Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical trial cohort.

Few epidemiologic studies describe longitudinal liver chemistry (LC) elevations in cancer patients. A population-based retrospective cohort was identified from 31 Phase 2-3 oncology trials (excluding targeted therapies) conducted from 1985 to 2005 to evaluate background rates of LC elevations in patients (n = 3998) with or without liver metastases. Patients with baseline liver metastases (29% of patients) presented with a 3% prevalence of alanine transaminase (ALT) ≥ 3x upper limits normal (ULN) and 0.2% prevalence of bilirubin ≥ 3xULN. During follow-up, the incidence (per 1000 person-months) of new onset ALT elevations ≥3xULN was 6.1 (95% CI: 4.5, 8.0) and 2.2 (95% CI: 0.9, 4.5) in patients without and with liver metastases, respectively. No new incident cases of ALT and bilirubin elevations suggestive of severe liver injury occurred among those with liver metastases; a single case occurred among those without metastasis. Regardless of the presence of liver metastases, LC elevations were rare in cancer patients during oncology trials, which may be due to enrollment criteria. Our study validates uniform thresholds for detection of LC elevations in oncology studies and serves as an empirical referent point for comparing liver enzyme abnormalities in oncology trials of novel targeted therapies. These data support uniform LC stopping criteria in oncology trials.

NF-KB Activation and Severity of Gastritis in Helicobacter pylori-Infected Children and Adults.

In contrast to adults, Helicobacter pylori gastritis in children is reported as milder and ulcer disease as uncommon, but unequivocal data are lacking.

Muscle activation patterns in shoulder impingement patients

Introduction: Shoulder impingement is one of the most common presentations of shoulder joint problems 1. It appears to be caused by a reduction in the sub-acromial space as the humerus abducts between 60o -120o – the 'painful arc'. Structures between the humeral head and the acromion are thus pinched causing pain and further pathology 2. Shoulder muscle activity can influence this joint space but it is unclear whether this is a cause or effect in impingement patients. This study aimed to observe muscle activation patterns in normal and impingement shoulder patients and determine if there were any significant differences. Method: 19 adult subjects were asked to perform shoulder abduction in their symptomatic arm and non-symptomatic. 10 of these subjects (age 47.9 ± 11.2) were screened for shoulder impingement, and 9 subjects (age 38.9 ± 14.3) had no history of shoulder pathology. Surface EMG was used to collect data for 6 shoulder muscles (Upper, middle and lower trapezius, serratus anterior, infraspinatus, middle deltoids) which was then filtered and fully rectified. Subjects performed 3 smooth unilateral abduction movements at a cadence of 16 beats of a metronome set at 60bpm, and the mean of their results was recorded. T-tests were used to indicate any statistical significance in the data sets. Significance was set at P<0.05. Results: There was a significant difference in muscle activation with serratus anterior in particular showing a very low level of activation throughout the range when compared to normal shoulder activation patterns (<30%). Middle deltoid recruitment was significantly reduced between 60-90o in the impingement group (30:58%).Trends were noted in other muscles with upper trapezius and infraspinatus activating more rapidly and erratically (63:25%; 60:27% respectively), and lower trapezius with less recruitment (13:30%) in the patient group, although these did not quite reach significance. Conclusion: There appears to be some interesting alterations in muscle recruitment patterns in impingement shoulder patients when compared against their own unaffected shoulders and the control group. In particular changes in scapula control (serratus anterior and trapezius) and lateral rotation (infraspinatus), which have direct influence on the sub-acromial space, should be noted. It is still not clear whether these alterations are causative or reactionary, but this finding gives a clear indication to the importance of addressing muscle reeducation as part of a rehabilitation programme in shoulder impingement patients.

Reinforcement corrosion initiation and activation times in concrete structures exposed to severe marine environments

The corrosion of steel reinforcement bars in reinforced concrete structures exposed to severe marine environments usually is attributed to the aggressive nature of chloride ions. In some cases in practice corrosion has been observed to commence already within a few years of exposure even with considerable concrete cover to the reinforcement and apparently high quality concretes. However, there are a number of other cases in practice for which corrosion initiation took much longer, even in cases with quite modest concrete cover and modest concrete quality. Many of these structures show satisfactory long-term structural performance, despite having high levels of localized chloride concentrations at the reinforcement. This disparity was noted already more than 50 years ago, but appears still not fully explained. This paper presents a systematic overview of cases reported in the engineering and corrosion literature and considers possible reasons for these differences. Consistent with observations by others, the data show that concretes made from blast furnace cements have better corrosion durability properties. The data also strongly suggest that concretes made with limestone or non-reactive dolomite aggregates or sufficiently high levels of other forms of calcium carbonates have favourable reinforcement corrosion properties. Both corrosion initiation and the onset of significant damage are delayed. Some possible reasons for this are explored briefly.

Heat Dissipation And Energetic Efficiency In Animal Anoxibiosis - Economy Contra Power

This survey on calorimetry and thermodynamics of anoxibiosis applies classical and irreversible thermodynamics to interpret experimental, direct calorimetric results in order to elucidate the sequential activation of various biochemical pathways. First, the concept of direct and indirect calorimetry is expanded to incorporate the thermochemistry of aerobic and anoxic metabolism in living cells and organisms. Calorimetric studies done under normoxia as well as under physiological and environmental anoxia are presented and assessed in terms of ATP turnover rate. Present evidence suggests that unknown sources of energy in freshwater and marine invertebrates under long-term anoxia may be important. During physiological hypoxia, thermodynamically grossly inefficient pathways sustain high metabolic rates for brief periods. On the contrary, under long-term environmental anoxia, low steady-state heat dissipation is linked to the more efficient succinate, propionate, and acetate pathways. In the second part of this paper these relationships are discussed in the context of linear, irreversible thermodynamics. The calorimetric and biochemical trends during aerobic-anoxic transitions are consistent with thermodynamic optimum functions of catabolic pathways. The theory predicts a decrease of rate with an increase of thermodynamic efficiency; therefore maximum rate and maximum efficiency are mutually exclusive. Cellular changes of pH and adenylate phosphorylation potential are recognized as regulatory mechanisms in the energetic switching to propionate production. While enzyme kinetics provides one key for understanding metabolic regulation, our insight remains incomplete without a complementary thermodynamic analysis of kinetic control in energetically coupled pathways.