Observation of a field induced transition in the vortex solid of DyBa2Cu3O7/(Y1-xPrx)Ba2Cu3O7 superlattices.
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Biomedical subjects
Publications and source records attributed to M Andersson.
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The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria. The patients were given a single dose of 2 mg nicotine from the nasal spray with and without concurrent administration of a nasal vasoconstrictor decongestant, xylometazoline, in randomised order. Control session measurements were made in the disease-free state. Applying strict bioequivalence criteria, we found that common cold/rhinitis slightly reduced the bioavailability of nicotine, both in its rate and extent; the geometric mean of the ratio of Cmax, AUC and tmax were 0.81, 0.93 and 1.36, respectively. The nasal vasoconstrictor, xylometazoline, normalised the extent of the bioavailability of nicotine, but further prolonged the time for absorption to almost twice that measured in the disease-free state, increasing the tmax ratio to 1.72. The results suggest that a minor proportion of people stopping smoking with the help of a nicotine nasal spray may experience a minor reduction in the effect of the spray during common cold/rhinitis. However, the nicotine self-titration behaviour found with most smoking cessation products (except the nicotine patch) will automatically lead to an adjustment of the dosage to achieve the desired effect.
Hyper-reactivity to non-specific challenges has been considered a hallmark of asthma and is defined as an abnormal responsiveness of the bronchial airways to a variety of provocative agents. The mechanisms underlying hyper-reactivity in the upper and lower airways are not known. By using the nose to study the inflammatory response possible abnormalities can be investigated carefully and pathophysiology of specific airway hyper-reactivities can be better understood. Other factors than merely constriction of the bronchial smooth muscles can cause narrowing of the free lumen to airflow. Functionally different and very distinct mucosal end-organ reactivities may also be increased. If these reactivities can be well assessed, specific airway hyper-reactivity can be defined. In the present report, specific mucosal end-organ hyper-reactivities in the allergic nasal mucosa are presented. Certain widespread hypotheses, such as the role of the eosinophil and the "increased absorption permeability theory", are disputed.
S-(4-hydroxybenzyl)glutathione was isolated as the major principle responsible for the inhibition of the in vitro binding of kainic acid to brain glutamate receptors by water extracts of the plant Gastrodia elata. The affinity (IC50 value) of the compound is slightly lower compared to glutamate and glutathione.
The results from a prospective randomized trial comparing two different radiation schedules for treatment of painful bone metastases in women with recurrent breast cancer are presented. A total of 217 patients with painful bone metastases were randomized to either 30 Grey (Gy) in ten fractions, five fractions a week (5F/W) or 15 Gy in three fractions 2F/W. The effect of treatment was evaluated by pain assessment, the radiological response and the degree of side-effects. The patients were rated at start of treatment and after 1, 3, 6 and 12 months. No difference between the two radiation regimes was found, neither in achieved pain relief, improvement in level of activity and medication, nor was there any difference in radiological response and side-effects from treatment. Both regimes resulted in a significant improvement in both pain score and level of activity 1 month after treatment, an improvement which persisted during the follow-up period. We conclude that 15 Gy given in three fractions 2F/W is as effective as 30 Gy in ten fractions 5F/W, but more convenient to the patient and of less cost to society.
Ascorbate is known to be cytotoxic by generating free oxygen radicals, a property shared with the diabetogenic drug alloxan. Some reports indicate that also ascorbate may be diabetogenic. In this study the cytotoxicity of ascorbate on isolated mouse islet cells has been investigated. Ascorbate (0.5-2.0 mmol/l) induced a concentration-dependent increase of trypan blue uptake by the cells, indicating an increase of membrane permeability to the dye. Trypan blue uptake induced by 2.0 mmol/l ascorbate was inhibited by concomitant incubation of the cells with 200 mg/l superoxide dismutase, 200 mg/l catalase, 3.0 mmol/l cytochrome-c or 50 mumol diethylenetriaminepentacetic acid (DTPA), but not by 50 mmol/l D-mannitol. The results indicate that ascorbate is cytotoxic to islet cells by metal-catalysed free radical generation.
