A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

Background  

The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy.     

Mineral oil paraffins in human body fat and milk.

Paraffins of mineral oil origin (mineral paraffins) were analyzed in tissue fat collected from 144 volunteers with Caesarean sections as well as in milk fat from days 4 and 20 after birth of the same women living in Austria. In the tissue samples, the composition of the mineral paraffins was largely identical and consisted of an unresolved mixture of iso- and cycloalkanes, in gas chromatographic retention times ranging from n-C(17) to n-C(32) and centered at n-C(23)/C(24). Since the mineral oil products we are exposed to range from much smaller to much higher molecular mass and may contain prominent n-alkanes, the contaminants in the tissue fat must be a residue from selective uptake, elimination by evaporation and metabolic degradation. Concentrations varied between 15 and 360 mg/kg fat, with an average of 60.7 mg/kg and a median of 52.5 mg/kg. Mineral paraffins might be the largest contaminant of our body, widely amounting to 1g per person and reaching 10 g in extreme cases. If food were the main source, exposure data would suggest the mineral paraffins being accumulated over many years or even lifetime. The milk samples of day 4 contained virtually the same mixture of mineral paraffins as the tissue fat at concentrations between 10 and 355 mg/kg (average, 44.6 mg/kg; median, 30 mg/kg). The fats from the day 20 milks contained <5-285 mg/kg mineral paraffins (average, 21.7; median, 10mg/kg), whereby almost all elevated concentrations were linked with a modified composition, suggesting a new source, such as the use of breast salves. The contamination of the milk fat with mineral paraffins seems to decrease more rapidly than for other organic contaminants, and the transfer of mineral paraffins to the baby amounts to only around 1% of that in the body of the mother.     

Tolerability and efficacy of N-chlorotaurine in epidemic keratoconjunctivitis--a double-blind, randomized, phase-2 clinical trial.

The aim of this study was to assess the tolerability and efficacy of N-chlorotaurine (NCT), an endogenous antimicrobial agent, in epidemic keratoconjunctivitis. In a prospective double-blind, randomized phase 2b study, the infected eyes were treated for 7 days with eye drops containing 1% aqueous solution of N-chlorotaurine (33 subjects) or gentamicin (27 subjects, control group). Adenovirus types 3, 4, 8, 19, and 37 were detected in 39 subjects (65%), enteroviruses in 8 (13.3%), and staphylococci in 5 (8.3%). Subjective and objective symptoms were scaled and added to a subjective and objective score, respectively, on day 1 (baseline), day 4, and day 8. Analyzing the whole study population, the subjective score on day 8 was lower in the NCT group (P = 0.016), whereas there were no differences in the objective score. However, in severe infections caused by adenovirus type 8 (n = 20) both the subjective and objective score were lower in the NCT group on day 4 (P = 0.003 and 0.015, respectively), which was also true for the subjective score on day 8 (P = 0.004) in this subgroup. The frequency of subepithelial infiltrates was similar in both groups. N-chlorotaurine was well-tolerated, shortened the duration of illness, and seems to be a useful causative therapeutic approach in severe epidemic keratoconjunctivitis.     

Value of magnetic resonance imaging in patients with a recent myocardial infarction: Comparison with planar thallium-201 scintigraphy

The diagnostic accuracy of spin-echo Magnetic Resonance (MR) imaging in the detection and localization of a recent myocardial infarction (mean 4 days old) was compared to planar thallium-201 scintigraphy in 20 patients with a documented myocardial infarction. A control group of 10 subjects underwent a similar MR imaging procedure without thallium-201 scintigraphy. T1-weighted MR images (TE 30 msec) showed abnormal thinning of the infarcted left ventricular wall during systole (<50% of the opposite wall) in 11 patients (55%). On T2-weighted multi-echo MR images, (TE 30–60–90–120 msec) abnormally increased signal intensity was found in 17 patients and coincided with the location of the infarction. Thallium-201 scintigraphy detected the infarction in 18 patients. Comparison of T2-MR imaging and thallium-201 scintigraphy showed concordant findings in 82% of the left ventricular segments. In 9% of segements, thallium uptake was reduced with normal T2-MR and in 9% we found a normal thallium uptake with abnormal T2-MR findings. In all subjects of the control group, T1-MR images were normal, and only one subject showed increased signal intensity on T2-MR images. We conclude that the diagnostic accuracy of MR imaging in detecting a myocardial infarction is similar to that of T1-201 scintigraphy.     

