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F Madsen

Publications and source records attributed to F Madsen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evaluation of Göttingen minipig skin for transdermal in vitro permeation studies.

The optimal skin type for in vitro permeability studies depends on the purpose of the specific transdermal study. In a number of cases, it may be advantageous to use animal skin as an alternative to human skin although they have different characteristics. Recently, Göttingen minipigs have been reported as good models in toxicological and pharmacokinetic studies of drug substances. In this paper, the potential use of skin from the Göttingen minipig is evaluated by studying three model drug substances (nicotine, salicylic acid and testosterone) through skin from humans, domestic pigs and three ages of the Göttingen minipig. An analysis of variance and a Student's t-test showed that both the skin from the Göttingen minipig and the domestic pig possessed transdermal permeabilities, which correlated with human skin and exhibited a lower intra- and intervariation. Furthermore, it was shown that permeability and variation of fluxes through skin from Göttingen minipigs were dependent on the age of the minipig and of the drug substance. It is concluded that the Göttingen minipig, like the domestic pig, is a good skin model for in vitro permeation through human skin.

Administration, Cutaneous↗
PubMed2000

The prevalence of skin-test-positive allergic rhinitis in Danish adults: two cross-sectional surveys 8 years apart. The Copenhagen Allergy Study.

BACKGROUND: It is disputed whether increases in self-reported respiratory allergy represent a true increase or merely increased recognition. We aimed to investigate whether the prevalence of skin-prick-test (SPT)-positive allergic rhinitis had increased in an adult general population in Copenhagen, Denmark. METHODS: Two cross-sectional surveys were carried out in 1990 and 1998. A screening questionnaire on respiratory symptoms in random samples of 15-41-year-olds preceded both surveys. Among the responders, random samples were invited to a health examination including SPT. Totals of 312 (participation rate 74.6%) and 482 (participation rate 53.4%) subjects were examined in 1990 and 1998, respectively. Diagnoses of SPT-positive allergic rhinitis were based on a history of nasal symptoms on exposure to allergens and SPT positivity to allergens. RESULTS: The prevalence of a diagnosis of SPT-positive allergic rhinitis increased from 12.9% to 22.5% (adjusted odds ratio 1.94, 95% CI 1.30-2.90), whereas the prevalence of a positive SPT (allergen histamine wheal ratio > or = 0.5) to one or more of 10 allergens increased from 27.7% to 33.9% (adjusted odds ratio 1.47, 95% CI 1.05-2.05). CONCLUSIONS: The prevalence of SPT-positive allergic rhinitis has increased significantly. Our findings indicate that a true increase in respiratory allergy has occurred.

Adult↗
PubMed2000

Accuracy of recorded asthma deaths in Denmark in a 12-months period in 1994/95.

Many studies of asthma mortality rely on official registration. The aim of this study was to evaluate the accuracy of death certificates, where asthma was coded as cause of death. In a 12-month period, medical information on all subjects with asthma officially coded as the underlying cause of death in Denmark, was obtained by reviewing hospital records, contacting general practitioners and sometimes close relatives. A panel of four pulmonologists each examined the obtained information and independently assessed the cause of death. Of a total of 218 death certificates, 39 were excluded as the cause of death could not be validated. In 16 (9%) of the subjects death from asthma was judged to be the definite cause of death and in 12 (7%) death from asthma was possible. Of 151 non-asthma deaths coded as due to asthma, 109 were judged to have suffered or died from COPD and 14 from heart disease. The accuracy of Danish death certification in asthma deaths is poor, especially in the elderly, where COPD is often classified as asthma. We conclude that the true asthma mortality in Denmark is substantially lower than officially recorded.

Adult↗
PubMed2000

Increasing prevalence of specific IgE to aeroallergens in an adult population: two cross-sectional surveys 8 years apart: the Copenhagen Allergy Study.

