Biomedical subjects
Publications and source records attributed to S Johnson.
An ICP sets out best practice guidance. One health-care team applied ICPs to stroke care, which can be unpredictable. Stroke care was arranged in 'bite-sized chunks' with ICPs for each separate aspect.
Insomnia is the most common sleep complaint reported to physicians. Treatment has traditionally involved medication. Behavioral approaches have been available for decades, but lack of physician awareness and training, difficulty in obtaining reimbursements, and questions about efficacy have limited their use. These practice parameters review the current evidence with regards to a variety of nonpharmacologic treatments for insomnia. Using a companion paper which provides a background review, the available literature was analyzed. The evidence was graded by previously reported criteria of the American Academy of Sleep Medicine with references to American Psychological Association criteria. Treatments considered include: stimulus control, progressive muscle relaxation, paradoxical intention, biofeedback, sleep restriction, multicomponent cognitive behavioral therapy, sleep hygiene education, imagery training, and cognitive therapy. Improved experimental design has significantly advanced the process of evaluation of nonpharmacologic treatments for insomnia using guidelines outlined by the American Psychological Association (APA). Recommendations for individual therapies using the American Academy of Sleep Medicine recommendation levels for each are: Stimulus Control (Standard); Progressive Muscle Relaxation, Paradoxical Intention, and Biofeedback (Guidelines); Sleep Restriction, and Multicomponent Cognitive Behavioral Therapy (Options); Sleep Hygiene Education, Imagery Training, and Cognitive Therapy had insufficient evidence to be recommended as a single therapy. Optimal duration of therapy, who should perform the treatments, long term outcomes and safety concerns, and the effect of treatment on quality of life are questions in need of future research.
CD2 is a 50-kDa transmembrane glycoprotein that plays an important role in T and natural killer (NT) lymphocyte functions. CD2 serves as both an adhesion molecule and as a costimulatory molecule through interactions with its ligand, CD58, on antigen presenting or target cells. Consistent with earlier studies using a rat anti-CD2 mAb, we have shown that treatment of alloantigen stimulated T lymphocytes with a humanized mAb, MEDI-507 (IgG1, kappa), induced hyporesponsiveness to subsequent stimulation with alloantigen but not to mitogen (phytohemagglutinin). Fluorescence-activated cell sorting analysis of cells from mixed lymphocyte reaction (MLR) treated with MEDI-507 revealed pronounced deletion of T and NK cells, consistent with lack of proliferation in the MLR. MEDI-507 F(ab')2 fragments did not have inhibitory activity or induce deletion of lymphocytes in the MLR. Removal of the NK cell subset by magnetic bead depletion using anti-CD16 and anti-CD56 mAbs eliminated both the T cell deletion and the inhibitory effect. Reconstitution of NK depleted responder populations using autologous NK cells restored the MEDI-507-mediated deletion activity to levels measured in the original MLR. Formaldehyde-fixed NK cells failed to mediate the MEDI-507-induced deletion effect. Altogether, our studies indicate that activated T cells with MEDI-507 bound to CD2 are preferential targets for autologous NK cells through a nonapoptotic cytotoxic mechanism.
BACKGROUND: Large outbreaks of diarrhea caused by a newly recognized strain of Clostridium difficile occurred in four hospitals located in different parts of the United States between 1989 and 1992. Since frequent use of clindamycin was associated with the outbreak in one of the hospitals, we examined the resistance genes of the epidemic-strain isolates and studied the role of clindamycin use in these outbreaks. METHODS: Case-control studies were performed at three of the four hospitals to assess the relation of the use of clindamycin to C. difficile-associated diarrhea. All isolates of the epidemic strain and representative isolates of other strains identified during each outbreak were tested for susceptibility to clindamycin. Chromosomal DNA from these representative isolates was also analyzed by dot blot hybridization and amplification with the polymerase chain reaction (PCR) with the use of probes and primers from a previously described determinant of erythromycin resistance - the erythromycin ribosomal methylase B (ermB) gene - found in C. perfringens and C. difficile. RESULTS: In a stratified analysis of the case-control studies with pooling of the results according to the Mantel-Haenszel method, we found that the use of clindamycin was significantly increased among patients with diarrhea due to the epidemic strain of C. difficile, as compared with patients whose diarrhea was due to nonepidemic strains (pooled odds ratio, 4.35; 95 percent confidence interval, 2.02 to 9.38; P<0.001). Exposure to other types of antibiotics or hospitalization in a surgical ward was not significantly associated with the risk of C. difficile-associated diarrhea due to the epidemic strain. All epidemic-strain isolates were highly resistant to clindamycin (minimal inhibitory concentration, >256 microg per milliliter). DNA hybridization and PCR analysis showed that all these isolates had an ermB gene, which encodes a 23S ribosomal RNA methylase that mediates resistance to macrolide, lincosamide, and streptogramin antibiotics. Only 15 percent of the nonepidemic strains were resistant to clindamycin. CONCLUSIONS: A strain of C. difficile that is highly resistant to clindamycin was responsible for large outbreaks of diarrhea in four hospitals in different states. The use of clindamycin is a specific risk factor for diarrhea due to this strain. Resistance to clindamycin further increases the risk of C. difficile-associated diarrhea, an established complication of antimicrobial use.
