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Biomedical subjects

P Wollmer

Publications and source records attributed to P Wollmer.

At least 19 recordsLinked to original sources

Metaiodobenzylguanidine (MIBG) scintigraphy and computed tomography (CT) in clinical practice. Primary and secondary evaluation for localization of phaeochromocytomas.

OBJECTIVE: To determine the diagnostic value of metaiodobenzylguanidine (MIBG) scintigraphy compared with computed tomography (CT) for the localization of phaeochromocytomas in clinical practice. DESIGN: Retrospective comparison between MIBG scintigrams and CT for localization of phaeochromocytomas in all patients successively examined with MIBG scintigraphy in Malmö from 1984 until January 1997. SETTING: Malmö University Hospital, Sweden. SUBJECTS: Sixty-four patients with clinically suspected phaeochromocytomas. MAIN OUTCOME MEASURES: MIBG scintigrams and CTs classified as positive or negative based on original interpretations (primary evaluation) and in a secondary evaluation by one blinded examiner are assessed through histological confirmation or clinical rule out of phaeochromocytomas. RESULTS: Twenty-five patients had surgically removed phaeochromocytomas. The remaining 39 patients had no proof of phaeochromocytomas. In the secondary evaluation, sensitivity for MIBG scintigraphy was 88% (22/25) and for CT was 100% (25/25). The specificity for MIBG scintigraphy was 89% (35/39) but only 50% for CT (18/36). Two out of a total of six extra-adrenal tumours were amongst the false-negative MIBG scintigrams. CONCLUSIONS: MIBG scintigraphy for the localization of phaeochromocytomas is superior to CT as far as specificity, whereas CT has a higher sensitivity. After biochemical diagnosis, CT will detect most phaeochromocytomas. MIBG scintigraphy can be of value in patients who show inconclusive results with biochemical testing and CT.

3-Iodobenzylguanidine↗

Sympathetic dysfunction in patients with primary Sjögren's syndrome.

OBJECTIVE: To investigate autonomic nervous system function in patients with primary Sjögren's syndrome (SS) and relate the findings to clinical variables. METHODS: Autonomic nervous system function was determined in 30 patients with primary SS using the finger skin blood flow test [vasoconstrictory (VAC) index], deep-breathing test [expiration/inspiration (E/I) ratio], and the tilt table (orthostatic) test [acceleration index (AI), brake index (BI), and orthostatic blood pressure]. The results were compared with age matched control materials (finger skin blood flow test, n = 80, and deep-breathing and tilt table tests, n = 56). RESULTS: The VAC index was found to be significantly increased and the E/I ratio significantly decreased in patients compared to controls, indicating both a sympathetic and a parasympathetic dysfunction. Further, the patients, especially the anti-SSA and anti-SSB antibody seropositives, were found to have an abnormal blood pressure reaction to tilt compared to controls. No correlations were found between autonomic nerve function variables measured and the clinical ophthalmologic or the oral tests, performed at the time of diagnosis. CONCLUSION: Patients with primary SS show signs of both sympathetic and parasympathetic dysfunction. Further, immunological mechanisms seem to influence blood pressure in patients with primary SS.

Adolescent↗

[Rapid increase of the use of PET in cancer investigation--but Sweden lags behind].

Glucose consumption in tissue can be measured using positron emission tomography (PET) and 18F-deoxyglucose (18FDG). Malignant tumors rely largely on anaerobic glycolysis and show very rapid glucose consumption, and can therefore be imaged using PET and 18FDG. PET has been shown to be useful in the evaluation of patients with e.g. lung cancer, colo-rectal cancer, malignant melanoma and malignant lymphoma, in terms of both diagnostic accuracy and cost-effectiveness. The clinical use of PET for workup of cancer patients is increasing rapidly in North America as well as in the European Union, but Sweden is lagging behind.

Fluorine Radioisotopes↗

[Rapid increase of the use of PET in cancer investigation--but Sweden lags behind].

