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Biomedical subjects

S Lindberg

Publications and source records attributed to S Lindberg.

At least 19 recordsLinked to original sources

The effects of formoterol, a long-acting beta 2-adrenoceptor agonist, on mucociliary activity.

The effect on mucociliary function of formoterol, a beta 2-adrenoceptor agonist bronchodilator with a prolonged duration of action (as compared with salbutamol or terbutaline), was investigated both in vitro and in vivo with a photoelectric technique. Formoterol, and its (R,R)-enantiomer, increased ciliary beat frequency in vitro in guinea pig trachea preparations (peak increase 17.2 +/- 2.0% at a concentration of 10(-7) M) and in vivo in the rabbit maxillary sinus (peak increase 23.0 +/- 4.0% at a dosage of 1 nmol/kg). Formoterol was approximately 100 times more potent than terbutaline in vitro, as judged from the dose-response curve. The main difference between their effect in vivo was the 2-fold longer duration of the mucociliary acceleration after formoterol at 1 nmol/kg than after terbutaline at the equi-effective dosage of 10 nmol/kg terbutaline (20 vs. 10 min, respectively). The findings indicate formoterol to be a powerful, long-acting ciliostimulant, a property which may be of clinical advantage in the treatment of airway disease.

Adrenergic beta-2 Receptor Agonists

Effects of halothane on mucociliary activity in vivo.

The effect of halothane on mucociliary activity in the rabbit maxillary sinus in vivo was recorded photoelectrically. Administration of halothane (1%, 2% or 4%) into the maxillary sinus induced a temporary acceleration of mucociliary activity. The peak increase (39.1% +/- 9.1%, p < 0.05, n = 5) was seen after the 4% concentration. Long-term exposure (60 minutes) of the maxillary sinus to halothane (2%) first induced an increase of 28.4% +/- 4.6% (p < 0.05, n = 6), lasting approximately four minutes, and followed after about 15 minutes by a decrease of mucociliary activity. The maximum decrease during the 60-minute period was 19.6% +/- 2.8% (p < 0.05, n = 6). Mucociliary activity returned to its baseline level approximately 25 minutes after withdrawal of halothane. Halothane delivered to the rabbit through a tracheal cannula at 1.1% for 60 minutes did not impair mucociliary activity in the maxillary sinus. On the contrary, it initially stimulated mucociliary activity, 19.9% +/- 2.7% (p < 0.05, n = 5). There was also an initial increase in respiratory rate from 62 +/- 7.3 to 89 +/- 12.9 breaths per minute (p < 0.05), which was noticeable after approximately 10 seconds and lasted 4 to 5 minutes. The dose-dependent increase in mucociliary activity seen after short-term exposure to halothane is probably due to stimulation of afferent C fibers, because halothane may be considered an airway irritant. The reversible depressant effect seen after 15 minutes of exposure is in accordance with findings in previous studies in vitro. The mechanism by which halothane impairs mucociliary activity is at present not known. However, halothane administered to the lower airways does not impair mucociliary activity in the maxillary sinus, indicating that halothane affects the ciliated epithelium directly and that the state of anesthesia itself has no effect on mucociliary activity.

Anesthesia

Improving the usefulness of the Karolinska Psychodynamic Profile in research: proposals from a reliability study.

The interrater reliability of data obtained by use of the Karolinska Psychodynamic Profile (KAPP) was tested among 60 women seeking treatment for drinking problems. The first rater had a psychodynamic background but was minimally trained rating the KAPP subscales and performing KAPP interviews. Independent, blind ratings of audiotaped interviews by an experienced KAPP rater revealed that 8 of the subscales obtained satisfactory reliability, whereas 6 subscales showed unsatisfactory reliability. Furthermore, data for one subscale (normopathy) showed a zero correlation between raters, probably due to the novelty of the construct. Additionally 3 subscales related to bodily aspects were of little clinical significance among the present study group. Our data were compared with data from previous KAPP reliability studies, and the reasons for similarities and discrepancies of results are discussed.

Adult

Cyclic adenosine monophosphate stimulation of mucociliary activity in the upper airways in vivo.

