Increased nitric oxide elimination from the airways after smoking cessation

Smokers have been found to have low exhaled nitric oxide (NO) levels. The aim of the present study was to investigate where in the respiratory system the decrease in NO occurs, and whether this decrease was affected by smoking cessation. Measurements of exhaled NO were carried out in smokers (n=20) and non-smoking control subjects (n=30). In nine of the smokers, exhaled NO was analysed 1, 2 and 4 weeks after smoking cessation. The level of exhaled NO at a flow rate of 0.1 litre/s was significantly lower in smokers (4+/-2 p.p.b.) than in non-smokers (7+/-5 p.p.b.; P=0.007). A calculation of the contributions from different areas of the lung showed that the NO flux from the airways was significantly lower (14+/-10 compared with 36+/-26 nl/min; P=0.0001) and the alveolar fraction was significantly higher (2.1+/-0.8 compared with 1.5+/-0.9 p.p.b.; P=0.006) in smokers than in non-smokers. Nine smoking subjects refrained from smoking for 4 weeks, and this resulted in increased NO flux from the airways of 28+/-17 nl/min, which was no longer significantly different from controls. In conclusion, endogenous production of NO in the airways is decreased in smokers, but can be restored to normal values by 4 weeks after cessation of smoking. Smokers have an increased alveolar fraction of NO, and this might be a diagnostic sign of lung damage. Thus NO monitoring can be used to indicate improvements when a smoker decides to stop smoking.     

A supportive climate and low strain promote well-being and sustainable working life in the operation theatre

Abstract

Background: Shortage of health-care workers e.g. in operating theatres is a global problem. A shortage of staff negatively affects patient outcomes, making it important to keep the employees from quitting. The aim of this survey was to study if well-being, zest for work, and thoughts about leaving work in an operating theatre can be related to the psychosocial work environment, as described by the job demand-control-support (JDCS) model.

Methods: A questionnaire was provided to personnel in operating theatres of seven Swedish hospitals (n?=?1405, with a response rate of 68%) that included the JDCS model, personal factors, work ability, well-being, zest for work, and thoughts about leaving their position. Ordinal scale regression was used for analyses.

Results: A majority reported moderate to high zest for work (76%). A minority (30%) had sometimes thought during at least one month in the last year of leaving their position. Lower social support scores and high demands together with low control (high-strain) scores were related to lower well-being, lower zest for work, and more thoughts about leaving the position. Anaesthetists scored in the low-strain field, nurse anaesthetists and assistant nurses in the passive field, and operating nurses in the active field, in comparison to all personnel.

Conclusion: According to the JDCS model, both lower social support and high strain were related to lower well-being and negative thoughts about the position. Social support scores were about the same for different occupational groups in the operating theatre, and no occupation scored on average in the high-strain field.     

CD46 accelerates macrophage‐mediated host susceptibility to meningococcal sepsis in a murine model

CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement‐mediated attack. Human transgenic CD46 homozygous mice (CD46^+/+) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined thatCD46^+/+ mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro‐inflammatory mediators such as IL‐6, TNF, IL‐12, and IL‐1β In the presence of M‐CSF or GM‐CSF, CD46 signaling enhances monocyte‐macrophage differentiation. Additionally, CD46^+/+ macrophages rapidly undergo apoptosis upon LPS challenge or meningococcal infection, which could contribute to uncontrolled bacterial dissemination in vivo. Adoptive transfer of CD46^+/+ peritoneal macrophages aggravated septic responses in wild‐type mice, but the depletion of macrophages partially alleviated septic reactions in CD46^+/+ mice after N. meningitidis infection. Our findings reveal a novel role of CD46 in accelerating inflammatory responses upon meningococcal infection or LPS stimulation by regulating the functional polarization and survival of macrophages.     

