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Biomedical subjects

K Strandberg

Publications and source records attributed to K Strandberg.

At least 19 recordsLinked to original sources
PubMed1991

The intrauterine contraceptive device, "Multiload Cu 250": a regulatory problem.

Reports to the control agencies in Sweden and Australia of fractures of the intrauterine contraceptive device. Multiload Cu 250, led to a review of the safety of this device in these countries. The review revealed that fractures of the device had occurred in 15 other countries but in these countries only 5% of reports had been directed to the relevant national control authorities. The remainder either had been reported to the sponsor or had appeared in the published literature. An additional problem identified was one of thread rupture with the resultant difficulty in removal and the need for surgical intervention. It is apparent that the sponsor of the device was aware of the problems for some time since it made several significant changes to the device marketed in Sweden. These changes were made in 1983, without informing the Swedish agency and without its approval. These were 1622 Multiload Cu 250 devices returned to the Swedish agency for examination from 1988 to 1989. An analysis of 1516 of them found that the overall incidence of device fracture was 1:405 and of broken threads, 1:8. However, evidence suggests that the modifications conducted in 1983 and 1984 resulted in a device with very much less chance of fracture and/or ruptured threads on removal. Stress testing of 106 used devices suggested that the risk of fracture may increase with the length of time left in utero. Regulatory action in both Sweden and Australia involved changes in the information provided to physicians and patients. In Sweden, the additional step of withdrawing all earlier devices suspected of being associated with fracture and/or ruptured threads was taken.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia↗
PubMed1988

Variations in histamine concentration in nasal secretion in patients with allergic rhinitis.

The histamine concentration and content in nasal secretion and the volume of nasal secretion in nasal washing samples were measured under different conditions in 28 patients with allergic rhinitis sensitive to birch pollen. The mean histamine concentration was significantly lower after intranasal birch pollen challenge (2.08 micrograms/ml) than in prechallenge samples (6.96 micrograms/ml), and was also significantly lower in untreated patients during the birch pollen season (2.30 micrograms/ml) than off-season (7.18 micrograms/ml). The same relationship was found between the histamine content of the secretion samples obtained on these occasions. The mean secretion volume was greater after than before challenge, but not significantly higher during the season than off-season. A partial reversion of the changes in histamine concentration and content that occurred during the season was observed during intranasal corticosteroid therapy. The concentration and content of histamine in nasal secretion from symptomatic patients after intranasal histamine challenge did not differ significantly from those in asymptomatic subjects before challenge. It was concluded that although the histamine level in nasal secretion can be used as a marker of changes in the severity of allergic rhinitis, it is not ideal for this purpose.

Beclomethasone↗
PubMed1987

Histamine concentrations in nasal secretion and secretory activity in allergic rhinitis.

The prerequisites for using the assayed histamine concentration in nasal secretion as an objective measure of disease activity in allergic rhinitis were investigated. It was demonstrated that in histamine determination procedures the presence of quenching substances in the nasal secretion could lead to underestimation of the histamine concentration. This bias was eliminated in a modified spectrofluorometric assay. Only an insignificant fraction of the histamine in samples collected by nasal spray washing was bound to unfiltrable particles or cells. The mean histamine concentration in nasal secretions from 15 healthy subjects was 11.2 micrograms/ml and in a group of nine patients with allergic rhinitis out of season 3.36 micrograms/ml. The histamine concentration in the latter group decreased during the pollen season and after positive allergen challenge. It is suggested that this decrease is caused by the increase in volume of the secretion during the allergic response. The use of lithium as an exogenous marker permitted quantitation of the increase in the relative amount of nasal secretion recovered by washing in the symptomatic subjects.

Adult↗
PubMed1987

Post-mortem concentrations of salbutamol, terbutaline and theophylline in asthma patients.