These are the first clinical guidelines published for the treatment of Restless Legs Syndrome (RLS) and Periodic Limb Movement Disorder (PLMD) providing evidence-based practice parameters. They were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The guidelines provide recommendations for the practice of sleep medicine in North America regarding the treatment of RLS and PLMD. Recommendations are based on the accompanying comprehensive review of the medical literature regarding treatment of RLS and PLMD which was developed by a task force commissioned by the American Academy of Sleep Medicine. Recommendations are identified as standards, guidelines, or options, based on the strength of evidence from published studies that meet criteria for inclusion. Dopaminergic agents are the best studied and most successful agents for treatment of RLS and PLMD. Specific recommendations are also given for the use of opioid, benzodiazepine, anticonvulsant, and adrenergic medications, and for iron supplementation. In general, pharmacological treatment should be limited to individuals who meet diagnostic criteria and especially who experience insomnia and/or excessive sleepiness that is thought to occur secondary to RLS or PLMD. Individuals treated with medication should be followed by a physician and monitored for clinical response and adverse effects. It would be desirable for future investigations to employ multicenter clinical trials, with expanded numbers of subjects using double-blind, placebo-controlled designs, and an assessment of long-term response, side effects, and impact of treatment on quality of life. Evaluation of special groups such as children, pregnant women, and the elderly is warranted.
These clinical guidelines were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The guidelines provide recommendations for the practice of sleep medicine in North America regarding the use of light therapy for treatment of various sleep disorders. This paper is based on a series of articles in the Journal of Biological Rhythms and also includes evidence tables from an updated Medline review covering the period January 1994 to December 1997. Evidence is presented by grade and level. Recommendations are identified as standards, guidelines, or options. Recommendations are provided for delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome (ASPS), non-24-hour sleep-wake syndrome, jet lag, shift work, dementia, and sleep complaints in the healthy elderly. Light therapy appears generally safe if used within recommended intensity and time limits. Light therapy can be useful in treatment of DSPS and ASPS. Benefits of light therapy are less clear and treatment is an option in jet lag, shift work, and non-24-hour sleep-wake syndrome in some blind patients.
Adenosine deaminase (ADA; adenosine aminohydrolase, E.C. 3.5.4.4), a purine catabolic enzyme, was studied in Candida albicans, an opportunistic yeast that causes diseases ranging from superficial infections to the deep systemic disease, candidiasis, in immunosuppressed humans. The fungus was grown as a yeast form in LEE's synthetic medium, pH 4.5, at room temperature for various growth periods. Adenosine deaminase (ADA) activity was determined from the cell free extract by measuring the change in absorbance 265 nm resulting from the deamination of adenosine. In yeast form, maximum growth and ADA activity were found at 72 and 24 hours, respectively, whereas in the mycelial form both the growth and ADA activity were maximum after 48 hours. Among the three media tested, tryptic soy broth supported maximum growth and enzyme production, compared to LEE synthetic medium or SABOURAUD dextrose broth. The enzyme was active over the pH range 4-8 and the optimum temperature for ADA activity was found to be 37 degrees C.
BACKGROUND: This study examines whether the adoption of a more community based model in an inner city psychiatry service is accompanied by increasing "burnout", deteriorating mental health and decreasing job satisfaction amongst staff. METHOD: Questionnaires were sent annually for 3 consecutive years to all mental health staff working in three adult mental health sectors in inner London. Main outcome measures were the 12-item General Health Questionnaire, Maslach Burn-out Inventory and a general job satisfaction measure. RESULTS: There was no significant change over time in the outcome measures, once confounding by job and demographic variables was examined. Being based in the community was associated with higher GHQ-12 scores (P = 0.02) when compared to in-patient staff over the 3 years. CONCLUSIONS: These results suggested that working in the community may be more stressful than working in in-patient services. However, there was no evidence to suggest that levels of stress are increasing over time, either in community-based or hospital-based staff.