Glucose consumption in tissue can be measured using positron emission tomography (PET) and 18F-deoxyglucose (18FDG). Malignant tumors rely largely on anaerobic glycolysis and show very rapid glucose consumption, and can therefore be imaged using PET and 18FDG. PET has been shown to be useful in the evaluation of patients with e.g. lung cancer, colo-rectal cancer, malignant melanoma and malignant lymphoma, in terms of both diagnostic accuracy and cost-effectiveness. The clinical use of PET for workup of cancer patients is increasing rapidly in North America as well as in the European Union, but Sweden is lagging behind.

Deoxyglucose↗

Evaluation of pulsed and breath-synchronized nebulization of budesonide as a means of reducing nebulizer wastage of drug.

The aim of this open, randomized, crossover study was to compare the inhaled mass of budesonide suspension delivered by nebulization, using constant output, breath-synchronized, or pulsed jet nebulization techniques. The inhaled mass was defined as the amount of drug deposited on a filter between the inspiratory port of the nebulizer and the face mask or mouthpiece used by the subjects. The breath-synchronized nebulization delivered aerosol during the whole inspiration, whereas the pulsed nebulization was adjusted to deliver aerosol for up to 1 sec from the start of inspiration. Budesonide suspensions, 2 mL of 0.5 mg mL(-1), or 2 mL of 0.25 mg mL(-1), in single-dose respules, were used (AstraZeneca R&D Lund, Lund, Sweden). Eleven children (7 boys, age range 2.5-5.8 years) with either a clinical suspicion or a confirmed diagnosis of asthma and 11 healthy adolescents and adults (6 male, age range 13-52 years) were enrolled. With constant output nebulization, the median inhaled mass of budesonide was about 17.6% (range 9.6-21.2%) of the nominal dose (i. e., dose of drug in the respule per label claim) in adolescents and adults, and 18.1% in children (15.7-21.4%). With pulsed nebulization the median inhaled mass increased to 23.4% (22.0-28.1%) in children and to 32.8% (24.8-38.0%) in adolescents and adults (P < 0.001). With breath-synchronized nebulization median inhaled mass increased to 30.1% (21.7-28.1%) in children, but was unchanged (30.8%, 27.0-38. 0%) in adolescents and adults. The mode of nebulization (i.e., constant or breath-synchronized) had a statistically significant effect on the inhaled mass in children and adolescents or adults (P < 0.001). There was a statistically significant difference in inhaled mass between the breath-synchronized and pulsed nebulization in children only (P < 0.05). The results support the use of breath-synchronized but not pulsed nebulization with conventional nebulizers. The results of pulsed nebulization in children warrants further clinical studies.

Adolescent↗

Evaluation of [O-methyl-(11)C]fluvoxamine as a tracer for serotonin re-uptake sites.

We evaluated [(11)C]fluvoxamine as a tracer for the serotonin re-uptake site. Studies of the distribution of the tracer in rat and primate brain showed adequate uptake of [(11)C]fluvoxamine, but failed to reveal regions with known high density of serotoninergic re-uptake sites. Pretreatment with unlabeled fluvoxamine did not substantially change the distribution. In rat brain tissue, nearly all radioactivity represented intact [(11)C]fluvoxamine. [(11)C]Fluvoxamine does not function as a tracer for serotonin re-uptake sites, owing to high nonspecific binding in the brain.

Animals↗

Surface active agents as enhancers of alveolar absorption.

