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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 253 records · Page 14Linked to original sources

Dopamine and nicotinic receptor binding and the levels of dopamine and homovanillic acid in human brain related to tobacco use.

Reports of a reduction in the risk of developing Parkinson's disease and Alzheimer's disease in tobacco smokers, together with the loss of high-affinity nicotine binding in these diseases, suggest that consequences of nicotinic cholinergic transmission may be neuroprotective. Changes in brain dopaminergic parameters and nicotinic receptors in response to tobacco smoking have been assessed in this study of autopsy samples from normal elderly individuals with known smoking histories and apolipoprotein E genotype. The ratio of homovanillic acid to dopamine, an index of dopamine turnover, was reduced in elderly smokers compared with age matched non-smokers (P<0.05) in both the caudate and putamen. Dopamine levels were significantly elevated in the caudate of smokers compared with non-smokers (P<0.05). However there was no significant change in the numbers of dopamine (D1, D2 and D3) receptors or the dopamine transporter in the striatum, or for dopamine D1 and D2 receptors in the hippocampus in smokers compared with non-smokers or ex-smokers. The density of high-affinity nicotine binding was higher in smokers than non-smokers in the hippocampus, entorhinal cortex and cerebellum (elevated by 51-221%) and to a lesser extent in the striatum (25-55%). The density of high-affinity nicotine binding in ex-smokers was similar to that of the non-smokers in all the areas investigated. The differences in high-affinity nicotine binding between smokers and the non- and ex-smokers could not be explained by variation in apolipoprotein E genotype. There were no differences in alpha-bungarotoxin binding, measured in hippocampus and cerebellum, between any of the groups. These findings suggest that chronic cigarette smoking is associated with a reduction of the firing of nigrostriatal dopaminergic neurons in the absence of changes in the numbers of dopamine receptors and the dopamine transporter. Reduced dopamine turnover associated with increased numbers of high-affinity nicotine receptors is consistent with attenuated efficacy of these receptors in smokers. A decrease in striatal dopamine turnover may be a mechanism of neuroprotection in tobacco smokers that could delay basal ganglia pathology. The current findings are also important in the interpretation of measurements of nicotinic receptors and dopaminergic parameters in psychiatric conditions such as schizophrenia, in which there is a high prevalence of cigarette smoking.

Age Factors↗

Quantitative forced ductions in an animal model--characterization of passive forces.

PURPOSE: Our purpose was to characterize the passive tissue forces involved in ocular rotation in a controlled animal model and to evaluate the influence of manual versus mechanized ductions, repeated measurements, speed of rotation, and the influence of the nondepolarizing muscle relaxant mivacurium. METHODS: Forced ductions were performed under general anesthesia on 20 eyes of 10 pigs, with or without mivacurium, with use of a highly sensitive force gauge attached to the eye by a traction suture. The eye was moved either manually or at constant speed with a motorized platform. Eyes were rotated a total of 8 mm from their resting position under anesthesia. The force-displacement relationship was analyzed and compared between groups. RESULTS: A linear (elastic) relationship between force and displacement was noted, with a slope of 0.4 g per degree with use of the mechanized technique. Neither speed of rotation, use of mivacurium, nor repeated ductions significantly influenced the shape or slope of the relationship. Hysteresis averaged 2 to 4 g. Measurements performed with use of the motorized platform showed significantly improved reliability over those made manually. CONCLUSIONS: The passive length-tension data correlate well with data reported by others in humans. Within a wide range of eye movement, this force is elastic in nature. For relatively low angular velocities, such as might be produced in smooth pursuit, the passive forces do not change appreciably with changes in velocity. The nondepolarizing muscle relaxant mivacurium has no effect on accurate performance of passive forced ductions under general anesthesia. Studies collecting quantitative data on passive orbital forces should be performed, when feasible, with an automated duction and recording apparatus.

Anesthesia, General↗

Correlation between blood loss and inferior vena caval pressure during liver resection.

