Interrelationships between muscle structure,muscle strength,and running economy

PURPOSE: The present study was designed to investigate possible differences in running economy (RE) among elite middle-distance runners by examining muscle structure and maximal isometric force (MVC). METHODS: Ten young male runners ran at six different running speeds. During the running bouts, respiratory gases, and blood lactate were measured. Muscle biopsies were obtained from the vastus lateralis muscle for analyzing fiber type distribution, muscle fiber area, myosin heavy chain (MHC) composition, activities of a number of metabolic enzymes (citrate synthase, lactate dehydrogenase, phosphofruktokinase, and 3-hydroxyacyl-CoA-dehydrogenase), and titin isoforms. RESULTS: Energy expenditure (EE) increased linearly up to the speed of 6.0 m.s. The relative distribution of the MHC isoforms was MHC I: 67.0%, MHC IIA: 31.5%, and MHC IIX: 1.5%. The present results demonstrated that higher the area of Type II fibers, higher the MVC (r = 0.59, P< 0.05). The amount of MHC II correlated inversely with EE when running close to the competition speed (r = -0.61, P< 0.05). Enzyme activities did not correlate significantly with either RE or EE. Titin analysis revealed that a faster-mobility titin band was observed in all subjects, whereas a lower-mobility titin band was observed only in the most economical runner. CONCLUSION: Differences in RE among homogeneous group of middle-distance runners were observed at various running speeds. This may partly be explained by differences in muscle fiber distribution, MHC composition, and titin isoforms.     

Danish obstetricians' personal preference and general attitude to elective cesarean section on maternal request: a nation-wide postal survey

OBJECTIVE: To assess Danish obstetricians' and gynecologists' personal preference and general attitude towards elective cesarean section on maternal request in uncomplicated single cephalic pregnancies at term. DESIGN: Nation-wide anonymous postal questionnaire. POPULATION: Four hundred and fifty-five obstetricians and gynecologists identified in the records of the Danish Society of Obstetrics and Gynecology from January 2000. MAIN OUTCOME MEASURES: Personal preference on the mode of delivery and general attitude towards elective cesarean section on maternal request in an uncomplicated single cephalic pregnancies at term. RESULTS: Of Danish specialists in obstetrics and gynecology, 1.1% would prefer an elective cesarean section in an uncomplicated pregnancy at 37 weeks of gestation with fetal weight estimation of 3.0 kg. This rose to 22.5% when the fetal weight estimation was 4.5 kg at 37 weeks. The main reasons given for preferring abdominal deliveries was the risk to the fetus, risks of perineal injury, and urinary and anal incontinence. Of Danish specialists in obstetrics and gynecology, 37.6% agreed with a woman's right to have an elective cesarean section on maternal request without any medical indication. Obstetricians and gynecologists who had experienced a noninstrumental vaginal delivery themselves or practiced as a private gynecologist only, were less likely to agree with the woman's right to elective cesarean section on maternal request. CONCLUSION: The vast majority of Danish obstetricians and gynecologists would personally prefer vaginal delivery in uncomplicated pregnancies, but nearly 40% agree with the woman's right to request a cesarean section.     

Reasons for dropout in an in vitro fertilization/intracytoplasmic sperm injection program

OBJECTIVE: To gain more insight into psychological aspects of dropping out from IVF-ICSI. DESIGN: Prospective cohort study. SETTING: University hospital-based tertiary care fertility clinic. PATIENT(S): Women entering their first treatment cycle of IVF or ICSI. INTERVENTION(S): Standardized psychological questionnaires were administered before the start of the treatment and after treatment. MAIN OUTCOME MEASURE(S): Reasons for dropout, state and trait anxiety, depression, and marital and sexual satisfaction. RESULT(S): Baseline psychological factors and the probability of dropout after IVF-ICSI treatment were found to be associated in the group that stopped treatment for psychological reasons. Those who were denied further treatment by the medical team, the "actively censored" group, did not show pretreatment differences regarding psychological measures in comparison with those who continued treatment. After treatment, the group that was denied further treatment showed higher levels of anxiety and depression compared with those that continued. CONCLUSION(S): Dropout, being a well-known phenomenon in IVF-ICSI, is related to preexisting psychological factors in IVF-ICSI. Actively censored patients were psychologically well-adjusted before treatment, but this changed after censoring.     