Xanthine derivatives are known to accelerate mucociliary transport in the lower airways, probably by preventing degradation of cyclic adenosine monophosphate (cAMP) and thereby increasing its intracellular concentration. The purpose of this study was to investigate the effects of cAMP on mucociliary activity in the upper airways. The effect on the mucociliary activity in the rabbit maxillary sinus of the xanthine derivatives theophylline and enprophylline was compared to that of the cAMP analog dibutyryl cAMP. The compounds were administered into the maxillary artery, and the response was recorded with a photoelectric technique. Infusions of theophylline (1.0 and 10 mg/kg) increased mucociliary activity (22.8% +/- 5.9%, n = 6, and 21.6% +/- 4.9%, n = 7, p < .05, respectively). Infusions of enprophylline (1.0 and 10.0 mg/kg) accelerated mucociliary activity (at the highest dosage tested, 24.3% +/- 4.1%). Infusions of dibutyryl cAMP (0.1 and 1.0 mg/kg) stimulated mucociliary activity, with the maximum increase (20.1% +/- 3.0%, n = 13, p < .05) being observed at a dosage of 0.1 mg/kg. The infused substances increased mucociliary activity within 1 minute after the start of the infusion, the duration of the response being approximately 20 minutes for theophylline, 22 minutes for enprophylline, and 12 minutes for dibutyryl cAMP. The present results support the view that cAMP is involved in regulating mucociliary activity in the upper airways. It remains to be elucidated whether xanthines such as theophylline and enprophylline are beneficial in upper airway disease in which mucociliary function is impaired (eg, chronic sinusitis).

Animals

Cancer incidence after radiotherapy for skin haemangioma during infancy.

An infant cohort treated for skin haemangioma with 226Ra between 1930 and 1965 (n = 11,807) was studied. The median age at treatment was 5-months and 88% were treated before 12 months of age. This cohort was followed up in the Swedish Cancer Registry during the years 1958 to 1989, giving 370,517 person-years at risk. A total number of 248 malignancies have been observed and the standardized incidence ratio (SIR) was 1.21 (confidence interval (CI) 95%, 1.06-1.37). Significantly increased numbers of cancers were found in the central nervous system, 34 cases (SIR = 1.85, CI 95% 1.28-2.59), the thyroid, 15 cases (SIR = 1.88, CI 95% 1.05-3.09) and other endocrine glands, 23 cases (SIR = 2.58, CI 95% 1.64-3.87). The absorbed dose in 11 specified risk organs has been estimated using a phantom of the size of a 5-6-month-old child. The mean absorbed dose in the thyroid was 0.12 Gy and the excess relative risk (ERR) for thyroid cancer was 7.5 per Gy (CI 95% 0.4-18.1). The mean dose in the central nervous system was 0.077 Gy and the ERR for brain tumours was 10.9 per Gy (CI 95% 3.7-20.5). This cohort gives a unique opportunity to analyse long-term effects of low-dose irradiation during infancy.

Adolescent

Effect of beta-glucuronidase on urinary benzodiazepine concentrations determined by fluorescence polarization immunoassay.

In samples from patients treated with oxazepam, beta-glucuronidase increased the immunoreactivity of urinary benzodiazepines analyzed by fluorescence polarization immunoassay (FPIA). Increasing concentrations of beta-glucuronidase added to samples from drug-free controls did not influence the results. In the absence of beta-glucuronidase, 22 of 35 samples from patients undergoing detoxification gave positive results at a cutoff concentration of 200 micrograms/L. Pretreatment with beta-glucuronidase increased the number of drug-positive samples to 33. The drug-negative samples were obtained from two patients who had been oxazepam-free for at least 1 week. Thus, beta-glucuronidase can be used to increase the sensitivity of the urinary benzodiazepine FPIA without reducing the specificity of the method.

Benzodiazepines

Effects of inflammatory mediators on ciliary function in vitro.

Prostaglandins and histamine released during inflammatory and allergic reactions can affect the mucociliary system in different ways. By studying the effect of these mediators on ciliary beat frequency (CBF) with a photo-electrical technique in airway explants from different species, i.e. guinea-pig trachea, rabbit maxillary sinus, and human adenoid, the mechanisms underlying the effects of prostaglandin and histamine were further elucidated. Prostaglandin E1 (PGE1) produced a modest increase in CBF in preparations from guinea-pig trachea. The maximum response was 12.9 +/- 3.4% for the dose of 0.1 micrograms/ml, corresponding with 0.28 microM. Prostaglandin E1 produced a dose-dependent increase in explants from rabbit maxillary sinus, the maximum effect was 35.9 +/- 14.1% at a dose of 1.0 micrograms/ml. PGE1 produced a lesser increase in CBF in explants from human adenoids. A maximum increase of 4.1 +/- 1.6% was observed at a dose of 0.1 mg/ml. Histamine produced a moderate increase in CBF in explants from human adenoid at concentrations of 0.01-0.1 mM, corresponding with 1.84-18.4 micrograms/ml. In contrast, histamine did not significantly alter CBF in explants from the rabbit maxillary sinus or guinea-pig trachea. These results indicate that there are interspecies differences in the responsiveness to prostaglandins, and that PGE1 seems to have more powerful effects on CBF in the upper than in the lower airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoids

Method for in vivo measurement of mucociliary activity in the human nose.

