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Biomedical subjects

S Johnson

Publications and source records attributed to S Johnson.

At least 37 records · Page 2Linked to original sources

Perceived sources of work stress and satisfaction among hospital and community mental health staff, and their relation to mental health, burnout and job satisfaction.

This questionnaire study examined perceived sources of stress and satisfaction at work among 121 mental health staff members. Five factors were derived from principal component analysis of sources of work stress items (stress from: role, poor support, clients, future, and overload), and accounted for 70% of the total variance. Four factors were derived from the items related to sources of job satisfaction (satisfaction from: career, working with people, management, and money), accounting for 68% of the variance. The associations of these factors with sociodemographic and job characteristics were examined, and they were entered as explanatory variables into regression models predicting mental health, burnout, and job satisfaction. Stress from "overload" was associated with being based outside an in-patient ward, and with emotional exhaustion and worse mental health. Stress related to the "future" was associated with not being white. Stress from "clients" was associated with the "depersonalization" component of burnout. Higher job satisfaction was associated with "management" and "working with people" as sources of satisfaction, whereas emotional exhaustion and poorer mental health were associated with less "career" satisfaction.

Allied Health Personnel

Comparison of cycloserine-cefoxitin-fructose agar (CCFA) and taurocholate-CCFA for recovery of Clostridium difficile during surveillance of hospitalized patients.

The effectiveness of cycloserine-cefoxitin-fructose agar (CCFA) and taurocholate-CCFA (TCCFA) in isolating Clostridium difficile from swabs of the rectum or stools from 184 hospitalized patients who were monitored weekly and when they had diarrhea was compared. The number of surveillance time points ranged from two to eight per patient over a period of 4 to 34 days per patient, totalling 621 comparisons of the media. C. difficile was isolated more frequently by TCCFA than CCFA at seven of eight surveillance points, a significant trend (O'Brien test, p = 0.002). This difference reached statistical significance at the second surveillance time point when the prevalence of C. difficile was sufficiently high. At the second surveillance point, C. difficle was isolated only by TCCFA in 7 of 184 comparisons of the media, only by CCFA in none of the comparisons, and by both media in 19 comparisons (p = 0.016). C. difficle was first isolated at an earlier surveillance time point on TCCFA in 11 of 36 patients and on CCFA first only once (p = 0.005). Use of TCCFA media increased the rapidity and sensitivity of culture for C. difficle when doing patient surveillance but did not increase sensitivity when diagnosing patients with diarrhea.

Antibiotics, Antitubercular

Phase 1 safety trial of Filgrastim (r-metHuG-CSF) in non-neutropenic patients with severe community-acquired pneumonia.

The objectives of the present study were to: (1) evaluate the safety of Filgrastim therapy in non-neutropenic patients with severe community-acquired pneumonia; (2) determine the absolute neutrophil count (ANC) response to various dosages of Filgrastim in non-neutropenic patients with active infection; and (3) describe the impact of therapy with Filgrastim in combination with antibiotics on selected pneumonia-related clinical parameters. The study design was an open-label, dose-ranging, clinical trial, set in the General Clinical Research Unit of a large, public community hospital. The study population consisted of 30 patients who had presented to the Emergency Department with severe, community-acquired pneumonia. One of five dosages (75, 150, 300, 450 or 600 micrograms day-1) of Filgrastim (r-metHuG-CSF) was given subcutaneously daily for 10 days, until discharge or until the absolute neutrophil count > 75 x 10(9) l(-1), whichever was earlier. Vital signs, pulse oximetry, arterial blood gases, daily complete blood counts with differential, serum chemistries, coagulation profiles, electrocardiograms, chest radiographs, plasma G-CSF concentrations and duration of hospitalization were measured. There was no evidence of Filgrastim-related lung injury or evidence of extra-pulmonary toxicity. There was no apparent dose-response effect of Filgrastim on pneumonia-related clinical variables. Dosages of Filgrastim between 150 and 600 micrograms day-1 had similar effects on increasing the ANC. Filgrastim appeared to be safe in non-neutropenic patients with severe, community-acquired pneumonia when given in dosages of 75-600 micrograms day-1 in combination with appropriate antibiotic therapy. Further study is needed to determine the effect of Filgrastim on morbidity, mortality and duration of symptoms in this patient population.

Adult

Perceptions of parenting as predictors of boys' sibling and peer relations.