An alternative method for manufacturing fixed prostheses that uses machine digitalization and a combination of milling and spark erosion has been developed. The digitizer used has a contact probe with a ball-shaped tip. This study evaluated the accuracy of the device and the transfer of data from the individual die to the computer. The dimensions of a square gauge as read by the machine were compared with the known dimensions of the object with a computer, which allowed determination of the accuracy of the digitalization. Procera machining and the implications for reliable prosthodontic treatment are discussed.
BACKGROUND: Microvascular-epithelial exudation of bulk plasma may characterize inflammatory airway diseases. This study compares the acute allergen challenge-induced mast cell and exudative responses in nasal and bronchial airways. The focus is on alpha 2-macroglobulin as an index of luminal entry of plasma exudates. METHODS: Separate nasal and bronchial allergen challenges were carried out outside the pollen season in eight patients with pollen-induced seasonal allergic rhinitis. The levels of different-sized plasma proteins (albumin molecular weight, 66,000 d and alpha 2-macroglobulin molecular weight, 725,000 d) and tryptase were determined in pre- and postchallenge nasal lavage and bronchoalveolar lavage (BAL) fluids. Diluent and increasing doses of allergen were sprayed into the right nasal cavity, and each challenge was followed by a nasal lavage (volume, 15 ml) with a "nasal pool" device (recovery, > 80%). Endobronchial allergen challenge (individual doses) and BAL (volume, 2 x 25 ml) were performed in a lobe bronchus through a fiberoptic bronchoscope (recovery, 30%). Saline challenge and BAL were carried out in the contralateral lung as control. RESULTS: The levels of albumin, alpha 2-macroglobulin, and tryptase increased dose-dependently in postchallenge nasal lavage fluids (p < 0.05) and correlated to nasal symptoms. In particular, albumin and alpha 2-macroglobulin correlated (r = 0.98, p < 0.001). Both alpha 2-macroglobulin and tryptase, but not albumin, were increased in BAL fluids from the allergen-challenged side (p < 0.05). CONCLUSION: Local allergen challenge causes luminal entry of tryptase and alpha 2-macroglobulin in the nose and bronchi of patients with allergy. We suggest that mast cell and plasma exudation responses may be similar in human nasal and bronchial airways and that albumin levels (in BAL fluids) may not well reflect the exudation process in bronchial airways.
BACKGROUND: Despite the wide use of antihistamines in the treatment of allergic rhinitis, little is known about effects of these drugs on airway mucosal indices, which specifically reflect either mast cell release activity (tryptase) or microvascular-epithelial exudation of bulk plasma (alpha 2-macroglobulin). OBJECTIVE: This study, involving subjects with seasonal allergic rhinitis, examines the effects of loratadine treatment on allergen-induced nasal mucosal output of tryptase and alpha 2-macroglobulin. Effects on nasal symptoms and eosinophils are also examined. METHODS: Placebo and loratadine (20 mg) were given orally once daily for 5 days at 6-week intervals. Nasal diluent and allergen challenges were carried out on day 5. The mucosa was lavaged with saline solution after each challenge, and nasal lavage fluid levels of tryptase and alpha 2-macroglobulin were determined. Nasal symptoms were scored, and nasal peak expiratory flow rates were measured. Superficial cells (eosinophils) were obtained with a brush device before and 24 hours after the allergen challenges. RESULTS: Allergen dose-dependently increased the nasal symptoms and the lavage fluid levels of alpha 2-macroglobulin and tryptase. Allergen also reduced the nasal peak expiratory flow rates. Loratadine inhibited the exudation of alpha 2-macroglobulin and reduced tryptase levels, nasal symptoms, and obstruction, but did not affect the number of eosinophils. CONCLUSION: The inhibitory effects of loratadine on nasal lavage fluid levels of alpha 2-macroglobulin suggest that histamine, through effects on microvascular H1-receptors, mediates allergen challenge-induced exudation of bulk plasma in acute allergic rhinitis. The reduced lavage fluid levels of tryptase suggest either that loratadine directly attenuates mast cell release activity or that loratadine, through inhibition of the exudation process, simply attenuates luminal entry of tissue solutes (in this case, tryptase).
