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G Johnson

Publications and source records attributed to G Johnson.

At least 163 records · Page 9Linked to original sources

A method of estimating the numbers of human and mouse immunoglobulin V-genes.

Mutations in immunoglobulin V-genes can be due to gene multiplication, allelic variations, mutations induced by antigens or somatic mutations, etc., and various combinations of these. Since the number of different mouse lambda light V-gene nucleotide sequences is relatively small, a pairwise comparison between these sequences can provide a rough idea as to the contributions of the above mechanisms to the number of nucleotide differences between sequences. A plot of occurrences against the number of differences suggests that differences between one to five can be attributed to somatic mutations. Six to 12 differences can be allelic. Thirteen to 17 may be due to allelic variations together with somatic mutations. Differences > 17 appear to be derived from gene multiplication. Although these numbers are most likely somewhat different in humans, they can nevertheless provide a rough guide to sort out the effect of gene multiplication. Estimations of human heavy, kappa and lambda light chain immunoglobulin V-genes are in reasonably good agreement with recent experimental studies. For mouse kappa light and heavy chains, our estimations can provide some insight to future analyses by direct sequencing of these gene segments.

Animals↗

Paramedic use of nalbuphine in major injury.

Paramedic training and skills have been introduced in the United Kingdom in an attempt to improve prehospital patient care. There is presently little control and quality assurance in this potentially difficult environment and paramedic protocols have not been validated. We studied the use of nalbuphine by paramedics for patients with major injury in West Yorkshire. A case-control study was carried out using two cohorts of patients from the regional Major Trauma Outcome Study (MTOS) database; one group had received prehospital nalbuphine by paramedics (the intervention) and a matched group who had not (the control). Both groups of patients were reviewed by a panel of three consultants and a paramedic to assess which patients received or could have received nalbuphine appropriately. Only 85 patients from a database of 4170 patients received nalbuphine. Fifty-two (61%) patients were thought by the panel to have been given nalbuphine appropriately. The panel also concluded that 21 (18%) of the 115 patient control group could have been administered nalbuphine but did not receive the drug. This study demonstrates inadequate and sometimes inappropriate use of nalbuphine in prehospital trauma care. Quality assurance and audit systems should be implemented to identify and correct these deficiencies.

Adolescent↗

Effects of biologically modified surfaces of synthetic lenticules on corneal epithelialization in vivo.

PURPOSE: The present study investigated the association of extracellular matrix (ECM) glycoprotein coatings with initial epithelialization of artificial lenticules in vivo. METHODS: Collagen I, collagen IV, ECM and fibronectin were individually coated onto the surface of polycarbonate membranes. The membranes were then implanted in the anterior stroma of adult cats and were clinically assessed for rapidity and extent of epithelialization and the persistence of epithelial attachment. RESULTS/CONCLUSIONS: It was demonstrated that membrane surfaces modified by collagen I, collagen IV and ECM consistently supported initial migration and attachment of corneal epithelial cells and that the surface modified with collagen I performed best.

Animals↗

Malignant sustained ventricular tachyarrhythmias in women: characteristics and outcome of treatment with an implantable cardioverter defibrillator.

Clinical rhythm, heart disease, ejection fraction, defibrillation threshold, recurrent arrhythmias, and mortality were compared in 268 consecutive recipients (213 men and 55 women) of their first implantable cardioverter defibrillator for life-threatening ventricular tachycardia or fibrillation. Women were younger than men, less likely to have structural heart disease, and more likely to have clinical ventricular fibrillation, a higher ejection fraction, and a lower defibrillation threshold. Complications of defibrillator placement were similar in both sexes. Unadjusted survival tended to be higher in women than in men (97% vs 90%, respectively, at 2 years, P = 0.08), largely due to fewer deaths from noncardiac causes or cardiac causes other than arrhythmia (P = 0.04). Women also tended to be at lower, albeit still substantial, risk for recurrent arrhythmias during follow-up (37% vs 52% in men at 2 years, P = 0.11). After adjustment for baseline differences, overall survival, arrhythmia death-free survival, nonarrhythmia death-free survival, and frequency of recurrent arrhythmias were not found to be gender related. Despite their apparent "lower risk" status on initial presentation, women remained at substantial risk for recurrent arrhythmias. This underscores the need to avoid being unduly biased by the "appearance" of health in managing women with malignant arrhythmias. That survival and other clinical endpoints were all ultimately independent of gender emphasizes the importance of other clinical variables in assessing risk from ventricular tachyarrhythmias.

