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Biomedical subjects

J B Rasmussen

Publications and source records attributed to J B Rasmussen.

At least 37 records · Page 2Linked to original sources

Urinary LTE4 excretion in antigen-provoked asthmatic patients treated with the inhaled LTD4 antagonist, L-648,051.

Leukotriene (LT) E4 represents the major LT metabolite in man, and its urinary excretion can be used as an indirect marker of systemic LTC4 and/or LTD4 synthesis and release. In the present study LTE4 excretion was monitored for 24 h in 12 atopic patients with mild asthma undergoing antigen bronchoprovocation as part of a double-blind, placebo-controlled, two-period cross-over study of the aerosol-delivered LTD4 antagonist, L-648,051. Urinary LTE4 excretion was also studied separately in six of the patients after inhaling only diluent. Urine was sampled before, and serially after antigen challenge, at intervals corresponding to the immediate (0-3 h postchallenge) and late (3-6, 6-12, 12-24 h postchallenge) asthmatic reactions. LTE4 was determined by reversed-phase HPLC and radioimmunoassay. Forced expiratory volume in 1 s (FEV1) was recorded serially through 8 h after inhalation of antigen and diluent. Compared to base-line measurements, antigen bronchoprovocation induced significant increases in mean LTE4 excretion rates 0-3 h postchallenge (i.e. during the immediate asthmatic response) after treatment with both placebo (P < 0.01) and L-648,051 (P < 0.05). These mean LTE4 excretion rates in the immediate phase were also significantly higher than the mean rates in the late phase (3-6 h and beyond); the excretion rates of LTE4 at these later time intervals were similar to base-line values. After inhalation of diluent, the LTE4 excretion rates in the intervals 0-3, 3-6, 6-12 and 12-24 h were unchanged from base-line values.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Reduced nonspecific bronchial reactivity and decreased airway response to antigen challenge in atopic asthmatic patients treated with the inhaled leukotriene D4 antagonist, L-648,051.

We studied the effect of the inhaled leukotriene D4 antagonist, L-648,051, on antigen-induced bronchoconstriction and nonspecific bronchial reactivity. Ten males with mild atopic asthma completed a double-blind, randomized, two-period, placebo-controlled cross-over study. For a 7-day period patients inhaled either placebo or 6 mg of L-648,051 four times daily. Bronchial reactivity to methacholine was measured at base line (day 1) and after 6 days, treatment (day 7). On day 8, after inhaling 6 mg of the antagonist (or placebo), the patients were challenged by inhaled antigen; they received an additional 6 mg of the antagonist (or placebo) 3 h later. Pulmonary function (forced expiratory volume in 1 s, FEV1) was measured serially through an 8-h post-antigen challenge. Nonspecific airway reactivity was again measured on day 9. Compared to placebo, L-648,051 treatment diminished the methacholine reactivity, on both day 7 (NS) and on day 9 (P < 0.05). In addition, the immediate and late bronchial responses to antigen challenge on day 8 were attenuated in the patients when treated with L-648,051. In the immediate phase (0-3 h postchallenge), the airway response was significantly reduced at all recordings between 20 min and 1 h postchallenge. In the late phase (3-8 h postchallenge), the pulmonary response was also reduced. However, the reduction was statistically significant only at the 5-h recording. The results suggest that sulfidopeptide leukotrienes are of importance for nonspecific airway reactivity, and that leukotriene D4 is a significant mediator in the immediate asthmatic reaction.

Administration, Inhalation↗

Systemic Induction of Salicylic Acid Accumulation in Cucumber after Inoculation with Pseudomonas syringae pv syringae.