Spectral turbulence analysis of the signal-averaged electrocardiogram is a new method for identifying patients prone to sustained monomorphic ventricular tachycardia. In contrast to analysis in the time domain, it has been claimed to be applicable in patients with bundle branch block. The aim of this study was to assess the predictive value of spectral turbulence analysis, in relation to the inducibility of sustained monomorphic ventricular tachycardia, in patients with and without bundle branch block. One hundred and sixty nine patients, of whom 120 had a QRS duration > or = 120 ms, were studied. Forty-seven patients had inducible sustained monomorphic ventricular tachycardia and were compared to 122 control patients. The overall sensitivity of the spectral turbulence analysis for predicting inducible ventricular tachycardia was 77%, the specificity 35% and the total predictive accuracy 47%. The limited predictive accuracy was mainly due to a lack of difference between patients with and without ventricular tachycardia in patients with a QRS duration > or = 120 ms. In patients with QRS < 120 ms, however, there were significant differences in all spectral turbulence parameters and the method had a sensitivity of 75%, a specificity of 72% and a total predictive accuracy of 73%. The diagnostic usefulness of spectral turbulence analysis is dependent upon normal QRS duration and the method is applicable only to patients without bundle branch block.
BACKGROUND: Mucosal exudation of plasma is a non-injurious, physiological response of the airway microcirculation to different inflammatory processes. The exudative response is similar in the nose and bronchi and exudation occurs in both allergic asthma and rhinitis. The exudative response is a specific end-organ function of the mucosal microcirculation that may be altered in airway diseases. OBJECTIVE: This study examines the hypothesis of altered responsiveness of the superficial airway microcirculation to vascular permeability-increasing challenges in sustained allergic inflammation. METHODS: Fourteen patients with birch-pollen induced allergic rhinitis were studied for 7 weeks during a Swedish birch-pollen season. Nasal symptoms (itching, sneezing, blockage, and discharge) were recorded and the occurrence of pollen was determined. The plasma exudation response was examined by topical histamine challenges at the end (May) and well out of (December) the season. Challenge and lavage were carried out concomitantly using a 'nasal pool'-device. The unilateral nasal cavity was filled for consecutive 10 minute periods with saline and two concentrations of histamine (80 micrograms/mL and 400 micrograms/mL). The lavage fluid levels of different-sized plasma proteins (albumin-66,000 D, fibrinogen-340,000 D, and alpha 2-macroglobulin-725,000 D) were determined. RESULTS: The pollen season was mild resulting in only minor nasal symptoms. Histamine produced exudation of all plasma proteins across the microvascular epithelial barriers with particularly strong correlation between the levels of albumin and alpha 2-macroglobulin (r = 0.98; P < 0.001). The exudative response to histamine was concentration-dependent (P < 0.05) and, furthermore, it was significantly greater late into the season compared with outside the pollen season (albumin: P < 0.05, fibrinogen; P < 0.05, alpha 2-macroglobulin: P < 0.01). CONCLUSION: We conclude that histamine produced concentration-dependent nasal airway exudation of bulk plasma in subjects with seasonal rhinitis and that this response is abnormally great during the pollen season. Whether angiogenesis or increased responsiveness of the microvascular endothelium may explain this phenomenon now remains unknown. We suggest that a microvascular exudative hyperresponsiveness may characterize allergic airway disease.