BACKGROUND: There is evidence that the prevalence of respiratory allergy has increased in children in many countries. However, this evidence is largely based on questionnaire data, and little is known about similar trends in adults. OBJECTIVE: We investigated whether the prevalence of specific IgE to aeroallergens had increased in an adult general population over an 8-year period. METHODS: Two cross-sectional surveys were carried out in 1990 and 1998. A mailed screening questionnaire on respiratory symptoms sent to random samples of 15- to 41-year-old subjects living in Copenhagen (Denmark) preceded both surveys. Random samples of responders were invited to a health examination, including assessment of specific IgE to 6 common aeroallergens. Totals of 312 (74.6% of the invited subjects) and 482 (53.4% of the invited subjects) subjects were examined in 1990 and 1998, respectively. Analyses of serum samples from both surveys were performed in 1999. RESULTS: The prevalence of specific IgE to at least one allergen increased significantly from 1990 to 1998 (26.5% vs 33.9%; odds ratio adjusted for sex, age, and season of examination, 1.63; 95% confidence interval, 1.15-2.32; P = .006). This increase remained unexplained after adjustment for changes in questionnaire variables on lifestyle and home environment. The clinical significance of this increase was underlined by a corresponding increase in the prevalence of allergic rhinitis symptoms associated with specific IgE positivity. CONCLUSION: We found that the prevalence of specific IgE positivity to aeroallergens increased in an adult Danish general population from 1990 and 1998.

Adolescent↗
PubMed1999

Complexation graft copolymer networks: swelling properties, calcium binding and proteolytic enzyme inhibition.

Graft copolymer networks of poly(methacrylic acid-g-ethylene glycol) were prepared by free radical solution UV-polymerization of methacrylic acid (MAA) and poly(ethylene glycol) monomethacrylate. Dynamic swelling studies indicated that complexation/decomplexation processes occurred due to hydrogen bonding between the carboxylic groups of the poly(methacrylic acid) (PMAA) and the ether groups of poly(ethylene glycol) (PEG). The effects of copolymer composition, graft chain molecular weight, environmental pH and ion content on network structure and gel behavior were studied. The largest change in swelling ratio and mesh size of the gel structure was observed in gels containing the highest content of PEG and the longest molecular weight PEG grafts. Complexation was greatest in hydrogels containing the longest PEG grafts and equimolar amounts of MAA and PEG. The swelling was much less pronounced in the presence of calcium chloride compared to sodium chloride which could be attributed to the complexation of calcium of the carboxylic groups in the polymer. The copolymers showed significant but less binding of calcium compared to poly(acrylates) like Carbopol 934P and polycarbophil. The P(MAA-g-EG) copolymers inhibited trypsin but to a lesser extent than the known protease inhibitors Carbopol 934P and polycarbophil. Results suggest that P(MAA-g-EG) copolymers are good drug delivery carrier candidates due to their pH-sensitive and controllable swelling behavior. Additionally, they possess some protease inhibition effect along with their bioadhesive properties which make them promising carriers for peptides or proteins.

Biocompatible Materials↗
PubMed1999

Office spirometry: temperature conversion of volumes measured by the Vitalograph-R bellows spirometer is not necessary.

The aim of the present study was to investigate the relevance of BTPS (gas at body temperature, atmospheric pressure and saturated with water vapour) conversion of volumes measured with the Vitalograph bellows spirometer. The Vitalograph bellows were tested against a MicroMedical turbine spirometer in extreme temperatures (0-37 degrees C) using a biological control to deliver expired gas at BTPS. Before testing, it was shown that the accuracy of the DairyCard turbine was stable in the relevant temperature range. In a clinical trial six patients with emphysema performed home spirometry b.i.d for 1 month using both the Vitalograph and the turbine. Both the DairyCard and the Vitalograph showed stable accuracy at extreme temperatures when results were reported without any BTPS conversion. These findings were supported by the clinical trial but the conclusions from the clinical setting were weakened by the surprising fact that domiciliary temperatures showed almost no variation. We conclude that the Vitalograph bellows, during dynamic spirometry, measures expired volume at conditions closer to BTPS (than to ATPS) gas at ambient temperature, atmospheric pressure and saturated with water vapour). The use of the BTPS correction based on ambient temperature seems unjustified at office temperatures close to 23 degrees C and at extreme temperatures the conversion of volume will introduce significant over or underestimation.

Adult↗
PubMed1999

Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics.

Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P<0.01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo (P = 0.001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo (P<0.05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics.

Administration, Inhalation↗
PubMed1999

Increasing prevalence of allergic rhinitis symptoms in an adult Danish population.