Are cataract and iris atrophy toxic complications of medical treatment of acanthamoeba keratitis?

PURPOSE: Two cases of acanthamoeba keratitis with almost identical clinical courses developed mature cataract and iris atrophy after prolonged treatment with chlorhexidine 0.02% and propamidine isethionate 0.1%. It is suggested that these complications were caused by the chemicals, rather than resulting from the amoebae-induced inflammation. METHODS: Penetrating keratoplasty was performed in both cases when perforation from peripheral ulceration was threatening. RESULTS AND CONCLUSIONS: The immediate results were good. From these two cases it seems possible that there is a maximum level of intensity of the medical treatment and also that surgery should be considered at an earlier stage, before intraocular complications develop.     

Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity

Objective To study the distribution of the thiopurine methyltransferase (TPMT) genotype among azathioprine (Aza)-tolerant and -intolerant patients with various disorders, and to investigate a possible relationship with the Aza metabolite levels.Methods Forty-six Aza-tolerant and six Aza-intolerant patients had the TPMT genotype distribution determined using a polymerase chain reaction (PCR) assay and the forty-six Aza-tolerant patients had the Aza metabolite levels determined using a high-pressure liquid chromatography (HPLC) analysis.Results One non-functional TPMT mutant allele was demonstrated in 2 of the 46 Aza-tolerant patients (4.4%) and one or two non-functional mutant alleles in 2 of the 6 Aza-intolerant patients (33.3%). Of the 4 patients, with one or two non-functional mutant alleles 2 (50%) were intolerant to Aza compared with 4 of the 48 patients (8.3%) with no mutations detected. The time to hepatotoxicity did not differ significantly between the 2 patients with one or two non-functional mutant alleles and the remaining 3 patients (P=0.5). The TPMT genotype distribution differed slightly in the three different categories of disorders (P=0.05). The median E-6-TGN level among the 2 TPMT heterozygous patients was 275 pmol/8×10⁸ RBC (range 240–310), whereas the remaining 44 patients had a median E-6-TGN level of 110 pmol/8×10⁸ RBC (range 0–440) (P=0.07).Conclusion Although TPMT genotyping cannot be recommended on behalf of the present study, it is to be expected that half of the patients with one or two non-functional TPMT mutant alleles will develop Aza intolerance leading to withdrawal of therapy. Thus, clinicians may anticipate about 5% of the patients to develop intolerance to Aza therapy solely for that reason.     

Coronary artery bypass grafting within 30 days after treatment of acute myocardial infarctions with angioplasty or fibrinolysis - a surgical substudy of DANAMI-2

OBJECTIVE: To calculate the incidence and analyse the indications and outcome after surgical revascularization within the first 30 days after randomization of 1572 patients with acute myocardial infarction (MI) associated with ST-segment elevation (STEMI). DESIGN: Data regarding the patients undergoing heart surgery within the first 30 days after randomization were collected. RESULTS: Three patients (0.2%) with acute STEMI and randomized to percutaneous coronary intervention (PCI) underwent emergent coronary artery bypass grafting (CABG). A total of 50 patients (3.2%), 30 in the PCI group and 20 in the fibrinolysis group were revascularized by surgery within the first 30 days after randomization. The most frequent indication for surgery in both groups was unstable angina pectoris, followed by left main stenosis. The incidence of postoperative complications was higher compared with the outcome after elective CABG. CONCLUSIONS: The incidence of emergency CABG in this study was low (0.2%) after treatment of acute MI with either PCI or fibrinolysis. The overall incidence within 30 days was 3.2%, however, the mortality is increased with a 30-day mortality of 10% in this high-risk patient group.     