Inoculation of one true leaf of cucumber (Cucumis sativus L.) plants with Pseudomonas syringae pathovar syringae results in the systemic appearance of salicylic acid in the phloem exudates from petioles above, below, and at the site of inoculation. Analysis of phloem exudates from the petioles of leaves 1 and 2 demonstrated that the earliest increases in salicylic acid occurred 8 hours after inoculation of leaf 1 in leaf 1 and 12 hours after inoculation of leaf 1 in leaf 2. Detaching leaf 1 at intervals after inoculation demonstrated that leaf 1 must remain attached for only 4 hours after inoculation to result in the systemic accumulation of salicylic acid. Because the levels of salicylic acid in phloem exudates from leaf 1 did not increase to detectable levels until at least 8 hours after inoculation with P. s. pathovar syringae, the induction of increased levels of salicylic acid throughout the plant are presumably the result of another chemical signal generated from leaf 1 within 4 hours after inoculation. Injection of salicylic acid into tissues at concentrations found in the exudates induced resistance to disease and increased peroxidase activity. Our results support a role for salicylic acid as an endogenous inducer of resistance, but our data also suggest that salicylic acid is not the primary systemic signal of induced resistance in cucumber.

Journal Article↗

Reversal and prevention of airway response to antigen challenge by the inhaled leukotriene D4 antagonist (L-648,051) in patients with atopic asthma.

We examined the ability of the inhaled leukotriene D4 antagonist (L-648,051) to inhibit antigen-induced asthmatic responses. Twelve patients with stable exogenous asthma participated in two separate double-blind, placebo-controlled, cross-over trials. The ability of the antagonist to reverse or inhibit antigen-induced bronchoconstrictor response was examined; both the immediate and the late phases were studied. In the reversal study, patients inhaled 800 micrograms of L-648,051 during the immediate phase (15 min after antigen challenge) and again during in the late phase (7 h after antigen challenge). In the prevention study, the same dose (800 micrograms) of L-648,051 was inhaled before the expected immediate reaction (5 min before antigen challenge) as well as before the expected late reaction (2.5 h after antigen challenge). The LTD4 antagonist was not effective in reversing the airway response to inhaled antigen, as measured by airway resistance (Rt), forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC). When the antagonist was given prior to antigen challenge, a slight reduction in Rt was observed during the immediate phase, but not during the late phase. Some improvement in FEV1 and FVC during the immediate phase was also observed, but these changes did not reach statistical significance. These results suggest that LTD4 plays a role in the immediate phase of antigen-induced asthma.

Administration, Inhalation↗

Late airway response increases at repeat allergen challenge.

The relationship between the immediate and late responses to repeated inhalations of allergen was studied. Sixteen male atopic asthmatics were challenged twice with an interval of 2 weeks. Forced expiratory volume in 1 s (FEV1) was measured serially over an 8-hour period after challenge. The method of provocation used implied that only slight differences between the immediate responses on the two provocation days were observed. However, differences in the late responses were demonstrated. Thus, the maximum percent change in FEV1 at the first and second provocation differed significantly in the late (P less than 0.01), but not in the immediate phase. The increase in maximal late response was greater than the small change in maximal immediate response (P less than 0.05). Further, the FEV1 values from 4 to 8 h post-challenge were in each recording significantly lower on the second day suggesting a more pronounced late bronchial response to repeat challenge. The results suggest that after one challenge specific airway reactivity, i.e., reactivity to allergen, at a subsequent rechallenge is increased in the late phase. This late phase hyperreactivity seems to persist for at least 2 weeks after allergen provocation.

Adolescent↗

Older's classification of Colles' fractures. Good intraobserver and interobserver reproducibility in 185 cases.

To evaluate the reliability of the Older classification, 4 observers classified 185 distal radius fractures twice with 1 month's interval. Both the intraobserver agreement and the interobserver agreement were high, with kappa values of 0.75 (0.69-0.79) and 0.69 (0.60-0.77), respectively. The agreement was especially high for type 1 and type 4 fractures. Older's method of classifying distal radius fractures can thus be recommended for clinical use.

Colles' Fracture↗

[Testing and comparison of the accuracy and precision of 5 pulse oximeters].