The aim of the investigation was to develop a method for observing mucociliary activity in the human nose in vivo without possible artifacts introduced by anesthesia or surgical intervention. A probe containing an optical system was constructed for the purpose, mucociliary activity on the nasal septum being photoelectrically analyzed by computer. Challenges with pharmacologic substances were administered with a standardized nebulizer delivering an aerosol heated to 33 degrees C. The baseline mucociliary wave frequency in vivo was 691.7 +/- 93.0 waves per minute (11.5 +/- 1.6 Hz), and the corresponding ciliary beat frequency in vitro was 800.7 +/- 85.4 beats per minute (13.3 +/- 1.4 Hz). The coefficients of variation were 13.4% between individuals and 11.3% +/- 2.1% (range 8.3% to 14.3%) within a subject. The method showed good reproducibility regarding recordings from different spots on the mucosa and on a day-to-day basis. Challenge with the beta 2-agonist terbutaline sulfate produced an increase of mucociliary activity of 40.6% +/- 7.8% (mean +/- SEM), which is consistent with previous results in animal models. This is the first report of a method suitable for in vivo studies of the mucociliary effects of challenge with autonomic agonists and airway irritants in humans.

Adult

NK1 receptors mediate the increase in mucociliary activity produced by tachykinins.

The mucociliary activity of the rabbit maxillary sinus is increased after exposure to airway irritants such as cigarette smoke and capsaicin. This effect is partly due to a cholinergic reflex but involves an atropine-resistant response probably mediated by the release of tachykinins such as substance P or neurokinin A from sensory nerve endings. The aim of the present investigation was to evaluate the type of tachykinin receptor which mediates this increase in mucociliary activity. The mucociliary activity of the rabbit maxillary sinus was studied photoelectrically in vivo. It was found that a selective NK1 receptor agonist, [Sar9,Met(O2)11]substance P, dose dependently stimulated mucociliary activity, the maximum increase being 43.74 +/- 6.07% at a dose of 1 nmol/kg. A selective NK2 receptor agonist, [Nle10]neurokinin A-(4-10), produced a much weaker response, the maximum increase being 15.23 +/- 3.86% at a dose of 10 nmol/kg, whereas an NK3 receptor agonist, [Pro7]neurokinin B, was without effect. When the effects of the selective agonists were compared with the responses elicited by naturally occurring tachykinins at a dose of 1 pmol/kg, the order of the magnitude of the responses was [Sar9,Met(O2)11]substance P > substance P > neurokinin A. At this dosage the NK2 and NK3 receptor agonists did not have a significant effect. Pretreatment with the endopeptidase inhibitor phosphoramidon did not influence the magnitude of the responses but increased their duration. It is concluded that the NK1 receptor is responsible for the increase in mucociliary activity elicited by tachykinins released from sensory afferents in the upper airways.

Animals

Comparison of allergic rhinitis and vasomotor rhinitis patients on the basis of a computer questionnaire.

From 1 July 1990 to 31 December 1991, all patients referred to the Allergy Section of the ENT Department, University Hospital, Lund, Sweden, (n = 678) answered a 134-item questionnaire presented on the screen of a personal computer by pressing Y (for yes) or N (for no) on the keyboard. The objective of this study was to compare the questionnaire responses from patients with allergic rhinitis (AR) with those of patients with perennial nonallergic rhinitis or vasomotor rhinitis (VMR). Nasal blockage was the predominant symptom in the VMR group, whereas the AR patients mainly suffered from eye irritation, sneezing, and, to some extent, rhinorrhea. Concomitant asthma was more prevalent in the AR group than in the VMR group, whose histories were characterized by symptoms associated with airway infections. About 60% of both groups reported problems with such nonspecific airway irritants as cigarette smoke and perfumes. With respect to the diagnostic reliability of the history, in the AR group the order of accuracy (according to the skin prick test results) of reported hypersensitivity to allergens was as follows: cat > timothy > birch > dust mite > mugwort. A history of hypersensitivity to molds as a cause of symptoms was of no diagnostic value. The findings suggest that there are several differences in the medical histories of AR and VMR patients that merit further investigation.

Adult

The effect of noradrenaline on mucociliary activity in the rabbit maxillary sinus.