Metabolite phantom correction of the nonuniform volume-selection profiles in MR spectroscopic imaging: application to temporal lobe epilepsy

BACKGROUND AND PURPOSE: In MR spectroscopic imaging (MRSI), the volume-selection profiles of metabolites differ from each other. These differences cause variations in metabolite intensities, which are particularly prominent when the hippocampi are evaluated. We hypothesize that the errors arising from these effects cause notable artifact when temporal lobe epilepsy (TLE) is lateralized with MRSI. METHODS: We examined a metabolite phantom, control subjects, and patients with TLE by using MRSI. We calculated the error arising from the different volume-selection profiles of metabolites in vitro and evaluated this correction in the examination of the control subjects and in the lateralization of epilepsy in the patients. RESULTS: Without a correction, a considerable error in the metabolite content existed, even deep inside the spectroscopic volume of interest. The result was false asymmetry (P < .008) in the hippocampi of control subjects. Among the 11 patients, TLE was correctly lateralized in three only after the correction was made, and in one, TLE was incorrectly lateralized. CONCLUSION: The volume-selection profiles of N-acetylaspartate, choline, and creatine differ enough to cause a significant error, even in the metabolite ratios, when patients with TLE are examined with MRSI. We propose a simple phantom method to correct for this error without a need to modify the pulse sequence.     

Tweaking agonist efficacy at N-methyl-D-aspartate receptors by site-directed mutagenesis

The structural basis for partial agonism at N-methyl-D-aspartate (NMDA) receptors is currently unresolved. We have characterized several partial agonists at the NR1/NR2B receptor and investigated the mechanisms underlying their reduced efficacy by introducing mutations in the glutamate binding site. Key residues were selected for mutation based on ligand-protein docking studies using a homology model of NR2B-S1S2 built from the X-ray structure of NR1-S1S2 in complex with glycine. Wild-type and mutant forms of NR2B were coexpressed with NR1 in Xenopus laevis oocytes and characterized by two-electrode voltage-clamp electrophysiology. By combining mutagenesis of residues His486 or Val686 with activation by differently substituted partial agonists, we introduce varying degrees of steric clash between the ligand and the two binding domains S1 and S2. In cases where ligand-protein docking predicts increased steric clashes between agonists and the residues forming the S1-S2 interface, the agonists clearly show decreased relative efficacy. Furthermore, we demonstrate that the mutation S690A affects both potency and efficacy in an agonist-specific manner. The results indicate that essential residues in the ligand binding pocket of NR2B may adopt different conformations depending on the agonist bound. Together, these data indicate that agonist efficacy at the NR2B subunit can be controlled by the extent of steric clashes between the agonist and the ligand binding domains and by ligand-dependent arrangements of residues within the binding pocket.     

Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial

BACKGROUND: The concentration of osteopontin (SPP1) in plasma is associated with tumour hypoxia. The DAHANCA 5 trial found that the hypoxia radiosensitiser nimorazole significantly improved the outcome of radiotherapy for patients with head and neck cancer compared with placebo. However, whether all patients benefit from such modification of hypoxia is unclear. We aimed to assess whether the concentration of plasma osteopontin could predict response to the hypoxia radiosensitiser. METHODS: Plasma concentrations of osteopontin were measured by use of ELISA from stored samples of 320 patients randomised in the DAHANCA 5 trial. Samples were grouped into tertiles according to high (167-1382 microg/L), intermediate (69-166 microg/L), or low (0-68 microg/L) concentrations of plasma osteopontin, and analysed for locoregional tumour control and disease-specific survival at 5 years. FINDINGS: Overall, locoregional tumour failure and disease-specific mortality were more frequent in patients assigned placebo than in those assigned nimorazole (relative risk [RR] 0.51 [95% CI 0.32-0.79] and 0.54 [0.35-0.85], respectively). Locoregional tumour failure was more frequent in patients with high concentrations of osteopontin assigned placebo than in those with high concentrations assigned nimorazole (0.19 [0.08-0.44]), as was disease-specific mortality (0.25 [0.11-0.59]). However, neither locoregional tumour failure nor disease-specific mortality differed between groups for patients with low concentrations of plasma osteopontin (0.79 [0.26-1.70]) and (0.69 [0.31-1.51]) or for those with intermediate concentrations (0.90 [0.41-1.98] and 0.89 [0.41-1.96], respectively). INTERPRETATION: High plasma concentrations of osteopontin are associated with a poor outlook after radiotherapy for patients with head and neck cancer, but can be improved by use of nimorazole. High concentrations of osteopontin can predict clinically relevant hypoxia, and might identify patients who will benefit from modification of hypoxia during radiotherapy.