Determination of the oxygen saturation (SaO2) was carried out on 47 patients employing five pulse oxymeters. Measurements with Criticare CSI 501 (Simonsen & Weel), Criticare CSI 502 (Simonsen & Weel), Nellcor N 100 (Dräeger), Satlite (Datex) and Novametrix 500 (Vickers) were compared with arterial blood gas analyses with Radiometer ABL 3 (Radiometer, Copenhagen). Statistical calculation of the agreement with the pulse oxymetric and the invasive measurements were performed by the method recommended by Bland & Altman. The precision profiles for the pulse oxymeters varied from 1.84 to 2.25 (CV%) and the accuracy profiles from -0.90 to 1.44%. All of the apparatuses fulfilled the specifications made by the manufacturs. All were considered to be suitable and reliable for monitoring of decreases in oxygen saturation during and after operation.

Equipment Safety↗

BIO-Fully Automated Sample Treatment high-performance liquid chromatography and radioimmunoassay for leukotriene E4 in human urine from asthmatics.

BIO-Fully Automated Sample Treatment (BIO-FAST) high-performance liquid chromatography (HPLC) is a sophisticated column-switching technique in which a fresh pre-column is used for each sample prior to reversed-phase HPLC. The pre-columns, Varian Advanced Automated Sample Processor (AASP) cartridges, are held and automatically advanced by the Varian AASP. A rapid and efficient extraction and separation for leukotrienes C4 and E4 from human urine has been developed using a C8 cartridge and subsequent C18 analytical HPLC column. Quantitation of leukotriene E4, accomplished by post-column radioimmunoassay, shows significantly increased leukotriene E4 concentrations in urine samples from asthmatics after antigen challenge. This further confirms an active role for leukotrienes in the pathogenesis of bronchial asthma.

Asthma↗

Inflammatory indices for chronic bronchitis and chronic obstructive airway disease. Cell populations in bronchial and bronchoalveolar lavage.

The development of chronic bronchitis (CB) and chronic obstructive airway disease (COAD) seems to be related to inflammatory changes of airway structure. However, the cause and the exact location and type of these changes resulting in altered airway function are not known. Mucosal inflammation is characterized by the recruitment of granulocytes, macrophages and lymphocytes as well as by the shedding of epithelial cells. The present chapter discusses the usefulness of bronchial lavage (BL; 50 ml of lavage volume) directly followed by bronchoalveolar lavage (BAL; 200 ml), for the characterization and quantification of inflammation in proximal and peripheral airways, respectively. On the basis of results from the literature and a pilot study on CB patients with or without coexisting COAD, the following conclusions may be drawn: There is a profound difference in lavage cell composition and numbers between non-smokers and smokers. However, within the group of smokers there are few additional changes in cell numbers and composition when concomitant airway disease is present. The obstruction of the COAD patients is correlated to a reduced recovery of BL and BAL fluid. Furthermore, these patients seem to have a reduced number of most cell types in their BL. This diminitution is not just related to the reduced fluid recovery. The BL cells have a lower viability and BL macrophages have a reduced phagocytic capacity when compared with matching BAL cells. The viability of cells was lowest in BL from the COAD group. These findings may suggest that COAD entails a reduced transport of macrophages to the small airways and/or an enhanced turnover of these cells in the bronchi. Functional studies of lavage cells may supply additional, and perhaps more specific, information on the mechanisms involved in the inflammatory process.

Bronchi↗

Comparison of urinary leukotriene E4 and 16-carboxytetranordihydro leukotriene E4 excretion in allergic asthmatics after inhaled antigen.