This study included 71 target boys (8 to 10 years), their siblings, and mothers to examine the relations among mothering, fathering, sibling aggression, and peer outcomes. Siblings whose mothers were known to be more rejecting were observed and reported to be more aggressive with one another than siblings whose mothers were less rejecting. Moreover, boys who experienced more aggressive sibling interactions were more likely to be nominated by their peers as being aggressive and were less accepted by their peers. Although fathering failed to evince a direct influence on sibling aggression, an indirect effect was evidenced in that less accepting fathering related to more rejecting mothering. It appeared that boys' aggressive experiences with their siblings mediated, in part, the association between maternal rejection and their peer aggression and that peer aggression was a mediating link between sibling aggression and boys' acceptance by their peers.

Adolescent

Dual diagnosis of severe mental health problems and substance abuse/dependence: a major priority for mental health nursing.

It is now established that very significant numbers of people with severe mental illness abuse or depend on drugs and/or alcohol. This combination (Dual Diagnosis) leads to increased rates of violence and service use, a reduction in adherence to treatment regimes, an increase in susceptibility to human immunodeficiency virus (HIV) infection and is now found in in-patient populations. Because of their vulnerability to accidents and physical illnesses, dual diagnosis patients are found increasingly in accident and emergency departments, general medical wards and primary care settings. For this reason nurses and other health professionals working in general hospitals should be as aware as their mental health colleagues of the specific needs of this population. There are some excellent models of service organization and training for dealing with dual diagnoses populations in some parts of the USA. However, there is little such development in the UK. There are clear pathways to be followed, but the need for action is urgent.

Humans

The com locus controls genetic transformation in Streptococcus pneumoniae.

Genetic exchange by natural transformation in Streptococcus pneumoniae occurs in a cell-density dependent process and is initiated by a small extracellular signalling molecule, the competence-stimulating peptide (CSP). comC, the gene for this peptide, has previously been identified and encodes a 44 amino acid pre-peptide that is apparently processed to an active molecule that consists of the C-terminal 17 amino acids. We have sequenced the region adjacent to comC and shown that it is the first gene of an operon, com, consisting of two downstream elements, comD and comE, which encode members of the two-component family of sensor regulators. Null mutants with defects in either comC or comD were transformation deficient and failed to respond to exogenous CSP. A comC mutant did not exhibit any detectable CSP activity, while a comD mutant that contained an intact comC produced minimal CSP activity. In mixed-culture experiments consisting of isogenic pairs of pneumococci (Csp+ and Csp-), we showed that induction of competence by quorum sensing was independent of CSP. Northern analysis showed that com was transcribed as a single polycistronic message, while analysis of strains with transcriptional fusions showed that com was constitutively expressed under conditions that both promoted or repressed the development of competence. Finally, we showed genetically and biochemically a CSP-dependent transcription of rec, a competence-induced locus, and that ComD and ComE are required for this CSP-dependent expression.

Bacterial Proteins

Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus.

Neutralizing polyclonal antibody to respiratory syncytial virus (RSV) has been shown to be an effective prophylactic agent when administered intravenously in high-risk infants. This study describes the generation of a humanized monoclonal antibody, MEDI-493, that recognizes a conserved neutralizing epitope on the F glycoprotein of RSV. The affinity of MEDI-493 was found to be equal to or slightly better than an isotype-matched chimeric derivative of the parent antibody. In plaque reduction, microneutralization, and fusion-inhibition assays, MEDI-493 was significantly more potent than the polyclonal preparation. Broad neutralization of a panel of 57 clinical isolates of the RSV A and B subtypes was demonstrated. Pretreatment of cotton rats with MEDI-493 resulted in 99% reduction of lung RSV titers at a dose of 2.5 mg/kg, corresponding to a serum concentration of 25-30 microg/mL. Further, MEDI-493 did not induce increased RSV infection or pathology in either a primary or a secondary challenge.

Amino Acid Sequence

Multicenter typing comparison of sporadic and outbreak Clostridium difficile isolates from geographically diverse hospitals.

In a collaborative study by three laboratories, arbitrarily primed polymerase chain reaction (AP-PCR), HindIII restriction enzyme analysis (REA), and pulsed-field gel electrophoresis (PFGE) using SmaI were compared for typing of Clostridium difficile. The study included 30 isolates from nosocomial outbreaks in six geographically disparate hospitals and 15 isolates from sporadic cases of C. difficile diarrhea. REA distinguished a total of 23 types representing 10 groups; AP-PCR performed at Deaconess Hospital resolved 19 types; AP-PCR performed at the Centers for Disease Control resolved 15 types. Thirty isolates exhibited degradation of larger sized fragments during processing and therefore were nontypeable by PFGE; among the remaining 15 isolates, PFGE resolved 11 types. Outbreak isolates in five different hospitals represented REA group J and constituted a single AP-PCR strain. In summary, nosocomial outbreaks of C. difficile diarrhea in five hospitals were associated with a single genetic lineage as resolved by multiple strain typing systems.