PURPOSE: Small solutes which are deposited in the alveoli by aerosol inhalation will be absorbed across the alveolo-capillary barrier. Inhalation of dioctyl sodium sulfosuccinate (DOSS) enhances absorption while having little or no effect on lung function, suggesting that surface active agents may be used as enhancers of alveolar absorption of inhaled pharmaceuticals. The purpose of this study was to examine the effects of a selection of different surface active agents on alveolar absorption. METHODS: The absorption of 99mTc-diethylene triamine pentaacetate (99mTc-DTPA) from the lungs was studied in rabbits. We studied five different surface active agents: DOSS, sodium glycodioxycholate (GDCA), sodium lauryl sulphate (NaLS), lysophosphatidyl choline (LPC) and polyoxyethylene-23-laurylether (P23LE). RESULTS: DOSS and GDCA both dramatically enhanced the absorption of 99mTc-DTPA. There was a moderate effect of NaLS, no significant effect of LPC and P23LE reduced the rate of absorption. None of the compounds affected gas exchange or lung compliance. CONCLUSIONS: There is a wide spectrum of effects of inhaled surface active agents on the alveolar absorption of 99mTc-DTPA. Ionic compounds such as DOSS and GDCA have the greatest effect, and further studies of these classes of surface active agents for use as enhancers of alveolar absorption of pharmaceuticals seem warranted.

Absorption↗

Changes in transfer factor of the lung in response to bronchodilatation.

Measurement of the transfer factor for carbon monoxide (TLCO) is a widely used clinical lung function test. Although it is frequently applied in patients with bronchial obstruction, there is little information on the effects of bronchodilatation on the test. We therefore measured TLCO in 40 patients before and after inhalation of terbutaline. TLCO was measured with the single-breath technique in 20 patients and with the intra-breath technique in 20 patients. TLCO was also measured in 20 healthy subjects with the single-breath technique. Forced expiratory volume (FEV1) increased from 2.9 +/- 1. 1 to 3.2 +/- 1.2 l in patients with bronchial obstruction in response to terbutaline inhalation. TLCO increased from 8.2 +/- 2.6 to 8.6 +/- 2.7 mmol min-1 kPa-1 (P< 0.001) and alveolar volume (VA) from 5.74 +/- 1.21 to 5.90 +/- 1.21 l (P<0.001). There was no difference between the single-breath and the intra-breath techniques. There was little change in FEV1 in the healthy subjects in response to terbutaline. TLCO increased from 10.2 +/- 2.1 to 10.5 +/- 2.2 mmol min-1 kPa-1 (P< 0.01), but there was no change in VA. The increase in TLCO in patients may partly be explained by improved distribution of the inhaled gas. In healthy subjects, terbutaline may increase pulmonary capillary volume. We conclude that bronchodilatation results in a small increase in TLCO in patients with light to moderate bronchoconstriction as well as in healthy subjects. The effect is small and should in most cases be simple to account for in the interpretation of pulmonary function tests, provided the patient's treatment is known.

Adult↗

Efficient lung scintigraphy.

Lung scintigraphy is a first-choice method to diagnose lung embolism. The clinical routine in most centres is a perfusion study complemented with a ventilation study when judged necessary. We describe a routine with ventilation scintigraphy preceding perfusion scintigraphy, which is completed within one hour. Furthermore, the data acquired allow the determination of lung clearance of the tracer 99mTc-DTPA (diethylene triamine penta-acetate) used for the ventilation scintigraphy. An aerosol generator charged once a day with 99mTc-DTPA solution is used for all inhalations during the day. Inhalation is monitored with a counter and interrupted when the count rate corresponds to about 20 MBq. The ventilation imaging starts and ends with posterior projections. This allows calculation of lung clearance of 99mTc-DTPA. Perfusion scintigraphy is performed in a standard fashion with 100 MBq of 99mTc-MAA (macro-aggregated albumin). The ventilation study was considered to give some diagnostic information in the majority of the patients. The clearance determination allows detection of inflammatory lung disease. The background activity caused by the ventilation study comprised only 13% of the activity in the perfusion scintigraphy and did not significantly interfere with interpretation of the perfusion scan. The cost for the investigation is low because of the rational system for aerosol administration and the short time for a complete study.

Humans↗

One year follow-up of lung clearance of 99mTc-diethylene triamine penta-acetic acid and disease activity in sarcoidosis.