Antisera to 16-carboxytetranordihydro leukotriene E4 (tetranor LTE4), a major urinary oxidative metabolite (via omega- and beta-oxidation) of leukotriene E4 (LTE4) in primates, were obtained by immunisation of rabbits with a related, non-naturally occurring synthetic metabolite (16-carboxytetranordihydro leukotriene C4 ester) conjugated to Keyhole Limpit haemocyanin. Material which competed with [11, 12-3H]tetranor LTE4 for binding to this antisera was isolated from urine from allergic asthmatics by reversed-phase HPLC. This material eluted with the retention time of synthetic standards, and its mean urinary excretion was elevated during both the first three hours (6.13 +/- 2.15 ng/h) and 3-6 h (5.87 +/- 1.99 ng/h) after antigen inhalation, compared with baseline values (3.42 +/- 1.49 ng/h), in 5 allergic mild asthmatics. A much greater and statistically significant increase in urinary leukotriene E4 (LTE4) excretion, occurring in all subjects, was seen during acute antigen-induced bronchoconstriction (baseline, 1.62 +/- 0.66 ng/h; 0-3 h, 19.58 +/- 8.79 ng/h; p less than 0.05) in these subjects. These data support the suggestion that endogenous peptide leukotrienes are metabolised by omega- and subsequent beta-oxidation in man, but emphasize the relative importance of urinary LTE4 excretion after allergen elicited leukotriene generation, further substantiating a pathological role for peptide leukotrienes in allergic asthma.

Administration, Intranasal↗

Solutions to problems in enumerating sediment bacteria by direct counts.

We examined the effect of different sediment types on the staining effectiveness of the fluorochrome DAPI (4'-6-diamidino-2-phenylindole dihydrochloride) over a wide range of concentrations and on the masking effect of sediment particles on DAPI-stained bacteria. Sediment type greatly affects the staining efficiency of DAPI, and most published studies seem to have underestimated bacterial abundances by using suboptimal concentrations of the fluorochrome. A DAPI concentration of 5 mug ml is required to effectively stain the bacteria in most sediments that can be sampled with a gravity corer. When the sediments are diluted 687 times (a dilution factor similar to those most often used in the literature), sediment particle masking of stained bacteria is highly variable for different sediment types. By using a measure of turbidity (A(750)) to indicate masking and the quartz-corrected water content as a measure of the initial (in situ) dilution of each sediment type, it becomes possible to show a linear relationship between masking and the integrated (initial x experimental) dilution of various sediments. This relationship allows the development of a correction procedure for masking which makes accurate and unbiased counts possible. Data so obtained show a strong relationship between bacteria (cells per milliliter of fresh sediment) and sediment organic matter (grams [dry weight] per milliliter of fresh sediment), one that is not discernable without the correction. The proposed method of staining and correction for sediment masking provides the basis for a standardized interpretation of sediment bacterial counts.

Journal Article↗

Isolation and Biological Activities of Four Selective Toxins from Helminthosporium carbonum.

A new and simpler purification procedure was developed for host selective toxins from Helminthosporium carbonum race 1. Four analogs or forms of toxin with the same selectivity as the fungus were isolated from culture fluids; two forms (HC toxins III and IV) have not been reported by other workers. Crystals of the major form of toxin (HC toxin I) were recovered in high yields (>80 milligrams per liter of culture fluid) without the use of high performance or preparative thin layer liquid chromatography. ED(50) values, based on inhibition of root growth of susceptible seedlings, for HC toxins I, II, III, and IV were 0.2, 0.4, 2.0, and 20 micrograms per milliliter, respectively. The specific activity of crystalline HC toxin I matched the most active preparation reported previously; the preparation of HC toxin II was more active than that reported previously. Resistant seedlings tolerated 100-fold higher concentrations of each form of toxin than did susceptible seedlings. Hydrolysis of the epoxide group of HC toxin I to a diol destroyed toxicity to susceptible and resistant seedlings. The data suggest that the same mechanisms are affected in resistant and susceptible plants.

Journal Article↗

Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis.

The clinical effect of N-acetylcysteine (NAC) controlled-release tablets, 300 mg b.i.d., and placebo, in chronic bronchitis was investigated. The study was performed as a double-blind six month comparison between active drug and placebo in two parallel groups, with statistical evaluation after four and six months. The patients were chosen from nine centres. One hundred and sixteen out-patients were included and ninety one of them completed the six month study. The acetylcysteine-treated group had a significantly reduced number of sick-leave days caused by exacerbations of chronic bronchitis after the four winter months December-March compared with the control group (NAC 173, placebo 456). The number of exacerbation days was also very much reduced, however, not significantly (NAC 204, placebo 399). At the end of the six month trial, including also two spring months, the absolute numbers of sick-leave days and exacerbation days were still fewer in the acetylcysteine-treated group, (NAC 260, placebo 739) and (NAC 378, placebo 557) respectively. This study demonstrates a significant reduction in sick-leave days after four months of NAC-treatment. A constant tendency to reduction in the number of exacerbations and exacerbation days was also registered after four and six months. The differences in these parameters were, however, not statistically significant. This was probably due to the small number of patients participating.

