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Biomedical subjects

T Engel

Publications and source records attributed to T Engel.

At least 19 recordsLinked to original sources

Acute effects of tumor necrosis factor alpha or lymphotoxin on global blood flow, laser Doppler flux, and bioenergetic status of subcutaneous rodent tumors.

Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon application of the cytokines a significant drop in TBF was found at t greater than or equal to 90 min with a stronger action following rhLT than rhTNF-alpha. At relatively constant mean arterial blood pressure values following the cytokine injection, the microcirculatory function in the tumor periphery was found to be impaired somewhat earlier than TBF, indicating that the cytokines do not preferentially act on the poorly perfused tumor center in the model chosen. This finding is inconsistent with previous histological studies on murine tumors. Acute flow changes encompassed only substantial reductions (i.e., hypoperfusion) rather than a complete ischemia. TBF was slightly increased during the first hour following rhLT whereas after rhTNF-alpha a continuous drop was observed. This differential response could not be observed during laser Doppler flowmetry. Tumor vascular resistance changes largely reflected alterations in TBF. 31P-Nuclear magnetic resonance spectroscopy on murine Meth-A fibrosarcomas revealed dose- and time-dependent decreases of ATP/Pi and phosphocreatine/Pi ratios following i.v. administration of rhTNF-alpha. From comparisons of dose-response curves rhLT appears to be more detrimental than rhTNF-alpha with respect to the bioenergetic status. The observed changes in tumor energy metabolism are similar to those described for TBF. It may therefore be concluded that most of the cytokine effects on the bioenergetic status are secondary to the inhibition of the microcirculatory function. As a major causative factor for the latter, an arterial hypotension can be excluded in the tumor model chosen.

Adenosine Triphosphate

Effects, side effects and plasma concentrations of terbutaline in adult asthmatics after inhaling from a dry powder inhaler device at different inhalation flows and volumes.

1. The efficacy of a metered dose inhaler (MDI) is highly dependent on the mode of inhalation. The relatively high built-in resistance in the Turbohaler (TBH), a new dry powder inhaler device for inhalation of terbutaline sulphate and budesonide, reduces the flow during inhalation. We compared five different modes of inhalation using the terbutaline TBH in 10 stable asthmatic subjects, who were tested on 5 consecutive days. 2. Measurement of 10 different parameters of pulmonary function indicated that the full bronchodilatory effect of an inhaled dose was already achieved at 5 min after the inhalation. Inspiratory flows through the TBH varying from 34 to 88 l min-1 resulted in comparable bronchodilation, and a previous exhalation to residual volume proved of no value. However, if, prior to inhalation, an exhalation through the device was performed, a substantially reduced effect was seen. 3. Reducing the inspiratory flow to approximately 34 l min-1 produced slightly reduced side effects and lower plasma terbutaline concentrations.

Adult

Airway calibre as a confounder in interpreting bronchial responsiveness in asthma.

BACKGROUND: The relation between airway responsiveness to constrictor agents and forced expiratory volume in one second (FEV1) is important when interpreting change in airway responsiveness after an intervention. The aim of the study was to analyse the relation between FEV1 as a percentage of predicted values (% predicted) and airway responsiveness between and within asthmatic subjects. METHODS: Results of non-specific bronchial challenge tests were pooled from two randomised crossover studies comparing the effect of a non-sedative antihistamine with placebo in 35 patients with moderate asthma. The design of the two studies was similar: the provocative concentration of either histamine (first study) or methacholine (second study) resulting in a 20% decrease in ventilatory capacity (PC20) was repeated at two week intervals while patients were treated with the antihistamine or placebo. The dose of inhaled corticosteroid was gradually reduced during the study. Data were analysed with PC20 as the dependent variable in a general linear model so that the influence on PC20 of inhaled corticosteroid dose, antihistamine, and choice of bronchoconstricting agent could be separated from the influence of FEV1% predicted. RESULTS: The correlation coefficient between mean PC20 and mean prechallenge FEV1 for each patient was 0.45. In the general linear model two thirds (65%) of the variation in PC20 was due to variation between subjects. One third of the within subject variation in PC20 could be explained by variation in prechallenge FEV1% predicted (a change in FEV1 of 27% predicted was associated with one doubling or halving of PC20). Treatment with the antihistamine had no influence on PC20, except when histamine was used as the bronchoconstricting agent. The dose of inhaled corticosteroid had a small but significant effect. CONCLUSIONS: The variation in a patient's PC20 over time (several months) is related to changes in FEV1% predicted. Variation in FEV1% predicted explains less of the variation in bronchial responsiveness between subjects where a patient specific factor, which is probably related to the pathogenesis of bronchial asthma, seems to dominate.

