Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Accurate and objective infarct sizing by contrast-enhanced magnetic resonance imaging in a canine myocardial infarction model

OBJECTIVES: To identify an accurate and reproducible method to define myocardial infarct (MI) size, we conducted a study in a closed-chest canine model of acute myocardial infarction, in which MI size was measured using different thresholding techniques and by imaging at different delay times after contrast administration. BACKGROUND: The MI size by contrast-enhanced magnetic resonance imaging (CE-MRI) is directly related to long-term prognosis. However, previous measurements were done using nonuniform methods and tended to overestimate nonviable areas. METHODS: Thirteen animals underwent 90 min of coronary artery occlusion, followed by reperfusion. The CE-MRI data were acquired within 24 h after reperfusion and compared with triphenyltetrazolium chloride pathology. In the first nine animals, images were obtained approximately 15 min after gadolinium diethylene triamine penta-acetic acid (Gd-DTPA) using an inversion-recovery gradient-echo pulse sequence. To identify the most accurate method, MI size by CE-MRI was measured visually and by semi-automatic thresholding techniques, using different criteria. In four additional animals, images were acquired every 6 min until 30 min after Gd-DTPA. RESULTS: Postmortem MI size was 13.5 +/- 2.6% of left ventricular volume. Semi-automatic techniques, using full-width at half-maximum (FWHM) criterion, correlated best with postmortem data (r(2) = 0.94, p < 0.001; results confirmed by Bland-Altman plots). Using FWHM, there was no difference in MI size between different delay times after contrast (15.2 +/- 2.9% to 14.5 +/- 4.2% at 6 and 30 min, respectively; p = NS). CONCLUSIONS: When an objective technique is used to define MI size by CE-MRI, accurate infarct size measurements can be obtained from images obtained up to 30 min after contrast administration.     

High-intensity intermittent cycling increases purine loss compared with workload-matched continuous moderate intensity cycling

Purpose

Exercise at 50–60 % of peak oxygen consumption (VO_{2 peak}) stimulates maximal fat oxidation rates. Despite a lower estimated work performed; high-intensity intermittent exercise (HIIE) training produces greater fat mass reductions when compared with workload-matched continuous (CON) steady state exercise. No metabolic basis has been documented nor mechanisms offered to explain this anomaly. This study investigated the physiological and metabolic responses of two different workload-matched exercise protocols.

Methods

On separate occasions and at least 1 week apart, eight apparently healthy males cycled for 30 min at either 50 % VO_{2 peak} (CON) or performed repeated 20 s bouts of supramaximal exercise at 150 %VO_{2 peak} separated by 40 s rest (HIIE).

Results

The average heart rate, oxygen consumption, plasma glycerol and free fatty acid concentrations were not different during exercise and recovery between the trials. Plasma lactate and hypoxanthine (Hx) concentrations were elevated and urinary excretion rates of Hx and uric acid were greater following HIIE as compared to CON (P < 0.05).

Conclusion

Exercise-induced plasma Hx accumulation and urinary purine excretion are greater following HIIE and indirectly represents a net loss of adenosine triphosphate (ATP) from the muscle. The subsequent restorative processes required for intramuscular de novo replacement of ATP may contribute to a negative energy balance and in part, account for the potential accelerated fat loss observed with HIIE when compared with CON training programs.     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

Length of ovarian stimulation does not impact live birth rate in fresh donor oocyte cycles: a SART CORS study

PurposeTo evaluate the effect of controlled ovarian hyperstimulation length and total gonadotropin (GN) dose on recipient live birth rate (LBR) in fresh donor oocyte cycles.MethodsData was obtained from SART CORS on all fresh donor oocyte GnRH antagonist cycles (n = 1049) between 2014 and 2015 which resulted in a single embryo transferred. Donor and recipient demographic information and cycle characteristics were extracted. Binomial regression was used to estimate LBR with respect to days of stimulation (DOS) and total GN dose. Multivariate analysis was performed to evaluate these relationships after controlling for confounders.ResultsOverall LBR in fresh donor oocyte cycles was 57%. Average stimulation length was 14.3 ± 4.9 days, and total GN dose was 2464 ± 1062 IU. On univariate analysis, neither days of stimulation (p = 0.5) nor total GN dose (p = 0.57) was independently correlated with LBR. However, in prolonged stimulations (> 15 days) with high total GN dose (> 3000 IU), as both the cycle length and total GN dose increased, LBR significantly decreased from 63.81 to 48.15% (p = 0.02) and from 67.61 to 48.15% (p = 0.01), respectively. Multivariate analysis showed no significant effect of either DOS or total GN dose on LBR.ConclusionsLBR is significantly decreased in fresh donor oocyte cycles when cycles are prolonged with high total GN dose. However, after controlling for confounders neither DOS nor total GN dose significantly affects LBR.     

Adenomyosis — an unusual cause of sciatic pain

Summary We report the case of a female patient who presented with a 5-month history of sciatic pain. She was referred to us for investigation and eventual surgical treatment of a suspected herniated lumbar intervertebral disc. Because of an ill-defined clinical picture at admission, she was treated conservatively. After 2 weeks without any improvement, imaging of the spine by MR was performed. No signs of a herniated disc or intraspinal, space-occupying lesion were apparent, but a right paramedian pelvic mass was seen. Ultrasonography confirmed an enlarged, irregular uterus. Hysterectomy abolished the symptoms.