Absenteeism↗

Additive bronchodilator effects of terbutaline and enprofylline in asthma.

Enprofylline is a novel xanthine derivative with negligible adenosine antagonizing ability. It is eliminated almost exclusively by renal clearance with a half-life of about 2 h. Three i.v. infusions of enprofylline (1 mg/kg body weight over 10 min) were given at hourly intervals to 16 patients with stable, reversible airway obstruction. The patients were pretreated at random with i.v. terbutaline (4 micrograms/kg body weight) or placebo according to a double blind cross-over design. Lung function and drug concentrations in plasma were followed. Enprofylline produced significant and concentration-dependent bronchodilation between plasma levels of 1.24 and 3.22 mg/l. The improvement in ventilatory function was significantly enhanced by terbutaline pretreatment. At the highest plasma levels of enprofylline nausea and headache were found as subjective side effects. The results suggest that enprofylline and terbutaline might best be used in a low dose combination in the treatment of bronchial asthma.

Adult↗

Gas composition of the normal and the ventilated middle ear cavity.

Epidemiologic and controlled studies indicate that late minimal hearing impairment is a sequelae after the use of a ventilation tube in early childhood. The patho-physiology is unknown, but abnormal middle ear gas composition might be important. Therefore it is mandatory to measure middle ear gas composition in order to understand the gas exchange in the normal middle ear, as well as the change in gas composition associated with ventilation tubes. Accordingly, the aim of this study was to measure middle ear gas composition both in the physiologic state and in artificial ventilation by a transtympanic tube. Employing puncture of the typanic membrane, through a liquid seal, we aspirated 300 microliters of middle ear gas. The procedure was carried out under the otomicroscope on adults without any anesthesia. A total of 58 normals participated, along with 10 persons with unilateral ventilation tubes and 1 with a patent Eustachian tube. The mean values of physiologic state were: Partial pressure of oxygen in the middle ear cavity = 39 mm Hg, and partial pressure of carbondioxide in the middle ear cavity = 48 mm Hg. The mean values of artificially ventilated ears were: Partial pressure of oxygen in the middle ear cavity = 138 mm Hg, and partial pressure of carbondioxid in the middle ear cavity = 15 mm Hg. The total imprecision was 4.2/4.4 mm Hg and the accuracy seems fair,--especially because we found a quasi equilibrium to the "most probable value", the venous blood gases. It is concluded that artificial ventilation of the middle ear cavity, with a ventilation tube increases the oxygen content of the middle ear cavity with a factor 3.2. This constitutes a relative hyperoxic atmosphere with a subsequent possibility for a toxic tissue damage.

Adolescent↗

Rectal administration of choline theophyllinate in adult asthmatics on theophylline maintenance therapy.

The relief of bronchial obstruction from theophylline administered intravenously and as retention enema was compared in a controlled double-blind cross-over study in 21 adult patients with reversible bronchial obstruction, who were on continuous treatment with an individually adjusted maintenance dose of oral theophylline. In two sessions the patients received in random order a 10 ml aminophylline infusion intravenously (180 mg theophylline) and the equivalent of 400 mg theophylline rectally in the form of choline theophyllinate, followed by serial determinations of ventilatory function and plasma theophylline levels during the next 8 h. Significant improvement of FEV1 within 1 h was recorded with both treatments and the duration of the effect was very similar for the two routes of administration. The patients were in stable state while taking part in the experiment but the similarity in the outcome suggests that choline theophyllinate administered as retention enema, although slower acting, represents a useful alternative to intravenous aminophylline also in the management of acute episodes of bronchial obstruction.

Forced Expiratory Volume↗