The effect of noradrenaline (NA) on mucociliary activity in the rabbit maxillary sinus was investigated in vivo by injecting it at increasing dosages (10(-11) to 10(-4) mol/kg) into the maxillary artery, the mucociliary response being recorded photoelectrically. NA increased mucociliary activity at a dosage of 10(-5) mol/kg, the maximal increase being 16.1 +/- 2.6%. The NA-induced stimulation of mucociliary activity had a latency of 20 s, and the activity returned to base-line level within 3 min. Pretreatment with the alpha-antagonist phentolamine (0.2 and 1.0 mg/kg) or the cholinergic antagonist atropine (1 mg/kg) did not alter mucociliary response to NA. Blockade with the beta-antagonist propranolol did not significantly reduce the maximal response to NA, which was 16.1 +/- 2.6% before and 11.1 +/- 3.0% after pretreatment with propranolol (n = 7; p = 0.2). In contrast, pretreatment with the prostaglandin-synthesis inhibitor indomethacin reduced the response from 12.9 +/- 2.9% to 6.3 +/- 1.3% (n = 6; p < 0.05), suggesting that at high dosages NA stimulates mucociliary activity via the cyclo-oxygenase pathway.

Animals

Neuropeptide Y in the rabbit maxillary sinus modulates cholinergic acceleration of mucociliary activity.

The distribution of neuropeptide Y (NPY)-immunoreactivity was investigated in the rabbit maxillary sinus and adjacent ganglia. A moderate supply of NPY-containing nerve fibers occurred around seromucous glands and a denser supply around small blood vessels. Only a few immunoreactive nerve fibers were seen beneath the epithelium. Double immunostaining showed that vasoactive intestinal peptide (VIP) coexisted with NPY in the nerve fibers surrounding blood vessels and seromucous glands. NPY-containing nerve cell bodies were numerous in the superior cervical ganglion, and moderately numerous in the sphenopalatine ganglion. The finding of NPY-containing neurons in the latter parasympathetic ganglion suggests that NPY may influence the cholinergic regulation of mucociliary activity. The effect of NPY on the mucociliary activity of the maxillary sinus in connection with cholinergic stimulation has therefore been investigated in vivo using a photoelectric technique. At dosages of 2.5 and 5.0 micrograms/kg, the ganglionic stimulant nicotine bitartrate, which increases mucociliary activity by a cholinergic pathway, accelerated mucociliary activity by 28.0 +/- 7.5% and 36.8 +/- 6.2%, respectively. In the same experiment repeated during infusion of NPY (0.1 microgram/kg/min), the increase in mucociliary activity was reduced to 10.8 +/- 2.3% and 28.9 +/- 7.1%, respectively. Infusion of NPY did not affect the stimulating effect on mucociliary activity by bolus injections (0.1 and 0.5 microgram/kg) of the cholinergic agonist, methacholine. It is concluded that NPY-like immunoreactivity is present in nerve fibers in the rabbit maxillary sinus and in neurons in the sympathetic and parasympathetic ganglia that supply the nose and paranasal sinuses. NPY attenuates the effect of nicotine on mucociliary activity, probably via a prejunctional mechanism, and may act as a modulator of cholinergic regulation of the mucociliary system.

Animals

Skeletal metastases in 102 patients evaluated before surgery for renal cell carcinoma.

During a 3-year period a consecutive series of 102 patients were treated for renal cell carcinoma at one urological unit. Thirty-three patients (32.4%) had metastatic spread, but bone metastases were found in six patients only, i.e. 5.9% of the whole series and 18.2% of the patients with metastases preoperatively. The bone metastases had in all six patients given local symptoms first indicating radiography, and thereafter radionuclide scintigraphy of the entire skeleton. Bone scintigraphy performed merely by routine in 70 patients did not reveal one single case of bone metastasis. Only one patient had a solitary bone metastasis, and this metastasis was considered inoperable because of its location and size and the patient's age. The decision about nephrectomy was not in any case altered by the finding of bone metastases. Solitary bone metastasis must be diagnosed early since they may be radically removed. Routine scintigraphy of the skeleton in symptomless patients, however, has a low yield. Screening for skeletal metastases may therefore be best performed by careful physical examination and history-taking.

Adult

Cancer risks in thyroid cancer patients.

Cancer risks were studied in 834 thyroid cancer patients given 131I (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after 131I therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving 131I. In females treated with 131I overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of 131I. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following 131I treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of 131I with highest risk for patients exposed to greater than or equal to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose 131I exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower-dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation.

Female