There is evidence that the prevalence of respiratory allergy is increasing. This is mainly based on studies in children and young adults. The aim of the study was to compare the prevalences of self-reported symptoms of respiratory allergy among Danish adults in two surveys 8 years apart. Identical questionnaires were mailed to two random general population samples in 1989 and 1997. The response rates were 86.1% (n = 3603) and 86.4% (n = 817), respectively. The sampling frame and sampling method were identical in both surveys. The changes in the prevalences of symptoms were expressed by sex- and age-adjusted odds ratios comparing 1997 to 1989. We found a significant increase in the prevalence of seasonal rhinitis symptoms (OR=1.6, 95% CI 1.4-1.9), rhinitis symptoms on exposure to pollen (OR =1.6, 95% CI 1.4-1.9), rhinitis symptoms on exposure to furry animals (odds ratio 1.6, 95% CI 1.3-2.0), rhinitis symptoms on exposure to house dust (OR = 1.3, 95% CI 1.1-1.6), and breathlessness on exposure to pollen (OR = 1.5, 95% CI 1.0-2.0). The observed increases were independent of sex and age. The questionnaire was validated in relation to allergen skin test reactivity in a subgroup of the responders to the 1989 survey. When the estimated associations between symptoms and skin test reactivity were considered, the results suggested an increase in allergy to pollen and animal dander. In conclusion, we found evidence of increased prevalence of allergic rhinitis symptoms associated with skin test reactivity.

Adolescent↗
PubMed1999

A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

Double-Blind Method↗
PubMed1998

A rheological examination of the mucoadhesive/mucus interaction: the effect of mucoadhesive type and concentration.

The ability of mucoadhesive polymers to produce a large increase in the resistance to deformation when incorporated into a mucus gel, relative to when the mucus gel and test materials are evaluated separately at the same concentrations, has been reported in several previous studies. It has been proposed that this phenomenon, termed rheological synergism, can be used as a measure of the strength of the mucoadhesive interaction. In this investigation rheological synergism was investigated for a large range of putative mucoadhesive gels by dynamic oscillatory rheology. Changes in the storage modulus (G'), loss modulus (G"), and loss tangent (tan-delta) were found and the relative rheological synergism calculated. Rheological synergism was evident for a range of materials with known mucoadhesive properties giving behaviour between that of strongly cross-linked polymers gels and a physically entangled system. This effect was most marked with materials known to be of high mucoadhesive strength even when fully hydrated. Hence, polymers like sodium carboxymethylcellulose and high molecular weight poly(ethylene oxide) showed limited rheological synergism. When the effect of mucoadhesive concentration was investigated, relative rheological synergism occurred within a limited concentration range only, the values of which varied between materials. It was concluded that macromolecules possessing numerous hydrogen bond-forming groups and an open expanded network in the test environment gave pronounced rheological synergism, and the relevance of this to mucoadhesion studies will be investigated in further work. This study also confirmed the advantages of dynamic oscillatory rheology over simple viscosity measurement in the study of these systems.

Adhesiveness↗
PubMed1998

A rheological assessment of the nature of interactions between mucoadhesive polymers and a homogenised mucus gel.

The ability of mucoadhesive materials to produce a large increase in the resistance to deformation when incorporated into a mucus gel, relative to when the mucus gel and test materials are evaluated separately at the same concentration, has been reported in several previous studies. It has been proposed that this phenomenon, termed rheological synergism, can be used as a measure of the strength of the mucoadhesive interaction. This study investigated the interactions between four putative mucoadhesive polymers (Noveon, Pemulen TR-2, carageenan and sodium carboxymethylcellulose) and a homogenised mucus gel, using dynamic oscillatory rheology. It was shown that, with the exception of sodium carboxymethylcellulose, incorporating a mucoadhesive polymer into a mucus gel produces rheological behaviour indicative of a weakly cross-linked gel network, which suggested a structure containing physical chain entanglements and non-covalent (probably hydrogen) bonds. Optimum gel strengthening occurred in a weakly acidic environment, suggesting an optimum conformation and degree of ionisation of the polymer and mucus molecules. Subsequent work suggested that the macromolecular interactions between polymer and mucus are sensitive to temperature, with the dynamic moduli decreasing with increasing temperature, further indicating bonding of a non-covalent nature. This work provide further evidence that rheological methods can be used as a tool to evaluate the interactions between a mucoadhesive macromolecule and a mucus gel. It also adds to the perception that molecular interpenetration may be an important factor in mucoadhesion by strengthening the mucus in the mucoadhesive/mucosal interfacial layer.