The concentrations of theophylline, terbutaline and salbutamol in post-mortem blood samples from 68 patients (17-85 years old) with asthma or chronic obstructive lung disease, 54 of whom had died of asthma, were analysed. Information on recent prescriptions was obtained for 61 patients. There was agreement between prescription and drug analysis in the blood in 87% of the patients with regard to theophylline and in 92% for salbutamol and terbutaline combined. Theophylline levels were generally low; 30 patients had concentrations below 25 mumol/l and only three above 110 mumol/l (therapeutic interval 55-110 mumol/l). Both salbutamol and terbutaline were detected in most samples. Fourteen patients had blood concentrations above 200 nmol/l. No definite explanation for these high values could be found. The majority of patients who died from asthma had low drug levels and had not been prescribed corticosteroids.

Acute Disease↗
PubMed1986

Regulatory decisions. Emphasis on safety issues.

Effective post-marketing surveillance of drugs calls for an approach tuned to the individual problem. In Sweden, the combined use of spontaneous adverse drug reaction (ADR) reporting data and different registers has yielded much valuable information on safety problems with different drugs. However, the raw data must be interpreted with care and often be supplemented by in-depth studies. The advantage with registers is that they comprise the whole or a random sample of the population and that the reporting routines are fairly simple. Since much of the information is collected primarily for other purposes (like health care planning or budgeting) the cost of the information is low. The potential of spontaneous ADR reporting for detecting new rare ADRs is exemplified by the zimeldine case. Limitations of the system besides low and selective reporting are that the physicians must suspect the clinical manifestation to be drug-induced and that patient compliance is unknown. The greatest disadvantage with the patient- and disease-oriented registers is the frequent inaccuracy of the diagnoses and the delay in the appearance of the data. Improved education and more resources for updating the registers are required. The ICD-code should be adapted to the needs of drug monitoring. Since the registers contain sensitive information about individual patients, the confidentiality of the data must be secured. As a logical complement to these sources of information, systems for case control studies, to be adopted ad hoc when problems arise, should be instituted. Moreover, for certain kinds of long term drug reactions, record-linkage systems are probably the only means to disclose risks (e.g. of cancer) after long term drug exposure. In this respect, the computerisation of Swedish pharmacies offers unique possibilities for the retrieval of prescription data on individual patients.

Acidosis, Lactic↗
PubMed1985

Effect of betamethasone on the dual reaction to anti-human IgE in man: influence of time interval between administration of drug and anti-IgE.

The influence of the time interval between administration of a glucocorticoid, betamethasone, and anti-IgE on the effect of the drug on the early and late phase response (LPR) to anti-IgE was examined in 38 volunteers in a randomized controlled study. The immediate flare and wheal responses to intradermally (i.d.) injected anti-IgE were inhibited by approximately 20 and 30% respectively by a 10 day i.d. pretreatment period with repeated 50 micrograms doses (total 300 micrograms) of betamethasone (P less than 0.01), whereas responses to histamine were not influenced. A single i.d. injection of 50 micrograms betamethasone 24 h prior to anti-IgE challenge attenuated the wheal response (P less than 0.05), whereas injection of the drug 2 h prior to and together with anti-IgE had no influence on the early response. Corresponding LPRs were reduced approximately 30% throughout the observation period of 1-24 h (P less than 0.01). Injecting the drug i.d. 30 min following anti-IgE challenge had no significant influence on the total observation period (1-24 h) of the LPR but antagonized the LPR by 35% at 6-24 h (P less than 0.01). It is concluded that glucocorticoids inhibit IgE-dependent LPRs. When extending the topical pretreatment period with the compounds also the early part of the allergic reaction is attenuated.

Adolescent↗
PubMed1985

Equivalent inhibition by terbutaline of anti-human IgE skin responses in atopic and non-atopic subjects.

