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C Johnson

Publications and source records attributed to C Johnson.

At least 73 records · Page 4Linked to original sources

NOX 100, a nitric oxide scavenger, enhances cardiac allograft survival and promotes long-term graft acceptance.

BACKGROUND: We examined the role of nitrosative stress in allograft destruction. METHODS: Rats undergoing cardiac transplants received NOX-100, a water-soluble nitric oxide (NO) scavenger with antioxidant properties, with or without low-dose cyclosporine (CsA). Graft survival, NO production, and nuclear factor kappa B (NF-kappaB) activity were studied. RESULT: Using NOX-100 daily until rejection prolonged graft survival (11.6+/-0.6 vs. 7.4+/-0.2 days; P<0.05). Daily low-dose CsA (2.5 mg/kg im) for 7 days or until rejection also prolonged survival (12.6+/-0.5 and 21.6+/-1.6 days, respectively; P<0.01 vs. Controls). Low-dose CsA for 7 days and NOX-100 for 30 days prolonged graft survival (45.0+/-4.7 days; P<0.01 vs. all groups.). NOX-100 had no effect on whole blood CsA levels. Combination therapy until Day 100 resulted in 1 graft loss at Day 116 and indefinite survival in 3 animals (>300 days), which accepted a second WF strain heart without further immunosuppressive therapy but promptly rejected a third party (ACI) cardiac allograft. NOX-100 and CsA reduced nitrate and nitrite, and combination therapy completely normalized NO through to Day 30. Electron paramagnetic resonance spectroscopic analysis demonstrated reduction of signals for nitrosylmyoglobin and nitrosyl-heme with NOX-100 and elimination of signals with CsA alone or combination therapy. Activity of myocardial NF-kappaB decreased with monotherapy vs. untreated allografts. Combination therapy resulted in further inhibition of NF-kappaB up to Day 30. The extent of graft survival correlated with the extent of NO scavenging and NF-kappaB inhibition. Short-term combination therapy had no effect on graft lymphocytic infiltrate on Days 15, 20, and 30. CONCLUSION: These data support a role for both oxidative and nitrosative stress in rejection and the immunoregulatory potential of antioxidant therapy after transplantation.

Animals↗

Maternal bone lead contribution to blood lead during and after pregnancy.

We examined bone lead contribution to blood lead in a group of 311 immigrant women, 99% from Latin America, during the third trimester of pregnancy and 1 to 2 months after delivery. We measured in vivo tibia and calcaneus (heel) bone lead concentration in the postdelivery period with K shell X-ray fluorescence. Prenatal and postnatal geometric mean (range) blood lead level was 2.2 microg/dL (0.4 to 38.7) and 2.8 microg/dL (0.4 to 25.4), reflecting low current exposure. Postnatal blood lead level was significantly higher than prenatal (P<0.0001). Mean (range) tibia and calcaneus lead concentration was 6.7 microg/g (-33.7 to 62.2) and 8.4 microg/g (- 30.1 to 66.4), reflecting varying but elevated past lead exposure. Mean calcaneus lead concentration was significantly higher than mean tibia lead concentration (P = 0.055). Variance-weighted multiple regression and structural equation models showed that both calcaneus and tibia lead were directly associated with prenatal blood lead but only calcaneus lead was associated with postnatal blood lead. Increasing natural log years in the United States independently predicted decreasing calcaneus and third-trimester blood lead. The data suggest that while some exogenous lead sources and modulators of blood lead level, such as use of lead-glazed pottery and calcium in the diet, control lead exposure during and after pregnancy, endogenous lead sources from past exposure before immigration continue to influence blood lead levels in this sample.

Adolescent↗

Characterization of a Bacillus thuringiensis delta-endotoxin which is toxic to insects in three orders.