BACKGROUND: Blood loss and transfusion requirement are major determinants of mortality and morbidity following liver resection. This study was prompted by the observation that blood loss was excessive when the inferior vena cava (IVC) was distended, and determined whether a correlation exists between blood loss and pressure within the IVC during liver resection. METHODS: A 6-month prospective study was conducted on 20 consecutive patients undergoing liver resection in which two variables were measured, the pressure within the retrohepatic part of the IVC and blood loss during resection. RESULTS: It was observed that when the caval pressure was less than 6 mmHg the operating field was almost bloodless (mean blood loss 363 (range 305-465) ml). When the caval pressure was between 6 and 12 mmHg the liver became congested and bleeding from the liver surface became significantly greater (1259 (range 415-1789) ml). When caval pressure was greater than 13 mmHg bleeding became excessive (2703 (range 2360-3450) ml). Correlation between blood loss and caval pressure was strong (Pearson correlation coefficient 0.93, P < 0.001). CONCLUSION: This study suggests that one of the keys to decreasing blood loss and transfusion requirement during liver resection is to lower pressure within the IVC.

Blood Loss, Surgical↗

Needle-knife papillotomy: a helpful and safe adjunct to endoscopic retrograde cholangiopancreatography in a selected population.

BACKGROUND AND STUDY AIMS: Needle-knife papillotomy (NKP) has been shown to be a useful alternative when standard techniques fail to provide access during ERCP. A retrospective review was conducted to reevaluate the indications, efficacy, and complications of NKP at a tertiary referral center. PATIENTS AND METHODS: A total of 1205 therapeutic endoscopic retrograde cholangiography procedures (ERCPs) were reviewed. Sixty-eight patients (5.6%) had undergone NKP after an established algorithm of techniques had failed to provide access. The NKP results were analyzed in two periods, including initial experience with 470 ERCPs (group 1, NKP n = 22) and later experience with 735 patients (group 2, NKP n = 46). RESULTS: Immediate free cannulation in group 1 was achieved in 14 of 22 patients (64%), vs. 34 of 46 (74%) in group 2. The delayed cannulation rate was five of eight patients in group 1 (62.5%) vs. 11 of 12 in group 2 (92%). The success rate was 19 of 22 patients in group 1 (86%) vs. 45 of 46 in group 2 (98%). The overall success rate was 64 of 68 (94%). Successful cannulation led to a therapeutic intervention in 94% of these patients. A complication rate of 6%, without mortality, was noted. CONCLUSIONS: NKP is a valuable tool that allows a high success rate for cannulation, with a low complication rate. The success rate increases with operator experience. NKP should be carried out by experienced endoscopists after standard maneuvers fail to provide access, and when cannulation is likely to be followed by a therapeutic intervention.

Adolescent↗

Towards culturally competent health care: language use of bilingual staff.

The presence of diverse language skills within health staff provides opportunities to better meet the needs of a multicultural population. A cross-sectional survey of all staff within the South Western Sydney Area Health Service was undertaken to compare language skills with population needs and examine the context of language use. Thirty-one per cent of staff (n = 964) were bilingual or multilingual, with the predominant languages spoken being Tagalog (Filipino), Cantonese, Hindi, Spanish, Vietnamese and Italian. Thirty-seven per cent of bilingual staff used their language skills at least weekly, predominantly in situations of simple conversation and giving directions. Bilingual staff are a valuable resource for the organisation and the presence of a similar overall proportion of bilingual and bicultural staff may engender tolerance and adaptability in providing care to a diverse population. However, supply does not directly match community demand. This mismatch will continue unless recruitment is focused towards identified language groups. The high proportion of staff who rarely used their language skills (37%) may be due to lack of opportunity or limited need, and suggests that further research needs to examine service models that locate bilingual workers close to client need. This study takes a crucial first step towards realising equitable and culturally appropriate care utilising the principles of productive diversity.

Adult↗

HIV follow-up care at a London teaching hospital.