BACKGROUND: High levels of burnout and poor psychological well-being, but also relatively high levels of job satisfaction, have been found among mental health staff, especially those based in community settings. AIMS: In order to investigate the basis of these findings, a qualitative interview study was carried out, exploring mental health staff's views of their work and of its effects on them. METHOD: A semi-structured interview was administered to a purposive sample of 30 professionals, including junior and senior members of each profession in both hospital and community settings. Interviews were transcribed verbatim and analysed using QSR NUD.IST software. RESULTS: For most professionals, contact with colleagues was one of the major rewards of the job. There was surprisingly little evidence of conflict or difficulties defining roles between disciplines, except for the social workers, for whom difficulty in defining roles in relation to other professions was a major preoccupation. Reported stresses differed between community and hospital staff. Community staff tended to find their contacts with patients highly rewarding, but also to feel burdened by a strong and uncomfortable sense of being constantly responsible for their clients' well-being and actions. Ward staff, on the other hand, identified as central difficulties in their job lack of autonomy, responsibility and scope for developing an independent therapeutic role. They felt demoralised by revolving door' patients and by violence and the need to restrain patients.
BACKGROUND: High levels of both burnout and job satisfaction have been found in recent studies of mental health professionals. A qualitative methodology was used in a related study to explore reasons for these findings and to investigate staff's accounts of their strategies for coping with their work, and their views of support provided for them and how their jobs might be made less stressful and still more satisfying. METHOD: A semi-structured schedule was used to interview a purposive sample of 30 mental health staff drawn from three South London geographical sectors, selected to include junior and senior members of each profession in both hospital and community settings. Interviews were transcribed and analysed using QSR NUD.IST software. RESULTS: Informal contacts with colleagues were the most frequently mentioned way of coping with the difficult and demanding aspects of work in both hospital and community settings, closely followed by time management techniques. The main formal sources of support described by staff were individual supervision and staff support groups. Accounts of the former were generally positive, but there was great variation in opinions about whether support groups are useful. Almost all the interviewees believed that their jobs could be improved by further training. For community mental health staff the main training gaps were the development of skills in various forms of clinical intervention, whilst ward staff identified the need for further skills in diffusing potentially confrontational and aggressive situations.
PURPOSE: To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28-day schedule. METHODS: Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients). RESULTS: All 17 evaluable patients were evaluable for toxicity. At dose level III dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216. CONCLUSION: For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.
OBJECTIVE: The purpose of this study was to evaluate the usefulness of 17 hydroxyprogesterone (17OHP) determination in dried filter paper blood samples from patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency. It was hypothesized that these home samples would enhance patient treatment. STUDY DESIGN: Results of 17OHP determination in simultaneously collected venous and dried filter paper blood samples were compared to establish assay reliability. Thereafter, parents mailed dried filter paper blood samples collected before each hydrocortisone dose. RESULTS: The 17OHP levels in wet and dried blood samples correlated well (r = 0.98). Results did not change when stored for 2 weeks under various conditions. Blood sampling at different times of the day provided insights into the patterns of 17OHP secretion and identified times of inadequate adrenal suppression. Dose adjustments were then made considering the time of day when adrenal suppression was inadequate. CONCLUSION: Home monitoring of 17OHP is a reliable and practical approach for assessing adrenal steroid activity in patients with congenital adrenal hyperplasia. Considering the time of day of 17OHP elevations also facilitates hydrocortisone dosing adjustment.
The involvement of protein kinase C (PKC) and protein kinase A (PKA) in cholinergic signalling in CHO cells expressing the M3 subtype of the muscarinic acetylcholine receptor was examined. Muscarinic signalling was assessed by measuring carbachol-induced activation of phospholipase C (PLC), arachidonic acid release, and calcium mobilisation. Carbachol activation of PLC was not altered by inhibition of PKC with chelerythrine chloride, bisindolylmaleimide or chronic treatment with phorbol myristate acetate (PMA). Activation of PKC by acute treatment with PMA was similarly without effect. In contrast, inhibition of PKC blocked carbachol stimulation of arachidonic acid release. Likewise, PKC inhibition resulted in a decreased ability of carbachol to mobilise calcium, whereas PKC activation potentiated calcium mobilisation. Inhibition of PKA with H89 or Rp-cAMP did not alter the ability of carbachol to activate PLC. Similarly, PKA activation with Sp-cAMP or forskolin had no effect on PLC stimulation by carbachol. Carbachol-mediated release of arachidonic acid was decreased by H89 but only slightly increased by forskolin. Forskolin also increased calcium mobilisation by carbachol. These results suggest a function for PKC and PKA in M3 stimulation of arachidonic acid release and calcium mobilisation but not in PLC activation.