Acrylic Resins↗
PubMed1998

Clinical magnetic resonance imaging and arthroscopic findings in knees: a comparative prospective study of meniscus anterior cruciate ligament and cartilage lesions.

We compared the diagnostic and predictive value of magnetic resonance imaging (MRI) and clinical findings with arthroscopy in 61 knees in a prospective study. In meniscal tears, the accuracy and positive predictive value of MRI was found to be nearly twice that of clinical examination. The sensitivity, specificity, and negative predictive value of MRI were comparable to the figures found in other studies. We recommend MRI as a clarifying diagnostic tool when a clinical examination indicates a lesion of the meniscus. In our study, the clinical relevance of MRI in anterior cruciate ligament lesions and especially in cartilage lesions was more doubtful. The combination of clinical and MRI findings would reduce the number of blank arthroscopies to 5%. MRI is a valuable diagnostic tool in planning the type of anesthesia and treatment, and could significantly reduce the need for a second arthroscopy.

Adult↗
PubMed1998

Long-range correlations of serial FEV1 measurements in emphysematous patients and normal subjects.

In obstructive lung disease the annual change in lung function is usually estimated from serial measurements of forced expiratory volume in 1 s (FEV1). Frequent measurements in each patient may not improve this estimate because data are not statistically independent; i.e., the measurements are autocorrelated. The purpose of this study was to describe the correlation structure in time series of FEV1 measurements. Nineteen patients with severe alpha1-antitrypsin deficiency (phenotype PiZ) and moderate to severe emphysema and two subjects with normal lungs were followed for several years with daily self-administered spirometry. FEV1 measurements fulfilling standard criteria were detrended, and the autocorrelation profile and the power spectrum were calculated. On average the subjects were followed for >3 yr and performed >1,000 acceptable spirometries. The autocorrelation of FEV1 measurements in the emphysematous patients was approximately 0.35 for short intervals and decreased almost exponentially with a half time of 38 days. Between 3 and 4 mo, the autocorrelation function became negative. It reached a minimum of -0.1 at approximately 8 mo and then increased toward zero over the following 12 mo. The autocorrelation function in the two normal subjects showed a similar pattern, but with a faster decay toward zero. In the patients, the power spectrum had a peak at 1 cycle/wk and showed a 1/f pattern, where f is frequency, with a slope of -0.88 at lower frequencies. We conclude that serial spirometric measurements show long-range correlations. The practical implication is that FEV1 need not be measured more often than once every 3 mo in studies of the long-term trends in lung function.

Adult↗
PubMed1997

MR diffusion imaging of human intracranial tumours.

We used MRI for in vivo measurement of brain water self-diffusion in patients with intracranial tumours. The study included 28 patients (12 with high-grade and 3 with low-grade gliomas, 7 with metastases, 5 with meningiomas and 1 with a cerebral abscess). Apparent diffusion coefficients (ADC) were calculated in a single axial slice through the tumours, the sequence was sensitive to diffusion along the cephalocaudal axis. Our main finding was that ADC in contrast-enhancing areas within cerebral metastases was statistically significantly higher than ADC in contrast-enhancing areas in high-grade gliomas (P < or = 0.05). Furthermore, the ADC in oedema surrounding metastases were statistically significantly higher the ADC in oedema around high-grade gliomas (P < or = 0.02). The ADC in patients with meningiomas did not differ significantly from those seen with high-grade gliomas or cerebral metastases. The highest ADC were found within cystic or necrotic tumour areas. In one patient with a cerebral abscess, suspected of having a high-grade glioma, the ADC was similar to that in high-grade gliomas. The finding of higher ADC in cerebral metastases than in high-grade gliomas may be helpful in trying to distinguish between these tumours preoperatively; it suggests increased free extracellular and/or intracellular water fraction in cerebral metastases. The method seems to hold potential for further noninvasive characterisation of intracranial tumours.

Adult↗
PubMed1996

Patient-administered sequential spirometry in healthy volunteers and patients with alpha 1-antitrypsin deficiency.