Adult↗

Genetic and phenotypic analysis of the genes of the elbow-no-ocelli region of chromosome 2L of Drosophila melanogaster.

The elbow locus is found to be two genes elA and elB, each of which has a distinct phenotype when mutant. Mutations of the elA gene have a strong phenotype where the wing is markedly disrupted. Mutations of elB are weak, mainly affecting the alula and the wing bristles. The two genes are dominant enhancers of each other. Homozygous deletion of the complete elbow region results in lethality. Situated between the elbow genes is the pupal gene and a locus which when deleted causes a crippled leg phenotype. This locus may be a control region for elbow. Immediately adjacent on the proximal side of elA is the no-ocelli locus. The phenotypes of noc alleles vary from extreme, where the ocelli and associated bristles are absent, to weak where these structures are disrupted. The various noc phenotypes are associated with genetically distinct gene regions, mutations of which act as enhancers of each other. Alleles of el and noc show partial failure of complementation, heterozygotes having weak el or weak noc phenotypes. Alleles of both these genes interact with the antimorphic noc allele Sco.

Alleles↗

Higher specialist training in accident and emergency medicine--past, present and future.

OBJECTIVE: To assess the quality of accident and emergency (A&E) medicine higher specialist training as perceived by current trainees and those who have recently completed training. METHODS: Postal questionnaires to three groups of A&E specialists either currently in training or having recently completed training. RESULTS: Levels of satisfaction were generally high. Previously identified deficiencies in management training remained and the implementation of guidelines regarding formative assessment and time for study and research was inconsistent. CONCLUSIONS: While clinical training is largely satisfactory, areas where higher specialist training could be improved have been identified. Continued development is necessary to meet the challenges of the new specialist registrar grade and opportunities and threats to training in the future are proposed and discussed.

Curriculum↗

Medical involvement in prehospital care--a transatlantic comparison.

The role of doctors in prehospital care in the United Kingdom and the USA was compared using information obtained from a visit to the city of Houston emergency medical service (Houston, Texas) and from a review of published reports. The involvement of full time specialist emergency medical services physicians has been crucial to the development of improved standards of practice within American prehospital care. The specialty of accident and emergency medicine should support provision of medical advice to the ambulance services by closer liaison with ambulance service trusts and the formalisation of training in prehospital care to specialist registrars.

Emergency Medical Services↗

Suppression of venous signal in time-of-flight MR angiography of the lower extremities after administration of gadopentetate dimeglumine.

PURPOSE: To evaluate a magnetic resonance (MR) angiography time-of-flight technique that can effectively suppress venous signal after gadopentetate dimeglumine administration. MATERIALS AND METHODS: Twelve adult patients underwent MR angiography for the evaluation of peripheral vascular disease. Gradient-echo sequences were performed after the administration of 0.2 mmol/kg gadopentetate dimeglumine. Three sequences were compared: a nontriggered sequence; a gap sequence, an electrocardiographically triggered, segmented sequence with a 7-mm gap between saturation and imaging sections; and a no-gap sequence, a similar sequence as gap but with partially overlapping imaging and saturation sections. For each sequence, identical regions of interest were generated for arterial, venous, and background muscle tissue and noise. A paired Student t test was used to compare the signal-to-noise and contrast-to-noise ratios (C/Ns) among the sequences. In seven patients, the no-gap sequence was used to acquire MR angiograms of the distal lower extremities. RESULTS: The mean artery-muscle C/N was similar for the triggered sequences; both were statistically significantly greater than the ratios for the nontriggered sequence. Venous suppression was much better with the no-gap sequence. Overall, the best artery-vein C/N was also obtained with the no-gap sequence. MR angiograms with effective venous suppression could be obtained only with the no-gap sequence. CONCLUSION: Time-of-flight MR angiograms can be obtained with effective venous suppression after the administration of 0.2 mmol/kg gadopentetate dimeglumine.

