Per Wollmer

Quantitative measurement of regional lung ventilation using 3He MRI.

A new strategy for a quantitative measurement of regional pulmonary ventilation using hyperpolarized helium‐3 (3He) MRI has been developed. The method employs the build‐up of the signal intensity after a variable number of 3He breaths. A mathematical model of the signal dynamics is presented, from which the local ventilation, defined as the fraction of gas exchanged per breath within a given volume, is calculated. The model was used to create ventilation maps of coronal slices of guinea pig lungs. Ventilation values very close to 1 were found in the trachea and the major airways. In the lung parenchyma, regions adjacent to the hilum showed values of 0.6–0.8, whereas 0.2–0.4 was measured in peripheral regions. Monte Carlo simulations were used to investigate the accuracy of the method and its limitations. The simulations revealed that, at presently attainable signal‐to‐noise ratios, the ventilation parameter can be determined with a relative uncertainty of <5% over a wide range of values. Magn Reson Med 48:223–232, 2002.

Characterization of diffusing capacity and perfusion of the rat lung in a lipopolysaccaride disease model using hyperpolarized 129Xe

The ability to quantify pulmonary diffusing capacity and perfusion using dynamic hyperpolarized 129Xe NMR spectroscopy is demonstrated. A model of alveolar gas exchange was developed, which, in conjunction with 129Xe NMR, enables quantification of average alveolar wall thickness, pulmonary perfusion, capillary diffusion length, and mean transit time. The technique was employed to compare a group of naïve rats (n = 10) with a group of rats with acute inflammatory lung injury (n = 10), caused by instillation of lipopolysaccaride (LPS). The measured structural and perfusion‐related parameters were in agreement with reported values from studies using non‐NMR methods. Significant differences between the groups were found in total diffusion length (control 8.5 ± 0.5 μm, LPS 9.9 ± 0.6 μm, P < 0.001), in capillary diffusion length (control 2.9 ± 0.4 μm, LPS 3.9 ± 1.0 μm, P < 0.05), and in pulmonary hematocrit (control 0.55 ± 0.06, LPS 0.43 ± 0.08, P < 0.01), whereas no differences were observed in alveolar wall thickness, pulmonary perfusion, and mean transit time. These results demonstrate the ability of the method to distinguish two main aspects of lung function, namely, diffusing capacity and pulmonary perfusion. Magn Reson Med 50:1170–1179, 2003.

Daily physical activity related to aerobic fitness and body fat in an urban sample of children.

This study evaluates associations between objectively measured daily physical activity vs aerobic fitness and body fat in children aged 8–11 years. A cross‐sectional study of 225 children aged 7.9–11.1 years was performed. Abdominal fat mass (AFM) and total body fat (TBF) were quantified by dual‐energy x‐ray absorptiometry. TBF was calculated as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Aerobic fitness was measured by indirect calorimetry during a maximal cycle ergometer exercise test. Daily physical activity was assessed by accelerometers for 4 days and daily accumulation of moderate‐to‐vigorous and vigorous activity was calculated. Significant relationships (P<0.05) existed for vigorous activity vs ln BF% (r=−0.40), ln AFM (r=−0.35), TBF/AFM (r=−0.22) and aerobic fitness (r=0.38), whereas moderate‐to‐vigorous activity displayed weaker relationships (−0.22, −0.18, −0.12 NS, and 0.25). Multiple regression analyses with inclusion of possible confounders concluded that vigorous activity was independently related to aerobic fitness and ln BF% or ln AFM. Moderate‐to‐vigorous activity was only independently related to aerobic fitness. In this population, low daily accumulation of vigorous activity was, already in children aged 8–11 years, associated with more body fat and lower aerobic fitness. A similar relation was not found for daily accumulation of moderate‐to‐vigorous activity.

Hyperpolarized (3)He apparent diffusion coefficient MRI of the lung: Reproducibility and volume dependency in healthy volunteers and patients with emphysema.

To measure the apparent diffusion coefficient (ADC) of hyperpolarized (HP) 3He gas using diffusion weighted MRI in healthy volunteers and patients with emphysema and examine the reproducibility and volume dependency.

A pharmacoscintigraphic evaluation of oral budesonide given as controlled‐release (Entocort) capsules

Aims : To investigate the gastrointestinal pharmacokinetics of controlled‐release (Entocort) and standard budesonide capsules.

A 14-year prospective study of autonomic nerve function in Type 1 diabetic patients: association with nephropathy

Aims  Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients.

Dysphagia and dysmotility of the pharynx and oesophagus in patients with primary Sjögren's syndrome