The launching of cheap, pocket-sized spirometers, with data storage capability, has made patient-administered sequential spirometry (PASS) an attractive method of monitoring ventilatory capacity. At present, little information is available on the quality of PASS, compared to laboratory spirometry. The aim of this study was to investigate whether patients could perform PASS without loss of reliability and reproducibility as compared with traditional laboratory spirometry. Ten healthy volunteers performed spirometry for 1 month and 10 emphysematous patients with alpha 1-antitrypsin deficiency (type PiZ) performed spirometry twice daily for up to 2 yr. To fulfil Good Clinical Practice criteria on full data documentation, a traditional direct recording spirometer, the Vitalograph R-model, was used. A decompression device was used for calibration and a 3.8% annual drift in volume registration was noted. This drift was largest for the first year. After training, all patients were able to perform unsupervised spirometry, producing technically correct forced expiratory curves. Reproducibility of FEV1 and FVC obtained by PASS was found to be as good as for laboratory spirometry. After adjustment for the diurnal variation, the residual variation of FEV1 was 2.5% (range 1.6-4.2%) for healthy volunteers and 5.6% (range 4.2-7.7%) for emphysematous patients. Forced vital capacity showed the same pattern. In conclusion, PASS is possible in highly motivated individuals without loss of reliability and reproducibility when compared to laboratory spirometry.

Adult↗
PubMed1996

Neurosurgery for trigeminal neuralgia: comparison of alcohol block, neurectomy, and radiofrequency coagulation.

OBJECTIVES: We wished to assess the present condition of patients previously treated with a neurosurgical procedure or procedures for trigeminal neuralgia (TN) in 383 patients treated between 1976 and 1991, for TN at the Department of Neurosurgery, Hvidovre Hospital. Of these, 67 were lost to follow-up. The latest surgical intervention performed was radiofrequency coagulation (RFC) (64%), neurectomy (18%), alcohol block (16%), trigeminal tractotomy (1%), and microvascular decompression (1%); 72% of patients underwent only one neurosurgical procedure. METHODS: Questionnaires were sent to 316 patients treated neurosurgically for TN during the 16-year period; 288 (91%) patients responded. The follow-up period varied from 1 to 16 years (mean 8 years). Outcome measures were effect of RFC, neurectomy, and alcohol block; present pain conditions; and sequelae. RESULTS: After RFC, neurectomy, and alcohol block, 83, 51, and 42% of patients, respectively, experienced a pain-free postoperative period; 49, 78, and 84% of these patients had recurrence of pain. At present, 49, 17, and 18% are pain-free and 33, 21, and 36% now have less pain than they did preoperatively. Temporary or permanent analgesics for facial pain were required in 41, 72, and 69% of the patients. Sequelae were described by 65, 57, and 49% of the patients. The four most common sequelae were hypoesthesia, paresthesia, eye complaints, and dysesthesia. CONCLUSION: If relevant pharmacotherapy has been tried without benefit, RFC may still be considered as a treatment for TN.

Adult↗
PubMed1996

Long-term performance of a hand held spirometer.

BACKGROUND: A study was undertaken to test the long term performance of a small hand held spirometer for self-administered serial spirometric testing. METHODS: Thirty turbine pocket spirometers (MicroMedical DiaryCard) were used in a clinical trial on 22 emphysematous patients with severe alpha 1-antitrypsin deficiency. The spirometers were able to store the date, time, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and flow-volume loop for each blow. Every four weeks when the patients came for alpha 1-antitrypsin infusions the performance of their spirometer was checked before and after retrieval of the data from the spirometer. Calibration checks were threefold and included volume calibration with a 1.0 litre and 3.0 litre syringe, and flow calibration with a decompression calibrator. RESULTS: After two years of study the mean number of spirometric recordings performed per spirometer was 693 (range 237-1178), and the mean number of calibration checks was 33 (range 2-57). The coefficient of variation of the calibration signal was 1-2% for syringes and 0.5-1% for the decompression calibrator. The bearings of one turbine exhibited excessive friction after 17 months. None of the other 29 instruments showed drift, and a general drift of all spirometers towards larger or smaller readings could not be shown. However, unforeseen problems in the stability of the calibrating devices were observed. CONCLUSIONS: The small hand held turbine spirometers are suitable for long term patient-administered serial spirometric testing. The two year durability is acceptable and the long term reproducibility excellent.

Calibration↗