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The inhaled route is a promising new way for administering drugs to the human body. Flow and particle deposition in the human respiratory tract depends on the individual's anatomy as well as on the drug composition. A European Framework V Program supported project is currently developing a simulation tool for assessment of drug distribution and deposition. This tool relies heavily on the input of radiological data sets, which are obtained in humans. Both high temporal and spatial resolutions are required, and CT and MRI (including hyperpolarized helium-3 MRI) are applied. The radiological data are integrated into computation fluid dynamics software, which is capable of assessing air-flow profiles and compartmental behaviours. This is complemented by pharmacokinetic models, which should result in a simulation tool that will be of use for the theoretical design of new inhaled therapies. This article describes the special imaging requirements of each region of the respiratory tract and the feasibility of these sophisticated radiological techniques with a view of using these data in a simulation model of the lung. [ABSTRACT FROM AUTHOR]

Background: Percutaneous balloon dilatation of biliary tract strictures is generally accepted as a safe and inexpensive procedure. The effectiveness in selected groups of patients remains under discussion. The purpose of this study was to evaluate the results of percutaneous balloon dilatation in patients with a benign stricture of a hepaticojejunostomy.Methods: Fifteen patients with a benign stricture of a hepaticojejunostomy were examined between 1993 and July 1997. An ultrasound-guided percutaneous transhepatic cholangiography (PTC) procedure was performed, followed by a balloon dilatation. Follow-up was performed prospectively by outpatient visits and laboratory testing.Results: Percutaneous dilatation was successful in 14 patients. Three patients developed a recurrence. In one of these patients, the procedure was repeated successfully. Gastrointestinal bleeding occurred in one patient. The success rate for balloon dilatation in this group of patients was 73% after a mean follow-up of 30 months. When the procedure was repeated, the success rate was 80% after a mean follow-up of 33 months.Conclusions: Percutaneous balloon dilatation for benign hepaticojejunostomy strictures is feasible in the majority of patients and produces acceptable medium-term to long-term results. Advantages are its minimal invasive character and the fact that all options remain open in case of failure. [ABSTRACT FROM AUTHOR]

The aim this study was to evaluate potential additional information of pulmonary angiography in patients with suspected pulmonary embolism and non-diagnostic lung scan findings. In a series of 150 patients who underwent pulmonary angiography for suspected venous thromboembolism, the images for potential alternative diagnoses other than pulmonary embolism were evaluated. All patients had non-diagnostic lung scan findings. Angiography was performed both by conventional and by digital subtraction angiography techniques. Images were evaluated by at least two experienced readers. Angiograms were scored for both presence or absence of pulmonary embolism, as well as other diagnoses. Pulmonary embolism was proven in 40 patients (27 %) and excluded in 105 patients (70 %), whereas non-interpretable images were obtained in 5 patients (3 %). A range of alternative diagnoses were detected by angiography: atelectasis (n = 24), pleural effusion (n = 15), pneumonia (n = 11), emphysematous bullae (n = 8), neoplasm (n = 3), atrial septum defect (n = 2), chronic thromboembolism (n = 1), and other diagnoses (n = 3). Overall, only 54 patients (36 %) had completely normal angiograms. Although pulmonary angiography remains the reference method for the diagnosis of pulmonary embolism, one has to be aware of other, often unexpected, but equally important findings which could influence the management of the patient. This aspect of pulmonary angiography has been insufficiently emphasized in the literature. [ABSTRACT FROM AUTHOR]

The article discusses the involvement of Campylobacter coli (C. coli) strain to the development of Guillain-Barré syndrome (GBS). It relates a study on two female patients with GBS whose faecal specimens were examined, and their C. coli strains were separated and unequivocally demonstrated through surface protein profiling. Furthermore, the two C. coli strains were characterized wherein the strain of the first patient holds disialylated lipo-oligosaccharide (LOS), and the strain from the second patient contains a non-sialylated LOS depicting a zero cholera toxin bound for several gangliosides. It was determined that no basis will prove that the molecular mimicry is involved in the causation of GBS after the emergence of C. coli infection.

Objective:To obtain insight in the extent to which the human cell lines LiSa-2 and PAZ6 resemble isolated primary human adipocytes.Design:A combination of cDNA subtraction (representative difference analysis; RDA) and cDNA microarray analysis was used to select adipose specific genes to compare isolated (pre-)adipocytes with (un)differentiated LiSa-2 and PAZ6 cells.Measurements:RDA was performed on adipose tissue against lung tissue. A total of 1400 isolated genes were sequenced and cDNA microarray technology was used for further adipose related gene selection. 30 genes that were found to be enriched in adipose tissue were used to compare isolated human adipocytes and LiSa-2 and PAZ6 cells in the differentiated and undifferentiated states.Results:RDA and microarray analysis resulted in the identification of adipose enriched genes, but not in adipose specific genes. Of the 30 most differentially expressed genes, as expected, most were related to lipid metabolism. The second category consisted of methyltransferases, DNMT1, DNMT3a, RNMT and SHMT2, of which the expression was differentiation dependent and higher in differentiated adipocytes. Using the 30 adipose expressed genes, it was found that isolated adipocytes on one hand, and PAZ6 and LiSa-2 adipocytes on the other, differ primarily in lipid metabolism. Furthermore, LiSa-2 cells seem to be more similar to isolated adipocytes than PAZ6 cells.Conclusion:The LiSa-2 cell line is a good model for differentiated adipocytes, although one should keep in mind that the lipid metabolism in these cells deviates from the in vivo situation Furthermore, our results imply that methylation may have an important function in terminal adipocyte differentiation.International Journal of Obesity (2008) 32, 912–921; doi:10.1038/ijo.2008.10; published online 19 February 2008 [ABSTRACT FROM AUTHOR]