We report here the first Bacillus thuringiensis (Bt) toxin which is toxic to insects from three insect orders (Diptera, Coleoptera, and Lepidoptera). An oligonucleotide probe based on the delta-endotoxin N-terminal sequence was used to detect the gene. A 23-kb BamHI fragment containing the intact gene was identified and cloned from Bt strain YBT-226 plasmid DNA into the vector pBluescript II. Through a series of DNA manipulations the size of this fragment was reduced and the gene sequenced. The deduced amino acid sequence gave a predicted molecular mass of 137 kDa and was identical to a cry1Ba protein from Bt subsp. thuringiensis HD-2, which is now designated as Cry1Ba1 under a new classification scheme. This protein also showed 81.6% similarity with the Cry1B protein (Cry1Bb1) from Bt strain EG 5847. When the YBT-226 cry1Ba1 gene was expressed in an acrystalliferous Bt subsp. israelensis strain it produced irregular bipyramidal crystals during sporulation, which reacted specifically with anti-Cry1Ba antiserum. Bioassays using these crystals after purification resulted in significant mortality at low to moderate concentrations to larvae of the house fly (Musca domestica, Diptera), cottonwood leaf beetle (Chrysomela scripta, Coleoptera), and tobacco hornworm (Manduca sexta, Lepidoptera). This broad-spectrum toxicity was not dependent on presolubilization. In assays with insect cell lines not derived from midgut cells, the soluble toxin killed CH1t (Manduca sexta cells) but was inactive against CF1 (Choristoneura fumiferana cells), Aa(s) (Aedes aegypti), and C2 (Culex quinquefasciatus) mosquito cells.

Bacillus thuringiensis↗

Office systems intervention to improve diethylstilbestrol screening in managed care.

OBJECTIVE: To examine the effectiveness of a comprehensive office systems intervention for improving identification of diethylstilbestrol (DES) exposure, a low-incidence condition with potentially severe consequences. METHODS: We developed a comprehensive office systems intervention to facilitate screening and follow-up for women exposed to DES in utero, consisting of a DES toolkit and the clinical and administrative education necessary to use the tools effectively. The intervention was implemented in the internal medicine and obstetrics-gynecology departments at six free-standing health centers in a Boston-area staff-model health maintenance organization. Intervention sites were matched and paired with a comparison group of centers. Intervention effectiveness was assessed through pretest and posttest surveys of clinicians, medical record review of 3900 women, and review of a computerized medical records data base. RESULTS: There was significantly higher DES awareness and knowledge among clinical staff at intervention sites. Documentation of DES exposure in the medical record ranged from 1.14 to 2.31 times greater at intervention sites than in matched comparison sites, and rates of DES code use in pregnancy were 1.91 to 3.61 times greater. CONCLUSIONS: The office systems intervention improved documentation of DES exposure in a managed care environment. Because this approach was designed to accommodate the limited time allotted for each patient visit, it not only improved DES screening but could also serve as a model for integrating screening for other low-prevalence but potentially serious conditions into routine care.

Adult↗

Pressure sores in children--the acute hospital perspective.

There is very little published literature on pressure sores in children and most of the existing literature is qualitative. Using literature from paediatric and adult studies, a schedule was designed to collect quantitative data on aspects that may predispose children to pressure injury. The schedule was piloted in an incidence and a prevalence study at the Royal Liverpool Children's NHS Trust. The sample size was 82 children for the incidence study and 183 children for the prevalence study. Six children in the incidence study and 12 children in the prevalence study sustained pressure injury. Data indicated that factors most strongly associated with pressure injury were nutritional status, mobility and consciousness level. Other factors that were implicated in increasing susceptibility to pressure injury were skin condition, body weight, haemodynamic status and hydration. Infants and young children most frequently sustained pressure injury on the occipital scalp area and heels. Although this was a small study, it produced some useful preliminary data, and was a valuable exercise to develop a tool for data collection on a larger scale.

Acute Disease↗

Pharmacokinetics of ropivacaine following caudal analgesia in children.

Ropivacaine has a favourable toxicity profile for epidural anaesthesia in adults, so it may also be an appropriate agent for epidural analgesia in children. We therefore designed this study to determine the pharmacokinetic variables of ropivacaine relevant to the risk of toxicity, after caudal administration in children. We studied nine healthy children, aged 1-6 years who received 1 ml.kg-1 of ropivacaine 0.25% for caudal analgesia. Venous blood samples were collected at intervals for 12 h after injection. Total plasma concentration of ropivacaine was assayed by high performance liquid chromatography, and pharmacokinetic descriptors were estimated from the plasma concentration-time data. The median peak venous plasma concentration was 799 microg.l-1 [interquartile range (IQR) 707-1044 microg.l-1], and was reached at a median time of 1.5 h (IQR 0.5-2 h). The mean elimination half-life was 3.9 h (95% CI 2.7-5.0 h), and the mean apparent clearance and volume of distribution were 7.6+/-1. 6 ml.min-1.kg-1 (95% CI 6.1-9.1 ml.min-1.kg-1) and 2.4+/-0.6 l.kg-1 (95% CI 1.9-3.0 l.kg-1), respectively. Analgesia was satisfactory in all cases and no systemic ropivacaine toxicity was observed. Caudal administration of weight-adjusted doses of ropivacaine to children resulted in systemic exposure similar to that reported for adults. No systemic toxicity was observed. The findings strengthen predictions that the relative systemic safety of epidural ropivacaine in adults will apply to children. However, the pharmacokinetics and safety of epidural ropivacaine need to be studied further in children with circumstances that affect drug disposition and systemic tolerance.