Counselling around all stages of HIV infection is important for those infected and affected with HIV disease. Partner notification may promote safer sexual practices and increase HIV-related social support which might in turn prompt the psychological adjustment to a terminal illness. This paper describes the counselling service used at the Royal Free Hospital's HIV Unit and explores the notification patterns of an HIV diagnosis to family, partners and significant others. Retrospective data was abstracted from counselling notes for 100 HIV-positive patients attending the unit for the first time between November 1995 and March 1996. The majority of the sample were gay males who tested from 1995 onwards. Most patients tested at the Same Day Testing Clinic (SDTC) were gay males. In contrast, patients who tested elsewhere were more likely to be females. Rates of pre- and post-test counselling were high and the majority (85%) of the patients had notified a family member, partner or significant other. Few significant differences in demographics were found between those who had notified others and those who had not, although patients who had been diagnosed more recently were less likely to have notified other family members. The implication of the results are discussed.

Adolescent↗

Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome.

Mutations in the FBN1 gene, which encodes fibrillin-1, cause Marfan syndrome (MFS) and have been associated with a wide range of milder, overlap phenotypes. The factors that modulate phenotypic severity, both between and within families, remain to be determined. This study examines the relationship between the FBN1 genotype and phenotype in families with extremely mild phenotypes and in those that show striking clinical variation among apparently affected individuals. In one family, clinically similar but etiologically distinct disorders are segregating independently. In another, somatic mosaicism for a mutant FBN1 allele is associated with subdiagnostic manifestations, whereas germ-line transmission of the identical mutation causes severe and rapidly progressive disease. A third family cosegregates mild mitral valve prolapse syndrome with a mutation in FBN1 that can be functionally distinguished from those associated with the classic MFS phenotype. These data have immediate relevance for the diagnostic and prognostic counseling of patients and their family members.

Adult↗

Changes in lymphocyte subsets in human immunodeficiency virus-positive persons with < 5 CD4 T lymphocytes/mm3.

All patients seen at the Royal Free Hospital, London, who had at least one CD4 T lymphocyte count of < 5 cells/mm3 (n = 166) were prospectively followed to assess changes in their total T lymphocyte and CD8 T lymphocyte counts over time. While overall there were no clear trends towards a drop or increase in either count, persons who died during the study experienced a rapid drop in both CD8 T lymphocyte and total T lymphocyte levels in the months preceding death. Multivariate Cox proportional hazards models revealed that both the total T lymphocyte count and CD8 T lymphocyte count provided important prognostic information for survival. Despite almost a complete absence of CD4 T lymphocytes, lymphocyte subset monitoring is useful in identifying decreasing CD8 T lymphocyte levels that predict short-term prognosis.

CD4-Positive T-Lymphocytes↗

Bulimia: a primary care approach.

More common than anorexia and less easily detected, bulimia typically begins as an effort to control weight. Although the prognosis is better than that for anorexia nervosa, a number of medical complications can arise related to the mode of purging. Some of these complications can have profound deleterious sequelae if not diagnosed and treated.

Adolescent↗

Activation of latent transgenes in Arabidopsis using a hybrid transcription factor.

A hybrid transcription factor comprising a fusion of the DNA-binding domain of Saccharomyces cerevisiae GAL4 and the transcription activation domain of maize C1 was expressed in stably transformed Arabidopsis. Additional transgenic lines were created containing test genes controlled by a synthetic promoter consisting of concatemeric copies of the cis-acting site recognized by GAL4 (UASG) fused to a minimal promoter. The GAL4/C1 effector line was crossed to two lines containing a synthetic promoter/GUS fusion. Both histochemical staining and GUS activity assays indicate strong activation of GUS expression was achieved only after crossing. The GAL4/C1 effector line was also crossed to 15 lines containing a synthetic promoter/antisense adenylosuccinate synthetase gene. Severely retarded growth, and in some cases lethality, was observed in 40% of the F1 lines. This system of activation by crossing is generally useful for activating expression of test transgenes.

Arabidopsis↗

The CD4+ T lymphocyte is a site of steroid resistance in asthma.

Phytohaemagglutinin (PHA)-induced T-cell proliferation is suppressed completely in steroid-sensitive asthma (SSA) by fluticasone propionate (FP). By contrast, in patients with steroid-resistant asthma (SRA), this proliferative response is only partially attenuated by steroids, which suggests that the T lymphocyte may harbour a key molecular defect in these patients. Both CD4+ and CD8+ T cells may be involved in orchestrating the inflammation underlying asthma. We examined whether CD4+ or CD8+ T cells isolated from SRA and SSA patients are equally susceptible to steroid suppression of PHA-induced proliferation. Complete suppression of CD4+ T-lymphocyte proliferation was seen in both SSA and control subjects at concentrations of 10(-9) M FP. In contrast, proliferation of CD4+ T cells from SRA patients was only partially inhibited, even at 10(-6) M FP. CD8+ responses from SRA, SSA and controls were all similar, with only a partial suppression of proliferation at 10(-6) M FP. Differential suppression by FP of CD4+ T cells has thus been demonstrated between SRA and SSA patients.