BACKGROUND AND AIM OF THE WORK: In interstitial lung disease lung clearance of 99mTc-diethylenetriaminepentaacetic acid (DTPA) reflects alterations in the alveolar capillary barrier. Our objective was to describe changes in lung clearance during one year in sarcoidosis, and to relate clearance to other data of lung function and disease activity. METHODS: Twenty-three newly diagnosed patients were studied with respect to lung DTPA clearance, spirometry, 67Ga scintigraphy and serum angiotensin converting enzyme (SACE). Lung mechanics and arterial PO2 at rest and exercise were studied in patients with radiological parenchymal changes. Six of these patients were prescribed peroral steroids. RESULTS: At inclusion lung DTPA clearance measured over 30 minutes was 53 +/- 16 minutes and at follow-up 59 +/- 20 minutes (p > 0.05). The number of pathological clearance curves at inclusion was 10 and at follow-up 6. In treated patients lung DTPA clearance improved as did lung 67Ga score and SACE. However, lung clearance did not correlate significantly with changes in lung function or other activity parameters. CONCLUSIONS: Lung DTPA clearance reflects lung function from an aspect different from that of other methods. It seems sensitive to pathology reversed by steroids and may, in some cases, help in the evaluation of disease activity.

Adult↗

Glucose utilisation in the lungs of septic rats.

Sequestration and degranulation of leucocytes in the pulmonary microcirculation is considered to be a key event in the development of acute respiratory distress syndrome in patients with sepsis. Glucose serves as the main source of energy in activated leucocytes. The aim of this study was to assess whether glucose utilisation in the lungs can be used as an indicator of pulmonary leucocyte accumulation in an experimental model of sepsis of intra-abdominal origin. Sepsis was induced in rats by abdominal implantation of a gelatine capsule containing bacteria and rat colonic contents. Empty gelatine capsules were implanted in control animals. Animals were studied 6 and 12 h after sepsis induction. Glucose utilisation was measured as the tissue uptake of fluorine-18-fluorodeoxyglucose ((18)FDG) 1 h after intravenous injection of the tracer. Micro-autoradiography was also performed after injection of tritiated deoxyglucose. We found increased uptake of (18)FDG in the lungs of septic animals. The uptake also increased with time after sepsis induction. (18)FDG uptake in circulating leucocytes was increased in septic animals compared with controls, and micro-autoradiography showed intense accumulation of deoxyglucose in leucocytes in the lungs of septic animals. We conclude that glucose utilisation is increased in the lungs of septic rats. Measurements of pulmonary glucose utilisation as an index of leucocyte metabolic activity may open new possibilities for studies of the pathophysiology of sepsis and for evaluation of therapeutic interventions.

Animals↗

Lung clearance of intratracheally instilled 99mTc-tobramycin using pulmonary surfactant as vehicle.

1. The use of pulmonary exogenous surfactant as a vehicle for intratracheally administered antibiotics to improve local antimicrobial therapy has been proposed. The present study investigated lung clearance rates in the rat of intratracheally instilled technetium labelled tobramycin with and without the addition of surfactant to the antibiotic solution. 2. The influence of surfactant on 99mTc-tobramycin lung clearance rates was studied dynamically with a gamma-camera in anaesthetized spontaneously breathing animals and in mechanically ventilated animals. 3. The results show that instillation of 99mTc-tobramycin with use of surfactant as vehicle significantly increases 99mTc-tobramycin lung clearance compared to instillation of 99mTc-tobramycin solution alone (P=0.006 between the two spontaneously breathing groups of animals and P=0.02 between the two ventilated groups of animals, ANOVA for repeated time measurements). The half life (t1/2) of composite clearance curves in spontaneous breathing animals was 147 min for animals receiving 99mTc-tobramycin versus 61 min for animals receiving 99mTc-tobramycin with surfactant. In mechanically ventilated animals this was 163 min versus 51 min, respectively. 4. It is concluded that exogenous surfactant, used as vehicle for intratracheally instilled 99mTc-tobramycin, increases lung clearance rate of 99mTc-tobramycin in rats.