Adult↗

Measurement of blood flow in the vertebral artery using colour duplex Doppler ultrasound: establishment of the reliability of selected parameters.

This study was designed to determine the reliability of the ultrasound testing procedure for evaluating vertebral artery blood flow, and to determine a robust testing protocol for future studies. Blood flow parameters were tested in ten asymptomatic subjects (mean age 33 years, standard deviation 6 years 8 months) using colour duplex Doppler imaging. Volume flow rate data at C5-6 demonstrated good reliability from a single measurement (Intraclass correlation coefficient [ICC]=0.81). Peak velocity sampled at C1-2 showed poor reliability if a single measurement was used (ICC=0.26) improving to fair levels with three measurements (ICC=0.77). Reliability for this parameter was good if five measurements were taken (ICC=0.83-0.84). Systolic/diastolic ratio measured at C5-6 showed poor reliability (ICC=0.57) if a single measurement was taken in the manner of Thiel et al. (1994). This improved to fair reliability (ICC=0.75) if the mean of three measurements was used. There was no further improvement if five measures were sampled. Sampling at C2-3 in the manner of Refshauge (1994) was found to be technically difficult and it was not possible to detect a Doppler shift in three of the ten subjects at this level. Reliability of peak velocity at C2-3 was found to be poor, regardless of whether single or multiple averaged measurements were taken (ICC=0.37-0.63). Mean (time averaged) velocity measurements at C2-3 showed poor reliability if a single measurement was taken (ICC=0.39), fair reliability if the first three measurements were averaged (ICC=0.73) and good to high reliability levels if five measurements were sampled (ICC=0.88-0.91). A review of the literature suggests that sampling volume flow rate at C5-6 and peak velocity at C1-2 represents a clinically meaningful combination of parameters to detect narrowing in the VA. The results of this current study indicate the desirability of taking a single measurement of volume flow rate at C5-6 and the mean of three measurements of peak velocity at C1-2, with the additional calculation of the standard error of measurement, if reliable results are to be achieved.

Adult↗

Relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 overexpression in Barrett metaplasia.

BACKGROUND: There is a need for molecular markers of malignant progression in Barrett metaplasia (BM). The aim of this study is to determine the relationship between dysplasia, p53 protein accumulation, DNA ploidy, and Glut1 in BM. METHODS: Sections of esophageal biopsy specimens from 120 patients with BM were evaluated for dysplasia, p53 protein, and Glut1 expression by immunohistochemistry, and DNA ploidy by Feulgen stain and image analysis. In cases with diploid DNA histograms, the percentage cells in the G0G1 and G2M phases of the cell cycle were determined. RESULTS: Of 108 diploid cases 19 (28%) of 69 cases with G0G1 > or = 90% or G2M > or = 8.33% were p53-positive, in contrast to only 1 (3%) of 39 cases with lower G0G1 or G2M (P = 0.0008). Of 32 p53-positive cases 11 (32%) were aneuploid, in contrast to none (0%) of 88 p53-negative cases (P < 0.0001). Ten (91%) of 11 aneuploid cases were high-grade dysplasial adenocarcinoma (HGD/CA), compared with only 1 (1%) of 109 diploid cases (P < 0.0001). Five (45%) of 11 cases with HGD/CA were Glut1-positive, in contrast to none (0%) of 109 cases without HGD/CA (P < 0.0001). CONCLUSIONS: Our data strongly suggest that in BM, after oxidative DNA damage, as a result of gastroesophageal reflux, there is an increase in the percentage of cells in the G0G1 or G2M phases of the cell cycle to enable repair of damaged DNA; in some of these cases this is followed sequentially by p53 gene mutation and protein accumulation, DNA aneuploidy, HGD, and CA with or without Glut1 overexpression. These events can be detected in routinely processed biopsy samples.

Adenocarcinoma↗

Symptom severity and oesophageal chemosensitivity to acid in older and young patients with gastro-oesophageal reflux.