The aim of this study was to test the feasibility of a central production facility with distribution network for implementation of hyperpolarized 3-helium MRI. The 3-helium was hyperpolarized to 50-65% using a large-scale production facility based at a university in Germany. Using a specially designed transport box, containing a permanent low-field shielded magnet and dedicated iron-free glass cells, the hyperpolarized 3-helium gas was transported via airfreight to a university in the UK. At this location, the gas was used to perform in vivo MR experiments in normal volunteers and patients with chronic obstructive lung diseases. Following initial tests, the transport (road-air-road cargo) was successfully arranged on six occasions (approximately once per month). The duration of transport to imaging averaged 18 h (range 16-20 h), which was due mainly to organizational issues such as working times and flight connections. During the course of the project, polarization at imaging increased from 20% to more than 30%. A total of 4 healthy volunteers and 8 patients with chronic obstructive pulmonary disease were imaged. The feasibility of a central production facility for hyperpolarized 3-helium was demonstrated. This should enable a wider distribution of gas for this novel technology without the need for local start-up costs. [ABSTRACT FROM AUTHOR]

The aim of this study was to improve the understanding of interdependencies of dynamic changes in central airway dimensions, lung area and lung density on HRCT. The HRCT scans of 156 patients obtained at full inspiratory and expiratory position were evaluated retrospectively. Patients were divided into four groups according to lung function tests: normal subjects ( n=47); obstructive ( n=74); restrictive ( n=19); or mixed ventilatory impairment ( n=16). Mean lung density (MLD) was correlated with cross-sectional area of the lung (CSA(L)), cross-sectional area of the trachea (CSA(T)) and diameter of main-stem bronchi (D(B)). The CSA(L) was correlated with CSA(T) and D(B). MLD correlated with CSA(L) in normal subjects ( r=-0.66, p<0.0001) and patients with obstructive ( r=-0.62, p<0.0001), restrictive ( r=-0.83, p<0.0001) and mixed ventilatory impairment ( r=-0.86, p<0.0001). The MLD correlated with CSA(T) in the control group ( r=-0.50, p<0.0001) and in patients with obstructive lung impairment ( r-0.27, p<0.05). In patients with normal lung function a correlation between MLD and D(B) was found ( r=-0.52, p<0.0001). CSA(L) and CSA(T) correlated in the control group ( r=0.67, p<0.0001) and in patients with obstructive lung disease ( r=0.51, p<0.0001). The CSA(L) and D(B) correlated in the control group ( r=0.42, p<0.0001) and in patients with obstructive lung disease ( r=0.24, p<0.05). Correlations for patients with restrictive and mixed lung disease were constantly lower. Dependencies between central and peripheral airway dimensions and lung parenchyma are demonstrated by HRCT. Best correlations are observed in normal subjects and patients with obstructive lung disease. Based on these findings we postulate that the dependencies are the result of air-flow and pressure patterns. [ABSTRACT FROM AUTHOR]

The purpose of our study was to assess feasibility, safety and clinical utility of selective pulmonary angiography in patients with suspected pulmonary embolism and a nondiagnostic lung scan. The design was a prospective, descriptive study. The subjects were consecutive patients with clinically suspected pulmonary embolism and a nondiagnostic lung scintigram in whom pulmonary angiography was considered. Angiography was withheld in cases of manifest heart failure, renal failure, mean pulmonary artery pressure above 40 mmHg, or if there were compelling clinical reasons. All patients were followed-up for 6 months. The outcome measures were successful angiography, morbidity, mortality and recurrent pulmonary embolism in patients with normal angiogram in whom anticoagulants were withheld during 6 months of follow-up. Of 487 patients, 196 (40%) had nondiagnostic lung scan findings. In 46 patients (23%) pulmonary angiography was withheld. Pulmonary embolism was excluded in 105 patients (70%), and proven in 40 (27%) patients. In 5 (3%) patients the angiogram was inadequate for interpretation. No fatal complications were encountered [95% confidence interval (CI) 0-2.4%]. Nonfatal complications occurred in 3 patients (2%; 95% CI 0.4-6.0%); all recovered spontaneously. None of 105 patients with a normal angiogram returned with thromboembolism during follow-up (0%; 95% CI 0-3.4%). Pulmonary angiography is safe, rules out pulmonary embolism in two thirds of patients with a nondiagnostic lung scan and can be performed in almost 80% of these patients. It is safe to withhold long-term anticoagulants if a normal angiogram is obtained in this subgroup of patients with clinically suspected pulmonary embolism. [ABSTRACT FROM AUTHOR]

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients.Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated.Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m2), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups.Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients.Methods: Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients.Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated.Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m2), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups.Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients.Results: Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients.Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated.Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m2), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups.Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients.Conclusions: Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients.Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated.Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m2), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups.Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients.Key Points• RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis.• RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis.• HCQ may provide a protective effect against liver fibrosis in RA patients. [ABSTRACT FROM AUTHOR]