Adrenal Cortex Hormones

The interaction of electrosurgical bipolar forceps and generators on an animal model of fallopian tube sterilization.

Electrosurgical tubal sterilization with bipolar forceps has shown a variable and, in certain studies, a high failure rate. Some physicians have questioned if failure rates are due to an incompatibility between bipolar forceps and bipolar generators of different manufacturers. This manuscript presents data on tissue desiccations performed on a rat uterine horn model that uses two bipolar forceps of quite different designs and two popular bipolar generators. The data demonstrate that if an appropriate amount of energy, between 100 and 117 J, is applied to the tissue, consistent destruction occurs, regardless of the generator-forceps combination used. Histologic examination of the desiccated uterine horns displayed complete occlusion of all samples 8 weeks after the procedure. However, immediately and at 3 weeks after the procedure patent uterine horns were found. In the patent samples most samples displayed considerable electrosurgical damage.

Animals

Single-dose inhaled budesonide in subjects with chronic asthma.

In 30 stable asthmatics, a comparison was made between the changes in pulmonary function (FEV1, FVC, PEF, MEF75, MEF50 and MEF25) hourly for 9 h after a single dose of inhaled budesonide 1,600 micrograms, and placebo. All subjects used inhaled steroids daily; this medication was, however, withheld 8 days prior to the study. For all parameters of pulmonary function, a significant difference in favour of budesonide was demonstrated. The effect tended to decrease after 9 h, and had abated within 24 h. FEV1 age, sex, smoking habits, or results of an inhaled beta 2-agonist reversibility test could not be demonstrated as predictors of those subjects to react with the most pronounced responses to budesonide. In conclusion, our results demonstrate an effect 3 h after administration of an inhaled glucocorticosteroid in adult outpatients with chronic asthma. These results parallel previous findings in highly selected asthmatics and after systemic administration of glucocorticosteroids. Single-dose administration and subsequent monitoring for 8-9 h may therefore prove valuable in evaluating new prophylactic agents for the treatment of asthma.

Administration, Inhalation

Glucocorticosteroid therapy in acute severe asthma--a critical review.

Glucocorticosteroid (GCS) therapy is one of the corner-stones in the treatment of asthma. Its value in acute severe asthma is still open for debate. Many of the papers published on the topic are subject to methodological problems. In 8 of 13 placebo-controlled studies, GCS therapy proved to be superior to placebo, evaluated either as result of pulmonary function, blood gas tension, or hospital admission rate. The most important point for GCS therapy in acute severe asthma seems to be frequent dosage, typically 4 times daily. Oral and intravenous administration seem to have equal efficacy. Only 2 of 10 studies were able to prove a dose-response relationship. Both studies included very low doses of GCS. Doses of 100-200 mg of methylprednisolone for 24 h seem as effective as high doses. A protective effect against relapses within a certain time after the GCS therapy has been demonstrated only for periods not exceeding 4 weeks, and only in children. So far, no study has been able to depict the categories of patients who may or may not benefit by the addition of GCS therapy to the symptomatic treatment of acute severe asthma.

Acute Disease

Methylprednisolone pulse therapy in acute severe asthma. A randomized, double-blind study.

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.

Acute Disease

Peak inspiratory flow and inspiratory vital capacity of patients with asthma measured with and without a new dry-powder inhaler device (Turbuhaler).