Bacterial Typing Techniques

Antibody responses to clostridial infection in humans.

Serum antibody responses to the major toxins produced by Clostridium difficile, Clostridium perfringens, Clostridium septicum, Clostridium tetani, and Clostridium botulinum have been documented following infection. Effective toxoid vaccines for tetanus and enteritis necroticans due to C. perfringens type C demonstrate the potential of antitoxin responses. Although individual serum and mucosal antibody responses to C. difficile enterotoxin (toxin A) vary, one-third of patients with C. difficile diarrhea develop neutralizing serum antibodies. IgA in the serum, not IgG, is typically responsible for this neutralization, suggesting a unique role for serum IgA in response to C. difficile infection, an infection that is usually limited to the intestinal mucosa. The relationship of naturally occurring antitoxin antibodies to the clinical course of C. difficile infection is controversial. However, patients with chronic relapsing C. difficile diarrhea and low levels of IgG to toxin A have shown clinical responses following intravenous therapy with immune globulin. Antibody responses to non-toxin C. difficile proteins also occur, but their significance is only partially known.

Antibodies, Bacterial

The indications for polysomnography and related procedures.

This paper is a review of the literature on the use of polysomnography in the diagnosis of sleep disorders in the adult. It is based on a search of MEDLINE from January 1966 through April 1996. It has been reviewed and approved by the Board of Directors of the American Sleep Disorders Association and provides the background for the accompanying ASDA Standards of Practice Committee's Parameters for the Practice of Sleep Medicine in North America. The diagnostic categories reviewed are: sleep-related breathing disorders; other respiratory disorders; narcolepsy; parasomnias and sleep-related epilepsy; restless legs syndrome and periodic limb movement disorders: insomnia; and circadian rhythm sleep disorders. Where appropriate, previously published practice parameters papers are cited and discussed. The relevant published peer-reviewed literature used as the basis for critical decisions was compiled into accompanying evidence tables and is analyzed in the text. In the section on the assessment of sleep apnea syndrome, options for estimating pretest probability to select high risk patients are also reviewed. Sleep-testing procedures other than standard polysomnography are also addressed (daytime polysomnography, split-night studies, oximetry, limited full respiratory recordings, and less-than-full respiratory recording) and treatment-related follow-up studies are discussed.

Adult

Angiomatoid malignant fibrous histiocytoma revisited. An immunohistochemical and DNA ploidy analysis.

A histologic, immunohistochemical, and DNA ploidy analyses were performed on two cases of angiomatoid malignant fibrous histiocytoma to ascertain the histogenesis and relationship of endothelial, histiocytic, and fibroblastic elements. Both cases were slowly growing, grossly encapsulated. Subcutaneous masses resected from pediatric patients. Microscopically, the tumors were composed of solid masses of epithelioid and spindle cells with abnormal endothelial-lined and blood-filled cystic spaces surrounded by normal vascular structures and aggregates of lymphocytes occasionally forming germinal follicles. The tumor cells stained exclusively with CD34 and vimentin antibodies. Tumor-associated vessels stained for CD31, CD34, vimentin, and Ulex europaeus. Occasional cells within germinal follicles stained for lysozyme, CD68, and HAM56. Ploidy analysis of tumor cells showed intermediate aneuploidy with a DNA index of 1.14. Blood vessels within and surrounding the tumor as well as inflammatory cells were DNA euploid. These studies suggest that the tumor--though comprised of histologically and immunohistochemically benign-appearing euploid endothelial, fibroblastic, and inflammatory elements--contains an aneuploid population of undifferentiated mesenchymal cells.

Aneuploidy

Classification of the southern African sanga and east African shorthorned zebu.

Humped African cattle, which are differentiated into zebu and sanga types, have traditionally been classified as Bos indicus. This paper discusses existing evidence and presents new evidence supporting the classification of southern African sangas as Bos taurus and East African zebus as 'taurindicus'. Classification is based on karyotype, frequencies of DNA markers and protein polymorphisms. The Boran, an East African zebu, has an acrocentric Y chromosome typical of Bos indicus. The southern African sanga breeds have a submetacentric Y chromosome typical of Bos taurus. Frequencies of four DNA markers support the hypothesis that the Tuli, a southern African sanga, had taurine ancestors and the Boran had both taurine and indicine ancestors. Frequencies for several protein polymorphisms strongly suggest that southern African sangas have more in common with taurine than with indicine breeds, while East African zebus are an admixture of African taurine and Asian indicine breeds.

