Immuno-endocrine and metabolic responses to long distance ski racing in world-class male and female cross-country skiers

The purpose of this study was to characterize the extent of immune, endocrine, substrate and metabolic changes during a long-distance cross-country ski race in extremely well-trained athletes and evaluate if the blood perturbations would indicate signs of health risk. Ten male (M) and six female (F) national team skiers were investigated as they followed their usual routines of race preparations. Blood samples were drawn before and immediately after a World Cup 50-km M and 30-km F ski race with a mean finish time of 142 and 104 min, respectively. Hemoglobin, electrolytes, and C-reactive protein remained unchanged for both M and F. Serum testosterone remained unchanged in M, but doubled in F. Significant increases were observed in concentrations of granulocytes (F: 5 x, M: 5 x), natural killer cells (F: 2 x, M: 1.5 x), adrenaline (F: 12 x, M:10 x), noradrenaline (F: 7 x, M:5 x), growth hormone (F: 30 x, M: 2 x), cortisol (F: 1.5 x, M:2 x), glucose (F: 2 x, M:1.5 x), creatine kinase (F: 2 x, M:2 x), uric acid (F: 1.5 x, M: 1.5 x) and non-organic phosphate (F:2 x, M:2 x), while insulin concentration decreased (F: 0.5x, M: 0.8 x). Free fatty acid (FFA) concentration increased (F:2 x, M: 3 x). In conclusion, we observed substantial changes in several immuno-endocrine, substrate and metabolic measurements after long distance cross-country ski racing and suggest that some of these marked changes may reflect the large amount of muscle mass involved during skiing.     

Determination of the peptide binding motif and high-affinity ligands for HLA-DQ4 using synthetic peptide libraries

Juvenile idiopathic arthritis (JIA) is considered to be an autoimmune disease. Various human leukocyte antigen (HLA) associations for different subgroups of this heterogeneous disease have been found. For early-onset pauciarticular arthritis (now oligoarthritic JIA), a strong association with the HLA class II haplotype DQA1*0401/DQB1*0402 (DQ4) has been described. We determined the peptide-binding specificities of this HLA-DQ molecule by screening a synthetic acetylated nonapeptide amide library with one defined and eight random sequence positions. A characteristic binding motif could be deduced. By use of these data, we designed defined specific nonapeptides and identified high-affinity ligands binding to HLA-DQ4. The peptide binding motif of HLA-DQ4 is very similar to the motif of HLA-DQ7, also associated with oligoarthritic JIA. It is, however, different from binding motifs of neutral or protective HLA-DQ molecules. Our results further support the idea of differential peptide presentation in the pathogenesis of oligoarthritic JIA.     

Registration of clinical trials: a statement from the International Committee of Medical Journal Editors

Altruistic motives and trust are central to scientific investigations involving people. These prompt volunteers to participate in clinical trials. However, publication bias and other causes of the failure to report trial results may lead to an overly positive view of medical interventions in the published evidence available. Registration of randomised controlled trials right from the start is therefore warranted. The International Committee of Medical Journal Editors has issued a statement to the effect that the 11 journals represented in the Committee will not consider publication of the results of trials that have not been registered in a publicly accessible register such as www.clinicaltrials.gov. Patients who voluntarily participate in clinical trials need to know that their contribution to better human healthcare is available for decision making in clinical practice.     

Bulky nonproteinogenic amino acids permit the design of very small and effective cationic antibacterial peptides

The rate of multidrug-resistant infections is rapidly rising. Cationic antibacterial peptides are active against resistant pathogens and have low propensity for resistance development, but because of their unfavorable medicinal properties, cationic antibacterial peptides have been a limited clinical success. We have found that introduction of nongenetically coded amino acids and other lipophilic modifications opens the opportunity for development of extremely short and highly active antibacterial peptides with improved medicinal properties.     

Decision support in medicine: lessons from the HELP system

PURPOSE: This report describes an ongoing transition from the HELP Hospital Information System to HELP II, a replacement Health Information System built to manage clinical information captured in a variety of medical settings. The focus of the article is on the medical decision support provided by this system and studied by researchers at the University of Utah and Intermountain Health Care (IHC), a large health care organization in Utah, for many years. METHODS: Select success features of the original HELP system's decision support environment are identified and lessons learned are related. Plans for transferring these features to HELP II are discussed. RESULTS: The article focuses on four features: (1) the importance of easy access to patient data essential for decision support, (2) the commitment to continued measurement and revision of both the logic and the interventional strategy in a decision support application, (3) experience with data mining as a tool for developing decision support tools, and (4) the role of clinical reports in supporting the decision making process.     

Nasalance,nasality, voice,and articulation after uvulopalatopharyngoplasty

OBJECTIVES/HYPOTHESIS: The main purpose of the study was to determine the impact of uvulopalatopharyngoplasty (UPPP) on nasalance and nasality. It was hypothesized that nasalance would change from the presurgical to the postsurgical condition because the surgical protocol involves removal of palatal tissue. An additional objective of the study was to provide objective and subjective data about changes in voice and articulation after UPPP. Because the surgical procedure of UPPP does not involve laryngeal tissue, it was hypothesized that the voice characteristics remain relatively stable. Because of removal of effective velar length, articulation problems of the uvular /R/ can occur in the Dutch language. STUDY DESIGN: Prospective study in which 26 men were studied before (1 week before UPPP) and after (3 weeks after UPPP) surgery. METHODS: The Nasometer was used to obtain nasalance scores. The mirror-fogging test, a perceptual evaluation of each subject's readings, and the Gutzmann and the Bzoch hypernasality tests were used for the assessment of nasality. For the assessment of articulation, a phonetic analysis was performed. Voice assessment included a perceptual rating of the voice and a determination of fundamental frequency. RESULTS: No significant differences were found between the conditions before and after surgery regarding nasalance (except for the vowel /i/), nasality, and voice. Regarding articulation, only 1 patient showed a derhotacized /R/. CONCLUSIONS: The findings of the study indicate that UPPP does not have an impact on nasality, voice, and articulation. Regarding nasalance, no significant nasalance change occurred after UPPP, except for the high vowel /i/.     

Plates, screws, and children: their relationship in craniomaxillofacial trauma

The ideal modality for fixation of pediatric craniomaxillofacial fractures remains elusive for a number of reasons. Surgeons who manage these injuries have replaced wiring techniques with the introduction of some form of reconstructive implant. The most commonly used implants are either resorbable or semi-rigid titanium. This presentation is a synopsis of the past 30 years of the English-speaking scientific literature including plastic and reconstructive surgery, otolaryngology, head and neck surgery, oral and maxillofacial surgery, pediatric, trauma, craniofacial, materials, and biomaterials publications. While no consensus on ideal management was observed, various implant treatment options are discussed, including their indications, contraindications, considerations, and consequences after implant placement.     

Enhanced cyclosporine-itraconazole interaction with cola in lung transplant recipients

BACKGROUND: Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post-transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non-cystic fibrosis LTR and the interaction with cyclosporine (CSA). METHODS: Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine-2 (H-2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4-month period of time and compared using generalized estimating equations. RESULTS: The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p< or =0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019). CONCLUSIONS: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.