Aged↗

Peripheral vascular disease evaluated with reduced-dose gadolinium-enhanced MR angiography.

PURPOSE: To demonstrate the utility of low-dose gadolinium-enhanced magnetic resonance (MR) angiography of two consecutive anatomic areas for assessment of peripheral vascular disease. MATERIALS AND METHODS: Fifteen patients underwent gadolinium-enhanced MR angiography for evaluation of lower extremity peripheral vascular disease after conventional digital subtraction angiography (DSA). MR angiography was performed with three-dimensional coronal gradient-echo acquisitions before and during administration of gadopentetate dimeglumine. Two separate, contiguous areas were studied with separate doses of 0.075 and 0.1 mmol/kg gadopentetate dimeglumine. MR angiography findings were compared with DSA findings; DSA was the standard of reference. Treatment options were determined first with MR angiograms and then with DSA images. RESULTS: For distinguishing greater than 50% stenosis from 50% or less stenosis, gadolinium-enhanced MR angiography yielded a sensitivity of 97%, a specificity of 96%, and an accuracy of 97%. In 146 (97%) of 150 anatomic segments, there was essential or total agreement on treatments determined with MR angiography and DSA. In two cases (one case of vascular stent placement and one case of surgical anastomosis), extent of disease was overestimated with MR angiography. The MR study of one infrapopliteal area was insufficient for evaluation. CONCLUSION: Accurate gadolinium-enhanced MR angiography of multiple peripheral vascular areas of the lower extremities can be performed in most patients with less than 0.2 mmol/kg contrast material.

Aged↗

A review of the use of augmentation therapy for the treatment of resistant depression: implications for the clinician.

OBJECTIVE: To critically review the literature on augmentation therapy in resistant depression in order to assist the clinician to make a reasoned choice. Augmentation therapy is defined as the addition of a second agent to an existing antidepressant regimen with the aim of achieving improved clinical response. METHOD: The available literature which related specifically to currently popular augmentation strategies in treatment resistant depression for the past 20 years was examined. The scientific evidence supporting the efficacy of these regimens and their safety was reviewed. RESULTS: Considerable research on lithium augmentation has been undertaken, and on triiodothyronine augmentation to a lesser degree. A number of other drugs have been trialed as augmentation agents with claims of success; however, most of the evidence supporting these agents is anecdotal and in the form of case reports. There are very few well-performed double-blind placebo-controlled studies of augmentation therapy. CONCLUSIONS: Because of possible complex pharmacodynamic and pharmacokinetic interactions, augmentation therapy is not without its potential complications. Lithium augmentation of tricyclic antidepressants can be recommended as a safe and effective strategy and there is a body of scientific evidence supporting the addition of T3 as an effective augmentation agent. Recent research with pindolol augmentation of selective serotonin re-uptake inhibitors (SSRIs) is encouraging, but these findings require replication. There is no empirical evidence supporting buspirone, carbamazepine, sodium valproate, methylphenidate or amphetamine as effective augmentation agents, or that adding a tricyclic to a SSRI has usefulness in relieving depressive symptoms. There is a need for considerable research in this area, with more prospective well-controlled placebo studies.

Antidepressive Agents↗

Interaction of technetium-99m-N-NOET with blood elements: potential mechanism of myocardial redistribution.