Adult↗

The Nursing Outcomes Classification.

The Nursing Outcomes Classification (NOC) is a comprehensive taxonomy of patient outcomes influenced by nursing care. Each outcome is stated as a variable concept measured on a five-point Likert scale and includes a definition, indicators, and references. The classification provides outcomes that can be used across the care continuum to assess patient status following nursing interventions. The classification has a number of advantages, including being research-based, standardized, comprehensive, and flexible for clinical use. It was developed by a large research team that included clinical experts and has been subjected to testing.

Humans↗

The nursing outcomes taxonomy: development and coding.

Interest in the theoretical knowledgebase of nursing has increased over the last 25 years and has led to the current interest in middle-range theory development to describe the essence of nursing. This article describes the creation of a three-level taxonomy and coding structure for the Nursing Outcomes Classification (NOC) based on methods developed by the Nursing Interventions Classification (NIC) work. A model is presented depicting the importance of standardized nursing diagnoses, interventions, and outcomes in the development of the substantive component of nursing practice and to enable nurses to be accountable for care of their clients.

Abstracting and Indexing↗

Interferon-inducible Mx proteins in fish.

Mx proteins are members of a family of interferon-inducible genes expressed when cells are treated with double-stranded RNA or virus infection. These proteins are important components of the antiviral response and form the first line of the body's defense against virus infections. The exact mechanism of action for these proteins has not been discovered, but mice missing the Mx genes are extremely sensitive to influenza virus infection. Mammals have between two and three Mx genes whose functions may vary with regard to the inhibition of a specific virus, cellular localization, and activity. The cDNA of three rainbow trout Mx proteins has been cloned and a comparison of their sequences with that of avian and mammalian species reveals striking conservation of domains. They all maintain the tripartite ATP/GTP binding domain and the dynamin family signature in the amino terminal half of the protein. In the carboxyl terminal half of the Mx proteins are the localization signals and the leucine zipper motifs which account for the trimerization of Mx in the cell. Like the rat and human Mx proteins, the different trout Mx proteins exhibit distinctly different immunohistochemical staining patterns in cells transfected with plasmids expressing RBTMx1, RBTMx2, or RBTMx3. To date, the antiviral function of the trout Mx proteins has not been satisfactorily established.

Amino Acid Sequence↗

Activities of new fluoroquinolones against fluoroquinolone-resistant pathogens of the lower respiratory tract.

The activities of six new fluoroquinolones (moxifloxacin, grepafloxacin, gatifloxacin, trovafloxacin, clinafloxacin, and levofloxacin) compared with those of sparfloxacin and ciprofloxacin with or without reserpine (20 microg/ml) were determined for 19 Streptococcus pneumoniae isolates, 5 Haemophilus sp. isolates, and 10 Pseudomonas aeruginosa isolates with decreased susceptibility to ciprofloxacin from patients with clinically confirmed lower respiratory tract infections. Based upon the MICs at which 50% of isolates were inhibited (MIC50s) and MIC90s, the most active agent was clinafloxacin, followed by (in order of decreasing activity) trovafloxacin, moxifloxacin, gatifloxacin, sparfloxacin, and grepafloxacin. Except for clinafloxacin (and gatifloxacin and trovafloxacin for H. influenzae), none of the new agents had improved activities compared with that of ciprofloxacin for P. aeruginosa and H. influenzae. A variable reserpine effect was observed for ciprofloxacin and S. pneumoniae; however, for 9 of 19 (47%) isolates the MIC of ciprofloxacin was decreased by at least fourfold, suggesting the presence of an efflux pump contributing to the resistance phenotype. The laboratory parC (Ser79) mutant strain of S. pneumoniae required eightfold more ciprofloxacin for inhibition than the wild-type strain, but there was no change in the MIC of sparfloxacin and only a 1-dilution increase in the MICs of the other agents. For efflux pump mutant S. pneumoniae the activities of all the newer agents, except for levofloxacin, were reduced. Except for clinafloxacin, all second-step laboratory mutants required at least 2 microg of all fluoroquinolones per ml for inhibition.