Coronavirus-induced common cold and allergen-induced rhinitis are characterized by nasal mucosal exudation of bulk blood plasma. The mucosal exudation process involves 'flooding' of the lamina propria with plasma-derived binding proteins and it is possible that subepithelial inflammatory cytokines and mediators may be moved by the exudate to the mucosal surface. In this study, we have analysed cytokine levels in nasal lavage (NAL) fluids from non-allergic subjects inoculated with coronavirus (n = 20) and from subjects with allergic (birch pollen) rhinitis subjected to additional allergen challenge (samples were obtained 35 min post challenge) in the laboratory (n = 10). Ten of the 20 inoculated subjects developed common cold and 10 remained healthy. Interferon-gamma (IFN gamma), interleukin-1 beta (IL-1 beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-6 were analysed in unprocessed NAL fluids using immunoassays. The subjects who developed common cold had increased NAL fluid levels of IFN gamma (P < 0.05) that correlated well with the symptoms (P < 0.001). IFN gamma did not increase in subjects with allergic rhinitis. IL-1 beta levels were similar in NAL fluids obtained from all inoculated subjects. In the subjects with allergic rhinitis NAL fluid levels of both IL-1 beta and GM-CSF were increased (P < 0.05). GM-CSF was not detected in common cold. IL-4 and IL-6 were not detectable in any of the NAL fluids. The present cytokines may not only emanate from superficial mucosal cells. By aiding plasma exudation subepithelial cytokines may potentially also be retrieved on the mucosal surface.(ABSTRACT TRUNCATED AT 250 WORDS)
Mucosal exudation of nonsieved bulk plasma is a key feature of airway defense and inflammation. We have previously observed in guinea pig tracheobronchial airways that endogenous nitric oxide (NO) of the mucosa may tonically suppress the permeability of the subepithelial microcirculation, and that topical administration of the NO donor nitroprusside may reduce plasma exudation responses. The present study examines whether nitroprusside affects histamine-induced mucosal exudation of plasma in the human nasal airway. In a dose-finding tolerability experiment, using changes in nasal patency as response, placebo and nitroprusside (1.2 and 3.6 mg per nasal cavity) were applied on the mucosal surface with a nasal-spray device. Nasal peak expiratory flow (PEF) rates were measured before the application and thereafter every third minute for 15 min. Nitroprusside produced a dose-dependent decrease in nasal PEF rates compared to placebo. Placebo or nitroprusside (7.2 mg) was then given to the right nasal cavity, followed 3 min later by challenge with saline or histamine (600 micrograms). The drug and the challenge were both applied with a nasal-spray device. With a nasal pool-device, the same large part of the nasal mucosal surface was lavaged before and after the treatment/challenge. The lavage fluid levels of alpha 2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. The histamine-induced lavage fluid level of alpha 2-macroglobulin was significantly higher after treatment with placebo than with nitroprusside. The present data indicate that nitroprusside may have antiexudative effects in human airways. Hence, unlike other microvascular permeability active agents, this pharmacologic principle may be active in both guinea pig and human airways.
It is debatable whether beta 2-receptor agonists produce antiallergic effects in human airways. This question has been addressed in the present study by examination of both mast-cell indices and the physiologic response to allergen challenge in human nasal airways. Twelve asymptomatic patients with seasonal allergic rhinitis were investigated outside the pollen season. Intranasal allergen provocation was carried out with diluent and three increasing doses of allergen. Topical terbutaline sulfate (1.0 mg) was given 5 min prior to each allergen challenge and nasal lavage was carried out 10 min after each challenge. The study design was double-blind, placebo-controlled, crossover, and randomized. The allergen challenge-induced mast-cell activation and the ensuing physiologic response of the airway tissue were investigated by measuring a mast-cell-derived mediator (tryptase) and plasma proteins (albumin and alpha 2-macroglobulin), respectively, in the lavage fluids. Allergen provocation produced dose-dependent increments of nasal symptoms and lavage fluid levels of tryptase, albumin and alpha 2-macroglobulin. Both nasal symptoms (P < 0.05) and lavage fluid levels of tryptase (P < 0.05), albumin (P < 0.05), and alpha 2-macroglobulin (P < 0.01) were reduced by pretreatment with topical terbutaline sulfate. We conclude that high doses of topical terbutaline may produce significant antiallergic effects in human airways by equally reducing both tryptase release and plasma exudation in the acute allergic reaction in human airways. Further studies are now warranted to determine whether microvascular antipermeability effects of beta 2-receptor stimulation contribute to the present observations.