Previous studies have shown that pretreatment of skin with beta 2-adrenoceptor stimulants antagonizes anti-human IgE elicited wheal and flare reactions in atopic and non-atopic subjects. This experimental system was employed to further study the hypothesis that atopic disease and bronchial asthma unrelated to atopy might be associated with a beta-adrenoceptor defect. Eight patients with extrinsic and 10 patients with intrinsic asthma deprived of oral bronchodilator treatment and corticosteroids for at least a week, and in a clinically stable condition, 10 patients with extrinsic rhinitis and on no treatment, as well as age and sex matched healthy control subjects showed almost identical dose-response relations for the inhibitory effect of intradermally injected terbutaline (0.25-100 ng), on anti-IgE elicited skin reactions. In four asthmatic patients the inhibitory effect of terbutaline did not change following a treatment period with oral terbutaline and theophylline. The data do not support the presence of a cutaneous mast cell beta 2-adrenoceptor defect in patients with atopy or bronchial asthma unrelated to atopy.

Adrenergic beta-Agonists↗
PubMed1979

Anti-anaphylactic and bronchodilating action of a beta-adrenoceptor stimulator, KWD 2131, in human lung tissue.

The beta-adrenoceptor stimulating agent KWD 2131 has been studied with regard to inhibitory effect on allergen-induced histamine release from passively sensitized human lung tissue and relaxing effect on contracted small (diameter = 1 mm) and large (diameter greater than 3 mm) isolated human bronchi. The dose for 50% inhibition of the allergen-induced histamine release was 2 x 10(-11) M. The potency of KWD 2131 was approximately 0.15 times that of terbutaline and 0.05 times that of isoprenaline in this respect. The bronchodilating potency of KWD 2131 was 0.02-0.03 times that of terbutaline. The data indicate that KWD 2131 is a compound with preferably anti-anaphylactic potency in the human lung.

Adrenergic beta-Agonists↗
PubMed1979

Effect of terbutaline, a beta 2-adrenergic receptor stimulating compound, on cutaneous reponses to histamine, allergen, compound 48/80, and trypsin.

The beta-adrenoceptor stimulating agent terbutaline (2 ng-2 microgram) injected intradermally in eight atopic subjects produced a dose-dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 microgram terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min. The flare response induced by histamine, the histamine liberator compound 48/80 and the proteolytic enzyme trypsin was not inhibited by terbutaline in the doses used, suggesting a selective action of terbutaline on the allergen-induced response. The weal response elicited by histamine and compound 48/80 was slightly reduced by 2 microgram terbutaline. It is suggested that pretreatment of the skin with terbutaline interferes with the ability of the cutaneous mast cells to respond to challenge with allergen and that terbutaline produces this effect in doses lower than those needed to counteract the permeability increasing effect of released mediator substances.

Adolescent↗
PubMed1979

On the mechanism of relaxation of tracheal muscle by theophylline and other cyclic nucleotide phosphodiesterase inhibitors.

The mechamism of action of theophylline was studied by investigating the relationship between relaxant effect and inhibition of cyclic nucleotide phosphodiesterase (PDE) and by studying interactions with adenosine actions. Guinea pig tracheal smooth muscle cyclic AMP PDE had two apparent KmS': 0.4 and 70 microM for cyclic AMP. Theophylline and papaverine competetively inhibited the low Km form. Hydrolysis of 2.0 microM cyclic AMP and cyclic GMP was inhibited by several drugs. Some agents (e.g. ZK 62 711, ICI 63,197, Ro 20--1724, dipyridamol) were considerably more potent as inhibitors of cyclic AMP than of cyclic GMP hydrolysis, while other agents (M & B 22.948 and dilazep) selectively inhibited cyclic GMP breakdown, and some (theophylline, papaverine, IBMX and SQ 20,006) showed little selectivity. There was a weak but significant correlation between inhibition of cyclic AMP phosphodiesterase and relaxation of tracheal smooth muscle in vitro. There was also a correlation between the ratio of IC25 cyclic AMP/IC25 cyclic GMP and the smooth muscle relaxation, indicating that inhibition of cyclic AMP rather than cyclic GMP hydrolysis determined relaxation. However, there was a marked tachyphylaxis to the relaxant effect of the cyclic AMP selective PDE-inhibitors, while the nonselective methylxanthines did not show tachyphylaxis. The effect of theophylline was antagonized by low concentrations of adenosine, which by itself caused a weak tracheal contraction. The effect of PDI-inhibitors can be partly explained by decreased cyclic AMP breakdown but other mechanisms, such as antagonism of endogenous adenosine, may contribute to the observed relaxant action.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Elimination of test particles from the human tracheobronchial tract by voluntary coughing.

