Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.     

Standard-dose anti-CD20 antibody rituximab has efficacy in chronic lymphocytic leukaemia: results from a Nordic multicentre study

OBJECTIVES: This prospective multicentre study was conducted to assess the efficacy of the monoclonal anti-CD20 antibody rituximab in patients with chronic lymphocytic leukaemia (CLL). Secondary objectives were defined as the tolerability and feasibility of rituximab in patients with CLL. METHODS: Twenty-four heavily pretreated patients with CLL were treated with a standard dose of 375 mg m-2 of rituximab given once weekly for four doses. RESULTS: The overall response rate was 35% and all the responses were partial as defined by the revised NCI criteria. In 17 (85%) of 20 patients with initially measurable peripheral lymph nodes the size of lymph nodes decreased by at least 50%, while an improvement of the bone marrow infiltration was observed only in two (11%) of 18 evaluable patients. The median duration of the overall response was 12.5 wk. Rituximab was relatively well tolerated. Although side-effects were common (75%) they were usually mild or moderate. There was only one grade 3 adverse event and no grade 4 events. CONCLUSIONS: Standard-dose rituximab has activity in heavily pretreated patients with CLL, although the response is mainly limited to the lymph nodes and of short duration. Since rituximab has in vitro synergism with chemotherapeutic agents and is well tolerated by CLL patients, it is reasonable to investigate rituximab in combination with other treatments.     

Resistance to activated protein C due to a factor V gene mutation The most common inherited risk factor of thrombosis

The protein C anticoagulant pathway is of major importance in maintaining vascular patency. Resistance to the key enzyme of this system, activated protein C (APC), is a recently discovered congenital defect of the protein C system. This genetic defect is present in 20% to 60% of venous thrombosis patients, making it by far the most common known pathogenetic risk factor of thrombosis. APC resistance is due to a single point mutation in the factor V gene (G to A at nucleotide position 1691) that predicts the replacement of arginine(506) by glutamine. This is associated with the loss of one of three APC cleavage sites in factor Va, one of the substrates for APC, and hypercoagulability. The identification of APC resistance as an additional genetic risk factor in a large proportion of symptomatic protein C- and protein S-deficient families has provided evidence that thrombosis is a polygenetic disease. Thus, several genetic defects act in concert with environmental factors in the pathogenesis of venous thromboembolism.     

Some characteristics of platelet concentrates contaminated with Staphylococcus epidermidis

The study investigates platelet concentrates (PCs) contaminated with Staphylococcus epidermidis. The work was conducted using 12 pairs of PCs. Light transmission through the PCs was observed over 7 days. Immediately after preparation, one PC was inoculated with Staphylococcus epidermidis (17-43 colony forming units (CFU)/ ml) and the other served as a non-contaminated control. In the contaminated PCs the CFU/ml and swirling were determined on days 1, 3 and 7. In all PCs determination of pH and the extent of shape change (ESC) was carried out on days 3 and 7. All contaminated PCs had visible swirling on day 3 but they contained 2.0 X 10 4 to 9.0 X 10 8 CFU/ml. pH (P=0.05) and ESC (P<0.05) then were slightly lower. On day 7, eight of 12 of the contaminated PCs failed to display transmission changes despite deranged analytical results and impaired swirling. During early storage the contaminated units had unimpaired swirling and only slightly impaired in vitro quality. They appear to be difficult to identify in the routine.     

Effects of dynamic strength training on physical function,Valpar 9 work sample test,and working capacity in patients with recent-onset rheumatoid arthritis

OBJECTIVE: To study the impact of 24 months of strength training on the physical function of patients with early rheumatoid arthritis (RA). METHODS: Seventy patients were assigned to either the strength training (experimental) group (n = 35) or the control group (n = 35). Patients in the experimental group performed strength training for 24 months, and control patients were instructed to perform range of motion exercises. Maximal strength of the knee extensors, trunk flexors, and extensors, as well as grip strength were recorded with dynamometers. Disease activity was assessed by the erythrocyte sedimentation rate and Ritchie's articular index, joint damage was determined by the Larsen x-ray index, and functional capacity was assessed using the Valpar 9 test and the Stanford Health Assessment Questionnaire (HAQ). The employment status of each patient was recorded. RESULTS: In the experimental group, strength training led to significant increases (19-59%) in maximal strength of the trained muscles. Such increases in the control group varied from 1% to 31%. There was a clear training effect on muscular strength in favor of the experimental group, but significant improvements in the HAQ indices as well as in the Valpar 9 test were seen also in control patients. Results of the Valpar 9 and the HAQ were statistically significantly better in patients who remained gainfully employed compared with patients who retired preterm during followup. However, compared with patients who remained in the work force, patients who retired were older, and their work was physically more demanding. CONCLUSION: As expected, strength training led to increased muscle strength, but this increase did not correlate with improved physical function as assessed by the Valpar 9 work sample test. The increased muscle performance did not prevent a substantial proportion of patients from retiring preterm. The 2 items from the Valpar 9 test that were applied were not sensitive enough to differentiate the patients according to their working status.     