UNLABELLED: Technetium-99m-N-NOET is a new 99mTc-labeled, neutral cardiac perfusion imaging agent which has been shown to undergo apparent redistribution in animal models and in humans. The purpose of this study was to investigate the interaction of 99mTcN-NOET with red blood cells (RBCs) and to determine the effects of these interactions on myocardial uptake and clearance of 99mTcN-NOET. METHODS: After bolus administration, myocardial 99mTcN-NOET clearance was monitored for 1 hr using a sodium iodide detector in 22 isolated, buffer-perfused rat hearts. Hearts were perfused as follows: seven controls with Krebs-Henseleit (KH) buffer (Group 1), five hearts with KH containing RBCs (Group 2), five hearts with KH containing RBCs and albumin (Group 3), five hearts with KH containing RBCs and dextran (Group 4). In a separate protocol, RBCs were incubated in 99mTcN-NOET and then perfused through five hearts (Group 5). RESULTS: Technetium-99m-N-NOET myocardial uptake (%ID) was significantly lower in all RBC groups (RBCs = 5.0% +/- 1.7%; RBCs + albumin = 8.2% +/- 2.1%; RBCs + dextran = 4.0% +/- 0.8%; incubated RBCs = 8.8% +/- 1.5%) compared with controls (72.2% +/- 2.8%; p < 0.05). Retention (99.4% +/- 0.6%) was near linear in the KH control group with virtually no fractional clearance at 60 min. Retention in groups whose perfusates contained RBCs (RBCs = 62.2 +/- 4.2%; RBCs + albumin = 29.9 +/- 4.3%; RBCs + dextran = 69.3 +/- 3.6%) were all significantly lower than control. Addition of albumin to RBC perfusate resulted in significantly lower retention (29.9% +/- 4.3%; p < 0.01) than was observed in RBC perfusate alone (62.2% +/- 4.2%). Substitution of dextran for albumin produced retention similar to RBCs alone (69.3% +/- 3.6%; p = ns). In a separate protocol, RBC binding of 99mTcN-NOET was high (64.4% +/- 8.6%) in triple-washed RBCs. Technetium-99m-N-NOET bound to RBCs was subsequently extracted from red cells by the myocardium when those cells were infused into hearts. CONCLUSION: Technetium-99m-N-NOET has high binding affinity to blood elements and transfers bidirectionally between myocardium and blood. The interaction of 99mTcN-NOET with blood elements represents a potential mechanism of redistribution.

Animals↗

Kinetics of technetium-99m-teboroxime in reperfused nonviable myocardium.

UNLABELLED: This study evaluates 99mTc-teboroxime uptake and clearance kinetics in reperfused infarcted myocardium. METHODS: In 47 isolated buffer perfused rat hearts, 17 had normal flow (Control), 13 had 30 min of no flow followed by reflow (Noflow30) and 11 had 60 min of no flow followed by reflow (Noflow60). A 1-hr uptake phase was begun by normally perfusing all 41 hearts with 99mTc-teboroxime-doped buffer. After uptake, a 1-hr clearance phase was begun by switching to a 99mTc-teboroxime-free buffer. Technetium-99m activity was monitored with a Nal probe. Triton X-100, a membrane detergent, was given after tracer loading to six additional hearts. RESULTS: Control and Noflow30 hearts showed near linear and rapid uptake, while Noflow60 hearts showed curvilinear and significantly less uptake than predicted. All three of these groups showed biexponential clearance. Early t1/2 was not significantly different for the three groups (Control = 6.3 +/- 1.9 sem min, Noflow30 = 5.4 +/- 1.3 min, Noflow60 = 8.9 +/- 2.8 min). Late t1/2 was significantly shorter for Noflow30 (52.3 +/- 5.3 min) and the Noflow60 (50.9 +/- 4.3 min), compared to the Control hearts (74.1 +/- 6.6 min, p < 0.05). One-hour fractional clearances were significantly greater for the Noflow30 and Noflow60 hearts (0.65 +/- 0.01 and 0.65 +/- 0.01, respectively) compared to the Controls (0.55 +/- 0.01, p < 0.05). In hearts given Triton X-100, there was a markedly increased fractional clearance of 0.96 +/- 0.01 (p < 0.01 compared to Controls). Electron microscopy showed evidence of mild injury in the Noflow30 hearts, more extensive damage in the Noflow60 hearts and severe irreversible injury in Triton X-100 hearts. CONCLUSION: Myocardial 99mTc-teboroxime uptake and clearance kinetics are significantly altered in mildly and moderately injured reperfused myocardium. Technetium-99m-teboroxime clearance is markedly accelerated in the setting of overt damage to cell and organelle membranes induced by Triton X-100.