Administration, Inhalation↗

Time course of the inflammatory response to histamine and allergen skin prick test in guinea-pigs.

Plasma exudation and vasodilatation are key microvascular features of acute inflammation. Exudation and vasodilatation responses in the weal area after skin prick testing with histamine are essentially completed within 30 min. There is evidence to suggest that vasodilatation lasts considerably longer after provocation with allergen, but there is no information on the duration of plasma exudation. The purpose of this study was to measure the time course of the microvascular inflammatory response in the skin after histamine and allergen provocation. Skin prick tests were performed with histamine, allergen (ovalbumin) or saline (control) on guinea-pigs which were shaved on their backs. Radioactive 113mIn was used to label transferrin as a plasma tracer. Radioactivity was recorded from the superficial part of the skin by external detection of conversion electrons from the decay of 113mIn. The increase in count rate, corresponding to tracer accumulation by vasodilatation and/or plasma exudation, was used as a measure of the microvascular inflammatory response to skin prick test. The microvascular response was studied immediately and up to 30 min after provocation. The largest response to histamine and allergen occurred immediately after provocation. The exudative response then gradually declined to be absent after 25-30 min. Skin prick test with saline resulted in a small response of shorter duration. We conclude that the microvascular reaction to histamine as well as allergen provocation in guinea-pig skin has a rapid onset and a duration of approximately 30 min.

Allergens↗

Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo.

Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H2O2 on airway exudation and absorption in vivo. Vehicle or H2O2 (0.1 and 0.5 M) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. 125I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA was superfused 20 min after vehicle or H2O2 (0.1 and 0.5 M) had been given. A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of airway absorption. The high dose of H2O2 (0.5 M) produced epithelial damage, increased the absorption of 99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H2O2 differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.

Albumins↗

Changes in airway dead space in response to methacholine provocation in normal subjects.

Measurements of bronchial hyper-responsiveness rely on sensitive techniques for measurement of bronchoconstriction, ideally based on tidal breathing. A potentially useful technique is measurement of airway dead space (VDaw), which reflects the volume of the conducting airways. The aim of this study was to evaluate measurements of VDaw with the single breath test for CO2 (SBT-CO2), compared to spirometric measurements, as a method of measuring bronchial response to methacholine challenge. Nineteen healthy adults were studied. Dosimetric methacholine challenge tests were performed on two study days. Forced expirations or the SBT-CO2 were used to assess the response. There were dose-dependent reductions in the spirometric measurements, with a 10 +/- 10% reduction from the baseline value of forced expiratory volume at the highest dose of methacholine. There was a dose-dependent reduction from the baseline value of VDaw by 19 +/- 9% at the highest dose. There was also a dose-dependent increase in the slope of the alveolar plateau of the SBT-CO2. This study provides support for measurement of VDaw as a means of evaluating bronchial responsiveness after methacholine challenge. In a group of healthy adults, this method shows a greater response but with similar dispersion as measurement of forced expiratory volume after methacholine challenge.

Adolescent↗

Regional VA/Q ratios in man using 133Xe and single photon emission computed tomography (SPECT) corrected for attenuation.

We describe a technique to obtain non-invasively regional pulmonary ventilation-perfusion ratios (VA/Q) using single photon emission computed tomography (SPECT) and continuous infusion of 133Xe. Single photon transmission tomography was used for attenuation correction, for delineation of the lungs and for VA/Q calculations. Data are presented for six normal subjects and compared to those for two patients with moderate chronic obstructive pulmonary disease (COPD). The mean VA/Q for the whole lung of the normal subjects ranged from 0.49 to 0.65, group mean 0.56 +/- 0.07 (1 SD), and there was no significant difference between the right and left lung. The consistently too low VA/Q values are related to the inability to measure regional blood volume and the low resolution of the scintillation camera, giving an under-estimation of tracer input. For the normal subjects, the dispersion of VA/Q, as defined by the standard deviation of the individual distribution functions, ranged from 0.12 to 0.19. One of the patients was characterized by a low mean VA/Q of 0.35, and the other patient had a wide dispersion (SD) of VA/Q of 0.37. In the normal subjects, a consistent VA/Q gradient was found only in the ventrodorsal direction. 133Xe and SPECT can be used to obtain meaningful biological information regarding ventilation/perfusion relationships of potential clinical value.