The Effect of a Lifestyle Intervention on Type 2 Diabetes Pathophysiology and Remission: The Stevenshof Pilot Study

Although lifestyle interventions can lead to diabetes remission, it is unclear to what extent type 2 diabetes (T2D) remission alters or improves the underlying pathophysiology of the disease. Here, we assess the effects of a lifestyle intervention on T2D reversal or remission and the effects on the underlying pathology. In a Dutch primary care setting, 15 adults with an average T2D duration of 13.4 years who were (pharmacologically) treated for T2D received a diabetes subtyping (“diabetyping”) lifestyle intervention (DLI) for six months, aiming for T2D remission. T2D subtype was determined based on an OGTT. Insulin and sulphonylurea (SU) derivative treatment could be terminated for all participants. Body weight, waist/hip ratio, triglyceride levels, HbA1c, fasting, and 2h glucose were significantly improved after three and six months of intervention. Remission and reversal were achieved in two and three participants, respectively. Indices of insulin resistance and beta cell capacity improved, but never reached healthy values, resulting in unchanged T2D subtypes. Our study implies that achieving diabetes remission in individuals with a longer T2D duration is possible, but underlying pathology is only minimally affected, possibly due to an impaired beta cell function. Thus, even when T2D remission is achieved, patients need to continue adhering to lifestyle therapy.     

An algorithm for the calculation of three‐dimensional collagen fiber orientation in ligaments using angle‐sensitive MRI

A method based on angle‐sensitive magnetic resonance imaging for determining unknown orientations of collagen fibers in ligaments is presented. Collagen fibers were stepwise rotated around two independent axes within a 3T magnetic resonance tomograph (from 0° to 180°, step size = 10°). Analyzing the magnetic resonance signal intensity of each voxel as a function of the rotation angle, directions were calculated by means of a computational algorithm. The accuracy of the algorithm was validated using 1000 random test directions, revealing an average deviation of 4.4° (median ± standard deviation: 2.7° ± 9°). Subsequently, the presented method was applied to three specimens of the human iliotibial tract mounted in different directions in a rotatable plastic box. Polarized light microscopy was used to verify parallel alignment of the collagen fibers in the three specimens. The calculated directions were compared with the directions of the specimens. Analyzing each voxel separately, average deviations (median ± standard deviation) in the three specimens were: 11.2° (3.6° ± 20.4°), 12° (5° ± 24.1°), and 20.4° (8.7° ± 27°). If the magnetic resonance signal intensity of each voxel was averaged with the intensity of immediately neighboring voxels, average deviations (median ± standard deviation) were 8.5° (3.6° ± 17.4°), 6.2° (0° ± 18°), and 9.2° (5° ± 19.2°). The presented method has the potential to be applied in situ to anatomical structures like cartilage, ligaments, tendons and fascia. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Methods for testing theory and evaluating impact in randomized field trials: intent-to-treat analyses for integrating the perspectives of person, place, and time

Randomized field trials provide unique opportunities to examine the effectiveness of an intervention in real world settings and to test and extend both theory of etiology and theory of intervention. These trials are designed not only to test for overall intervention impact but also to examine how impact varies as a function of individual level characteristics, context, and across time. Examination of such variation in impact requires analytical methods that take into account the trial's multiple nested structure and the evolving changes in outcomes over time. The models that we describe here merge multilevel modeling with growth modeling, allowing for variation in impact to be represented through discrete mixtures--growth mixture models--and nonparametric smooth functions--generalized additive mixed models. These methods are part of an emerging class of multilevel growth mixture models, and we illustrate these with models that examine overall impact and variation in impact. In this paper, we define intent-to-treat analyses in group-randomized multilevel field trials and discuss appropriate ways to identify, examine, and test for variation in impact without inflating the Type I error rate. We describe how to make causal inferences more robust to misspecification of covariates in such analyses and how to summarize and present these interactive intervention effects clearly. Practical strategies for reducing model complexity, checking model fit, and handling missing data are discussed using six randomized field trials to show how these methods may be used across trials randomized at different levels.