility. The food being eaten made a major contribution to the variability. The timing of the chewing strokes was also more consistent than the dimensions of the chewing envelope.

Adult↗