INTRODUCTION: elderly patients appear to have a more aggressive form of gastro-oesophageal reflux disease than younger patients. Reduced pain perception with age is a possible underlying mechanism. AIMS: to compare the extent of oesophageal mucosal injury, acid exposure, symptom severity and perception thresholds for acid infusion in older (aged 60 or older) and younger patients with gastro-oesophageal reflux. METHODS: twenty-five younger and 23 older patients completed the study. We determined acid exposure and oesophageal mucosal injury by ambulatory 24-h oesophageal pH monitoring and upper endoscopy, respectively. We determined chemosensitivity by infusing 0.1 N hydrochloric acid into the mid-oesophagus for 10 min at 10 ml/min after a 2-min infusion of normal saline at a similar rate. We quantified acid perception thresholds by the lag time to initial typical symptom perception, intensity rating at the end of acid infusion and an acid perfusion sensitivity score, calculated from the fractional duration of symptom perception and intensity rating. RESULTS: mean percentage of total time with pH <4 was higher in the older (15.8+/-2.4) than in the younger patients (11.9+/-1.8; P = 0.18). Of the older group, 74% had erosive oesophagitis versus 64% in the younger group. Frequency of symptoms (heartburn, acid regurgitation and dysphagia) was lower in the elderly group. Older patients perceived heartburn and acid regurgitation as much less severe than younger patients (P < 0.05).Younger patients had a significantly shorter lag time to initial symptom perception (P < 0.05) and a higher sensory intensity rating (P < 0.08). The acid perfusion sensitivity score was significantly lower in the older group (P < 0.05). CONCLUSIONS: older patients with gastro-oesophageal reflux disease have reduced symptom severity for heartburn despite a tendency towards increased severity of oesophageal mucosal injury and acid exposure. Age-related reduction in chemosensitivity to acid is a possible underlying mechanism.

Adult↗

A guide to choosing technology to support the measurement of patient outcomes.

Personal computers, scanning systems, and hand-held computing devices are the latest tools being used to support the management of patient outcomes. Nurse executives can choose technologies needed to place nurses at the fore of multidisciplinary groups charged with improving the quality and cost-effectiveness of patient care. The authors review three types of patient data management technologies and answer questions executives may have in selecting systems for their departments.

Anticoagulants↗

Unifying organizational approaches to measuring and managing patient outcomes.

Information about patient outcomes is increasingly available to guide consumers in their selection of healthcare. By unifying the traditionally separate programs of performance improvement, case management, and research, nurse executives can take control of care processes and outcomes. This article provides four case examples of patient care improvements achieved using performance improvement, case management, and research approaches. The use of the technologies outlined in the Johnson and Nolan article in this issue, "A Guide to Choosing Technology to Support the Measurement of Patient Outcomes", also is described.

Anticoagulants↗

Fluorescence and 19F NMR evidence that phenylalanine, 3-L-fluorophenylalanine and 4-L-fluorophenylalanine bind to the L-leucine specific receptor of Escherichia coli.

The binding capacity of the L-leucine receptor from Escherichia coli was measured with L-phenylalanine and 4-fluoro-L-phenylalanine as substrates by fluorescence. The apparent dissociation constants (KD) for L-leucine, L-phenylalanine, and 4-fluoro-L-phenylalanine are 0.40, 0.18, and 0.26 respectively. 19F NMR data show protein-induced shifts for the 4-fluoro-L-phenylalanine peak and 3-fluoro-L-phenylalanine when receptor is present. Evidence points to the binding of only the L-isomers of these fluorine analogs.

Escherichia coli↗

Lead-field bases for electroencephalography source imaging.

In recent years, significant progress has been made in the area of electroencephalography (EEG) source imaging. Source localization on simple spherical models has become increasingly efficient, with consistently reported accuracy of within 5 mm. In contrast, source localization on realistic head models remains slow, with subcentimeter accuracy being the exception rather than the norm. A primary reason for this discrepancy is that most source imaging techniques are based on lead fields. While the lead field for simplified geometries can be easily computed analytically, an efficient method for computing realistic domain lead fields has, until now, remained elusive. In this paper, we propose two efficient methods for computing realistic EEG lead-field bases: the first is element oriented and the second is node oriented. We compare these two bases, discuss how they can be used to apply recent source imaging methods to realistic models, and report timings for constructing the bases.

Biomedical Engineering↗

Use of clindamycin disks To detect macrolide resistance mediated by ermB and mefE in Streptococcus pneumoniae isolates from adults and children.