In 101 asthmatic adults with varying degrees of bronchial obstruction, lung function tests including peak inspiratory flow (PIF), inspiratory vital capacity (IVC), peak expiratory flow (PEF), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) measurements were made. Significant correlations between inspiratory and expiratory volumes were found. In most patients, PIF was less reduced than the expiratory parameters of pulmonary function. When inhalation was performed through the new multi-dose, dry-powder inhalation device, Turbuhaler (PIF-TBH), it was significantly lower than PIF measured without Turbuhaler. In previous studies, PIF-TBH of 30 l.min-1 or more has proven sufficient to produce a therapeutic dose of terbutaline, and to produce significant bronchodilatation. Of 101 asthmatics in the present study, only four had PIF-TBH of less than 30 l.min-1. Although no parameters of spirometry could accurately predict PIF-TBH, there was a tendency for patients with severely impaired ventilatory capacity to produce lower PIF-TBH than patients with normal or near-normal ventilatory capacity. If patients with severely impaired ventilatory capacity are to receive inhalation therapy through Turbuhaler, either PIF or PIF-TBH should be measured, or the effect should be carefully monitored.

Adult

A comparison of two RAST methods and skin prick testing in the diagnosis of wasp venom allergy.

With the aim of evaluating the correlation between skin prick test and two radioallergosorbent tests (RAST) using paper (P-RAST) and Al(OH)3 (Al-RAST) as sorbent materials, 45 consecutive patients known to have been stung by wasp within 6 months were examined. Four patients had a normal reaction, four a large local reaction and 37 a systemic reaction. We found a good correlation between a systemic reaction and a positive P-RAST. Fifty-one per cent of patients with a systemic reaction had a negative Al-RAST, whereas only 8% had a negative P-RAST. Eight per cent of patients with a systemic reaction had a negative SPT. In the eight patients without a systemic reaction, the same patient reacted positively in Al-RAST and P-RAST.

Adolescent

Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler.

The aim of this open, randomized cross-over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurized metered dose inhaler with a 750 ml spacer attached, or via a new dry powder inhaler, Turbuhaler, in 28 patients with stable bronchial asthma. During the 2-week run-in period, the patients received their ordinary inhaled steroid treatment. This was followed by two 4-week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI. The patients were divided into two groups according to their previous, inhaled steroid doses. Group A received 400 micrograms of budesonide b.i.d, and Group B 800 micrograms of budesonide b.i.d. Diary cards were used by the patients at home to report asthma symptoms, beta 2-agonist consumption, and PEF twice daily, as well as the number of coughs experienced in a 5-min period after steroid inhalation. Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI. The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI. In all other parameters recorded (e.g. FEV1, evening PEF, histamine PC20 and other diary measurements) there were no statistically significant differences between the two devices. Turbuhaler was significantly more appreciated than MDI in all questions of preference. The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Effect of a non-sedative antihistaminic (loratadine) in moderate asthma. A double-blind controlled clinical crossover-trial.

Seventeen patients with perennial asthma, stable on a moderate dose of inhaled steroid, participated in a crossover study comparing the clinical effect of a non-sedative, potent and highly selective H1 antagonist (loratadine 10 mg) with placebo. Each treatment period began with 2 weeks run-in followed by 8 weeks on either antihistamine or placebo. During the 8-week periods inhaled steroid was gradually tapered according to a fixed scheme. One patient was withdrawn from active treatment and three from placebo periods because of decreasing lung function (P greater than 0.1). Among the remaining 13 patients there was a threefold (1.8-4.8) decrease in the bronchial sensitivity to histamine during treatment with antihistamine compared to placebo (P less than 0.01). There was a trend in favour of active treatment with regard to changes in all symptom scores, lung function and use of escape medication, but these differences were not statistically significant. The increase in FEV1 was less than 5% of predicted normal (P less than 0.05). We concluded that the bronchial response to histamine can be attenuated by loratadine, an oral H1 receptor antagonist, but further studies are necessary to assess the clinical usefulness and place of loratadine in the therapy of asthma.

Adult

A comparison of airway responsiveness in smokers with chronic bronchitis and in asthmatic subjects.

Fifty-two of 95 smokers with a forced expiratory volume in one second (FEV1) above 70% predicted and with chronic bronchitis were found to have increased bronchial responsiveness, expressed as PC20FEV1, upon challenge with inhaled histamine. The degree of responsiveness was significantly below that found in matched asthmatics, but substantially higher than that reported in normals. The degree of responsiveness was significantly correlated to prechallenge ventilatory capacity, age and tobacco consumption but not to sex. PC40MEF50 showed the same distribution as PC20FEV1, but did not add further information. The slope of the dose response curve expressing the maximum expiratory flow at 50% of vital capacity expired (MEF50) did not correlate with any of the parameters measured. The slope of the FEV1 dose-response curves showed significant correlation with tobacco consumption. The degree of bronchial responsiveness as an indication for future disability needs to be investigated.

