Reduced Serum Theophylline Concentrations after Discontinuation of Azithromycin: Evidence for an Unusual Interaction

A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease. Peak serum theophylline concentration was 20 μg/ml (normal 10–20 μg/ml). Azithromycin was discontinued and the theophylline dosage reduced by 33%. The subsequent 80% decrease in serum theophylline to 4.6 μg/ml was unexpectedly large. Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction. Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system. In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.     

Physical activity is associated with a low prevalence of musculoskeletal disorders in the Royal Norwegian Navy: a cross sectional study

Background  

Despite considerable knowledge about musculoskeletal disorders (MSD) and physical, psychosocial and individual risk factors there is limited knowledge about physical activity as a factor in preventing MSD. In addition, studies of physical activity are often limited to either leisure activity or physical activity at work. Studies among military personnel on the association between physical activity at work and at leisure and MSD are lacking. This study was conducted to find the prevalence of MSD among personnel in the Royal Norwegian Navy and to assess the association between physical activity at work and at leisure and MSD.     

Frequent diagnostic errors in cardiac PET/CT due to misregistration of CT attenuation and emission PET images: a definitive analysis of causes, consequences, and corrections.

Cardiac PET combined with CT is rapidly expanding despite artifactual defects and false-positive results due to misregistration of PET and CT attenuation correction data-the frequency, cause, and correction of which remain undetermined. METHODS: Two hundred fifty-nine consecutive patients underwent diagnostic rest-dipyridamole myocardial perfusion PET/CT using (82)Rb, a 16-slice PET/CT scanner, helical CT attenuation correction with breathing and also at end-expiratory breath-hold, and averaged cine CT data during breathing. Misregistration on superimposed PET/CT fusion images was objectively measured in millimeters and correlated with associated quantitative size and severity of PET defects. Misregistration artifacts were defined as PET defects with corresponding misregistration on helical CT-PET fusion images that resolved after correct coregistration using a repeat CT scan, cine CT averaged attenuation during normal breathing, or shifted cine CT data that coregistered with PET data. RESULTS: Misregistration of standard helical CT PET images caused artifactual PET defects in 103 of 259 (40%) patients that were moderate to severe in 59 (23%) (P = 0.0000) and quantitatively normalized on cine or shifted cine CT PET (P = 0.0000). Quantitative misregistration was a powerful predictor of artifact size and severity (P = 0.0000), particularly for transaxial misregistration >6 mm occurring in anterior or lateral areas in 76%, in inferior areas in 16%, and at the apex in 8% of 103 artifactual defects. CONCLUSION: Misregistration of helical CT attenuation and PET emission images causes artifactual defects with false-positive results in 40% of patients that normalize on cine CT PET using averaged CT attenuation data during normal breathing comparable to normal breathing during PET emission scanning and shifting cine CT images to coregister visually with PET.     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Severe Neurological Complications after Central Neuraxial Blockades in Sweden 1990-1999

Background: Central neuraxial blockades find widespread applications. Severe complications are believed to be extremely rare, but the incidence is probably underestimated.

Methods: A retrospective study of severe neurologic complications after central neuraxial blockades in Sweden 1990-1999 was performed. Information was obtained from a postal survey and administrative files in the health care system. During the study period approximately 1,260,000 spinal blockades and 450,000 epidural blockades were administered, including 200,000 epidural blockades for pain relief in labor.

Results: The 127 complications found included spinal hematoma (33), cauda equina syndrome (32), meningitis (29), epidural abscess (13), and miscellaneous (20). Permanent neurologic damage was observed in 85 patients. Incidence of complications after spinal blockade was within 1:20-30,000 in all patient groups. Incidence after obstetric epidural blockade was 1:25,000; in the remaining patients it was 1:3600 (P < 0.0001). Spinal hematoma after obstetric epidural blockade carried the incidence 1:200,000, significantly lower than the incidence 1:3,600 females subject to knee arthroplasty (P < 0.0001).     

Racial differences in the incidence of end-stage renal disease in types I and II diabetes mellitus

An increased risk of end-stage renal disease (ESRD) among blacks has been previously shown for most causes of chronic renal failure, including diabetes. Most previous studies have not considered the higher prevalence of diabetes in the black population and have not analyzed relative risk by type of diabetes. We found that the incidence of ESRD among blacks with diabetes was 3.6 times the rate in whites with diabetes. The relative risk for blacks increases progressively with age, reaching a maximum of 6.9 in persons over the age of 65. The incidence of ESRD due to diabetes is higher in the population with type I diabetes (492 per 100,000) than in the population with type II diabetes (71 per 100,000). Blacks have a higher incidence of ESRD in both type I diabetes (odds ratio, 2.96; 95% confidence interval, 1.8 to 4.9) and type II diabetes (odds ratio, 4.9; 95% confidence interval, 3.6 to 6.5). The incidence of ESRD in patients with diabetes varies with age, race, and type of diabetes.     

Comparison of some salivary variables between vegetarians and omnivores

The aim of the study was to compare salivary variables in a group of vegetarians with a group of omnivores. Twenty-nine vegetarians, 19 women and 10 men, mean age 35 yr, and 28 omnivores, 20 women and 8 men, mean age 35 yr, were compared in terms of salivary secretion rate, pH, buffer capacity, mutans streptococci and lactobacilli. The vegetarians had a significantly higher secretion rate, but there were no other significant differences regarding the salivary variables. The difference in secretion rate may have been caused by some lifestyle factor(s) differing between vegetarians and omnivores which probably mainly include nutrient(s), texture and roughness of the food.     

Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice

DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.