Africa, Eastern

Contribution of novel choline-binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae.

The surface of Streptococcus pneumoniae is decorated with a family of choline-binding proteins (CBPs) that are non-covalently bound to the phosphorylcholine of the teichoic acid. Two examples (PspA, a protective antigen, and LytA, the major autolysin) have been well characterized. We identified additional CPBs and characterized a new CBP, CbpA, as an adhesin and a determinant of virulence. Using choline immobilized on a solid matrix, a mixture of proteins from a pspA-deficient strain of pneumococcus was eluted in a choline-dependent fashion. Antisera to these proteins passively protected mice challenged in the peritoneum with a lethal dose of pneumococci. The predominant component of this mixture, CbpA, is a 75-kDa surface-exposed protein that reacts with human convalescent antisera. The deduced sequence from the corresponding gene showed a chimeric architecture with a unique N-terminal region and a C-terminal domain consisting of 10 repeated choline-binding domains nearly identical to PspA. A cbpA-deficient mutant showed a >50% reduction in adherence to cytokine-activated human cells and failed to bind to immobilized sialic acid or lacto-N-neotetraose, known pneumococcal ligands on eukaryotic cells. Carriage of this mutant in an animal model of nasopharyngeal colonization was reduced 100-fold. There was no difference between the parent strain and this mutant in an intraperitoneal model of sepsis. These data for CbpA extend the important functions of the CBP family to bacterial adherence and identify a pneumococcal vaccine candidate.

Amino Acid Sequence

Six new DPB1 alleles identified in a study of 1,302 unrelated bone marrow donor-recipient pairs.

Six new DPB1 alleles were identified by PCR-SSOP methodologies in the course of a retrospective study of the role of HLA matching in the outcome of unrelated donor bone marrow transplantation. Sequencing confirmed that five of these alleles (DPB1*5901, *6801, *7101, *7201, and *7301) represent novel combinations of previously described sequence motifs in the variable regions of DPB1; the sixth (DPB1*7001) appears to result from a novel point mutation. These data support previous observations which suggest that multiple mechanisms, including segmental exchange and mutation, appear to be responsible for generating sequence diversity at the DPB1 locus. The extremely low discrepancy rate of 0.1% between the two laboratories which typed the samples, and the ability to predict the new sequences from probe hybridization patterns, indicate that SSOP is an accurate and efficient method for studying polymorphism at DPB1.

Alleles

Identification of the DRB1*1313 allele in a sibling pair.

Sequence-specific oligonucleotide probe hybridization (PCR/SSOP), which is now routinely used in HLA laboratories to type for alleles of the class II loci, can also detect the presence of previously unknown alleles. In the course of clinical typing for DRB1, we identified two samples with probe hybridization patterns appropriate for DRB1*1313, a previously submitted sequence that had been withdrawn. Direct sequencing showed that the two individuals carried an allele with an exon 2 sequence identical to that previously submitted for DRB1*1313.

Alleles

Is parathyroid hormone-related protein a sensitive serum marker in advanced breast cancer?

BACKGROUND: To compare already used serum markers in advanced breast cancer, namely erythrocyte sedimentation rate (ESR), carcino-embryonic antigen (CEA), and polymorphic epithelial mucins (e.g. CA15-3) with a newer potential marker: parathyroid hormone related protein (PTHrP). METHODS: A study group of 33 patients of proven advanced breast cancer was compared with 11 patients with benign breast lumps who were undergoing surgery, and eight patients with humoral hypercalcaemia of malignancy of non-breast origin. ESR, CA15-3, CEA, PTHrP, parathormone (PTH), liver and renal function were measured using commercially available kits. Using given reference ranges, results were classified into normal versus abnormal, and univariate statistical comparisons were made using Fisher's exact test. For multivariate analysis, absolute serum levels were used, and multivariate logistic regression models were employed. RESULTS: By univariate analysis, only CA15-3 (P = 0.007), and CEA (P = 0.004), were significant markers of metastatic disease. By multivariate analysis the only independently significant serum marker was CA15-3 (P = 0.043). PTHrP was neither a sensitive (22%) nor specific (90.1%) serum marker when compared to CEA or CA15-3. ESR was the most sensitive single serum marker (93%). An incidental finding of elevations of serum parathormone was found in as many patients as in the study group as there were elevations of PTHrP. CONCLUSIONS: PTHrP would not have revealed any patients with metastatic disease that would not have been predicted by any existing tumour markers including CA15-3, CEA and ESR. The finding of elevated PTH in as many patients as PTHrP indicates the possible need for a study inclusive of other polypeptide hormones as markers in advanced breast cancer.

Adult