The Danish Thorotrast Study was recently reestablished and improved. The cohort has been reidentified and followed up, and now comprises 1003 Thorotrast-exposed patients. For all suspected haematological cases, cytological and histological material has been revised and malignant diseases have been reclassified. The numbers of cases of leukemia and other related haematological disorders were as follows: 16 acute myeloid leukemia (AML); 8 myelodysplastic syndrome (MDS); 1 acute lymphatic leukemia (ALL); 3 chronic myeloid leukemia (CML); 4 non-Hodgkin's lymphoma (NHL); 2 multiple myeloma (MM); 2 myelofibrosis (MF); 2 chronic lymphatic leukemia (CLL). Except for CLL, all cases might be Thorotrast-induced. (Expected number of leukemias: < 2.5.) The findings in the German, Japanese, Portuguese and Danish studies are very similar. Some of the characteristic features include a high incidence of AML with several erythroleukemias, many cases of MDS, and a relatively low incidence of CML. In several studies of leukemia induced by alkylating agents, erythroleukemia is also described as a prominent feature. The possibility exists that a phase of relative predominance of erythroid elements in the bone marrow may be a common and not an unusual feature in the pathogenesis of these secondary leukemias. The findings are also compared with histopathological data from a Danish control group of de novo leukemia patients and from atomic bomb survivors with radiation-induced leukemia. The relative frequency of AML is higher among the Thorotrast-exposed patients than among the Danish control group and the A-bomb survivors. In contrast, low relative frequencies are seen for ALL and CML in Thorotrast cases in comparison with de novo leukemia cases and A-bomb survivors. It can be concluded that differences in relative and absolute frequency of leukemias and myelodysplastic syndrome exist not only between the irradiated populations and the unexposed control group, but even between groups exposed to low-LET (linear energy transfer) and high-LET radiation.
On the basis of clinical observations, Irish wolfhounds were suspected as being subject to a relatively high incidence of soft testicular consistency and low semen quality. Thirty-seven Irish wolfhounds and 67 dogs of other breeds (control group) were therefore examined. Conventional andrological studies were performed in both groups, these included libido testing, palpation and measurement of testes and semen evaluation. Semen evaluation was performed both manually and by videomicrographic analysis. Testosterone concentrations were measured both before and after human chorionic gonadotropin challenge in the Irish wolfhounds. The Irish wolfhounds had lower libidos than the control group. More Irish wolfhounds (21.2 per cent) exhibited low semen quality than the control group (6.1 per cent). Soft testicular consistency occurred more frequently in Irish wolfhounds (25.7 per cent) than in the control group (10.5 per cent). In the control group, bodyweight correlated significantly with total sperm count. Serum testosterone concentration did not correlate with semen quality parameters.
BACKGROUND: Mucosal exudation (luminal entry) of bulk plasma is a key feature of airway defence and inflammation. In guinea pig and rat airways this response is readily produced by neurogenic irritants, notably capsaicin. Thus "neurogenic airway inflammation" has become an established concept. The present study examines whether capsaicin also produces mucosal exudation of plasma in human nasal airways both in health and disease (seasonal allergic rhinitis). METHODS: Pain-producing concentrations of capsaicin (30-300 ng/ml) were applied to the nasal mucosal surface both before and late into the pollen season. Levels of albumin in nasal lavage fluid were measured as an index of mucosal exudation of plasma. In a separate group of patients with seasonal allergic rhinitis nasal challenge with an exudative concentration of histamine was carried out before the birch pollen season and concentrations of albumin in lavage fluid were measured. RESULTS: Pollen counts and symptom scores revealed a mild pollen season. Capsaicin produced considerable nasal pain and this response was augmented late into the season when capsaicin also produced nasal blockage. However, capsaicin failed to produce any mucosal exudation of plasma either before or late into the pollen season. The exudative effect of histamine was confirmed. CONCLUSIONS: The augmented pain response to capsaicin suggests that a sensory nerve hyperresponsiveness may characterise allergic airways disease. In contrast to the effects on animal airways, capsaicin failed to produce mucosal exudation of plasma in the human nasal airway. The animal based neurogenic inflammation concept is therefore not valid for the human nasal airway, not even in inflamed airways when a neural hyperresponsiveness has developed.