Anti-Infective Agents↗

The beta-adrenoceptor.

The human beta-adrenoceptor is a member of the seven-transmembrane family of receptors, encoded by a gene on chromosome 5. beta-Adrenoceptors have been classified into beta1, beta2, and beta3 subgroups, with beta2-receptors being widely distributed in the respiratory tract, particularly in airway smooth muscle. Intracellular signaling following beta2-adrenoceptor activation is largely affected through a trimeric Gs protein coupled to adenylate cyclase. Cyclic AMP (cAMP) induces airway relaxation through phosphorylation of muscle regulatory proteins and attenuation of cellular Ca2+ concentrations. Alternative cAMP-independent pathways involving activation of membrane maxi-K+ channels and coupling through Gi to the MAP kinase system have also been described. Site-directed mutagenesis has identified Asp 113 and Ser 204/207 within the third and fourth membrane domains as the active site of the beta2-receptor, critical for beta2-agonist binding and activity. beta2-Agonists have been characterized as those that directly activate the receptor (albuterol), those that are taken up into a membrane depot (formoterol), and those that interact with a receptor-specific auxiliary binding site (salmeterol). These differences in mechanism of action are reflected in the kinetics of airway smooth muscle relaxation and bronchodilation in patients with asthma. beta-Adrenoceptor desensitization associated with beta2-agonist activation is a consequence of phosphorylation by beta-ARK and uncoupling of the receptor from Gs following beta-arrestin binding, of internalization and recycling of the receptor through processes of sequestration and resensitization and downregulation, modulated by an effect on receptor gene expression. The degree of receptor desensitization appears to differ, depending on the cell or tissue type, and is reflected in the different profiles of clinical tolerance to chronic beta2-agonist therapy. A number of polymorphisms of the beta2-receptor have been described that appear to alter the behavior of the receptor following agonist exposure. These include Arg-Gly 16, Glu-Gln 27, and Thr-lle 164. The Gly 16 receptor downregulates to a greater extent and is associated with increased airway hyperreactivity, nocturnal symptoms, and more severe asthma. The Glu 27 form appears to protect against downregulation and is associated with less reactive airways. An individual can be homozygous or heterozygous for given polymorphisms, and large populations will have to be studied to determine their importance to the asthma phenotype.

Adrenergic beta-Agonists↗

Hospital utilization and personality characteristics of veterans with psychiatric problems.

OBJECTIVE: The relationship between hospital utilization and psychometric, demographic, and diagnostic data was examined among veterans with psychiatric problems. METHODS: Data were obtained from the records of 500 psychiatric inpatients admitted to a Veterans Affairs medical center between 1984 and 1987 and followed for four years. All patients completed the Minnesota Multiphasic Personality Inventory, the California Personality Inventory, the Millon Clinical Multiaxial Inventory, and the Psychological Inventory of Personality and Symptoms. Stepwise linear regression analysis was used to predict the number and length of inpatient stays, and Cox and logistic regression analyses predicted rehospitalization. RESULTS: Higher rates of psychiatric hospital utilization were found among patients who were unmarried, who had disabilities connected with their military service, who had lower levels of adaptive functioning, and who were diagnosed as having posttraumatic stress disorder, drug or alcohol use disorder, or passive-aggressive or antisocial personality disorder. Higher utilization was also found among those whom psychometric data characterized as less responsible and more compulsive. The data also predicted the length of subsequent medical hospitalization and identified patients who stayed out of the hospital longer and who were not rehospitalized. CONCLUSIONS: Hospital utilization was found to be a function of psychiatric diagnosis, marital status, and various personality factors. Factors relating to social disadvantage also played a role. Axis I diagnoses, particularly substance use disorders, were as important as, if not more important than, axis II diagnoses in predicting utilization.

Adult↗