Adult↗

Increased aortic stiffness in women with type 1 diabetes mellitus is associated with diabetes duration and autonomic nerve function.

AIMS: The increase in risk for cardiovascular complications in diabetic women is even greater than that in diabetic men. We found arterial stiffness to be increased in women, but not in men, with Type 1 diabetes mellitus (DM). The aims of the present study were to evaluate whether the changes in arterial distensibility are influenced by diabetes duration and to evaluate any association between autonomic neuropathy and decreased arterial distensibility. METHODS: Stiffness of the abdominal aorta was measured noninvasively using echo-tracking sonography and parasympathetic function by heart rate variation during deep breathing (E/I ratio) in 40 women (mean age 33 years, range 20-61) and 38 men (mean age 36 years, range 22-56) with Type 1 DM. RESULTS: There was a significant correlation between aortic stiffness and duration of diabetes in women (r = 0.41, P = 0.008), but not in men (r = 0.15, P = 0.35). There was also a significant correlation between aortic stiffness and the E/I ratio in women (r = -0.49, P = 0.002), but not in men (r = -0.14, P = 0.41). When adjusted for diabetes duration, the significant association between the E/I ratio and aortic stiffness remained in diabetic women (r = -0.44, P = 0.008) and was stronger than the association between diabetes duration and aortic stiffness. There were no significant correlations between aortic stiffness and triglycerides or total cholesterol, respectively. CONCLUSIONS: Increased aortic wall stiffness found in women with Type 1 DM is related to diabetes duration. Further, in women with Type 1 DM there is a correlation between increased aortic stiffness and parasympathetic dysfunction. This may be of importance for the increased susceptibility to cardiovascular complications in diabetic women.

Adult↗

The conventional ultrasonic nebulizer proved inefficient in nebulizing a suspension.

A study was undertaken to compare the amount of nebulized budesonide suspension and nebulized terbutaline sulphate solution inhaled by healthy adult subjects when conventional jet and ultrasonic nebulizers were used. Ten healthy subjects (5 male; age range, 16-52 years) used two conventional nebulizers: the Spira Elektro 4 jet nebulizer (Respiratory Care Center, Hämeenlinna, Finland) and the Spira Ultra ultrasonic nebulizer (Respiratory Care Center) in a breath-synchronized mode with each drug. The amount of drug inhaled, the inhaled mass, was defined as the amount of drug deposited on a filter between the inspiratory port of the nebulizer and the mouthpiece. The amount of budesonide and terbutaline sulphate was determined by reversed-phase high-performance liquid chromatography. Single-dose respules were used (0.5 mg of budesonide and 5.0 mg of terbutaline sulphate), and nebulization time up to the defined gravimetric output was recorded. The inhaled mass of budesonide varied depending on the nebulizer used, whereas the inhaled mass of terbutaline was unaffected by the choice of nebulizer. The median inhaled mass of budesonide was 31.4% of the nominal dose (i.e., dose of drug in the respule per label claim) with the Spira Elektro 4 and 9.9% with the Spira Ultra, whereas the median inhaled mass of terbutaline was 50% with the Spira Elektro 4 and 52% with the Spira Ultra. It appears that a suspension is generally more difficult to nebulize than a solution and that the budesonide suspension should not be used in conventional ultrasonic nebulizers.

Administration, Inhalation↗