Objectives: To assess the prevalence of pharyngeal and oesophageal symptoms and dysmotility in patients with primary Sjögrens syndrome (pSS) and relate these to autonomic nervous function. Methods: Twenty consecutive pSS patients, according to the American–European Consensus Criteria (AECC), and 30 age‐ and sex‐matched controls from the Swedish general population registry were studied. All subjects completed a pharyngeal and oesophageal symptoms questionnaire and were examined by pharyngeal and oesophageal video radiography. In addition, the pSS patients were examined by two different autonomic nervous function tests, the deep breathing test [calculating the expiration/inspiration (E/I) ratio] and the finger skin blood flow test [the vasoconstriction (VAC) index]. Results: pSS patients experienced significantly more dysphagia compared with controls (65% vs. 3%; p<0.001). Pharyngeal (45% vs. 7%; p<0.01), oesophageal (80% vs. 7%; p<0.001) and gastro‐oesophageal reflux symptoms (60% vs. 23%; p<0.01) were also more prevalent in pSS patients compared with controls while pharyngeal (15% vs. 17%; p = NS) and oesophageal dysmotility (40% vs. 30%; p = NS) were not. Dysphagia was not associated with dysmotility but was found to be associated with a decreased E/I ratio [−1.05 (−1.51 to −0.40) in patients with dysphagia vs. −0.21 (−0.39 to 0.65) in patients without dysphagia; p<0.01]. Conclusion: Subjective swallowing difficulties were more common in pSS patients than in controls while objective signs of pharyngeal and oesophageal dysmotility were not. Dysphagia in pSS patients does not seem to be related to video radiographical signs of dysmotility but may be related to an impaired parasympathetic function.

Autonomic nervous symptoms in primary Sjögren's; syndrome

OBJECTIVES Objective signs of autonomic dysfunction (AD) have been reported in patients with primary SS (pSS) while the presence of associated symptoms has not been systematically studied. Therefore, the aims of this study were (i) to assess the presence and severity of various AD symptoms in pSS patients and (ii) to relate AD symptoms to other clinical features of pSS. METHODS Thirty-eight pSS patients and 200 population-based controls were studied for presence and severity of AD symptoms using the Autonomic Symptom Profile (ASP), a validated self-completed questionnaire evaluating various AD symptoms. In addition, patients were investigated by three different objective autonomic nervous function tests. RESULTS pSS patients scored significantly higher in the parasympathetic [secretomotor disorder, urinary disorder, gastroparesis (females only) and pupillomotor disorder] as well as sympathetic (orthostatic intolerance and vasomotor disorder) ASP domains compared with controls. Consequently, the standardized ASP total score was significantly increased in pSS patients [1.77 (0.57, 3.15) vs - 0.21 (-0.82, 0.72); P = 0.00] and 45% of pSS patients had an ASP total score >/=2 s.d. Furthermore, the autonomic nervous function tests showed signs of objective parasympathetic and sympathetic dysfunction as well. However, the ASP domain and total scores showed limited associations with the objective autonomic nervous function test parameters as well as clinical and serological factors of pSS. CONCLUSIONS pSS patients showed subjective and objective signs of both a parasympathetic and a sympathetic dysfunction. However, AD symptoms showed limited associations with objective autonomic nervous function as well as other clinical features of the disease.

Vascular effects of anandamide and N-acylvanillylamines in the human forearm and skin microcirculation.

The endocannabinoid anandamide is an emerging potential signalling molecule in the cardiovascular system. Anandamide causes vasodilatation, bradycardia and hypotension in animals and has been implicated in the pathophysiology of endotoxic, haemorrhagic and cardiogenic shock, but its vascular effects have not been studied in man. Human forearm blood flow and skin microcirculatory flow were recorded using venous occlusion plethysmography and laser‐Doppler perfusion imaging (LDPI), respectively. Each test drug was infused into the brachial artery or applied topically on the skin followed by a standardized pin‐prick to disrupt the epidermal barrier. Anandamide failed to affect forearm blood flow when administered intra‐arterially at infusion rates of 0.3–300 nmol min−1. The highest infusion rate led to an anandamide concentration of approximately 1 μM in venous blood as measured by mass spectrometry. Dermal application of anandamide significantly increased skin microcirculatory flow and coapplication of the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine inhibited this effect. The TRPV1 agonists capsaicin, olvanil and arvanil all induced concentration‐dependent increases in skin blood flow and burning pain when administered dermally. Coapplication of capsazepine inhibited blood flow and pain responses to all three TRPV1 agonists. This study shows that locally applied anandamide is a vasodilator in the human skin microcirculation. The results are consistent with this lipid being an activator of TRPV1 on primary sensory nerves, but do not support a role for anandamide as a circulating vasoactive hormone in the human forearm vascular bed.

Exhaled breath condensate-site and mechanisms of formation

Exhaled breath condensate (EBC) analysis is a promising tool for diagnosis and management of pulmonary diseases. Its clinical usefulness is still limited however due to unresolved issues around e.g. reproducibility, anatomical site of origin of EBC solutes and mechanisms of EBC formation. To gain some knowledge on these issues, three different airway deposition patterns of an aqueous aerosol containing technetium-99m were studied in eight healthy non-smoking subjects. EBC was collected 20 min after each radioaerosol administration and analyzed for gamma radiation and electrolytes. Radioaerosol deposition in preferentially central lung compared with preferentially peripheral lung resulted in 3.8 times higher EBC radioactivity. EBC concentrations of Na(+) and K(+) correlated significantly indicating dilution by water vapor to be a major source of variability. Since Na(+)/K(+)- and Na(+)/S(2-)-concentration ratios, but not Na(+)/Cl(-)- or Na(+)/Ca(2+)-, were comparable to those previously reported for alveolar lining fluid (ALF), some mechanisms other than dilution are likely also to be involved. In conclusion, our findings indicate that EBC derives mainly from the central airways, that the electrolyte composition of EBC does not consistently reflect that of ALF, and that EBC concentrations of electrolytes are determined not only by ALF dilution with water vapor but also by other mechanisms.