The effect of coughing on the elimination of inhaled 6 micrometer radioactively tagged teflon particles in humans was studied by external measurements of the radioactivity retained in the lungs before and after 1--2 min of voluntary coughing. In six healthy subjects coughing produced no substantial elimination of the particles. Six out of eight patients with lung disease produced expectorate and also eliminated particles from the lungs by coughing. The other two patients had no phlegm, did not produce any expectorate and did not eliminate particles by coughing. An increased amount of tracheobronchial secretion thus seems to be necessary for coughing to be effective. In the patients, the elimination of particles by coughing was fairly reproducible, suggesting that the test model may be useful for investigation of the influence of physiological and pharmacological factors on the elimination process.

Adult↗
PubMed1979

Effects of histamine receptor antagonists on histamine-induced responses in human skin.

The effects of intradermally administered histamine H1- and H2-receptor antagonists on the cutaneous responses--redness, weal, flare and itch--induced by intradermal injection of histamine were studied in man. Weal and redness were studied after blockade of the axon reflex by local infiltration with lidocaine. All responses were significantly inhibited by the H1-receptor antagonist mepyramine. The H2-antagonists cimetidine and metiamide reduced flare and itch significantly but not to the same extenet as mepyramine and not in a clearly dose-related manner. The size of weal and redness was not significantly reduced by cimetidine. No further reduction of flare, itch or weal was obtained by adding metiamide or cimetidine to mepyramine. After blockade of the axon reflex with lidocaine the histamine-induced weals turned white at the centre. This blanching was more prominent when histamine was injected in combination with cimetidine. Substituting mepyramine for cimetidine resulted in small weals with an intense red colour. It is concluded that, apart from being engaged in the direct vasodilatory response to histamine, H2-receptors do not seem to be involved in the other cutaneous responses to histamine studied.

Adult↗
PubMed1978

Bronchial and cardiovascular actions of prostaglandin endoperoxides and an endoperoxide analogue.

Effects of PGG2, PGH2 and the endoperoxide analogue, EPA, on bronchial and vascular smooth muscle were studied in vivo and in vitro. In the cat PGG2, PGH2 and particularly EPA proved potent stimulators of airway resistance, and they were all significantly more active than PGF2 alpha. They also increased pulmonary vascular resistance but EPA alone was more active than PGF2 alpha. In guinea pigs EPA was 90--190 times more active than PGF2 alpha in increasing tracheal insufflation pressure. Human bronchi contracted in response to PGG2, PGH2 and EPA. PGG2 and PGH2 were equiactive with PGF2 alpha and EPA was more than 500 times as potent. PGG2 and PGH2 lowered systemic arterial blood pressure and increased heart rate in cats. They were as active or more active than PGE2, EPA, on the other hand, resembled PGF2 alpha in producing biphasic changes of blood pressure and heart rate or decrease of blood pressure and bradycardia in guinea pig and cat. The results obtained in this study indicate that PGG2, PGH2 and EPA are potent stimulators of bronchial and pulmonary vascular smooth muscle. The data are also consistent with the view that a significant proportion of effects resulting from prostaglandin generation in the lung is due to prostaglandin endoperoxides rather than primary prostaglandins.

Airway Resistance↗