Inflammation markers in nasal lavage, and nasal symptoms in relation to relocation to a newly painted building: a longitudinal study

Introduction: There is a need to evaluate possible health effects of ventilation improvements and emissions from new buildings, in longitudinal studies. New methods to study biological effects on the eyes and upper airways are now available. Material and methods: A longitudinal study was performed on 83 trained social workers in two offices in Uppsala, Sweden. The exposed group (n= 57) moved to a newly redecorated building nearby. Low emitting building material had been used, including a new type of solvent-free water-based paint. The control group (n= 26) worked in the same office during the study period (November 1995 to February 1996). Hygiene management was carried out in both offices, at the beginning and the end of the investigation. Tear film stability (BUT) was measured. Nasal patency was measured by acoustic rhinometry, and eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin were analyzed in nasal lavage fluid (NAL). Results: The relocation resulted in an increase in the personal outdoor airflow rate from 11 to 22 l/s. Indoor concentrations of terpenes were higher in the new building, and powdering of the new linoleum floor was observed. Measurements showed low levels of volatile organic compounds (VOC), formaldehyde, carbon dioxide (CO₂), nitrogen dioxide, respirable dust, and microorganisms in the air of all buildings. The move resulted in an increased nasal patency and an increase of ECP and lysozyme in NAL, after adjusting for changes in the control group. No changes were observed for nasal or ocular symptoms. A seasonal effect, with a decrease of ECP, was observed in the control group. Conclusion: A well-ventilated office building can be redecorated without any major ocular or nasal effects, or measurable increase of indoor air pollution if low-emitting building materials are selected. In agreement with previous evidence, the improved ventilation flow may explain the increase of nasal patency. The increase of ECP and lysozyme in NAL suggested an inflammatory effect in the new building. Since this building had increased ventilation flow, increased concentrations of terpenes, and powdering from the polish on the new linoleum floor, identification of causative agents was difficult. The hygiene measures did not give any evidence that emissions from the new type of solvent-free water-based paints or building dampness were responsible for the observed nasal effects. Considering the higher emissions of VOC reported from older types of water-based latex paints and solvent-based wall paints, the new type of solvent-free water-based paint seems to be a good choice from the hygiene point of view. Received: 21 December 1998 / Accepted: 20 June 1999     

Further studies on the mechanism of antipsychotic action: Potentiation by α-methyltyrosine of thioridazine effects in chronic schizophrenics

Summary Six chronic schizophrenics with stationary symptomatology and treated since more than one year with thioridazine in a fixed dose schedule were examined by means of two different rating scales. The thioridazine dosage was then considerably reduced, leading to reappearance of schizophrenic symptoms. The tyrosine hydroxylase inhibitor, -methyltyrosine (2 g daily) was then given as additional treatment, and the thioridazine dosage necessary to reattain the pre-trial level of symptomatology was titrated. This dosage, as well as the simultaneous thioridazine plasma levels, were found to be considerably reduced by -methyltyrosine. The efficacy of this agent as an inhibitor of tyrosine hydroxylase was ascertained by demonstrating a marked reduction in cerebrospinal fluid homovanillic acid. The observations confirm our earlier data and lend additional support for the hypothesis that central catecholamine neurotransmission is involved in the antipsychotic action of neuroleptic agents.     

Tryptophan malabsorption in dementia. Improvement in certain cases after tryptophan therapy as indicated by mental behaviour and blood analysis

Twenty-four senile dementia patients in the age range 65–85 years were subjected to a new sensitive tryptophan loading test: Dopa-Tryptophan loading (“Dop-Try loading”) in order to determine whether Try malabsorption occurs in senile dementia and if so how frequent this is. For comparison the same loading test was performed on 23 subjects in the same age grouping but with normal mental function. The differences in Try absorption were statistically analyzed and this revealed that absorption was less effective in the senile dementia group. Four patients with Try malabsorption were treated with 3 G 1-Try + 50 mg d1-5-hydroxytryptophan (5-HTP) per day orally for 20–30 days and four patients with normal absorption were treated in the same way. The Dop-Try loading test was repeated after this treatment. Two patients showed improved absorption and coincident mental improvement, while one showed decreased absorption and mental deterioration. One died during the course of the treatment. None of the four patients with normal absorption showed mental improvement after the treatment. This pilot study suggests that increase in Try absorption following the Try treatment is a necessary condition for improvement in the mental state. The study is being continued with larger numbers of patients.     

Cost-effectiveness of clozapine treatment in therapy-refractory schizophrenia

The costs and effects of clozapine treatment of refractory schizophrenic patients have been discussed recently. This study shows that 18 months of clozapine treatment results in an improvement of symptoms and social functioning in approximately 70% of treatment-refractory schizophrenic patients, compared with treatment with conventional neuroleptics during a similar period of time. Treatment with clozapine reduces the cost of inpatient care but places increased demands on active rehabilitation resources in outpatient care. This leads to increased total costs in a short-term perspective, but clozapine treatment is cost-saving for annual maintenance therapy. These costs must be weighed against the positive effects on psychotic symptoms and social functioning.