Analysis of Variance↗

Blood phosphatidylethanol as a marker of alcohol abuse: levels in alcoholic males during withdrawal.

Phosphatidylethanol (PEth) is formed only in the presence of ethanol, via the action of phospholipase D. We studied PEth in blood as a possible marker of alcohol abuse in 15 male alcoholics admitted for detoxification. Blood was drawn on the first day after admission and up to 28 days thereafter. PEth in whole blood was 13.2 +/- 2.2 mumol liter-1 (mean +/- SE) at first sampling and remained detectable up to 14 days after admission. Blood ethanol was 0 on the morning after admission. The time courses of PEth disappearance varied among individuals. No PEth could be found in blood of control persons who had abstained from ethanol for 4 days. Levels of PEth and carbohydrate-deficient transferrin or gamma-glutamyltranspeptidase did not correlate. Its high specificity and prolonged detectability suggest PEth in blood as a marker of recent alcohol abuse.

Adult↗

Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT)

OBJECTIVES: This analysis sought to evaluate the clinical characteristics and outcome in heart failure with mild systolic dysfunction. BACKGROUND: Although heart failure with mild systolic dysfunction occurs commonly, this is an understudied area because clinical trials have usually excluded patients with ejection fraction >35%. METHODS: The 422 patients with left ventricular ejection fraction </=35% were compared with 172 with a left ventricular ejection fraction >35% in the Vasodilator in Heart Failure Trial (V-HeFT I), whereas in V-HeFT-II 554 patients with a left ventricular ejection fraction </=35% were compared with 218 patients with a left ventricular ejection fraction >35% for mortality and clinical care. For a left ventricular ejection fraction >35%, treatment with hydralazine/isosorbide dinitrate was compared with prazosin and placebo therapy in V-HeFT I, and hydralazine/isosorbide dinitrate was compared with enalapril in V-HeFT II for mortality, clinical course and change in physiologic variables: ejection fraction, plasma norepinephrine levels, ventricular tachycardia and echocardiographic variables. RESULTS: In both studies, patients with a left ventricular ejection fraction >35% differed principally in hypertensive history, higher functional capacity and radiographic and echocardiographic cardiac dimension from patients with a left ventricular ejection fraction </=35%, and plasma norepinephrine levels differed in V-HeFT II (p < 0.01). Patients with a left ventricular ejection fraction >35% had a lower cumulative mortality than those with a left ventricular ejection fraction </=35% (p < 0.0001) and less frequent hospital admissions for heart failure (p < 0.014, V-HeFT I; p < 0.005, V-HeFT II). Although cumulative mortality and morbidity did not differ between treatment groups in V-HeFT I, enalapril decreased overall mortality versus hydralazine/isosorbide dinitrate (p < 0.035) in V-HeFT II. For physiologic variables in V-HeFT II, enalapril decreased ventricular tachycardia at follow-up (p < 0.05). CONCLUSIONS: In V-HeFT, heart failure with mild systolic dysfunction was associated with different characteristics and a more favorable prognosis than heart failure with more severe systolic dysfunction. Enalapril decreased overall mortality and sudden death compared with hydralazine/isosorbide dinitrate. Prospective trials are needed to address therapy for heart failure with mild systolic dysfunction.

Aged↗

A comparison of phase encoding ordering schemes in T2-weighted GRASE imaging.