We studied 198 macrolide-resistant S. pneumoniae isolates obtained from adults and children to evaluate whether 2-microgram clindamycin disks can distinguish between isolates manifesting ermB- versus mefE-mediated resistance to clarithromycin and to determine the relative frequency with which each resistance mechanism occurred in these populations. The mefE gene was predominant among 109 isolates from children, occurring in 73.4% versus 50.6% of 89 isolates from adults. Three isolates (1.5%) did not amplify either gene. Among 125 mefE(+) isolates, the MIC of clarithromycin at which 90% of the isolates tested were inhibited, determined by Etest, was 32 microgram/ml versus >256 microgram/ml in 70 ermB(+) isolates. All ermB(+) isolates were highly resistant to clindamycin (MICs >256 microgram/ml), whereas all mefE(+) isolates were susceptible to clindamycin using the 2-microgram disk. Testing S. pneumoniae from the respiratory tract for susceptibility to clindamycin by agar disk diffusion is an easy and inexpensive method to estimate the frequency of resistance mediated by ermB in specific patient populations. Macrolide resistance mediated by ermB is usually of greater magnitude than that due to mefE. Clinical studies are needed to determine the significance of high- versus low-level macrolide resistance in S. pneumoniae.

Adult↗

Reduced concentrations of thalamic N-acetylaspartate in male patients with schizophrenia.

OBJECTIVE: The authors measured N-acetylaspartate (a putative neuronal marker) in the right and left thalamus of 17 male patients with schizophrenia using in vivo proton magnetic resonance spectroscopic imaging ((1)H MRSI). METHOD: (1)H MRSI was performed on 17 medicated male patients with schizophrenia and 10 male comparison subjects. Concentrations of N-acetylaspartate, creatine, and choline were determined in the thalamic regions bilaterally. RESULTS: The patients with schizophrenia demonstrated significantly lower concentrations of N-acetylaspartate than the comparison subjects in both the right and left thalamic regions. Right thalamic N-acetylaspartate and left thalamic N-acetylaspartate were significantly correlated in the patients but not in the comparison subjects. There was no association between N-acetylaspartate and duration of illness or medication dose. No group differences or lateralized asymmetries in choline or creatine were noted. CONCLUSIONS: The finding of reduced concentrations of N-acetylaspartate bilaterally suggests neuronal dysfunction and/or loss in both the right and left thalamic regions in male patients with schizophrenia.

Adult↗

Sustained swimming at low velocity following a bout of exhaustive exercise enhances metabolic recovery in rainbow trout.

Sustained swimming at 0.9 BL s(-)(1), where BL is fork body length, following a bout of exhaustive exercise enhanced recovery of metabolite and acid-base status in rainbow trout compared with fish held in still water. The most striking effect of an active recovery was a total absence of the elevation cortisol concentration typically associated with exhaustive exercise. In fish swimming at 0. 9 BL s(-)(1), plasma cortisol levels averaged 20-25 ng ml(-)(1) throughout the 6 h recovery period. In contrast, plasma cortisol increased to a peak level of 128.4+/-11.2 ng ml(-)(1) (mean +/- s.e. m., N=6) in fish recovering in still water. Muscle glycogen was completely resynthesized and lactate cleared within 2 h of exercise in swimming fish compared with more than 6 h required in the fish held in still water. Similarly, blood lactate level and acid-base status were restored more quickly in the swimming fish. These observations suggest that the prolonged recovery usually associated with exhaustive exercise in rainbow trout is due to elevations in plasma cortisol concentration and that the stimulus for cortisol release is not exercise per se, but rather post-exercise inactivity.

Acid-Base Equilibrium↗

Social categorization and stereotyping: 'You mean I'm one of "them"?'.

What happens when people discover that they are members of a group about which they have previously formed some stereotype? To address this question, procedures previously shown to induce negative stereotypes of minority groups were combined with a social categorization manipulation. Participants in a distinctiveness-based illusory correlation paradigm (Hamilton & Gifford, 1976) either knew nothing about their group membership, or learned that they were a member of the minority group or the majority group either before or after being presented the stereotype-engendering stimulus materials. Results revealed that social categorization into the minority group before stimulus presentation eliminated the perceived stereotype and reversed the evaluative bias, whereas social categorization into the minority group after stimulus presentation had no effect on the perceived stereotype and only a weak effect in reducing the evaluative bias. Social categorization into the majority group either before or after stimulus presentation had little effect on the perceived stereotype and evaluative bias. These results clarify the process underlying the influence of social categorization on stereotype formation, underscore the distinction between affective and cognitive influences on stereotype formation and stereotype change, and offer insights into 'autostereotyping' among members of minority groups.

Humans↗