The diagnostic value of the amino acid absorption test in detection of a disorder of exocrine pancreatic function]

The amino acid consumption test (AACT) during exogenous stimulation with secretin and CCK was proposed as a sensitive and highly specific test for detection of exocrine pancreatic insufficiency. To further investigate the diagnostic value of this test we measured the AACT in comparison with the pancreolauryl serum test (PLT) in patients with chronic pancreatitis and in patients with gastrointestinal diseases but without pancreatic disease. A total of 48 patients, 23 patients with chronic pancreatitis (CP) and 25 patients with gastrointestinal diseases, were included in the study. Diagnosis of chronic pancreatitis was established by standardized morphological criteria in ultrasound, ERCP, CT, and was confirmed by surgery in 11 cases. The PLT was abnormal in 83% of patients with chronic pancreatitis and normal in 92% of the control subjects (diagnostic accuracy 88%). Basal amino acid concentration was comparable in patients with chronic pancreatitis and in control subjects (300 +/- 12 [symbol: see text] 325 +/- 16 mumol/l). The peak decrease of amino acids occurred after 30 min during combined stimulation with secretin and ceruletide and was not different between the two groups (CP: 11.2 +/- 1.7%, controls: 13.9 +/- 1.9% below basal values). With a 12% decrease of amino acids as cutoff, sensitivity was 74% and specificity 52% (diagnostic accuracy 63%). Integrated amino acid decrease did not show any significant differences between CP and controls (CP: 228 +/- 63% min, controls: 397 +/- 80% min). Determination of the individual amino acids serine, valine, histidine, and isoleucine could also not discriminate between patients with chronic pancreatitis and other gastrointestinal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Previous pain experience in women with fibromyalgia and inflammatory arthritis and nonpainful controls

OBJECTIVE: To examine the frequency of commonly occurring pain and adverse experiences throughout life by self-report in women with fibromyalgia (FM) and chronic inflammatory arthritis (IA) and nonpainful healthy women. METHODS: Fifty-one patients with FM and 44 with IA and 52 nonpainful healthy controls were consecutively interviewed in a tertiary clinic setting regarding the occurrence of lifetime common pain experience and adverse events, as well as a family history of FM and/or a childhood pain environment. RESULTS: Patients with FM reported significantly more irritable bowel syndrome, migraine headaches, severe menstrual pain, physical and psychological trauma affecting well being, family history of FM, and family pain environment than subjects with IA or controls. Both patient groups had more adult hospitalizations and surgeries than the controls. CONCLUSION: Patients with FM report a high rate of varied pain and adverse experiences throughout life. This real or perceived experience of pain supports the concept that FM is a lifetime disorder of pain processing.     

Measurement of the Fowler dead space in patients with pulmonary emphysema using C18O2

In patients with lung emphysema, changes in lung volumes as well as changes in airway resistance are well known. The change in airway resistance is caused by obstruction of central airways, which is supposed to reduce the respiratory dead space. Until now, it was not possible to measure the respiratory dead space in patients with lung emphysema using the method of Fowler [2], because in this method distinction of the three phases of an inert gas expirogram is essential. While this distinction is easy in healthy subjects (fig. 1; expirogram 3), the separation of the three phases in patients with lung emphysema is not possible due to gradual transition of phase II into phase III in these patients (fig. 1; expirogram 2). The use of C18O2 as tracer gas allows to separate phase II and phase III even if the patients have severe emphysema (fig. 1; expirogram 1). CO2 labeled with the stable oxygen isotope 18O (C18O2) is completely taken up in the gas exchanging region of the lung, but not from the conducting airways. Therefore C18O2 is only expired from the dead space of the lung, but not from the alveolar region. Hence, C18O2 allows exact measurement of the respiratory dead space in patients with lung emphysema. 21 healthy nonsmoking subjects and 29 patients with clinical signs of lung emphysema participated in this study. There was a good correlation between respiratory dead space, measured by the use of Ar-gas and C18O2-gas in healthy subjects (fig. 2). This indicates, that the use of C18O2 is a valid method to measure the functional dead space. As expected, there was also a correlation between the airway resistance and respiratory dead space in patients with lung emphysema (fig. 3), but not in healty subjects. There was no significant difference of the mean values of the respiratory dead space between these two groups (223 +/- 43 ml in healthy subjects vs. 227 +/- 52 ml in patients), even though there were large differences in airway resistance (0.20 +/- 0.10 kPa/l/s vs. 0.49 +/- 0.27 kPa/l/s). This may be due to a loss of alveolar function in the area of the terminal bronchioli, which is typical for emphysematous patients. This entails a shift of functional dead space towards lung periphery and therefore causes an increase of the volume of functional dead space. But this enlargement may be compensated by the volume reduction, caused by the airway obstruction. Hence, these two oppositional mechanisms may result in only minimal change of dead space volume.     

Robotic Assistance System for Cone-Beam Computed Tomography-Guided Percutaneous Needle Placement

CardioVascular and Interventional Radiology - The study aimed to evaluate a new robotic assistance system (RAS) for needle placement in combination with a multi-axis C-arm angiography system for...     

“Salt mummification” — atypical method of embalming a corpse

International Journal of Legal Medicine - It is extremely rare for table salt to be used to preserve a dead body in criminal cases. In the case presented here, after the death of his 85-year-old...