Adult

A trial of inhaled budesonide on airway responsiveness in smokers with chronic bronchitis.

The aim of the present randomized, double-blind study was to evaluate the effect of inhaled budesonide on daily symptoms, ventilatory capacity, and airway responsiveness in smokers with chronic bronchitis. Twenty-five subjects with a provocative concentration producing a 20% fall in forced expiratory volume in one second PC20(FEV1) less than 2.0 mg.ml-1, by bronchial histamine challenge, were included. Eighteen subjects accomplished the entire 12 week study, eight receiving inhaled budesonide 400 micrograms b.i.d. and ten receiving placebo. Cough decreased significantly in the actively treated group during the treatment period, but no change could be demonstrated in expectoration, dyspnoea, or sleep disturbances. No changes in any of these symptoms were found in the placebo group, and no differences in symptoms scores were found between the groups. No significant differences in ventilatory capacity or bronchial responsiveness could be demonstrated. In conclusion, a moderately high dose of inhaled steroid in eight subjects with chronic bronchitis did not improve the symptom scores, ventilatory capacity, or airway responsiveness to any clinically relevant degree.

Administration, Inhalation

Reducing bipolar sterilization failures.

Many bipolar sterilization failures have occurred because of incomplete desiccation of the endosalpinx. This study compared the effect upon human fallopian tubes of different waveforms of electrical energy at advancing power settings. When the Valleylab SSE2-L generator was attached to the Kleppinger bipolar forceps, complete desiccation was confirmed with the power set at 25 W in a cutting waveform. Other waveforms (coagulation and blend) failed to complete the task at the same power setting. An inline current meter assures the operator that all the available energy is delivered. This information should help to reduce bipolar sterilization failures.

Electric Conductivity

Allergy to venom from bee or wasp: the relation between clinical and immunological reactions to insect stings.

Sixty-three patients, applying to the casualty ward after a bee or wasp sting, were tested. On the day of admission, and 4 weeks later, blood was sampled to measure specific IgE and IgG against bee and wasp venom and total IgE. Four weeks after the insect sting, all patients were examined with skin-prick test (1, 10 and 100 micrograms/ml), and intracutaneous test (0.05 ml of extract 1.0 microgram/ml). The amount of venom-specific IgE and IgG increased significantly during the 4-week period, venom-specific IgE was most pronounced in patients experiencing the most severe clinical reactions. However, no significant correlations were found between the results of the immunological tests carried out 4 weeks after the insect sting and the clinical reaction upon the insect sting.

Animals

Basophil histamine release in insect venom allergy.

The aim of the present study was to investigate venom-related and venom-non-related immunological reactions in patients stung by bee or wasp. Sixteen consecutive patients (7 with local and 9 with systemic reactions) were tested with skin tests, RAST and basophil histamine release (BHR) test immediately after the insect sting and 2, 4, and 16 weeks later. No test was useful immediately after the insect sting, the "anergic period". In agreement with earlier findings, the SPT was the only allergy test that showed statistically significant differences between patients with local and systemic reactions, although a great overlap was found. Release of histamine from basophils after incubation with anti-IgE also showed statistically significant differences between local and systemic reactions. Further studies are needed, especially measurement of BHR after incubation with anti-IgE before insect stings.

Adult

Prognosis of patients reacting with urticaria to insect sting. Results of an in-hospital sting challenge.

Insect sting challenge in 14 patients with urticarial reaction to last insect sting resulted in two systemic reactions (95% confidence limits 0-6 patients), a reaction rate of 14%. Skin prick test, basophil histamine release, RAST, and allergen-specific IgG, alone or in conjunction, could not indicate the patients to react systemically after sting challenge. Further, the systemic reactions were uninfluenced by type of insect and time elapsed since last insect sting. It is concluded that the reaction to future insect stings cannot be predicted by the immunological tests presently available.

Adolescent