Gradient and spin echo (GRASE) imaging is an echo train imaging sequence that combines gradient and RF refocusing. This combination introduces phase modulations into the echo train. If the phase encoding order is linear with echo time, these modulations cause severe ghosting artifacts. Changing the order of phase encoding can greatly reduce these artifacts. Several phase encoding orders for T2-weighted sequences are compared in this paper, linear, partially randomized, standard GRASE ordering, and k-banded (kb) GRASE ordering. Different possible implementations of GRASE and kbGRASE are also considered. Computer simulation is used to compare resolution and artifact levels. Phantom and volunteer images are presented. The linear order is most sensitive to ghosting artifacts associated with chemical shift, susceptibility differences and static field inhomogeneities. The standard GRASE order is least sensitive to these but most vulnerable to artifacts associated with short T2 signals, kb-GRASE is a good intermediate between linear and standard GRASE and generally shows the lowest artifact levels. The partially randomized order gives the most diffuse artifacts. Computer simulations show that spatial resolution and contrast with all phase encoding orders are similar.

Artifacts↗

Developmental effects of fumonisin B1 in mice.

Developmental and toxic effects of aqueous extracts of F. moniliforme culture material containing known levels of fumonisin B1 were recently reported in mice and included maternal hepatotoxicity and lethality, maternal body weight gain reduction, increased embryonic resorptions, reduced offspring body weights, and fetal malformations including cleft palate, hydrocephalus, malformed ribs and incomplete digital and sternal ossification. These studies also suggested that the effects of the fungal extract on the mouse offspring may be mediated via maternal effects. The contribution of fumonisin B1 (FB1), a major toxic metabolite of F. moniliforme, in the induction of these effects was evaluated in this study by administering 0 to 100 mg pure FB1/kg of body weight on gestational days (GD) 7 through 15 to pregnant Charles River CD1 mice and assessing maternal health and fetal development till the end of gestation. Doses of 25 mg/kg or higher of pure FB1 induced maternal liver lesions (mostly necrotic changes), associated with ascites and increased hepatocytic nuclear diameter. Fumonisin doses of 50 mg/kg or higher also resulted in significantly increased maternal ALT on GD12, and reduced offspring bodyweights on GD18. Increased resorptions and decreased numbers of live offspring were only evident at 100 mg FB1/kg body weight. Offspring exhibited dose-dependent increase in the incidence and severity of hydrocephalus of both the lateral and third ventricles at doses of 25 mg/kg or higher. Doses of 25 mg/kg or higher also increased the sphinganine/sphingosine (Sa/So) ratios in maternal but not fetal livers. These results suggest that FB1 may be a developmental toxicant accounting for most but not all earlier reported effects of F. moniliforme culture extract. Association of FB1 effects on the offspring with maternal hepatoxicity and with alteration of Sa/So ratio in maternal but not fetal liver supported the earlier claim that FB1 effects on the mouse offspring are mediated by maternal hepatotoxicity.

Alanine Transaminase↗

Effects of low flow and hypoxia on myocardial retention of technetium-99m BMS181321.

The purpose of the present study was to determine whether graded levels of low-flow ischemia would lead to graded differences in uptake and clearance of BMS181321. Using a perfused rat heart model, 7.4 MBq (200 microCi) of BMS181321 was infused over 20 min, followed by a 60-min clearance phase. Activity was monitored using an NaI detector. Four groups were studied using Krebs-Henseleit buffer perfusion using low flow or hypoxia: group 1=12 ml/min, group 2=3 ml/min, and group 3=1 ml/min during uptake and clearance phases, and group 4=12 ml/min with hypoxia during clearance. Control and low-flow groups were also perfused using red blood cells and albumin. There was a stepwise increase in peak myocardial uptake (% injected dose) as flow progressively decreased (group 1=2.4%+/-0.2% SEM, group 2=13.1%+/-0.7%, group 3=28.6%+/-2.4%, P <0.05). Group 3/group 1 mean peak activity ratio was 12:1. Mean 1-h fractional retention significantly increased in a stepwise manner as flow decreased (group 1=0.32+/-0.02, group 2=0.43+/-0.03, group 3=0.59+/-0.05, P <0.05). Group 3/group 1 mean 1-h clearance activity ratio was 30:1. Groups 5 and 6 perfused with red blood cells and albumin demonstrated similar increases in peak uptake and 1-h retention in the low-flow hearts. This study demonstrates a stepwise increase in uptake and a stepwise increase in retention rate of BMS181321 with progressive reduction in flow.

Animals↗