HLA-DP genotyping of 500 donor recipient pairs in a retrospective analysis sponsored by the National Marrow Donor Program (NMDP) identified four new DP alleles, two DPB1 and two DPA1. DNA sequencing confirmed that DPB1*8001 and *8101, each found in a single individual, are novel combinations of previously described sequence motifs in the six variable regions of DPB1. DPA1*02014, found in two individuals, is identical to DPA1*02011 except for a novel silent substitution, a G to A transition at the third position of codon 14. DPA1*01032, found in one individual, is identical to DPB1*01031 except for a silent G to A transition at the third position of codon 20. The identification of these novel alleles brings the total number of reported DPB1 alleles to 85 and DPA1 alleles to 15.
This study uses structural equation models to describe how objective neighborhood, perceived neighborhood, and environmental support predict mental health; 792 adolescents responded to highly structured interviews. The effect of objective environment on mental health was mediated through its influence on perceived neighborhood. Environmental support mitigated negative perceptions of environment and the effect of perceived environment on mental health, while exposure to violence augmented the negative effect of perceived environment.
Seventeen patients (aged 50-85 years) with relapsed or refractory non-Hodgkin's lymphoma (NHL, 10 patients) or chronic lymphocytic leukaemia (CLL, seven patients) were treated with a combination of fludarabine 25 mg/m2/d and cyclophosphamide 250 mg/m2/d for 3 d repeated every 4 weeks. 12 patients had previously received purine analogue therapy of which four had progressive disease during treatment. The overall response rate of patients with CLL was 71% (28% CR, 43% PR) and for NHL was 50% (0% CR, 50% PR). Toxicity consisted of nausea and vomiting which was maximal in the 3 d after therapy, infections and haematological suppression which was prolonged in some patients. This combination, which is based on a rational prediction of synergistic activity, is highly effective but associated with significant problems with tolerance.
We describe two cases of interstitial lung disease in patients with non-Hodgkin's lymphoma who were treated with combination chemotherapy including mitozantrone. In both we had radiological and histological evidence of interstitial lung disease, with patterns of organizing pneumonia and hypersensitivity without a clear aetiological agent. Clinical resolution occurred on withdrawal of chemotherapy. One patient required a course of corticosteroid treatment. To date, both patients are well and in remission, and there has been no recurrence of their respiratory disease. We postulate that these observations are hitherto undescribed pulmonary abnormalities secondary to mitozantrone therapy.
OBJECTIVE: The aim of this study was to determine the feasibility of screening for hand osteoarthritis (OA) using a postal survey. METHODS: Men and women aged 40-79, selected at random from a general practice in Nottingham, were sent a postal survey concerning arm pain. Subjects were asked to identify presence of any nodes, based on a diagrammatic example, and to document specific distal (DIP) and proximal (PIP) nodes. One hundred and thirty-nine subjects were subsequently assessed by a nurse metrologist, blinded to the subjects assessment. Subject-observer agreement was measured by calculating unweighted kappa (kappa). In addition, sensitivity and specificity were calculated, taking observer-identified nodes as the 'gold standard'. Intraobserver reproducibility was assessed on 10 subjects with nodes. RESULTS: Intraobserver reproducibility was reasonable at all sites (kappa>/=0.59). Of the 56 subjects with observer-identified 'any nodes', 40 subjects had correctly identified them (sensitivity 71.4%); with three subjects incorrectly identifying nodes (specificity 96.4%). Corresponding kappa was 0.70. Subject-observer agreement was higher for presence/absence of any DIP nodes than PIP nodes (kappa=0.67 and 0.36 respectively). As with nodes overall, specificity was high (100% and 96.6% respectively). Agreement was generally poor for specific joint involvement. CONCLUSION: A postal survey is a useful screening tool for identifying subjects with nodes. Although sensitivity may not be sufficient to permit assessment of prevalence of hand OA in the community, it has potential applications in terms of identifying and defining cases for further study.